The feasibility and acceptability of integrating dogs into inpatient rehabilitation therapy with children with acquired brain injury.

INTRODUCTION: Children with acquired brain injury (ABI) are at risk for poor therapeutic engagement due to cognitive impairment, affect lability, pain, and fatigue. Animal-assisted therapy (AAT) has the potential to improve patient engagement in rehabilitation therapies; however, the feasibility of integrating AAT into the rigorous therapy schedule of inpatient clinical care or its reception by patients, families, and staff is unknown. OBJECTIVE: To examine the feasibility and acceptability of incorporating dogs into physical therapy and occupational therapy sessions with pediatric patients being treated on an inpatient rehabilitation unit for acquired brain injury. DESIGN: A feasibility study of AAT within the context of a within-subjects crossover study. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: Sixteen patients, aged 7-28 years (mean = 13.6 years, standard deviation [SD] = 5.2 years; 50% male), being treated on the inpatient rehabilitation unit following ABI. INTERVENTION: AAT - the integration of dogs into inpatient physical therapy and occupational therapy sessions. MAIN OUTCOME MEASURES: Feasibility measures: enrollment rate, the proportion of AAT sessions a dog attended, adverse events, instances where therapist or handler ended session early, patient animal closeness, and utilization of dog in session. Satisfaction measures: parent satisfaction questionnaires and therapist feedback. RESULTS: Feasibility was supported by high enrollment rate (88.9%) and dog attendance rate of 93%-95%; 84.3% of sessions used the dog in multiple ways and patients reported a high level of closeness with the dog in session, indicating that the dogs were integrated in meaningful ways. No adverse events were noted, therapists reported that intervention was convenient, and clinical care was not negatively impacted. A high level of satisfaction was reported by families and therapists. CONCLUSIONS: Findings suggest that AAT is feasible and acceptable, and it may be a valuable tool for therapists working with patients with ABI on an inpatient rehabilitation unit.

Dynamics of magnetization at infinite temperature in a Heisenberg spin chain.

Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.

A Toxic Sterolysin From a 1950s Culture of Gymnodinium Veneficum Ballantine.

In 1957 Abbott and Ballentine described a highly toxic activity from a dinoflagellate isolated from the English Channel. in 1949 by Mary Park. From a culture maintained at Plymouth Laboratory since 1950, we have been able to isolate two toxic molecules (Abbotoxin and 59-E-Chloro-Abbotoxin), determine the planar structures by analysis of HRMS and 1D and 2D NMR spectra and found them to be karlotoxin (KmTx) congeners. Both toxins kill larval zebrafish with symptoms identical to that described by Abbot and Ballantine for gobies (Gobius virescens). Using surface plasma resonance the sterol binding specificity of karlotoxins is shown to require desmethyl sterols. Our results with black lipid membranes indicate that karlotoxin forms large-conductance channels in the lipid membrane, which are characterized by large ionic conductance, poor ionic selectivity, and a complex gating behavior that exhibits strong voltage dependence and multiple gating patterns. In addition, we show that KmTx 2 pore formation is a highly targeted mechanism involving sterol-specificity. This is the first report of the functional properties of the membrane pores formed by karlotoxins and are consistent with the intial observations of Abbott and Ballentine from 1957.

Blinded by wistfulness: on how nostalgia strengthens attitudes.

Across four studies, we explored how feeling nostalgic about an attitude object impacts the metacognitive characteristics of the attitude toward that object and how those metacognitions predict the evaluation's underlying strength. In each study, participants reflected on and evaluated a song or television show that either did or did not elicit nostalgia. Across these studies, we found support for the hypotheses that nostalgic attitude objects are viewed more positively, appraised with greater attitudinal importance, and exhibited less objective ambivalence. In Study 4, we observed that nostalgic attitudes are associated with greater behavioural intentions and that this relationship was mediated both by attitudinal importance and objective ambivalence. These studies contribute to our understanding of how nostalgia affects attitude formation processes.

Riboformer: a deep learning framework for predicting context-dependent translation dynamics.

Translation elongation is essential for maintaining cellular proteostasis, and alterations in the translational landscape are associated with a range of diseases. Ribosome profiling allows detailed measurements of translation at the genome scale. However, it remains unclear how to disentangle biological variations from technical artifacts in these data and identify sequence determinants of translation dysregulation. Here we present Riboformer, a deep learning-based framework for modeling context-dependent changes in translation dynamics. Riboformer leverages the transformer architecture to accurately predict ribosome densities at codon resolution. When trained on an unbiased dataset, Riboformer corrects experimental artifacts in previously unseen datasets, which reveals subtle differences in synonymous codon translation and uncovers a bottleneck in translation elongation. Further, we show that Riboformer can be combined with in silico mutagenesis to identify sequence motifs that contribute to ribosome stalling across various biological contexts, including aging and viral infection. Our tool offers a context-aware and interpretable approach for standardizing ribosome profiling datasets and elucidating the regulatory basis of translation kinetics.

Multi-scale geometric network analysis identifies melanoma immunotherapy response gene modules.

Melanoma response to immune-modulating therapy remains incompletely characterized at the molecular level. In this study, we assess melanoma immunotherapy response using a multi-scale network approach to identify gene modules with coordinated gene expression in response to treatment. Using gene expression data of melanoma before and after treatment with nivolumab, we modeled gene expression changes in a correlation network and measured a key network geometric property, dynamic Ollivier-Ricci curvature, to distinguish critical edges within the network and reveal multi-scale treatment-response gene communities. Analysis identified six distinct gene modules corresponding to sets of genes interacting in response to immunotherapy. One module alone, overlapping with the nuclear factor kappa-B pathway (NFkB), was associated with improved patient survival and a positive clinical response to immunotherapy. This analysis demonstrates the usefulness of dynamic Ollivier-Ricci curvature as a general method for identifying information-sharing gene modules in cancer.

A brief overview of pilot studies and their sample size justification.

Pilot studies, when properly designed and implemented, are an important tool that provide critical information for the development and potential success of a subsequent, larger trial. In fact, these small-scale studies are commonly used to assess the feasibility of whether a larger trial should be initiated. A popular investigator question is whether a pilot study requires a formal statistical power calculation. In general, the answer is "no"; however, the sample size needs to be justified on the basis of the goal of the pilot study.

[(F6acac)Pd(µ-HNC6F5)]2, a Large Family of Polymorphs and Solvates with Short F···F Contacts.

Highly fluorinated [(F6acac)Pd(µ-HNC6F5)]2 was prepared by the reaction of palladium bis(hexafluoroacetylacetonate), Pd(F6acac)2, with pentafluoroaniline. This compound generates a large family of crystalline polymorphs and solvates. In this paper, we present a study on the synthesis, solution phase dynamics, and crystal structures of highly fluorinated [(F6acac)Pd(µ-HNC6F5)]2. Pd3(µ-F6acac)2(µ-HNC6F5)4 is produced as a minor byproduct. We also describe the synthesis and structural characterization of trinuclear Pd3(µ-F6acac)3[µ-(CF3)2C=N]3 prepared by the reaction of Pd(F6acac)2 with hexafluoroacetone imine.

Does value-based prioritization at working memory enhance long-term memory?

Research has demonstrated that individuals can direct their attention to valuable information in both working memory and long-term memory tasks with observable effects on performance. However, it is currently unclear whether prioritising an item for a working memory task automatically translates into a boost at long-term memory. This was examined in two experiments using relatively short (250 ms per item; Experiment 1) and longer (500 ms per item; Experiment 2) encoding times. Participants first completed a visual working memory task, in which they were presented with series of photographs of everyday objects. Following a brief delay (1,000 ms), they completed a four-alternative forced-choice test. Prior to encoding, participants were informed of the point values associated with each item. In some trials, the first item in the sequence was worth more points than the rest. In other trials, all items were equally valuable. After a filled delay, participants completed a surprise long-term memory task. At working memory, a value effect was reliably observed on recognition accuracy, along with some evidence of faster response times for high-value items. However, there was little consistent evidence of this effect automatically persisting into long-term memory. Thus, the benefits of attentional prioritization in working memory do not always translate into longer-term performance. More broadly, this provides further evidence that manipulations that enhance working memory performance do not necessarily enhance long-term memory.

Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting.

BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

B. subtilis MutS2 splits stalled ribosomes into subunits without mRNA cleavage.

Stalled ribosomes are rescued by pathways that recycle the ribosome and target the nascent polypeptide for degradation. In E. coli, these pathways are triggered by ribosome collisions through the recruitment of SmrB, a nuclease that cleaves the mRNA. In B. subtilis, the related protein MutS2 was recently implicated in ribosome rescue. Here we show that MutS2 is recruited to collisions by its SMR and KOW domains, and we reveal the interaction of these domains with collided ribosomes by cryo-EM. Using a combination of in vivo and in vitro approaches, we show that MutS2 uses its ABC ATPase activity to split ribosomes, targeting the nascent peptide for degradation through the ribosome quality control pathway. However, unlike SmrB, which cleaves mRNA in E. coli, we see no evidence that MutS2 mediates mRNA cleavage or promotes ribosome rescue by tmRNA. These findings clarify the biochemical and cellular roles of MutS2 in ribosome rescue in B. subtilis and raise questions about how these pathways function differently in diverse bacteria.

Unbalanced regularized optimal mass transport with applications to fluid flows in the brain.

As a generalization of the optimal mass transport (OMT) approach of Benamou and Brenier's, the regularized optimal mass transport (rOMT) formulates a transport problem from an initial mass configuration to another with the optimality defined by the total kinetic energy, but subject to an advection-diffusion constraint equation. Both rOMT and the Benamou and Brenier's formulation require the total initial and final masses to be equal; mass is preserved during the entire transport process. However, for many applications, e.g., in dynamic image tracking, this constraint is rarely if ever satisfied. Therefore, we propose to employ an unbalanced version of rOMT to remove this constraint together with a detailed numerical solution procedure and applications to analyzing fluid flows in the brain.

Understanding the Information Needs of Pharmacy Staff Using CancelRx: A Qualitative Study of the Use of Prescription E-cancellation.

Background: Although electronic prescription cancellation such as via CancelRx can facilitate critical communication between prescribers and pharmacy staff about discontinued medications, there is little work that explores whether CancelRx meets the needs of pharmacy staff users. Objective: This study leverages qualitative interviews with pharmacy staff to address the following question: When medication changes are made by a prescriber using CancelRx, what information is needed by pharmacy staff to make correct and effective decisions in their roles in medication management? Methods: We conducted an inductive thematic analysis of interviews with 11 pharmacy staff members (pharmacists and pharmacy technicians) across three outpatient community pharmacy sites within an academic health care system. Results: Three information needs themes were consistently identified by both pharmacists and pharmacy technicians: prescriber intent when initiating the CancelRx, clinical rationale for the medication change, and intended medication regimen. Notably, both pharmacists and pharmacy technicians often reported seeking multiple information needs not fully addressed by CancelRx in the electronic health record (EHR) to achieve the shared goals of correct dispensing of medications and supporting patient self-management. Conclusions: Our qualitative analysis reveals that outpatient community pharmacy staff in an academic health care system often seek additional information from the (EHR) following medication changes communicated by CancelRx to meet their information needs. Ideally, the prescriber would provide sufficient information through CancelRx to automatically identify all discontinued prescriptions. These limitations highlight the need for design features that support routine communication of needed information at the time of a medication change, such as structured data elements.

Division time (td) for in situ growth measurements demonstrates thermal ecotypes of Karlodinium veneficum.

The toxic dinoflagellate Karlodinium veneficum forms fish killing blooms in temperate estuaries worldwide. These blooms have variable toxicity which may be related to bloom stage and in situ growth rates of the constituent K. veneficum cells. Measurement of in situ growth rates is challenging and methods such as the mitotic index technique require knowledge of the dynamics of cell division. In order to better understand these dynamics, we determined the duration of cell division (td) in four geographically distinct laboratory strains of K. veneficum at three different environmentally relevant temperatures. The results demonstrated that the td value for each strain, growing at strain-specific optimal temperatures, was 1.6 ± 0.1 h. This value corresponded to a range of growth rates from 0.17 ± 0.08 d-1 to 0.62 ± 0.07 d-1. Equivalent values of td spread across four geographically distinct laboratory strains and a nearly fourfold range of growth rates implies that 1.6 h represents the td value of K. veneficum. Additionally, temperature conditions yielding this value for td and the highest growth rates varied among strains, indicating cold-adapted (Norway), warm-adapted (Florida, USA), and eurythermally-adapted (Maryland, USA) strains. These differences have been apparently retained in culture over many years, indicating a conserved genetic basis that suggests distinct thermal ecotypes of the morphospecies K. veneficum. This knowledge together with the first estimate of td for K. veneficum will be useful in future field studies aimed at correlating bloom toxicity with in situ growth rate using the mitotic index technique.

Paraspinal muscles in individuals undergoing surgery for lumbar spine pathology lack a myogenic response to an acute bout of resistance exercise.

Background: Lumbar spine pathology (LSP) is a common source of low back or leg pain, and paraspinal muscle in these patients demonstrates fatty and fibrotic infiltration, and cellular degeneration that do not reverse with exercise-based rehabilitation. However, it is unclear of this lack of response is due to insufficient exercise stimulus, or an inability to mount a growth response. The purpose of this study was to compare paraspinal muscle gene expression between individuals with LSP who do and do not undergo an acute bout of resistance exercise. Methods: Paraspinal muscle biopsies were obtained from 64 individuals with LSP undergoing spinal surgery. Eight participants performed an acute bout of machine-based lumbar extension resistance exercise preoperatively. Gene expression for 42 genes associated with adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic pathways was measured, and differential expression between exercised and non-exercised groups was evaluated for (a) the full cohort, and (b) an age, gender, acuity, and etiology matched sub-cohort. Principal components analyses were used to identify gene expression clustering across clinical phenotypes. Results: The exercised cohort demonstrated upregulation of inflammatory gene IL1B, inhibition of extracellular matrix components (increased MMP3&9, decreased TIMP1&3, COL1A1) and metabolic/adipogenic genes (FABP4, PPARD, WNT10B), and downregulation of myogenic (MYOD, ANKRD2B) and atrophic (FOXO3) genes compared to the non-exercised cohort, with similar patterns in the matched sub-analysis. There were no clinical phenotypes significantly associated with gene expression profiles. Conclusion: An acute bout of moderate-high intensity resistance exercise did not result in upregulation of myogenic genes in individuals with LSP. The response was characterized by mixed metabolic and fibrotic gene expression, upregulation of inflammation, and downregulation of myogenesis.

Insights into oscillator network dynamics using a phase-isostable framework.

Networks of coupled nonlinear oscillators can display a wide range of emergent behaviors under the variation of the strength of the coupling. Network equations for pairs of coupled oscillators where the dynamics of each node is described by the evolution of its phase and slowest decaying isostable coordinate have previously been shown to capture bifurcations and dynamics of the network, which cannot be explained through standard phase reduction. An alternative framework using isostable coordinates to obtain higher-order phase reductions has also demonstrated a similar descriptive ability for two oscillators. In this work, we consider the phase-isostable network equations for an arbitrary but finite number of identical coupled oscillators, obtaining conditions required for the stability of phase-locked states including synchrony. For the mean-field complex Ginzburg-Landau equation where the solutions of the full system are known, we compare the accuracy of the phase-isostable network equations and higher-order phase reductions in capturing bifurcations of phase-locked states. We find the former to be the more accurate and, therefore, employ this to investigate the dynamics of globally linearly coupled networks of Morris-Lecar neuron models (both two and many nodes). We observe qualitative correspondence between results from numerical simulations of the full system and the phase-isostable description demonstrating that in both small and large networks, the phase-isostable framework is able to capture dynamics that the first-order phase description cannot.

Dynamic network curvature analysis of gene expression reveals novel potential therapeutic targets in sarcoma.

Network properties account for the complex relationship between genes, making it easier to identify complex patterns in their interactions. In this work, we leveraged these network properties for dual purposes. First, we clustered pediatric sarcoma tumors using network information flow as a similarity metric, computed by the Wasserstein distance. We demonstrate that this approach yields the best concordance with histological subtypes, validated against three state-of-the-art methods. Second, to identify molecular targets that would be missed by more conventional methods of analysis, we applied a novel unsupervised method to cluster gene interactomes represented as networks in pediatric sarcoma. RNA-Seq data were mapped to protein-level interactomes to construct weighted networks that were then subjected to a non-Euclidean, multi-scale geometric approach centered on a discrete notion of curvature. This provides a measure of the functional association among genes in the context of their connectivity. In confirmation of the validity of this method, hierarchical clustering revealed the characteristic EWSR1-FLI1 fusion in Ewing sarcoma. Furthermore, assessing the effects of in silico edge perturbations and simulated gene knockouts as quantified by changes in curvature, we found non-trivial gene associations not previously identified.

Functional transcriptional signatures for tumor-type-agnostic phenotype prediction.

Cancer transcriptional patterns exhibit both shared and unique features across diverse cancer types, but whether these patterns are sufficient to characterize the full breadth of tumor phenotype heterogeneity remains an open question. We hypothesized that cancer transcriptional diversity mirrors patterns in normal tissues optimized for distinct functional tasks. Starting with normal tissue transcriptomic profiles, we use non-negative matrix factorization to derive six distinct transcriptomic phenotypes, called archetypes, which combine to describe both normal tissue patterns and variations across a broad spectrum of malignancies. We show that differential enrichment of these signatures correlates with key tumor characteristics, including overall patient survival and drug sensitivity, independent of clinically actionable DNA alterations. Additionally, we show that in HR+/HER2-breast cancers, metastatic tumors adopt transcriptomic signatures consistent with the invaded tissue. Broadly, our findings suggest that cancer often arrogates normal tissue transcriptomic characteristics as a component of both malignant progression and drug response. This quantitative framework provides a strategy for connecting the diversity of cancer phenotypes and could potentially help manage individual patients.

Quantifying a potential protective effect of buprenorphine on fatality risk during acute fentanyl exposures.

INTRODUCTION: Buprenorphine is an important therapy for opioid use disorder and may also reduce the risk of fatal overdoses in fentanyl exposures. However, the role of buprenorphine in reducing this risk has not been quantified. This cross-sectional study examined the association between buprenorphine presence, decedent characteristics, and other factors with the predicted fentanyl concentrations in overdose deaths. METHODS: The study identified unintentional fentanyl overdose decedents (n = 3036) from the West Virginia Forensic Drug Database, 2011 through mid-2020. The main outcome was fentanyl concentrations in overdose deaths in the presence and absence of buprenorphine. A multiple linear regression model examined the association of fentanyl concentrations with buprenorphine presence based on the concentrations of the parent drug buprenorphine (B) and its metabolite norbuprenorphine (N), adjusting for demographics, toxicological characteristics (presence of multiple opioids, benzodiazepines, stimulants, marijuana, and alcohol), and comorbidities. We used a B/N concentration ratio < 1 as an indirect indicator of longer-term buprenorphine exposure prior to drug overdose death. RESULTS: The median fentanyl concentration was 65 % higher when buprenorphine was present (N = 168) vs. absent (N = 2868) (0.028 vs. 0.017 µg/mL, p < 0.001). In the multivariable model, statistically significant associations occurred between buprenorphine presence and increased fentanyl concentrations (+28.7 %) with a B/N ratio < 1. Obesity, male sex, alcohol presence, and comorbid cardiovascular diseases were statistically significantly associated with lower (-11.3 % to -20.7 %) fentanyl concentrations, whereas marijuana presence and a history of substance use disorder were associated with statistically significant higher fentanyl concentrations (+8.8 % to +31.3 %). CONCLUSIONS: These findings suggest that sustained or longer-term buprenorphine intake might exert some protective effect on fatalities resulting from fentanyl exposure as documented by the association of higher fentanyl blood concentrations with buprenorphine presence among fatal drug overdoses. As fentanyl availability and overdose rates increase nationally, buprenorphine is a vital tool for effective opioid use disorder treatment that might also reduce the risk of fatality in an acute fentanyl exposure.