bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late‐career unemployment and risk of frailty among older adults in Taiwan: An 8‐year population‐based cohort study
Authors: Chu Wei‐Min , Ho Hsin‐En , Yeh Chih‐Jung , Tsan Yu‐Tse , Lee Shu‐Hsin , Lee Meng‐Chih 
Published: February 2021

AimTo evaluate whether late‐career unemployment is associated with increased physical frailty among older adults in Taiwan by the design of a population‐based cohort study.MethodsData were retrieved from the Taiwan Longitudinal Study on Aging. The study examined data from the period 1999 to 2007. A total of 652 subjects were included in the final analysis, and they were categorized as normally employed or unemployed depending on their employment status in 1999. Frailty was defined using the Fried criteria. Multiple confounding factors were adjusted in a multilevel analysis.ResultsThe average age of the participants in 1999 was 59.0 years. A total of 491 participants were normally employed, and 161 participants were unemployed. After adjustment for gender, age, level of education, income, marital status, and number of chronic diseases, late‐career unemployment was associated with increased frailty [odds ratio (OR) = 1.61; 95% confidence interval (CI) = 1.00–2.59]. The risk of developing frailty was higher for participants who were unemployed during late career and had poor self‐rated health [OR = 3.54; 95% CI = 1.37–9.20].ConclusionsLate‐career unemployment is associated with increased frailty, especially for those who also have poor self‐rated health. Older adults should be encouraged to maintain normal employment during the later stages of their career before retirement. Employers should apply strategies to prevent possible late‐career unemployment, and the government should provide resources and help to unemployed older workers so that they can minimize poor health outcomes in late life. Geriatr Gerontol Int 2021; 21: 353–358.
Sonic hedgehog signals hinder the transcriptional network necessary for pancreatic endoderm formation from human embryonic stem cells
Authors: Dumasia Niloufer P. , Khanna Aparna P. , Pethe Prasad S. 
Published: February 2021

AbstractHedgehog morphogens govern multiple aspects of pancreas organogenesis and functioning with diverse outcomes across species. Although most current differentiation protocols repress Sonic hedgehog (SHH) signals during in vitro endocrine specification, the role and mechanisms through which the SHH pathway antagonizes pancreas development during in vitro human embryonic stem (hES) cell differentiation remain unclear. We modulated SHH signaling at transitory stages of hES cell‐derived pancreatic progenitors and analyzed the effect on cellular fate decisions. We identify the Hedgehog pathway as a negative regulator of pancreatic endoderm formation through up‐regulation of a set of pancreatobiliary markers required for ductal specification, including SOX17, FOXA2, HNF1β, HNF6, PDX1, and SOX9. Surprisingly, active Hedgehog signals impeded a group of pancreatic epithelium markers, including HNF4α, HHEX, PAX6, and PTF1α. To understand how SHH signals repress the transcription of these specific markers, we analyzed Polycomb group proteins. We found differential expression of Polycomb Repressive Complex 1 subunit, BMI1 upon Shh pathway modulation in the pancreatic progenitors. Ectopic activation of Sonic hedgehog results in over‐expression of BMI1 and its associated repressive histone mark, H2AK119Ub1, in the multipotent progenitors. Our data suggest that Sonic hedgehog restricts the pancreatic differentiation program by limiting progenitor cells acquiring pancreatic epithelial fates and instead promotes pancreatobiliary differentiation. We further provide mechanistic cues of an association between Hedgehog signaling and epigenetic silencers during pancreatic lineage decisions.
A simple digital image analysis system for automated Ki67 assessment in primary breast cancer
Authors: Alataki Anastasia , Zabaglo Lila , Tovey Holly , Dodson Andrew , Dowsett Mitch 
Published: February 2021

AimsKi67 is a well‐established immunohistochemical marker associated with cell proliferation that has prognostic and predictive value in breast cancer. Quantitative evaluation of Ki67 is traditionally performed by assessing stained tissue slides with light microscopy. Automated image analysis systems have become available and, if validated, could provide greater standardisation and improved precision of Ki67 scoring. Here, we aimed to evaluate the use of the Cognition Master Professional Suite (CogM) image analysis software, which is a simple system for scoring Ki67 in primary breast cancer samples.Methods and resultsSections from 94 core‐cut biopsies, 20 excision specimens and 29 pairs of core‐cut biopsies and excision specimens were stained for Ki67 with MIB1 antibody and the Dako EnVision FLEX Detection System. Stained slides were scanned to convert them to digital data. Computer‐based Ki67 scoring was performed with CogM. Manual Ki67 scoring assessment was conducted on previously stained sections from the same biopsies with a clinically validated system that had been calibrated against the risk of recurrence. A high correlation between manual and digital scores was observed [rCores = 0.92, 95% confidence interval (CI) 0.87–0.94, P < 0.0001; rExcisions = 0.95, 95% CI 0.86–0.98, P < 0.0001] and there was no significant bias between them (P = 0.45). There was also a high correlation of Ki67 scores between paired core‐cut biopsies and excision specimens when CogM was used (r = 0.78, 95% CI 0.59–0.89, P < 0.0001).ConclusionsCogM image analysis allows for standardised automated Ki67 scoring that accurately replicates previously clinically validated and calibrated manual scores.
The human‐in‐the‐loop: an evaluation of pathologists’ interaction with artificial intelligence in clinical practice
Authors: Bodén Anna C S , Molin Jesper , Garvin Stina , West Rebecca A , Lundström Claes , Treanor Darren 
Published: February 2021

AimsOne of the major drivers of the adoption of digital pathology in clinical practice is the possibility of introducing digital image analysis (DIA) to assist with diagnostic tasks. This offers potential increases in accuracy, reproducibility, and efficiency. Whereas stand‐alone DIA has great potential benefit for research, little is known about the effect of DIA assistance in clinical use. The aim of this study was to investigate the clinical use characteristics of a DIA application for Ki67 proliferation assessment. Specifically, the human‐in‐the‐loop interplay between DIA and pathologists was studied.Methods and resultsWe retrospectively investigated breast cancer Ki67 areas assessed with human‐in‐the‐loop DIA and compared them with visual and automatic approaches. The results, expressed as standard deviation of the error in the Ki67 index, showed that visual estimation (‘eyeballing’) (14.9 percentage points) performed significantly worse (P < 0.05) than DIA alone (7.2 percentage points) and DIA with human‐in‐the‐loop corrections (6.9 percentage points). At the overall level, no improvement resulting from the addition of human‐in‐the‐loop corrections to the automatic DIA results could be seen. For individual cases, however, human‐in‐the‐loop corrections could address major DIA errors in terms of poor thresholding of faint staining and incorrect tumour–stroma separation.ConclusionThe findings indicate that the primary value of human‐in‐the‐loop corrections is to address major weaknesses of a DIA application, rather than fine‐tuning the DIA quantifications.
Increasing ferritin predicts early death in adult hemophagocytic lymphohistiocytosis
Authors: Abou Shaar Rand , Eby Charles S. , van Dorp Suzanne , de Witte Theo , Otrock Zaher K. 
Published: February 2021

AbstractIntroductionHemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathologic immune activation. Most studies on adult HLH have evaluated prognostic factors for overall survival; factors predicting early mortality have not been sufficiently investigated.MethodsThis was a collaborative study between Henry Ford Hospital and Barnes‐Jewish Hospital. We identified all adult HLH patients with at least 2 ferritin levels within 30 days from admission.ResultsOne‐hundred twenty‐four patients were identified. There were 77 males and 47 females; the median age at diagnosis was 48 years. Multivariate analysis showed that age (OR = 11.41; 95% CI:2.71‐48.04; P = .001), hepatomegaly (OR = 15.68; 95% CI:3.24‐75.96; P = .001), hyponatremia (OR = 5.94; 95% CI:1.76‐20.1; P = .004), hypoalbuminemia (OR = 7.47; 95% CI:2.08‐26.85; P = .002), and increasing ferritin levels (OR = 19.46; 95% CI:4.69‐80.71; P < .001) were significant predictors of 30‐day mortality. Patients with declining ferritin by more than 35% from the ferritin peak were more likely to survive the first 30 days of admission (OR = 4.33; 95% CI:1.04‐18.1; P = .033). By risk stratifying our cohort, we identified changes in ferritin levels to be the most significant prognostic factor of 30‐day mortality among other risk factors. Further investigating the prognostic utility of ferritin showed that increasing ferritin during the 1st week of admission (data available for 44 patients) was the only significant predictor of 30‐day mortality.ConclusionsTo the best of our knowledge, this is the first study reporting changes in ferritin to be a predictor for early death in adult HLH. Changes in ferritin might be a useful indicator of adult HLH disease activity and early prognosis.
Periodontitis and the outcome of atrial fibrillation ablation: Porphyromonas gingivalis is related to atrial fibrillation recurrence
Authors: Miyauchi Shunsuke , Tokuyama Takehito , Shintani Tomoaki , Nishi Hiromi , Hamamoto Yuta , Ouhara Kazuhisa , Furusho Hisako , Miyauchi Mutsumi , Komatsuzawa Hitoshi , Nakano Yukiko 
Published: February 2021

AbstractIntroductionInflammation is one of the main causes of atrial fibrillation (AF) recurrence after ablation. Porphyromonas gingivalis is a key periodontal pathogen in the oral–systemic disease connection and serum immunoglobulin G (IgG) antibody titers against P. gingivalis reflect the clinical status of periodontitis. This study aimed to investigate the relationship between late recurrence of AF after radiofrequency catheter ablation (RFCA) and serum IgG antibody titers against P. gingivalis.MethodsA total of 596 AF patients (mean age, 64.9 ± 10.0 years; 69% male; 61% paroxysmal AF) who underwent a first session of RFCA were enrolled. Patients were carefully examined for late recurrence during a mean follow‐up period of 17.1 ± 14.5 months. Serum IgG antibody titers against P. gingivalis (types I–IV) were measured using enzyme‐linked immunosorbent assay. The results of serum antibody titers were divided into a high‐value and a low‐value group.ResultsAmong the five P. gingivalis subtypes, serum antibody titer against P. gingivalis type IV was associated with late recurrence (odds ratio, 1.937; 95% confidence interval [CI], 1.301–2.884; p = .002). Multivariate Cox proportional‐hazards regression analysis revealed that high‐value serum antibody titer against P. gingivalis type IV independently predicted late recurrence (paroxysmal AF: adjusted hazard ratio [HR], 1.569; 95% CI, 1.010–2.427; p = .04; non‐paroxysmal AF: adjusted HR, 1.909; 95% CI, 1.213–3.005; p = .004).ConclusionPeriodontitis was related to the late recurrence of AF after RFCA. P. gingivalis type IV may be pathogenic for AF recurrence after RFCA.
Effect of metformin on outcomes of catheter ablation for atrial fibrillation
Authors: Deshmukh Amrish , Ghannam Michael , Liang Jackson , Saeed Mohammed , Cunnane Ryan , Ghanbari Hamid , Latchamsetty Rakesh , Crawford Thomas , Batul Syeda A. , Chung Eugene , Bogun Frank , Jongnarangsin Krit , Pelosi Frank , Chugh Aman , Morady Fred , Oral Elif , Oral Hakan 
Published: February 2021

AbstractBackgroundDiabetes mellitus (DM) is a risk factor for atrial fibrillation (AF). The effect of antidiabetic medications on AF or the outcomes of catheter ablation (CA) has not been well described. We sought to determine whether metformin treatment is associated with a lower risk of atrial arrhythmias after CA in patients with DM and AF.Methods and ResultsA first CA was performed in 271 consecutive patients with DM and AF (age: 65 ± 9 years, women: 34%; and paroxysmal AF: 51%). At a median of 13 months after CA (interquartile range: 6–30), 100/182 patients (55%) treated with metformin remained in sinus rhythm without antiarrhythmic drug therapy, compared with 36/89 patients (40%) not receiving metformin (p = .03). There was a significant association between metformin therapy and freedom from recurrent atrial arrhythmias after CA in multivariable Cox hazards models (hazard ratio [HR]: 0.66; ±95% confidence interval [CI]: 0.44–0.98; p = .04) that adjusted for age, sex, body mass index, AF type (paroxysmal vs. nonparoxysmal), antiarrhythmic medication, obstructive sleep apnea, chronic kidney disease, coronary artery disease, left ventricular ejection fraction, and left atrial diameter. A Cox model that also incorporated other antidiabetic agents and fasting blood glucose demonstrated a similar reduction in the risk of recurrent atrial arrhythmias with metformin treatment (HR: 0.63; ±95% CI: 0.42–0.96; p = .03).ConclusionsIn patients with DM, treatment with metformin appears to be independently associated with a significant reduction in the risk of recurrent atrial arrhythmias after CA for AF. Whether this effect is due to glycemic control or pleiotropic effects on electroanatomical mechanisms of AF remains to be determined.
Efficacy and safety of the fixed‐ratio combination of insulin degludec and liraglutide by baseline glycated hemoglobin, body mass index and age in Japanese individuals with type 2 diabetes: A subgroup analysis of two phase III trials
Authors: Komatsu Mitsuhisa , Watada Hirotaka , Kaneko Shizuka , Ross Agner Bue F , Nishida Tomoyuki , Kaku Kohei 
Published: February 2021

AbstractAims/IntroductionTo assess efficacy and safety of insulin degludec/liraglutide (IDegLira) in Japanese participants with type 2 diabetes across different baseline characteristics.Materials and MethodsData from two randomized controlled trials were used: DUAL I Japan (n = 819 insulin‐naïve participants) and DUAL II Japan (n = 210 insulin‐experienced participants). Outcomes were assessed according to baseline glycated hemoglobin ( HbA1c; <8.0%, ≥8.0–<9.0%, ≥9.0%), body mass index (<25, ≥25–<30, ≥30 kg/m2) and age (<65, ≥65 years).ResultsIn DUAL I Japan, reductions in HbA1c with IDegLira versus degludec and liraglutide were observed across all subgroups (treatment differences: −0.48% to −0.72% vs degludec, −0.29% to −0.73% vs liraglutide). Results were similar with IDegLira versus degludec in DUAL II Japan (treatment differences: −0.82% to −1.61%). Treatment‐by‐subgroup interactions were significant for IDegLira versus liraglutide for baseline HbA1c and age in DUAL I Japan, and for IDegLira versus degludec for baseline HbA1c in DUAL II Japan. In DUAL I Japan, IDegLira was associated with less weight gain than degludec in most subgroups. In DUAL II Japan, IDegLira was associated with a small mean weight loss (except for baseline HbA1c ≥9.0%) versus a small gain for degludec (except for age ≥65 years subgroup); treatment‐by‐subgroup interactions were not significant. Total daily insulin dose was lower with IDegLira versus degludec across all categories, except for age >65 years in DUAL II Japan.ConclusionsIDegLira reduced HbA1c in Japanese participants with type 2 diabetes across baseline HbA1c, body mass index and age categories, without unexpected safety issues.
Garcinia mangostana extract inhibits the attachment of chicken isolates of Listeria monocytogenes to cultured colorectal cells potentially due to a high proanthocyanidin content
Authors: Wang Yi , Baptist Jolene A. , Dykes Gary A. 
Published: February 2021

AbstractListeria monocytogenes are pathogenic microorganisms and of particular concern in the poultry industry. They are frequently isolated from raw chicken products due to their ability to attach to a wide variety of food and food‐contact surfaces. The application of synthetic antimicrobial agents is often limited by potential emergence of antimicrobial resistance and regulations associated to organic poultry products. Development of natural antimicrobial agents controlling Listeria monocytogenes contamination and pathogenesis represent an alternative approach. This study screened a range of plant extracts (including those from cranberry, mangosteen, persimmon, and roselle) for their ability to affect five Listeria monocytogenes strains with respect to their bacterial surface hydrophobicity, auto‐aggregation, and attachment to cultured human colorectal cells. Results show that mangosteen extracts showed significant inhibitory effects on the attachment of Listeria monocytogenes to the cell line, potentially due to a high level of proanthocyanidin content. In addition, the plant extracts influenced bacterial auto‐aggregation (increase in most of the cases) by increasing bacterial surface hydrophobicity. These results may support future development of alternative antimicrobial agents controlling the contamination and pathogenesis of Listeria monocytogenes.
Extending urban stocks and flows analysis to urban greenhouse gas emission accounting: A case of Odense, Denmark
Authors: Lanau Maud , Herbert Luca , Liu Gang 
Published: February 2021

AbstractCities generate greenhouse gas (GHG) emissions both in the construction phase of their built environment stocks and durable goods and in their operation phase with energy and material flows. Existing urban GHG accounting methods, however, focus largely on emissions related to energy and material flows and have rarely considered the role of urban stocks. In this article, we have extended urban stocks and flows analysis to urban GHG accounting, using bottom‐up and high‐resolution urban stocks and flows information for a case of Odense, Denmark. We introduced a complementary indicator of carbon replacement value (CRV) to account for emissions embodied in the urban stocks and determined the CRV of Odense as 10.7 megatons of CO2 equivalent (or 53 metric tons per capita) in 2017, equivalent to 13 years of Odense's operational emissions. The comparison between CRV and operational emissions across urban activities facilitates a better understanding of the carbon profile of the city and opportunities for decarbonization. Such urban metabolic based GHG accounting and inclusion of stocks can help to estimate the amount of GHG emissions to be expected from the further urbanization in developing countries as their urban stocks continue to increase and inform their potentials for leapfrogging in emission reduction.
Influence of perceived stress and workload on work engagement in front‐line nurses during COVID‐19 pandemic
Authors: Zhang Meng , zhang Ping , Liu Yu , Wang Hui , Hu Kaili , Du Meichen 
Published: February 2021

ABSTRACTAims and objectivesTo clarify both the potential influencing factors and the current status of front‐line nurses’ work engagement, and thus provide a reference for targeted interventions.BackgroundAfter coronavirus disease 2019 outbreak, front‐line nurses embraced remarkable potential stress and huge workload when caring for coronavirus disease 2019 patients, which may lead to new challenges to work engagement.DesignA large sample survey was conducted at the end of February 2020 in a designated hospital treating coronavirus disease 2019 patients in Wuhan, the capital of Hubei Province, in China. t Test, one‐way ANOVA, chi‐squared test, Pearson's correlation and hierarchical multiple regression were performed among 1,040 nurses using SPSS 24.0. The STROBE checklist was followed for observational studies.ResultsThe final model interpreted 27.3% of the variance, of which each block could explain 11.7%, 10.3% and 7.9% R2 changes including sociodemographic characteristics, stress and workload, respectively. Work engagement was negatively correlated with stress and workload. The potential influencing factors included sociodemographic characteristics (married, rescue staff, cabin ward), stress (infection control, PPE discomfort) and workload (mental demand, performance, frustration).ConclusionsFront‐line nurses perceived low stress and workload, but high work engagement, especially in self‐dedication. However, infection control, PPE discomfort and frustration were negatively associated with nurses’ work engagement, while mental demand and good performance were positively associated with nurses’ work engagement. Future interventions focused on decreasing front‐line staff's infection risk and enhancing their self‐confidence may be recommendable to promote their work engagement.
Academic‐clinical nursing partnership use an evidence‐based practice model
Authors: Bowles Wendy , Buck Jacalyn , Brinkman Bevra , Hixon Brenda , Guo Jinhong , Zehala Anita 
Published: February 2021

AbstractAims and objectivesThe purpose of this study was to compare the experience of a new clinical model with traditional clinical teaching and examine the effects of evidence‐based practice strategies among staff and student nurses.BackgroundThis provides an innovative approach to nursing student clinical learning that emphasised the academic‐clinical partnership with the use of a new model called the Evidence‐based Clinical Academic Partnership (ECAP) model. The model incorporates three main components (a) unit transformation into an innovative hybrid version of a dedicated education unit (hDEU); (b) Evidence‐in‐Action (EIA) rounding; and (c) the cognitive apprenticeship theoretical framework.DesignThis pilot study used a mixed‐method, quasi‐experimental design.MethodsThe quantitative portion included a pre‐test, post‐test non‐randomised quasi‐experimental design using self‐reported survey data. The qualitative methodology used was a hermeneutic phenomenological approach to data interpretation of three focus groups with staff nurses and unit leaders. SQUIRE 2.0 guidelines were followed (Ogrinc et al., 2016).ConclusionsThe themes that emerged emphasised relationships and the partnership with this innovative approach to clinical teaching. The staff nurses emphasised the need for a collaborative approach and having the presence of the academic faculty member as a way to support the teaching and learning aspects with students.Relevance to clinical practiceThis study did provide significant contributions to the development of an innovative clinical model and highlighted the importance of the academic‐clinical partnership with the education of undergraduate nursing students. The study results provided insight to the ways the hDEU framework may be strengthened, such as increased communication and partnership in the implementation of the ECAP model. Implementing curricular change to include innovative clinical models within a nursing programme is vital in this time of healthcare transformation.