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The interface between soft and hard tissues is constituted by a gradient change of cell types and matrix compositions that are optimally designed for proper load transmission and injury protection. In the musculoskeletal system, the soft-hard tissue interfaces at tendon-bone, ligament-bone, and meniscus-bone have been extensively researched as regenerative targets. Similarly, extensive research efforts have been made to guide the regeneration of multi-tissue complexes in periodontium. However, the other soft-hard tissue interfaces in the dental and craniofacial system have been somewhat neglected. This review discusses the clinical significance of developing regenerative strategies for soft-hard tissue interfaces in the dental and craniofacial system. It also discusses the research progress in the field focused on bioengineering approaches using 3D scaffolds equipped with spatially controlled bioactivities. The remaining challenges, future perspectives, and considerations for the clinical translation of bioactive scaffolds are also discussed. [Display omitted] •This review provides an overview of the research progress in regenerating soft-hard tissue interfaces.•This review also discusses the research outcomes, advantages, and limitations of various bioactive scaffolds.•It also discusses perspectives for future research directions in consideration of the remaining challenges.

Studies in Saccharomyces cerevisiae show that many proteins influence cellular survival upon exposure to DNA damaging agents. We hypothesized that human orthologs of these S. cerevisiae proteins would also be required for cellular survival after treatment with DNA damaging agents. For this purpose, human homologs of S. cerevisiae proteins were identified and mapped onto the human protein-protein interaction network. The resulting human network was highly modular and a series of selection rules were implemented to identify 45 candidates for human toxicity-modulating proteins. The corresponding transcripts were targeted by RNA interference in human cells. The cell lines with depleted target expression were challenged with three DNA damaging agents: the alkylating agents MMS and 4-NQO, and the oxidizing agent t-BuOOH. A comparison of the survival revealed that the majority (74%) of proteins conferred either sensitivity or resistance. The identified human toxicity-modulating proteins represent a variety of biological functions: autophagy, chromatin modifications, RNA and protein metabolism, and telomere maintenance. Further studies revealed that MMS-induced autophagy increase the survival of cells treated with DNA damaging agents. In summary, we show that damage recovery proteins in humans can be identified through homology to S. cerevisiae and that many of the same pathways are represented among the toxicity modulators.

Purpose This paper aims to explore the effect of employees’ state mindfulness, a short period of mindful presence, on the quality of the service they provide in a service encounter. Design/methodology/approach Three studies are conducted. A pilot study explores the relationship between state mindfulness and service encounter quality. Experiment 1 examines whether a 15-min mindfulness exercise results in an increase in service employees’ state mindfulness. Experiment 2 tests whether induced state mindfulness produces higher service quality and whether a reminding technique can prolong state mindfulness between service encounters. Findings The results demonstrate the following. First, that more mindful employees provide better service quality. Second, that a short, easily implemented, mindfulness exercise can reliably increase employees’ state mindfulness. Third, induced mindfulness has an impact on subsequent service quality in terms of reliability, assurance, empathy and responsiveness. These effects persist regardless of the service encounter structure (high vs low structure) or the degree of emotional labor involved (high vs low emotionally charged). Finally, the reminding technique developed as part of this research suggests that state mindfulness can be maintained between service encounters. Research limitations/implications As simulated (programmed) customers are used, independent evaluators to assess service quality are used. Service providers in this study are college students; future field studies should consider a wider range of service providers. The research focuses on state mindfulness; exploration of trait mindfulness offers future research opportunities. Originality/value To the best of the authors’ knowledge, this research is the first to empirically examine the link between mindfulness and service quality. It shows that mindfulness can be induced, and through a reminding technique be maintained, and improve service quality across service interactions. This is a powerful finding for marketing managers, for it offers a new method to enhance service provision. Moreover, this research implies that the increase in service quality is likely to be accompanied by reduced job burnout: a double win for employees, employers and customers.

Alzheimer's disease (AD) is hallmarked by amyloid-β (Aβ) plaques and hyperphosphorylated tau (p-tau) neurofibrillary tangles. While Aβ-centric therapies have shown promise, the complex pathology of AD requires a multifaceted therapeutic approach. The weak association between Aβ levels and cognitive decline highlights the need for alternative theranostic strategies. Currently, oxidative stress and tau hyperphosphorylation are now recognized as critical pathological events in AD. Thus, therapies that concurrently attenuate oxidative stress damage and inhibit tau pathology hold great potential for AD treatment. Herein, a multifunctional neuron-targeted nanocomposite is devised to realize dual imaging-guided AD therapy, integrating the inhibition of tau pathology and reactive oxygen species (ROS)-neutralizing biofunctions. The construction of the nanocomposite incorporates polyphenolic antioxidants tannic acid (TA)-based nanoparticles carrying manganese ions (Mn ) and fluorescent dye IR780 iodide (IR780), coupled with a neuron-specific TPL peptide. The resulting IR780-Mn@TA-TPL nanoparticles (NPs) are comprehensively evaluated in both and AD models to assess their imaging capabilities and therapeutic efficacy. The nanocomposite facilitates Mn-enhanced magnetic resonance (MR) imaging and near-infrared (NIR) fluorescence imaging. It effectively neutralizes toxic ROS and reduces tau hyperphosphorylation and aggregation. In AD rat models, the nanocomposite restores neuronal density in the hippocampus and significantly improves spatial memory. Such a neuron‑targeting multifunctional nanocomposite represents a potential theranostic strategy for AD, signifying a shift towards bimodal imaging-guided treatment approaches.

This dissertation examines whether the issuers of high-quality green bonds differentiate themselves by bonding with two reputable organizations that impose high green bond transparency standards -- the Climate Bonds Initiative (CBI) and the Luxembourg Green Exchange (LGX), and whether the bonding mechanism effectively mitigates investors' greenwashing concerns. I document evidence that is consistent with a separating equilibrium. Specifically, I find that the bonding issuers (i.e., issuers that obtain CBI certifications for their green bonds or list their green bonds on LGX) demonstrate higher post-issuance transparency and a larger reduction in carbon emissions while also receiving a larger green premium than the non-bonding issuers. Further analyses document differences between the CBI and LGX regimes. The CBI regime, which requires certification against a green taxonomy but allows for private communication, is more effective at screening issuers that achieve larger carbon reduction, whereas the LGX regime, which accepts broad categories of green projects but requires public disclosure on a centralized platform, is more effective at screening issuers that provide higher post-issuance transparency. Interestingly, only the LGX-listed green bonds receive a significant green premium. Moreover, green premium is more concentrated in the LGX-listed green bonds with high ex-ante transparency commitment. Furthermore, in the secondary market, green bonds from issuers that end up providing high post-issuance transparency tend to have higher liquidity. The CBI-certified or LGX-listed green bonds with high post-issuance transparency tend to have even larger liquidity benefits. Taken together, consistent with prior survey evidence in Chiang (2017) and Sangiorgi and Schopohl (2021), the findings in this dissertation corroborate that high post-issuance transparency may effectively mitigate investors’ greenwashing concerns, facilitate low-cost environmental financing, and bolster market liquidity.

This article utilizes option markets to determine the information content of dividend-initiation announcements. Pre-event informed options trading, measured by abnormal implied volatility spread and skew, predicts the cumulative abnormal returns around dividend-initiation announcements. Options trading is more informative on dividend-initiation announcement returns when the options market is more liquid, the underlying stock market is less informed, and the dividend initiations are of a greater surprise to the market. The results are robust to a randomization test and support the conclusion that pre-event options trading contains information about the market reaction to dividend-initiation announcements. TOPICS: Derivatives, options, legal/regulatory/public policy, information providers/credit ratings Key Findings • The information content of options trading is stronger when the options market is more liquid relative to the underlying stock market. • The information content of options trading is higher when the dividend-initiating firms have relatively lower pre-initiation cash flows. • The predictive power of informed options trading is weaker when the underlying stock market is subject to more-informed trading.

The progressive nature of Parkinson’s disease, its complex treatment regimens and the high rates of comorbid conditions make self-management and treatment adherence a challenge. Clinicians have limited face-to-face consultation time with Parkinson’s disease patients, making it difficult to comprehensively address non-adherence. Here we share the results from a multi-centre (seven centres) randomised controlled trial conducted in England and Scotland to assess the impact of using a smartphone-based Parkinson’s tracker app to promote patient self-management, enhance treatment adherence and quality of clinical consultation. Eligible Parkinson’s disease patients were randomised using a 1:1 ratio according to a computer-generated random sequence, stratified by centre and using blocks of variable size, to intervention Parkinson’s Tracker App or control (Treatment as Usual). Primary outcome was the self-reported score of adherence to treatment (Morisky medication adherence scale −8) at 16 weeks. Secondary outcomes were Quality of Life (Parkinson’s disease questionnaire −39), quality of consultation for Parkinson’s disease patients ( Patient-centred questionnaire for Parkinson’s disease ), impact on non-motor symptoms (Non-motor symptoms questionnaire), depression and anxiety (Hospital anxiety and depression scale) and beliefs about medication (Beliefs about Medication Questionnaire) at 16 weeks. Primary and secondary endpoints were analysed using a generalised linear model with treatment as the fixed effect and baseline measurement as the covariate. 158 patients completed the study (Parkinson’s tracker app = 68 and TAU = 90). At 16 weeks Parkinson’s tracker app significantly improved adherence, compared to treatment as usual (mean difference: 0.39, 95%CI 0.04–0.74; p  = 0.0304) with no confounding effects of gender, number of comorbidities and age. Among secondary outcomes, Parkinson’s tracker app significantly improved patients’ perception of quality of consultation (0.15, 95% CI 0.03 to 0.27; p  = 0.0110). The change in non-motor symptoms was −0.82 (95% CI −1.75 to 0.10; p  = 0.0822). 72% of participants in the Parkinson’s tracker app group continued to use and engage with the application throughout the 16-week trial period. The Parkinson’s tracker app can be an effective and novel way of enhancing self-reported medication adherence and quality of clinical consultation by supporting self-management in Parkinson’s disease in patients owning smartphones. Further work is recommended to determine whether the benefits of the intervention are maintained beyond the 16 week study period. Digital healthcare: App helps patients stick to plan A smartphone-based application improves treatment adherence of patients with Parkinson’s disease (PD). Rashmi Lakshminarayana, from uMotif Ltd, and researchers from the UK and The Netherlands describe the results of a 16 week trial of a Parkinson’s tracker app (PTA) that randomised 215 patients from seven different health centres. Patients using the app reported significantly better adherence to their medication plan compared with control patients who continued their treatment as usual. Interestingly, using the PTA also improved the patients’ perception of the quality of their clinical care, possibly as a result of feeling more involved and in control of their care. These findings suggest that by sending medication reminders and tracking symptoms, the app can help patients with Parkinson’s self-manage their increasingly complex treatment regimen as the disease progresses.

Intra- and interspecific resource competition are potentially important factors affecting host plant use by phytophagous insects. In particular, escape from competitors could mediate a successful host shift by compensating for decreased feeding performance on a new plant. Here, it examined the question of host plant-dependent competition for apple (Malus pumila)- and hawthorn (Crataegus mollis)-infesting larvae of the apple maggot fly, Rhagoletis pomonella (Diptera: Tephritidae) at a field site near Grant, Michigan, USA. Interspecific competition from tortricid (Cydia pomonella, Grapholita prunivora, and Grapholita packardi) and agonoxenid (subfamily Blastodacninae) caterpillars and a curculionid weevil (Conotrachelus crataegi) was much stronger for R. pomonella larvae infesting the ancestral host hawthorn than the derived host apple. Egg to pupal survivorship was estimated as 52.8% for fly larvae infesting hawthorn fruit without caterpillars and weevils compared to only 27.3% for larvae in harthorns with interspecific insects. Survivorship was essentially the same between fly larvae infesting apples in the presence (44.8%) or absence (42.6%) of interspecific insects. Intraspecific competition among maggots was also stronger in hawthorns than apples. The order or time that a larva exited a hawthorn fruit was a significant determinant of its pupal mass, with earlier emerging larvae being heavier than later emerging larvae. This was not the case for larvae in apples, as the order or time that a larva exited an apple fruit had relatively little influence on its pupal mass.

•We assess influenza-related economic burden among managed care population.•Influenza seasons with matched or mismatched circulating and vaccine influenza B strain lineages considered.•Medical costs and productivity losses compared between matched and mismatched seasons.•Influenza-related direct and indirect costs higher during the mismatched seasons. To assess and compare direct medical costs (incurred by payers) and indirect productivity losses (incurred by employers) associated with influenza seasons with matched or mismatched circulating and vaccine containing influenza B lineages. A retrospective analysis, using two MarketScan databases, for the years 2000–2009. Each influenza season was categorized as matched or mismatched after comparing that season's circulating influenza B lineage and the vaccine influenza B lineage. Patients selected had at least one diagnosis claim for influenza (ICD-9-CM code 487.xx [influenza] or 488.1 [H1N1]) during an influenza season. We assessed the incidence of influenza (overall and influenza B), influenza-related medical utilization and associated costs, and productivity losses for each season. The four matched seasons had lower average influenza incidence (overall incidence per 100,000 plan members: 509; 95% confidence interval [CI]: 505–512) than the five mismatched seasons (748; 95% CI: 745–751). The mismatched seasons had lower influenza B incidence (average incidence per 100,000 plan members: 126; 95% CI: 125–128) than the matched seasons (165; 95% CI: 163–167). The average, per-patient, total influenza-related medical costs in the mismatched seasons ($300.83; range: $245.38–$371.58) were approximately $61.00 higher than in the matched seasons ($239.43; range: $201.49–$264.01). The mismatched seasons had greater average per-patient, influenza-related productivity-loss costs than the matched seasons (mean: $237.31 vs. $175.10). CDC data showed that influenza A was the predominant circulating strain during seasons in which the circulating influenza B lineage did not match the vaccine influenza B lineage. This resulted in lower influenza B incidence during the mismatched seasons. However, the average, per-patient, influenza-related direct medical costs and indirect productivity losses were higher during the mismatched seasons. Additional research is required to determine if these higher costs can be attributed to influenza B infections and if the influenza severity varies during mismatched seasons

Protein tyrosine phosphatases (PTPs) are key signaling enzymes with essential functions in health and disease development, but they are difficult to be selectively targeted via inhibitors due to their similarities of active-site structures and mechanisms, and their versatility. To provide an alternative solution to the problem, this thesis focuses on protein tyrosine phosphatase 1B from the PTP family and delves into the allosteric network and its role in substrate specificity by elucidating the kinetic, structural, and dynamical underpinnings of its allosteric regulation. Kinetic experiments – both steady-state and transient, with para-nitrophenol phosphate and various phosphorylated peptides, reveals how allosteric mutations in previously identified distal sites affect the catalytic efficiencies of PTP1B. NMR approaches, including chemical shift perturbations and relaxation dispersion, identify the regions experiencing changes of structures and dynamics in the apo and ligand-bound enzymes. Molecular dynamics simulation provides atomic level visualization of interactions between amino acid residues and the measurement of temporal atomistic fluctuations. This thesis proposes the communication among helices α1’, α2’, α3, α6, and α7 and the P- and E-loop contribute to ligand preference.