Search

PurposeThis study aims at investigating the effects of two-way review system and how reach and richness of information influence the perceptions of risks and benefits among service providers and their intention to continue sharing their property on sharing economy.Design/methodology/approachTo generate the variance, a 2 × 2 × 2 full factorial experiment was conducted to collect data. The research model was then tested using the structural equation model technique.FindingsThe study finds that reach of information predicts the social and economic benefits among service providers, while richness of information negatively relates to perceived informational privacy risks, which, in turn, significantly influence the decision of the service providers to continue sharing. The results also suggest that the existence of the two-way review system weakens the effects of reach on perceived social benefits and of richness on perceived informational privacy risks.Originality/valueThe present study investigates the two-way review system as the intervention of platforms to protect the service providers. Also, the emphasis is on the service providers rather than on consumers on sharing economy platforms to investigate their behavioral intention as customers on such platforms.

There are numerous opportunities for antimicrobial stewardship programs (ASPs) to utilize technology to maximize their impact on patient care. Herein we describe different technology platforms, strengths and limitations of each, and provide some examples of their use in clinical settings. Electronic medical record (EMR) upgrades and clinical decision support tools can enhance existing stewardship functions such as audit and feedback, de-escalation, “time-outs” among others. Antimicrobial utilization and resistance data reporting enables a deeper understanding of local trends in the context of benchmarked national data. User-friendly smartphone apps are prescriber-oriented platforms which house stewardship guidelines, antibiograms, and other information which can potentially reach thousands of prescribers. Finally, harnessing social media platforms can increase the visibility of stewardship and infection prevention research. There are multiple options for consuming stewardship technology, from free social media and online resources to costly EMR upgrades and clinical decision support tools. There are multiple benefits to incorporating technology into daily stewardship operations, but costs, design, and implementation challenges must be considered. Stewardship programs should evaluate the strengths and limitations of each type of technology to understand which will best suit their needs and goals.

The Nation’s Report Card reveals that lower performing students exhibited greater achievement decline than their average/high performing peers based on 2022 long-term trend mathematics assessments for age 9 students. Technology including computer-assisted instruction plays an important role in today’s dynamic learning environments. Currently, there is a lack of computer-assisted intervention programs that systematically teach generalized word problem-solving skills that is driven by mathematical models. Model-based problem solving (MBPS) is one of the essential emphases in the Common Core mathematical practice standards. This study investigated the effects of a web-based computer tutor, MBPS, on enhancing word problem-solving performance of elementary students who are struggling in mathematics. The MBPS tutor incorporates best practices that are identified by the Institute of Educational Sciences’ (IES) latest practice guide including providing systematic instruction, visual and verbal supports, and teaching of precise mathematical language. Findings indicate that the MBPS tutor boosted participants’ performance above and beyond the business-as-usual comparison group.

The microbiota generates diverse metabolites that can engage multiple pathways to modulate host physiology and disease, but their protein targets and mechanism(s) of action have not been fully elucidated. To address this challenge, we focused on indole-3-acetic acid (IAA), a prominent microbiota metabolite, and developed IAA-based chemical reporters for proteomic studies. We discovered that IAA interacts with many proteins in host cells, including small-molecule transporters, receptors and metabolic enzymes. Notably, our functional studies revealed that IAA binds to orphan G protein-coupled receptors such as GPRC5A, but only aromatic monoamines were capable of inducing GPRC5A signaling. Functional profiling of microbiota uncovered specific bacterial species and enzymes that generate GPRC5A agonists. Finally, biochemical characterization of GPRC5A activation identified more potent synthetic agonists as well as key amino acid residues involved in ligand binding. These studies highlight the utility of chemoproteomics to dissect protein targets and mechanisms of action for microbiota metabolites.

BACKGROUND Medulloblastoma (MB) is the most common pediatric brain tumor. MB can be dividing into 4 genetically distinct subgroups (Sonic Hedgehog (SHH), Wingless (WNT), Group 3, and Group 4). Most patients receive radiation and cisplatin backbone therapy. SHH and Group3 patients demonstrate poor prognosis, especially in cases of MYC amplification or p53 mutation. Given the continued reliance on DNA damage therapies, and our groups previous findings that YB1 regulates IGF2 transcription in SHH MB, we chose to investigate the role of YB1 in the DNA damage response and we performed RIPseq to understand mRNAs regulated by YB1 that may be targeted as novel therapeutics. METHODS Cell lines include primary MBCs derived from NeuroD2-SmoA1 SHH mice, ONS-76 human SHH, Daoy human SHH, D341 and D425 Human Group 3. YB1 overexpression or knockdown followed by radiation and assessment of yH2AX (a marker of DNA de-condensation following damage), Comet assay (a marker of physical damage), and proliferation time courses were used to assess effects of YB1 modulation on radiation response. RIPseq and YB1 knockdown were used to assess the effects of YB1 on PLXND1 levels. Scratch assay and western blotting of EMT markers were used to assess effects of PLXND1 silencing on migration. RESULTS (Radiation Studies) Overexpression of YB1 in primary MBCs followed by allograft into BL6 mice results in decreased overall survival. YB1 silencing followed by radiation results in faster resolution of yH2AX, faster resolution of damage, and lack of pRPA32 accumulation. YB1 silencing sensitizes cells to radiation resulting in substantial decreases in proliferation. (RNA Binding Protein Studies) YB1 binds and positively regulates PLXND1 translation. Silencing PLXND1 results in decreased migration and EMT mark expression. CONCLUSIONS YB1 drives a more error prone non-homologous End-Joining based mechanism of repair and binds and regulates PLXND1 post-transcriptionally. PLXND1 drives a migratory phenotype in SHH MB.

INTRODUCTION AND OBJECTIVE:Ideal length of neoadjuvant chemotherapy (NAC) before cystectomy for muscle-invasive bladder cancer (MIBC) is uncertain. Trials initially studied 3 cycles, but 4 cycles a...

Enterococcus faecium is a ubiquitous Gram-positive bacterium that has been recovered from the environment, food, and microbiota of mammals. Commensal strains of E. faecium can confer beneficial effects on host physiology and immunity, but antibiotic usage has afforded antibiotic-resistant and pathogenic isolates from livestock and humans. However, the dissection of E. faecium functions and mechanisms has been restricted by inefficient gene-editing methods. To address these limitations, here, we report that the expression of E. faecium RecT recombinase significantly improves the efficiency of recombineering technologies in both commensal and antibiotic-resistant strains of E. faecium and other Enterococcus species such as E. durans and E. hirae. Notably, the expression of RecT in combination with clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 and guide RNAs (gRNAs) enabled highly efficient scarless single-stranded DNA recombineering to generate specific gene-editing mutants in E. faecium. Moreover, we demonstrate that E. faecium RecT expression facilitated chromosomal insertions of double-stranded DNA templates encoding antibiotic-selectable markers to generate gene deletion mutants. As a further proof of principle, we use CRISPR-Cas9-mediated recombineering to knock out both sortase A genes in E. faecium for downstream functional characterization. The general RecT-mediated recombineering methods described here should significantly enhance genetic studies of E. faecium and other closely related species for functional and mechanistic studies. IMPORTANCE Enterococcus faecium is widely recognized as an emerging public health threat with the rise of drug resistance and nosocomial infections. Nevertheless, commensal Enterococcus strains possess beneficial health functions in mammals to upregulate host immunity and prevent microbial infections. This functional dichotomy of Enterococcus species and strains highlights the need for in-depth studies to discover and characterize the genetic components underlying its diverse activities. However, current genetic engineering methods in E. faecium still require passive homologous recombination from plasmid DNA. This involves the successful cloning of multiple homologous fragments into a plasmid, introducing the plasmid into E. faecium, and screening for double-crossover events that can collectively take up to multiple weeks to perform. To alleviate these challenges, we show that RecT recombinase enables the rapid and efficient integration of mutagenic DNA templates to generate substitutions, deletions, and insertions in the genomic DNA of E. faecium. These improved recombineering methods should facilitate functional and mechanistic studies of Enterococcus.

Postmastectomy pain syndrome (PMPS) or breast conservation surgery (BCS) pain syndrome could be long-term and lead to disability and impairment on body and social function. The pain syndromes are not uncommon in breast cancer patients. It can affect social, psychological, physical and behavioral aspects of a patient. Surgery, radiation, chemotherapy and psychological factors can all contribute to the development of pain syndromes. Axillary dissection is a strong predictor for pain development. Pain medications, ganglion blocks are typically given to the patient for management. Integrative medicine such as acupuncture and psychological management methods are promising modalities in the management arsenal. In this study, we summarized the up-to-date literature to elucidate the etiology, risk factors and management strategies for PMPS.

There is currently a lack of level 1 evidence regarding the relative efficacy of radical prostatectomy compared with radiotherapy combined with androgen deprivation therapy for high-risk prostate cancer. There has recently been an improved optimization of treatment, achieving superior biochemical outcomes and cancer-specific mortality through the use of combined modality therapy strategies. Combined modality therapies have also increasingly incorporated brachytherapy boost. Although available observational data must be interpreted with caution because of the effects of potential residual confounding, we present here a narrative review of recent advances in understanding the relative efficacy of the principal combined modality approaches for treating high-risk prostate cancer. As the trend has demonstrated approaching equivalence between well-selected combined modality therapies, an increasing emphasis should be placed on selecting therapy tailored toward a patient's goals regarding quality of life. We present here an outline of efforts to date to understand the implications of treatment on functional outcomes and quality-of-life endpoints.

Purpose Recent technological advances have led to the growing popularity of traffic-related social media platforms which facilitate drivers to easily share, consume and exchange traffic information instead of the traditional ways using TV or radio. By integrating the information systems success model, social capital theory and dedication-based commitment mechanism, the purpose of this paper is to examine the varying degree of effectiveness in maintaining user’s continuance intention between two different social media platforms for traffic information. Design/methodology/approach The data were collected through online questionnaires from two platforms. One is a multi-channel traffic information community that has been specialized in traffic information for many years and has adopted several kinds of social media to engage with its audience. The other is a community-based traffic application created to help people exchange and contribute traffic information with real-time navigation. Findings The findings show that the effects of satisfaction and affective commitment on continuance intention are stronger in the community-based traffic application while their antecedents play different roles in shaping satisfaction and affective commitment due to the nature and characteristics of these two groups. Originality/value This study will be the first attempt to understand what matters to users and what can retain users to routinely use a specific traffic-related social media platform in their daily lives. This is also one of the first empirical studies that examine both transactional and relational points of view on users’ continuance intention.

(2019). How smell can help visually impaired in health and well-being – a cognitive experiment. The Design Journal: Vol. 22, Running with Scissors: 13th International Conference of the European Academy of Design, Dundee, 10-12th April, 2019, edited by Louise Valentine, Joanna Bletcher and Leon Cruickshank, pp. 371-386.

(2019). Improving Design Software Based On Fuzzy Kano Model: A Case Study of Virtual Reality Interior Design Software. The Design Journal: Vol. 22, Running with Scissors: 13th International Conference of the European Academy of Design, Dundee, 10-12th April, 2019, edited by Louise Valentine, Joanna Bletcher and Leon Cruickshank, pp. 1983-1992.

(2019). Collaborative governance in the sharing economy. A case of free-floating bicycle sharing with visualized analyzation. The Design Journal: Vol. 22, Running with Scissors: 13th International Conference of the European Academy of Design, Dundee, 10-12th April, 2019, edited by Louise Valentine, Joanna Bletcher and Leon Cruickshank, pp. 777-788.

(2019). Design Thinking Driven Interdisciplinary Entrepreneurship. A Case Study of College Students Business Plan Competition. The Design Journal: Vol. 22, Running with Scissors: 13th International Conference of the European Academy of Design, Dundee, 10-12th April, 2019, edited by Louise Valentine, Joanna Bletcher and Leon Cruickshank, pp. 99-110.

Enterococcus faecium is a ubiquitous Gram-positive bacterium that has been recovered from the environment, food, and microbiota of mammals. Commensal strains of E. faecium can confer beneficial effects on host physiology and immunity, but antibiotic usage has afforded antibiotic-resistant and pathogenic isolates from livestock and humans. However, the dissection of E. faecium functions and mechanisms has been restricted by inefficient gene-editing methods. To address these limitations, here, we report that the expression of E. faecium RecT recombinase significantly improves the efficiency of recombineering technologies in both commensal and antibiotic-resistant strains of E. faecium and other Enterococcus species such as E. durans and E. hirae. Notably, the expression of RecT in combination with clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 and guide RNAs (gRNAs) enabled highly efficient scarless single-stranded DNA recombineering to generate specific gene-editing mutants in E. faecium. Moreover, we demonstrate that E. faecium RecT expression facilitated chromosomal insertions of double-stranded DNA templates encoding antibiotic-selectable markers to generate gene deletion mutants. As a further proof of principle, we use CRISPR-Cas9-mediated recombineering to knock out both sortase A genes in E. faecium for downstream functional characterization. The general RecT-mediated recombineering methods described here should significantly enhance genetic studies of E. faecium and other closely related species for functional and mechanistic studies. IMPORTANCEEnterococcus faecium is widely recognized as an emerging public health threat with the rise of drug resistance and nosocomial infections. Nevertheless, commensal Enterococcus strains possess beneficial health functions in mammals to upregulate host immunity and prevent microbial infections. This functional dichotomy of Enterococcus species and strains highlights the need for in-depth studies to discover and characterize the genetic components underlying its diverse activities. However, current genetic engineering methods in E. faecium still require passive homologous recombination from plasmid DNA. This involves the successful cloning of multiple homologous fragments into a plasmid, introducing the plasmid into E. faecium, and screening for double-crossover events that can collectively take up to multiple weeks to perform. To alleviate these challenges, we show that RecT recombinase enables the rapid and efficient integration of mutagenic DNA templates to generate substitutions, deletions, and insertions in the genomic DNA of E. faecium. These improved recombineering methods should facilitate functional and mechanistic studies of Enterococcus.

As wearable devices move toward the face (i.e. smart earbuds, glasses), there is an increasing need to facilitate intuitive interactions with these devices. Current sensing techniques can already detect many mouth-based gestures; however, users' preferences of these gestures are not fully understood. In this paper, we investigate the design space and usability of mouth-based microgestures. We first conducted brainstorming sessions (N=16) and compiled an extensive set of 86 user-defined gestures. Then, with an online survey (N=50), we assessed the physical and mental demand of our gesture set and identified a subset of 14 gestures that can be performed easily and naturally. Finally, we conducted a remote Wizard-of-Oz usability study (N=11) mapping gestures to various daily smartphone operations under a sitting and walking context. From these studies, we develop a taxonomy for mouth gestures, finalize a practical gesture set for common applications, and provide design guidelines for future mouth-based gesture interactions., 14 page, 5 figures; Accepted to DIS 2021

RAS mutations occur in a broad spectrum of human hematopoietic malignancies. Activating Ras mutations in blood cells leads to hematopoietic malignancies in mice. In murine hematopoietic stem cells (HSCs), mutant N-RasG12D activates Stat5 to dysregulate stem cell function. However, the underlying mechanism remains elusive. In this study, we demonstrate that Stat5 activation induced by a hyperactive Nras mutant, G12D, is dependent on Jak2 activity. Jak2 is activated in Nras mutant HSCs and progenitors (HSPCs), and inhibiting Jak2 with ruxolitinib significantly decreases Stat5 activation and HSPC hyper-proliferation in vivo in NrasG12D mice. Activation of Jak2-Stat5 is associated with downregulation of Socs2, an inhibitory effector of Jak2/Stat5. Restoration of Socs2 blocks NrasG12D HSC reconstitution in bone marrow transplant recipients. SOCS2 downregulation is also observed in human acute myeloid leukemia (AML) cells that carry RAS mutations. RAS mutant AML cells exhibited suppression of the enhancer active marker H3K27ac at the SOCS2 locus. Finally, restoration of SOCS2 in RAS mutant AML cells mitigated leukemic growth. Thus, we discovered a novel signaling feedback loop whereby hyperactive Ras signaling activates Jak2/Stat5 via suppression of Socs2.

We partnered with the US Department of Health and Human Services to treat high-risk, nonadmitted coronavirus disease 2019 (COVID-19) patients with bamlanivimab in the Bronx, New York per Emergency Use Authorization criteria. Increasing posttreatment hospitalizations were observed monthly between December 2020 and March 2021 in parallel to the emergence of severe acute respiratory syndrome coronavirus 2 variants in New York City., Graphical Abstract

Background Infection is a leading cause of admission to intensive care units (ICUs), with critically ill patients often receiving empiric broad-spectrum antibiotics. Nevertheless, a dedicated infectious diseases (ID) consultation and stewardship team is not routinely established. An ID–critical care medicine (ID-CCM) pilot program was designed at a 400-bed tertiary care hospital in which an ID attending was assigned to participate in daily rounds with the ICU team, as well as provide ID consultation on select patients. We sought to evaluate the impact of this dedicated ID program on antibiotic utilization and clinical outcomes in patients admitted to the ICU. Methods In this single-site retrospective study, we analyzed antibiotic utilization and clinical outcomes in patients admitted to an ICU during the postintervention period from January 1 to December 31, 2017, and compared it to antibiotic utilization in the same ICUs during the preintervention period from January 1 to December 31, 2015. Results Our data showed a statistically significant reduction in usage of most frequently prescribed antibiotics including vancomycin, piperacillin-tazobactam, and cefepime during the intervention period. When compared to the preintervention period there was no difference in-hospital mortality, hospital length of stay, and readmission. Conclusions With this multidisciplinary intervention, we saw a decrease in the use of the most frequently prescribed broad-spectrum antibiotics without a negative impact on clinical outcomes. Our study shows that the implementation of an ID-CCM service is a feasible way to promote antibiotic stewardship in the ICU and can be used as a strategy to reduce unnecessary patient exposure to broad-spectrum agents.

CD40 agonistic antibody is emerging as a front-line immunotherapy for patients with cancer. However, despite its remarkable curative effects, serious immune-related adverse reactions limit the clinical application of CD40 agonists. Crosslinking-dependent activation is one of the promising approaches to diminish the adverse effects of CD40 agonists. Agonistic CD40 stimulation on antigen presenting cells (APCs) not only promotes activation of T cells, but also results in PD-L1 upregulation on APCs, thus creating a negative feedback loop to dampen the anti-tumor immune response. Therefore, we hypothesized that the combination of CD40 agonist and blockade of PD-1/PD-L1 interaction may further induce a synergistic effect on T cell activation and anti-tumor activity. Here, we report a novel PD-L1xCD40 Bispecific Antibody (BsAb) designed to have synergistic curative effects as well as improved safety profiles. The PD-L1/CD40 BsAb was generated using the Harbour HBICE࣪® platform. It exhibited superior binding activities to both PD-L1 and CD40, respectively. CD40 activation was fully relied on the PD-L1 crosslinking. The PD-L1xCD40 BsAb showed potent tumor growth inhibition in preclinical efficacy models. Meanwhile, it showed much improved safety profile compared to a reference anti-CD40 agonistic antibody in the preclinical tox models. Overall, the PD-L1xCD40 BsAb demonstrated remarkable in vivo anti-tumor efficacy and improved safety profiles in preclinical models, which presents it as a promising candidate for the development of next-generation cancer immune therapeutics. Citation Format: Haishan luo, Zihong Meng, Jimmy Rong, Yuandong Wang, Yunxing Yang, Fei Chen, Youhong Wang, Victor Chen, Gang Deng, Yebo He, Xin Gan, Yiping Rong. Development of a novel PD-L1xCD40 bispecific antibody with excellent efficacy and safety profile for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5559.

Augmented Reality (AR) technology has been increasingly utilised in mobile shopping apps to enhance consumers’ mobile shopping experiences, thereby affecting consumers’ impulse buying behaviour. Drawing upon the Spatial Presence Theory and the Elaboration Likelihood Model, the current study aims to empirically investigate AR-related factors (vividness, spatial accuracy, local presence) and their impacts on impulse buying behaviour related factors (arousal, perceived diagnosticity, and urge to buy impulsively) in the context of AR mobile shopping apps. In this study, an experiment employing a full 2X2 factorial between-subject experimental design was carried out. There were a total of 137 participants actively involved in this experiment. The data analysis results and findings, along with the implications of this study, are provided in the paper.