bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hippo Signaling Modulates the Inflammatory Response of Chondrocytes to Mechanical Compressive Loading
Authors: Cai Xiaomin , Warburton Christopher , Perez Olivia F. , Wang Ying , Ho Lucy , Finelli Christina , Ehlen Quinn T. , Wu Chenzhou , Rodriguez Carlos D. , Kaplan Lee , Best Thomas M. , Huang Chun-Yuh , Meng Zhipeng 
Published: June 2023

AbstractKnee osteoarthritis (KOA) is a degenerative disease resulting from mechanical overload, where direct physical impacts on chondrocytes play a crucial role in disease development by inducing inflammation and extracellular matrix degradation. However, the signaling cascades that sense these physical impacts and induce the pathogenic transcriptional programs of KOA remain to be defined, which hinders the identification of novel therapeutic approaches. Recent studies have implicated a crucial role of Hippo signaling in osteoarthritis. Since Hippo signaling senses mechanical cues, we aimed to determine its role in chondrocyte responses to mechanical overload. Here we show that mechanical loading induces the expression of inflammatory and matrix-degrading genes by activating the nuclear factor-kappaB (NFκB) pathway in a Hippo-dependent manner. Applying mechanical compressional force to 3-dimensional cultured chondrocytes activated NFκB and induced the expression of NFκB target genes for inflammation and matrix degradation (i.e., IL1β and ADAMTS4). Interestingly, deleting the Hippo pathway effector YAP or activating YAP by deleting core Hippo kinases LATS1/2 blocked the NFκB pathway activation induced by mechanical loading. Consistently, treatment with a LATS1/2 kinase inhibitor abolished the upregulation of IL1β and ADAMTS4 caused by mechanical loading. Mechanistically, mechanical loading activates Protein Kinase C (PKC), which activates NFκB p65 by phosphorylating its Serine 536. Furthermore, the mechano-activation of both PKC and NFκB p65 is blocked in LATS1/2 or YAP knockout cells, indicating that the Hippo pathway is required by this mechanoregulation. Additionally, the mechanical loading-induced phosphorylation of NFκB p65 at Ser536 is blocked by the LATS1/2 inhibitor Lats-In-1 or the PKC inhibitor AEB-071. Our study suggests that the interplay of the Hippo signaling and PKC controls NFκB-mediated inflammation and matrix degradation in response to mechanical loading. Chemical inhibitors targeting Hippo signaling or PKC can prevent the mechanoresponses of chondrocytes associated with inflammation and matrix degradation, providing a novel therapeutic strategy for KOA.
Prevalence of mild behavioral impairment among a Chinese cohort of elderly with mild cognitive impairment and subjective cognitive impairment
Authors: Pan Yining , Song You-qiang , Chu Leung wing , Shea Yat-fung 
Published: June 2023

IntroductionMild behavioural impairment (MBI) describes later-life onset of sustained and meaningful neuropsychiatric symptoms (NPS) of any degree of severity before the onset of dementia or even the onset of cognitive symptoms. To our knowledge, there was only one study conducted in China and it only included non-dementia patients but did not differentiate among the cognitive groups.MethodsA total of 88 subjects (28 cognitively normal, 15 subjective cognitive impairment, and 45 mild cognitive impairment) were recruited from Memory Clinic from 1st August 2020 through 16th Dec 2021. Inclusion criteria were that subjects should be of Chinese Han ethnicity. MBI was diagnosed according to the International Society to Advance Alzheimer’s Research and Treatment - Alzheimer’s Association (ISTAART-AA) criteria. MBI-checklist (MBI-C) score was either self-rated or informant-rated. NPI severity of 0 was defined as having a score of 0 for all Neuropsychiatric Inventory Questionnaire (NPI-Q) questions. NPI severity of 1 was given when the subject had a maximum score of 1-3. NPI severity of 2 referred to a subject having a score of four or over for at least one question. This cross-sectional study aimed to 1) calculate the prevalence of MBI among SCI/CN and MCI subjects in the Chinese population; 2) compare the performance of MBI-C and NPI-Q scales in MBI case ascertainment.ResultsOur results showed that the prevalence of MBI was 7% in CN/SCI group and 11.1% in MCI group assessed by MBI-C. The prevalence of NPS (severity >0) was 69% in CN/SCI group and 72.7% in MCI group assessed by NPI-Q. Spearman’s correlation test showed that the correlations of MBI and NPI severity were significant in overall subjects (correlation coefficient=0.3460, p=0.0011) and MCI group (correlation coefficient=0.3710, p=0.0131), and showing a trend of significance in CN/SCI group (correlation coefficient=0.3040, p=0.0503). However, Cohen’s kappa test showed that MBI-C and NPI-Q scale had only slight agreement in the overall and the both cognitive groups (overall: κ=0.0101; CN/SCI: κ=0.0667; MCI: κ=0.0917).ConclusionIn conclusion, prevalence of MBI is around 7-11% among CN/SCI and MCI subjects in the Chinese population. MBI-C and NPI-Q were different tools and the former should be relied on to detect MBI. Further studies should validate an optimal cut-off score on MBI-C for each cognitive group in the Chinese population.
Ablation ofMaxexpression induces meiotic onset in sexually undifferentiated germ cells
Authors: Suzuki Ayumu , Uranishi Kousuke , Nishimoto Masazumi , Mizuno Yosuke , Mizuno Seiya , Takahashi Satoru , Eisenman Robert N. , Okuda Akihiko 
Published: June 2023

AbstractMeiosis is a specialized type of cell division that occurs only in germ cells physiologically. We have previously demonstrated that MYC-associated factor X (MAX) is involved in blocking ectopic and precocious meiotic onsets in embryonic and germline stem cells, respectively, as a central component of the PRC1 subtype PRC1.6. In this study, we investigated the role of theMaxgene in germ cellsin vivo. Our data revealed that mitotically active germ cell-specific disruption ofMaxwas coupled to meiotic onset in male and female germ cells. However, suchMax-null germ cells did not undergo meiotic processes progressively, but were stalled at its relatively early stages and eventually eliminated by apoptosis. Our data also revealed thatMax, which is generally known as an obligate heterodimerization partner for MYC and MXD transcription factors, showed high expression in sexually undifferentiated male and female germ cells, but female germ cells exhibited an abrupt decline in its expression at the timing of or immediately prior to physiological meiotic onset. Moreover, computational analyses identified the regulatory region that supported high levels ofMaxexpression in sexually undifferentiated germ cells.
A single DPE core promoter motif contributes toin vivotranscriptional regulation and affects cardiac function
Authors: Sloutskin Anna , Itzhak Dekel , Vogler Georg , Ideses Diana , Alter Hadar , Shachar Hadar , Doniger Tirza , Frasch Manfred , Bodmer Rolf , Duttke Sascha H , Juven-Gershon Tamar 
Published: June 2023

AbstractTranscription is initiated at the core promoter, which confers specific functions depending on the unique combination of core promoter elements. The downstream core promoter element (DPE) is found in many genes related to heart and mesodermal development. However, the function of these core promoter elements has thus far been studied primarily in isolated,in vitroor reporter gene settings.tinman(tin) encodes a key transcription factor that regulates the formation of the dorsal musculature and heart. Pioneering a novel approach utilizing both CRISPR and nascent transcriptomics, we show that a substitution mutation of the functionaltinDPE motif within the natural context of the core promoter results in a massive perturbation of Tinman’s regulatory network orchestrating dorsal musculature and heart formation. Mutation of endogenoustinDPE reduced the expression oftinand distinct target genes, resulting in significantly reduced viability and an overall decrease in adult heart function. We demonstrate the feasibility and importance of characterizing DNA sequence elementsin vivoin their natural context, and accentuate the critical impact a single DPE motif has duringDrosophilaembryogenesis and functional heart formation.
Can elevated plasma Adiponectin and Ghrelin counteract inflammation in the aging heart?
Authors: Nahar Harsika , Chandan Shivanshu 
Published: June 2023

AbstractThe adaptability of the heart helps in sustaining its function under severe pressure overload conditions, including myocardial infarction and heart failure. Immune response and inflammatory changes are among the adaptive changes the heart relies on when challenged with stress or pressure stimuli. However, the immune system homeostasis declines with advancing age and increases the susceptibility to develop heart failure. Dissecting the inflammatory changes associated with age could develop novel rejuvenating therapies for an aging population. The older mice show tremendous cardiac adaptations with advancing age. However, how the old heart adapts and survives the chronic stress that increases with age are unclear. The potential involvement of inflammatory alterations in older heart has not been recognized previously.We performed a screen of genes and proteins from RNA-seq and proteome profiles for regulators of cardiac inflammation in the old heart. We identified several pro-inflammatory and anti-inflammatory factors that belong to several immune response pathways. The inflammatory mediator plasma leptin levels increase at 3 months and decrease in the 18 months older mice. We found that the activated inflammatory gene program is associated with reduced left ventricular ejection fraction and vice-versa in the old mice. We also observed that elevated plasma levels of adiponectin and ghrelin are associated with reduced inflammatory molecules, including leptin, in these animals. We speculate that the induction of adiponectin and ghrelin secretion and downregulation of leptin secretion appears to encounter the elevated inflammatory gene program observed in the aging heart.
Flexibility of learning in complex worlds
Authors: Leimar Olof , Quiñones Andrés E , Bshary Redouan 
Published: June 2023

AbstractLearning to adjust to changing environments is an important aspect of behavioral flexibility. Here we investigate the possible advantages of flexible learning rates in volatile environments, using learning simulations. We compare two established learning mechanisms, one with fixed learning rates and one with flexible rates that adjust to volatility. We study three types of ecological and experimental volatility: transitions from a simpler to a more complex foraging environment, reversal learning, and learning set formation. For transitions to a complex world, we use developing cleaner fish as an example, having more types of client fish to choose between as they become adult. There are other similar transitions in nature, such as migrating to a new and different habitat. Performance in reversal learning and in learning set formation are commonly used experimental measures of behavioral flexibility. Concerning transitions to a complex world, we show that both fixed and flexible learning rates perform well, losing only a small proportion of available rewards in the period after a transition, but flexible rates perform better than fixed. For reversal learning, flexible rates improve the performance with each successive reversal, because of increasing learning rates, but this does not happen for fixed rates. For learning set formation, we find no improvement in performance with successive shifts to new stimuli to discriminate for either flexible or fixed learning rates. Flexible learning rates might thus explain increasing performance in reversal learning, but not in learning set formation. We discuss our results in relation to current ideas about behavioral flexibility.
Stress and resilience in British Indian parents with an autistic child: a comparative study with white British and Indian parents
Authors: Stagg Steven , Kodakkadan Fathima , Rajan Santhosh Kareepadath 
Published: June 2023

Purpose
This study aims to examine the levels of stress and resilience in a sample of British Indian parents bringing up a child with autism.

Design/methodology/approach
A total of 52 British Indian parents took part in a survey that included measures of stress, resilience, support and child adaptive functioning. Results were compared to a sample of white British (n = 120) and Indian parents (n = 120).

Findings
The British Indian parents recorded higher levels of stress and less perceived social support than their white British counterparts. British Indian parents took longer to register concern about their child’s development and sought a diagnosis at a later age than the white British group. The delay in concern and diagnosis was similar to that found in the India group.

Originality/value
The research suggests that British Indian parents are disadvantaged in social support and mental well-being compared to white British parents and may face similar community pressures to parents bringing up a child in India.
A post-occupancy evaluation of in-house facilities management service quality and user satisfaction in multi-tenanted office buildings in Ghana
Authors: Tannor Oliver , Appau Williams Miller , Attakora-Amaniampong Elvis 
Published: June 2023

Purpose
The purpose of this study is to explore user satisfaction with in-house facility management (FM) services in multi-tenanted office buildings in Accra, Ghana using a post-occupancy evaluation (POE) approach.

Design/methodology/approach
The study assessed user satisfaction with FM service quality by using a POE of their perceptions about the attitude and courtesy of the FM personnel, the reliability of the FM services they provide, the responsiveness and the competence of the service providers. The study used walk-throughs and questionnaire surveys as the POE methods. One hundred and twenty-one users from 22 multi-tenanted office buildings, who have actively used the FM services for at least a year, were purposively sampled. The data was collected via a survey using a structured questionnaire. The data was analysed using descriptive statistics and principal component analysis in version 25 of statistical package for the social sciences.

Findings
The study revealed that users were dissatisfied with the quality of in-house FM services across all 15 services The results also showed that users’ satisfaction with the services is not affected by the differences in their age, gender, educational level, job role and number of years in the buildings. The results further demonstrated that the most critical factors that resulted in users’ dissatisfaction were electric facilities, building fabric maintenance, emergency coordination, waste management and the decoration of the buildings during festive seasons.

Originality/value
To the best of the authors’ knowledge, the present study based on POE to assess user satisfaction with FM services for multi-tenant office buildings has, presumably, not been tackled before in Ghana. The results of the study are very essential to the owners of the buildings and facility managers in decision-making concerning the delivery of FM services. Building industry-wise, the results demonstrate the need for in-house FM managers in multi-tenanted office buildings in Ghana to adopt FM service delivery methods that increase user satisfaction. The results also call for further research into user satisfaction with outsourced FM services in multi-tenanted office buildings and further research on the use of the in-house strategy on other types of buildings to ascertain whether the dissatisfaction with FM is due to other factors such as the choice of FM strategy, the property type etc.
Exploring online consumer reviews of customized apparel products
Authors: Shin Eonyou , Kincade Doris H. , Han Jinhee 
Published: June 2023

PurposeVirtual try-on (VTO) technology with three-dimensional (3D) body scanning in a mobile application is a relatively new technique for selling custom-fit apparel. VTO involves scanning and measuring one's body and visualizing the fit of a garment on a 3D avatar. The purpose of this study is to explore consumers' experiences toward the custom-fit T-shirts and online mass customization (MC) services using the VTO technology found in online consumer reviews (OCRs).Design/methodology/approachA total of 297 OCRs were collected from the Amazon's Made for You site that uses VTO technology for the MC process. A qualitative content analysis, within a mixed method research process, was used to determine systematically the meanings within qualitative data with quantitative results. In the qualitative approach, combinations of two coding processes were employed, which were concept-driven (i.e., deductive/a priori) and data-driven (i.e., inductive/emergent) coding processes. In the quantitative approach, the prevalence of each coding in terms of its valence was calculated based on frequencies. Intercoder reliability reached 96 per cent.FindingsIn OCRs of customized apparel products and online MC services using VTO technology, consumers described expectations, perceived performance, dis/confirmation, dis/satisfaction, outcomes of dis/satisfaction and descriptive information. Those with expectations often expressed skepticism about the product and the MC process using VTO technology at the pre-consumption stage. In OCRs, they used four product dimensions and two service dimensions of perceived performance. Consumers had positive (negative) confirmation when the performance of the T-shirts and/or services worked better (worse) than their expectations. The OCRs also included dis/satisfaction with a product and/or service, its outcomes and descriptive information.Originality/valueThis study identified a resulting framework to identify the content in OCRs of the custom-fit T-shirts and online MC services that use VTO technology. This study extends the expectation confirmation theory by adding multiple dimensions (i.e., four product dimensions and two service dimensions) as well as more outcomes of dis/satisfaction (not limited to repurchase intentions). This study provides practical suggestions for online MC companies who are using or planning to use VTO technology on how to improve consumers' satisfaction with customized T-shirts using VTO technology.
Digitalization capability and sustainable performance in emerging markets: mediating roles of in/out-bound open innovation and coopetition strategy
Authors: Lee Min-Jae , Roh Taewoo 
Published: June 2023

PurposeStudies concentrating on digitalization and interconnected capabilities have increased over the past several decades. Digitalization capability and open innovation are perceived as sources of sustained competitiveness across disciplines. This study investigated how digitalization capability and coopetition strategy affect the sustainable performance of firms by exploring the role of internal and external factors in influencing the adoption and success of open innovation in emerging markets.Design/methodology/approachTo test the hypothesis, the authors conducted a structural equation model analysis on 509 firm datasets from the hub cities in China, an innovative battlefield where multilateral cooperation and competition are interwoven for globalization, clean development and the enhancement of economic growth.FindingsThe authors found that a firm's digitalization capability positively impacts outbound/inbound open innovation, coopetition strategy and sustainable performance. This study’s results support a series of mediating effects through outbound/inbound open innovation and coopetition strategy. Also, it provides a nuanced understanding of how digitalization capability and open innovation can affect sustainable performance in emerging markets.Originality/valueThe present study provides a nuanced understanding of how digitalization capability and in/out-bound open innovation can affect sustainable performance in emerging markets. The authors believe this model contributes to current knowledge by filling several research gaps, and this study’s findings offer valuable and practical implications for achieving open innovation and creating sustainable performance.
The effects of the (fentanyl‐fueled) drug overdose epidemic on medicolegal death investigation in the United States
Authors: Davis Gregory G. , Fligner Corinne L. 
Published: June 2023

AbstractThe evolving opioid epidemic in the United States, fueled by illicit fentanyl, has greatly increased deaths from illicit drug use. These nonnatural deaths require formal death investigation. The National Association of Medical Examiners states in its Forensic Autopsy Performance Standards that autopsy remains a necessary component for proper investigation of suspected acute overdose deaths. If a death investigation office lacks adequate resources to investigate all deaths under its jurisdiction while meeting expected standards, then that office may be forced to consider altering its protocols for investigation by changing the types of deaths investigated or the extent of its investigations. Drug death investigations take longer to complete because novel illicit drugs and mixtures of drugs complicate toxicological analyses, prolonging a family's wait for completion of a death certificate and autopsy report. Public health agencies must also wait for results, but some agencies have developed mechanisms for rapid notification of preliminary results to allow timely deployment of public health resources. The increased deaths have strained the resources of medicolegal death investigation systems throughout the United States. Given the significant workforce shortage of forensic pathologists, newly trained forensic pathologists are too few to meet the demand. Nevertheless, forensic pathologists (and all pathologists) must make time to present their work and themselves to medical students and pathology trainees to encourage an understanding of the importance of quality medicolegal death investigation and autopsy pathology and to provide a model that can encourage interest in a career in forensic pathology.
Does preoperative imaging for scalp non‐melanocytic skin cancer accurately predict invasion of the cranial vault? A systematic review and meta‐analysis
Authors: Rowse Benjamin M. , Yu Ann C. X. , Faulkner Harrison , Sandler Gideon , Howle Julie R. , Ch'ng Sydney , Rao Prashanth J. , Varey Alexander H. R. 
Published: June 2023

AbstractPurposeThis study aimed to determine the diagnostic accuracy of CT and MRI in the preoperative detection of bone involvement for non‐melanoma skin cancers (NMSCs) located on the scalp. This study further aimed to evaluate the predictive value of these imaging modalities in determining the need for craniectomy and to identify gaps in the existing literature.MethodsElectronic searches of the MEDLINE, Embase, Cochrane and Google Scholar databases were performed for English language studies of any type. Studies reporting detection or exclusion of histopathologically confirmed bone involvement through preoperative imaging were identified according to PRISMA guidelines. Studies reporting dural involvement, non‐scalp tumours, and lacking tumour type(s) or outcome data were excluded. Outcomes were preoperative imaging result and histopathologically confirmed bone invasion. Meta‐analysis was performed and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated (excluding case report and MRI data due to insufficient quality and quantity respectively).ResultsFour studies with a total of 69 patients were included in the final review, of which two studies totalling 66 patients were included in the meta‐analysis. Preoperative CT had a sensitivity of 38%, specificity of 98%, PPV of 90% and NPV of 73%.ConclusionsThe available data suggests that a preoperative CT finding of calvarial involvement by a scalp NMSC is likely to be real, but the absence of such a finding is unreliable. Current evidence suggests that preoperative imaging cannot exclude the necessity for craniectomy and future research is needed, particularly on the role of MRI.