Hematological and immunological profiles of podoconiosis patients in West Gojjam Zone, Ethiopia: A comparative cross-sectional study.

Background: Podoconiosis is a geo-chemically induced, non-infectious, familial, chronic lymphedema of the legs that occurs among barefoot people in rural, farming communities with extreme poverty. Despite a growing body of research surrounding the disease, the pathogenesis of the disease is relatively unknown. This study aims to investigate the immunological and hematological profiles of individuals affected by podoconiosis in comparison to healthy controls.

Regulatory T cells crosstalk with tumor cells and endothelium through lymphotoxin signaling.

Regulatory T cells (Tregs) with multifaceted functions suppress anti-tumor immunity by signaling surrounding cells. Here we report Tregs use the surface lymphotoxin (LT)α1β2 to preferentially stimulate LT beta receptor (LTβR) nonclassical NFκB signaling on both tumor cells and lymphatic endothelial cells (LECs) to accelerate tumor growth and metastasis. Selectively targeting LTβR nonclassical NFκB pathway inhibits tumor growth and migration in vitro.

Engineered Immune Constructs Alter Antigen-Specific Immune Tolerance and Confer Durable Protection in Myelin-Driven Autoimmunity.

Autoimmune diseases are broadly characterized as a failure in immune tolerance. In multiple sclerosis (MS), autoreactive immune cells attack the protective myelin sheath lining neurons in the central nervous system. Therapeutic strategies that selectively and durably restore immune tolerance without broad immunosuppression are urgently needed for MS.

Digital Maturity as a Predictor of Quality and Safety Outcomes in US Hospitals: Cross-Sectional Observational Study.

Background: This study demonstrates that digital maturity contributes to strengthened quality and safety performance outcomes in US hospitals. Advanced digital maturity is associated with more digitally enabled work environments with automated flow of data across information systems to enable clinicians and leaders to track quality and safety outcomes. This research illustrates that an advanced digitally enabled workforce is associated with strong safety leadership and culture and better patient health and safety outcomes.

Inter-subject correlation of audience facial expressions predicts audience engagement during theatrical performances.

During performances, audiences experience various emotional states, and these are reflected in their ongoing facial expressions. We investigated if audience engagement could be determined by measuring the inter-subject correlation (ISC) of non-invasively recorded audience facial expressions. We filmed the faces of multiple audience members at theatrical performances and determined the intensity of their different facial expressions throughout the performances.

Advancing immunotherapy using biomaterials to control tissue, cellular, and molecular level immune signaling in skin.

Immunotherapies have been transformative in many areas, including cancer treatments, allergies, and autoimmune diseases. However, significant challenges persist in extending the reach of these technologies to new indications and patients. Some of the major hurdles include narrow applicability to patient groups, transient efficacy, high cost burdens, poor immunogenicity, and side effects or off-target toxicity that results from lack of disease-specificity and inefficient delivery.

Microneedle array delivery of recapitulates bubonic plague.

Fleas transmit directly within the dermis of mammals to cause bubonic plague. Syringe-mediated inoculation is widely used to recapitulate bubonic plague and study pathogenesis. However, intradermal needle inoculation is tedious, error prone, and poses a significant safety risk for laboratorians.

Dissecting regulatory T cell expansion using polymer microparticles presenting defined ratios of self-antigen and regulatory cues.

Biomaterials allow for the precision control over the combination and release of cargo needed to engineer cell outcomes. These capabilities are particularly attractive as new candidate therapies to treat autoimmune diseases, conditions where dysfunctional immune cells create pathogenic tissue environments during attack of self-molecules termed self-antigens. Here we extend past studies showing combinations of a small molecule immunomodulator co-delivered with self-antigen induces antigen-specific regulatory T cells.

Transforming bioengineering with unbiased teams and tools.

Scientific bias originates from both researchers and techniques. Evidence-based strategies to mitigate this bias include the assembly of diverse teams, development of rigorous experimental designs, and use of unbiased analytical techniques. Here, we highlight potential starting points to decrease bias in bioengineering research.

Tuning innate immune function using microneedles containing multiple classes of toll-like receptor agonists.

Microneedle arrays (MNAs) are patches displaying hundreds of micron-scale needles that can penetrate skin. As a result, these arrays efficiently and painlessly access this immune cell-rich niche, motivating significant clinical interest in MNA-based vaccines. Our lab has developed immune polyelectrolyte multilayers (iPEMs), nanostructures built entirely from immune signals employing electrostatic self-assembly.

Engineering the lymph node environment promotes antigen-specific efficacy in type 1 diabetes and islet transplantation.

Antigen-specific tolerance is a key goal of experimental immunotherapies for autoimmune disease and allograft rejection. This outcome could selectively inhibit detrimental inflammatory immune responses without compromising functional protective immunity. A major challenge facing antigen-specific immunotherapies is ineffective control over immune signal targeting and integration, limiting efficacy and causing systemic non-specific suppression.

Self-Assembly of Immune Signals to Program Innate Immunity through Rational Adjuvant Design.

Recent clinical studies show activating multiple innate immune pathways drives robust responses in infection and cancer. Biomaterials offer useful features to deliver multiple cargos, but add translational complexity and intrinsic immune signatures that complicate rational design. Here a modular adjuvant platform is created using self-assembly to build nanostructured capsules comprised entirely of antigens and multiple classes of toll-like receptor agonists (TLRas).

Mapping the Mechanical and Immunological Profiles of Polymeric Microneedles to Enable Vaccine and Immunotherapy Applications.

Biomaterials hold great promise for vaccines and immunotherapy. One emerging biomaterials technology is microneedle (MNs) delivery. MNs are arrays of micrometer-sized needles that are painless and efficiently deliver cargo to the specialized immunological niche of the skin.

Clinical outcomes and the impact of prior oral anticoagulant use in patients with coronavirus disease 2019 admitted to hospitals in the UK - a multicentre observational study.

Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease 2019 (COVID-19). Patients on oral anticoagulants (OAC) prior to diagnosis of COVID-19 may therefore have better outcomes. In this multicentre observational study of 5 883 patients (≥18 years) admitted to 26 UK hospitals between 1 April 2020 and 31 July 2020, overall mortality was 29·2%.

The clinical course of COVID-19 in pregnant versus non-pregnant women requiring hospitalisation: results from the multicentre UK CA-COVID-19 study.

The impact of COVID-19 infection on pregnant women remains relatively unknown but the physiological changes of pregnancy and hypercoagulability of COVID-19 may further increase thrombotic risk. In this retrospective multicentre observational study, we report clinical characteristics and outcomes in 36 pregnant women requiring hospitalisation for COVID-19 compared to a propensity-matched cohort of non-pregnant women. Pregnant women had a lower haemoglobin and higher lymphocyte counts but no differences in other haematological or biochemical parameters on admission compared to non-pregnant women.

Biophysical Properties of Self-Assembled Immune Signals Impact Signal Processing and the Nature of Regulatory Immune Function.

Outcomes during immunotherapy are impacted not only by the specific therapeutic signals and pharmacodynamics, but also by the biophysical forms in which signals are delivered. This integration is determinative in autoimmunity because the disease is caused by immune dysregulation and inflammation. Unfortunately, the links between nanomaterial design, biophysical properties, and immune regulation are poorly defined.

Exploiting Rational Assembly to Map Distinct Roles of Regulatory Cues during Autoimmune Therapy.

Autoimmune diseases like multiple sclerosis (MS), type 1 diabetes, and lupus occur when the immune system attacks host tissue. Immunotherapies that promote selective tolerance without suppressing normal immune function are of tremendous interest. Here, nanotechnology was used for rational assembly of peptides and modulatory immune cues into immune complexes.

Engineered immunological niches to monitor disease activity and treatment efficacy in relapsing multiple sclerosis.

Relapses in multiple sclerosis can result in irreversible nervous system tissue injury. If these events could be detected early, targeted immunotherapy could potentially slow disease progression. We describe the use of engineered biomaterial-based immunological niches amenable to biopsy to provide insights into the phenotype of innate immune cells that control disease activity in a mouse model of multiple sclerosis.

Human lung organoids develop into adult airway-like structures directed by physico-chemical biomaterial properties.

Tissues derived from human pluripotent stem cells (hPSCs) often represent early stages of fetal development, but mature at the molecular and structural level when transplanted into immunocompromised mice. hPSC-derived lung organoids (HLOs) transplantation has been further enhanced with biomaterial scaffolds, where HLOs had improved tissue structure and cellular differentiation. Here, our goal was to define the physico-chemical biomaterial properties that maximally enhanced transplant efficiency, including features such as the polymer type, degradation, and pore interconnectivity of the scaffolds.

High Frequency Spectral Ultrasound Imaging to Detect Metastasis in Implanted Biomaterial Scaffolds.

For most cancers, metastasis is the point at which disease is no longer curable. Earlier detection of metastasis, when it is undetectable by current clinical methods, may enable better outcomes. We have developed a biomaterial implant that recruits metastatic cancer cells in mouse models of breast cancer.

Microporous scaffolds loaded with immunomodulatory lentivirus to study the contribution of immune cell populations to tumor cell recruitment in vivo.

Metastases are preceded by stochastic formation of a hospitable microenvironment known as the premetastatic niche, which has been difficult to study. Herein, we employ implantable polycaprolactone scaffolds as an engineered premetastatic niche to independently investigate the role of interleukin-10 (IL10), CXCL12, and CCL2 in recruiting immune and tumor cells and impacting breast cancer cell phenotype via lentiviral overexpression. Lentivirus delivered from scaffolds in vivo achieved sustained transgene expression for 56 days.