EV DNA from pancreatic cancer patient-derived cells harbors molecular, coding, non-coding signatures and mutational hotspots.

DNA packaged into cancer cell-derived EV is not well appreciated. Here, we uncovered signatures of EV DNA secreted by pancreatic cancer cells. The cancer cells and non-cancer counterparts exhibit distinct low vs.

Systemic Therapies for Pediatric Alopecia Areata.

Alopecia areata (AA) is an autoimmune hair loss disorder that commonly affects children. While mild disease may improve spontaneously or with topical therapies, patients with more extensive involvement typically require systemic treatment. This narrative review examines the literature describing systemic therapies for pediatric AA.

A Recombinant Antibody Against ALK2 Promotes Tissue Iron Redistribution and Contributes to Anemia Resolution in a Mouse Model of Anemia of Inflammation.

Patients with chronic inflammation are burdened with anemia of inflammation (AI), where inflammatory cytokines inhibit erythropoiesis, impede erythropoietin production, and limit iron availability by inducing the iron regulator hepcidin. High hepcidin hinders iron absorption and recycling, thereby worsening the impaired erythropoiesis by restricting iron availability. AI management is important as anemia impacts quality of life and potentially affects morbidity and mortality.

Wavelength-dependent DNA damage induced by single wavelengths of UV-C radiation (215 to 255 nm) in a human cornea model.

Scientific bodies overseeing UV radiation protection recommend safety limits for exposure to ultraviolet radiation in the workplace based on published peer-reviewed data. To support this goal, a 3D model of the human cornea was used to assess the wavelength dependence of corneal damage induced by UV-C radiation. In the first set of experiments the models were exposed with or without simulated tears; at each wavelength (215-255 nm) cells with DNA dimers and their distribution within the epithelium were measured.

Wavelength-Dependent DNA Damage Induced by Single Wavelengths of UVC Light (215 to 255 nm) in a Human Cornea Model.

Scientific bodies overseeing UV radiation protection recommend safety limits for exposure to ultraviolet light in the workplace based on published peer-reviewed data. To support this goal, a 3D model of the human cornea was used to assess the wavelength dependence of corneal damage induced by UVC light. In the first set of experiments the models were exposed with or without simulated tears; at each wavelength (215-255 nm) cells with DNA dimers and their distribution within the epithelium were measured.

Spatial and temporal transmission dynamics of respiratory syncytial virus in New Zealand before and after the COVID-19 pandemic.

Human respiratory syncytial virus (RSV) is a major cause of acute respiratory infection. In 2020, RSV was eliminated from New Zealand due to non-pharmaceutical interventions (NPI) used to control the spread of SARS-CoV-2. However, in 2021, following a brief quarantine-free travel agreement with Australia, there was a large-scale nationwide outbreak of RSV that led to reported cases more than five-times higher than typical seasonal patterns.

Extending the acute skin response spectrum to include the far-UVC.

Guidance on maximal limits for ultraviolet (UV) exposure has been developed by national and international organizations to protect against adverse effects on human skin and eyes. These guidelines consider the risk of both acute effects (i.e.

Music Listening as Exploratory Behavior: From Dispositional Reactions to Epistemic Interactions with the Sonic World.

Listening to music can span a continuum from passive consumption to active exploration, relying on processes of coping with the sounds as well as higher-level processes of sense-making. Revolving around the major questions of "what" and "how" to explore, this paper takes a naturalistic stance toward music listening, providing tools to objectively describe the underlying mechanisms of musical sense-making by weakening the distinction between music and non-music. Starting from a non-exclusionary conception of "coping" with the sounds, it stresses the exploratory approach of treating music as a sound environment to be discovered by an attentive listener.

Identification of ATP-Competitive Human CMG Helicase Inhibitors for Cancer Intervention that Disrupt CMG-Replisome Function.

The human CMG helicase (Cdc45-MCM-GINS) is a novel target for anticancer therapy. Tumor-specific weaknesses in the CMG are caused by oncogene-driven changes that adversely affect CMG function, and CMG activity is required for recovery from replicative stresses such as chemotherapy. Herein, we developed an orthogonal biochemical screening approach and identified CMG inhibitors (CMGi) that inhibit ATPase and helicase activities in an ATP-competitive manner at low micromolar concentrations.

Improving Safety and Satisfaction in the Safety Monitoring Unit.

BACKGROUND: The safety monitoring unit (SMU) is a 4-bed unit designated for patients who require continual observation. Most experience some form of dementia, and agitation and aggression are not uncommon. When deescalation techniques do not work, request for help may be necessary.

Film dosimetry for occupant exposure monitoring within Far-UVC installations.

Far-UVC radiation between 200 and 230 nm is a promising technology for reducing airborne disease transmission. Previous work with far-UVC lamps has demonstrated the efficacy of far-UVC radiation to inactivate bacteria and viruses while presenting minimal human health hazards. While far-UVC intentionally exposes the occupied space, effectively disinfecting air between occupants, installations must still ensure that occupant eye and skin exposure is within the recommended daily limits.

Susceptibility of extremophiles to far-UVC light for bioburden reduction in spacecraft assembly facilities.

The prevention and reduction of microbial species entering and leaving Earth's biosphere is a critical aspect of planetary protection research. While various decontamination methods exist and are currently utilized for planetary protection purposes, the use of far-UVC light (200-230 nm) as a means for microbial reduction remains underexplored. Unlike conventional germicidal ultraviolet at 254 nm, which can pose a health risk to humans even with small exposure doses, far-UVC light poses minimal health hazard making it a suitable candidate for implementation in occupied areas of spacecraft assembly facilities.

Remote or in-clinic? The effect of service delivery mode on hearing aid output: study protocol for a double-blinded, randomised trial in adults with mild to moderate sensorineural hearing loss.

Background: Teleaudiology can potentially improve access to hearing healthcare services. Remote hearing aid fittings offer a new mode of service delivery that removes barriers of geography and access to an audiologist. Real-ear measurements (REMs) are the gold standard for hearing aid output verification but require in-clinic appointments.

222 nm far-UVC light markedly reduces the level of infectious airborne virus in an occupied room.

An emerging intervention for control of airborne-mediated pandemics and epidemics is whole-room far-UVC (200-235 nm). Laboratory studies have shown that 222-nm light inactivates airborne pathogens, potentially without harm to exposed occupants. While encouraging results have been reported in benchtop studies and in room-sized bioaerosol chambers, there is a need for quantitative studies of airborne pathogen reduction in occupied rooms.

Summer Cancer Research Experience for High School Students from Historically Marginalized Populations in Kansas City.

The Accelerate Cancer Education (ACE) summer research program at The University of Kansas Cancer Center (KUCC) is a six-week, cancer-focused, summer research experience for high school students from historically marginalized populations in the Kansas City metropolitan area. Cancer affects all populations and continues to be the second leading cause of death in the United States, and a large number of disparities impact racial and ethnic minorities, including increased cancer incidence and mortality. Critically, strategies to bolster diversity, equity, inclusion, and accessibility are needed to address persistent cancer disparities.

Audiological Service Delivery and Uptake in New Zealand Regional Areas.

Background: In New Zealand, as in many places, a significant proportion of the population lives outside the main urban centres. People living in regional areas have similar needs for audiological services as those living in urban centres; however, economic and geographical barriers can be a barrier to accessible services. The objective of this research was to explore factors that influence equitable audiological service provision and user uptake of services in regional areas of New Zealand.

Selective Reduction of Cysteine Mutant Antibodies for Site-Specific Antibody-Drug Conjugates.

Developing site-specific conjugation technologies for antibody-drug conjugates (ADCs) aims to produce more homogeneous and controlled drug-loaded ADCs to reduce variability and thereby improve the therapeutic index. This article presents a technology that uses cysteine mutant antibodies and mild phosphine-based reductants to prepare site-specific ADCs. The two types of cysteine mutant antibodies, designated C6v1 and C6v2, have one of the interchain disulfide-forming cysteines in the Fab region in the light chain (LC214) or in the heavy chain (HC220) substituted by alanine (or other amino acids), respectively.

Discovery of ABBV-154, an anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody-Drug Conjugate (iADC).

Stable attachment of drug-linkers to the antibody is a critical requirement, and for maleimide conjugation to cysteine, it is achieved by ring hydrolysis of the succinimide ring. During ADC profiling in our in-house property screening funnel, we discovered that the succinimide ring open form is in equilibrium with the ring closed succinimide. Bromoacetamide (BrAc) was identified as the optimal replacement, as it affords stable attachment of the drug-linker to the antibody while completely removing the undesired ring open-closed equilibrium.