Search

This study has employed mammalian transient expression systems to generate afucosylated antibodies and antibody Fc mutants for rapid candidate screening in discovery and early development. While chemical treatment with the fucose analogue 2-fluoro-peracetyl-fucose during transient expression only partially produced antibodies with afucosylated N-glycans, the genetic inactivation of the FUT8 gene in ExpiCHO-S™ by CRISPR/Cas9 enabled the transient production of fully afucosylated antibodies. Human IgG

Numerosity effects have been investigated in the psychology and marketing literatures. While the effects are documented in outcomes including money and temperature judgments, the potential application and effects of numerosity for nutrition labeling remain unexplored. In this work, we propose that vigilance offers one circumstance when individuals might succumb to numerosity effects. Within the context of nutrition labeling, we propose that the increased vigilance that people with diet-sensitive illnesses have for specific nutrients on nutrition labels, counter-intuitively, exacerbates the numerosity effect. We demonstrate that those with diabetes and those with hypertension, for example, are more vigilant for information on nutrition labels relevant to their condition, sugar, and salt, and this greater vigilance counterintuitively leads them to exhibit greater numerosity effects for those nutrients, influencing their food perceptions. As an illustration, we find that a person with hypertension would consider a food product with, say, 3 g of sodium to have less sodium content and be more healthful than one with 3000 mg, although the quantities are equivalent. Our research highlights to policymakers that a "one-size-fits-all" solution for nutrition labeling is not appropriate. Refereed/Peer-reviewed

PURPOSE OF REVIEW Although a standard of care in the treatment of organ-confined prostate cancer, use of radiation for treatment in the high-risk, metastatic and salvage settings is evolving rapidly. RECENT FINDINGS Recent clinical trials have explored the role of increased treatment for high-risk disease with the addition of adjuvant chemotherapy and expanded the role of radiation in settings previously reserved for systemic therapy. Addition of adjuvant chemotherapy for high-risk prostate cancer is controversial and recent evidence is discussed that continues to refine the patient population for further evaluation. Evidence recently published demonstrates that for patients with low burden metastatic disease and those with oligometastatic disease may have a survival benefit with radiation treatment to all sites of known disease. Finally, reirradiation after prior radiotherapy-based treatment offers a potential salvage option for patients with locally recurrent prostate cancer. SUMMARY As treatment paradigms evolve for prostate cancer, recent evidence continues to demonstrate benefit for the use of local therapy, both in patients with organ-confined disease and, more increasingly, in those with limited metastatic or locally recurrent disease. Further work is needed to identify subgroups of patients who may benefit from available treatment escalation approaches.

P-cadherin-LP-DART is a bispecific antibody targeting P-cadherin expressed on the tumor cells and CD3 on the T-cells. Previously we demonstrated the development and efficacy of P-cadherin-LP-DART in in vitro and in vivo models. Here, we evaluated the three pillars: exposure, targeting specificity and pharmacodynamic modulation for P-cadherin-LP-DART using fluorescence molecular tomography (FMT). Bispecific antibodies and T-cells were conjugated with a near-infrared fluorophores: VivoTag®680XL (VT680) and CellVue®NIR815 (CV815), respectively. In vitro binding and cytotoxic T-lymphocyte assay demonstrated that P-cadherin-LP-DART significantly retained its properties after VT680 conjugation. In vivo FMT imaging was performed to determine the bispecific biodistribution and T-cell trafficking in HCT-116 xenograft model. Peak tumor exposure (2.71%ID) was observed at 96 hr post-injection with measurable quantity even at 240 hr (1.46%ID) (Pillar 1). P-cadherin-LP-DART accumulation in tumor was 20-25 fold higher compared to Control-LP-DART demonstrating the targeting specificity (Pillar 2). Imaging after engraftment of CV815 labeled T-cells showed P-cadherin-LP-DART mediated T-cell trafficking in tumors (Pillar 3). This study harnessed the multichannel capability of FMT and demonstrated the targeting of drug and trafficking of T cells to tumors, simultaneously. Our results show the impact of molecular imaging in demonstrating three pillars of pharmacology, longitudinally and non-invasively.

Unit pricing (i.e., displaying prices per unit of volume or weight) is deemed helpful for grocery shoppers. Many countries mandate that supermarkets provide unit prices. However, consumers only make limited use of unit pricing. Consumer advocates attribute this to the poor and inconsistent presentation of the unit price information. Using eye-tracking, the present research tests how unit price label design factors (position, font size, signposting and color highlighting on the price label) affect consumers' eye-movements during the product decision process. Additionally, the study assesses how the effects of the design factors depend on the consumer's price consciousness. The research also tests how the consistency of the label presentation affects eye-movements and choice. Findings from an experimentally designed shopping task using natural stimuli reveal that an enhanced label design leads to an increase in the number of eye fixations, in particular when the unit price is color highlighted and especially for consumers who are less price conscious. These increased fixations, however, do not result in changes in product choice. Refereed/Peer-reviewed

This research provides nuanced insights from a consumer-centric behavioural psychology perspective, by developing a theoretically grounded motivational process model of product evaluation, viewed through a country-of-origin (COO) lens, incorporating the focal constructs of product involvement, product knowledge, consumer ethnocentrism (CET) and antecedents related to wine buying in China. An online survey of 934 consumers across China in a range of 12 tier-1 and tier-2 cities investigates the effects of several independent variables on COO product category evaluation. The findings provide valuable contrasting insights between evaluations of products originating from developed economies (France and Australia) and a transitional economy (China), the home country. We validate a 10-item version of the CETSCALE and apply multiple linear regression (MLR) modelling to test the hypothesised relationships. We further contribute by examining both main and interaction effects of the empirically enhanced model. We conclude that CET, product involvement, product purchase experience and, travel exposure significantly impact COO product evaluations, through actual product purchase experience, while product purchase frequency does not. CET also has a significant mediating effect on product evaluation through both involvement and actual product purchasing experience. Gender has direct effects on CET and product evaluation, as does household income on product evaluation. Refereed/Peer-reviewed

Background: Same-day discharge after mastectomy has been demonstrated to be safe in appropriately selected candidates. However, the association between same-day discharge after mastectomy and quality of life (QOL) is unclear. Patient-reported outcome (PRO) measures represent important indicators of QOL among patients undergoing treatment for breast cancer. In this study, we aimed to evaluate the effect of same-day discharge after mastectomy on PROs. Methods: We performed a retrospective review of a prospectively collected, longitudinal PRO registry of female breast cancer patients treated at an academic breast center between June 2019 and June 2022. Patients were invited to complete the BREAST-Q module, a validated PRO questionnaire measuring QOL domains such as psychosocial wellbeing, physical wellbeing, satisfaction with their surgeon, and satisfaction with their medical team. Preoperative and 2-week postoperative questionnaire responses were analyzed in this study. Patients who had a mastectomy with or without reconstruction were included in this analysis. Those who underwent immediate reconstruction with autologous tissue were excluded as these operations are not conducive to same-day discharge. Patients were divided into two groups: the first was discharged on the date of surgery while the second was admitted to the hospital for a minimum of one night. Clinical and demographic factors were collected from a review of the electronic medical record. The primary endpoints were mean satisfaction scores as well as differences between postoperative and preoperative scores for the psychosocial and physical wellbeing domains. T-tests were used to evaluate differences between groups. A multiple regression model was fit to adjust for the effects of relevant clinical and demographic factors. Results: A total of 104 patients within the registry underwent mastectomy during the study period and were offered questionnaires. Of these, 58 completed both the preoperative and 2-week postoperative questionnaire (56% response rate); 20 (34%) in the same-day discharge group and 38 (66%) in the inpatient admission group. The groups were similar in age, stage, American Society of Anesthesiologists’ classification group, body mass index, frequency of unplanned readmission or reoperation, and receipt of bilateral mastectomy, axillary lymph node dissection, post-mastectomy reconstruction, and neoadjuvant chemotherapy. Mean patient satisfaction scores and mean changes in psychosocial and physical wellbeing scores were similar between the groups 2 weeks after surgery (Table 1). After controlling for age, type of reconstructive operation, receipt of unplanned reoperation, and preoperative score, same-day discharge did not have a significant effect on satisfaction with the surgeon (Beta=-4.3, p=0.37), satisfaction with the medical team (Beta=0.2, p=0.97), physical wellbeing score (Beta=-0.1, p=0.99), or psychosocial wellbeing score (Beta=8.0, p=0.15). Conclusions: Patients who are discharged from the hospital on the same day of a mastectomy display similar levels of satisfaction with their care team and similar short-term trends in physical and psychosocial wellbeing compared to those who are admitted to the hospital. While further data are being accrued, these early results suggest patients tolerate same-day discharge after mastectomy well. Table 1 Patient-reported outcomes at 2 weeks after mastectomy for patients discharged on the date of surgery compared to those admitted inpatient Citation Format: Sudheer Vemuru, Kathryn Colborn, Laura Leonard, Victoria Huynh, Christodoulos Kaoutzanis, Justin Cohen, David Mathes, Nicole Christian, Gretchen M. Ahrendt, Christine M. Fisher, Simon Kim, Sarah Tevis. Comparing Patient-Reported Outcomes for Same-day Discharge and Inpatient Admission After Mastectomy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-58.

This study proposes an approach for bridging the gap between B2B and B2C research by showing how a method commonly used to understand consumer preferences – Discrete Choice Experiments (DCEs) – can be applied to examine choice drivers in a B2B context. Few studies have analysed consumer choices and, simultaneously, whether trade operators' choices towards the same product match. A DCE was created by combining 11 product attributes important to wine choice. The resulting choice sets were distributed among representative samples of 1,762 U.S. wine consumers and 423 U.S. wine trade operators, who were asked to complete the same task. First, the results show that the product choices of consumers and those made by trade operators across the two separate samples can be quantitatively compared, which only a handful of studies have attempted in the past. Second, a Latent Class Analysis (LCA) affirms the presence of three significantly different segments among both consumers and trade operators. These segments' choices are comparable pairwise by the relative importance respondents assign to the choice drivers. The segments are only marginally significantly different in relation to the socio-demographics of consumers or the business characteristics of trade operators. Refereed/Peer-reviewed

Contains fulltext : 248601.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To examine how global health institutions are reducing the greenhouse gas emissions from their own operations and analyse the facilitators and barriers to achieving decarbonisation goals. METHODS: We reviewed the sustainability goals and implementation plans of 10 global health universities from the 'TropEd' network. We systematically collected information from institutional websites and annual reports. Through online interviews, 11 key informants validated the information from 9 of the institutions and shared their opinions regarding what factors are helping their institutions decarbonise and what factors are hindering progress. RESULTS: 4/10 institutions sampled have a sustainability strategy and implementation plan, only 3/10 have specific decarbonisation goals, and 3/10 are reporting on progress. 5/10 institutions reported that they are in the process of determining emission reduction targets. CONCLUSION: This paper identifies common success factors that facilitate decarbonisation as well as common challenges and how they are being tackled, and makes recommendations on sustainability efforts in academic institutions.

Low carbohydrate diets have a promising mechanistic rationale in the treatment of cancer with favorable preclinical data. The strongest data suggest synergistic effects of dietary interventions with traditional cancer therapies. Recent prospective clinical trials suggest that low carbohydrate diets are safely and feasibly added within a busy oncology clinic, with hopeful additive effects in treatment enhancement.

Site Specific Integration (SSI) expression systems offer robust means of generating highly productive and stable cell lines for traditional monoclonal antibodies. As complex modalities such as antibody-like molecules comprised of greater than two peptides become more prevalent, greater emphasis needs to be placed on the ability to produce appreciable quantities of the correct product of interest (POI). The ability to screen several transcript stoichiometries could play a large role in ensuring high amounts of the correct POI. Here we illustrate implementation of an SSI expression system with a single site of integration for development and production of a multi-chain, bi-specific molecule. A SSI vector with a single copy of all of the genes of interest (GOIs) was initially selected for stable Chinese hamster ovary (CHO) transfection. While the resulting transfection pools generated low levels of the desired heterodimer, utilizing an intensive clone screen strategy, we were able to identify clones having significantly higher levels of POI. An in-depth genotypic characterization of clones having the desirable phenotype revealed that a duplication of the light chain within the landing pad was responsible for producing the intended molecule. Retrospective transfection pool analysis using a vector configuration mimicking the transgene configuration found in the clones, as well as other vector configurations, yielded more favorable results with respect to % POI. Overall, the study demonstrated that despite the theoretical static nature of the SSI expression system, enough heterogeneity existed to yield clones having significantly different transgene phenotypes/genotypes and support production of a complex multi-chain molecule. This article is protected by copyright. All rights reserved.

Breast-conserving therapy (BCT) offers oncologic outcomes similar to those of mastectomy, yet many patients, when provided the option, choose mastectomy. This study aimed to evaluate the relationship between patient-reported distress and surgical decisions and to determine factors predictive of choosing BCT versus mastectomy. Patients with newly diagnosed breast cancer deemed candidates for BCT who completed a distress screen at their initial visit to an academic institution between 2016 and 2019 were retrospectively reviewed. This screening tool captures distress in emotional, social, health, and practical domains on a scale of 0 to 10. The distress scores were compared against surgical decisions using nonparametric Wilcoxon rank-sum tests. Patient factors associated with surgical choice were analyzed using chi-square, Fisher’s exact, and Student’s t tests. A two-sided p value lower than 0.05 was considered significant. Of 506 patients deemed eligible for BCT, 430 (85%) chose BCT and 76 (15%) pursued mastectomy. The distress levels did not differ significantly between the surgical options. The patients who underwent mastectomy were on the average younger (50.7 vs 60.4 years; p

This article describes Dr. M. Michael Cohen, Jr.'s passion for art and music. His two sons share family memories and photos. Dr. Cohen developed a keen interest in the visual arts, collecting lithographs, enjoying many art exhibits, and conducting original research on Picasso's art. His interest in faces formed a central connection between his professional life and his artistic interest. His love of music began as a young boy. Classical music and opera were the soundtrack to his creative pursuits. He enjoyed sharing music with his family immensely, especially opera performances.

This study examines how wine by-the-glass (WBG) consumption by diners in USA restaurants is affected by their risk perception, product involvement, information seeking and dissemination-related behaviours and, how these constructs interact in this situation. We model their motivational process by developing a structural equation model (SEM) to examine these effects using a sample of 532 diners representing all restaurant categories in the USA. In the process we develop and validate a 17-item scale to measure the risk perception specific to WBG consumption. This empirical study supports all hypotheses tested in the motivational process model, which explicates the processes by which consumer WBG risk perception and product involvement are caused and influence one another, as well as the subsequent information processing behaviour-related responses of restaurant diners. Refereed/Peer-reviewed

Hylauronic acid (HA) is used as a viscoelastic in Ophthalmology during cataract surgery based on its high viscosity at rest, its ability to shear thin and dissipate energy during phacoemulsification. However, these properties of HA solutions would make them susceptible to migration when used as dermal filler materials. In this study, we apply a new technique termed vibrational optical coherence tomography (VOCT) to compare the physical properties of different HA solutions and fillers used in facial aesthetics. Results presented in this study suggest that HA solutions and HA dermal fillers have markedly different physical properties. HA solutions are highly viscoelastic with high % viscous losses while fillers tend to have lower viscous energy dissipation properties. Clinical observations suggest that the high loss fillers are injected more superficially in the face where tension and internal and external forces are more likely minimized giving tissue of the hands and lips more volume and allowing more natural movement. In contrast, the lower loss gels that are used to lift tissue, generally have a higher G’, and are injected deeper into the face where injection and internal forces are likely to be higher. It is concluded that HA filler gel design can be optimized by use of VOCT to evaluate the % viscous energy loss both in vitro and in vivo.

Background Previous studies have demonstrated that the A1A2A3 domains of von Willebrand factor (VWF) play a key role in regulating macrophage-mediated clearance in vivo. In particular, the A1-domain has been shown to modulate interaction with macrophage low-density lipoprotein receptor-related protein-1 (LRP1) clearance receptor. Furthermore, N-linked glycans within the A2-domain have been shown to protect VWF against premature LRP1-mediated clearance. Importantly, however, the specific regions within A1A2A3 that enable macrophage binding have not been defined. Objective and methods To address this, we utilized site-directed PEGylation and introduced novel targeted N-linked glycosylation within A1A2A3-VWF and subsequently examined VWF clearance. Results Conjugation with a 40-kDa polyethylene glycol (PEG) moiety significantly extended the half-life of A1A2A3-VWF in VWF-/- mice in a site-specific manner. For example, PEGylation at specific sites within the A1-domain (S1286) and A3-domain (V1803, S1807) attenuated VWF clearance in vivo, compared to wild-type A1A2A3-VWF. Furthermore, PEGylation at these specific sites ablated binding to differentiated THP-1 macrophages and LRP1 cluster II and cluster IV in-vitro. Conversely, PEGylation at other positions (Q1353-A1-domain and M1545-A2-domain) had limited effects on VWF clearance or binding to LRP1.Novel N-linked glycan chains were introduced at N1803 and N1807 in the A3-domain. In contrast to PEGylation at these sites, no significant extension in half-life was observed with these N-glycan variants. Conclusions These novel data demonstrate that site specific PEGylation but not site specific N-glycosylation modifies LRP1-dependent uptake of the A1A2A3-VWF by macrophages. This suggests that PEGylation, within the A1- and A3-domains in particular, may be used to attenuate LRP1-mediated clearance of VWF.

This paper compares the sales effectiveness of front versus back located end-of-aisle promotional displays (endcaps) in a supermarket, through measuring sales from the endcaps alone, as well as total brand sales, across three experiments. This paper reveals that rear endcaps generate a higher total brand sales uplift than front endcaps, acting like "billboards" to draw shoppers into the main aisle. On average, rear endcaps generated 416% sales uplift, while front endcaps generated 346% sales uplift. However, front endcaps deliver higher endcap-only sales uplift. These findings challenge industry assumptions about one of the most commonly used promotional tools. Refereed/Peer-reviewed

Manufacturers pay premiums for endcap real estate because shoppers navigate the perimeter of stores, avoiding the aisles. Research has not established how the physical and visual reach of endcaps-product displays strategically placed at the end of a shopping aisle-might vary across locations in a store. This study explores how foot traffic and visual reach of endcaps differ by location. The most prominent endcaps, in terms of both foot traffic and visual reach, were at the back of the store. These had 24 percent more foot traffic and 30 percent more visual reach than front endcaps. Evidence from this study will help marketers reach more shoppers in different endcap locations in the supermarket. Refereed/Peer-reviewed

Cellular senescence is a central component of the aging process. This cellular response has been found to be induced by multiple forms of molecular damage and senescent cells increase in number with age in all tissues examined to date. We have examined the correlation with age of two key proteins involved in the senescence program, p16INK4a and HMGB2. These proteins are involved in cell cycle arrest and chromatin remodeling during senescence. Circulating levels of these markers increases with age and correlates with functional status. The levels of HMGB2 appear to be significantly correlated with functional status, whereas p16INK4a levels are more weakly associated. Interestingly, there is a strong correlation between the two proteins independent of age. In particular, a single high-functioning individual over 90 years of age displays a disproportionately low level of HGMB2. The results suggest that with improved testing methodology, it may be possible to monitor circulating protein markers of senescence in human populations.

A well-established empirical generalization is that brand users are more likely than non-users to recall advertising for the brand they use. The pairing of a corporate and charity brand in advertising should create an expanded brand-user base, which should, in turn, lead to higher ad-memorability than either brand advertising alone. This study tests this hypothesis for consumer-packaged good sand charity brands in the United Kingdom and Australia. We find evidence that extends the generalization that ad-memorability is higher among brand users to charity supporters in non- profit contexts. We also find that when two brands are present, ad-memorability is highest among those who use the brand and support the partner charity. However, the uplift in ad-memorability among these dual-brand users is dampened by the lower ad-memorability experienced by those who use only one brand, due to a suspected information overload. The findings challenge accepted wisdom on the benefits of co-branded advertising and have implications for partner-selection for co-branded activities. Refereed/Peer-reviewed

Co-branded advertising, where advertisements feature two partnered brands from different categories, should ideally benefit both brands. We test this assertion by studying the effect of featuring a second brand in advertisements on ad and brand name memorability, and the role of category context on which brand is recalled. Our test covers online display advertisements for consumer-packaged brands paired with charity and retailer brands in three markets (USA, UK, and Australia). Independent sample comparisons across 54 brand pairs show that advertising two brands has a neutral effect on ad memorability and negative effect on brand memorability. Furthermore, the advertisement’s category context determines which of the brands is recalled. Our findings support a competitive interference theory of dual-brand processing, whereby the two brands compete for attention resources. The results have implications for the return on investment from advertising expenditure, which will vary substantively depending on whether the costs of advertising are shared or borne by one brand in the pair.

Radio remains popular, delivering an audience reach of over 90 percent, but radio ratings may overestimate real advertising exposure. Little is known about audience and media factors affecting radio-advertising avoidance. Many advertisers have believed as much as one-third of the audience switch stations during radio-advertising breaks. In the current study, the authors combined Canadian portable people-meter data ratings to measure loss of audience during advertising. They discovered a new benchmark of 3 percent (across conditions) for mechanical (or actual physical) avoidance of radio advertising, such as switching stations or turning off the radio. This rate is about one-tenth of current estimates, but was higher for music versus talk stations, out-of-home versus in-home listening, and early versus late dayparts. Refereed/Peer-reviewed

China has become the second biggest economy in the world and growth in wine consumption has been part of the overall economic trend. This chapter provides an overview of wine consumption trends in China starting with an overview of alcohol consumption. The Chinese have always been alcohol consumers; what has changed is the move away from spirits into wine made from grapes. The reasons for this change over the last 50 years are provided as an introduction to the current market for wine in China. Very little consumption data is available from the Chinese government or from reliable data firms; so, much of this chapter is based on the two authors’ research in China over the last 6 years. Overall, there has been a move from high-priced prestige wines to lower-priced wines for informal consumption. Even with all the news about online shopping in China, just over 29% is purchased through these channels. The chapter also provides information on the key countries selling wine to China, Chinese consumers’ awareness of different countries of origin and recommendations for growing wine sales and doing market research in China.

PurposeThe purpose of this study is to adopt a functional perspective to integrate and extend three streams of research, the first distinguishing between global affect and discrete emotional episodes, the second highlighting the capability of places to elicit emotions and the third demonstrating the differential impact of discrete emotions on consumer response. Doing so shows that four positive place emotions have a significant and variable influence on consumer purchase intentions for brands originating there.Design/methodology/approachA focus group pilot corroborates that places relate to contentment, enchantment, happiness and pride, which impact consumer response. Study 1 uses landscape photographs to show the four place emotions influence purchase intention for bottled water. Study 2 retests the impact of place emotions, using short vignettes and establishes the moderating role of product hedonic nature. Study 3 replicates emotion effects, corroborating their non-conscious nature and establishing their impact in the presence of place cognitions.FindingsTogether, the empirical studies provide evidence for effects of four discrete place emotions, especially with hedonic products and under conditions of cognitive load. Effects are robust when a person’s mood, buying volume, category knowledge, impulse buying tendencies and place cognitions are included as controls.Research limitations/implicationsThe study contributes to a better understanding of the emotional dimension of origin effects by adopting a novel, theory-based perspective on discrete positive place emotions impacting consumer response.Practical implicationsManagers invest substantially in places to elicit positive feelings, gravitating toward the view that all they need to do is create a global positive effect with consumers. The study informs this perspective by demonstrating how discrete emotions influence consumer response.Originality/valueThis study is among the first to examine discrete positive place emotions as possible drivers of consumers’ purchase intention.

This study uses a sample of approximately 60,000 US households to document fundamental shopping basket size patterns across a range of retail types, and examines them in relation to retailer performance metrics (unit sales and dollar revenue). Specifically, this research addresses two main questions: 1) how do shopping basket metrics (mean and median number of items, the distribution of one, two, three ... n items) differ by retail type, and 2) how does the Pareto ratio (sales generated by the heaviest 20%, and lightest 80% of buyers) apply to shopping baskets. The results show that basket size patterns in retailers are predictable. Shoppers purchase more items on average in retailers that offer a greater variety of items, and the distribution of basket sizes follows the Poisson lognormal model. The results also show that the largest 20% of shopping baskets on average generate 50% of unit sales, and 40% of dollar revenue. These results set additional benchmarks of the patterns that can be expected when looking at data on a basket-level. This research offers implications to practitioners by showing the importance of small and large baskets for retailer revenue and growth, which can guide more informed decision making to better manage their stores and brands. Refereed/Peer-reviewed

The fortuitously discovered antiaging membrane protein αKlotho (Klotho) is highly expressed in the kidney, and deletion of the Klotho gene in mice causes a phenotype strikingly similar to that of chronic kidney disease (CKD). Klotho functions as a co-receptor for fibroblast growth factor 23 (FGF23) signaling, whereas its shed extracellular domain, soluble Klotho (sKlotho), carrying glycosidase activity, is a humoral factor that regulates renal health. Low sKlotho in CKD is associated with disease progression, and sKlotho supplementation has emerged as a potential therapeutic strategy for managing CKD. Here, we explored the structure-function relationship and post-translational modifications of sKlotho variants to guide the future design of sKlotho-based therapeutics. Chinese hamster ovary (CHO)- and human embryonic kidney (HEK)-derived WT sKlotho proteins had varied activities in FGF23 co-receptor and β-glucuronidase assays in vitro and distinct properties in vivo. Sialidase treatment of heavily sialylated CHO-sKlotho increased its co-receptor activity 3-fold, yet it remained less active than hyposialylated HEK-sKlotho. MS and glycopeptide-mapping analyses revealed that HEK-sKlotho is uniquely modified with an unusual N-glycan structure consisting of N,N′-di-N-acetyllactose diamine at multiple N-linked sites, one of which at Asn-126 was adjacent to a putative GalNAc transfer motif. Site-directed mutagenesis and structural modeling analyses directly implicated N-glycans in Klotho's protein folding and function. Moreover, the introduction of two catalytic glutamate residues conserved across glycosidases into sKlotho enhanced its glucuronidase activity but decreased its FGF23 co-receptor activity, suggesting that these two functions might be structurally divergent. These findings open up opportunities for rational engineering of pharmacologically enhanced sKlotho therapeutics for managing kidney disease.

Purpose Regional nodal irradiation improves disease-free and distant disease–free survival in patients with high-risk breast cancer (BC). Trials demonstrating this used 2- or 3-dimensional conformal radiation therapy (2-dimensional or 3-dimensional [3D] conformal radiotherapy [CRT]) fields based on bony anatomy. Modern volumetric-modulated arc therapy (VMAT) and pencil beam scanning proton therapy (PBSPT) may underdose regional nodes (RNs) not contoured but covered by 3D CRT. Multiple atlases guide modern treatment planning. This study addresses the risk of underdosing when relying on published atlases and treating with 3D CRT, VMAT, and PBSPT. Methods and Materials Targets per the Radiation Therapy Oncology Group (RTOG), European Society for Radiotherapy and Oncology (ESTRO), and Radiotherapy Comparative Effectiveness Consortium (RADCOMP) atlases were contoured on a representative patient CT scan. 3D CRT plans based on anatomic borders and VMAT and PBSPT plans for each set of target volumes were generated. Positron emission tomography/computed tomography (PET/CT) scans were reviewed. CT-positive and 18F-fluorodeoxyglucose (18F-FDG)–avid RNs (n = 389) were mapped from 102 patients with locally advanced (n = 51; median 2; range, 1-8 nodes) and metastatic (n = 51; median 4; range, 1-19 nodes) BC: axillary (AX; n=284), supraclavicular (SCV; n = 60), and internal mammary nodal (IMN; n=45). 18F-FDG-avid RNs falling within the 95% isodose line were considered adequately covered. Results 3D CRT plans provided excellent RN coverage. Low AX nodes were covered (≥99%) in all plans. Underdosing of 18F-FDG–avid RNs falling in the high AX (78%-92%), SCV (52%-75%), and IMN (84%-89%) volumes was observed following the RTOG and ESTRO atlases for VMAT and PBSPT plans. Use of the RADCOMP atlas provided coverage of these areas (89%-100%) with slightly increased heart and lung doses. Atlas guided VMAT/PBSPT plans provided cumulative nodal coverage as follows: ESTRO (89%/88%), RTOG (93%/91%), and RADCOMP (98%/96%). Conclusions VMAT and PBSPT for regional nodal irradiation in patients with high-risk BC risks underdosage in the high AX, SCV, and IMN nodal regions unless comprehensive target delineation is performed.

This paper investigates the relationship between the choice drivers for wine among Chinese consumers with their personal values, using two sets of Best-Worst Scaling data.We first provide a ranking of the personal values and wine choice drivers of the population at hand. We then classify the respondents in terms of their choice drivers by means of a Latent Class Clustering. Lastly, we analyse the personal values and socio-demographic variables in each class. The sample (n=1,141) is sociodemographically representative in terms of age, gender, and income of the Chinese upper-middle class urban population.The results reveal the presence of three clusters, which are clearly identifiable in relation to their choice drivers, personal values and, partially, to their sociodemographic characteristics. The linking of value statements to the clusters strengthens the types of activities on-premise venues can use to attract different groups of customers. If on-premise operators know more about the personality of their clients and their choice drivers, they can engage their customers more appropriately throughout the choice process.The approach proposed in this paper can be extended to any research that aims to analyse the relationship between the elements driving the choice of a product and attitudinal variables. Refereed/Peer-reviewed

Retailers often feature manufacturer brands in their advertising with the aim to drive sales for those brands and, at the same time, increase in-store traffic. The adoption of such co-operative advertising strategies should reach an expanded audience base comprising of store and brand buyers. Based on empirical evidence in non-retail settings, these buyers are more likely to remember the advertising than non-buyers. This usage-bias effect implies that co-operative advertisements achieve greater cut through than would be the case if either brand advertised alone. Our paper tests this hypothesis in the context of retailer advertisements that feature manufacturer brands in the US, UK and Australia. Our results confirm that a retail brand's shoppers are more likely to recall its advertisements than non-shoppers, extending the usage-bias generalisation to a retailing context. However, while co-operative advertising does expand the buyer-base reach, any uplift in ad-memorability is negated by a reduced ability for buyers of only one of the two brands to recall the advertisement. Information overload on cognitive processing is a possible explanation for this finding, and has implications for extracting value from any investment in co-operative advertising. Refereed/Peer-reviewed