Quantum Equation of Motion with Orbital Optimization for Computing Molecular Properties in Near-Term Quantum Computing.

Determining the properties of molecules and materials is one of the premier applications of quantum computing. A major question in the field is how to use imperfect near-term quantum computers to solve problems of practical value. Inspired by the recently developed variants of the quantum counterpart of the equation-of-motion (qEOM) approach and the orbital-optimized variational quantum eigensolver (oo-VQE), we present a quantum algorithm (oo-VQE-qEOM) for the calculation of molecular properties by computing expectation values on a quantum computer. We perform noise-free quantum simulations of BeH2 in the series of STO-3G/6-31G/6-31G* basis sets and of H4 and H2O in 6-31G using an active space of four electrons and four spatial orbitals (8 qubits) to evaluate excitation energies, electronic absorption, and, for twisted H4, circular dichroism spectra. We demonstrate that the proposed algorithm can reproduce the results of conventional classical CASSCF calculations for these molecular systems.

Improving healthcare professionals' ultrasound-guided peripheral vascular access ability utilizing self-assembled ultrasound phantoms: A prospective, observational quality improvement project.

BACKGROUND: Ultrasound guidance can reduce the number of attempts to gain peripheral IV access while improving the success rate and satisfaction in patients with difficult IV access. Education and simulation are effective tools for improving the skills and knowledge related to ultrasound-guided peripheral IV access. Ultrasound phantom models allow for skill development without the risk of patient harm. METHODS: Twenty-nine registered nurses and nurse practitioners were recruited for education and simulation regarding ultrasound-guided peripheral IV (USGPIV) placement. Participants completed a survey evaluating the efficacy of the phantom models in addition to pre- and post-intervention confidence, perceived competence, knowledge surveys, and a Directly Observed Procedural Skills Evaluation (DOPSE). The intervention included an educational PowerPoint and open practice session using the phantom models. RESULTS: Statistically significant improvements were found in participants' confidence (p < 0.001; 95% CI: 5.287, 9.499; d = 1.31), perceived competence (p < 0.001; 95% CI: 1.231, 2.742; d = 1.20), knowledge (p < 0.001; 95% CI: 1.079, 2.163; d = 1.47), and skills (p < 0.001; 95% CI: 2.499; 5.501; d = 1.29). Participants improved in maintaining needle visualization (p < 0.001; 95% CI: 0.272, 0.9; d = 0.79) and decreasing their cannulation attempts (0.045; 95% CI: 0.013, 1.022; d = 0.48). Participants with no and novice experience saw statistically significant improvement across all categories (p < 0.02) compared to those with intermediate, advanced, or expert experience with ultrasound. 96.5% of participants could perform ultrasound-guided peripheral IV cannulation independently or with indirect supervision following the intervention. CONCLUSIONS: At $36.52 per model, the self-assembled ultrasound phantom models provided a cost-effective and sustainable solution to teaching ultrasound-guided peripheral IV cannulations. Education and simulation for ultrasound-guided peripheral vascular access may benefit individuals with no or novice ultrasound experience.

Acute Effect of E-Cigarette Inhalation on Mucociliary Clearance in E-Cigarette Users.

Background: Recent studies show e-cigarette (EC) users have increased rates of chronic bronchitic symptoms that may be associated with depressed mucociliary clearance (MCC). Little is known about the acute or chronic effects of EC inhalation on in vivo MCC. Methods: In vivo MCC was measured in young adult vapers (n = 5 males, mean age = 21) after controlled inhalation of a radiolabeled (Tc99m sulfur colloid) aerosol. Whole-lung clearance of radiolabeled deposited particles was measured over a 90-minute period for baseline MCC and associated with controlled periodic vaping over the first 60 minutes of MCC measurements. The vaping challenge was administered from a fourth generation box mod EC containing unflavored e-liquid (65% propylene glycol/35% vegetable glycerin, 3 mg/mL freebase nicotine). The challenge was administered at the start of each 10-minute interval of MCC measurements and consisted of 1 puff every 30 seconds for 5 minutes (i.e., 10 puffs for each 10-minute period for a total of 60 puffs during the initial 60 minutes of MCC measurements). Results: Compared with baseline, peripheral lung average clearance (%) over the 90 minutes of MCC measures was enhanced, associated with EC challenge, 12 (±6) versus 24 (±6), respectively (p < 0.05 by Wilcoxon signed-rank test). Conclusions: Acute enhancement of in vivo MCC during EC challenge is contrary to recent studies showing nicotine-associated slowing of ciliary beat and mucus transport at higher nicotine levels than those used here. However, our findings are consistent with an acute increase in fluid volume and mucin secretion to the bronchial airway surface that is likely short lived. Research reported in this publication was supported by the National Institutes of Health R01HL139369 and registered with ClinicalTrials.gov (NCT03700892).

Producing high-quantity and high-quality recombinant adeno-associated virus by low-cis triple transfection.

Recombinant adeno-associated virus (rAAV)-based gene therapy is entering clinical and commercial stages at an unprecedented pace. Triple transfection of HEK293 cells is currently the most widely used platform for rAAV manufacturing. Here, we develop low-cis triple transfection that decreases transgene plasmid use by 10- to 100-fold and overcomes several major limitations associated with standard triple transfection. This new method improves packaging of yield-inhibiting transgenes by up to 10-fold, and generates rAAV batches with reduced plasmid backbone contamination that otherwise cannot be eliminated in downstream processing. When tested in mice and compared with rAAV produced by standard triple transfection, low-cis rAAV shows comparable or superior potency and results in diminished plasmid backbone DNA and RNA persistence in tissue. Mechanistically, low-cis triple transfection relies on the extensive replication of transgene cassette (i.e., inverted terminal repeat-flanked vector DNA) in HEK293 cells during production phase. This cost-effective method can be easily implemented and is widely applicable to producing rAAV of high quantity, purity, and potency.

Which Options Exist for NISQ-Friendly Linear Response Formulations?

Linear response (LR) theory is a powerful tool in classic quantum chemistry crucial to understanding photoinduced processes in chemistry and biology. However, performing simulations for large systems and in the case of strong electron correlation remains challenging. Quantum computers are poised to facilitate the simulation of such systems, and recently, a quantum linear response formulation (qLR) was introduced [Kumar et al., J. Chem. Theory Comput. 2023, 19, 9136-9150]. To apply qLR to near-term quantum computers beyond a minimal basis set, we here introduce a resource-efficient qLR theory, using a truncated active-space version of the multiconfigurational self-consistent field LR ansatz. Therein, we investigate eight different near-term qLR formalisms that utilize novel operator transformations that allow the qLR equations to be performed on near-term hardware. Simulating excited state potential energy curves and absorption spectra for various test cases, we identify two promising candidates, dubbed "proj LRSD" and "all-proj LRSD".

Barriers to Cervical Cancer Screening by Sexual Orientation Among Low-Income Women in North Carolina.

We sought to examine cervical cancer screening barriers by sexual orientation among low-income women in North Carolina. The MyBodyMyTest-3 Trial recruited low-income women (< 250% of federal poverty level) aged 25-64 years who were 1+ year overdue for cervical cancer screening. We compared perceptions of cervical cancer screening among those who self-identified as lesbian, gay, bisexual, or queer (LGBQ; n = 70) to straight/heterosexual women (n = 683). For both LGBQ and straight respondents, the greatest barriers to screening were lack of health insurance (63% and 66%) and cost (49% and 50%). LGBQ respondents were more likely than straight respondents to report forgetting to screen (16% vs. 8%, p = .05), transportation barriers (10% vs. 2%, p = .001), and competing mental or physical health problems (39% vs. 27%, p = .10). Addressing access remains important for improving cervical cancer screening among those under-screened. For LGBQ women, additional attention may be needed for reminders, co-occurring health needs, and transportation barriers.

The variational quantum eigensolver self-consistent field method within a polarizable embedded framework.

We formulate and implement the Variational Quantum Eigensolver Self Consistent Field (VQE-SCF) algorithm in combination with polarizable embedding (PE), thereby extending PE to the regime of quantum computing. We test the resulting algorithm, PE-VQE-SCF, on quantum simulators and demonstrate that the computational stress on the quantum device is only slightly increased in terms of gate counts compared to regular VQE-SCF. On the other hand, no increase in shot noise was observed. We illustrate how PE-VQE-SCF may lead to the modeling of real chemical systems using a simulation of the reaction barrier of the Diels-Alder reaction between furan and ethene as an example.

Two Gender Medicine: Provider-Side Barriers to Caring for Transgender and Gender Diverse Patients.

Experienced and anticipated discrimination during health care visits result in lower health care utilization rates, which contribute to persistent health disparities between transgender and gender diverse (TGD) individuals and the general population. Most strategies for improving health care delivery to TGD patients place the responsibility on providers, overlooking the role of medical systems and institutions in creating the environments where negative health care experiences occur. Relying on the inhabited institutionalism framework, this study explores system- and institutional-level barriers to the provision of quality care to TGD patients identified by health care providers and administrators, including relevant contextual details of, and interactions between, these barriers. Based on interview data from health care providers and administrators from a variety of practices across Texas, we identified two overarching themes and six subthemes. We demonstrate how our interviewees' responses reveal an institutional logic of "two-gender medicine," which creates barriers to health care provision in both formal medical education and training and throughout the managed care model of practice. We also illustrate how health care workers find ways to resist this logic in the course of their practice. Addressing these barriers to delivering competent and compassionate care to TGD patients that providers encounter could make long overdue strides toward addressing health disparities.

Intention to Use Different Formulations of Longer Acting HIV Pre-Exposure Prophylaxis Among Transgender and Gender Expansive Individuals: The Roles of Social Vulnerability and Medical Mistrust.

In 2012, the Federal Drug Administration approved daily oral pre-exposure prophylaxis (PrEP) for HIV prevention in adults. Longer acting injectable PrEP (LA PrEP) has been approved and other formulations are in development. A successful LA PrEP rollout requires examining potential facilitators and barriers to PrEP uptake. Given that transgender and gender expansive (TGE) individuals experience more social vulnerability and higher levels of medical mistrust compared to other populations, examining the role of these two factors in LA PrEP uptake is important. This study, PrEP for ALL, is a community-based participatory research project in Texas that engaged TGE community members and organizational partners through a community advisory board. In total, 482 TGE individuals were recruited and responded to all relevant questions in an online survey, including their intentions to use three formulations: a monthly oral pill, a bimonthly intramuscular injection, and an annual subdermal implant. Multiple regression analysis was used to examine the influence of social vulnerability and medical mistrust on intention to use each LA PrEP formulation adjusting for other relevant factors. Findings suggest that individuals with higher levels of social vulnerability had greater intentions to use the monthly oral pill (ß = 0.12, p = 0.009), the bimonthly intramuscular injection (ß = 0.18, p < 0.001), and annual subdermal implant (ß = 0.17, p < 0.001), whereas medical mistrust reduced intentions to use the bimonthly intramuscular injection (ß = -0.18, p < 0.001) and annual subdermal implant (ß = -0.11, p = 0.021). Improvements in gender-affirming clinical care are needed along with LA PrEP formulations that allow for greater autonomy and reduced clinical contact. Clinical Trial Registration number: NCT05044286.

Adverse Childhood Experiences, Substance Use, and Self-Reported Substance Use Problems Among Sexual and Gender Diverse Individuals: Moderation by History of Mental Illness.

Recent research has highlighted the alarmingly high rates at which sexual and gender diverse (SGD) individuals experience Adverse Childhood Experiences (ACE). ACE, in turn, are strongly related to mental illness-an important correlate of substance use. The present study explores whether mental illness moderates the relationship between ACE and substance use outcomes among SGD adults. As part of a larger community-based participatory research study, we assessed ACE, self-reported mental illness, and past-year substance use and misuse among a large and diverse sample of SGD community members in South Central Texas (n = 1,282). Multivariate logistic regression models were used to assess relationships between ACE, mental illness, substance use, and substance misuse (DAST > 3). Interaction terms between ACE and history of mental illness were created to assess moderation effects. Cumulative ACE scores were associated with a significantly higher odds of self-reported past year substance use (AOR = 1.43, 95% CI = 1.34-1.54) and substance misuse (AOR = 1.21, 95% CI = 1.11-1.32). History of mental illness was associated with an increased odds of self-reported substance misuse (AOR = 2.07, 95% CI = 1.20-3.55), but not past year substance use. There was a significant interaction of ACE and history of mental illness on the odds of past year substance use (AOR = 0.78, 95% CI = 0.69-0.89), but not for substance misuse. These results provide support for theoretical models linking ACE, mental illness, and substance use among SGD adults. Longitudinal research designs are needed to address temporality of outcomes and test mediation models of trauma, mental illness, and substance use. Future directions for prevention and intervention are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-023-00560-y.

Vaping product exposure system (VaPES): a novel in vitro aerosol deposition system.

OBJECTIVE: Due to recent increases in the use of vaping devices, there is a high demand for research addressing the respiratory health effects of vaping products. Given the constantly changing nature of the vaping market with new devices, flavors, metals, and other chemicals rapidly emerging, there is a need for inexpensive and highly adaptable vaping device exposure systems. Here, we describe the design and validation of a novel in vitro aerosol exposure system for toxicity testing of vaping devices. MATERIALS AND METHODS: We developed an inexpensive, open-source in vitro vaping device exposure system that produces even deposition, can be adapted for different vaping devices, and allows for experiments to be performed under physiological conditions. The system was then validated with deposition testing and a representative exposure with human bronchial epithelial cells (hBECs). RESULTS: The Vaping Product Exposure System (VaPES) produced sufficient and uniform deposition for dose-response studies and was precise enough to observe biological responses to vaping exposures. VaPES was adapted to work with both pod and cartridge-based vaping devices. CONCLUSION: We have designed and validated a novel vaping device exposure system that will eliminate the need to use high-cost commercial exposure systems, lowering the barrier to entry of physiologically relevant vaping studies.

Missing a "Missing Self" Mechanism: Modeling and Detection of Ly49 Expression in Canine NK Cells.

NK cells are a key focus in immuno-oncology, based on their ability to eliminate malignant cells without prior sensitization. Dogs are valuable models for translational immunotherapy studies, especially for NK cells, where critical species differences exist between mice and humans. Given that the mechanism for recognition of "self" by canine NK cells is currently unknown, we sought to evaluate expression of Ly49 in canine NK cells using in silico and high-throughput techniques. We interrogated the identified polymorphism/mutation in canine Ly49 and assessed the potential impact on structure using computational modeling of three-dimensional protein structure and protein-protein docking of canine Ly49 with MHC class I (MHC-I). Bulk and single-cell RNA-sequencing analysis was performed to detect gene expression of Ly49/KLRA1 in resting and activated NK cells. Tertiary protein structure demonstrated significant structural similarity to the known murine system. Molecular docking of canine Ly49 with MHC-I was favorable, converging at a single low-energy conformation. RNA sequencing revealed expression of Ly49/KLRA1 in both resting and activated NK cells and demonstrated almost exclusive expression of the gene in the NK cluster at the single-cell level. Despite prior reports of a mutated, nonfunctional canine Ly49, our data support that the protein product is predicted to bind to MHC-I in a comparable conformation to the murine system and is expressed in canine NK cells with upregulation following activation. Taken together, these data suggest that Ly49 is capable of recognizing MHC-I and therefore regulating NK cell function in dogs.

Nickel-catalyzed ester carbonylation promoted by imidazole-derived carbenes and salts.

Millions of tons of acetyl derivatives such as acetic acid and acetic anhydride are produced each year. These building blocks of chemical industry are elaborated into esters, amides, and eventually polymer materials, pharmaceuticals, and other consumer products. Most acetyls are produced industrially using homogeneous precious metal catalysts, principally rhodium and iridium complexes. We report here that abundant nickel can be paired with imidazole-derived carbenes or the corresponding salts to catalyze methyl ester carbonylation with turnover frequency (TOF) exceeding 150 hour-1 and turnover number (TON) exceeding 1600, benchmarks that invite comparisons to state-of-the-art rhodium-based systems and considerably surpass known triphenylphosphine-based nickel catalysts, which operate with TOF ~7 hour-1 and TON ~100 under the same conditions.

Patterns of Variation in the Usage of Fatty Acid Chains among Classes of Ester and Ether Neutral Lipids and Phospholipids in the Queensland Fruit Fly.

Modern lipidomics has the power and sensitivity to elucidate the role of insects' lipidomes in their adaptations to the environment at a mechanistic molecular level. However, few lipidomic studies have yet been conducted on insects beyond model species such as Drosophila melanogaster. Here, we present the lipidome of adult males of another higher dipteran frugivore, Bactrocera tryoni. We describe 421 lipids across 15 classes of ester neutral lipids and phospholipids and ether neutral lipids and phospholipids. Most of the lipids are specified in terms of the carbon and double bond contents of each constituent hydrocarbon chain, and more ether lipids are specified to this degree than in any previous insect lipidomic analyses. Class-specific profiles of chain length and (un)saturation are broadly similar to those reported in D. melanogaster, although we found fewer medium-length chains in ether lipids. The high level of chain specification in our dataset also revealed widespread non-random combinations of different chain types in several ester lipid classes, including deficits of combinations involving chains of the same carbon and double bond contents among four phospholipid classes and excesses of combinations of dissimilar chains in several classes. Large differences were also found in the length and double bond profiles of the acyl vs. alkyl or alkenyl chains of the ether lipids. Work on other organisms suggests some of the differences observed will be functionally consequential and mediated, at least in part, by differences in substrate specificity among enzymes in lipid synthesis and remodelling pathways. Interrogation of the B. tryoni genome showed it has comparable levels of diversity overall in these enzymes but with some gene gain/loss differences and considerable sequence divergence from D. melanogaster.

Arthroplasty for Treating Proximal Femur Metastatic Lesions May Be Associated with Lower Mortality Rates Compared to Intramedullary Nailing within the VA Healthcare System.

Metastatic bony disease is a significant health issue, with approximately 700,000 new cases annually that tend to metastasize to bones. The proximal femur in the appendicular skeleton is commonly affected. Our study aimed to investigate mortality rates and hospital stay duration in patients with pathologic proximal femur fractures treated with either intramedullary nailing or arthroplasty within the Veterans Health Administration system. In total, 679 patients (265 arthroplasty, 414 intramedullary nails) were identified through ICD-9 and CPT codes from 30 September 2010 to 1 October 2015. Hospital stays were similar for both groups (arthroplasty: 10.5 days, intramedullary nails: 11 days, p = 0.1). Mortality was associated with increased age and Gagne comorbidity scores (p < 0.001). Arthroplasty showed a survival benefit in the log-rank test (p = 0.018), and this difference persisted in the multivariate analysis after adjusting for age and comorbidities, with a hazard ratio of 1.3. Our study reported evidence that arthroplasty is associated with increased patient survival even when accounting for age and comorbidities in treating metastatic disease of the proximal femur.

The Sexual and Gender Minority Adverse Childhood Experiences Scale.

INTRODUCTION: Sexual and gender minority (SGM) adverse childhood experiences (ACEs) are identity-based forms of early life adversity. Exposure to SGM ACEs is associated with increased odds of depression, anxiety, and post-traumatic stress disorder in SGM adults. The purpose of this study was to further test a revised version of the measure in a U.S. sample with more robust and clinically relevant mental health outcomes. METHODS: In May and June 2022, a national sample of SGM adults (N=4,445) was recruited from a Qualtrics Panel to complete a 20-minute online survey that included questions regarding ACEs, SGM ACEs, depression, anxiety, and post-traumatic stress disorder. Exploratory factor analysis and confirmatory factor analysis were used to examine factor structure. Multivariable regression was used to assess criterion validity, and a sensitivity analysis was conducted. Data were analyzed in February 2023. RESULTS: Respondents indicate that vicarious trauma (81%) and school bullying (67%) were the most common experiences and that all SGM ACEs were frequently occurring before adulthood. Confirmatory factor analysis determined a 1-factor solution. Participants with more SGM adverse childhood experiences exposure had worse anxiety, depression, and post-traumatic stress disorder symptoms (ß=0.16, ß=0.18, ß=0.26, respectively, p<0.0001) after controlling for ACEs exposure and demographic factors. A sensitivity analysis indicated that estimates were similar in terms of magnitude and direction. CONCLUSIONS: SGM ACEs commonly and frequently occur before adulthood and impact adult SGM mental health. Overall, the measure had good-to-excellent psychometric properties. Future research should consider integrating SGM ACEs and Minority Stress Theory.

Mental Health and Substance Misuse Indicators Associated with First-Time Homelessness among a Community Sample of Sexual and Gender Minority Adults.

Homelessness is a priority public health issue in the United States (U.S.) given its strong associations with multiple adverse health outcomes. While overall rates of homelessness have decreased over the last decade, some populations-such as sexual and gender minorities-have not seen equitable decreases. The present study explores the relationship between experiences of first-time homelessness with substance misuse (assessed via the DAST-10) and depression and anxiety (assessed via the PHQ-4) in an adult sample of SGM individuals in South Central Texas. The analytic sample (n = 907) was majority gay/lesbian or same-gender loving (55.8%) followed by bisexual or pansexual (34.7%) or another sexual identity (9.5%) and 12.5% were transgender. First-time homelessness was more common in childhood than adulthood. Multivariate logistic regression models were used to evaluate relationships between first-time homelessness and outcomes of interest. The odds of substance misuse (DAST > 3) were marginally higher for those experiencing first-time homelessness in childhood and significantly higher for those reporting first-time homelessness in adulthood. The odds of experiencing past 2-week depression were significantly greater for those reporting homelessness in childhood or adulthood. However, only first-time homelessness in adulthood was significantly associated with past two-week anxiety. These findings underscore the need to consider intersectionality when exploring solutions to existing health disparities, as this work suggests that both sexual and gender identity and homelessness are important factors in shaping mental and behavioral health outcomes.

Sexual and gender minority adverse childhood experiences (SGM-ACEs), perceived social support, and adult mental health.

BACKGROUND: Building on decades of research into the long-term developmental impacts of adverse childhood experiences (ACEs), researchers have called for expanding the ACEs framework to include experiences specific to minoritized identities. Recent empirical research has led to the development of a measure of sexual and gender minority adverse childhood experiences (SGM-ACEs). Within the SGM-specific ACEs framework, research on the long-term impact to adult mental health and the role of perceived social support are not well studied. OBJECTIVE: The purpose of this paper was two-fold. First, examine whether SGM-ACEs adversely impact mental health in SGM adults. Second, examine the role of perceived social support in the association between SGM-ACEs and adult mental health. PARTICIPANTS AND SETTING: Data were collected using a multifaceted sampling strategy. In total, 1819 self-identified SGM Texans completed an online survey inquiring about ACEs, SGM-ACEs, mental health, and demographic characteristics. RESULTS: We estimated two competing structural equation models (SEM) examining the associations between SGM-ACEs and anxiety and depressive symptoms, and whether perceived social support may moderate or mediate his association. While both models demonstrated that SGM-ACEs were significantly associated with higher anxiety and depressive symptoms. However, we found more support for the mediation model such that SGM-ACEs had direct effects on anxiety and depressive symptoms, and an indirect effect on anxiety symptoms through family support. CONCLUSIONS: Our findings confirmed that exposure to SGM-ACE is associated with poorer adult mental health. Additionally, SGM-ACEs exposure undermines SGM individuals' perceptions of family support, which increases symptoms of anxiety.

Querying Recombination Junctions of Replication-Competent Adeno-Associated Viruses in Gene Therapy Vector Preparations with Single Molecule, Real-Time Sequencing.

Clinical-grade preparations of adeno-associated virus (AAV) vectors used for gene therapy typically undergo a series of diagnostics to determine titer, purity, homogeneity, and the presence of DNA contaminants. One type of contaminant that remains poorly investigated is replication-competent (rc)AAVs. rcAAVs form through recombination of DNA originating from production materials, yielding intact, replicative, and potentially infectious virus-like virions. They can be detected through the serial passaging of lysates from cells transduced by AAV vectors in the presence of wildtype adenovirus. Cellular lysates from the last passage are subjected to qPCR to detect the presence of the rep gene. Unfortunately, the method cannot be used to query the diversity of recombination events, nor can qPCR provide insights into how rcAAVs arise. Thus, the formation of rcAAVs through errant recombination events between ITR-flanked gene of interest (GOI) constructs and expression constructs carrying the rep-cap genes is poorly described. We have used single molecule, real-time sequencing (SMRT) to analyze virus-like genomes expanded from rcAAV-positive vector preparations. We present evidence that sequence-independent and non-homologous recombination between the ITR-bearing transgene and the rep/cap plasmid occurs under several events and rcAAVs spawn from diverse clones.