bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep increases propagation speed of physiological brain pulsations
Authors: Elabasy Ahmed , Helakari Heta , Väyrynen Tommi , Rajna Zalán , Huotari Niko , Raitamaa Lauri , Isokoski Ville , Järvelä Matti , Kaakinen Mika , Piispala Johanna , Kallio Mika , Korhonen Vesa , Seppänen Tapio , Kiviniemi Vesa 
Published: January 2025

AbstractDuring sleep, there is an increase in the brain cerebrospinal fluid (CSF) solute convection driven by physiological pulsations. Although the main drivers of CSF flow, namely cardiac, respiratory, and vasomotor pulsations, become more powerful during sleep, there is relatively little information regarding their effects on CSF flow velocity across human brain during sleep. Here, we used functional magnetic resonance encephalography (MREG) to measure non-invasively changes in brain water flow during to sleep by tracking the propagating ultrafast signal changes induced by physiological brain pulsations. We first undertook a phantom study confirming that dense optical flow analysis of MREG data accurately detects water flow velocity, and reflects the power of the physiological pulsations. We then applied the method to quantify CSF water flow velocity in brain of healthy volunteers during EEG-verified awake and sleep recordings of ultrafast MREG data. Sleep induced an increase in CSF flow speed, as demonstrated by elevated vasomotor and respiratory pulsation speeds, while the speed of cardiovascular impulse propagation remained unchanged. The speed increases match previous findings of respective pulsation power changes, and correlated with slow delta EEG power. The sleep-induced CSF flow speed increases occurred dynamically over both pulsation cycles, without the large effects on flow directions reported previously in several neurological conditions. In conclusion, sleep increases 3D water flow speed dynamically in human brain regions showing concomitant pulse power increases, supporting a porous media model of hydrodynamics in brain cortex.
Identification of a novel GREMLIN1 uptake pathway in epithelial cells that requires BMP binding
Authors: Gao Zhichun , Gao Yuhan , Dutton Louise R. , Todd Grace , Gipson Gregory R. , Browne Connor , Kerr Emma M. , Daly Carole , Plouffe Bianca , Dunne Philip D. , Brazil Derek P. 
Published: January 2025

AbstractGremlin1 is a member of a cysteine-knot containing family of secreted antagonists of bone morphogenetic protein signaling. GREM1 binding to BMP targets prevents their engagement with cognate BMP receptors, attenuating BMP-dependent gene expression. Some evidence suggests that GREM1 can directly bind to receptor tyrosine kinases on the plasma membrane, further complicating our understanding of GREM1 biology. To attempt to clarify the modalities of GREM1 signaling, we show that GREM1 protein is produced and secreted by intestinal fibroblasts and endocytosed by neighbouring epithelial cells. GREM1 uptake is a slow process and occurs by both clathrin- and caveolin-mediated endocytosis. Cell membrane heparin sulfate proteoglycans are required for GREM1 binding and uptake, and once internalised, GREM1 appears to localise to the early endosomes. Addition of BMP2 enhanced GREM1 uptake into cells. Remarkably, generation of a BMP-resistant GREM1 mutant abolished GREM1 uptake both in the presence and absence of BMP2. These data suggest that GREM1 binding and uptake into cells requires BMP binding, a process that may contribute to the antagonism of BMP signaling by GREM1.SummaryIn this article, we demonstrate differential GREM1 mRNA versus protein expression in mouse intestine. We also identify a novel GREM1 endocytosis pathway whereby mammalian cells take up GREM1 protein in what appears to be a BMP-dependent mechanism.
Cerebral Metabolic Rate of Oxygen and Accelerometry-Based Fatigability in Community-Dwelling Older Adults
Authors: Gay Emma L. , Rosano Caterina , Coen Paul M. , Bohnen Nicholaas , Huppert Theodore , Qiao Yujia (Susanna) , Glynn Nancy W. 
Published: January 2025

AbstractAlterations in energy metabolism may drive fatigue in older age, but prior research primarily focused on skeletal muscle energetics without assessing other systems, and utilized self-reported measures of fatigue. We tested the association between energy metabolism in the brain and an objective measure of fatigability in the Study of Muscle, Mobility and Aging (N=119, age 76.8±4.0 years, 59.7% women). Total brain cerebral metabolic rate of oxygen (CMRO2) was measured using arterial spin labeling and T2-relaxation under spin tagging MRI protocols. Accelerometry-based fatigability status during a fast-paced 400m walk was determined using the Pittsburgh Fatigability Index (PPFI, higher=worse). Confounders included skeletal muscle energetics, measured in vivo using spectroscopy and ex vivo using respirometry, cardiorespiratory fitness (VO2peak), weight, medication count, and multimorbidity.Multivariable logistic regression models were used to estimate the association (odds ratio (OR)) of CMRO2with PPFI>0 compared to the referent group PPFI=0. Models were first adjusted for age and sex, and further adjusted for confounders. In this sample, 41.2% had PPFI>0 (median 3.3% [0.4-8.0%]). CMRO2was positively associated with PPFI>0 (age and sex adjusted OR=1.61, 95% CI: 1.06, 2.45, p=0.03); adjustment for confounders attenuated the association. The positive association of brain energetics and fatigability warrants further study in older adults.
Survival-Inferred Fragility of Statistical Significance in Phase III Oncology Trials
Authors: Sherry Alexander D. , Liu Yufei , Msaouel Pavlos , Lin Timothy A. , Koong Alex , Lin Christine , Abi Jaoude Joseph , Patel Roshal R. , Kouzy Ramez , El-Alam Molly B. , Miller Avital M. , Owiwi Mohannad , Ofer Jonathan , Bomze David , McCaw Zachary R. , Meirson Tomer , Ludmir Ethan B. 
Published: January 2025

ABSTRACTBackgroundStatistical significance currently defines superiority in phase III oncology trials. However, this practice is increasingly questioned. Here, we estimated the fragility of phase III oncology trials.MethodsUsing Kaplan-Meier curves for the primary endpoints of 230 two-arm superiority phase III oncology trials, we reconstructed data for individual patients. We estimated the survival-inferred fragility index (SIFI) by iteratively flipping the best responder from the experimental arm to the control arm (SIFIB) until the interpretation was changed according to the significance threshold of each trial. Severe fragility was defined by SIFI≤1%.ResultsThis study included 230 trials enrolling 184,752 patients. The median number of patients required to change trial interpretation was 8 (interquartile range, 4 to 19) or 1.4% (interquartile range, 0.7% to 3%) per SIFIB. Estimations of SIFI by multiple methods were largely consistent. For trials with an overall survival primary endpoint, the median SIFIBwas 1% (IQR, 0.5% to 1.9%). Severe fragility was found in 87 trials (38%). As a continuous statistic, the originalPvalue—but not its binary significance interpretation—was associated with fragility and severe fragility. Trials with subsequent FDA approval had lower odds of severe fragility. Lastly, the underlying survival model had differential effects on SIFI estimation.ConclusionsEven among phase III oncology trials, which directly inform patient care, changes in the outcomes of few patients are often sufficient to change statistical significance and trial interpretation. These findings imply that current definitions of statistical significance used in phase III oncology are inadequate to identify replicable findings.
Systematic characterization of zinc in a series of breast cancer cell lines reveals significant changes in zinc homeostasis
Authors: Woyciehowsky Mena , Larson Portia , Stephan Annika R. , Dandridge Sharee L. , Idonije Doreen , Berg Kylie A. , Lanthier Alyx , Acuna Stephanie Araiza , Stites Saskia W. , Gebhardt Waverly J. , Holtzen Samuel E. , Rakshit Ananya , Palmer Amy E. 
Published: January 2025

AbstractAn optimal amount of labile zinc (Zn2+) is essential for proliferation of human cells, where Zn2+levels that are too high or too low cause cell cycle exit. Tumors of the breast have been characterized by high levels of total Zn2+. Given the role of Zn2+in proliferation of human cells and elevation of zinc in breast cancer tumors, we examined the concentration of total and labile Zn2+across a panel of 5 breast cancer cell lines, compared to the normal MCF10A cell line. We found that three cell lines (MDA-MB-231, MDA-MB-157, and SK-Br-3) showed elevated labile Zn2+in the cytosol, while T-47D showed significantly lower Zn2+, and MCF7 showed no change compared to MCF10A cells. There was no change in total Zn2+across the cell lines, as measured by ICP-MS, but we did observe a difference in the cells ability to accumulate Zn2+when Zn2+in the media was elevated. Therefore, we examined how proliferation of each cell line was affected by increases and decreases in the media. We found striking differences, where three cancer cell lines (MDA-MB-231, MDA-MB-157, and MCF7) showed robust proliferation in high Zn2+at concentrations that killed MCF10A, T-47D, and SK-Br-3 cells. We also discovered that 4 of the 5 cancer cell lines demonstrate compromised proliferation and increased cell death in low Zn2+, suggesting these cells may be addicted to Zn2+. Overall, our study suggests significant differences in Zn2+homeostasis and regulation in different types of breast cancer cells, with consequences for both proliferation and cell viability.
Abdominal myosteatosis is associated with lower processing speed in a multiethnic cohort of older adults
Authors: McNeish Brendan L. , Miljkovic Iva , Allison Matthew A. , Hughes Timothy , Nasrallah Ilya , Terkpertey Eric , Rosano Caterina 
Published: January 2025

BackgroundPrior research linking myosteatosis with cognition in older adults has been conducted in relatively homogenous populations with narrow age ranges. We evaluated if abdominal myosteatosis was associated with processing speed in a multiethnic cohort of middle aged and older adults.MethodsThe analytical sample included 1,268 adults (46-86 years old, mean 63±9 years, 53% female of 41% White, 20% Black, 14% Chinese, and 25% Hispanic), a subset from the Multi-Ethnic Study of Atherosclerosis (MESA). Bivariate analyses were performed between abdominal computed tomography derived muscle densities (a myosteatosis measure) at year 3 with Digit Symbol Coding (DSC) with cytokines. Multivariable models were first adjusted for demographics, education, and general cognition, and further adjusted for other known predictors of dementia:APOE-4, physical activity, diabetes, cholesterol, smoking, and blood pressure. We further assessed whether central adiposity, general adiposity, and cytokines modified this association. We tested interactions by ethnicity, sex, and age.ResultsRectus abdominis myosteatosis was significantly associated with worse DSC (B= −0.247, 95% CI: 0.098,0.396, p=0.001) independent of demographics, education, general cognition, and dementia risk factors. Adjustment for central adiposity, and cytokines did not attenuate the associations. Tests for interactions by ethnicity, sex, and age were not statistically significant.ConclusionsRectus abdominis myosteatosis is associated with worse processing speed in this middle and older aged multiethnic population of men and women, independent of other known predictors of cognition. Longitudinal studies should assess the interplay of myosteatosis with other markers of adiposity, inflammation, and circulating mediators and their combined impact on processing speed.HighlightsAbdominal myosteatosis correlated with lower cognitive processing speed in older adults.Myosteatosis links muscle density to cognitive function beyond dementia risk factors.Pro-inflammatory cytokines do not mediate the muscle-cognition association.Ethnicity, sex, and adiposity measures do not modify myosteatosis-cognition links.Abdominal CT scans could serve as diagnostic tools for cognitive health insights
Real-world datasets for the International Registry for Alzheimer’s Disease and Other Dementias (InRAD) and other registries: an international consensus
Authors: Perneczky Robert , Darby David , Frisoni Giovanni B. , Hyde Robert , Iwatsubo Takeshi , Mummery Catherine J. , Park Kee Hyung , van Beek Johan , van der Flier Wiesje M. , Jessen Frank 
Published: January 2025

ABSTRACTBACKGROUNDMany dementia and Alzheimer’s disease (AD) registries operate at local or national levels without standardization or comprehensive real-world data (RWD) collection. This initiative sought to achieve consensus among experts on priority outcomes and measures for clinical practice in caring for patients with symptomatic AD, particularly in the mild cognitive impairment and mild to moderate dementia stages.OBJECTIVEThe primary aim was to define a minimum dataset (MDS) and extended dataset (EDS) to collect RWD in the new International Registry for AD and Other Dementias (InRAD) and other AD registries. The MDS and EDS focus on informing routine clinical practice, covering relevant comorbidities and safety, and are designed to be easily integrated into existing data capture systems.METHODS AND RESULTSAn international steering committee (ISC) of AD clinician experts lead the initiative. The first drafts of the MDS and EDS were developed based on a previous global inter-societal Delphi consensus on outcome measures for AD. Based on the ISC discussions, a survey was devised and sent to a wider stakeholder group. The ISC discussed the survey results, resulting in a consensus MDS and EDS covering: patient profile and demographics; lifestyle and anthropometrics; co-morbidities and diagnostics; imaging; treatment; clinical characterization; safety; discontinuation; laboratory tests; patient and care partner outcomes; and interface functionality.CONCLUSIONBy learning from successful examples in other clinical areas, addressing current limitations, and proactively enhancing data quality and analytical rigor, the InRAD registry will be a foundation to contribute to improving patient care and outcomes in neurodegenerative diseases.
Extracellular stiffness regulates site-specific lung development
Authors: Liao Zhiying , Lv Junjie , Wang Dong , Chen Xuepeng , Zhao Jincun , Xu Tao , Meng Hao , Liu Huisheng 
Published: January 2025

AbstractExtracellular matrix (ECM) stiffness plays a crucial role in regulating cell fate and maturation, but its influence on lung development is limited known. Here we utilized stiffness-tunable gelatin methacryloyl (GelMA) hydrogels to investigate how ECM stiffness influences site-specific lung development in a stem cell-derived lung organoid model. We found increased stiffness promoted NKX2-1+ lung progenitor cells (LPCs) generation. In airway organoids (hAWOs), stiff hydrogels directed proximal airway differentiation enriched with goblet, ciliated, and basal cells; whereas the decreased stiffness favored emergence of secretory cells in the proximal-distal transition zone and distal airway. In alveolar organoids (hALOs), increased stiffness enhanced AT2 and AT1 cells transition. Moreover, infection assays with Omicron BA.1.1 and Delta variants recapitulated the proximal-to-distal tropism of SARS-CoV-2 in the lung. Transcriptomic sequencing revealed ECM stiffness regulates lung development via Hippo, TGF-β, HIF and Wnt pathways. These findings advance mechanism understanding of ECM stiffness on lung development and provide a novel mechanical regulation for generating site-specific lung organoids.
Employee personal hygiene, visible cleanliness and microbial contamination of beverages at coffee outlets in Busan: a pilot study
Authors: Choe Yunseon , Lee Seungjun , Yeo Sohyun , Choi Jinkyung 
Published: January 2025

PurposeThe study objective was to investigate the microbial status of the coffee, ice and cups used in coffee outlets. This study compared food safety practices and microbial status between franchised and single-unit outlets.Design/methodology/approachThe study subjects included franchised and single-unit coffee outlets. This study adopted two different methods: self-answered checklists and microbial laboratory tests. We compared the two datasets by operation type (franchised vs single-unit). We analysed the data using independent t-test and chi-square tests.FindingsFranchised outlets were more likely to apply food safety practices than single-unit outlets; however, microbial testing showed that franchised outlets had a worse microbial status than single-unit outlets. A restaurant sanitation certificate did not influence microbial status. In addition, an analysis of food safety practice checklist items and microbial status showed that the checklist items did not impact food safety.Originality/valueThese study results suggest that regular employee training programmes are needed for food safety and sanitation. Current inspection items should be revised and new items added for target operations (outlets that make and serve beverages). The current restaurant certification system should be revised, and certified food service outlets should be inspected regularly.
It’s not all fun and games: gamification in e-commerce on consumers’ impulse buying of retail food products
Authors: Lim Song-Yik , Tan Yiqi , Loh Xiu-Ming , Cham Tat-Huei , Ooi Mun-Yee , Tan Garry Wei-Han 
Published: January 2025

PurposeThis study aims to look into the role of gamification as an effective marketing tool to engage with consumers and influence purchase behaviours. As there are a plethora of gamified elements, it is crucial to determine which of them can significantly facilitate consumer purchase behaviour. Therefore, a unique stimulus–organism–response (SOR) framework which encompasses four popular gamified elements (i.e. fun, rewards, competition and badges) was employed to investigate consumers’ engagement.Design/methodology/approachAn online survey was utilized to collect the data which yielded 307 responses. Subsequently, partial least squares-structural equation modeling (PLS-SEM) was used to analyse the data.FindingsAmong the gamification elements assessed in this study, fun was revealed to be the strongest facilitating antecedent of shopping engagement. However, reward was revealed to have an insignificant effect on shopping engagement. In addition, it was found that consumers undergo a processual development with regard to their impulse buying of retail food products. More precisely, shopping engagement is a significant facilitator of customer satisfaction which subsequently motivates impulse buying.Originality/valueThis is among the pioneering studies to provide detailed insights into the effect of different gamified elements on consumer engagement. Furthermore, a number of practical and theoretical implications for the relevant stakeholders were discussed.
Fukushima twelve years after the nuclear accident
Authors: Kawasaki Kota 
Published: January 2025

PurposeThis paper analyzes the structure of recovery policies in Fukushima, discusses the current situation of the affected areas and the affected people of Fukushima 12 years after the Fukushima nuclear accident occurred and points out issues concerning revitalization of Fukushima based on the results of field surveys of the affected areas, as well as interviews and questionnaires of the affected people and literature reviews.Design/methodology/approachAfter the Fukushima nuclear accident occurred in March 2011, what policies have been implemented? To what extent have the affected areas of Fukushima been regenerated? To what extent have the affected people of Fukushima rebuilt their lives? What are the issues that need to be addressed for the revitalization of Fukushima? Since the Fukushima nuclear accident occurred, the author has continued to conduct field surveys of the affected areas, as well as interviews and questionnaires of the affected people, and literature review. This paper aims to answer three questions based on the results of these surveys and reviews.FindingsFirst, the nuclear disaster is characterized by its wide-area and long-term nature. Second, recovery of the affected areas by public projects do not have sufficient effect on rebuilding of the lives of the affected people since most of the affected people do not return to the affected areas. Third, it is necessary to establish a legal system for disaster prevention, recovery and revitalization suited to the characteristics of the nuclear disaster in order to promote rebuilding of the lives of the affected people and for the recovery of the affected areas.Originality/valueThere is little literature that has been systematically examined regarding the recovery from the Fukushima nuclear accident. This paper discusses the current status and issues of recovery from nuclear disaster 12 years after the nuclear accident, based on my experiences as the chairperson of the Fukushima Prefecture Recovery Planning Committee and the chairperson of the Recovery Planning Committee in several municipalities where evacuation orders were issued after the Fukushima nuclear accident occurred.
Adapting to change: redefining employee utilization in construction projects through lessons learnt from COVID-19
Authors: Arshad Muneeb , Sumbal Muhammad Saleem , Akhtar Muhammad Naseer , Nauman Shazia 
Published: January 2025

PurposeThe study aims to understand the challenges of effective employee utilization in construction projects during the coronavirus disease 2019 (COVID-19) pandemic in a developing country and to develop mitigation strategies for post-pandemic workforce management.Design/methodology/approachWe used a qualitative research design to conduct semi-structured interviews with elite informants of various construction firms and analyze the data using thematic analysis.FindingsThe results showed that numerous factors, including supply chain issues, inadequate worker healthcare, ineffective knowledge management and job losses, have negatively impacted the construction industry. The prominent outcomes of the study are a conceptual framework for effective workforce management post-pandemic and beyond, including recommendations for managers and executives and future research.Originality/valueThe workforce management framework with knowledge management developed in this study provides a new theoretical view of post-pandemic mitigation strategies through the theoretical lens of dynamics capabilities and knowledge management. The findings cover industrial insights, particularly from the stakeholders’ perspective, and provide a solid foundation for future research in this domain.