Redox Gating for Colossal Carrier Modulation and Unique Phase Control.

Redox gating, a novel approach distinct from conventional electrolyte gating, combines reversible redox functionalities with common ionic electrolyte moieties to engineer charge transport, enabling power-efficient electronic phase control. This study achieves a colossal sheet carrier density modulation beyond 1016 cm-2, sustainable over thousands of cycles, all within the sub-volt regime for functional oxide thin films. The key advantage of this method lies in the controlled injection of a large quantity of carriers from the electrolyte into the channel material without the deleterious effects associated with traditional electrolyte gating processes such as the production of ionic defects or intercalated species. The redox gating approach offers a simple and practical means of decoupling electrical and structural phase transitions, enabling the isostructural metal-insulator transition and improved device endurance. The versatility of redox gating extends across multiple materials, irrespective of their crystallinity, crystallographic orientation, or carrier type (n- or p-type). This inclusivity encompasses functional heterostructures and low-dimensional quantum materials composed of sustainable elements, highlighting the broad applicability and potential of the technique in electronic devices.

Intermittent Defect Fluctuations in Oxide Heterostructures.

The heterogeneous nature, local presence, and dynamic evolution of defects typically govern the ionic and electronic properties of a wide variety of functional materials. While the last 50 years have seen considerable efforts into development of new methods to identify the nature of defects in complex materials, such as the perovskite oxides, very little is known about defect dynamics and their influence on the functionality of a material. Here, the discovery of the intermittent behavior of point defects (oxygen vacancies) in oxide heterostructures employing X-ray photon correlation spectroscopy is reported. Local fluctuations between two ordered phases in strained SrCoOx with different degrees of stability of the oxygen vacancies are observed. Ab-initio-informed phase-field modeling reveals that fluctuations between the competing ordered phases are modulated by the oxygen ion/vacancy interaction energy and epitaxial strain. The results demonstrate how defect dynamics, evidenced by measurement and modeling of their temporal fluctuations, give rise to stochastic properties that now can be fully characterized using coherent X-rays, coupled for the first time to multiscale modeling in functional complex oxide heterostructures. The study and its findings open new avenues for engineering the dynamical response of functional materials used in neuromorphic and electrochemical applications.

Assessment of a non-invasive approach to pregnancy diagnosis in gray whales through drone-based photogrammetry and faecal hormone analysis.

Knowledge of baleen whales' reproductive physiology is limited and requires long-term individual-based studies and innovative tools. We used 6 years of individual-level data on the Pacific Coast Feeding Group gray whales to evaluate the utility of faecal progesterone immunoassays and drone-based photogrammetry for pregnancy diagnosis. We explored the variability in faecal progesterone metabolites and body morphology relative to observed reproductive status and estimated the pregnancy probability for mature females of unknown reproductive status using normal mixture models. Individual females had higher faecal progesterone concentrations when pregnant than when presumed non-pregnant. Yet, at the population level, high overlap and variability in progesterone metabolite concentrations occurred between pregnant and non-pregnant groups, limiting this metric for accurate pregnancy diagnosis in gray whales. Alternatively, body width at 50% of the total body length (W50) correctly discriminated pregnant from non-pregnant females at individual and population levels, with high accuracy. Application of the model using W50 metric to mature females of unknown pregnancy status identified eight additional pregnancies with high confidence. Our findings highlight the utility of drone-based photogrammetry to non-invasively diagnose pregnancy in this group of gray whales, and the potential for improved data on reproductive rates for population management of baleen whales generally.

Probing lithium mobility at a solid electrolyte surface.

Solid-state electrolytes overcome many challenges of present-day lithium ion batteries, such as safety hazards and dendrite formation1,2. However, detailed understanding of the involved lithium dynamics is missing due to a lack of in operando measurements with chemical and interfacial specificity. Here we investigate a prototypical solid-state electrolyte using linear and nonlinear extreme-ultraviolet spectroscopies. Leveraging the surface sensitivity of extreme-ultraviolet-second-harmonic-generation spectroscopy, we obtained a direct spectral signature of surface lithium ions, showing a distinct blueshift relative to bulk absorption spectra. First-principles simulations attributed the shift to transitions from the lithium 1 s state to hybridized Li-s/Ti-d orbitals at the surface. Our calculations further suggest a reduction in lithium interfacial mobility due to suppressed low-frequency rattling modes, which is the fundamental origin of the large interfacial resistance in this material. Our findings pave the way for new optimization strategies to develop these electrochemical devices via interfacial engineering of lithium ions.

Benefits and Barriers of Technology for Home Function and Mobility Assessment: Perspectives of Older Patients With Blood Cancers, Caregivers, and Clinicians.

PURPOSE: Advances in digital health technology can overcome barriers to measurement of function and mobility for older adults with blood cancers, but little is known about how older adults perceive such technology for use in their homes. METHODS: To characterize potential benefits and barriers associated with using technology for home functional assessment, we conducted three semistructured focus groups (FGs) in January 2022. Eligible patients came from the Older Adult Hematologic Malignancies Program at Dana-Farber Cancer Institute (DFCI), which includes adults 73 years and older enrolled during their initial consult with their oncologist. Eligible caregivers were 18 years and older and identified by enrolled patients as their primary caregiver. Eligible clinicians were practicing DFCI hematologic oncologists, nurse practitioners, or physician assistants with ≥2 years of clinical experience. A qualitative researcher led thematic analysis of FG transcripts to identify key themes. RESULTS: Twenty-three participants attended the three FGs: eight patients, seven caregivers, and eight oncology clinicians. All participants valued function and mobility assessments and felt that technology could overcome barriers to their measurement. We identified three themes related to potential benefits: making it easier for oncology teams to consider function and mobility; providing standardized, objective data; and facilitating longitudinal data. We also identified four themes related to barriers to home functional assessment: concerns related to privacy and confidentiality, burden of measuring additional patient data, challenges in operating new technology, and concerns related to data improving care. CONCLUSION: These data suggest that specific concerns raised by older patients, caregivers, and oncology clinicians must be addressed to improve acceptability and uptake of technology used to measure function and mobility in the home.

Evaluating Dermal Bone as a Novel Source of Endocrine Information in Ninespine and Threespine Stickleback Fish.

Monitoring the physiology of small aquatic and marine teleost fish presents challenges. Blood samples, often the first choice for endocrinologists, can be difficult or even impossible to obtain and alternative matrices currently used for hormone analyses do not occur in fishes (e.g., hair, feathers etc.) or are not easily collected from small aquatic organisms (e.g., urine and feces). Some teleosts, however, have enlarged bony dermal elements that possibly accumulate and store steroid hormones in physiological relevant concentrations. Both threespine stickleback (Gasterosteus aculeatus) and ninespine stickleback (Pungitius pungitius) have a series of external, lateral bony plates, dorsal spines, and a pair of pelvic spines attached to the pelvic girdle. We investigated if cortisol, the primary circulating glucocorticoid in teleosts, could be extracted from stickleback dermal bone and quantified using a commercially available enzyme immunoassay (EIA). We successfully validated a cortisol EIA for dermal bone extracts, determined that cortisol was detectable in both species, and found that dermal bone cortisol levels significantly correlated with cortisol levels in whole body homogenate. Ninespine stickleback had significantly higher dermal bone cortisol concentrations than threespine stickleback and female threespine stickleback tended to have over twice the mean dermal bone cortisol concentration than males. Because both stickleback species are widely used for ecotoxicological studies, using dermal bone as a source of endocrine information, while leaving the body for contaminant, genomic, histological, and stable isotope analyses, could be a powerful and parsimonious tool. Further investigation and physiological validations are necessary to fully understand the utility of this new sample matrix.

Spanish (translation provided by Luis C. Beltran)El monitoreo de la fisiología de pequeños peces teleósteos acuáticos y marinos presenta desafíos. Las muestras de sangre, a menudo la primera opción para los endocrinólogos, pueden ser difíciles o incluso imposibles de obtener y las matrices alternativas que se utilizan actualmente para los análisis hormonales no son aplicables en peces (p. ej., pelo, plumas, etc.) o no se obtienen fácilmente de pequeños organismos acuáticos (p. ej., orina y heces). Sin embargo, algunos teleósteos tienen elementos dérmicos óseos agrandados que posiblemente acumulan y almacenan hormonas esteroides en concentraciones fisiológicas relevantes. Tanto el espinoso de tres espinas (Gasterosteus aculeatus) como el espinoso de nueve espinas (Pungitius pungitius) tienen una serie de placas óseas laterales externas, espinas dorsales y un par de espinas pélvicas unidas a la cintura pélvica. Nosotros investigamos si el cortisol, el principal glucocorticoide circulante en los teleósteos, podría extraerse del hueso dérmico del espinoso y cuantificarse mediante un inmunoensayo enzimático (EIA, por sus siglas en inglés) disponible comercialmente. Validamos con éxito un EIA de cortisol para extractos óseos dérmicos, determinamos que el cortisol era detectable en ambas especies, y descubrimos que los niveles de cortisol óseo dérmico se correlacionaron significativamente con los niveles de cortisol en el cuerpo entero homogeneizado. El espinoso de nueve espinas tenía concentraciones de cortisol óseo dérmico significativamente más altas que el espinoso de tres espinas y el espinoso de tres espinas hembra tendía a tener más del doble de la concentración media de cortisol óseo dérmico que los machos. Debido a que ambas especies de espinosos se usan ampliamente para estudios ecotoxicológicos, el uso del hueso dérmico como fuente de información endocrina, mientras se deja el cuerpo para análisis de contaminantes, genómicos, histológicos e isótopos estables, podría ser una herramienta poderosa y parsimoniosa. Se necesitan más investigaciones y validaciones fisiológicas para comprender completamente la utilidad de esta nueva matriz de muestra.

Portuguese (translation provided by Jonathan M. Branco)Monitorar a fisiologia de pequenos peixes teleósteos aquáticos e marinhos apresenta desafios. Amostras de sangue, muitas vezes a primeira escolha para endocrinologistas, podem ser difíceis ou mesmo impossíveis de obter e matrizes alternativas atualmente usadas para análises hormonais não ocorrem em peixes (e.g., pelos, penas etc.) ou não são facilmente coletadas em pequenos organismos aquáticos (e.g., urina e fezes). Alguns teleósteos, no entanto, possuem elementos dérmicos ósseos ampliados que possivelmente acumulam e armazenam hormônios esteroides em concentrações fisiológicas relevantes. Ambos Gasterosteus aculeatus e Pungitius pungitius apresentam uma série de Placas ósseas externas laterais, espinhos dorsais e um par de espinhos pélvicos ligados à cintura pélvica. Investigamos se o cortisol, o principal glicocorticoide circulante em teleósteos, poderia ser extraído do osso dérmico de G. aculeatus e P. pungitius e quantificado usando um imunoensaio enzimático (EIA) comercialmente disponível. Validamos com sucesso um EIA de cortisol para extratos de ósseos dérmicos, determinamos que o cortisol era detectável em ambas as espécies e descobrimos o cortisol ósseo dérmico em níveis significativamente correlacionados com os níveis de cortisol em todo o corpo homogeneizado. P. pungitius apresentou concentrações de cortisol ósseo dérmico significativamente mais altas do que G. aculeatus e fêmeas de G. aculeatus tenderam a ter mais que o dobro da concentração média de cortisol ósseo dérmico de machos. Como ambas as espécies são amplamente utilizadas para estudos ecotoxicológicos, usando o osso dérmico como fonte de informação endócrina, deixando o corpo para análises de contaminantes, genômicas, histológicas e de isótopos estáveis, pode ser uma ferramenta poderosa e parcimoniosa. Mais investigações e validações fisiológicas são necessários para entender completamente a utilidade desta nova matriz de amostra.

Complex Oxides for Brain-Inspired Computing: A Review.

The fields of brain-inspired computing, robotics, and, more broadly, artificial intelligence (AI) seek to implement knowledge gleaned from the natural world into human-designed electronics and machines. In this review, the opportunities presented by complex oxides, a class of electronic ceramic materials whose properties can be elegantly tuned by doping, electron interactions, and a variety of external stimuli near room temperature, are discussed. The review begins with a discussion of natural intelligence at the elementary level in the nervous system, followed by collective intelligence and learning at the animal colony level mediated by social interactions. An important aspect highlighted is the vast spatial and temporal scales involved in learning and memory. The focus then turns to collective phenomena, such as metal-to-insulator transitions (MITs), ferroelectricity, and related examples, to highlight recent demonstrations of artificial neurons, synapses, and circuits and their learning. First-principles theoretical treatments of the electronic structure, and in situ synchrotron spectroscopy of operating devices are then discussed. The implementation of the experimental characteristics into neural networks and algorithm design is then revewed. Finally, outstanding materials challenges that require a microscopic understanding of the physical mechanisms, which will be essential for advancing the frontiers of neuromorphic computing, are highlighted.

PACK syndrome: A case series and review.

A rare overlap syndrome between CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome and primary biliary cholangitis (PBC) is described as PACK syndrome, an acronym for primary biliary cholangitis, anticentromere antibodies, CREST syndrome, and keratoconjunctivitis sicca. In this retrospective cohort analysis and review, we present fourteen patients who meet diagnostic criteria for PACK syndrome in one of the largest case series of this group. All patients were female, 86% of whom were White with an average age of 66.7 years (range 39-78 years). The prevalence was 5.08% in our PBC cohort (n=256) similar to previous findings. CREST syndrome was diagnosed prior to PBC in 58% of our patients and limited pulmonary and renal involvement were observed. This syndrome is rare, but given its insidious development, clinicians should be aware of this potential overlap in CREST-only and PBC-only patients.

Phase Transition Dynamics in a Complex Oxide Heterostructure.

Understanding the behavior of defects in the complex oxides is key to controlling myriad ionic and electronic properties in these multifunctional materials. The observation of defect dynamics, however, requires a unique probe-one sensitive to the configuration of defects as well as its time evolution. Here, we present measurements of oxygen vacancy ordering in epitaxial thin films of SrCoO_{x} and the brownmillerite-perovskite phase transition employing x-ray photon correlation spectroscopy. These and associated synchrotron measurements and theory calculations reveal the close interaction between the kinetics and the dynamics of the phase transition, showing how spatial and temporal fluctuations of heterointerface evolve during the transformation process. The energetics of the transition are correlated with the behavior of oxygen vacancies, and the dimensionality of the transformation is shown to depend strongly on whether the phase is undergoing oxidation or reduction. The experimental and theoretical methods described here are broadly applicable to in situ measurements of dynamic phase behavior and demonstrate how coherence may be employed for novel studies of the complex oxides as enabled by the arrival of fourth-generation hard x-ray coherent light sources.

Nanoscale Control of the Metal-Insulator Transition at LaAlO3/KTaO3 Interfaces.

Recent reports of superconductivity at KTaO3 (KTO) (110) and (111) interfaces have sparked intense interest due to the relatively high critical temperature as well as other properties that distinguish this system from the more extensively studied SrTiO3 (STO)-based heterostructures. Here, we report the reconfigurable creation of conducting structures at intrinsically insulating LaAlO3/KTO(110) and (111) interfaces. Devices are created using two distinct methods previously developed for STO-based heterostructures: (1) conductive atomic-force microscopy lithography and (2) ultralow-voltage electron-beam lithography. At low temperatures, KTO(110)-based devices show superconductivity that is tunable by an applied back gate. A one-dimensional nanowire device shows single-electron-transistor (SET) behavior. A KTO(111)-based device is metallic but does not become superconducting. These reconfigurable methods of creating nanoscale devices in KTO-based heterostructures offer new avenues for investigating mechanisms of superconductivity as well as development of quantum devices that incorporate strong spin-orbit interactions, superconducting behavior, and nanoscale dimensions.

Controlled Formation of Conduction Channels in Memristive Devices Observed by X-ray Multimodal Imaging.

Neuromorphic computing provides a means for achieving faster and more energy efficient computations than conventional digital computers for artificial intelligence (AI). However, its current accuracy is generally less than the dominant software-based AI. The key to improving accuracy is to reduce the intrinsic randomness of memristive devices, emulating synapses in the brain for neuromorphic computing. Here using a planar device as a model system, the controlled formation of conduction channels is achieved with high oxygen vacancy concentrations through the design of sharp protrusions in the electrode gap, as observed by X-ray multimodal imaging of both oxygen stoichiometry and crystallinity. Classical molecular dynamics simulations confirm that the controlled formation of conduction channels arises from confinement of the electric field, yielding a reproducible spatial distribution of oxygen vacancies across switching cycles. This work demonstrates an effective route to control the otherwise random electroforming process by electrode design, facilitating the development of more accurate memristive devices for neuromorphic computing.

Patient willingness to receive full-body skin exams based on the sex and/or gender and training level of provider: a survey study.

Full-body skin examinations (FBSEs) involve examination of the patient's skin from head to toe, and may be uncomfortable for some patients. While many patients prefer same-sex providers for pelvic, genital and rectal exams, desire for same-sex providers for FBSEs is not well characterized. This may be further magnified when FBSE is performed by medical trainees. We surveyed 566 subjects using Amazon Mechanical Turk (AMT), an online crowdsourcing platform, to assess the public's willingness to receive FBSEs based on the sex and/or gender and the level of training of the healthcare provider (HCP). The overall willingness by all respondents to undergo FBSE performed by a dermatologist, dermatology resident and medical student was 84.3%, 77.5% and 65.7%, respectively, if the HCP was the same sex/gender, compared with 60.6%, 54.8% and 45.7% if the HCP was a different sex/gender (P < 0.001). In our cohort, unwillingness for FBSEs was greater if the patient was female, if the HCP was a different gender/sex from the patient and if the HCP was a medical student.

Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients: A Systematic Review of Tumor Profiling Studies.

As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients.

Sequencing of Cutaneous Squamous Cell Carcinoma Primary Tumors and Patient-Matched Metastases Reveals ALK as a Potential Driver in Metastases and Low Mutational Concordance in Immunocompromised Patients.

Cutaneous squamous cell carcinoma is a common skin cancer that is responsible for 1,000,000 cases and up to 9,000 deaths annually in the United States. Metastases occur in 2-5% of patients and are responsible for significant morbidity and mortality. The objective of this study is to perform targeted next-generation sequencing on a cohort of squamous cell carcinoma primary tumors and patient-matched lymph node metastases. An oncology 76-gene panel was run from formalin-fixed paraffin-embedded samples of patient-matched primary squamous cell carcinomas (10) and resultant metastases (10). ALK was discovered to be a driver mutation in metastases using two different algorithms, oncoCLUSTand dNdScv. Mutational concordance between primary tumors and metastases was notably lower in immunosuppressed patients, especially among pathogenic mutations (41.7% vs. 83.3%, P = 0.01). Sequencing of matched squamous cell carcinoma primary tumors and lymph node metastases identified genes and pathways that may have clinical importance, most notably ALK as a potential driver mutation of metastasis. Sequencing of both primary tumors and metastases may improve the efficacy of targeted therapies.

Origin of the 2D Electron Gas at the SrTiO3 Surface.

Bulk SrTiO3 is a well-known band insulator and the most common substrate used in the field of complex oxide heterostructures. Its surface and interface with other oxides, however, have demonstrated a variety of remarkable behaviors distinct from those expected. In this work, using a suite of in situ techniques to monitor both the atomic and electronic structures of the SrTiO3 (001) surface prior to and during growth, the disappearance and re-appearance of a 2D electron gas (2DEG) is observed after the completion of each SrO and TiO2 monolayer, respectively. The 2DEG is identified with the TiO2 double layer present at the initial SrTiO3 surface, which gives rise to a surface potential and mobile electrons due to vacancies within the TiO2-x adlayer. Much like the electronic reconstruction discovered in other systems, two atomic planes are required, here supplied by the double layer. The combined in situ scattering/spectroscopy findings resolve a number of longstanding issues associated with complex oxide interfaces, facilitating the employment of atomic-scale defect engineering in oxide electronics.

Self-healing Growth of LaNiO3 on a Mixed-Terminated Perovskite Surface.

Developing atomic-scale synthesis control is a prerequisite for understanding and engineering the exotic physics inherent to transition-metal oxide heterostructures. Thus, far, however, the number of materials systems explored has been extremely limited, particularly with regard to the crystalline substrate, which is routinely SrTiO3. Here, we investigate the growth of a rare-earth nickelate─LaNiO3─on (LaAlO3)(Sr2AlTaO6) (LSAT) (001) by oxide molecular beam epitaxy (MBE). Whereas the LSAT substrates are smooth, they do not exhibit the single surface termination usually assumed necessary for control over the interface structure. Performing both nonresonant and resonant anomalous in situ synchrotron surface X-ray scattering during MBE growth, we show that reproducible heterostructures can be achieved regardless of both the mixed surface termination and the layer-by-layer deposition sequence. The rearrangement of the layers occurs dynamically during growth, resulting in the fabrication of high-quality LaNiO3/LSAT heterostructures with a sharp and consistent interfacial structure. This is due to the thermodynamics of the deposition window as well as the nature of the chemical species at interfaces─here, the flexible charge state of nickel at the oxide surface. This has important implications regarding the use of a wider variety of substrates for fundamental studies on complex oxide synthesis.

In situ analysis of the nucleation of O- and Zn-polar ZnO nanowires using synchrotron-based X-ray diffraction.

The selection of the polarity of ZnO nanowires grown by chemical bath deposition offers a great advantage for their integration into a wide variety of engineering devices. However, the nucleation process of ZnO nanowires and its dependence on their polarity is still unknown despite its importance for optimizing their morphology and properties and thus to enhance the related device performances. To tackle this major issue, we combine an in situ analysis of the nucleation process of O- and Zn-polar ZnO nanowires on O- and Zn-polar ZnO single crystals, respectively, using synchrotron radiation-based grazing incidence X-ray diffraction with ex situ transmission and scanning electron microscopy. We show that the formation of ZnO nanowires obeys three successive phases from the induction, through nucleation to growth phases. The characteristics of each phase, including the nucleation temperature, the shape and dimension of nuclei, as well as their radial and axial development are found to depend on the polarity of ZnO nanowires. A comprehensive description reporting the dominant physicochemical processes in each phase and their dependence on the polarity of ZnO nanowires is presented, revisiting their formation process step-by-step. These findings provide a deeper understanding of the phenomena at work during the growth of ZnO nanowires by chemical bath deposition and open the perspective to develop a more accurate control of their properties at each step of the formation process.

Methotrexate Hepatotoxicity Monitoring Guidelines in Psoriasis and Rheumatoid Arthritis: Is There a Consensus?

Methotrexate therapy has evolved over the years to become a fundamental component in the management of rheumatoid arthritis and psoriasis. Liver toxicity remains an ever-present concern when prescribing methotrexate. As such, methotrexate liver toxicity monitoring guidelines have been developed independently by rheumatologists and dermatologists. The main differentiating factor between the dermatology and rheumatology guidelines is risk stratification. Dermatology guidelines are largely based off of the presence or absence of hepatoxicity risk factors (alcohol usage, obesity, type II diabetes, among other) while the rheumatology guidelines do not emphasize this distinction. Thus, the aim of this review is to identify why these screening guidelines differences exist and discuss if the differences in stratification and screening are valid. We will also briefly examine alternatives to the current gold standard hepatoxicity screening test: the liver biopsy.