Oncolytic virus V937 in combination with PD-1 blockade therapy to target immunologically quiescent liver and colorectal cancer.

V937 is an investigational, genetically unmodified Kuykendall strain of coxsackievirus A21, which has been evaluated in the clinic for advanced solid tumor malignancies. V937 specifically infects and lyses tumor cells that overexpress intercellular adhesion molecule-1 (ICAM-1). Intratumoral V937 as a monotherapy and in combination with anti-PD-1 antibody pembrolizumab has shown clinical response in patients with metastatic melanoma, which overexpresses ICAM-1. Here, we investigate in preclinical studies the potential bidirectional cross-talk between hepatocellular carcinomas (HCC) or colorectal carcinomas (CRC) and immune cells when treated with V937 alone or in combination with pembrolizumab. We show that while V937 treatment of tumor cell lines or organoids or peripheral blood mononuclear cells (PBMCs) alone induced a minimal immunological response, V937 treatment of non-contact co-cultures of tumor cell lines or CRC organoids with PBMCs led to robust production of proinflammatory cytokines and immune cell activation. In addition, both recombinant interferon-gamma and pembrolizumab increased ICAM-1 on tumor cell lines or organoids and, in turn, amplified V937-mediated oncolysis and immunogenicity. These findings provide critical mechanistic insights on the cross-talk between V937-mediated oncolysis and immune responses, demonstrating the therapeutic potential of V937 in combination with PD-1 blockade to treat immunologically quiescent cancers.

Anti-inflammatory effect of Piper longum L. fruit methanolic extract on lipopolysaccharide-treated RAW 264.7 murine macrophages.

Context: The Piper species was studied several potential properties such as anti-tumor, anti-inflammatory and antioxidant activity. However, the specific anti-inflammatory activity of the extract from the fruits of P. longum L. has not been investigated. Objectives: Our study want to examine the anti-inflammatory effects of P. longum L. fruit methanolic extracts (PLE) on lipopolysachharide (LPS)-stimulated RAW 264.7 murine macrophages to understand the mechanism of this effect. Method: This study examined the chemical profiling of PLE by LC-HRMS analysis and measured the presence of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the supernatant using the Griess reagent assay and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA expression of IL-6, TNF-α, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) were evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR). Furthermore, the protein expression of COX-2, iNOS and the phosphorylation of MAPK family, c-Jun N-terminal kinase (JNK), p38 in protein level were observed by western blotting. Result: PLE have detected 66 compounds which belong to different classes such as alkaloids, flavonoids, terpenoids, phenolics, lactones, and organic acids inhibited nitric oxide products with the IC50 = 28.5 ± 0.91 µg/mL. Moreover, PLE at 10-100 µg/mL up-regulate HO-1 protein expression from 3 to 10 folds at 3 h. It also downregulated the mRNA and protein expression of iNOS, COX-2, decreased IL-6 and TNF-α secretion by modulating the mitogen-activated protein kinase (MAPK) signaling pathway, specifically by decreasing the phosphorylation of p38 and JNK. Conclusion: These results shown chemical profiling of PLE and demonstrated that PLE exhibits anti-inflammatory effects by regulating the MAPK family and could be a potential candidate for the treatment of inflammatory diseases.

GENA: A knowledge graph for nutrition and mental health.

While a large number of knowledge graphs have previously been developed by automatically extracting and structuring knowledge from literature, there is currently no such knowledge graph that encodes relationships between food, biochemicals and mental illnesses, even though a large amount of knowledge about these relationships is available in the form of unstructured text in biomedical literature articles. To address this limitation, this article describes the development of GENA - (Graph of mEntal-health and Nutrition Association), a knowledge graph that represents relations between nutrition and mental health, extracted from biomedical abstracts. GENA is constructed from PubMed abstracts that contain keywords relating to chemicals, food, and health. A hybrid named entity recognition (NER) model is firstly applied to these abstracts to identify various entities of interest. Subsequently, a deep syntax-based relation extraction model is used to detect binary relations between the identified entities. Finally, the resulting relations are used to populate the GENA knowledge graph, whose relationships can be accessed in an intuitive and interpretable manner using the Neo4J Database Management System. To evaluate the reliability of GENA, two annotators manually assessed a subset of the extracted relations. The evaluation results show that our methods obtain high precision for the NER task and acceptable precision and relative recall for the relation extraction task. GENA consists of 43,367 relationships that encode information about nutrition and health, of which 94.04% are new relations that are not present in existing ontologies of food and diseases. GENA is constructed based on scientific principles, and has the potential to be used within further applications to contribute towards scientific research within the domain. It is a pioneering knowledge graph in nutrition and mental health, containing a diverse range of relationship types. All of our source code and results are publicly available at https://github.com/ddlinh/gena-db.

Microbial engineering of Methylorubrum extorquens AM1 to enhance CO2 conversion into formate.

Methylorubrum extorquens AM1 has the potential to consume C1 feedstock to produce a wide range of biomaterials, from bioplastic to pharmaceutical. However, the synthetic biology tools for engineering M. extorquens AM1 need to be employed for precise control of recombinant enzyme expression. In this study, we presented an approach to improve the expression level of formate dehydrogenase 1 from M. extorquens AM1 (MeFDH1) using an efficient terminator and 5'-untranslated region (5'-UTR) design for enhanced carbon dioxide (CO2) conversion activity of whole-cell biocatalyst. The rrnB terminator significantly increased mRNA levels of MeFDH1 alpha and beta subunits by 8.2-fold and 11-fold, respectively, compared to the T7 terminator. Moreover, enzyme production was 1.6-fold higher with 2.1 mg/wet cell weight (WCW) using rrnB terminator. Homologous 5'-untranslated regions (5'-UTR) determined based on proteomics data and UTR designer also influenced the expression level of MeFDH1. The 5'-UTR of the formaldehyde activating enzyme (fae) was the strongest, with 2.5-fold higher expression than that of the control sequence (T7g-10L). Furthermore, the electrochemical reaction of recombinant strains as whole-cell biocatalysts was investigated for their applicability to CO2 conversion, showing enhanced formate productivity. The recombinant strain containing the 5'-UTR sequence of fae exhibited formate productivity of 5.0 mM/h, 2.3-fold higher than that of the control strain (T7). Overall, this study suggested practical applications for CO2 conversion into bioavailable formate and provided valuable insights for recombinant expression systems in methylotrophic strains.

Engineering Oncolytic Coxsackievirus A21 with Small Transgenes and Enabling Cell-Mediated Virus Delivery by Integrating Viral cDNA into the Genome.

Coxsackievirus A21 (CVA21) is a naturally occurring RNA virus that, in preclinical studies and clinical trials, has demonstrated promising potential in treating a range of malignancies. Other oncolytic viruses, such as adenovirus, vesicular stomatitis virus, herpesvirus, and vaccinia virus, all can be engineered to carry one or more transgenes for various purposes, including immune modulation, virus attenuation, and induction of apoptosis of tumor cells. However, it remained unknown whether CVA21 can express therapeutic or immunomodulatory payloads due to its small size and high mutation rate. Using reverse genetics techniques, we demonstrated that a transgene encoding a truncated green fluorescent protein (GFP) of up to 141 amino acids (aa) can be successfully carried in the 5' end of the coding region. Furthermore, a chimeric virus carrying an eel fluorescent protein, UnaG (139 aa), was also made and shown to be stable, and it maintained efficient tumor cell-killing activity. Similar to other oncolytic viruses, the likelihood of delivering CVA21 by the intravenous route is low due to issues like blood absorption, neutralizing antibodies, and liver clearance. To address this problem, we designed the CVA21 cDNA under the control of a weak RNA polymerase II promoter, and subsequently, a stable cell pool in 293T cells was made by integrating the resulting CVA21 cDNA into the cell genome. We showed that the cells are viable and able to persistently generate rCVA21 de novo. The carrier cell approach described here may pave the way to designing new cell therapy strategies by arming with oncolytic viruses. IMPORTANCE As a naturally occurring virus, coxsackievirus A21 is a promising oncolytic virotherapy modality. In this study, we first used reverse genetics to determine whether A21 can stably carry transgenes and found that it could express up to 141 amino acids of foreign GFP. The chimeric virus carrying another fluorescent eel protein UnaG (139 amino acids) gene also appeared to be stable over at least 7 passages. Our results provided guidance on how to select and engineer therapeutic payloads for future A21 anticancer research. Second, the challenges of delivering oncolytic viruses by the intravenous route hamper the broader use of oncolytic viruses in the clinic. Here, we used A21 to show that cells could be engineered to stably carry and persistently release the virus by harboring the viral cDNA in the genome. The approach we presented here may pave a new way for oncolytic virus administration using cells as carriers.

Targeted degradation of PCNA outperforms stoichiometric inhibition to result in programed cell death.

Biodegraders are targeted protein degradation constructs composed of mini-proteins/peptides linked to E3 ligase receptors. We gained deeper insights into their utility by studying Con1-SPOP, a biodegrader against proliferating cell nuclear antigen (PCNA), an oncology target. Con1-SPOP proved pharmacologically superior to its stoichiometric (non-degrading) inhibitor equivalent (Con1-SPOPmut) as it had more potent anti-proliferative effects and uniquely induced DNA damage, cell apoptosis, and necrosis. Proteomics showed that PCNA degradation gave impaired mitotic division and mitochondria dysfunction, effects not seen with the stoichiometric inhibitor. We further showed that doxycycline-induced Con1-SPOP achieved complete tumor growth inhibition in vivo. Intracellular delivery of mRNA encoding Con1-SPOP via lipid nanoparticles (LNPs) depleted endogenous PCNA within hours of application with nanomolar potency. Our results demonstrate the utility of biodegraders as biological tools and highlight target degradation as a more efficacious approach versus stoichiometric inhibition. Once in vivo delivery is optimized, biodegraders may be leveraged as an exciting therapeutic modality.

STUB1 is an intracellular checkpoint for interferon gamma sensing.

Immune checkpoint blockade (ICB) leads to durable and complete tumour regression in some patients but in others gives temporary, partial or no response. Accordingly, significant efforts are underway to identify tumour-intrinsic mechanisms underlying ICB resistance. Results from a published CRISPR screen in a mouse model suggested that targeting STUB1, an E3 ligase involved in protein homeostasis, may overcome ICB resistance but the molecular basis of this effect remains unclear. Herein, we report an under-appreciated role of STUB1 to dampen the interferon gamma (IFNγ) response. Genetic deletion of STUB1 increased IFNGR1 abundance on the cell surface and thus enhanced the downstream IFNγ response as showed by multiple approaches including Western blotting, flow cytometry, qPCR, phospho-STAT1 assay, immunopeptidomics, proteomics, and gene expression profiling. Human prostate and breast cancer cells with STUB1 deletion were also susceptible to cytokine-induced growth inhibition. Furthermore, blockade of STUB1 protein function recapitulated the STUB1-null phenotypes. Despite these encouraging in vitro data and positive implications from clinical datasets, we did not observe in vivo benefits of inactivating Stub1 in mouse syngeneic tumour models-with or without combination with anti-PD-1 therapy. However, our findings elucidate STUB1 as a barrier to IFNγ sensing, prompting further investigations to assess if broader inactivation of human STUB1 in both tumors and immune cells could overcome ICB resistance.

Unbiased Analysis of Temporal Changes in Immune Serum Markers in Acute COVID-19 Infection With Emphasis on Organ Failure, Anti-Viral Treatment, and Demographic Characteristics.

Identification of novel immune biomarkers to gauge the underlying pathology and severity of COVID-19 has been difficult due to the lack of longitudinal studies. Here, we analyzed serum collected upon COVID-19 admission (t1), 48 hours (t2), and seven days later (t3) using Olink proteomics and correlated to clinical, demographics, and therapeutic data. Older age positively correlated with decorin, pleiotrophin, and TNFRS21 but inversely correlated with chemokine (both C-C and C-X-C type) ligands, monocyte attractant proteins (MCP) and TNFRS14. The burden of pre-existing conditions was positively correlated with MCP-4, CAIX, TWEAK, TNFRS12A, and PD-L2 levels. Individuals with COVID-19 demonstrated increased expression of several chemokines, most notably from the C-C and C-X-C family, as well as MCP-1 and MCP-3 early in the course of the disease. Similarly, deceased individuals had elevated MCP-1 and MCP-3 as well as Gal-9 serum levels. LAMP3, GZMB, and LAG3 at admission correlated with mortality. Only CX3CL13 and MCP-4 correlated positively with APACHE score and length of stay, while decorin, MUC-16 and TNFRSF21 with being admitted to the ICU. We also identified several organ-failure-specific immunological markers, including those for respiratory (IL-18, IL-15, Gal-9) or kidney failure (CD28, VEGF). Treatment with hydroxychloroquine, remdesivir, convalescent plasma, and steroids had a very limited effect on the serum variation of biomarkers. Our study identified several potential targets related to COVID-19 heterogeneity (MCP-1, MCP-3, MCP-4, TNFR superfamily members, and programmed death-ligand), suggesting a potential role of these molecules in the pathology of COVID-19.

Meteorological factors associated with hand, foot and mouth disease in a Central Highlands province in Viet Nam: an ecological study.

BACKGROUND: Hand, foot and mouth disease (HFMD) is a public health problem in Viet Nam, and studies have reported seasonal fluctuation in the occurrence of HFMD. This study sought to describe the occurrence of HFMD and its associated meteorological factors in Dak Lak province, Viet Nam. METHODS: Monthly data on HFMD cases were collected from all commune health stations in Dak Lak province from 2012 through 2013. An HFMD case was defined as a brief febrile illness accompanied by a typical skin rash with or without mouth ulcers. Average temperature, maximum temperature, minimum temperature, humidity, rainfall, evaporation, sunshine duration and wind speed were recorded monthly at five local meteorological stations throughout Dak Lak.Data were aggregated at the district level, and the association between these meteorological factors and HFMD cases were examined by Poisson regression. RESULTS: In 2012 through 2013, there were 7128 HFMD patients in Dak Lak. The number of HFMD cases increased during the rainy season. An increased risk of HFMD was associated with higher average temperature (risk ratio and 95% confidence interval: 1.06; 1.03-1.08 per 1 °C increase), higher rainfall (1.19; 1.14-1.24 per 200 mm increase) and longer sunshine duration (1.14; 1.07-1.22 per 60 hours increase). The risk of HFMD was inversely associated with wind speed (0.77; 0.73-0.81 per 1 m/s increase). CONCLUSION: This study suggests that there is a significant association between HFMD occurrence and climate. Temperature, rainfall, wind speed and sunshine duration could be used as meteorological predictors of HFMD occurrence in Viet Nam's Central Highlands region. Intensified surveillance for HFMD during the rainy season is recommended.

Data on motivations of food choices obtained by two techniques: Online survey and in-depth one-on-one interview.

This data article provides the data related to the research article entitled "Motivations for meal and snack times: Three approaches reveal similar constructs" (Phan et al., 2018). The data consists of two datasets collected from two research techniques: online survey questionnaire and one-on-one interview. The data include details of the food and beverage items the participants consumed at specific eating occasions together with the motivations associated with consumption of those foods. The data also provides the food groups to which the food items belong, to facilitate different levels of data analysis to explore the relationship between food, eating occasions and people׳s motivations.

Is establishing a specialist back pain assessment and management service in primary care a safe and effective model? Twelve-month results from the Back pain Assessment Clinic (BAC) prospective cohort pilot study.

OBJECTIVES: To report on the design, implementation and evaluation of the safety and effectiveness of the Back pain Assessment Clinic (BAC) model. DESIGN: BAC is a new, community-based specialist service for assessing and managing neck and low back pain (LBP). The BAC pilot was supported by a Victorian Department of Health and Human Services grant and was evaluated using the Victorian Innovation Reform Impact Assessment Framework (VIRIAF). Data were obtained by auditing BAC activity (22 July 2014 to 30 June 2015) and conducting surveys and interviews of patients, stakeholders and referrers. SETTING: Tertiary and primary care. PARTICIPANTS: Adult patients with neck and LBP referred for outpatient surgical consultation. MAIN OUTCOME MEASURES: VIRIAF outcomes: (1) access to care; (2) appropriate and safe care; (3) workforce optimisation and integration; and (4) efficiency and sustainability. RESULTS: A total of 522 patients were seen during the pilot. Most were referred to hospital services by general practitioners (87%) for LBP (63%) and neck pain (24%). All patients were seen within 10 weeks of referral and commenced community-based allied health intervention within 2-4 weeks of assessment in BAC. Of patients seen, 34% had medications adjusted, 57% were referred for physiotherapy, 3.2% to pain services, 1.1% to rheumatology and 1.8% for surgical review. Less MRI scans were ordered in BAC (6.4%) compared with traditional spinal surgical clinics (89.8%), which translated to a cost-saving of $52 560 over 12 months. Patient and staff satisfaction was high. There have been no patient complaints or adverse incidents. CONCLUSION: Evaluation of the BAC pilot suggests it is a potentially safe and cost-saving alternative model of care. Results of the BAC pilot merit further evaluation to determine the potential cost-effectiveness, longer term and broader societal impact of implementing BAC more widely.

Advanced musculoskeletal physiotherapy: Barriers and enablers to multi-site implementation.

OBJECTIVES: Advanced musculoskeletal physiotherapy (AMP) services are a safe, effective model of care, but without broad-scale healthcare implementation to date. The aim of the present study was to identify the barriers and enablers to implementation of 12 AMP services from the perspective of clinical staff. METHODS: In a qualitative study, 12 participants (physiotherapists), from 12 different healthcare networks (seven metropolitan, three regional, two rural), were included. Their departments implemented AMP services (orthopaedic postoperative joint replacement review, n = 10; general orthopaedic, n = 1; emergency, n = 1; and neurosurgery n = 1) over a 12-month period. Participants completed a structured survey specifically designed for the study. Thematic analysis was used, with themes mapped to the validated Theoretical Domains Framework. RESULTS: Nine major themes emerged from the data regarding barriers and enablers to the implementation of the AMP services from the perspective of clinical staff. These were: demand/capacity; model of care; the organization; stakeholders; communication; planning and processes; evaluation; workforce; and learning and assessment framework. Important enablers included engagement and buy-in from key stakeholders and medical staff, and well-established AMP learning frameworks for training and operational frameworks. Barriers included competitive funding environment, and issues that hindered effective communication. The knowledge, skills, availability, motivation and experience of the advanced musculoskeletal physiotherapists had a large impact on the implementation. CONCLUSIONS: The study identified a number of factors that should be considered for successful implementation of AMP services across healthcare services or wider healthcare networks.

Advanced musculoskeletal physiotherapists in post arthroplasty review clinics: a state wide implementation program evaluation.

OBJECTIVE: To evaluate outcomes following a state-wide implementation of post arthroplasty review (PAR) clinics for patients following total hip and knee arthroplasty, led by advanced musculoskeletal physiotherapists in collaboration with orthopaedic specialists. DESIGN AND SETTING: A prospective observational study analysed data collected by 10 implementation sites (five metropolitan and five regional/rural centres) between September 2014 and June 2015. MAIN OUTCOME MEASURES: The Victorian Innovation and Reform Impact Assessment Framework was used to assess efficiency, effectiveness (access to care, safety and quality, workforce capacity, utilisation of skill sets, patient and workforce satisfaction) and sustainability (stakeholder engagement, succession planning and availability of ongoing funding). RESULTS: 2362 planned occasions of service (OOS) were provided for 2057 patients. Reduced patient wait times from referral to appointment were recorded and no adverse events occurred. Average cost savings across 10 sites was AUD$38 per OOS (Baseline $63, PAR clinic $35), representing a reduced pathway cost of 44%. Average annual predicted total value of increased orthopaedic specialist capacity was $11,950 per PAR clinic (range $6149 to $23,400). The Australian Orthopaedic Association review guidelines were met (8/10 sites, 80%) and patient-reported outcome measures were introduced as routine clinical care. High workforce and patient satisfaction were expressed. Eighteen physiotherapists were trained creating a sustainable workforce. Eight sites secured ongoing funding. CONCLUSIONS: The PAR clinics delivered a safe, cost-efficient model of care that improved patient access and quality of care compared to traditional specialist-led workforce models.

Clinical characteristics of hand, foot and mouth disease in Daklak Province, Vietnam and associated factors of severe cases.

The Hand, Foot and Mouth Disease (HFMD) outbreaks occurred throughout Daklak province, Vietnam in 2011. This study reviewed all 744 medical records of HFMD patients admitted to Daklak Hospital in 2011 to describe the clinical characteristics of HFMD patients and determined factors associated with severe illness. Among 744 patients, 63 (8.5%) cases were severe. Most (695, 93.4%) of the cases were 3 years old or younger, and 464 (62.4%) were boys. The number of cases peaked between August and November. Most (726, 97.6%) recovered, 17 severe cases (2.3%) were transferred to higher level hospitals, and one death. Symptoms at admission included fever (93.5% had a fever ≥ 38.5 °C), blisters (99.1%), myoclonus (58.5%), and leukocytosis (> 11,300/mm3: 38.8%). Viral cultures were performed for 61 of 63 severe cases, of which 26.2% were positive for Enteroviruses. Multivariable analysis found that oral ulcers (Odds Ratio (OR) 3.74; 95% Confidence Interval (CI) 2.13-6.58), myoclonus (OR 44.75; 95% CI 6.04-331.66) and high white blood cell count (OR 1.08; 95% CI 1.01-1.16 per 1000/mm3 increase) were significantly associated with severe illness. HFMD mainly occurs in children younger than 3 years old and rainy season. Oral ulcers, myoclonus, and leukocytosis should be closely monitored to promptly detect severe cases of HFMD.

Motivations for choosing various food groups based on individual foods.

Understanding "why people eat what they eat" is important for improving the lives of people around the world by helping provide industrial and social solutions for people to have greater pleasure and health from the foods they choose. The objective of this study was to investigate the motivations behind everyday choices of different food groups using a bottom-up approach that targeted the specific choices of foods and beverages people consumed at various times of a day. This study was conducted using an online survey included questions related to demographics, the most recent meal including specific food choices, and a slightly modified Eating Motivation Surveys (2 motivations were added, and Check-All-That-Apply procedure was used), which contained 50 sub-scales to measure 17 motivations including such topics as Liking, Pleasure, Convenience, Health, Price, Variety Seeking etc. A total of 198 participants have completed the surveys. Data were analyzed by Correspondence Analysis. Liking was found to be the strongest motivation that drove people to select all sorts of foods. Need and Hunger and Convenience were the main motivations for baked products, "fast" foods, sausages and meats, and snack foods while Health and Weight Control were found to be the main driving factors for vegetables, fruits & fruit juices, nuts, seeds, dairy & egg, and poultry products. Sweets were linked to Pleasure. For beverages, people were motivated most by Heath and Weight Control to choose water and tea. Coffee was used due to Habits; soda was because of Pleasure and alcoholic was for socialization purposes. This study provided developers, marketers, health educators, etc. With a new method to understand food choice in order to promote better eating.

Investigation of Fucoidan-Oleic Acid Conjugate for Delivery of Curcumin and Paclitaxel.

Nanoparticles for a specific delivery are likely to be designed for cancer therapeutic effectiveness and improvement. In this study, a fucoidan-oleic acid conjugate was prepared and investigated in terms of loading capacity for poorly water-soluble anti-cancer drugs to maximize effectiveness of the treatment. Fucoidan was used as a hydrophilic portion of an amphiphilic structure for improving cancer therapeutic effects. Paclitaxel and curcumin were chosen as other model drugs loaded in the conjugates. The results showed that self-assembled nanoparticles with different sizes and morphologies could be prepared with two different concentrations of oleic acid as hydrophobic portion. Moreover, loading efficiency and release patterns of these drugs were mainly dependent on the hydrophobic interaction between drugs and oleic acid. It was also revealed that fucoidan and curcumin were released higher at pH 4.5 than at the physiological condition (pH 7.4), thus, facilitating the delivery and maximizing effects of the anticancer agents on cancer cells. On the contrary, paclitaxel from fucoidan nanoparticles was released faster at pH 7.4. The exploration of fucoidan-oleic acid conjugate could be considered as promising nanomedicines for cancer therapeutics.

Motivations for Food Consumption during Specific Eating Occasions in Turkey.

Several studies in different countries have been conducted to investigate factors affecting food choices. The objective of this study was to understand the motivations of specific food and beverage choices for different eating occasions in a typical diet of the Turkish people. A convenience sample of 141 respondents from seven different geographical regions in Turkey completed an online survey questionnaire that included questions about demographic information and details about their latest eating occasion. Respondents reported all of their motivations for choosing each food/beverage item reported for that specific eating occasion. Results indicated that different motivations played different roles in food choices of people in Turkey. Liking was a key characteristic for all eating occasions, but key natural concerns were even more important at breakfast, and need and hunger were more important for a mid-afternoon snack. Lunch involved additional motivations such as Sociability, Variety Seeking, and Social Norms. In addition to Liking, choices of different food groups were also driven by other motivations such as Habits, Convenience, Need and Hunger, Natural Concerns, and Health. This study helped better understand the current dietary patterns of Turkish people as well as the motives underlying their choices of foods and beverages for different meals and snacks. These findings could be useful for dietary campaigns that aim to improve eating behaviors in Turkey.

Development and characterization of APRIL antagonistic monoclonal antibodies for treatment of B-cell lymphomas.

APRIL (A proliferation-inducing ligand) is a TNF family member that binds two TNF receptor family members, TACI and BCMA. It shares these receptors with the closely related TNF family member, B-cell activating factor (BAFF). Contrary to BAFF, APRIL binds heparan sulfate proteoglycans (HSPGs), which regulates cross-linking of APRIL and efficient signaling. APRIL was originally identified as a growth promoter of solid tumors, and more recent evidence defines APRIL also as an important survival factor in several human B-cell malignancies, such as chronic lymphocytic leukemia (CLL). To target APRIL therapeutically, we developed two anti-human APRIL antibodies (hAPRIL.01A and hAPRIL.03A) that block APRIL binding to BCMA and TACI. Their antagonistic properties are unique when compared with a series of commercially available monoclonal anti-human APRIL antibodies as they prevent in vitro proliferation and IgA production of APRIL-reactive B cells. In addition, they effectively impair the CLL-like phenotype of aging APRIL transgenic mice and, more importantly, block APRIL binding to human B-cell lymphomas and prevent the survival effect induced by APRIL. We therefore conclude that these antibodies have potential for further development as therapeutics to target APRIL-dependent survival in B-cell malignancies.

A high affinity human antibody antagonist of P-selectin mediated rolling.

We have characterized the IgG form of a previously isolated and engineered single-chain Fv (scFv), named RR2r3s4-1, that binds to human PSGL-1. This fully human IgG was determined to have a Kd of 1.8+/-0.7 nM by fluorescence quenching titration. It better inhibits P-selectin-PSGL-1 interactions than a commercially available murine monoclonal antibody KPL1 and better inhibits neutrophil rolling than KPL1. Thus, RR2r3s4-1 is the most effective antibody at inhibiting P-selectin-PSGL-1 interactions known. Specificity analysis reveals that RR2r3s4-1 does not cross react with murine PSGL-1 and thus requires more than tyrosine sulfate for binding to human PSGL-1. This evidence demonstrates the therapeutic potential of this antibody as a potent anti-inflammatory therapeutic.