bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundThe 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.MethodsSeventy-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.ResultsIntensity-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).ConclusionOur 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

AbstractBackgroundObservational 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.MethodsWe 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).ResultsWe 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).ConclusionsOur 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

Abstract
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

Abstract
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

Abstract
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

AbstractLimited 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

AbstractIn 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

Abstract
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

Abstract

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 &gt;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

ABSTRACT
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

ABSTRACT
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.