A real-world study of treatment sequences and second-line clinical outcomes in patients with HER2-positive metastatic breast cancer in US community practice.

Purpose: Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US).

Differences and Disparities Among Self-Referred and Physician-Referred Populations Undergoing Coronary Artery Calcium Scanning.

Background: Coronary artery calcium computed tomography (CAC) is an important tool for identifying subclinical atherosclerosis and cardiovascular risk stratification. Despite robust evidence and inclusion in current guidelines, CAC is considered investigational by some US insurance carriers and requires out-of-pocket expenses. CAC can be obtained via self-referral (SR) or physician referral (PR).

Myocardial Work in Echocardiography.

Myocardial work is an emerging tool in echocardiography that incorporates left ventricular afterload into global longitudinal strain analysis. Myocardial work correlates with myocardial oxygen consumption, and work efficiency can also be assessed. Myocardial work has been evaluated in a variety of clinical conditions to assess the added value of myocardial work compared to left ventricular ejection fraction and global longitudinal strain.

Age-associated thin hair displays molecular, structural and mechanical characteristic changes.

Hair thinning occurs during normal chronological aging in women and in men leading to an increased level of thinner hair shafts alongside original thicker shafts. However, the characteristics of age-associated thin hairs remain largely unknown. Here we analyzed these characteristics by comparing at multiscale thin and thick hairs originated from Caucasian women older than 50 years.

Erratum: Attractive Spin-Orbit Potential from the Skyrme Model [Phys. Rev. Lett. 125, 042501 (2020)].

This corrects the article DOI: 10.1103/PhysRevLett.125.

The susceptibility of disulfide bonds to modification in keratin fibers undergoing tensile stress.

Cysteine residues perform a dual role in mammalian hairs. The majority help stabilize the overall assembly of keratins and their associated proteins, but a proportion of inter-molecular disulfide bonds are assumed to be associated with hair mechanical flexibility. Hair cortical microstructure is hierarchical, with a complex macro-molecular organization resulting in arrays of intermediate filaments at a scale of micrometres.

Insights in Human Hair Curvature by Proteome Analysis of Two Distinct Hair Shapes.

Scalp hair is a universal human characteristic, and a wide range of hair shape and color variations exists. Although differences in human scalp hair shape are visually apparent, the underpinning molecular insights are yet to be fully explored. This work reports the determination of differences at the protein level between two distinct groups of hair shape: very straight samples versus very curly hair samples.

Wool fiber curvature is correlated with abundance of K38 and specific keratin-associated proteins.

Curvature in mammalian fibers, such as wool and human hair, is an important feature of the functional trait of coat structure-it affects mechanical resilience and thermo-insulation. However, to examine the relationship between fiber curvature, ultrastructure and protein composition fiber diameter variability has to be minimal. To achieve this we utilised the progeny of straight-wool domestic sheep mutant rams (crimp mutants) and wild-type ewes.

Processing hair follicles for transmission electron microscopy.

Transmission electron microscopy (TEM) has greatly advanced our knowledge of hair growth and follicle morphogenesis, but complex preparations such as fixation, dehydration and embedding compromise ultrastructure. While recent developments with cryofixation have been shown to preserve the ultrastructure of biological materials close to native state, they do have limitations. This review will focus on each stage of the TEM sample preparation process and their effects on the structural integrity of follicles.

Three-dimensional cellular aggregates formed by in liquid culture with potential for use as a biocontrol agent of the African black beetle ().

formed three-dimensional aggregates of cells (CAs) in liquid culture. CAs were formed mainly by blastospores and conidia, distinct from microsclerotia formed through adhesion of hyphae. The formation, germination and sporulation of CAs were studied, as well as the pathogenicity of conidia produced from them against adults of black beetle.

A detailed mapping of the readily accessible disulphide bonds in the cortex of wool fibres.

Trichocyte keratin intermediate filament proteins (keratins) and keratin associated proteins (KAPs) differ from their epithelial equivalents by having significantly more cysteine residues. Interactions between these cysteine residues within a mammalian fiber, and the putative regular organization of interactions are likely important for defining fiber mechanical properties, and thus biological functionality of hairs. Here we extend a previous study of cysteine accessibility under different levels of exposure to reducing compounds to detect a greater resolution of statistically non-random interactions between individual residues from keratins and KAPs.

Feasibility of exercise treadmill N-ammonia positron emission tomography myocardial perfusion imaging using an off-site cyclotron.

Background: Myocardial perfusion imaging with treadmill exercise nitrogen-13 (N)-ammonia positron emission tomography (PET) presents a logistical challenge. We investigated the feasibility of exercise treadmill (GXT) N-ammonia PET MPI using an off-site cyclotron for production of N-ammonia.

Methods: Thirty-three patients underwent GXT N-ammonia PET MPI over 23 months.

Attractive Spin-Orbit Potential from the Skyrme Model.

We derive the nucleon-nucleon isoscalar spin-orbit potential from the Skyrme model and find good agreement with the Paris potential. This solves a problem that has been open for more than 30 years and gives a new geometric understanding of the spin-orbit force. Our calculation is based on the dipole approximation to skyrmion dynamics and higher order perturbation theory.

Multi-parameter evaluation of the effect of processing conditions on meat protein modification.

Evaluating the interconnecting effects of pH, temperature and time on food proteins is of relevance to food processing, and food functionality. Here we describe a matrix-based approach in which meat proteins were exposed to combinations of these parameters, selected to cover coordinates in a realistic processing space, and analyzed using redox proteomics. Regions within the matrix showing high levels of protein modification were evaluated for oxidative and other modifications.

The wool proteome and fibre characteristics of three distinct genetic ovine breeds from Portugal.

Wool properties and commodity value vary considerably between breeds. In Portugal, three major ovine groups exist: Churros, Bordaleiros and Merinos. This work studies the effect of the ovine genotype on the wool proteome of such groups.

High-pressure freezing followed by freeze substitution of a complex and variable density miniorgan: the wool follicle.

Cryofixation by high-pressure freezing (HPF) followed by freeze substitution (FS) is a preferred method to prepare biological specimens for ultrastructural studies. It has been shown to achieve uniform vitrification and ultrastructure preservation of complex structures in different cell types. One limitation of HPF is the small sample volume of <200 µm thickness and about 2000 µm across.

Giant Congenital Left Atrial Appendage Aneurysm Presenting With Recurrent Supraventricular Tachycardia and Chest Pain.

• LAAA is a rare anomaly characterized by appendage enlargement. • Clinical presentations of LAAA range from asymptomatic to life threatening. • Multimodality imaging, including TTE, is the mainstay of diagnosis.

Differences between ultrastructure and protein composition in straight hair fibres.

Mammalian hairs are internally patterned from both a morphological and proteomic perspective to exhibit specific functional traits, including curvature, which is important for coat structure affecting thermo-insulation. Most functional traits in mammalian coats are complex emergent phenomena associated with single-fibre properties that are themselves multi-variate and poorly understood. Here we compare hair curvature, ultrastructure, microstructure, protein composition and felting (a functional attribute) between fibres from natural straight-wool mutants of domestic sheep (felting lustre-mutant sheep), their wild-type relatives and also with a straight-haired semi-lustrous breed, English Leicester.

Helical twist direction in the macrofibrils of keratin fibres is left handed.

Macrofibrils, the main structural features within the cortical cells of mammalian hair shafts, are long composite bundles of keratin intermediate filaments (KIFs) embedded in a matrix of keratin-associated proteins. The KIFs can be helically arranged around the macrofibril central axis, making a cylinder within which KIF helical angle relative to macrofibril axis increases approximately linearly from macrofibril centre to edge. Mesophase-based self-assembly has been implicated in the early formation of macrofibrils, which first appear as liquid-crystal tactoids in the bulb of hair follicles.

Hair Shaft Formation and Mitochondrial Bioenergetics: Combining Biology, Chemistry, and Physics.

Research into biological manipulation of hair "quality" has ebbed and waned but today is in a resurgence. Hair appearance is regulated by multiple intervention opportunities-adding more hairs; increasing hair "amount" by modulating shaft diameter or shape; or, in principle, by altering shaft physical properties by changing its synthesis. It is likely that improved benefits may be achieved by combining multiple areas-minimizing follicle loss and miniaturization, maximizing shaft production, and treating the existing shaft.

Electron microscopy and tomography reveal that sodium 2-naphthalene sulfonate incorporated into perming solutions swells and tilts trichocyte intermediate filaments causing straightening of curly Japanese human hair.

Objective: A new hair-care process has been specifically developed for the straightening of curved Japanese woman's hair . The process included sodium 2-naphthalene sulfonate (SNS) in the reduction and oxidation steps of a conventional perming process. Our objective was to develop an understanding of how this process caused hair straightening by measuring the changes to morphology and ultrastructure between untreated, conventionally permed and SNS permed hair.

Wanted, dead and alive: Why a multidisciplinary approach is needed to unlock hair treatment potential.

Human recorded history is littered with attempts to improve the perceived appearance of scalp hair. Throughout history, treatments have included both biological and chemical interventions. Hair "quality" or "perceived appearance" is regulated by multiple biological intervention opportunities: adding more hairs by flipping follicles from telogen to anagen, or delaying anagen follicles transiting into catagen; altering hair "apparent amount" by modulating shaft diameter or shape; or, in principle, altering shaft physical properties changing its synthesis.