Enhancing patient outcomes: the role of clinical utility in guiding healthcare providers in curating radiology AI applications.

With advancements in artificial intelligence (AI) dominating the headlines, diagnostic imaging radiology is no exception to the accelerating role that AI is playing in today's technology landscape. The number of AI-driven radiology diagnostic imaging applications (digital diagnostics) that are both commercially available and in-development is rapidly expanding as are the potential benefits these tools can deliver for patients and providers alike. Healthcare providers seeking to harness the potential benefits of digital diagnostics may consider evaluating these tools and their corresponding use cases in a systematic and structured manner to ensure optimal capital deployment, resource utilization, and, ultimately, patient outcomes-or clinical utility. We propose several guiding themes when using clinical utility to curate digital diagnostics.

Characterization of Regolith And Trace Economic Resources (CRATER): An Orbitrap-based laser desorption mass spectrometry instrument for in situ exploration of the Moon.

RATIONALE: Characterization of Regolith And Trace Economic Resources (CRATER), an Orbitrap™-based laser desorption mass spectrometry instrument designed to conduct high-precision, spatially resolved analyses of planetary materials, is capable of answering outstanding science questions about the Moon's formation and the subsequent processes that have modified its (sub)surface. METHODS: Here, we describe the baseline design of the CRATER flight model, which requires <20 000 cm3  volume, <10 kg mass, and <60 W peak power. The analytical capabilities and performance metrics of a prototype that meets the full functionality of the flight model are demonstrated. RESULTS: The instrument comprises a high-power, solid-state, pulsed ultraviolet (213 nm) laser source to ablate the surface of the lunar sample, a custom ion optical interface to accelerate and collimate the ions produced at the ablation site, and an Orbitrap mass analyzer capable of discriminating competing isobars via ultrahigh mass resolution and high mass accuracy. The CRATER instrument can measure elemental and isotopic abundances and characterize the organic content of lunar surface samples, as well as identify economically valuable resources for future exploration. CONCLUSION: An engineering test unit of the flight model is currently in development to serve as a pathfinder for near-term mission opportunities.

B-factor prediction in proteins using a sequence-based deep learning model.

B factors provide critical insight into protein dynamics. Predicting B factors of an atom in new proteins remains challenging as it is impacted by their neighbors in Euclidean space. Previous learning methods developed have resulted in low Pearson correlation coefficients beyond the training set due to their limited ability to capture the effect of neighboring atoms. With the advances in deep learning methods, we develop a sequence-based model that is tested on 2,442 proteins and outperforms the state-of-the-art models by 30%. We find that the model learns that the B factor of a site is prominently affected by atoms within a 12-15 Å radius, which is in excellent agreement with cutoffs from protein network models. The ablation study revealed that the B factor can largely be predicted from the primary sequence alone. Based on the abovementioned points, our model lays a foundation for predicting other properties that are correlated with the B factor.

Increase in Charge and Density Improves the Strength and Toughness of Mussel Foot Protein 5 Inspired Protein Materials.

Mussel foot protein 5 (fp5) found in the adhesive byssal plaque of Mediterranean mussel Mytilus galloprovincialis exhibits exceptional underwater adhesion to diverse surfaces to the extent that adhesion strength typically exceeds the cohesive strength of the plaque. While sequence effects such as presence of charged residues, metal ion coordination, and high catechol content have been identified to govern fp5's interaction with surfaces, molecular contributors to its cohesive strength remain to be fully understood. Addressing this issue is critical for designing mussel-inspired sequences for new adhesives and biomaterials enabled by synthetic biology. Here we carry out all-atom molecular dynamics simulations on hydrated model fp5 biopolymer melts to understand how sequence features such as tyrosine and charge content affect packing density and inter-residue and ionic interaction strengths and consequently influence the cohesive strength and toughness. Systematic serine (S) substitutions for lysine (K), arginine (R) and tyrosine (Y) residues reveal that Y to S substitution surprisingly results in improvement of cohesive strength due to densification of the material by removal of steric hindrances, whereas the removal of charge in K and R to S substitutions has a detrimental impact on strength and toughness as it reduces cohesive interactions facilitated by electrostatic interactions. Additionally, melts formed from split fp5 sequences with only C or N terminal halves show distinct mechanical responses that further illustrate the role of charge. Our findings provide new insights for designing materials that could potentially surpass the performance of existing biomolecular and bioinspired adhesives, specifically by tailoring sequences for balancing charge and excluded volume effects.

Detection of Short Peptides as Putative Biosignatures of Psychrophiles via Laser Desorption Mass Spectrometry.

Studies of psychrophilic life on Earth provide chemical clues as to how extraterrestrial life could maintain viability in cryogenic environments. If living systems in ocean worlds (e.g., Enceladus) share a similar set of 3-mer and 4-mer peptides to the psychrophile Colwellia psychrerythraea on Earth, spaceflight technologies and analytical methods need to be developed to detect and sequence these putative biosignatures. We demonstrate that laser desorption mass spectrometry, as implemented by the CORALS spaceflight prototype instrument, enables the detection of protonated peptides, their dimers, and metal adducts. The addition of silicon nanoparticles promotes the ionization efficiency, improves mass resolving power and mass accuracies via reduction of metastable decay, and facilitates peptide de novo sequencing. The CORALS instrument, which integrates a pulsed UV laser source and an Orbitrap™ mass analyzer capable of ultrahigh mass resolving powers and mass accuracies, represents an emerging technology for planetary exploration and a pathfinder for advanced technique development for astrobiological objectives. Teaser: Current spaceflight prototype instrument proposed to visit ocean worlds can detect and sequence peptides that are found enriched in at least one strain of microbe surviving in subzero icy brines via silicon nanoparticle-assisted laser desorption analysis.

A prospective cohort study of renal function and bone turnover in adults with hepatitis B virus (HBV)-HIV co-infection with high prevalence of tenofovir-based antiretroviral therapy use.

OBJECTIVE: Tenofovir disoproxil fumarate (TDF) is a common component of antiretroviral therapy in hepatitis B virus (HBV)-HIV co-infected adults but few studies have evaluated worsening renal function and bone turnover, known effects of TDF. METHODS: Adults from eight North American sites were enrolled in this cohort study. Research assessments were conducted at entry and every 24 weeks for ≤192 weeks. Bone markers were tested at baseline, week 96 and week 192 from stored serum. We evaluated changes in markers of renal function and bone turnover over time and potential contributing factors. RESULTS: A total of 115 patients were prospectively followed; median age 49 years, 91% male and 52% non-Hispanic Black. Duration of HIV was 20.5 years. TDF use ranged from 80% to 92% throughout follow-up. Estimated glomerular filtration rate (eGFR) (ml/min/1.73m2 ) decreased from 87.1 to 79.9 over 192 weeks (p < 0.001); however, the prevalence of eGFR <60 ml/min/1.73m2 did not appear to differ over time (always <16%; p = 0.43). From baseline to week 192, procollagen type I N-terminal propeptide (P1NP) (146.7 to 130.5 ng/ml; p = 0.001), osteocalcin (14.4 to 10.2 ng/ml; p < 0.001) and C-terminal telopeptides of type I collagen (CTX-1) (373 to 273 pg/ml; p < 0.001) decreased. Younger age, male sex and overweight/obesity versus normal weight predicted a decrease in eGRF. Black race, healthy weight versus underweight, advanced fibrosis, undetectable HBV DNA, and lower parathyroid hormone level predicted worsening bone turnover. CONCLUSION: In this HBV-HIV cohort with high prevalence of TDF use, several biomarkers of renal function and bone turnover indicated worsening status over approximately 4 years, highlighting the importance of clinical awareness in co-infected adults.

Extracellular Vesicle MicroRNA in Malignant Pleural Effusion.

Lung and breast cancer are the two most common causes of malignant pleural effusion (MPE). MPE diagnosis plays a crucial role in determining staging and therapeutic interventions in these cancers. However, our understanding of the pathogenesis and progression of MPE at the molecular level is limited. Extracellular Vesicles (EVs) and their contents, including microRNAs (miRNAs), can be isolated from all bodily fluids, including pleural fluid. This study aims to compare EV-miRNA patterns of expression in MPE caused by breast (BA-MPE) and lung (LA-MPE) adenocarcinomas compared to the control group of heart-failure-induced effusions (HF-PE). We conducted an analysis of 24 pleural fluid samples (8 LA-MPE, 8 BA-MPE, and 8 HF-PE). Using NanoString technology, we profiled miRNAs within EVs isolated from 12 cases. Bioinformatic analysis demonstrated differential expression of miR-1246 in the MPE group vs. HF-PE group and miR-150-5p and miR-1246 in the BA-MPE vs. LA-MPE group, respectively. This difference was demonstrated and validated in an independent cohort using real-time PCR (RT-PCR). miRNA-1246 demonstrated 4-fold increased expression (OR: 3.87, 95% CI: 0.43, 35) in the MPE vs. HF-PE group, resulting in an area under the curve of 0.80 (95% CI: 0.60, 0.99). The highest accuracy for differentiating MPE vs. HF-PE was seen with a combination of miRNAs compared to each miRNA alone. Consistent with prior studies, this study demonstrates dysregulation of specific EV-based miRNAs in breast and lung cancer; pleural fluid provides direct access for the analysis of these EV-miRNAs as biomarkers and potential targets and may provide insight into the underlying pathogenesis of tumor progression. These findings should be explored in large prospective studies.

A combined helium atom scattering and density-functional theory study of the Nb(100) surface oxide reconstruction: Phonon band structures and vibrational dynamics.

Helium atom scattering and density-functional theory (DFT) are used to characterize the phonon band structure of the (3 × 1)-O surface reconstruction of Nb(100). Innovative DFT calculations comparing surface phonons of bare Nb(100) to those of the oxide surface show increased resonances for the oxide, especially at higher energies. Calculated dispersion curves align well with experimental results and yield atomic displacements to characterize polarizations. Inelastic helium time-of-flight measurements show phonons with mixed longitudinal and shear-vertical displacements along both the ⟨1̄00⟩, Γ̄X̄ and ⟨11̄0⟩, Γ̄M̄ symmetry axes over the entire first surface Brillouin zone. Force constants calculated for bulk Nb, Nb(100), and the (3 × 1)-O Nb(100) reconstruction indicate much stronger responses from the oxide surface, particularly for the top few layers of niobium and oxygen atoms. Many of the strengthened bonds at the surface create the characteristic ladder structure, which passivates and stabilizes the surface. These results represent, to our knowledge, the first phonon dispersion data for the oxide surface and the first ab initio calculation of the oxide's surface phonons. This study supplies critical information for the further development of advanced materials for superconducting radiofrequency cavities.

Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers With No Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial.

INTRODUCTION: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking is unclear. This exploratory analysis examined the effects of ENDS delivering different amounts of nicotine on cigarette abstinence up to 24-week follow-up, in comparison to placebo or a behavioral substitute. METHODS: This four-arm parallel-group, randomized, placebo-controlled trial took place at two academic medical centers in the United States (Penn State Hershey and Virginia Commonwealth University). Participants were current adult smokers (N = 520) interested in reducing but not planning to quit. They received brief advice and were randomized to one of four 24-week conditions, receiving either an eGo-style ENDS paired with 0, 8, or 36 mg/ml nicotine liquid (double-blind) or a cigarette-shaped tube, as a cigarette substitute (CS). Self-reported daily cigarette consumption and exhaled carbon monoxide (CO) were measured at all study visits. Outcomes included intent-to-treat, self-reported 7-day cigarette abstinence, biochemically confirmed by exhaled CO at 24 weeks after randomization. RESULTS: At 24 weeks, significantly more participants in the 36 mg/ml condition (14/130, 10.8%) than in the 0 mg/ml condition (1/130, 0.8%) and the CS condition (4/130, 3.1%) were abstinent (relative risk = 14 [95% CI = 1.9-104.9] and 3.5 [95% CI = 1.2-10.4], respectively). The abstinence rate in the 8 mg/ml condition was 4.6% (6/130). CONCLUSIONS: When smokers seeking to reduce smoking tried ENDS, few quit smoking in the short term. However, if smokers continued to use an ENDS with cigarette-like nicotine delivery, a greater proportion completely switched to ENDS, as compared with placebo or a cigarette substitute. IMPLICATIONS: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking was unclear. This randomized trial found that ENDS with nicotine delivery approaching that of a cigarette are more effective in helping ambivalent smokers to quit cigarette smoking.

Photoelectron spectroscopic study of dipole-bound and valence-bound nitromethane anions formed by Rydberg electron transfer.

Close-lying dipole-bound and valence-bound states in the nitromethane anion make this molecule an ideal system for studying the coupling between these two electronically different states. In this work, dipole-bound and valence-bound nitromethane anions were generated by Rydberg electron transfer and characterized by anion photoelectron spectroscopy. The presence of the dipole-bound state was demonstrated through its photoelectron spectral signature, i.e., a single narrow peak at very low electron binding energy, its strong Rydberg quantum number, n*, dependence, and its relatively large anisotropy parameter, ß. This work goes the furthest yet in supporting the doorway model of electron attachment to polar molecules.

Community Tele-pal: A community-developed, culturally based palliative care tele-consult randomized controlled trial for African American and White Rural southern elders with a life-limiting illness.

BACKGROUND: Patients living in rural areas experience a variety of unmet needs that result in healthcare disparities. The triple threat of rural geography, racial inequities, and older age hinders access to high-quality palliative care (PC) for a significant proportion of Americans. Rural patients with life-limiting illness are at risk of not receiving appropriate palliative care due to a limited specialty workforce, long distances to treatment centers, and limited PC clinical expertise. Although culture strongly influences people's response to diagnosis, illness, and treatment preferences, culturally based care models are not currently available for most seriously ill rural patients and their family caregivers. The purpose of this randomized clinical trial (RCT) is to compare a culturally based tele-consult program (that was developed by and for the rural southern African American (AA) and White (W) population) to usual hospital care to determine the impact on symptom burden (primary outcome) and patient and care partner quality of life (QOL), care partner burden, and resource use post-discharge (secondary outcomes) in hospitalized AA and White older adults with a life-limiting illness. METHODS: Community Tele-pal is a three-site RCT that will test the efficacy of a community-developed, culturally based PC tele-consult program for hospitalized rural AA and W older adults with life-limiting illnesses (n = 352) and a care partner. Half of the participants (n = 176) and a care partner (n = 176) will be randomized to receive the culturally based palliative care consult. The other half of the patient participants (n = 176) and care partners (n = 176) will receive usual hospital care appropriate to their illness. DISCUSSION: This is the first community-developed, culturally based PC tele-consult program for rural southern AA and W populations. If effective, the tele-consult palliative program and methods will serve as a model for future culturally based PC programs that can reduce patients' symptoms and care partner burden. TRIAL REGISTRATION: ClinicalTrials.gov NCT03767517 . Registered on 27 December 2018.

The ground state, quadrupole-bound anion of succinonitrile revisited.

Using a combination of Rydberg electron transfer and negative ion photoelectron spectroscopy, we revisited an earlier study which, based on several separate pieces of evidence, had concluded that trans- and gauche-succinonitrile can form quadrupole bound anions (QBAs) and dipole bound anions (DBAs), respectively. In the present work, succinonitrile anions were formed by Rydberg electron transfer and interrogated by negative ion photoelectron spectroscopy. The resulting anion photoelectron spectra exhibited distinctive spectral features for both QBA and DBA species in the same spectrum, thereby providing direct spectroscopic confirmation of previous indirect conclusions. Just as importantly, this work also introduces the integrated combination of Rydberg electron transfer and anion photoelectron spectroscopy as a powerful, tandem technique for studying diffuse excess electron states.

Observation of the dipole- and quadrupole-bound anions of 1,4-dicyanocyclohexane.

Quadrupole-bound anions are negative ions in which their excess electrons are loosely bound by long-range electron-quadrupole attractions. Experimental evidence for quadrupole-bound anions has been scarce; until now, only trans-succinonitrile had been experimentally confirmed to form a quadrupole-bound anion. In this study, we present experimental evidence for a new quadrupole-bound anion. Our combined Rydberg electron transfer/anion photoelectron spectroscopy study demonstrates that the ee conformer of 1,4-dicyanocyclohexane (DCCH) supports a quadrupole-bound anion state, and that the cis-DCCH conformer forms a dipole-bound anion state. The electron binding energies of the quadrupole- and dipole-bound anions are measured as 18 and 115 meV, respectively, both of which are in excellent agreement with theoretical calculations by Sommerfeld.

An ultrasonographic analysis of the activation patterns of abdominal muscles in children with spastic type cerebral palsy and in typically developing individuals: a comparative study.

BACKGROUND: Abdominal muscles have stiffer appearance in individuals with spastic type cerebral palsy (STCP) than in their typically developing (TD) peers. This apparent stiffness has been implicated in pelvic instability, mal-rotation, poor gait and locomotion. This study was aimed at investigating whether abdominal muscles activation patterns from rest to activity differ in the two groups. METHOD: From ultrasound images, abdominal muscles thickness during the resting and active stages was measured in 63 STCP and 82 TD children. The thickness at each stage and the change in thickness from rest to activity were compared between the two groups. RESULTS: Rectus abdominis (RA) muscle was the thickest muscle at rest as well as in active stage in both groups. At rest, all muscles were significantly thicker in the STCP children (p <  0.001). From rest to active stages muscle thickness significantly increased (p <  0.001) in the TD group and significantly decreased (p <  0.001) in the STCP children, except for RA, which became thicker during activity in both groups. In active stages, no significant differences in the thickness in the four abdominal muscles were found between the STCP and the TD children. CONCLUSION: Apart from the RA muscle, the activation pattern of abdominal muscles in individuals with STCP differs from that of TD individuals. Further studies required for understanding the activation patterns of abdominal muscles prior to any physical fitness programmes aimed at improving the quality of life in individuals with STCP. TRIAL REGISTRATION: HREC REF: 490/2011. Human Research Ethics Committee, Faculty of Health Sciences, University of Cape Town, South Africa. November 17, 2011.

Separation of Isotopes in Space and Time by Gas-Surface Atomic Diffraction.

The separation of isotopes in space and time by gas-surface atomic diffraction is presented as a new means for isotopic enrichment. A supersonic beam of natural abundance neon is scattered from a periodic surface of methyl-terminated silicon, with the ^{20}Ne and ^{22}Ne isotopes scattering into unique diffraction channels. Under the experimental conditions presented in this Letter, a single pass yields an enrichment factor 3.50±0.30 for the less abundant isotope, ^{22}Ne, with extension to multiple passes easily envisioned. The velocity distribution of the incident beam is demonstrated to be the determining factor in the degree of separation between the isotopes' diffraction peaks. In cases where there is incomplete angular separation, the difference in arrival times of the two isotopes at a given scattered angle can be exploited to achieve complete temporal separation of the isotopes. This study explores the novel application of supersonic molecular beam studies as a viable candidate for separation of isotopes without the need for ionization or laser excitation.

Electrophilicity of oxalic acid monomer is enhanced in the dimer by intermolecular proton transfer.

We have analyzed the effect of excess electron attachment on the network of hydrogen bonds in the oxalic acid dimer (OA)2. The most stable anionic structures may be viewed as complexes of a neutral hydrogenated moiety HOA˙ coordinated to an anionic deprotonated moiety (OA-H)-. HOA˙ acts as a double proton donor and (OA-H)- as a double proton acceptor. Thus the excess electron attachment drives intermolecular proton transfer. We have identified several cyclic hydrogen bonded structures of (OA)2-. Their stability has been analyzed in terms of the stability of the involved conformers, the energetic penalty for deformation of these conformers to the geometry of the dimer, and the two-body interaction energy between the deformed HOA˙ and (OA-H)-. There are at least seven isomers of (OA)2- with stabilization energies in the range of 1.26-1.39 eV. These energies are dominated by attractive two-body interaction energies. The anions are vertically bound electronically by 3.0-3.4 eV and adiabatically bound by at least 1.6 eV. The computational predictions are consistent with the anion photoelectron spectrum of (OA)2-. The spectrum consists of a broad feature, with an onset of 2.5 eV and spanning to 4.3 eV. The electron vertical detachment energy (VDE) is assigned to be 3.3 eV.

The impact of a preloaded intraocular lens delivery system on operating room efficiency in routine cataract surgery.

PURPOSE: The aim of this study was to evaluate the operational impact of using preloaded intraocular lens (IOL) delivery systems compared with manually loaded IOL delivery processes during routine cataract surgeries. METHODS: Time and motion data, staff and surgery schedules, and cost accounting reports were collected across three sites located in the US, France, and Canada. Time and motion data were collected for manually loaded IOL processes and preloaded IOL delivery systems over four surgery days. Staff and surgery schedules and cost accounting reports were collected during the 2 months prior and after introduction of the preloaded IOL delivery system. RESULTS: The study included a total of 154 routine cataract surgeries across all three sites. Of these, 77 surgeries were performed using a preloaded IOL delivery system, and the remaining 77 surgeries were performed using a manual IOL delivery process. Across all three sites, use of the preloaded IOL delivery system significantly decreased mean total case time by 6.2%-12.0% (P<0.001 for data from Canada and the US and P<0.05 for data from France). Use of the preloaded delivery system also decreased surgeon lens time, surgeon delays, and eliminated lens touches during IOL preparation. CONCLUSION: Compared to a manual IOL delivery process, use of a preloaded IOL delivery system for cataract surgery reduced total case time, total surgeon lens time, surgeon delays, and eliminated IOL touches. The time savings provided by the preloaded IOL delivery system provide an opportunity for sites to improve routine cataract surgery throughput without impacting surgeon or staff capacity.

The onset of electron-induced proton-transfer in hydrated azabenzene cluster anions.

The prospect that protons from water may be transferred to N-heterocyclic molecules due to the presence of an excess electron is studied in hydrated azabenzene cluster anions using anion photoelectron spectroscopy and computational chemistry. In the case of s-triazine (C3H3N3), which has a positive adiabatic electron affinity, proton transfer is not energetically favored nor observed experimentally. Heterocyclic rings with only 1 or 2 nitrogen atoms have negative electron affinities, but the addition of solvating water molecules can yield stable negative ions. In the case of the diazines (C4H4N2: pyrazine, pyrimidine, and pyridazine) the addition of one water molecule is enough to stabilize the negative ion, with the majority of the excess electron density in a π* orbital of the heterocycle but not significantly extended over the hydrogen bonded water network. Pyridine (C5H5N), with the most negative electron affinity, requires three water molecules to stabilize its negative ion. Although our computations suggest proton transfer to be energetically viable in all five N-heterocyclic systems studied here when three or more water molecules are present, proton transfer is not observed experimentally in the triazine nor in the diazine series. In pyridine, however, proton transfer competes energetically with hydrogen bonding (solvation), when three water molecules are present, i.e., both motifs are observed. Pyridine clusters containing four or more water molecules almost exclusively exhibit proton transfer along with solvated [C(6-x)H(6-x+1)N(x)·OH](-) ions.