bluuebunny/crossref_metadata_2025 huggingface dataset:
Step‐by‐step protocol for alternative injury models in newt cardiac regeneration
Authors: Ikuta Hiromi , Uemasu Hitoshi , Kyakuno Mitsuki , Satoh Yukio , Namba Noriyuki , Takeuchi Takashi , Hayashi Toshinori
Published: May 2023

Although the heart is one of the most important organs for animal survival, its regenerative capacity varies among animal species. Notably, adult mammals cannot regenerate their hearts after damage such as acute myocardial infarction. In contrast, some vertebrate animals can regenerate the heart throughout their lives. Cross‐species comparative studies are important to understand the full picture of cardiac regeneration in vertebrates. Among the animal species able to regenerate the heart, some urodele amphibians, such as newts, possess a remarkable capacity for this process. Standardized methods of inducing cardiac regeneration in the newt are needed as a platform for studies comparing newts and other animal models. The procedures presented here describe amputation and cryo‐injury techniques for the induction of cardiac regeneration in Pleurodeles waltl, an emerging model newt species. Both procedures consist of simplified steps that require no special equipment. We additionally show some examples of the regenerative process obtained using these procedures. This protocol has been developed for P. waltl. However, these methods are also expected to be applicable to other newt and salamander species, facilitating comparative research with other model animals.
The novel left atrial appendage strain parameters are associated with thrombosis risk in patients with non‐valvular atrial fibrillation
Authors: Su Bo , Sun Shi‐kun , Dai Xin‐jia , Ma Chang‐sheng , Zhou Bing‐yuan
Published: May 2023

Objectives

We sought to explore a novel left atrial appendage (LAA) strain parameter which could represent the cumulative adverse impact of chronic Atrial fibrillation (AF) on the LAA function, and the relationship between the LAA strain parameter and thrombosis risk in patients with non‐valvular AF.

Methods

We enrolled 268 patients with non‐valvular AF and 58 sinus rhythm subjects who underwent transesophageal echocardiography in the study. LAA longitudinal strain amplitude (LAA LSA) was defined as the sum of the value of the maximum positive peak strain (LAA PLS) and the absolute value of the minimum negative peak strain (LAA NLS). Dense spontaneous echo contrast (SEC) was defined as grade 3 or 4 SEC.

Results

Compared to sinus rhythm group, the global LAA strain parameters were significantly lower in paroxysmal AF (n = 148), and the lowest of them were found in persistent AF (n = 120), which suggested that the global LAA strain parameters could evaluate LAA function in sinus rhythm, paroxysmal AF and persistent AF. Compared with patients in AF without SEC/thrombus (n = 113), the regional and global LAA strain parameters were significantly depressed in AF with SEC/thrombus (n = 155). Multivariate logistic regression analyses showed that LAA global LSA (OR 0.768; 95% CI:0.569, 0.970; p = 0.027) was an independent predicter of the SEC/thrombus. Compared with patients in AF without dense SEC or thrombus (n = 210), the regional and global LAA strain parameters were significantly impaired in the patients with dense SEC/thrombus(n = 58). LAA global LSA (AUC 0.884) had the best predictable accuracy for dense SEC or thrombus, and outperformed LAA PLS, LAA NLS, CHA2DS2‐VASc score and conventional LAA functional parameters that have been used in the evaluation blood flow stasis in LAA. LAA LSA showed excellent interobserver and intra‐observer agreement beyond LAA PLS and LAA NLS.

Conclusion

The novel LAA strain parameters, which were feasible and reproducible parameters for evaluation LAA mechanic function, had good predictive accuracy for blood flow stasis in LAA beyond conventional LAA functional parameters.
Humoral and cellular immune responses after three or four doses of BNT162b2 in patients with hematological malignancies
Authors: Heftdal Line Dam , Hamm Sebastian Rask , Pérez‐Alós Laura , Madsen Johannes Roth , Armenteros Jose Juan Almagro , Fogh Kamille , Kronborg Christoffer Cronwald , Vallentin Anders Pommer , Hasselbalch Rasmus Bo , Møller Dina Leth , Hansen Cecilie Bo , Pries‐Heje Mia , Gang Anne Ortved , Ostrowski Sisse Rye , Frikke‐Schmidt Ruth , Sørensen Erik , Hilsted Linda , Bundgaard Henning , Iversen Kasper , Garred Peter , Nielsen Susanne Dam , Grønbæk Kirsten
Published: May 2023

Objectives

Initial responses to coronavirus disease 2019 vaccination are impaired in patients with hematological malignancies. We investigated immune responses after three or four doses of BNT162b2 in patients with myeloid and lymphoid malignancies compared to controls, and identified risk factors for humoral and cellular nonresponse 1 year after first vaccination.

Methods

In 407 hematological patients (45 myeloid, 362 lymphoid) and 98 matched controls, we measured immunoglobulin G (IgG) and neutralizing antibodies specific for the receptor‐binding domain of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) at baseline, 3 weeks, 2, 6, and 12 months, and interferon‐γ release at 12 months.

Results

In patients with lymphoid malignancies, SARS‐CoV‐2 receptor‐binding domain IgG concentration and mean neutralizing capacity was lower than in controls at all time points. A diagnosis of chronic lymphocytic B‐cell leukemia (CLL) or lymphoma was associated with humoral nonresponse at 12 months compared to having multiple myeloma/amyloidosis (p < .001 and p = .013). Compared to controls, patients with lymphoid malignancies had increased risk of cellular nonresponse. A lymphoma diagnosis was associated with lower risk of cellular nonresponse compared to patients with multiple myeloma/amyloidosis, while patients with CLL had comparable response rates to patients with multiple myeloma/amyloidosis (p = .037 and p = .280).

Conclusions

In conclusion, long‐term humoral and cellular immune responses to BNT162b2 were impaired in patients with lymphoid malignancies.
Ambient and substrate energy influence decomposer diversity differentially across trophic levels
Authors: Kriegel Peter , Vogel Sebastian , Angeleri Romain , Baldrian Petr , Borken Werner , Bouget Christophe , Brin Antoine , Bussler Heinz , Cocciufa Cristiana , Feldmann Benedikt , Gossner Martin M. , Haeler Elena , Hagge Jonas , Hardersen Sönke , Hartmann Henrik , Hjältén Joakim , Kotowska Martyna M. , Lachat Thibault , Larrieu Laurent , Leverkus Alexandro B. , Macagno Anna L. M. , Mitesser Oliver , Müller Jörg , Obermaier Elisabeth , Parisi Francesco , Pelz Stefan , Schuldt Bernhard , Seibold Sebastian , Stengel Elisa , Sverdrup‐Thygeson Anne , Weisser Wolfgang , Thorn Simon
Published: May 2023

The species‐energy hypothesis predicts increasing biodiversity with increasing energy in ecosystems. Proxies for energy availability are often grouped into ambient energy (i.e., solar radiation) and substrate energy (i.e., non‐structural carbohydrates or nutritional content). The relative importance of substrate energy is thought to decrease with increasing trophic level from primary consumers to predators, with reciprocal effects of ambient energy. Yet, empirical tests are lacking. We compiled data on 332,557 deadwood‐inhabiting beetles of 901 species reared from wood of 49 tree species across Europe. Using host‐phylogeny‐controlled models, we show that the relative importance of substrate energy versus ambient energy decreases with increasing trophic levels: the diversity of zoophagous and mycetophagous beetles was determined by ambient energy, while non‐structural carbohydrate content in woody tissues determined that of xylophagous beetles. Our study thus overall supports the species‐energy hypothesis and specifies that the relative importance of ambient temperature increases with increasing trophic level with opposite effects for substrate energy.
Improved automatic identification of isolated rapid eye movement sleep behavior disorder with a 3D time‐of‐flight camera
Authors: Cesari Matteo , Ruzicka Laurenz , Högl Birgit , Ibrahim Abubaker , Holzknecht Evi , Heidbreder Anna , Bergmann Melanie , Brandauer Elisabeth , Garn Heinrich , Kohn Bernhard , Stefani Ambra
Published: May 2023

Background and purpose

Automatic 3D video analysis of the lower body during rapid eye movement (REM) sleep has been recently proposed as a novel tool for identifying people with isolated REM sleep behavior disorder (iRBD), but, so far, it has not been validated on unseen subjects. This study aims at validating this technology in a large cohort and at improving its performances by also including an analysis of movements in the head, hands and upper body.

Methods

Fifty‐three people with iRBD and 128 people without RBD (of whom 89 had sleep disorders considered RBD differential diagnoses) were included in the study. An automatic algorithm identified movements from 3D videos during REM sleep in four regions of interest (ROIs): head, hands, upper body and lower body. The movements were divided into categories according to duration: short (0.1–2 s), medium (2–15 s) and long (15–300 s). For each ROI and duration range, features were obtained from the identified movements. Logistic regression models using as predictors the features from one single ROI or a combination of ROIs were trained and tested in a 10‐runs 10‐fold cross‐validation scheme on the task of differentiating people with iRBD from people without RBD.

Results

The best differentiation was achieved using short movements in all four ROIs (test accuracy 0.866 ± 0.007, test F1 score = 0.783 ± 0.010). Single group analyses showed that people with iRBD were distinguished successfully from subjects with RBD differential diagnoses.

Conclusions

Automatic 3D video analysis might be implemented in clinical routine as a supportive screening tool for identifying people with RBD.
Clinical response following hypertension induction for clinical delayed cerebral ischemia following subarachnoid hemorrhage: A retrospective, multicenter, cohort study
Authors: Tjerkstra Maud A. , Müller Marcella C. A. , Coert Bert A. , Hoefnagels Friso W. A. , Vergouwen Mervyn D. I. , van Vliet Peter , Ooms Lizzy , Rinkel Gabriël J. E. , Slooter Arjen J. C. , Moojen Wouter A. , Jellema Korné , Vandertop W. Peter , Verbaan Dagmar
Published: May 2023

Background

Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high‐quality studies on its efficacy are lacking. We studied immediate and 3−/6‐month clinical efficacy of HTI in aSAH patients with clinical DCI.

Methods

A retrospective, multicenter, comparative, observational cohort study in aSAH patients with clinical deterioration due to DCI, admitted to three tertiary referral hospitals in the Netherlands from 2015 to 2019. Two hospitals used a strategy of HTI (HTI group) and one hospital had no such strategy (control group). We calculated adjusted relative risks (aRR) using Poisson regression analyses for the two primary (clinical improvement of DCI symptoms at days 1 and 5 after DCI onset) and secondary outcomes (DCI‐related cerebral infarction, in‐hospital mortality, and poor clinical outcome [modified Rankin Scale 4–6] assessed at 3 or 6 months), using the intention‐to‐treat principle. We also performed as‐treated and per‐protocol analyses.

Results

The aRR for clinical improvement on day 1 after DCI in the HTI group was 1.63 (95% CI 1.17–2.27) and at day 5 after DCI 1.04 (95% CI 0.84–1.29). Secondary outcomes were comparable between the groups. The as‐treated and per‐protocol analyses yielded similar results.

Conclusions

No clinical benefit of HTI is observed 5 days after DCI due to spontaneous reversal of DCI symptoms in patients treated without HTI. The 3−/6‐month clinical outcome was similar for both groups. Therefore, these data suggest that one may consider to not apply HTI in aSAH patients with clinical DCI.
Risk of myocardial infarction in Parkinson's disease: A systematic review and meta‐analysis
Authors: Nabizadeh Fardin , Valizadeh Parya , Sharifi Parisa , Zafari Rasa , Mirmosayyeb Omid
Published: May 2023

Background and purpose

Previous studies investigating cardiovascular disorders in patients with Parkinson's disease (PD) showed heterogeneous results regarding whether there is a higher or lower risk of myocardial infarction (MI) in these patients compared to the general population. Because of the inconsistency in findings, herein the aim was to perform a systematic review and meta‐analysis to investigate the risk of MI in patients with PD.

Methods

A comprehensive literature search was performed using four databases, PubMed, Web of Science, Scopus and Embase, in June 2022. Peer‐reviewed observational studies comprising case–controls, cohort, cross‐sectional and longitudinal studies that reported MI in the PD population were included.

Results

After the screening, 20 studies with a total of 80,441 patients with PD and 802,857 controls were included in our qualitative and quantitative synthesis. The pooled estimated odds ratio for MI in PD patients compared to controls was 0.80 (95% confidence interval [CI] 0.56–1.05) which indicates that there is no association. The pooled prevalence of MI was 5% (95% CI 3%–7%) with a range of 1%–20% amongst patients with PD. The men (6%, 95% CI 1%–13%) and women (6%, 95% CI 1%–14%, Q = 29.27, I2 = 98.50%, p < 0.001) had similar MI prevalence.

Conclusion

This comprehensive systematic review and meta‐analysis provide compelling evidence that PD is associated with a reduced risk of MI. Whilst the exact mechanism underlying this association remains to be fully elucidated, it is clear that certain risk factors for cardiac events appear to be less present in PD patients, which may serve as a protective factor. However, given the reports of increased risk for cerebrovascular events in PD patients, it is possible that the major risk factors for MI and cardiovascular accidents in this population differ. These findings have important implications for clinical management and further research in this area is warranted.
Characterizing the treatment gap in the United States among adult patients with a new diagnosis of epilepsy
Authors: Decker Barbara M. , Ellis Colin A. , Schriver Emily , Fischbein Kelly , Smith Debbie , Moyer Jason T. , Kulick‐Soper Catherine V. , Mowery Danielle , Litt Brian , Hill Chloe E.
Published: May 2023

Objective

Epilepsy is largely a treatable condition with antiseizure medication (ASM). Recent national administrative claims data suggest one third of newly diagnosed adult epilepsy patients remain untreated 3 years after diagnosis. We aimed to quantify and characterize this treatment gap within a large US academic health system leveraging the electronic health record for enriched clinical detail.

Methods

This retrospective cohort study evaluated the proportion of adult patients in the health system from 2012 to 2020 who remained untreated 3 years after initial epilepsy diagnosis. To identify incident epilepsy, we applied validated administrative health data criteria of two encounters for epilepsy/seizures and/or convulsions, and we required no ASM prescription preceding the first encounter. Engagement with the health system at least 2 years before and at least 3 years after diagnosis was required. Among subjects who met administrative data diagnosis criteria, we manually reviewed medical records for a subset of 240 subjects to verify epilepsy diagnosis, confirm treatment status, and elucidate reason for nontreatment. These results were applied to estimate the proportion of the full cohort with untreated epilepsy.

Results

Of 831 patients who were automatically classified as having incident epilepsy by inclusion criteria, 80 (10%) remained untreated 3 years after incident epilepsy diagnosis. Manual chart review of incident epilepsy classification revealed only 33% (78/240) had true incident epilepsy. We found untreated patients were more frequently misclassified (p < .001). Using corrected counts, we extrapolated to the full cohort (831) and estimated <1%–3% had true untreated epilepsy.

Significance

We found a substantially lower proportion of patients with newly diagnosed epilepsy remained untreated compared to previous estimates from administrative data analysis. Manual chart review revealed patients were frequently misclassified as having incident epilepsy, particularly patients who were not treated with an ASM. Administrative data analyses utilizing only diagnosis codes may misclassify patients as having incident epilepsy.
Flexible, high‐resolution cortical arrays with large coverage capture microscale high‐frequency oscillations in patients with epilepsy
Authors: Barth Katrina J. , Sun James , Chiang Chia‐Han , Qiao Shaoyu , Wang Charles , Rahimpour Shervin , Trumpis Michael , Duraivel Suseendrakumar , Dubey Agrita , Wingel Katie E. , Voinas Alex E. , Ferrentino Breonna , Doyle Werner , Southwell Derek G. , Haglund Michael M. , Vestal Matthew , Harward Stephen C. , Solzbacher Florian , Devore Sasha , Devinsky Orrin , Friedman Daniel , Pesaran Bijan , Sinha Saurabh R. , Cogan Gregory B. , Blanco Justin , Viventi Jonathan
Published: May 2023

Objective

Effective surgical treatment of drug‐resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High‐frequency oscillations (HFOs) are potential biomarkers of the EZ. Previous research has shown that HFOs often occur within submillimeter areas of brain tissue and that the coarse spatial sampling of clinical intracranial electrode arrays may limit the accurate capture of HFO activity. In this study, we sought to characterize microscale HFO activity captured on thin, flexible microelectrocorticographic (μECoG) arrays, which provide high spatial resolution over large cortical surface areas.

Methods

We used novel liquid crystal polymer thin‐film μECoG arrays (.76–1.72‐mm intercontact spacing) to capture HFOs in eight intraoperative recordings from seven patients with epilepsy. We identified ripple (80–250 Hz) and fast ripple (250–600 Hz) HFOs using a common energy thresholding detection algorithm along with two stages of artifact rejection. We visualized microscale subregions of HFO activity using spatial maps of HFO rate, signal‐to‐noise ratio, and mean peak frequency. We quantified the spatial extent of HFO events by measuring covariance between detected HFOs and surrounding activity. We also compared HFO detection rates on microcontacts to simulated macrocontacts by spatially averaging data.

Results

We found visually delineable subregions of elevated HFO activity within each μECoG recording. Forty‐seven percent of HFOs occurred on single 200‐μm‐diameter recording contacts, with minimal high‐frequency activity on surrounding contacts. Other HFO events occurred across multiple contacts simultaneously, with covarying activity most often limited to a .95‐mm radius. Through spatial averaging, we estimated that macrocontacts with 2–3‐mm diameter would only capture 44% of the HFOs detected in our μECoG recordings.

Significance

These results demonstrate that thin‐film microcontact surface arrays with both highresolution and large coverage accurately capture microscale HFO activity and may improve the utility of HFOs to localize the EZ for treatment of drug‐resistant epilepsy.
Spatial transcriptomics in human skin research
Authors: Tekkela Stavroula , Theocharidis Georgios , McGrath John A. , Onoufriadis Alexandros
Published: May 2023

Spatial transcriptomics is a revolutionary technique that enables researchers to characterise tissue architecture and localisation of gene expression. A plethora of technologies that map gene expression are currently being developed, aiming to facilitate spatially resolved, high‐dimensional assessment of gene transcription in the context of human skin research. Knowing which gene is expressed by which cell and in which location within skin, facilitates understanding of skin function and dysfunction in both health and disease. In this review, we summarise the available spatial transcriptomic methods and we describe their application to a broad spectrum of dermatological diseases.
Pro‐inflammatory cytokines mediating senescence of vascular endothelial cells in atherosclerosis
Authors: Shang Dongsheng , Liu Hanqing , Tu Zhigang
Published: May 2023

Atherosclerosis (AS) is a chronic inflammatory vascular disease, and aging is a major risk factor. The accumulation of senescent vascular endothelial cells (VECs) often leads to chronic inflammation and oxidative stress and induces endothelial dysfunction, contributing to the occurrence and development of AS. Senescent cells can secrete a variety of pro‐inflammatory cytokines to induce the senescence of adjacent cells in a paracrine manner, leading to the transmission of signaling of cellular senescence to neighboring cells and the accumulation of senescent cells. Recent studies have demonstrated that several pro‐inflammatory cytokines, including IL‐17, TNF‐α, and IFN‐γ, can induce the senescence of VECs. This review summarizes and focuses on the pro‐inflammatory cytokines that often induce the senescence of VECs and the molecular mechanisms of these pro‐inflammatory cytokines inducing senescence of VECs. Targeting the senescence of VECs induced by pro‐inflammatory cytokines may provide a potential and novel strategy for the prevention and treatment of AS.
Assessment on anisotropy degree and fracture modes for weakly anisotropic sandstone using the acoustic emission technique
Authors: Zheng Kun , Wang Chaolin , Zhao Yu , Bi Jing , Zhang Hua
Published: May 2023

Comprehensive understanding of anisotropy characteristics and fracture modes for weakly anisotropic rocks is required for engineering safety and energy exploitation. To investigate the fracture mechanisms, the uniaxial compression testing with AE (acoustic emission) technique is implemented on the weakly anisotropic sandstone because of its capability to provide the essential and frequently‐used mechanical parameters. This research first adopts the longitudinal wave velocity and T2 spectrum to validate the weak anisotropy of the bedded sandstone. The results experimentally indicate that both uniaxial compressive strength and Young's modulus have a negligible dependence on different bedding orientation angles, but both permeability and macroscopic failure patterns are considerably controlled by the bedding direction. The conventional AE index analysis indicates that the tension‐dependent failure occurs in the bedded sandstone under the uniaxial compression. Interestingly, the developed k‐means clustering method is consistent with both the latest crack classification concept and macroscopic failure patterns.
Analysis on fatigue behavior of water hydraulic artificial muscles under different elastic loads in underwater environment
Authors: Zhang Zengmeng , Zhang Dewen , Che Jinkai , Xie Yuqing , Yang Yong , Gong Yongjun
Published: May 2023

As a novel and flexible actuator, the water hydraulic artificial muscle (WHAM) has become at the forefront of bionic robot research. In order to explore the fatigue behavior of WHAM, the lifetime of WHAM was analyzed based on the crack propagation of neoprene rubber and the S‐N curve of aramid fiber. Meanwhile, WHAM's fatigue tests were carried out, and the fatigue life exceeded 56,000 cycles under the pressure of 2 MPa and the elastic load of 1030.7 N/mm. In addition, WHAM's fatigue failure is represented as the burst of the rubber tube after fiber fracture. Moreover, heavy load aggravates fibrillation that leads to severe fracture of fibrils under similar friction, and the fatigue life of WHAM is aggravatingly shortened by the coupling of fibrillation and friction. Finally, an empirical model of fatigue life was obtained, which can predict the lifetime of WHAM.
CATCHMENT AREAS, STRATIFICATION, AND ACCESS TO BETTER SCHOOLS
Authors: Calsamiglia Caterina , Miralles Antonio
Published: May 2023

School Choice provides students with the opportunity to attend better schools than those in their neighborhood. This is crucial for students from disadvantaged areas where schools may be of lower quality. Our theoretical model and numerical simulations show that the widely used Deferred Acceptance (DA) algorithm has limitations in providing access to better schools (ABS). When schools have varying levels of quality and when there are priorities linked to neighborhood schools, the DA algorithm experiences significant limitations in providing ABS. Top Trading Cycles, when compared to DA, offers greater ABS, particularly for disadvantaged students.
Infections in inflammatory bowel disease patients on immunomodulator and biologic therapy are not associated with high serum drug levels
Authors: Gazelakis Kathryn , Chu Isabel , Martin Catherine , Sparrow Miles P.
Published: May 2023

Background

Inflammatory bowel disease (IBD) therapies now utilise higher doses of immunomodulatory and biologic therapies, predisposing patients to an increased risk of infections.

Aims

We aimed to determine whether infections were associated with high anti‐tumour necrosis factor (TNF) drug levels in IBD and to quantify the risk and consequences of infections.

Methods

Two retrospective studies were performed, a descriptive cohort study and a matched case–control study. For the matched case–control study, cases of infection occurring on anti‐TNF agents were matched in a 1:2 ratio to controls of anti‐TNF treated patients without infections.

Results

In the descriptive study, 76 infections occurred in 60 patients, including 49 bacterial, 24 viral, four fungal and four parasitic. Of these, 61 (80.3%) were on biologics, 49 (64.5%) on immunomodulators and 11 (14.5%) on corticosteroids. Thirty‐four (44.7%) were on combination therapy, 27 (35.5%) on biologic monotherapy and 15 (19.7%) on immunomodulator monotherapy. Median anti‐TNF drug levels in infection cases were 3.9 μg/mL for infliximab and 6.0 μg/mL for adalimumab. In the case–control study, 32 cases of infection in 27 anti‐TNF treated patients were matched with 64 anti‐TNF treated controls without infections. Among infection cases, 59.5% were on combination therapy versus 40.6% on biologic monotherapy (P = 0.59). Median drug levels for cases and controls respectively were 3.9 μg/mL versus 5.5 μg/mL for infliximab (P = 0.72) and 6.0 μg/mL versus 9.9 μg/mL for adalimumab (P = 0.34).

Conclusion

Infections in patients with IBD were common, and the risk was highest with combination therapy. Infections were not associated with high serum anti‐TNF levels.
Promoting sleep in hospitals: An integrative review of nurses' attitudes, knowledge and practices
Authors: Mohedat Heba , Somayaji Darryl
Published: May 2023

Aims

To explore nurses' knowledge, attitudes and practices related to improving hospitalized patients' sleep.

Design

Integrative review.

Data Sources

We searched CINAHL, PubMed and PsycInfo electronically including a manual search of references listed within the relevant studies. Original, peer‐reviewed studies published in English between 2000 and 2022 evaluating nurses' sleep knowledge, attitudes, or practices to improve inpatients’ sleep were reviewed.

Review Methods

This review was guided by Whittemore and Knafl method and followed PRISMA guidelines to search the literature. Fifteen articles reporting nurses' sleep knowledge, attitudes or practices to improve inpatients’ sleep were included. The quality appraisal was done using the Mixed Methods Appraisal Tool version 2018.

Results

Inadequate training of nurses regarding sleep hygiene and insufficiency in sleep‐promoting practices were apparent. Most studies reported that nurses hold positive attitudes about sleep. The acuity of patients' health conditions affected their perception of sleep priorities. Lack of organizational sleep policies/protocols and coworkers' attitudes negatively impacted nurses' motivation to implement sleep hygiene interventions. Interventions reported in the studies were reducing noise and nursing interventions at night, using a clock for time orientation, earplugs, reducing light, keeping patients awake during the daytime, maintaining comfortable room temperature and managing patients' stress. These practices were hindered by poor knowledge, negative attitudes, patients' acuity and lack of sleep assessment tools.

Conclusion

It is essential to support nursing practice to improve patients' sleep in hospitals through interventions that target nurses' knowledge, attitudes and confidence towards implementing sleep hygiene interventions to improve patients' sleep and, consequently, their health outcomes during hospitalization.

Impact

This integrative review explored nurses' knowledge, attitudes and practices to improve patients' sleep during hospitalization. It revealed that expanding nurses' sleep knowledge and empowering them to implement sleep promotion practices are needed. Nursing educators and leaders need to be involved.

No Patient or Public Contribution

This paper is an integrative review and does not include patient or public contribution.
Embryo survival and fertility differ in lines divergently selected for birth weight homogeneity in mice
Authors: Formoso‐Rafferty Nora , El‐Ouazizi El‐Kahia Laila , Arias‐Álvarez María , Gutiérrez Juan Pablo , Cervantes Isabel
Published: May 2023

The selection of animals for lower environment sensitivity around the optimum trait value can also provide benefits in productivity and welfare. A divergent selection experiment for birth weight environmental variability in mice was successfully conducted over 17 generations. Animals from low variability selected line (L‐line) were more robust by having a higher litter size and survival at weaning in a common breeding environment, than those from high variability line (H‐line). The objective of this study was to analyze the differences between those divergently selected lines for embryo and fetal survival and for fertility and prolificacy rate. To study embryo survival and ovulation rate, a total of 98 females (34 H‐line and 50 L‐line) were studied in four generations of the divergent experiment. To analyze fetal survival and fertility rate, 378 female mice (138 H‐line and 240 L‐line) in 10 generations or the divergent experiment were studied. Ultrasound scans were performed at day 14 of gestation to establish the number of total fetal and the embryo absorptions. Mortality was addressed as the difference between litter size at birth and the number of fetuses at 14 days of gestation. The number of pregnant females in the first 3 days after mating was used to measure fertility. A linear model was also fitted to analyze embryo mortality, litter size, and the number of embryos at 14 days of gestation. A categorical model was then used to study fertility, including line, generation, and its interaction as effects. Despite the fact that there were no significant differences in the ovulation rate, litter size at birth was significantly higher in the L‐line than in the H‐line (9.82 vs. 8.36 pups, p < 0.001). Moreover, embryo mortality was significantly lower in the L‐line than in the H‐line (1.39 vs. 2.87 fetuses, p < 0.001). L‐line females were more fertile (53.49% vs. 23.26% for the H‐line). According to these results, the line selected for low environmental variance would be preferable for robustness and animal welfare.
Neurovascular coupling is optimized to compensate for the increase in proton production from nonoxidative glycolysis and glycogenolysis during brain activation and maintain homeostasis of pH, pCO2, and pO2
Authors: DiNuzzo Mauro , Dienel Gerald A. , Behar Kevin L. , Petroff Ognen A. , Benveniste Helene , Hyder Fahmeed , Giove Federico , Michaeli Shalom , Mangia Silvia , Herculano‐Houzel Suzana , Rothman Douglas L.
Published: May 2023

During transient brain activation cerebral blood flow (CBF) increases substantially more than cerebral metabolic rate of oxygen consumption (CMRO2) resulting in blood hyperoxygenation, the basis of BOLD‐fMRI contrast. Explanations for the high CBF versus CMRO2 slope, termed neurovascular coupling (NVC) constant, focused on maintenance of tissue oxygenation to support mitochondrial ATP production. However, paradoxically the brain has a 3‐fold lower oxygen extraction fraction (OEF) than other organs with high energy requirements, like heart and muscle during exercise. Here, we hypothesize that the NVC constant and the capillary oxygen mass transfer coefficient (which in combination determine OEF) are co‐regulated during activation to maintain simultaneous homeostasis of pH and partial pressure of CO2 and O2 (pCO2 and pO2). To test our hypothesis, we developed an arteriovenous flux balance model for calculating blood and brain pH, pCO2, and pO2 as a function of baseline OEF (OEF0), CBF, CMRO2, and proton production by nonoxidative metabolism coupled to ATP hydrolysis. Our model was validated against published brain arteriovenous difference studies and then used to calculate pH, pCO2, and pO2 in activated human cortex from published calibrated fMRI and PET measurements. In agreement with our hypothesis, calculated pH, pCO2, and pO2 remained close to constant independently of CMRO2 in correspondence to experimental measurements of NVC and OEF0. We also found that the optimum values of the NVC constant and OEF0 that ensure simultaneous homeostasis of pH, pCO2, and pO2 were remarkably similar to their experimental values. Thus, the high NVC constant is overall determined by proton removal by CBF due to increases in nonoxidative glycolysis and glycogenolysis. These findings resolve the paradox of the brain's high CBF yet low OEF during activation, and may contribute to explaining the vulnerability of brain function to reductions in blood flow and capillary density with aging and neurovascular disease.

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Association between HIF‐1α, BNIP3, and autophagy in the chorionic villi of missed abortion
Authors: Kou Junna , Yuan Enwu , Yan Guangwei
Published: May 2023

Aim

To investigate the expression of autophagy mediated by the hypoxia‐inducible factor 1α (HIF‐1α)/BNIP3 signaling pathway in villus tissues of missed abortion and HTR‐8/SVneo cells and to elucidate the association of HIF‐1α and BNIP3 in autophagy of missed abortion.

Methods

Villus tissues from 30 healthy women with induced abortion and 35 patients with missed abortion were collected, and HTR‐8/SVneo cells were cultured under hypoxia and transfected with HIF‐1α‐siRNA. Real‐time polymerase chain reaction was utilized to measure the mRNA levels of HIF‐1α and BNIP3; Western blotting was performed to determine the protein levels of HIF‐1α, BNIP3, LC3 II/I, and Beclin 1 in villus tissues and HTR‐8/SVneo cells. Cellular invasion activity was detected by transwell matrigel assay. The level of autophagy was confirmed by transmission electron microscopy of autophagosome formation.

Results

The mRNA levels of HIF‐1α and BNIP3 were significantly lower in the missed abortion villi than in the induced abortion samples. The protein levels of HIF‐1α, BNIP3, Beclin 1, and LC3II/I were significantly decreased in villus tissues from missed abortion, and autophagosomes were significantly decreased in villus tissues from missed abortion. Under hypoxia, the mRNA expression of HIF‐1α and BNIP3 was inhibited after silencing HIF‐1α by RNAi, while the protein expression of HIF‐1α, BNIP3, Beclin1, and LC3II/I was significantly downregulated. The number of invading cells was significantly decreased, and autophagosomes were significantly decreased after silencing HIF‐1α by RNAi in HTR‐8/SVneo cells.

Conclusions

Autophagy mediated by the HIF‐1α/BNIP3 signaling pathway in villous trophoblast cells may be associated with the progression and development of missed abortion.
Cementum protein 1 gene‐modified adipose‐derived mesenchymal stem cell sheets enhance periodontal regeneration in osteoporosis rat
Authors: Wang Meijie , He Mengjiao , Xu Xiongcheng , Wu Zekai , Tao Jing , Yin Fan , Luo Kai , Jiang Jun
Published: May 2023

Background and Objectives

Osteoporosis (OP) and periodontitis are both diseases with excessive bone resorption, and the number of patients who suffer from these diseases is expected to increase. OP has been identified as a risk factor that accelerates the pathological process of periodontitis. Achieving effective and safe periodontal regeneration in OP patients is a meaningful challenge. This study aimed to assess the efficacy and biosecurity of human cementum protein 1 (hCEMP1) gene‐modified cell sheets for periodontal fenestration defect regeneration in an OP rat model.

Materials and Methods

Rat adipose‐derived mesenchymal stem cells (rADSCs) were isolated from Sprague–Dawley rats. After primary culture, rADSCs were subjected to cell surface analysis and multi‐differentiation assay. And rADSCs were transduced with hCEMP1 by lentiviral vector, and hCEMP1 gene‐modified cell sheets were generated. The expression of hCEMP1 was evaluated by reverse transcription polymerase chain reaction and immunocytochemistry staining, and transduced cell proliferation was evaluated by Cell Counting Kit‐8. The hCEMP1 gene‐modified cell sheet structure was detected by histological analysis and scanning electron microscopy. Osteogenic and cementogenic‐associated gene expression was evaluated by real‐time quantitative polymerase chain reaction. In addition, an OP rat periodontal fenestration defect model was used to evaluate the regeneration effect of hCEMP1 gene‐modified rADSC sheets. The efficacy was assessed with microcomputed tomography and histology, and the biosecurity of gene‐modified cell sheets was evaluated by histological analysis of the spleen, liver, kidney and lung.

Results

The rADSCs showed a phenotype of mesenchymal stem cells and possessed multi‐differentiation capacity. The gene and protein expression of hCEMP1 through lentiviral transduction was confirmed, and there was no significant effect on rADSC proliferation. Overexpression of hCEMP1 upregulated osteogenic and cementogenic‐related genes such asrunt‐related transcription factor 2,bone morphogenetic protein 2,secreted phosphoprotein 1 and cementum attachment proteinin the gene‐modified cell sheets. The fenestration lesions in OP rats treated with hCEMP1 gene‐modified cell sheets exhibited complete bone bridging, cementum and periodontal ligament formation. Furthermore, histological sections of the spleen, liver, kidney and lung showed no evident pathological damage.

Conclusion

This pilot study demonstrates that hCEMP1 gene‐modified rADSC sheets have a marked ability to enhance periodontal regeneration in OP rats. Thus, this approach may represent an effective and safe strategy for periodontal disease patients with OP.
Sclerostin deficiency effectively promotes bone morphogenetic protein‐2‐induced ectopic bone formation
Authors: Nakamura Keigo , Koide Masanori , Kobayashi Yasuhiro , Yamashita Teruhito , Matsushita Mai , Yasuda Hisataka , Ishihara Yuichi , Yoshinari Nobuo , Udagawa Nobuyuki
Published: May 2023

Background and Objective

Severe periodontitis causes alveolar bone resorption, resulting in tooth loss. Developments of tissue regeneration therapy that can restore alveolar bone mass are desired for periodontal disease. The application of bone morphogenetic protein‐2 (BMP‐2) has been attempted for bone fractures and severe alveolar bone loss. BMP‐2 reportedly induces sclerostin expression, an inhibitor of Wnt signals, that attenuates bone acquisition. However, the effect of sclerostin‐deficiency on BMP‐2‐induced bone regeneration has not been fully elucidated. We investigated BMP‐2‐induced ectopic bones in Sost‐knockout (KO) mice.

Methods

rhBMP‐2 were implanted into the thighs of C57BL/6 (WT) and Sost‐KO male mice at 8 weeks of age. The BMP‐2‐induced ectopic bones in these mice were examined on days 14 and 28 after implantation.

Results

Immunohistochemical and quantitative RT‐PCR analyses showed that BMP‐2‐induced ectopic bones expressed sclerostin in osteocytes on days 14 and 28 after implantation in Sost‐Green reporter mice. Micro‐computed tomography analysis revealed that BMP‐2‐induced ectopic bones in Sost‐KO mice showed a significant increased relative bone volume and bone mineral density (WT = 468 mg/cm3, Sost‐KO = 602 mg/cm3) compared with those in WT mice on day 14 after implantation. BMP‐2‐induced ectopic bones in Sost‐KO mice showed an increased horizontal cross‐sectional bone area on day 28 after implantation. Immunohistochemical staining showed that BMP‐2‐induced ectopic bones in Sost‐KO mice had an increased number of osteoblasts with osterix‐positive nuclei compared with those in WT mice on days 14 and 28 after implantation.

Conclusion

Sclerostin deficiency increased bone mineral density in BMP‐2‐induced ectopic bones.
Impact of sleep chronotype on in‐laboratory polysomnography parameters
Authors: Colelli David R. , Dela Cruz Gio R. , Kendzerska Tetyana , Murray Brian J. , Boulos Mark I.
Published: May 2023

Morningness–eveningness preference, also known as chronotype, is the tendency for a person to sleep during certain hours of the day and is broadly categorised into morning and evening types. In‐laboratory polysomnography (iPSG) is the gold‐standard to assess sleep, however, an individual's chronotype is not accounted for in current protocols, which may confound collected sleep data. The objective of our study was to assess if chronotype had an association with sleep physiology. Patients who completed the diagnostic iPSG and the Morningness–Eveningness Questionnaire (MEQ), which categorises patients into morning type, neither or evening type, were assessed. Multivariable linear regression models were used to assess if chronotype was associated with sleep quality, duration, and physiology during iPSG. The study sample included 2612 patients (mean age of 53.6 years, 48% male) recruited during 2010–2015. Morning type, compared with neither type, was significantly associated with an increase in total sleep time and rapid eye movement (REM) sleep, and a decrease in sleep onset latency and the arousal index. Evening type, compared with neither type, was significantly associated with a decrease in total sleep time, sleep efficiency, and REM sleep, and an increase in sleep onset latency and wake after sleep onset. Additionally, iPSG lights out time was significantly different between the different chronotypes. Overall, a morningness chronotype was associated with favourable sleep quality and duration while an eveningness chronotype was associated with reduced sleep quality. Our study quantifies the association of chronotype with iPSG metrics and suggests that laboratory protocols should consider chronotype in their evaluations.
Approximate Bayesian Computation applied to time series of population genetic data disentangles rapid genetic changes and demographic variations in a pathogen population
Authors: Saubin Méline , Tellier Aurélien , Stoeckel Solenn , Andrieux Axelle , Halkett Fabien
Published: May 2023

Adaptation can occur at remarkably short timescales in natural populations, leading to drastic changes in phenotypes and genotype frequencies over a few generations only. The inference of demographic parameters can allow understanding how evolutionary forces interact and shape the genetic trajectories of populations during rapid adaptation. Here we propose a new Approximate Bayesian Computation (ABC) framework that couples a forward and individual‐based model with temporal genetic data to disentangle genetic changes and demographic variations in a case of rapid adaptation. We test the accuracy of our inferential framework and evaluate the benefit of considering a dense versus sparse sampling. Theoretical investigations demonstrate high accuracy in both model and parameter estimations, even if a strong thinning is applied to time series data. Then, we apply our ABC inferential framework to empirical data describing the population genetic changes of the poplar rust pathogen following a major event of resistance overcoming. We successfully estimate key demographic and genetic parameters, including the proportion of resistant hosts deployed in the landscape and the level of standing genetic variation from which selection occurred. Inferred values are in accordance with our empirical knowledge of this biological system. This new inferential framework, which contrasts with coalescent‐based ABC analyses, is promising for a better understanding of evolutionary trajectories of populations subjected to rapid adaptation.
Developmental stress does not induce genome‐wide DNA methylation changes in wild great tit (Parus major) nestlings
Authors: Sepers Bernice , Mateman A. Christa , Gawehns Fleur , Verhoeven Koen J. F. , van Oers Kees
Published: May 2023

The environment experienced during early life is a crucial factor in the life of many organisms. This early life environment has been shown to have profound effects on morphology, physiology and fitness. However, the molecular mechanisms that mediate these effects are largely unknown, even though they are essential for our understanding of the processes that induce phenotypic variation in natural populations. DNA methylation is an epigenetic mechanism that has been suggested to explain such environmentally induced phenotypic changes early in life. To investigate whether DNA methylation changes are associated with experimentally induced early developmental effects, we cross‐fostered great tit (Parus major) nestlings and manipulated their brood sizes in a natural study population. We assessed experimental brood size effects on pre‐fledging biometry and behaviour. We linked this to genome‐wide DNA methylation levels of CpG sites in erythrocyte DNA, using 122 individuals and an improved epiGBS2 laboratory protocol. Brood enlargement caused developmental stress and negatively affected nestling condition, predominantly during the second half of the breeding season, when conditions are harsher. Brood enlargement, however, affected nestling DNA methylation in only one CpG site and only if the hatch date was taken into account. In conclusion, this study shows that nutritional stress in enlarged broods does not associate with direct effects on genome‐wide DNA methylation. Future studies should assess whether genome‐wide DNA methylation variation may arise later in life as a consequence of phenotypic changes during early development.
Relatives' experiences of the transition from intensive care to home for acutely admitted intensive care patients—A qualitative study
Authors: Meiring‐Noordstra Aaltje , van der Meulen Ingeborg C. , Onrust Marisa , Hafsteinsdóttir Thóra B. , Luttik Marie Louise
Published: May 2023

Background

Acute admission to an intensive care unit (ICU) can negatively affect quality of life for patients and their relatives. Relatives play an important caregiving role after the patient's admission. More knowledge and understanding of their needs are necessary as the patient transitions home.

Aim

This study aims to explore relatives' experiences of acutely admitted ICU patients' transition from the ICU to a general ward and then home.

Study design

A qualitative study with a phenomenological approach was conducted. Interviews were in‐depth and featured open‐ended questions. The interviews took place after the patients transitioned from ICU to home and were conducted online by videoconference. Data were analysed using Colaizzi's seven‐step method.

Results

Twelve relatives of acutely admitted ICU patients were interviewed.

Five main themes emerged: (1) mixed feelings, (2) sense of not being involved, (3) limited information provision, (4) lack of acknowledgement as a caregiver, and (5) an uncertain future perspective. Relatives experience major uncertainties during transitions and prefer to be actively involved in care and care decisions.

Conclusions

This study indicates that relatives of ICU patients experience a lack of guidance during the transitions from the ICU to a general ward and to home, or a follow‐up facility.

More focus is needed on the themes of mixed feelings, the sense of not being involved, limited information provision, lack of acknowledgement as a caregiver, and an uncertain future perspective. This increased focus might improve the guidance during these transitions.

Relevance to clinical practice

The insights from this study may help to improve the care of patients and their relatives during the transitions.