Breast Imaging During a Cyberattack and Global Pandemic: What We Did to Pick Up the Pieces.

Cybersecurity in healthcare is a very real threat with the potential to severely disrupt patient care, place extra burden on an already strained system, and result in significant financial losses for a hospital or healthcare network. In October 2020, on the backdrop of the ongoing COVID-19 pandemic, our institution experienced one of the most significant cyberattacks on a healthcare system to date, lasting for nearly 40 days. By sharing our experience in radiology, and specifically in breast imaging, including the downtime procedures we relied upon and the lessons that we learned emerging from this cyberattack, we hope to help future victims of a healthcare cyberattack successfully weather such an experience.

Unraveling the Role of Charge Patterning in the Micellar Structure of Sequence-Defined Amphiphilic Peptoid Oligomers by Molecular Dynamics Simulations.

Electrostatic interactions play a significant role in regulating biological systems and have received increasing attention due to their usefulness in designing advanced stimulus-responsive materials. Polypeptoids are highly tunable N-substituted peptidomimetic polymers that lack backbone hydrogen bonding and chirality. Therefore, polypeptoids are suitable systems to study the effect of noncovalent interactions of substituents without complications of backbone intramolecular and intermolecular hydrogen bonding. In this study, all-atom molecular dynamics (MD) simulations were performed on micelles formed by a series of sequence-defined ionic polypeptoid block copolymers consisting of a hydrophobic segment and a hydrophilic segment in an aqueous solution. By combining the results from MD simulations and experimental small-angle neutron scattering data, further insights were gained into the internal structure of the formed polypeptoid micelles, which is not always directly accessible from experiments. In addition, information was gained into the physics of the noncovalent interactions responsible for the self-assembly of weakly charged polypeptoids in an aqueous solution. While the aggregation number is governed by electrostatic repulsion of the negatively charged carboxylate (COO-) substituents on the polypeptoid chain within the micelle, MD simulations indicate that the position of the charge on singly charged chains mediates the shape of the micelle through the charge-dipole interactions between the COO- substituent and the surrounding water. Therefore, the polypeptoid micelles formed from the single-charged series offer the possibility for tailorable micelle shapes. In contrast, the polypeptoid micelles formed from the triple-charged series are characterized by more pronounced electrostatic repulsion that competes with more significant charge-sodium interactions, making it difficult to predict the shape of the micelles. This work has helped further develop design principles for the shape and structure of self-assembled micelles by controlling the position of charged moieties on the backbone of polypeptoid block copolymers.

Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts.

Growth factors (GF) are critical cytokines in wound healing. However, the direct delivery of these biochemical cues into a wound site significantly increases the cost of wound dressings and can lead to a strong immunological response due to the introduction of a foreign source of GFs. To overcome this challenge, we designed a poly(ethylene glycol) diacrylate (PEGDA) hydrogel with the potential capacity to sequester autologous GFs directly from the wound site. We demonstrated that synthetic peptide sequences covalently tethered to PEGDA hydrogels physically retained human transforming growth factor beta 1 (hTGFß1) and human vascular endothelial growth factor (hVEGF) at 3.2 and 0.6 ng/mm2, respectively. In addition, we demonstrated that retained hTGFß1 and hVEGF enhanced human dermal fibroblasts (HDFa) average cell surface area and proliferation, respectively, and that exposure to both GFs resulted in up to 1.9-fold higher fraction of area covered relative to the control. After five days in culture, relative to the control surface, non-covalently bound hTGFß1 significantly increased the expression of collagen type I and hTGFß1 and downregulated vimentin and matrix metalloproteinase 1 expression. Cumulatively, the response of HDFa to hTGFß1 aligns well with the expected response of fibroblasts during the early stages of wound healing.

Imaging Health and Radiology Care of Transgender Patients: A Call to Build Evidence-Based Best Practices.

Transgender people have a gender identity that differs from their natal sex and experience many forms of discrimination, including within the health care field. Although transgender patients only comprise 0.6% of the adult US population, they frequently require imaging evaluation. Few published articles provide data-driven research on optimizing education of the radiology care team and delivery of inclusive and respectful imaging care to this vulnerable population; existing data suggest prior areas of success and prior areas of failure. Here, we offer specific recommendations on how radiology care team members can better serve transgender patients and begin generating much needed evidence-based best practices to improve their imaging health and care.

Lifestyle, Behavioral, and Dietary Risk Factors in Relation to Mammographic Breast Density in Women at High Risk for Breast Cancer.

BACKGROUND: Women at high risk for breast cancer due to genetics or risk factor profiles are counseled to adopt lifestyle, behavioral, and dietary changes to help reduce their risk. These recommendations are based on studies of women at average risk, so their effectiveness in high-risk women is unclear. METHODS: We evaluated the impact of physical activity, smoking, alcohol consumption, and intake of folate and carotenoids on mammographic breast density-a proxy for breast cancer risk-among 387 high-risk women. Exposures were self-reported on questionnaires. Breast dense area, nondense area, and percent dense area were measured from screening mammograms with Library for Breast Radiodensity Assessment software. Cross-sectional associations were estimated with multivariable quantile regression models. RESULTS: After adjusting for age, adiposity, reproductive history, and use of postmenopausal hormones, no breast density measure was associated with physical activity level, smoking status, alcohol consumption, or estimated intake of folate, alpha-carotene, beta-carotene, lutein/zeaxanthin, and beta-cryptoxanthin. Lycopene intake was associated with lower dense area when comparing the highest and lowest intake categories (adjusted difference in median = -14 cm2, 95% confidence interval: -29 to 1.3 cm2). This association may be explained by incomplete adjustment for adiposity. CONCLUSIONS: Recommended lifestyle, behavioral, and dietary changes to mitigate personal risk of breast cancer do not substantially impact mammographic breast density measures. IMPACT: Alternative strategies, such as increased uptake of chemoprevention, may better serve risk reduction efforts in women at high risk for breast cancer.

Slow hydrogen atom transfer reactions of oxo- and hydroxo-vanadium compounds: the importance of intrinsic barriers.

Reactions are described that interconvert vanadium(IV) oxo-hydroxo complexes [V(IV)O(OH)(R(2)bpy)(2)]BF(4) (1a-c) and vanadium(V) dioxo complexes [V(V)O(2)(R(2)bpy)(2)]BF(4) (2a-c) [R(2)bpy = 4,4'-di-tert-butyl-2,2'-bipyridine ((t)Bu(2)bpy), a; 4,4'-dimethyl-2,2'-bipyridine (Me(2)bpy), b; 2,2'-bipyridine (bpy), c]. These are rare examples of pairs of isolated, sterically unencumbered, first-row metal-oxo/hydroxo complexes that differ by a hydrogen atom (H(+) + e(-)). The V(IV)-(t)Bu(2)bpy derivative 1a has a useful (1)H NMR spectrum, despite being paramagnetic. Complex 2a abstracts H(*) from organic substrates with weak O-H and C-H bonds, converting 2,6-(t)Bu(2)-4-MeO-C(6)H(2)OH (ArOH) and 2,2,6,6-tetramethyl-N-hydroxypiperidine (TEMPOH) to their corresponding radicals ArO(*) and TEMPO, hydroquinone to benzoquinone, and dihydroanthracene to anthracene. The equilibrium constant for 2a + ArOH <==> 1a + ArO(*) is (4 +/- 2) x 10(-3), implying that the VO-H bond dissociation free energy (BDFE) is 70.6 +/- 1.2 kcal mol(-1). Consistent with this value, 1a is oxidized by 2,4,6-(t)Bu(3)C(6)H(2)O(*). All of these reactions are surprisingly slow, typically occurring over hours at ambient temperatures. The net hydrogen-atom pseudo-self-exchange 1a + 2b <==> 2a + 1b, using the (t)Bu- and Me-bpy substituents as labels, also occurs slowly, with k(se) = 1.3 x 10(-2) M(-1) s(-1) at 298 K, DeltaH(double dagger) = 15 +/- 2 kcal mol(-1), and DeltaS(double dagger) = 16 +/- 5 cal mol(-1) K. Using this k(se) and the BDFE, the vanadium reactions are shown to follow the Marcus cross relation moderately well, with calculated rate constants within 10(2) of the observed values. The vanadium self-exchange reaction is ca. 10(6) slower than that for the related Ru(IV)O(py)(bpy)(2)(2+)/Ru(III)OH(py)(bpy)(2)(2+) self-exchange. The origin of this dramatic difference has been probed with DFT calculations on the self-exchange reactions of 1c + 2c and on monocationic ruthenium complexes with pyrrolate or fluoride in place of the py ligands. The calculations reproduce the difference in barrier heights and show that transfer of a hydrogen atom involves more structural reorganization for vanadium than the Ru analogues. The vanadium complexes have larger changes in the metal-oxo and metal-hydroxo bond lengths, which is traced to the difference in d-orbital occupancy in the two systems. This study thus highlights the importance of intrinsic barriers in the transfer of a hydrogen atom, in addition to the thermochemical (bond strength) factors that have been previously emphasized.

Collagen Based Multicomponent Interpenetrating Networks as Promising Scaffolds for 3D Culture of Human Neural Stem Cells, Human Astrocytes, and Human Microglia.

This work describes for the first time the fabrication and characterization of multicomponent interpenetrating networks composed of collagen I, hyaluronic acid, and poly(ethylene glycol) diacrylate for the 3D culture of human neural stem cells, astrocytes, and microglia. The chemical composition of the scaffolds can be modulated while maintaining values of complex moduli within the range of the mechanical performance of brain tissue (∼6.9 kPa) and having cell viability exceeding 84%. The developed scaffolds are a promising new family of biomaterials that can potentially serve as 3D in vitro models for studying the physiology and physiopathology of the central nervous system.