A Novel B7-H6-Targeted IgG-Like T Cell-Engaging Antibody for the Treatment of Gastrointestinal Tumors.

Purpose: Advanced-stage gastrointestinal cancers represent a high unmet need requiring new effective therapies. We investigated the antitumor activity of a novel T cell-engaging antibody (B7-H6/CD3 ITE) targeting B7-H6, a tumor-associated antigen that is expressed in gastrointestinal tumors.

Experimental Design: Membrane proteomics and IHC analysis identified B7-H6 as a tumor-associated antigen in gastrointestinal tumor tissues with no to very little expression in normal tissues.

LY6G6D is a selectively expressed colorectal cancer antigen that can be used for targeting a therapeutic T-cell response by a T-cell engager.

Colorectal cancer (CRC) is one of the most common cancers worldwide and demands more effective treatments. We sought to identify tumor selective CRC antigens and their therapeutic potential for cytotoxic T-cell targeting by transcriptomic and immunohistochemical analysis. LY6G6D was identified as a tumor selectively expressed CRC antigen, mainly in the microsatellite stable (MSS) subtype.

What is the Evidence for Over the Counter Laxatives to Treat Childhood Constipation?

Purpose Of Review: Functional constipation is a common pediatric GI disorder that is responsible for a significant portion of pediatric office visits each year. It presents a significant stressor for patients, their families, and providers alike. There are a variety of over the counter agents available for treatment of pediatric constipation.

A Novel Antagonistic CD73 Antibody for Inhibition of the Immunosuppressive Adenosine Pathway.

Despite some impressive clinical results with immune checkpoint inhibitors, the majority of patients with cancer do not respond to these agents, in part due to immunosuppressive mechanisms in the tumor microenvironment. High levels of adenosine in tumors can suppress immune cell function, and strategies to target the pathway involved in its production have emerged. CD73 is a key enzyme involved in adenosine production.

Discovery Strategies to Maximize the Clinical Potential of T-Cell Engaging Antibodies for the Treatment of Solid Tumors.

T-cell Engaging bispecific antibodies (TcEs) that can re-direct cytotoxic T-cells to kill cancer cells have been validated in clinical studies. To date, the clinical success with these agents has mainly been seen in hematologic tumor indications. However, an increasing number of TcEs are currently being developed to exploit the potent mode-of-action to treat solid tumor indications, which is more challenging in terms of tumor-cell accessibility and the complexity of the tumor microenvironment (TME).

A Bispecific DLL3/CD3 IgG-Like T-Cell Engaging Antibody Induces Antitumor Responses in Small Cell Lung Cancer.

Purpose: Small cell lung cancer (SCLC) is the most lethal and aggressive subtype of lung carcinoma characterized by highly chemotherapy-resistant recurrence in the majority of patients. To effectively treat SCLC, we have developed a unique and novel IgG-like T-cell engaging bispecific antibody (ITE) that potently redirects T-cells to specifically lyse SCLC cells expressing Delta-like ligand 3 (DLL3), an antigen that is frequently expressed on the cell surface of SCLC cells, with no to very little detectable expression in normal tissues.

Experimental Design: The antitumor activity and mode of action of DLL3/CD3 ITE was evaluated using SCLC cell lines and primary human effector cells and in an SCLC xenograft model reconstituted with human CD3 T-cells.

Antitumor Activity of the IGF-1/IGF-2-Neutralizing Antibody Xentuzumab (BI 836845) in Combination with Enzalutamide in Prostate Cancer Models.

Androgen deprivation therapy and second-generation androgen receptor signaling inhibitors such as enzalutamide are standard treatments for advanced/metastatic prostate cancer. Unfortunately, most men develop resistance and relapse; signaling via insulin-like growth factor (IGF) has been implicated in castration-resistant prostate cancer. We evaluated the antitumor activity of xentuzumab (IGF ligand-neutralizing antibody), alone and in combination with enzalutamide, in prostate cancer cell lines (VCaP, DuCaP, MDA PCa 2b, LNCaP, and PC-3) using established assays, and , using LuCaP 96CR, a prostate cancer patient-derived xenograft (PDX) model.

Supporting Spartina: Interdisciplinary perspective shows Spartina as a distinct solid genus.

In 2014, a DNA-based phylogenetic study confirming the paraphyly of the grass subtribe Sporobolinae proposed the creation of a large monophyletic genus Sporobolus, including (among others) species previously included in the genera Spartina, Calamovilfa, and Sporobolus. Spartina species have contributed substantially (and continue contributing) to our knowledge in multiple disciplines, including ecology, evolutionary biology, molecular biology, biogeography, experimental ecology, biological invasions, environmental management, restoration ecology, history, economics, and sociology. There is no rationale so compelling to subsume the name Spartina as a subgenus that could rival the striking, global iconic history and use of the name Spartina for over 200 yr.

Acquired Resilience: An Evolved System of Tissue Protection in Mammals.

This review brings together observations on the stress-induced regulation of resilience mechanisms in body tissues. It is argued that the stresses that induce tissue resilience in mammals arise from everyday sources: sunlight, food, lack of food, hypoxia and physical stresses. At low levels, these stresses induce an organised protective response in probably all tissues; and, at some higher level, cause tissue destruction.

eHealth Technologies, Multimorbidity, and the Office Visit: Qualitative Interview Study on the Perspectives of Physicians and Nurses.

Background: eHealth is a broad term referring to the application of information and communication technologies in the health sector, ranging from health records to telemedicine and multiple forms of health education and digital tools. By providing increased and anytime access to information, opportunities to exchange experiences with others, and self-management support, eHealth has been heralded as transformational. It has created a group of informed, engaged, and empowered patients as partners, equipped to take part in shared decision making and effectively self-manage chronic illness.

Genetic Risk for Inflammatory Bowel Disease Is a Determinant of Crohn's Disease Development in Chronic Granulomatous Disease.

Background: Approximately, one-third to one-half of children with chronic granulomatous disease (CGD) develop gastrointestinal inflammation characteristic of idiopathic inflammatory bowel disease (IBD), usually Crohn's disease. We hypothesized that the overall IBD genetic risk, determined by IBD genetic risk score (GRS), might in part determine IBD development in CGD.

Methods: We reviewed medical records to establish IBD diagnoses in CGD subjects seen at NIAID.

Decitabine enhances anti-CD33 monoclonal antibody BI 836858-mediated natural killer ADCC against AML blasts.

Acute myeloid leukemia (AML) is the most common type of acute leukemia, affecting older individuals at a median age of 67 years. Resistance to intensive induction chemotherapy is the major cause of death in elderly AML; hence, novel treatment strategies are warranted. CD33-directed antibody-drug conjugates (gemtuzumab ozogamicin) have been shown to improve overall survival, validating CD33 as a target for antibody-based therapy of AML.

eHealth, Participatory Medicine, and Ethical Care: A Focus Group Study of Patients' and Health Care Providers' Use of Health-Related Internet Information.

Background: The rapid explosion in online digital health resources is seen as transformational, accelerating the shift from traditionally passive patients to patients as partners and altering the patient-health care professional (HCP) relationship. Patients with chronic conditions are increasingly engaged, enabled, and empowered to be partners in their care and encouraged to take responsibility for managing their conditions with HCP support.

Objective: In this paper, we focus on patients' and HCPs' use of health-related Internet information and how it influences the patient-HCP relationship.

Proof-of-concept study of a Web-based methotrexate decision aid for patients with rheumatoid arthritis.

Objective: To assess the extent to which an online patient decision aid reduced decisional conflict and improved self-management knowledge/skills in patients who were considering methotrexate for rheumatoid arthritis (RA).

Methods: We used a mixed-methods pre-post study design. Eligible participants had a diagnosis of RA, had been prescribed methotrexate but were unsure about starting it, and had access to the internet.

Women's accounts of help-seeking in early rheumatoid arthritis from symptom onset to diagnosis.

Background: As interest in gender and health grows, the notion that women are more likely than men to consult doctors is increasingly undermined as more complex understandings of help seeking and gender emerge. While men's reluctance to seek help is associated with practices of masculinities, there has been less consideration of women's help-seeking practices. Rheumatoid arthritis (RA) is a chronic disease that predominantly affects women and requires prompt treatment but considerable patient-based delays persist along the care pathway.

Shared patterns of species turnover between seaweeds and seed plants break down at increasing distances from the sea.

We tested for correlations in the degree of spatial similarity between algal and terrestrial plants communities along 5500 km of temperate Australian coastline and whether the strength of correlation weakens with increasing distance from the coast. We identified strong correlations between macroalgal and terrestrial plant communities within the first 100 km from shore, where the strength of these marine-terrestrial correlations indeed weakens with increasing distance inland. As such, our results suggest that marine-driven community homogenization processes decompose with increasing distance from the shore toward inland.

Pharmacodynamic and antineoplastic activity of BI 836845, a fully human IGF ligand-neutralizing antibody, and mechanistic rationale for combination with rapamycin.

Insulin-like growth factor (IGF) signaling is thought to play a role in the development and progression of multiple cancer types. To date, therapeutic strategies aimed at disrupting IGF signaling have largely focused on antibodies that target the IGF-I receptor (IGF-IR). Here, we describe the pharmacologic profile of BI 836845, a fully human monoclonal antibody that utilizes an alternative approach to IGF signaling inhibition by selectively neutralizing the bioactivity of IGF ligands.

Usability testing of ANSWER: a web-based methotrexate decision aid for patients with rheumatoid arthritis.

Background: Decision aids are evidence-based tools designed to inform people of the potential benefit and harm of treatment options, clarify their preferences and provide a shared decision-making structure for discussion at a clinic visit. For patients with rheumatoid arthritis (RA) who are considering methotrexate, we have developed a web-based patient decision aid called the ANSWER (Animated, Self-serve, Web-based Research Tool). This study aimed to: 1) assess the usability of the ANSWER prototype; 2) identify strengths and limitations of the ANSWER from the patient's perspective.

Exploring eHealth Ethics and Multi-Morbidity: Protocol for an Interview and Focus Group Study of Patient and Health Care Provider Views and Experiences of Using Digital Media for Health Purposes.

Background: eHealth is a broad term referring to the application of information and communication technologies in the health sector, ranging from health records to medical consultations (telemedicine) and multiple forms of health education, support, and tools. By providing increased and anytime access to information, opportunities to exchange experiences with others, and self-management support, eHealth has been heralded as transformational. It has the potential to accelerate the shift from traditional "passive patient" to an informed, engaged, and empowered "patient as partner," equipped to take part in shared decision-making, and take personal responsibility for self-managing their illness.

A qualitative interview study: patient accounts of medication use in early rheumatoid arthritis from symptom onset to early postdiagnosis.

Objective: To examine accounts of medication use in participants with early rheumatoid arthritis (RA) from symptom onset to early postdiagnosis.

Design: Qualitative study with in-depth, personal interviews.

Participants: 37 women and one man, aged 30-70s, with a diagnosis of RA <12 months.

Climate change and intertidal wetlands.

Intertidal wetlands are recognised for the provision of a range of valued ecosystem services. The two major categories of intertidal wetlands discussed in this contribution are saltmarshes and mangrove forests. Intertidal wetlands are under threat from a range of anthropogenic causes, some site-specific, others acting globally.

The effect of a simulation-based training intervention on the performance of established critical care unit teams.

Objective: We evaluated the effectiveness of a simulation-based intervention on improving teamwork in multidisciplinary critical care teams managing airway and cardiac crises and compared simulation-based learning and case-based learning on scores for performance.

Design: Self-controlled randomized crossover study design with blinded assessors.

Setting: A simulated critical care ward, using a high-fidelity patient simulator, in a university simulation center.

Evaluation of an instrument to measure teamwork in multidisciplinary critical care teams.

Introduction: Teamwork failures contribute to adverse events causing harm to patients. Establishing and maintaining a team and managing the tasks are active processes. Medical education largely ignores teamwork skills.