bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of institutionalization in users of day care facilities with mild cognitive impairment to moderate dementia
Authors: Spiegl Klara , Luttenberger Katharina , Graessel Elmar , Becker Linda , Scheel Jennifer , Pendergrass Anna
Published: September 2021

Background

Most people with dementia wish to remain at home for as long as possible. Therefore, it is important to know the predictors of institutionalization, especially those that can be influenced. The aim of the present study is to identify predictors of the institutionalization of people with mild cognitive impairment (MCI) to moderate dementia who attend day care facilities (DCFs) throughout Germany.

Methods

This study is a secondary analysis of longitudinal data from 371 dyads comprising a cognitively impaired care receiver (CR) and a caregiver (CG). The data were collected in DCFs and via telephone interviews at three measurement points. To investigate the extent to which 16 variables could predict the institutionalization of the CRs between the 6- and 12-month follow-up, in the first step bivariate Cox regressions were calculated. In the second step, significant predictors were included in a model using multivariate Cox regression.

Results

Between the 6- and 12-month evaluations, 39 CRs moved into an institution. The risk of institutionalization of people with MCI to moderate dementia attending a DCF increased significantly (p < .05) when the CRs showed more neuropsychiatric symptoms (Hazard ratio (HR) = 1.237), when the CRs and their CGs did not live together in the same house (HR = 2.560), or when the care level of the CRs is low (HR = 2.241).

Conclusions

Neuropsychiatric symptoms could be a possible starting point for therapeutic interventions that are designed to delay or prevent institutionalization. CG who do not live with their CR in the same house and CG who care for a CR with impairment in performing daily routine tasks care are particularly likely to make the decision to institutionalize the CR. For this group, advice and support are particularly important.

Trail registration

ISRCTN16412551.
Cervical cancer screening programs and their context-dependent effect on inequalities in screening uptake: a dynamic interplay between public health policy and welfare state redistribution
Authors: De Prez Vincent , Jolidon Vladimir , Willems Barbara , Cullati Stéphane , Burton-Jeangros Claudine , Bracke Piet
Published: September 2021

Background

While organized and opportunistic cervical cancer screening (CCS) programs implemented across the European Union have increased participation rates, barriers to socioeconomically deprived women remain substantial, implying high levels of inequality in CCS uptake.

Aim

This study assesses how the screening strategy (as a score based on the availability of organized population-based CCS programs), accessibility of the healthcare system (as an index of out-of-pocket expenditure as a proportion of total healthcare costs, public health expenditure as a percentage of total GDP, and general practitioner (GP) density per 10′000 inhabitants) and social protection (as a decommodification index), impact education- and income-based inequalities in CCS uptake.

Methods

A two-level design with 25–64-year-old women (N = 96′883), eligible for Pap smear screening, nested in 28 European countries, was used to analyze data from the European Health Interview Survey’s second wave, using multilevel logistic regression modelling.

Results

Clear educational and income gradients in CCS uptake were found, which were smaller in countries with organized CCS programs, higher accessibility of the healthcare system and a higher level of decommodification. Furthermore, three-way interaction terms revealed that these gradients were smaller when organized CCS programs were implemented in countries with better accessibility of the healthcare system or a high level of decommodification.

Conclusion

This study indicates that the combination of organized screening and high accessibility of the healthcare system or social protection is essential for having lower levels of inequality in CCS uptake. In such countries, the structural threshold for poorer and lower educated women to engage in CCS is lower. This may be explained by them having a better interaction with their GP, who may convince them of the screening test, lower out-of-pocket payments, and financial support to buffer against a disadvantageous position on the labor market.
Antimicrobial and antibiofilm activities of Cu(II) Schiff base complexes against methicillin-susceptible and resistant Staphylococcus aureus
Authors: Chung Pooi Yin , Khoo Ranon Earn Yueh , Liew Hui Shan , Low May Lee
Published: September 2021

Background

Methicillin-resistance S. aureus (MRSA) possesses the ability to resist multiple antibiotics and form biofilm. Currently, vancomycin remains the last drug of choice for treatment of MRSA infection. The emergence of vancomycin-resistant S. aureus (VRSA) has necessitated the development of new therapeutic agents against MRSA. In this study, the antimicrobial and antibiofilm activities of two copper-complexes derived from Schiff base (SBDs) were tested individually, and in combination with oxacillin (OXA) and vancomycin (VAN) against reference strains methicillin-susceptible and methicillin-resistant Staphylococcus aureus. The toxicity of the SBDs was also evaluated on a non-cancerous mammalian cell line.

Methods

The antimicrobial activity was tested against the planktonic S. aureus cells using the microdilution broth assay, while the antibiofilm activity were evaluated using the crystal violet and resazurin assays. The cytotoxicity of the SBDs was assessed on MRC5 (normal lung tissue), using the MTT assay.

Results

The individual SBDs showed significant reduction of biomass and metabolic activity in both S. aureus strains. Combinations of the SBDs with OXA and VAN were mainly additive against the planktonic cells and cells in the biofilm. Both the compounds showed moderate toxicity against the MRC5 cell line. The selectivity index suggested that the compounds were more cytotoxic to S. aureus than the normal cells.

Conclusion

Both the SBD compounds demonstrated promising antimicrobial and antibiofilm activities and have the potential to be further developed as an antimicrobial agent against infections caused by MRSA.
Obesity induces morphological and functional changes in female reproductive system through increases in NF-κB and MAPK signaling in mice
Authors: Gao Xiuxiu , Li Yangyang , Ma Zhuoyao , Jing Jia , Zhang Zhengqing , Liu Yue , Ding Zhide
Published: September 2021

Background

Recently, human infertility incidence is increasing in obese women causing it to become an emerging global health challenge requiring improved treatment. There is extensive evidence that obesity caused female reproductive dysfunction is accompanied by an endocrinological influence. Besides, systemic and tissue-specific chronic inflammatory status are common characteristics of obesity. However, the underlying molecular mechanism is unclear linking obesity to infertility or subfertility.

Methods

To deal with this question, we created an obese mouse model through providing a high fat diet (HFD) and determined the fertility of the obese mice. The morphological alterations were evaluated in both the reproductive glands and tracts, such as uterus, ovary and oviduct. Furthermore, to explore the underlying mechanism of these functional changes, the expressions of pro-inflammatory cytokines as well as the activations of MAPK signaling and NF-κB signaling were detected in these reproductive tissues.

Results

The obese females were successful construction and displayed subfertility. They accumulated lipid droplets and developed morphological alterations in each of their reproductive organs including uterus, ovary and oviduct. These pathological changes accompanied increases in pro-inflammatory cytokine expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in all of these sites. Such effects also accompanied increases in nuclear factor kappa B (NF-kB) expression and mitogen-activated protein kinase (MAPK) signaling pathway stimulation based on uniform time dependent increases in the NF-κB (p-NF-κB), JNK (p-JNK), ERK1/2 (p-ERK) and p38 (p-p38) phosphorylation status.

Conclusions

These HFD-induced increases in pro-inflammatory cytokine expression levels and NF-κB and MAPKs signaling pathway activation in reproductive organs support the notion that increases of adipocytes resident and inflammatory status are symptomatic of female fertility impairment in obese mice.
Smoothness metric during reach-to-grasp after stroke: part 2. longitudinal association with motor impairment
Authors: Saes Mique , Mohamed Refai Mohamed Irfan , van Kordelaar Joost , Scheltinga Bouke L. , van Beijnum Bert-Jan F. , Bussmann Johannes B. J. , Buurke Jaap H. , Veltink Peter H. , Meskers Carel G. M. , van Wegen Erwin E. H. , Kwakkel Gert
Published: September 2021

Background

The cause of smoothness deficits as a proxy for quality of movement post stroke is currently unclear. Previous simulation analyses showed that spectral arc length (SPARC) is a valid metric for investigating smoothness during a multi-joint goal-directed reaching task. The goal of this observational study was to investigate how SPARC values change over time, and whether SPARC is longitudinally associated with the recovery from motor impairments reflected by the Fugl-Meyer motor assessment of the upper extremity (FM-UE) in the first 6 months after stroke.

Methods

Forty patients who suffered a first-ever unilateral ischemic stroke (22 males, aged 58.6 ± 12.5 years) with upper extremity paresis underwent kinematic and clinical measurements in weeks 1, 2, 3, 4, 5, 8, 12, and 26 post stroke. Clinical measures included amongst others FM-UE. SPARC was obtained by three-dimensional kinematic measurements using an electromagnetic motion tracking system during a reach-to-grasp movement. Kinematic assessments of 12 healthy, age-matched individuals served as reference. Longitudinal linear mixed model analyses were performed to determine SPARC change over time, compare smoothness in patients with reference values of healthy individuals, and establish the longitudinal association between SPARC and FM-UE scores.

Results

SPARC showed a significant positive longitudinal association with FM-UE (B: 31.73, 95%-CI: [27.27 36.20],P < 0.001), which encompassed significant within- and between-subject effects (B: 30.85, 95%-CI: [26.28 35.41],P < 0.001 and B: 50.59, 95%-CI: [29.97 71.21],P < 0.001, respectively). Until 5 weeks post stroke, progress of time contributed significantly to the increase in SPARC and FM-UE scores (P < 0.05), whereafter they levelled off. At group level, smoothness was lower in patients who suffered a stroke compared to healthy subjects at all time points (P < 0.05).

Conclusions

The present findings show that, after stroke, recovery of smoothness in a multi-joint reaching task and recovery from motor impairments are longitudinally associated and follow a similar time course. This suggests that the reduction of smoothness deficits quantified by SPARC is a proper objective reflection of recovery from motor impairment, as reflected by FM-UE, probably driven by a common underlying process of spontaneous neurological recovery early post stroke.
Accelerated diastolic dysfunction in premenopausal women with rheumatoid arthritis
Authors: Kim Gee Hee , Park Yune-Jung
Published: September 2021

Background

Disturbances of diastolic function precede systolic heart failure and, although clinically silent, represent the earliest sign of cardiac involvement. Diastolic dysfunction (DD) is associated with age, gender (female), and hypertension. However, little is known about the age-specific incidence rates and risk factors for DD in patients with rheumatoid arthritis (RA).

Methods

We used standard two-dimensional/Doppler echocardiography to screen for the presence of diastolic dysfunction in 61 patients with RA and 107 healthy subjects. All participants were premenopausal women with no history of hypertension. DD includes an impaired relaxation with or without increased left ventricular (LV) filling pressures, pseudonormal filling, and restrictive filling based on parameters measured using echocardiography.

Results

The two groups were similar with respect to age (P=0.269). Patients with RA had significantly higher LV mass index, LV filling pressure, and lower E/A velocity than controls. All patients had preserved ejection fraction (EF ≥50%). DD was more common in patients with RA at 47% compared to 26% in the controls (P=0.004). Women with RA in the 30- to 49-year age range were over 3.5 times more likely to have DD than those of similar age in the control group (OR=3.54; 95% CI 1.27 to 9.85). Among patients with RA, high CRP levels were independently associated with DD even after adjustment for cardiovascular risk factors (P=0.009).

Conclusions

In premenopausal women with RA, DD is much more common and the age of onset is reduced. Early screening of myocardial function may provide an opportunity for preventing future cardiovascular disease.
Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer’s disease, but not in cerebral amyloid angiopathy
Authors: De Kort Anna M. , Kuiperij H. Bea , Alcolea Daniel , Kersten Iris , Versleijen Alexandra A. M. , Greenberg Steven M. , Stoops Erik , Schreuder Floris H. B. M. , Klijn Catharina J. M. , Lleó Alberto , Claassen Jurgen A. H. R. , Verbeek Marcel M.
Published: September 2021

Background

Neuroleukin (NLK) is a protein with neurotrophic properties and is present in a proportion of senile plaques and amyloid laden vessels. It has been suggested that NLK is part of a neuroprotective response to amyloid β-induced cell death. The aim of our study was to investigate the value of cerebrospinal fluid (CSF) NLK levels as a biomarker of vascular amyloid deposition in patients with cerebral amyloid angiopathy (CAA) and in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD).

Methods

CSF NLK levels were quantified by ELISA in CAA patients (n = 25) and controls (n = 27) and in two independent samples of aMCI patients, AD patients, and controls: (1) From the Radboud University Medical Center (Nijmegen), we included n = 19 aMCI patients, n = 40 AD patients, and n = 32 controls. (2) From the Hospital of Sant Pau (Barcelona), we included n = 33 aMCI patients, n = 17 AD patients, and n = 50 controls.

Results

CSF NLK levels were similar in CAA patients and controls (p = 0.95). However, we found an elevated CSF concentration of NLK in aMCI (p < 0.0001) and AD patients (p < 0.0001) compared to controls in both samples sets. In addition, we found a correlation of CSF NLK with CSF YKL-40 (age-adjusted-spearman-rank-coefficient = 0.82, p < 0.0001) in aMCI/AD patients, a well-known glial marker of neuro-inflammation.

Conclusions

We found that CSF NLK levels are elevated in aMCI and AD patients compared to controls, but are not increased in CAA patients. CSF NLK levels may be related to an increased neuroinflammatory state in early stages of AD, given its association with YKL-40.
Associations between locus coeruleus integrity and nocturnal awakenings in the context of Alzheimer’s disease plasma biomarkers: a 7T MRI study
Authors: Van Egroo Maxime , van Hooren Roy W. E. , Jacobs Heidi I. L.
Published: September 2021

Background

The brainstem locus coeruleus (LC) constitutes the intersection of the initial pathophysiological processes of Alzheimer’s disease (AD) and sleep-wake dysregulation in the preclinical stages of the disease. However, the interplay between in vivo assessment of LC degeneration and AD-related sleep alterations remains unknown. Here, we sought to investigate whether MRI-assessed LC structural integrity relates to subjective sleep-wake measures in the context of AD plasma biomarkers, in cognitively unimpaired older individuals.

Methods

Seventy-two cognitively unimpaired older individuals aged 50–85 years (mean age = 65.2 ± 8.2 years, 37 women, 21APOEε4 carriers) underwent high-resolution imaging of the LC at 7 Tesla, and LC structural integrity was quantified using a data-driven approach. Reports on habitual sleep quality and nocturnal awakenings were collected using sleep questionnaires. Plasma levels of total tau, p-tau181, Aβ40, and Aβ42were measured using single-molecule array technology.

Results

Intensity-based cluster analyses indicated two distinct LC segments, with one covering the middle-to-caudal LC and displaying lower intensity compared to the middle-to-rostral cluster (t70= −5.12,p< 0.0001). After correction for age, sex, depression, andAPOEstatus, lower MRI signal intensity within the middle-to-caudal LC was associated with a higher number of self-reported nocturnal awakenings (F1,63= 6.73,pFDR= 0.03). Furthermore, this association was mostly evident in individuals with elevated levels of total tau in the plasma (F1,61= 4.26,p= 0.04).

Conclusion

Our findings provide in vivo evidence that worse LC structural integrity is associated with more frequent nocturnal awakenings in the context of neurodegeneration, in cognitively unimpaired older individuals. These results support the critical role of the LC for sleep-wake regulation in the preclinical stages of AD and hold promises for the identification of at-risk populations for preventive interventions.
Herpesvirus infections and Alzheimer’s disease: a Mendelian randomization study
Authors: Huang Shu-Yi , Yang Yu-Xiang , Kuo Kevin , Li Hong-Qi , Shen Xue-Ning , Chen Shi-Dong , Cui Mei , Tan Lan , Dong Qiang , Yu Jin-Tai
Published: September 2021

Background

Observational studies have suggested that herpesvirus infection increased the risk of Alzheimer’s disease (AD), but it is unclear whether the association is causal. The aim of the present study is to evaluate the causal relationship between four herpesvirus infections and AD.

Methods

We performed a two-sample Mendelian randomization analysis to investigate association of four active herpesvirus infections with AD using summary statistics from genome-wide association studies. The four herpesvirus infections (i.e., chickenpox, shingles, cold sores, mononucleosis) are caused by varicella-zoster virus, herpes simplex virus type 1, and Epstein-Barr virus (EBV), respectively. A large summary statistics data from International Genomics of Alzheimer’s Project was used in primary analysis, including 21,982 AD cases and 41,944 controls. Validation was further performed using family history of AD data from UK Biobank (27,696 cases of maternal AD, 14,338 cases of paternal AD and 272,244 controls).

Results

We found evidence of a significant association between mononucleosis (caused by EBV) and risk of AD after false discovery rates (FDR) correction (odds ratio [OR] = 1.634, 95% confidence interval [CI] = 1.092–2.446,P = 0.017, FDR-correctedP = 0.034). It has been verified in validation analysis that mononucleosis is also associated with family history of AD(OR [95% CI] = 1.392 [1.061, 1.826],P = 0.017). Genetically predicted shingles were associated with AD risk (OR [95% CI] = 0.867 [0.784, 0.958],P = 0.005, FDR-correctedP = 0.020), while genetically predicted chickenpox was suggestively associated with increased family history of AD (OR [95% CI] = 1.147 [1.007, 1.307],P = 0.039).

Conclusions

Our findings provided evidence supporting a positive relationship between mononucleosis and AD, indicating a causal link between EBV infection and AD. Further elucidations of this association and underlying mechanisms are likely to identify feasible interventions to promote AD prevention.
Graves’ disease coexisted with resistance to thyroid hormone: a case report
Authors: Akahori Hiroshi , Usuda Rika
Published: September 2021

Background

Resistance to thyroid hormone is a rare autosomal dominant disorder characterized by reduced responsiveness to thyroid hormone and can cause syndrome of inappropriate secretion of thyroid stimulating hormone. Although Graves’ disease is a common autoimmune thyroid disorder, the coexistence of these two diseases is extremely rare and makes the diagnosis and treatment complicated, leading to the delayed diagnosis of resistance to thyroid hormone. We describe the case of a Japanese man with resistance to thyroid hormone coexisting with Graves’ disease, in which the correct diagnosis of resistance to thyroid hormone was delayed by masking of the signs of syndrome of inappropriate secretion of thyroid stimulating hormone, with final diagnosis 30 years after the initial treatment for Graves’ disease.

Case presentation

A 30-year-old Japanese man presented with diffuse goiter and thyrotoxicosis. Anti-thyroid stimulating hormone receptor antibody was positive. He was diagnosed with Graves’ disease. Anti-thyroid medication was chosen as the initial treatment for Graves’ disease. However, this treatment failed to normalize the free triiodothyronine, free thyroxine, and thyroid stimulating hormone levels. His thyroid hormone levels indicated syndrome of inappropriate secretion of thyroid stimulating hormone. After cessation of methimazole treatment by remission of Graves’ disease, his state of syndrome of inappropriate secretion of thyroid stimulating hormone persisted. Magnetic resonance imaging revealed no pituitary tumor lesions. The results of thyroid stimulating hormone-releasing hormone stimulation test showed a normal response of thyroid stimulating hormone. He was suspected to have resistance to thyroid hormone. Direct sequencing analysis of the thyroid hormone receptor β gene identified a heterozygous missense mutation, R282S. Coexistence of resistance to thyroid hormone with Graves’ disease was confirmed. He has no signs of thyrotoxic symptoms, and is capable in activities of daily living at the present time.

Conclusion

We described a rare case of resistance to thyroid hormone simultaneously existing with Graves’ disease. This case demonstrated that these diseases can coexist, and indicated some of the difficulties in diagnosis of resistance to thyroid hormone with coexisting Graves’ disease. The diagnosis of resistance to thyroid hormone did not become apparent until after anti-hyperthyroidism treatment. Although rare, careful follow-up after the initial treatment of Graves’ disease is necessary. The coexistence of these two diseases should be considered in patients showing occasional syndrome of inappropriate secretion of thyroid stimulating hormone.
Characterization and identification of Chinese historical rubbings preserved in Wuyuan Museum by Pyrolysis–Gas Chromatography/Mass Spectrometry
Authors: Yao Na , Zhan Xiangsheng , Ma Qinglin , Wei Shuya
Published: September 2021

For conservation and restoration purposes, the precious historical rubbings preserved in Wuyuan Museum were studied by multi-analytical techniques including 14C radiocarbon dating, scanning electron microscopy (SEM), Pyrolysis–Gas Chromatography/Mass Spectrometry (Py-GC/MS) and Herzberg staining method. The results showed that the Py-GC/MS method is an efficient method for identifying the raw materials of paper and ink in historical rubbings simultaneously. Through Py-GC/MS analysis, five types of constituents could be detected: (1) polycyclic aromatic hydrocarbons (PAHs) from soot; (2) compounds related to tar of conifer wood: retene and methyl dehydroabietate; (3) marker compounds from the whole egg; (4) additive compounds: menthol and curcumene, which were found for the first time in ink; (5) biochemical compounds from bark paper: β-amyrin and α-amyrin. Based on the above results, the ink type, binding media and additives in ink, as well as the fiber origin of the rubbing paper could be concluded. This study could not only provide scientific support for conservation and restoration of the historical rubbings preserved in Wuyuan museum, but also give method guidance for analysis of the uncharacterized rubbings from different origins.
Ixekizumab improves sleep and work productivity in patients with non-radiographic axial spondyloarthritis: results from the COAST-X trial at 52 weeks
Authors: Deodhar Atul , Mease Philip , Marzo-Ortega Helena , Hunter Theresa , Sandoval David , Kronbergs Andris , Lauzon Steven , Leung Ann , Navarro-Compán Victoria
Published: September 2021

Background

Patients with non-radiographic axial spondyloarthritis experience negative impacts on sleep, work productivity, and activity impairment. Ixekizumab, a monoclonal antibody selectively targeting interleukin-17A, has shown efficacy in treating the signs and symptoms of non-radiographic axial spondyloarthritis. This analysis evaluated the effect of ixekizumab treatment on sleep, work productivity, and activity impairment in patients with non-radiographic axial spondyloarthritis.

Methods

COAST-X (NCT02757352) was a 52-week, phase 3, multicenter, randomised placebo-controlled trial evaluating 80-mg ixekizumab every 2 weeks and every 4 weeks in patients with active non-radiographic axial spondyloarthritis. Sleep disturbance was measured with the Jenkins Sleep Evaluation Questionnaire (JSEQ) and analysed using mixed-effects models for repeated measures. Work productivity and activity impairment were measured using the Work Productivity and Activity Impairment Questionnaire for Spondyloarthritis and analysed using analysis of covariance. Absenteeism, presenteeism, and overall work impairment were assessed for patients reporting paid work; activity impairment was assessed regardless of work status.

Results

Overall, patients treated with both dosing regimens of ixekizumab reported numerically greater improvements in sleep than placebo through Week 52. At Weeks 16 and 52, patients treated with ixekizumab every 4 weeks had significantly greater improvements in presenteeism (p = 0.007 and p = 0.003, respectively) and overall work impairment (p = 0.014 and p = 0.005, respectively) and numeric improvements in absenteeism than placebo. Patients treated with ixekizumab every 2 weeks had numerically greater improvements in absenteeism, presenteeism, and overall work impairment than placebo. Both dosing regimens of ixekizumab were associated with significantly greater improvements in activity impairment than placebo (ixekizumab every 4 weeks: p = 0.003 at Week 16 and p = 0.004 at Week 52; ixekizumab every 2 weeks: p = 0.007 at Week 16 and p = 0.006 at Week 52).

Conclusions

Treatment with ixekizumab improved sleep, work productivity, and activity impairment in patients with nr-axSpA. Improvements in presenteeism and overall work impairment were sustained and consistent in the patients treated with ixekizumab every 4 weeks from Week 16 to Week 52. Improvements in activity impairment were sustained and consistent in both ixekizumab-treated groups from Week 16 to Week 52.

Trial registration

NCT02757352, May 2, 2016.
A multi-objective optimization platform for artificial lighting system in commercial greenhouses
Authors: Qu Ying , Clausen Anders , Jørgensen Bo Nørregaard
Published: September 2021

Limited natural daylight in Nordic Countries means artificial lighting is a critical factor in industrial plant production. The electricity cost of artificial lights accounts for a large percentage of the overall cost of plant production. The optimal use of artificial lighting in plant production can be formulated as a multi-objective problem (MOP) to achieve optimal plant growth while minimizing electricity cost. In previous work, for solving this MOP, a Genetic Algorithm (GA) was used to create a Pareto Frontier (PF), which contains solutions representing a trade-off for using artificial lighting against plant production objectives. The PF was updated immediately once a non-dominated child-solution was found by comparing the dominance with solutions in the PF. Besides, in addition to the PF, the initial random population is also reused as a parent source in the evolution process. When the genetic evolution process terminated, a priority-based selection mechanism was used to select a final solution from the PF. In this paper, an alternative evolution strategy is proposed and compared with the previous GA evolution strategy. By this alternative strategy, all child-solutions are only compared with their parents during the evolution process, and the non-dominated child-solutions are collected into a candidate list. The PF is then updated at the end of each generation by comparing solutions on the PF with the collected candidate solutions. In this alternative strategy, the PF is the only source of parent-solution during the evolution process. In addition, a posterior normalization is implemented in the dominance evaluation, and social welfare metrics (SWs) are applied as an alternative to the priority-based selection mechanism to avoid the explicit ranking of objectives. The experimental results show that the proposed alternative evolution strategy outperforms the previous strategy on dramatically avoiding local minima.
Analysis and forecasting of crude oil price based on the variable selection-LSTM integrated model
Authors: Lu Quanying , Sun Shaolong , Duan Hongbo , Wang Shouyang
Published: September 2021

In recent years, the crude oil market has entered a new period of development and the core influence factors of crude oil have also been a change. Thus, we develop a new research framework for core influence factors selection and forecasting. Firstly, this paper assesses and selects core influence factors with the elastic-net regularized generalized linear Model (GLMNET), spike-slab lasso method, and Bayesian model average (BMA). Secondly, the new machine learning method long short-term Memory Network (LSTM) is developed for crude oil price forecasting. Then six different forecasting techniques, random walk (RW), autoregressive integrated moving average models (ARMA), elman neural Networks (ENN), ELM Neural Networks (EL), walvet neural networks (WNN) and generalized regression neural network Models (GRNN) were used to forecast the price. Finally, we compare and analyze the different results with root mean squared error (RMSE), mean absolute percentage error (MAPE), directional symmetry (DS). Our empirical results show that the variable selection-LSTM method outperforms the benchmark methods in both level and directional forecasting accuracy.
Survival in the Real World: A National Analysis of Patients Treated for Early-Stage Breast Cancer
Authors: Gidwani Risha , Franks Jeffrey A. , Enogela Ene M. , Caston Nicole E. , Williams Courtney P. , Aswani Monica S. , Azuero Andres , Rocque Gabrielle B.
Published: September 2021

PURPOSE:

Many patient population groups are not proportionally represented in clinical trials, including patients of color, at age extremes, or with comorbidities. It is therefore unclear how treatment outcomes may differ for these patients compared with those who are well-represented in trials.

METHODS:

This retrospective cohort study included women diagnosed with stage I-III breast cancer between 2005 and 2015 in the national CancerLinQ Discovery electronic medical record–based data set. Patients with comorbidities or concurrent cancer were considered unrepresented in clinical trials. Non-White patients and/or those age < 45 or ≥ 70 years were considered under-represented. Patients who were White, age 45-69 years, and without comorbidities were considered well-represented. Cox proportional hazards models were used to evaluate 5-year mortality by representation group and patient characteristics, adjusting for cancer stage, subtype, chemotherapy, and diagnosis year.

RESULTS:

Of 11,770 included patients, 48% were considered well-represented in trials, 45% under-represented, and 7% unrepresented. Compared with well-represented patients, unrepresented patients had almost three times the hazard of 5-year mortality (adjusted hazard ratio [aHR], 2.71; 95% CI, 2.08 to 3.52). There were no significant differences in the hazard of 5-year mortality for under-represented patients compared with well-represented patients (aHR, 1.19; 95% CI, 0.98 to 1.45). However, among under-represented patients, those age < 45 years had a lower hazard of 5-year mortality (aHR, 0.63; 95% CI, 0.48 to 0.84) and those age ≥ 70 years had a higher hazard of 5-year mortality (aHR, 2.21; 95% CI, 1.76 to 2.77) compared with those age 45-69 years.

CONCLUSION:

More than half of the patients were under-represented or unrepresented in clinical trials, because of age, comorbidity, or race. Some of these groups experienced poorer survival compared with those well-represented in trials. Trialists should ensure that study participants reflect the disease population to support evidence-based decision making for all individuals with cancer.
Evolution of cooperation under the aspiration-based interactive diversity in the spatial prisoner's dilemma game
Authors: Gao Hongyu , Wang Juan , Zhang Fan , Li Xiaopeng , Xia Chengyi
Published: September 2021

In the real world, an individual may have different attitudes towards his friends. From the perspective of the evolutionary game theory, it can be reflected that individuals tend to adopt different strategies towards different opponents, which can be defined as the interactive diversity. Up to now, the evolution of cooperation with individual characteristics under the interactive diversity still needs to be further explored. Herein, under the framework of interactive diversity, we consider the influence of individual aspiration on the evolution of cooperation in the prisoner's dilemma game, in which the parameter α is introduced to represent the individual aspiration level and used to measure individual satisfaction to the neighbors in the process of strategy updating. We find that for different temptations to defect, there is an optimal interval about the aspiration level α, which can significantly promote the evolution of cooperation. Moreover, we observe that the phase transition phenomenon for the cooperation exists, and the reason for this phenomenon to occur is also analyzed from the microscopic views. Overall, the current findings can provide some interesting insights into the role of individual aspiration and the interactive diversity in solving social dilemmas.
Selective Glucocorticoid Replacement Following Unilateral Adrenalectomy for Hypercortisolism and Primary Aldosteronism
Authors: DeLozier Olivia M , Dream Sophie Y , Findling James W , Carroll Ty B , Evans Douglas B , Wang Tracy S
Published: September 2021

Context

An institutional study previously demonstrated that cosyntropin stimulation testing on postoperative day 1 (POD1-CST) identified patients at risk for adrenal insufficiency (AI) following unilateral adrenalectomy (UA) for adrenal-dependent hypercortisolism (HC) and primary aldosteronism (PA), allowing for selective glucocorticoid replacement (GR).

Objective

This study re-evaluates the need for GR following UA for patients with HC and PA in a larger cohort.

Methods

A prospective database identified 108 patients who underwent UA for mild autonomous cortisol excess (MACE) (n = 47), overt hypercortisolism (OH) (n = 27), PA (n = 22), and concurrent PA/HC (n = 12) from September 2014 to October 2020; all underwent preoperative evaluation for HC. MACE was defined by the 1 mg dexamethasone suppression test (cortisol >1.8 μg/dL), with ≥5 defined as OH. GR was initiated for basal cortisol ≤5 or stimulated cortisol ≤14 (≤18 prior to April 2017) on POD1-CST.

Results

Fifty-one (47%) patients had an abnormal POD1-CST; 54 (50%) were discharged on GR (27 MACE, 20 OH, 1 PA, 6 PA/HC). Median duration of GR was OH: 6.0 months, MACE: 2.1 months, PA: 1 month, PA/HC: 0.8 months. Overall, 26% (n = 7) of patients with OH and 43% (n = 20) of patients with MACE did not require GR. Two (2%) patients with OH had normal POD1-CST but developed AI several weeks postoperatively requiring GR. None experienced life-threatening AI.

Conclusion

POD1-CST identifies patients with HC at risk for AI after UA, allowing for selective GR. One-quarter of patients with OH and nearly half of patients with MACE can forgo GR after UA. Patients with PA do not require evaluation for AI if concurrent HC has been excluded preoperatively.
Characterization of nuclear pore complex targeting domains in Pom152 in Saccharomyces cerevisiae
Authors: Brown Jacqueline T. , Haraczy Alexandra J. , Wilhelm Christopher M. , Belanger Kenneth D.
Published: September 2021

Pom152 is a transmembrane protein within the nuclear pore complex (NPC) of fungi that is important for NPC assembly and structure. Pom152 is comprised of a short amino-terminal region that remains on the cytosolic side of the nuclear envelope (NE) and interacts with NPC proteins, a transmembrane domain, and a large, glycosylated carboxy-terminal domain within the NE lumen. Here we show that the N-terminal 200 amino acids of Pom152 that include only the amino-terminal and transmembrane regions are sufficient for localization to the NPC. Full-length, glycosylation-deficient, and truncated Pom152-GFP chimeras expressed in cells containing endogenous Pom152 localize to both NPCs and cortical endoplasmic reticulum (ER). Expression of Pom152-GFP fusions in pom152Δ cells results in detectable localization at only the NE by full-length and amino-terminal Pom152-GFP fusions, but continued retention at both the NE and ER for a chimera lacking just the carboxy-terminal 377 amino acids. Neither deletion of Pom152 nor its carboxy-terminal glycosylation sites altered the nuclear protein export rate of an Msn5/Kap142 protein cargo. These data narrow the Pom152 region sufficient for NPC localization and provide evidence that alterations in other domains may impact Pom152 targeting or affinity for the NPC.
Trp53 ablation fails to prevent microcephaly in mouse pallium with impaired minor intron splicing
Authors: White Alisa K. , Baumgartner Marybeth , Lee Madisen F. , Drake Kyle D. , Aquino Gabriela S. , Kanadia Rahul N.
Published: September 2021

Minor spliceosome inhibition due to mutations in RNU4ATAC are linked to primary microcephaly. Ablation of Rnu11, which encodes a minor spliceosome snRNA, inhibits the minor spliceosome in the developing mouse pallium, causing microcephaly. There, cell cycle defects and p53-mediated apoptosis in response to DNA damage resulted in loss of radial glial cells (RGCs), underpinning microcephaly. Here, we ablated Trp53 to block cell death in Rnu11 cKO mice. We report that Trp53 ablation failed to prevent microcephaly in these double knockout (dKO) mice. We show that the transcriptome of the dKO pallium was more similar to the control compared with the Rnu11 cKO. We find aberrant minor intron splicing in minor intron-containing genes involved in cell cycle regulation, resulting in more severely impaired mitotic progression and cell cycle lengthening of RGCs in the dKO that was detected earlier than in the Rnu11 cKO. Furthermore, we discover a potential role of p53 in causing DNA damage in the developing pallium, as detection of γH2aX+ was delayed in the dKO. Thus, we postulate that microcephaly in minor spliceosome-related diseases is primarily caused by cell cycle defects.
Wnt/beta-catenin signalling is dispensable for adult neural stem cell homeostasis and activation
Authors: Austin Sophie H. L. , Gabarró-Solanas Rut , Rigo Piero , Paun Oana , Harris Lachlan , Guillemot François , Urbán Noelia
Published: September 2021

Adult mouse hippocampal neural stem cells (NSCs) generate new neurons that integrate into existing hippocampal networks and modulate mood and memory. These NSCs are largely quiescent and are stimulated by niche signals to activate and produce neurons. Wnt/β-catenin signalling acts at different steps along the hippocampal neurogenic lineage, but whether it has a direct role in the regulation of NSCs remains unclear. Here we used Wnt/β-catenin reporters and transcriptomic data from in vivo and in vitro models to show that adult NSCs respond to Wnt/β-catenin signalling. Wnt/β-catenin stimulation instructed neuronal differentiation of NSCs in an active state and promoted the activation or differentiation of quiescent NSCs in a dose-dependent manner. However, we found that deletion of β-catenin in NSCs did not affect their activation or maintenance of their stem cell characteristics. Together, our results indicate that whilst NSCs do respond to Wnt/β-catenin stimulation in a dose-dependent and state-specific manner, Wnt/β-catenin signalling is not cell-autonomously required to maintain NSC homeostasis, which reconciles some of the contradictions in the literature as to the role of Wnt/β-catenin signalling in adult hippocampal NSCs.
Influence of Lipid Bilayer on the GPCR Structure: Comparison of All-Atom Lipid Force Fields
Authors: Mahmood Md Iqbal , Yamashita Takefumi
Published: September 2021

Lipid bilayers affect the structure and dynamics of membrane proteins significantly. In this study, to examine three AMBER-compatible force fields (GAFFlipid, Slipids, and Lipid14), we conducted molecular dynamics (MD) simulations of β2 adrenergic receptor (β2AR) embedded in the palmitoyl-oleoyl-phosphatidyl-choline (POPC) bilayer. We found that the lipid force field affected protein structures (e.g., stability of the ionic lock) largely, even though they were distant from lipids. For example, while the R131-E268 salt bridge (ionic lock), which is involved in protein activation, opened frequently in GAFFlipid and Lipid14 systems, it mostly remained closed in the Slipids system. This difference should be attributed to the difference in the interaction energy between β2AR and POPC bilayer; this energy was much smaller in the Slipids system than in the GAFFlipid and Lipid14 systems.
Factors Associated with the Willingness to Perform a Physical Employment Standard in Probation Officers
Authors: GIULIANI-DEWIG HAYDEN K. , KERR ZACHARY Y. , REGISTER-MIHALIK JOHNA K. , MOTA JACOB A. , RYAN ERIC D.
Published: September 2021

Purpose

This study examined worker characteristics and behaviors and the perceived importance of job-related tasks associated with the willingness to perform a proposed probation officer physical ability test (PROPAT).

Methods

North Carolina probation officers (N = 1213, 46.2% female, 39.8 ± 10.1 yr, 30.7 ± 6.6 kg·m−2) completed a survey including demographics, health history, and job-related tasks. A multivariable logistic regression model estimated the odds of being willing to perform the PROPAT. Adjusted odds ratios (ORadjusted) with 95% confidence intervals (CI) were calculated, with those excluding 1.00 deemed statistically significant.

Results

The majority (72%) of probation officers were willing to perform the PROPAT. Being male (compared with female) (ORadjusted = 1.50, 95% CI = 1.12–2.02) and having moderate (ORadjusted = 1.51, 95% CI = 1.10–2.08) and high physical activity status (ORadjusted = 2.89, 95% CI = 1.97–4.28) (compared with low) increased the odds of being willing to perform the PROPAT. Additionally, reporting a greater importance of tasks, including running to pursue a suspect (TASKRUN, 1-unit increase, ORadjusted = 1.25, 95% CI = 1.10–1.43) and dragging an unresisting person (TASKDRAG, 1-unit increase, ORadjusted = 1.16, 95% CI = 1.01–1.32), increased the odds of being willing to perform the PROPAT. Increasing age (1-yr increase, ORadjusted = 0.96, 95% CI = 0.94–0.98), class II (ORadjusted = 0.45, 95% CI = 0.28–0.71) and class III obesity (compared with normal weight, ORadjusted = 0.55, 95% CI = 0.32–0.93), and a previous musculoskeletal injury (ORadjusted = 0.57, 95% CI = 0.35–0.93) all decreased the odds of being willing to perform the PROPAT.

Conclusions

These results suggest being older, previously injured, obese (body mass index ≥ 35 kg·m−2), and less active is associated with being less willing to participate in the PROPAT, whereas males and reporting a higher importance of the TASKRUN and TASKDRAG activities is associated with being more willing to participate in the PROPAT. Departments can use these findings to identify feasible strategies (e.g., education and physical training) to improve the implementation of physical employment standards.
One-stop preoperative assessment of renal vessels for living donors with 3.0 T non-contrast-enhanced magnetic resonance angiography: compared with computerized tomography angiography and surgical results
Authors: Li Xiaotian , Xia Fangjie , Chen Lihua , Zhang Xiaodong , Mo Chunbai , Shen Wen
Published: September 2021

Objective:

The study was to investigate the feasibility and accuracy of assessment for living renal donors before transplantation by using 3.0 T non-contrast-enhanced magnetic resonance angiography (NCE-MRA).

Methods:

30 renal donors were investigated and underwent computed tomography angiography (CTA) and 3.0 T NCE-MRA before nephrectomy. Two radiologists independently assessed arterial and venous anatomy and potential kidney lesions. The image quality score, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), diameters and lengths of renal arteries and veins were compared between CTA and NCE-MRA. Imaging findings were compared with the surgical results served as reference standard. Agreement was assessed using κ test. The Wilcoxon test and paired sample t test were used for statistically significant differences.

Results:

The results of image quality score for renal arteries and veins were highly consistent between the two radiologists in NCE-MRA (p < 0.001). There was no significant difference in the scores of renal arterial and venous branches between NCE-MRA and CTA (p > 0.05). The SNR and CNR of renal vessels were higher than CTA (p < 0.001). There were no statistically significant differences in the length of renal vessels measured by the two methods (p > 0.05), and the diameter was smaller than that of CTA (p < 0.05). The detection of normal renal arteries and early branches by both examination techniques was consistent with intraoperative findings. Both methods showed good consistency between the anatomical variation of renal vein and the intraoperative diagnosis (p < 0.001).

Conclusion:

3.0 T NCE-MRA can be used for evaluation of main renal arteries and veins with high accuracy for anatomy and variation classification, and can be used for pre-operative vascular evaluation of living donor kidney transplantation.

Advances in knowledge:

3.0 T NCE-MRA can be used for evaluation of main renal arteries and veins with high accuracy for anatomy and variation classification, and can be used for pre-operative vascular evaluation of living donor kidney transplantation.
Diagnostic accuracy of a urine dipstick for detecting albuminuria in hypertensive patients
Authors: Panta Phornwipa , Techakehakij Win
Published: September 2021

Background: Screening for albuminuria is generally recommended among patients with hypertension. While the urine dipstick is commonly used for screening urine albumin, there is little evidence about its diagnostic accuracy among these patients in Thailand. This study aimed to assess the diagnostic accuracy of a dipstick in Thai hypertensive patients for detecting albuminuria.

Methods: This study collected the data of 3,067 hypertensive patients, with the results of urine dipstick and urine albumin-to-creatinine ratio (ACR) from random single spot urine being examined in the same day at least once, at Lampang Hospital, Thailand, during 2018. For ACR, a reference standard of ≥ 30 mg/g was applied to indicate the presence of albuminuria.

Results: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of the trace result from dipsticks were 53.6%, 94.5%, 86.5%, and 75.5%, respectively. The area under the receiver operating characteristic curve of the dipstick was 0.748.

Conclusion: Using the dipstick for screening albuminuria among hypertensive patients should not be recommended for mass screening due to its low sensitivity. In response to high PPV, a trace threshold of the dipstick may be used to indicate presence of albuminuria.