Leakage Mechanism and Cycling Behavior of Ferroelectric Al0.7Sc0.3N.

Ferroelectric scandium-doped aluminum nitride (Al1-xScxN) is of considerable research interest because of its superior ferroelectricity. Studies indicate that Al1-xScxN may suffer from a high leakage current, which can hinder further thickness scaling and long-term reliability. In this work, we systematically investigate the origin of the leakage current in Al0.7Sc0.3N films via experiments and theoretical calculations. The results reveal that the leakage may originate from the nitrogen vacancies with positively charged states and fits well with the trap-assisted Poole-Frenkel (P-F) emission. Moreover, we examine the cycling behavior of ferroelectric Al0.7Sc0.3N-based FeRAM devices. We observe that the leakage current substantially increases when the device undergoes bipolar cycling with a pulse amplitude larger than the coercive electric field. Our analysis shows that the increased leakage current in bipolar cycling is caused by the monotonously reduced trap energy level by monitoring the direct current (DC) leakage under different temperatures and the P-F emission fitting.

Affordable housing through the Low-Income Housing Tax Credit program and opioid overdose emergency department visits.

INTRODUCTION: The United States continues to experience an opioid overdose crisis. As a key social determinant of health, housing insecurity may contribute to initiation of substance use and can threaten outcomes for those with substance use disorders by increasing stress, risky substance use, discontinuity of treatment, and return to use, all of which may increase the risk of overdose. The Low-Income Housing Tax Credit (LIHTC) program supports access to rental housing for low-income populations. By facilitating access to affordable housing, this program may improve housing security, thereby reducing overdose risk. METHODS: We used data from LIHTC Property Data and the State Emergency Department Database (SEDD) to identify the number of LIHTC units available and opioid overdoses discharged from the emergency department (ED) in 13 states between 2005 and 2014. RESULTS: Between 2005 and 2014, mean opioid overdose ED visits were higher in states with fewer LIHTC units (<28 LIHTC units per 100,000 population) at 26.5 per 100,000 population as compared to states with higher LIHTC units (≥28 LIHTC units per 100,000 population) at 21.1 per 100,000. We find that greater availability of LIHTC units was associated with decreased rates of opioid overdose ED visits (RR 0.94; CI 0.90, 1.00). CONCLUSIONS: Given the importance of housing as a key social determinant of health, the provision of affordable housing may mitigate substance misuse and prevent nonfatal opioid overdose.

Shape complementarity processes for ultrashort-burst sensitive M13-PEG-WS2-powered MCF-7 cancer cell sensors.

Biomarkers have the potential to be utilized in disease diagnosis, prediction and monitoring. The cancer cell type is a leading candidate for next-generation biomarkers. Although traditional digital biomolecular sensor (DBS) technology has shown to be effective in assessing cell-based interactions, low cell-population detection of cancer cell types is extremely challenging. Here, we controlled the electrical signature of a two-dimensional (2D) nanomaterial, tungsten disulfide (WS2), by utilizing a combination of the Phage-integrated Polymer and the Nanosheet (PPN), viz., the integration of the M13-conjugated polyethylene glycol (PEG) and the WS2, through shape-complementarity phenomena, and developed a sensor system, i.e., the Phage-based DBS (P-DBS), for the specific, rapid, sensitive detection of clinically-relevant MCF-7 cells. The P-DBS attains a detection limit of 12 cells per µL, as well as a contrast of 1.25 between the MCF-10A sample signal and the MCF-7 sample signal. A reading length of 200 µs was further achieved, along with a relative cell viability of ∼100% for both MCF-7 and MCF-10A cells and with the PNN. Atomistic simulations reveal the structural origin of the shape complementarity-facilitated decrease in the output impedance of the P-DBS. The combination of previously unreported exotic sensing materials and digital sensor design represents an approach to unlocking the ultra-sensitive detection of cancer cell types and provides a promising avenue for early cancer diagnosis, staging and monitoring.

Towards a robust test to detect gene doping for anabolic enhancement in human athletes.

Success in gene therapy in treating human disease makes this technology attractive to enhance athletic performance, creating the need for gene doping detection. In 2021, World Anti-Doping Agency (WADA) approved the first gene doping test. Here, we describe a new method to detect doping with four additional genes, follistatin, growth hormone 1, growth hormone-releasing hormone and insulin-like growth factor 1, that may improve performance by increasing muscle size and strength. The method utilises four hydrolysis probe-based polymerase chain reaction (PCR) assays that target the transgenes based on the coding sequence of the four endogenous genes. The assays are specific, reproducible and capable to detect five copies of transgene in the presence of very similar endogenous gene in 25,000 times excess. To underpin reliable and comparable routine method performance by doping testing laboratories, a synthetic reference material for the method was designed and generated following the ISO Guide 35. The complete method was validated in blood samples using plasma as extraction matrix and QIAamp DNA blood midi DNA extraction kit. All blood samples from different donors (n = 8) simulated to be negative or positive (1500 transgene copies spiked per millilitre of blood) for the transgenes were reported correctly. The new method that targets four additional genes will extend the capabilities of laboratories involved in doping control to protect athletes' health, fairness and equality.

Ultrafast Near-Ideal Phase-Change Memristive Physical Unclonable Functions Driven by Amorphous State Variations.

There is an ever-increasing demand for next-generation devices that do not require passwords and are impervious to cloning. For traditional hardware security solutions in edge computing devices, inherent limitations are addressed by physical unclonable functions (PUF). However, realizing efficient roots of trust for resource constrained hardware remains extremely challenging, despite excellent demonstrations with conventional silicon circuits and archetypal oxide memristor-based crossbars. An attractive, down-scalable approach to design efficient cryptographic hardware is to harness memristive materials with a large-degree-of-randomness in materials state variations, but this strategy is still not well understood. Here, the utilization of high-degree-of-randomness amorphous (A) state variations associated with different operating conditions via thermal fluctuation effects is demonstrated, as well as an integrated framework for in memory computing and next generation security primitives, viz., APUF, for achieving secure key generation and device authentication. Near ideal uniformity and uniqueness without additional initial writing overheads in weak memristive A-PUF is achieved. In-memory computing empowers a strong exclusive OR (XOR-) and-repeat A PUF construction to avoid machine learning attacks, while rapid crystallization processes enable large-sized-key reconfigurability. These findings pave the way for achieving a broadly applicable security primitive for enhancing antipiracy of integrated systems and product authentication in supply chains.

WS2/Polyethylene Glycol Nanostructures for Ultra-Efficient MCF-7 Cancer Cell Ablation and Electrothermal Therapy.

Developing novel nanostructures and advanced nanotechnologies for cancer treatment has attracted ever-increasing interest. Electrothermal therapy offers many advantages such as high efficiency and minimal invasiveness, but finding a balance between increasing stability of the nanostructure state and, at the same time, enhancing the nanostructure biodegradability presents a key challenge. Here, we modulate the biodegradation process of two-dimensional-material-based nanostructures by using polyethylene glycol (PEG) via nanostructure disrupt-and-release effects. We then demonstrate the development of a previously unreported alternating current (AC) pulse WS2/PEG nanostructure system for enhancing therapeutic performance. A decrease in cell viability of ∼42% for MCF-7 cells with WS2/PEG was achieved, which is above an average of ∼25% for current electrothermal-based therapeutic methods using similar energy densities, as well as degradation time of the WS2 of ∼1 week, below an average of ∼3.5 weeks for state-of-the-art nanostructure-based systems in physiological media. Moreover, the incubation time of MCF-7 cells with WS2/PEG reached ∼24 h, which is above the average of ∼4.5 h for current electrothermal-based therapeutic methods and with the use of the amount of time harnessed to incubate the cells with nanostructures before applying a stimulus as a measure of incubation time. Material characterizations further disclose the degradation of WS2 and the grafting of PEG on WS2 surfaces. These WS2-based systems offer strong therapeutic performance and, simultaneously, maintain excellent biodegradability/biocompatibility, thus providing a promising route for the ablation of cancer.

Ultrasensitive Detection of MCF-7 Cells with a Carbon Nanotube-Based Optoelectronic-Pulse Sensor Framework.

Biosensors are of vital significance for healthcare by supporting the management of infectious diseases for preventing pandemics and the diagnosis of life-threatening conditions such as cancer. However, the advancement of the field can be limited by low sensing accuracy. Here, we altered the bioelectrical signatures of the cells using carbon nanotubes (CNTs) via structural loosening effects. Using an alternating current (AC) pulse under light irradiation, we developed a photo-assisted AC pulse sensor based on CNTs to differentiate between healthy breast epithelial cells (MCF-10A) and luminal breast cancer cells (MCF-7) within a heterogeneous cell population. We observed a previously undemonstrated increase in current contrast for MCF-7 cells with CNTs compared to MCF-10A cells with CNTs under light exposure. Moreover, we obtained a detection limit of ∼1.5 × 103 cells below a baseline of ∼1 × 104 cells for existing electrical-based sensors for an adherent, heterogeneous cell population. All-atom molecular dynamics (MD) simulations reveal that interactions between the embedded CNT and cancer cell membranes result in a less rigid lipid bilayer structure, which can facilitate CNT translocation for enhancing current. This as-yet unconsidered cancer cell-specific method based on the unique optoelectrical properties of CNTs represents a strategy for unlocking the detection of a small population of cancer cells and provides a promising route for the early diagnosis, monitoring, and staging of cancer.

Ultralong recovery time in nanosecond electroporation systems enabled by orientational-disordering processes.

The growing importance of applications based on molecular medicine and genetic engineering is driving the need to develop high-performance electroporation technologies. The electroporation phenomenon involves disruption of the cell for increasing membrane permeability. Although there is a multitude of research focused on exploring new electroporation techniques, the engineering of programming schemes suitable for these electroporation methods remains a challenge. Nanosecond stimulations could be promising candidates for these techniques owing to their ability to generate a wide range of biological responses. Here we control the membrane permeabilization of cancer cells using different numbers of electric-field pulses through orientational disordering effects. We then report our exploration of a few-volt nanosecond alternating-current (AC) stimulation method with an increased number of pulses for developing electroporation systems. A recovery time of ∼720 min was achieved, which is above the average of ∼76 min for existing electroporation methods using medium cell populations, as well as a previously unreported increased conductance with an increase in the number of pulses using weak bias amplitudes. All-atom molecular dynamics (MD) simulations reveal the orientation-disordering-facilitated increase in the degree of permeabilization. These findings highlight the potential of few-volt nanosecond AC-stimulation with an increased number of pulse strategies for the development of next-generation low-power electroporation systems.

The Association of Low-Income Housing Tax Credit Units and Reports of Child Abuse and Neglect.

INTRODUCTION: Poverty broadly and financial stress owing to housing insecurity specifically are associated with an increased risk of child maltreatment. Therefore, it is possible that a program designed to increase access to affordable housing such as the Low-Income Housing Tax Credit program could reduce child maltreatment. The purpose of this study is to examine the association of the availability of housing units through the Low-Income Housing Tax Credit Program with the rates of child maltreatment reports, including reports for physical abuse and neglect, at the state and county levels. METHODS: Data were from the 2005‒2015 National Child Abuse and Neglect Data System and the Low-Income Housing Tax Credit Program database. Generalized estimating equations were conducted in 2021 to calculate rate ratios and 95% CIs, adjusting for relevant confounders. RESULTS: At the state level, ≥25 compared with <25 Low-Income Housing Tax Credit Program units per 100,000 population was associated with a lower rate of overall child maltreatment (i.e., neglect and physical abuse; rate ratio=0.96, 95% CI=0.93, 0.99), neglect (rate ratio=0.96, 95% CI=0.94, 0.99), and physical abuse (rate ratio=0.96, 95% CI=0.93, 1.00) reports. Similarly, at the county level, ≥1 compared with 0 Low-Income Housing Tax Credit Program units per 100,000 population was associated with a lower rate of overall child maltreatment (rate ratio=0.94, 95% CI=0.92, 0.97), neglect (rate ratio=0.96, 95% CI=0.93, 0.98), and physical abuse (rate ratio=0.94, 95% CI=0.91, 0.98) reports. CONCLUSIONS: Increasing access to affordable housing may be an effective strategy to reduce child maltreatment at both the state and county levels.

Lack of Maternal Social Capital Increases the Likelihood of Harsh Parenting.

Does low maternal social capital increase the likelihood of parents using harsh parenting behaviors? We analyzed random digit dial telephone survey data from 661 female primary caregivers across Colorado. Positive reports of the use of either physically or psychologically harsh parenting methods were classified as harsh parenting. Absence of social capital was assessed within the family and the community; lack of social capital within the family was measured in terms of an absence of support from a partner and an additional caregiver. Absence of social capital within the community was measured as lack of interpersonal resources from neighbors and religious activities. Nearly 30% admitted to one or more physically harsh parenting behaviors in the prior year, and 85.8% reported at least one psychologically harsh parenting behavior. Lower levels of neighborhood connectedness were associated with physically harsh parenting (odds ratio = 1.50). Conflict between partners (odd ratio = 2.50) and the absence of an additional caregiver (odds ratio = 1.88) increased psychologically harsh parenting. One practical implication is that mental health and medical providers should help new parents value, access, or develop social networks within the community to prevent children from experiencing harsh parenting.

Affordable housing through the low-income housing tax credit program and intimate partner violence-related homicide.

The most severe outcome of intimate partner violence (IPV) is IPV-related homicide. Access to affordable housing may both facilitate exit from abusive relationships and reduce financial stress in intimate relationships, potentially preventing IPV-related homicide. We examined the association of the availability of rental housing through the Low-Income Housing Tax Credit (LIHTC) program, a federal program providing tax incentives to support the development of affordable housing, with IPV-related homicide and assessed whether this association differed by eviction rates at the state-level. We used 2005-2016 National Violent Death Reporting System, LIHTC Property, and Eviction Lab data for 13 states and compared the rate of IPV-related homicide in state-years with ≥30 to state-years with <30 LIHTC units per 100,000 population, overall and stratified by eviction rates. We conducted analyses in fall 2020. Adjusting for potential state-level confounders, the rate of IPV-related homicide in state-years with ≥30 LIHTC units per 100,000 population was lower than in state-years with <30 LIHTC units per 100,000 population (RR = 0.89, 95% CI 0.81, 0.98). The reduction in the rate of IPV-related homicide was slightly larger in state-years with higher eviction rates (≥3500 evictions per 100,000 renter population; RR = 0.83, 95% CI 0.74, 0.93) compared to state-years with lower eviction rates (<3500 evictions per 100,000 renter population; RR = 0.91, 95% CI 0.81, 1.03). Overall, at the state-level, increased availability of affordable housing through the LIHTC program was associated with lower rates of IPV-related homicide. Increasing the availability of affordable housing may be one tool for preventing IPV-related homicide.

Multi-omics of a pre-clinical model of diabetic cardiomyopathy reveals increased fatty acid supply impacts mitochondrial metabolic selectivity.

The incidence of type 2 diabetes (T2D) is increasing globally, with long-term implications for human health and longevity. Heart disease is the leading cause of death in T2D patients, who display an elevated risk of an acute cardiovascular event and worse outcomes following such an insult. The underlying mechanisms that predispose the diabetic heart to this poor prognosis remain to be defined. This study developed a pre-clinical model (Rattus norvegicus) that complemented caloric excess from a high-fat diet (HFD) and pancreatic ß-cell dysfunction from streptozotocin (STZ) to produce hyperglycaemia, peripheral insulin resistance, hyperlipidaemia and elevated fat mass to mimic the clinical features of T2D. Ex vivo cardiac function was assessed using Langendorff perfusion with systolic and diastolic contractile depression observed in T2D hearts. Cohorts representing untreated, individual HFD- or STZ-treatments and the combined HFD + STZ approach were used to generate ventricular samples (n = 9 per cohort) for sequential and integrated analysis of the proteome, lipidome and metabolome by liquid chromatography-tandem mass spectrometry. This study found that in T2D hearts, HFD treatment primed the metabolome, while STZ treatment was the major driver for changes in the proteome. Both treatments equally impacted the lipidome. Our data suggest that increases in ß-oxidation and early TCA cycle intermediates promoted rerouting via 2-oxaloacetate to glutamate, γ-aminobutyric acid and glutathione. Furthermore, we suggest that the T2D heart activates networks to redistribute excess acetyl-CoA towards ketogenesis and incomplete ß-oxidation through the formation of short-chain acylcarnitine species. Multi-omics provided a global and comprehensive molecular view of the diabetic heart, which distributes substrates and products from excess ß-oxidation, reduces metabolic flexibility and impairs capacity to restore high energy reservoirs needed to respond to and prevent subsequent acute cardiovascular events.

An Efficient, Short Stimulus PANC-1 Cancer Cell Ablation and Electrothermal Therapy Driven by Hydrophobic Interactions.

Promising results in clinical studies have been demonstrated by the utilization of electrothermal agents (ETAs) in cancer therapy. However, a difficulty arises from the balance between facilitating the degradation of ETAs, and at the same time, increasing the electrothermal performance/stability required for highly efficient treatment. In this study, we controlled the thermal signature of the MoS2 by harnessing MoS2 nanostructures with M13 phage (MNM) via the structural assembling (hydrophobic interaction) phenomena and developed a combined PANC-1 cancer cell-MNM alternating current (AC)-stimulus framework for cancer cell ablation and electrothermal therapy. A percentage decrease in the cell viability of ~23% was achieved, as well as a degradation time of 2 weeks; a stimulus length of 100 µs was also achieved. Molecular dynamics (MD) simulations revealed the assembling kinetics in integrated M13 phage-cancer cell protein systems and the structural origin of the hydrophobic interaction-enabled increase in thermal conduction. This study not only introduced an 'ideal' agent that avoided the limitations of ETAs but also provided a proof-of-concept application of MoS2-based materials in efficacious cancer therapy.

Activating Silent Synapses in Sulfurized Indium Selenide for Neuromorphic Computing.

The transformation from silent to functional synapses is accompanied by the evolutionary process of human brain development and is essential to hardware implementation of the evolutionary artificial neural network but remains a challenge for mimicking silent to functional synapse activation. Here, we developed a simple approach to successfully realize activation of silent to functional synapses by controlled sulfurization of chemical vapor deposition-grown indium selenide crystals. The underlying mechanism is attributed to the migration of sulfur anions introduced by sulfurization. One of our most important findings is that the functional synaptic behaviors can be modulated by the degree of sulfurization and temperature. In addition, the essential synaptic behaviors including potentiation/depression, paired-pulse facilitation, and spike-rate-dependent plasticity are successfully implemented in the partially sulfurized functional synaptic device. The developed simple approach of introducing sulfur anions in layered selenide opens an effective new avenue to realize activation of silent synapses for application in evolutionary artificial neural networks.

Optimizing the discovery and assessment of therapeutic targets in heart failure with preserved ejection fraction.

There is an urgent need for models that faithfully replicate heart failure with preserved ejection fraction (HFpEF), now recognized as the most common form of heart failure in the world. In vitro approaches have several shortcomings, most notably the immature nature of stem cell-derived human cardiomyocytes [induced pluripotent stem cells (iPSC)] and the relatively short lifespan of primary cardiomyocytes. Three-dimensional 'organoids' incorporating mature iPSCs with other cell types such as endothelial cells and fibroblasts are a significant advance, but lack the complexity of true myocardium. Animal models can replicate many features of human HFpEF, and rodent models are the most common, and recent attempts to incorporate haemodynamic, metabolic, and ageing contributions are encouraging. Differences relating to species, physiology, heart rate, and heart size are major limitations for rodent models. Porcine models mitigate many of these shortcomings and approximate human physiology more closely, but cost and time considerations limit their potential for widespread use. Ex vivo analysis of failing hearts from animal models offer intriguing possibilities regarding cardiac substrate utilisation, but are ultimately subject to the same constrains as the animal models from which the hearts are obtained. Ex vivo approaches using human myocardial biopsies can uncover new insights into pathobiology leveraging myocardial energetics, substrate turnover, molecular changes, and systolic/diastolic function. In collaboration with a skilled cardiothoracic surgeon, left ventricular endomyocardial biopsies can be obtained at the time of valvular surgery in HFpEF patients. Critically, these tissues maintain their disease phenotype, preserving inter-relationship of myocardial cells and extracellular matrix. This review highlights a novel approach, where ultra-thin myocardial tissue slices from human HFpEF hearts can be used to assess changes in myocardial structure and function. We discuss current approaches to modelling HFpEF, describe in detail the novel tissue slice model, expand on exciting opportunities this model provides, and outline ways to improve this model further.

Improving Outcome of Superior Mediastinal Lymph Node Dissection During Esophagectomy: A Novel Approach Combining Continuous and Intermittent Recurrent Laryngeal Nerve Monitoring.

OBJECTIVE: This study aimed at demonstrating the effects and learning curve of utilizing combined intermittent and continuous recurrent laryngeal nerve (RLN) monitoring for lymphadenectomy during esophagectomy. BACKGROUND: RLN lymphadenectomy is oncologically important but is technically demanding. Vocal cord (VC) palsy as a result from RLN injury, carries significant morbidities. METHODS: This is a retrospective study of consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent transthoracic esophagectomy from 2010 to 2020. Combined nerve monitoring (CNM) included: CNM which involved a periodic stimulating left vagal electrode and intermittent nerve monitoring which utilized a stimulating probe to identify the RLNs. The integrity of the RLNs was assessed both intermittently and continuously. This technique was introduced in 2014. Patients were divided into "before CNM" and "CNM" groups. The primary outcome was the difference in number of RLN lymph nodes harvested and VC palsy rate. Learning curves were demonstrated by cumulative sum (CUSUM) analysis. RESULTS: Two hundred and fifty-five patients were included with 157 patients in "CNM" group. The mean number of RLN lymph nodes harvested was significantly higher (4.31 vs 0.45, P < 0.0001) for the "CNM" group. VC palsy rates were significantly lower (17.8% vs 32.7%, P = 0.007). There was an initial increase in VC palsy rate, peaked at around 46 cases. The increase in lymph nodes harvested above the mean plateaued at around 96 cases. CONCLUSIONS: CNM helped improve bilateral RLN lymphadenectomy. Lymph node harvesting was increased with reduction of VC palsy after a learning curve.

Ultrasensitive two-dimensional material-based MCF-7 cancer cell sensor driven by perturbation processes.

Changes in lipid composition and structure during cell development can be markers for cell apoptosis or various diseases such as cancer. Although traditional fluorescence techniques utilising molecular probes have been studied, these methods are limited in studying these micro-changes as they require complex probe preparation and cannot be reused, making cell monitoring and detection challenging. Here, we developed a direct current (DC) resistance sensor based on two-dimensional (2D) molybdenum disulfide (MoS2) nanosheets to enable cancer cell-specific detection dependent on micro-changes in the cancer cell membrane. Atomistic molecular dynamics (MD) simulations were used to study the interaction between 2D MoS2 and cancer lipid bilayer systems, and revealed that previously unconsidered perturbations in the lipid bilayer can cause an increase in resistance. Under an applied DC sweep, we observed an increase in resistance when cancer cells were incubated with the nanosheets. Furthermore, a correlation was observed between the resistance and breast cancer epithelial cell (MCF-7) population, illustrating a cell population-dependent sensitivity of our method. Our method has a detection limit of ∼3 × 103 cells, below a baseline of ∼1 × 104 cells for the current state-of-the-art electrical-based biosensors using an adherent monolayer with homogenous cells. This combination of a unique 2D material and electrical resistance framework represents a promising approach for the early detection of cancerous cells and to reduce the risk of post-surgery cancer recurrence.