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Purpose: Adolescent idiopathic scoliosis is a chronic disease that may require correction surgery. The finite element method (FEM) is a popular option to plan the outcome of surgery on a patient-based model. However, it requires considerable computing power and time, which may discourage its use. Machine learning (ML) models can be a helpful surrogate to the FEM, providing accurate real-time responses. This work implements ML algorithms to estimate post-operative spinal shapes., Methods: The algorithms are trained using features from 6400 simulations generated using the FEM from spine geometries of 64 patients. The features are selected using an autoencoder and principal component analysis. The accuracy of the results is evaluated by calculating the root-mean-squared error and the angle between the reference and predicted position of each vertebra. The processing times are also reported., Results: A combination of principal component analysis for dimensionality reduction, followed by the linear regression model, generated accurate results in real-time, with an average position error of 3.75 mm and orientation angle error below 2.74 degrees in all main 3D axes, within 3 ms. The prediction time is considerably faster than simulations based on the FEM alone, which require seconds to minutes., Conclusion: It is possible to predict post-operative spinal shapes of patients with AIS in real-time by using ML algorithms as a surrogate to the FEM. Clinicians can compare the response of the initial spine shape of a patient with AIS to various target shapes, which can be modified interactively. These benefits can encourage clinicians to use software tools for surgical planning of scoliosis., (© 2024. Crown.)

Echocardiography is one the most commonly used imaging modalities for the diagnosis of congenital heart disease. Echocardiographic image analysis is crucial to obtaining accurate cardiac anatomy information. Semantic segmentation models can be used to precisely delimit the borders of the left ventricle, and allow an accurate and automatic identification of the region of interest, which can be extremely useful for cardiologists. In the field of computer vision, convolutional neural network (CNN) architectures remain dominant. Existing CNN approaches have proved highly efficient for the segmentation of various medical images over the past decade. However, these solutions usually struggle to capture long-range dependencies, especially when it comes to images with objects of different scales and complex structures. In this study, we present an efficient method for semantic segmentation of echocardiographic images that overcomes these challenges by leveraging the self-attention mechanism of the Transformer architecture. The proposed solution extracts long-range dependencies and efficiently processes objects at different scales, improving performance in a variety of tasks. We introduce Shifted Windows Transformer models (Swin Transformers), which encode both the content of anatomical structures and the relationship between them. Our solution combines the Swin Transformer and U-Net architectures, producing a U-shaped variant. The validation of the proposed method is performed with the EchoNet-Dynamic dataset used to train our model. The results show an accuracy of 0.97, a Dice coefficient of 0.87, and an Intersection over union (IoU) of 0.78. Swin Transformer models are promising for semantically segmenting echocardiographic images and may help assist cardiologists in automatically analyzing and measuring complex echocardiographic images., (Creative Commons Attribution license.)

Objective: Although telehealth psychotherapies have been studied for over 20 years, mental health services remained largely delivered in person until the COVID-19 pandemic forced clinics to reconsider the utility of telehealth psychotherapy. This study aims to compare patient engagement in in-person versus telehealth services in outpatient psychotherapy for mood and anxiety disorders., Method: A cohort investigation was conducted, using a propensity score matched sample, extracted from an electronic health record (EHR) to compare engagement in psychotherapy for 762 patients who used in-person services before the pandemic to a cohort of 762 patients who used telehealth psychotherapy after the onset of COVID-19. The authors compared cohorts on initial engagement in psychotherapy services following an initial intake, number of psychotherapy sessions attended, and the rate of missed sessions., Results: There was a 26% increase in the total number of individual psychotherapy sessions attended when the clinics transitioned to telehealth services ( p  < .001). In addition, patients who received telehealth psychotherapy were five times more likely to not cancel or miss any scheduled sessions ( p  < .001)., Conclusion: These results indicate that telehealth services may result in improved treatment engagement for outpatient centers focused on brief evidence-based psychotherapies for mood and anxiety disorders.

Purpose: There is a lack of systematic solutions to manage supportive care issues in racial/ethnic minorities (REM) receiving treatment for cancer. We developed and implemented an electronic patient-reported outcome (ePRO)-driven symptom management tool led by oncology pharmacists in a majority-minority cancer center located in Southern California. This study was designed to evaluate the implementation outcomes of our multilevel intervention., Methods: This was a prospective, pragmatic, implementation study conducted between July 2021 and June 2023. Newly diagnosed adult patients with cancer receiving intravenous anticancer therapies completed symptom screening using ePRO that consists of the Patient-Reported Outcomes Measurement Information System measures at each infusion visit during the study. ePRO results were presented to an oncologist pharmacist for personalized symptom management and treatment counseling. The RE-AIM framework was used to guide implementation outcomes. Differences in symptom trajectories and clinical outcomes between groups were tested using generalized estimating equations., Results: We screened 388 patients of whom 250 were enrolled (acceptance rate: 64.4%), with 564 assessments being completed. The sample consisted of non-Hispanic White (NHW, 42.4%), Hispanic/Latinx (H/L, 30.8%), and non-Hispanic Asian (20.4%), with one (21.6%) of five participants preferring speaking Spanish. Compared with NHW, H/L participants had greater odds of reporting mild to severe pain interference (odds ratio [OR], 1.91 [95% CI, 1.18 to 3.08]; P = .008) and nausea and vomiting (OR, 2.08 [95% CI, 1.21 to 3.58]; P = .008), and higher rates of urgent care utilization (OR, 1.92 [95% CI, 1.04 to 3.61]; P = .04) within 30 days. Nausea and vomiting (n = 131, 23.2%), pain (n = 91, 16.1%), and fatigue (n = 72, 12.8%) were most likely to be intervened, with 90% of the participants expressing satisfaction across all visits., Conclusion: Our multilevel ePRO-driven intervention led by oncology pharmacists helps facilitate symptom assessments and management and potentially reduce health disparities among REM.

The gastrointestinal system is a hollow organ affected by fibrostenotic diseases that cause volumetric compromise of the lumen via smooth muscle hypertrophy and fibrosis. Many of the driving mechanisms remain unclear. Yes-associated protein-1 (YAP) is a critical mechanosensory transcriptional regulator that mediates cell hypertrophy in response to elevated extracellular rigidity. In the type 2 inflammatory disorder, eosinophilic esophagitis (EoE), phospholamban (PLN) can induce smooth muscle cell hypertrophy. We used EoE as a disease model for understanding a mechanistic pathway in which PLN and YAP interact in response to rigid extracellular substrate to induce smooth muscle cell hypertrophy. PLN-induced YAP nuclear sequestration in a feed-forward loop caused increased cell size in response to a rigid substrate. This mechanism of rigidity sensing may have previously unappreciated clinical implications for PLN-expressing hollow systems such as the esophagus and heart., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Simultaneous inhibition of soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH) with a single small molecule represents a novel therapeutic approach in treating inflammatory pain, since both targets are involved in pain and inflammation processes. In this study using multi-target directed ligands methodology we designed and synthesized 7 quinolinyl-based dual sEH/FAAH inhibitors, using an optimized microwave-assisted Suzuki-Miyaura coupling reaction and tested their potency in human FAAH and human, rat, and mouse sEH inhibition assays. The structure-activity relationship study showed that quinolinyl moiety is well tolerated in the active sites of both enzymes, yielding several very potent dual sEH/FAAH inhibitors with the IC 50 values in the low nanomolar range. The most potent dual inhibitor 4d was further evaluated in stability assay in human and rat plasma where it performed better than the standard Warfarin while in vivo study revealed that 1 mg/kg 4d can inhibit acute inflammatory pain in male rats to a similar degree as the traditional nonsteroidal anti-inflammatory drug ketoprofen (30 mg/kg) after intraperitoneal injection. ADMET prediction studies for this dual inhibitor show favorable pharmacokinetic properties which will guide the future in vivo evaluations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

In view of the competing assignments regarding the most stable isomer of the B 70 boron cluster including the quasi-planar and bilayer structures, we reinvestigated the structural motifs of B 70 using a genetic algorithm for structure search (MEGA) in conjunction with density functional theory computations using the PBE functional. The quasi-planar structure was also constructed using the topological leapfrog algorithm. The latter search aimed to give us unique insight into its formation and the growth pattern of boron clusters. Also, the di-anionic state of B 70 was explored. Our extensive search suggested a competition between the quasi-planar, tubular and bilayer isomers for the ground state of B 70 in both neutral and dianionic states. While the bilayer form is more stable in the neutral state, the quasi-planar counterpart becomes more stable in the dianionic B 70 2- . The stability arises due to the fact that the B 70 2- dianion possesses 50 π electrons that satisfy the disk aromaticity model rule. These results tend to extend the stabilization of the quasi-planar structure upon negative charge addition previously found in small size boron clusters to larger sizes.

Resistance to immune checkpoint blockade (ICB) therapy represents a formidable clinical challenge limiting the efficacy of immunotherapy. In particular, prostate cancer poses a challenge for ICB therapy due to its immunosuppressive features. A ketogenic diet (KD) has been reported to enhance response to ICB therapy in some other cancer models. However, adverse effects associated with continuous KD were also observed, demanding better mechanistic understanding and optimized regimens for using KD as an immunotherapy sensitizer. In this study, we established a series of ICB-resistant prostate cancer cell lines and developed a highly effective strategy of combining anti-PD1 and anti-CTLA4 antibodies with histone deacetylase inhibitor (HDACi) vorinostat, a cyclic KD (CKD), or dietary supplementation of the ketone body β-hydroxybutyrate (BHB), which is an endogenous HDACi. CKD and BHB supplementation each delayed prostate cancer tumor growth as monotherapy, and both BHB and adaptive immunity were required for the antitumor activity of CKD. Single-cell transcriptomic and proteomic profiling revealed that HDACi and ketogenesis enhanced ICB efficacy through both cancer cell-intrinsic mechanisms, including upregulation of MHC class I molecules, and -extrinsic mechanisms, such as CD8+ T-cell chemoattraction, M1/M2 macrophage rebalancing, monocyte differentiation toward antigen-presenting cells, and diminished neutrophil infiltration. Overall, these findings illuminate a potential clinical path of using HDACi and optimized KD regimens to enhance ICB therapy for prostate cancer., Significance: Optimized cyclic ketogenic diet and 1,3-butanediol supplementation regimens enhance the efficacy of immune checkpoint blockade in prostate cancer through epigenetic and immune modulations, providing dietary interventions to sensitize tumors to immunotherapy., (©2024 American Association for Cancer Research.)

Targeting programmed cell death protein 1 (PD-1) is an important component of many immune checkpoint blockade (ICB) therapeutic approaches. However, ICB is not an efficacious strategy in a variety of cancer types, in part due to immunosuppressive metabolites in the tumor microenvironment. Here, we find that αPD-1-resistant cancer cells produce abundant itaconate (ITA) due to enhanced levels of aconitate decarboxylase (Acod1). Acod1 has an important role in the resistance to αPD-1, as decreasing Acod1 levels in αPD-1-resistant cancer cells can sensitize tumors to αPD-1 therapy. Mechanistically, cancer cells with high Acod1 inhibit the proliferation of naive CD8 + T cells through the secretion of inhibitory factors. Surprisingly, inhibition of CD8 + T cell proliferation is not dependent on the secretion of ITA but is instead a consequence of the release of small inhibitory peptides. Our study suggests that strategies to counter the activity of Acod1 in cancer cells may sensitize tumors to ICB therapy., Competing Interests: Declaration of interests R.G.J. is a scientific advisor for Agios Pharmaceuticals and Servier Pharmaceuticals and is a member of the scientific advisory board of ImmunoMet Therapeutics., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study presents a thorough reinvestigation of the B 15 +/0/- isomers, first employing coupled-cluster theory CCSD(T) calculations to validate the performance of different DFT functionals. The B 15 + cation has two planar lowest-lying isomers, while the first 3D isomer is less stable than the global minimum by ∼10 kcal mol -1 . The PBE functional, within this benchmark survey, has proved to be reliable in predicting relative energies for boron isomers. Other functionals such as the TPSSh, PBE0 and HSE06 result in good energy ordering of isomers but warrant reconsideration when distinguishing between 2D and 3D forms. Caution is needed for structures having high spin contamination, as it may lead to significant errors. The anomalously lower stability of the B 15 - anion with respect to its neighbours, in terms of electron detachment energy, was explained through a competition between both rectangle and disk models for its geometry. This elucidates its stability with 12 electrons in rectangle model and instability with 10 electrons in disk-shaped structure, emphasizing the value of employing such geometric models. The proximity of the σ* LUMO to the π HOMO also contributes to the weakening of the B 15 - stability.

Background: Dyspnea is frequently a debilitating symptom of chronic obstructive pulmonary disease (COPD). Cannabinoid receptor agonists have the potential to alter dyspnea in these patients., Objective: Our objective was to determine if dronabinol, a pure cannabinoid, improves dyspnea and exercise tolerance in COPD., Methods: In this double-blind randomized, crossover pilot study, COPD patients received up to 20mg of oral dronabinol or placebo daily for 6 weeks with an intervening washout period. Dyspnea and fatigue were assessed using the Borg scale at rest and after an incremental shuttle walk. Functional status, mood, and depression were measured using the St George's Respiratory Questionnaire (SGRQ), the Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ), and the Geriatric Depression Scale (GDS)., Results: A total of 11 participants (with mean forced expiratory volume in 1 second 50.8 ± 24.8%) completed the study with no improvement in dyspnea at rest or postexercise taking dronabinol versus placebo (Borg scale 0.27, 95% confidence interval [CI] -0.59 to 1.14 versus 0.23 points, 95% CI -0.71 to 1.07 at rest and 0.82, 95% CI -0.59 to 2.22 versus 0.36 points, 95% CI 0.13 to 2.78 post exercise; p =0.94 and p =0.69 respectively). Dronabinol compared with placebo showed no significant change in PFSDQ dyspnea scores (0.64, 95% CI -3.92 to 5.20 versus 5.0, 95% CI -6.29 to 16.29; p =0.43) or shuttle walk distances (20.7m, 95% CI -21.5 to 62.8 versus 13.7m, 95% CI -24.8 to 52.2; p =0.69). There were no significant differences in fatigue at rest and postexercise, SGRQ scores, or GDS scores., Conclusion: In this pilot study, dronabinol did not significantly improve dyspnea or exercise capacity compared with placebo., (JCOPDF © 2024.)

Acute lymphoblastic leukemia (ALL) stands as the most prevalent form of pediatric cancer in North America, with a current five-year survival rate of 85%. While more children achieved ALL remission and transition into adulthood, the prevalence of long-term treatment-related effects, especially neurocognitive sequelae, remains significant. This study pursues two objectives. Firstly, it investigates if Magnetization Transfer Ratio (MTR), a method assessing myelin integrity, is sensitive to white matter (WM) microstructural changes in long-term ALL survivors and whether these relate to cognitive impairments. Secondly, it examines the dose-related effects of chemotherapy agents on the MTR and its relationship to other risk factors such as female sex, early age diagnosis, and cranial radiotherapy. Magnetization transfer imaging was utilized to assess WM integrity in 35 survivors at a mean of 18.9 years after the onset of ALL (range since diagnosis: 6.9-26.8). Additionally, 21 controls matched for age, sex, and education level, with no history of cancer, were included. MTR was extracted from both the entire brain's WM and the corpus callosum through semi-automated procedures. The results indicated lower MTR means in survivors, which is linked to cognitive function. Negative associations between MTR means and intrathecal agents' (MTX, cytarabine, and hydrocortisone) cumulative doses received were highlighted. This study offers valuable insights into the connections between myelin deterioration, cognitive impairment, and the implications of IT chemotherapy, enhancing our understanding of ALL survivorship dynamics. It underscores MTR's relevance in monitoring neurotoxicity during oncological drug follow-up examinations.

Purpose: Medical image analysis suffers from a sparsity of annotated data necessary in learning-based models. Cardiorespiratory simulators have been developed to counter the lack of data. However, the resulting data often lack realism. Hence, the proposed method aims to synthesize realistic and fully customizable angiograms of coronary arteries for the training of learning-based biomedical tasks, for cardiologists performing interventions, and for cardiologist trainees., Methods: 3D models of coronary arteries are generated with a fully customizable realistic cardiorespiratory simulator. The transfer of X-ray angiography style to simulator-generated images is performed using a new vessel-specific adaptation of the CycleGAN model. The CycleGAN model is paired with a vesselness-based loss function that is designed as a vessel-specific structural integrity constraint., Results: Validation is performed both on the style and on the preservation of the shape of the arteries of the images. The results show a PSNR of 14.125, an SSIM of 0.898, and an overlapping of 89.5% using the Dice coefficient., Conclusion: We proposed a novel fluoroscopy-based style transfer method for the enhancement of the realism of simulated coronary artery angiograms. The results show that the proposed model is capable of accurately transferring the style of X-ray angiograms to the simulations while keeping the integrity of the structures of interest (i.e., the topology of the coronary arteries)., (© 2023. CARS.)

In this paper we describe the analysis, planning, design, development, implementation and evaluation of a new online Graduate Certificate in Genomic Counselling and Variant Interpretation (GCGCVI) at The University of British Columbia (UBC). Genetic counselling is now a prerequisite for diagnostic genomic testing in many countries, demanding that genetic counselling practitioners have up-to-the-moment genomic counselling skills and knowledge. Current practitioners reported a desire for more training in this rapidly developing field: our international survey revealed substantial interest in online continuing education addressing themes such as testing and clinical bioinformatics, applied variant interpretation, evidence-based genomic counselling, and other emerging genomic topics. However, our market analysis found no post-graduate program globally that offered such training. To fill this gap, our oversight team of genetic counsellors and geneticists therefore guided development of curriculum and materials, and online learning specialists developed rigorous interactive asynchronous online graduate courses through collaboration with subject matter experts, following best practices in online learning design. Since launch in September 2020, we have gathered learner feedback using surveys and focus groups, and we have used learning analytics to understand how learners engaged with each other and with course materials. Together, these have helped us understand learner behaviour and guide the continuous process of design improvement to support the learning goals of this audience of professional learners. Our courses have been reviewed and approved by the UBC Faculty of Medicine, UBC Senate, and the Province of British Columbia Ministries of Advanced Education and Health, and assessed by the National Society of Genetic Counselors (NSGC, USA) and the Canadian Association of Genetic Counsellors (CAGC) to enable learners to receive North American continuing education credits. To date, 151 individuals from 18 countries have succeeded in one or more course and 43 have completed the entire certificate., (© 2023 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

The geometric and electronic structures of a small series of mixed gold and platinum Au x Pt y 2+ clusters, with x + y = 10, were investigated using quantum chemical methods. A consistent tetrahedral pyramid structure emerges, displaying two patterns of structural growth by a notable critical point at y = 5. This affects the clusters' electron population, chemical bonding, and stability. For the Pt-doped Au clusters with y values from 2 to 5, the bonds enable Pt atoms to assemble into symmetric line, triangle, quadrangle, and tetragonal pyramidal Pt y blocks, respectively. For the Au-doped Pt clusters, with larger values of y > 5, the structures are more relaxed and the d electrons of Pt atoms become delocalized over more centers, leading to lower symmetry structures. A certain aromaticity arising from delocalization of d electrons over the multi-center framework in the doped Pt clusters contributes to their stability, with Pt 10 2+ at y = 10 exhibiting the highest stability. While the ground electronic state of the neutral platinum atom [Xe]. 4f 14 5d 9 6s 1 leads to a triplet state ( 3 D 3 ), the total magnetic moments of Au x Pt y 2+ are large increasing steadily from 0 to 10 μB and primarily located on Pt atoms, corresponding to the increase of the number of Pt atoms from 0 to 10 and significantly enhancing the magnetic moments. An admixture of both Au and Pt atoms thus emerges as an elegant way of keeping a small pyramidal structure but bringing in a high and controllable magnetic moment., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

This paper explores a deep-learning approach to evaluate the position of circular delimiters in cartridge case images. These delimiters define two regions of interest (ROI), corresponding to the breech face and the firing pin impressions, and are placed manually or by an image-processing algorithm. This positioning bears a significant impact on the performance of the image-matching algorithms for firearm identification, and an automated evaluation method would be beneficial to any computerized system. Our contribution consists in optimizing and training U-Net segmentation models from digital images of cartridge cases, intending to locate ROIs automatically. For the experiments, we used high-resolution 2D images from 1195 samples of cartridge cases fired by different 9MM firearms. Our results show that the segmentation models, trained on augmented data sets, exhibit a performance of 95.6% IoU (Intersection over Union) and 99.3% DC (Dice Coefficient) with a loss of 0.014 for the breech face images; and a performance of 95.9% IoU and 99.5% DC with a loss of 0.011 for the firing pin images. We observed that the natural shapes of predicted circles reduce the performance of segmentation models compared with perfect circles on ground truth masks suggesting that our method provide a more accurate segmentation of the real ROI shape. In practice, we believe that these results could be useful for firearms identification. In future work, the predictions may be used to evaluate the quality of delimiters on specimens in a database, or they could determine the region of interest on a cartridge case image., (© 2023 Ultra Electronics Forensic Technology Inc and The Authors. Journal of Forensic Sciences published by Wiley Periodicals LLC on behalf of American Academy of Forensic Sciences.)

Magnetic resonance imaging is currently the gold standard for the evaluation of spinal cord injuries. Automatic analysis of these injuries is however challenging, as MRI resolutions vary for different planes of analysis and physiological features are often distorted around these injuries. This study proposes a new CNN-based segmentation method in which information is exchanged between two networks analyzing the scans from different planes. Our aim was to develop a robust method for automatic segmentation of the spinal cord in patients having suffered traumatic injuries. The database consisted of 106 sagittal MRI scans from 94 patients with traumatic spinal cord injuries. Our method used an innovative approach where the scans were analyzed in series under the axial and sagittal plane by two different convolutional networks. The results were compared with those of Deepseg 2D from the Spinal Cord Toolbox (SCT), which was taken as state-of-the-art. Comparisons were evaluated using K-Fold cross-validation combined with statistical t-test results on separate test data. Our method achieved significantly better results than Deepseg 2D, with an average Dice coefficient of 0.95 against 0.88 for Deepseg 2D (p <0.001). Other metrics were also used to compare the segmentations, all of which showed significantly better results for our approach. In this study, we introduce a robust method for spinal cord segmentation which is capable of adequately segmenting spinal cords affected by traumatic injuries, improving upon the methods contained in SCT., (© 2023 The Authors. Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

Two new chlorinated guaianane-type sesquiterpenes (named chlosigesolides A and B) together with eight known compounds were isolated from the leaves and twigs of Sigesbeckia orientalis . Their structures were determined by analysis of HR-ESI-MS, 1D- and 2D-NMR spectral data as well as comparison with the literature. Absolute configurations of new compounds were elucidated by NOESY and ECD methods. Chlosigesolide A inhibited NO production in LPS-stimulated RAW264.7 macrophages with IC 50 value of 10.9 ± 0.8 μM. Other compounds exhibited inhibitory activity at IC 50 in range of 26.5 to 49.7 μM.

Inhaled therapy confers key advantages for the treatment of topical pulmonary diseases and offers potential for systemic delivery of medicines. Dry powder inhalers (DPIs) are generally the preferred devices for pulmonary delivery due to improved stability and satisfactory patient compliance. However, the mechanisms governing drug powder dissolution and availability in the lung and poorly understood. Here, we report a new in vitro system to study epithelial absorption of inhaled dry powders in lung barrier models of the upper and lower airway. The system is based on a CULTEX® RFS (Radial Flow System) cell exposure module joined to a Vilnius aerosol generator and allows the coupling of drug dissolution and permeability assessments. The cellular models recapitulate the barrier morphology and function of healthy and diseased pulmonary epithelium and incorporate the mucosal barrier to enable the investigation of drug powder dissolution in biorelevant conditions. With this system, we found differences in permeability across the airway tree and pinpointed the impact of diseased barriers in paracellular drug transport. Furthermore, we identified a different rank order of permeability for compounds tested in solution or powder form. These results highlight the value of this in vitro drug aerosolization setup for use in research and development of inhaled medicines., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A. M. L., E. G., D. R., S. T., T. D., E. A., L. D. and D. S. declare to work at Novartis AG. E. G., D. R., S. T., E. A., L. D. and D. S. declare to hold stock in Novartis AG. The authors declare no other potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The Novartis Discovery Postdoctoral Fellowships provided financial support for the conduct of the research but had no role in study design, data collection, analysis and interpretation of data, writing of the report or the decision to submit the article for publication., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Patient trust/respect toward their therapists may be an important component of patient-therapist relationships. This randomized controlled trial evaluated the impact of providing weekly feedback to therapists regarding patient ratings of trust/respect toward their therapist., Method: Adult patients seeking mental health treatment at four community clinics (two community mental health centers and two community-based intensive treatment programs) were randomized to either having their primary therapist receive weekly symptom feedback-only or symptoms plus trust/respect feedback. Data were collected both prior to and during COVID-19. The primary outcome measure was a measure of functioning obtained weekly at baseline and the subsequent 11 weeks, with the primary analysis focusing on patients who received any treatment. Secondary outcomes included measures of symptoms and trust/respect., Results: Among 233 consented patients, 185 had a postbaseline assessment and were analyzed for the primary and secondary outcomes (median age of 30 years; 5.4% Asian, 12.4% Hispanic, 17.8% Black, 67.0% White, 4.3% more than 1 race, and 5.4% unknown; 64.4% female). On the Patient-Reported Outcomes Measurement Information System Social Roles and Activities scale (primary outcome), the trust/respect plus symptom feedback group had significantly greater improvements over time than the symptom alone feedback group ( p = .0006, effect size d = .22). Secondary outcome measures of symptoms and trust/respect also showed statistically significant greater improvement for the trust/respect feedback group., Conclusions: In this trial, trust/respect feedback to therapists was associated with significantly greater improvements in treatment outcomes. Evaluation of the mechanisms of such improvements is needed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Objective: Psychotherapy randomized trials rarely have tested for the best fitting model for time effects. We examined the fit of different statistical models for examining time when repeated assessments of depressive symptoms are the primary outcome., Method: We used data from three studies comparing psychotherapy treatments for major depressive disorder. Outcome measures were self-report ratings for Study 1 ( N  = 237) and Study 2 ( N  = 100) and clinician ratings for Study 3 ( N  = 120) of depressive symptoms measured at every session (Studies 1 and 2) or monthly (Study 3). We examined the fit of the following time patterns: linear, quadratic, cubic, log transformation of time, piece-wise linear, and unstructured., Results: In Study 1, a log-linear model had the best fit (Δ Akaike information criterion [AICc] = 7.5). In Study 2, all models had essentially no support (Δ AICcs > 10) in comparison to the best fitting model, which was the unstructured model. In Study 3, the cubic model had the best fit, but it was not significantly better than a log-linear (Δ AICc = 3.5) or unstructured model (Δ AICc = 2.5)., Conclusions: Trials should routinely compare different time models, including an unstructured model, when repeated measures of depressive symptoms are the primary outcome.

Selective plane illumination microscopy (SPIM), or light sheet microscopy, is a powerful imaging approach. However, access to and interfacing microscopes with microfluidics have remained challenging. Complex interfacing with microfluidics has limited the SPIM's utility for studying the hydrodynamics of freely moving multicellular organisms. We developed SPIM-Flow, an inexpensive light sheet platform that enables easy integration with microfluidics. We used SPIM-Flow to investigate the hydrodynamics of a freely moving Hydra polyp via particle tracking in millimeter-sized chambers. Initial experiments across multiple animals, feeding on a chip ( Artemia franciscana nauplii used as food), and baseline behaviors (tentacle swaying, elongation, and bending) indicated the organisms' health inside the system. Fluidics were used to investigate Hydra 's response to flow. The results suggested that the animals responded to an established flow by bending and swaying their tentacles in the flow direction. Finally, using SPIM-Flow in a proof-of-concept experiment, the shear stress required to detach an animal from a surface was demonstrated. Our results demonstrated SPIM-Flow's utility for investigating the hydrodynamics of freely moving animals.

Objective. To develop a novel patient-specific cardio-respiratory motion prediction approach for X-ray angiography time series based on a simple long short-term memory (LSTM) model. Approach. The cardio-respiratory motion behavior in an X-ray image sequence was represented as a sequence of 2D affine transformation matrices, which provide the displacement information of contrasted moving objects (arteries and medical devices) in a sequence. The displacement information includes translation, rotation, shearing, and scaling in 2D. A many-to-many LSTM model was developed to predict 2D transformation parameters in matrix form for future frames based on previously generated images. The method was developed with 64 simulated phantom datasets (pediatric and adult patients) using a realistic cardio-respiratory motion simulator (XCAT) and was validated using 10 different patient X-ray angiography sequences. Main results. Using this method we achieved less than 1 mm prediction error for complex cardio-respiratory motion prediction. The following mean prediction error values were recorded over all the simulated sequences: 0.39 mm (for both motions), 0.33 mm (for only cardiac motion), and 0.47 mm (for only respiratory motion). The mean prediction error for the patient dataset was 0.58 mm. Significance. This study paves the road for a patient-specific cardio-respiratory motion prediction model, which might improve navigation guidance during cardiac interventions., (Creative Commons Attribution license.)

Purpose: Our goal was to develop brief pragmatic assessments of Behavioral Activation (BA) fidelity to support its dissemination in low-resource settings., Methods: We used qualitative and quantitative methods across three investigations to develop pragmatic assessments rated from the perspective of therapists, patients, and observers: (1) we developed an initial comprehensive pool of 119 items and adapted/refined the item pool to 32 items through stakeholder focus groups and cognitive interviews; (2) independent blind judges rated each of items in the refined item pool on an early session of BA for 64 patients to support the selection of items based on predictive validity; and (3) we conducted a preliminary evaluation of the acceptability and feasibility of the assessments of BA fidelity from the perspective of therapists and patients., Results: The internal consistency reliability for the 10-item total score was .83 rated from the perspective of independent observers. The assessment was completed by patients following 90% of sessions and by clinicians following 93% of sessions. Items were rated high on overall satisfaction by both therapists (M = 4.6, SD = 0.89) and patients (M = 4.8, SD = 0.41)., Conclusion: Our findings suggest that these brief assessments of BA fidelity are reliable, feasible, and acceptable to community stakeholders., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Background:Postpancreaticoduodenectomy (PD) hemorrhage (PPH) is a life-threatening complication after PD. The main objective of this study was to evaluate incidence and factors associated with late PPH as well as the management strategy and outcomes. Methods: Between May 2017 and March 2020, clinical data from 192 patients undergoing PD were collected prospectively in the CHIRPAN Database (NCT02871336) and retrospectively analyzed. In our institution, all patients scheduled for a PD are routinely admitted for monitoring and management in intensive/intermediate care unit (ICU/IMC). Results: The incidence of late PPH was 17% (32 of 192), whereas the 90-day mortality rate of late PPH was 19% (6 of 32). Late PPH was associated with 90-day mortality (P = 0.001). Using multivariate analysis, independent risk factors for late PPH were postoperative sepsis (P = 0.036), and on day 3, creatinine (P = 0.025), drain fluid amylase concentration (P = 0.023), lipase concentration (P < 0.001), and C-reactive protein (CRP) concentration (P < 0.001). We developed two predictive scores for PPH occurrence, the PANCRHEMO scores. Score 1 was associated with 68.8% sensitivity, 85.6% specificity, 48.8% predictive positive value, 93.2% negative predictive value, and an area under the receiver operating characteristic curves of 0.841. Score 2 was associated with 81.2% sensitivity, 76.9% specificity, 41.3% predictive positive value, 95.3% negative predictive value, and an area under the receiver operating characteristic curve of 0.859. Conclusions: Routine ICU/IMC monitoring might contribute to a better management of these complications. Some predicting factors such as postoperative sepsis and biological markers on day 3 should help physicians to determine patients requiring a prolonged ICU/IMC monitoring., Competing Interests: The author reports no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Cathepsin K (Cat K) is a cysteine protease involved in bone remodeling. In addition to its role in bone biology, Cat K is upregulated in osteoclasts, chondrocytes and synoviocytes in osteoarthritic (OA) disease states making it a potential therapeutic target for disease-modifying OA. Starting from a prior preclinical compound, MK-1256, lead optimization efforts were carried out in the search for potent Cat K inhibitors with improved selectivity profiles with an emphasis on cathepsin F. Herein, we report the SAR studies which led to the discovery of the highly selective oxazole compound 23, which was subsequently shown to inhibit cathepsin K in vivo as measured by reduced levels of urinary C-telopeptide of collagen type I in dog., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Metal ions (Fe, Cu, and Zn) are essential to a healthy brain function, with the amount, localisation, and chemical form often tightly controlled. Evidence points towards loss of metal ion homeostasis within the ageing brain; in particular brain Fe accumulation appears to be a hallmark of ageing, which may place the brain at a greater risk of neurodegenerative disease. Unfortunately, the cause or consequence of altered brain metal ion homeostasis during ageing remains unknown, and there is a lack of data comparing brain metal ion homeostasis with other events of the ageing process (e.g. brain metabolism, brain inflammation). This study has utilised a multi-modal approach that incorporated: X-ray fluorescence microscopy for elemental mapping of metal ion homeostasis, Perl's Fe histochemistry, FTIR spectroscopic biochemical imaging of lactate and protein aggregates, and immuno-fluorescence analysis of markers of brain inflammation and Fe storage proteins (heavy-chain ferritin, light-chain ferritin, and mitochondrial ferritin). Interestingly, while age-related Fe accumulation was observed in corpus callosum white matter of murine (C56BL/6J) brain tissue (concomitant with elevated levels of markers of brain inflammation and altered metabolism), Fe content was not altered within the hippocampus (a decrease in total Zn within the mossy fibres was observed). Ultimately, the results of this study demonstrate an important association between elevated brain Fe and brain inflammation during natural ageing. This study also highlights that future research is required to image different chemical forms of Fe with respect to changes in brain metabolism and inflammation, as well as localising these changes to specific cell types., (© The Author(s) 2022. Published by Oxford University Press.)

This post hoc analysis and modeling study examined the mechanism of action of odanacatib using a statistical model to explain sCTx response in ODN-treated patients as a function of other bone-turnover biomarkers that, with other observed biomarker changes, showed that odanacatib persistently inhibited osteoclastic bone removal activity without preventing osteoclastogenesis., Introduction: Odanacatib (ODN) is an oral selective cathepsin K (CatK) inhibitor, previously in development for osteoporosis treatment. A post hoc analysis examined ODN's mechanism of action on bone-turnover biomarkers., Methods: A subset of patients who completed 60 months' treatment in the Long-Term Odanacatib Fracture Trial (LOFT; NCT00529373) (N = 112 [57 ODN, 55 placebo]) were evaluated. Serum (s) and urine (u) samples were assayed at baseline and months 6-60 for 10 known bone-remodeling biomarkers: sCTx, uαα- and uββCTx/Cr, uNTx/Cr, sNTx, uDPD/Cr, sICTP, sTRAP5b, sPINP, and sBSAP. Because the CrossLaps® CTx assay identifies the CTx peptide as well as larger molecular weight CTx-containing peptides, including ICTP, a best-fit model was developed to explain the transient sCTx reduction in ODN-treated patients., Results: ODN persistently reduced the bone-resorption markers sNTx, uNTx/Cr, uαα- and uββCTx/Cr, and uDPD/Cr, and gradually increased the target-engagement marker sICTP and osteoclast number (sTRAP5b), versus placebo from baseline to month 60. sCTx was transiently reduced with ODN within 12 months, returning to baseline by month 48. Modeling suggested that sCTx changes in the ODN group were primarily due to increased accumulation of larger CTx species, including sICTP. The bone-formation markers sPINP and sBSAP showed partial reductions, versus placebo, in the first 6 months but approached baseline by months 48-60., Conclusion: Observed changes in bone-turnover biomarkers support the persistent efficacy of ODN in direct inhibition of osteoclastic bone-resorption activity, without inhibition of osteoclastogenesis. Long-term evaluation also underscores the unique mechanism of ODN on osteoclastic collagen processing and subsequently osteoblastic bone formation., Trial Registration: NCT00529373., (© 2022. Merck & Co., Inc., Rahway, NJ, USA and its affiliates, under exclusive licence to International Osteoporosis Foundation and National Osteoporosis Foundation.)

Purpose: Transesophageal echocardiography (TEE) is the preferred imaging modality in a hybrid procedure used to close ventricular septal defects (VSDs). However, the limited field of view of TEE hinders the maneuvering of surgical instruments inside the beating heart. This study evaluates the accuracy of a method that aims to support navigation guidance in the hybrid procedure., Methods: A cardiologist maneuvered a needle to puncture the patient's heart and to access a VSD, guided by information displayed in a virtual environment. The information displayed included a model of the patient's heart and a virtual needle that reproduced the position and orientation of the real needle in real time. The physical and the virtual worlds were calibrated with a landmark registration and an iterative closest point algorithms, using an electromagnetic measurement system (EMS). For experiments, we developed a setup that included heart phantoms representing the patient's heart., Results: Experimental results from two pediatric cases studied suggested that the information provided for guidance was accurate enough when the landmark registration algorithm was fed with coordinates of seven points clearly identified on the surfaces of the physical and virtual hearts. Indeed, with a registration error of 2.28 mm RMS, it was possible to successfully access two VSDs (6.2 mm and 6.3 mm in diameter) in all the attempts with a needle (5 attempts) and a guidewire (7 attempts)., Conclusion: We found that information provided in a virtual environment facilitates guidance in the hybrid procedure for VSD closure. A clear identification of anatomical details in the heart surfaces is key to the accuracy of the procedure., (© 2022. CARS.)

Purpose: Ventricular septal defects (VSD) are congenital heart malformations and, in severe cases, they require complex interventions under echocardiography guidance. Heart phantoms can be helpful to train and to understand the complex hemodynamics of VSD. The goal of this study was to characterize the best blood mimicking fluids in such heart phantoms for modelling the hemodynamics of VSD patients using echocardiography., Methods: Four fluid compositions were considered. Distilled water was used as a baseline, while the other three fluids were developed based on physical properties of human blood, such as the viscosity and the refractive index. Three bi-ventricular heart phantoms of three different pediatric patients with complex VSD were designed from preoperative CT imaging. Custom molds were printed in 3-D and the anatomical structure was casted in polyvinyl alcohol cryogel. The VSD in each heart phantom were observed using echocardiography and color Doppler imaging was used for the hemodynamic study., Results: Heart phantoms with blood mimicking fluids of 30% glycerol and 27% glycerol, 10% sodium iodide were found to be anatomically realistic under echocardiography imaging. Hemodynamic parameters such as the pressure gradient and the volume of the shunt were characterized using color Doppler imaging., Conclusion: Proper composition of blood mimicking fluids are important for improving the realism in echocardiographic heart phantoms and they contribute to better understand the complex hemodynamic of VSD under echocardiography., (© 2022. CARS.)

Food is one of the most traded goods, and the conflict in Ukraine, one of the European breadbaskets, has triggered a significant additional disruption in the global food supply chains after the COVID-19 impact. The disruption to food output, supply chains, availability, and affordability could have a long-standing impact. As a result, the availability and supply of a wide range of food raw materials and finished food products are under threat, and global markets have seen recent increases in food prices. Furthermore, the Russian-Ukrainian conflict has adversely affected food supply chains, with significant effects on production, sourcing, manufacturing, processing, logistics, and significant shifts in demand between nations reliant on imports from Ukraine. This paper aims to analyze the impacts of the conflict between Russia and Ukraine on the effectiveness and responsiveness of the global food supply chains. A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach, including grey literature, was deployed to investigate six key areas of the food supply chains that would be impacted most due to the ongoing war. Findings include solutions and strategies to mitigate supply chain impacts such as alternative food raw materials, suppliers and supply chain partners supported by technological innovations to ensure food safety and quality in warlike situations.

Transport properties of the halogeno-alkali oxides A 3 OX (A = Li, Na, X = Cl, Br) nanocrystalline samples with the presence of ∑3(111) grain boundaries were computed using large-scale molecular dynamic simulations. Results on the diffusion/conduction process show that these nanocrystalline samples are characterized with higher activation energies as compared to previous theoretical studies, but closer to experiment. Such a performance can be attributed to the larger atomic density at the ∑3(111) grain boundary regions within the nanocrystals. Despite a minor deterioration of transport properties of the mixed cation Li 2 NaOX and Na 2 LiOX samples, these halogeno-alkali oxides can also be considered as good inorganic solid electrolytes in both Li- and Na-ion batteries., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To investigate the association between the number of pushing contractions and the likelihood of spontaneous vaginal delivery, operative vaginal delivery, cesarean delivery and maternal and neonatal complications., Methods: This was a retrospective analysis of patients who entered the second stage of labor with singleton, term pregnancies at Harbor-UCLA Medical Center from January 1, 2017, to December 31, 2019. Probabilities of spontaneous vaginal delivery, operative vaginal delivery, and cesarean delivery were calculated for each hour of pushing and for every 10 maternal pushing contractions. Maternal and neonatal morbidities were assessed in relation to second-stage pushing contractions., Results: Four hundred thirty-nine nulliparous and 424 multiparous patients who entered the second stage of labor were included. Nulliparous patients had significantly more pushing contractions than multiparous patients (20.3±1.8 vs 7.8±1.0 pushes, P<.001). In nulliparous patients, 91.8% (326/355 patients) of spontaneous vaginal deliveries and 50.0% (12/24 patients) of cesarean deliveries occurred by 40 pushing contractions. In multiparous patients, 94.3% (369/391) of spontaneous vaginal deliveries and 50.0% of cesarean deliveries (4/8) occurred by 20 pushing contractions. The probabilities of cesarean delivery were at their highest after 80 pushing contractions in nulliparous patients and after 50 pushing contractions in multiparous patients. In both nulliparous and multiparous patients, there was no significant change in maternal and neonatal composite morbidities as the number of pushing contractions increased., Conclusion: Results from this study suggest that pushing contractions may be a viable alternative method for prediction of the likelihood of spontaneous vaginal delivery and probabilities of operative vaginal delivery and cesarean delivery for patients reaching the second stage of labor. Providing patients with a goal for expected number of pushing contractions may be of motivational benefit., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Navigation guidance in cardiac interventions is provided by X-ray angiography. Cumulative radiation exposure is a serious concern for pediatric cardiac interventions., Purpose: A generative learning-based approach is proposed to predict X-ray angiography frames to reduce the radiation exposure for pediatric cardiac interventions while preserving the image quality., Methods: Frame predictions are based on a model-free motion estimation approach using a long short-term memory architecture and a content predictor using a convolutional neural network structure. The presented model thus estimates contrast-enhanced vascular structures such as the coronary arteries and their motion in X-ray sequences in an end-to-end system. This work was validated with 56 simulated and 52 patients' X-ray angiography sequences., Results: Using the predicted images can reduce the number of pulses by up to three new frames without affecting the image quality. The average required acquisition can drop by 30% per second for a 15 fps acquisition. The average structural similarity index measurement was 97% for the simulated dataset and 82% for the patients' dataset., Conclusions: Frame prediction using a learning-based method is promising for minimizing radiation dose exposure. The required pulse rate is reduced while preserving the frame rate and the image quality. With proper integration in X-ray angiography systems, this method can pave the way for improved dose management., (© 2022 American Association of Physicists in Medicine.)

Increased cancer incidence occurs with the emergence of immunosenescence, highlighting the indispensability of the immune system in preventing cancer and its dysregulation with aging. Tumor-associated macrophages (TAMs) are often present in high numbers and are associated with poor clinical outcomes in solid cancers, including mesothelioma. Monocytes and macrophages from the bone marrow and spleen can respond to tumor-derived factors, such as CSF-1, and initiation of the CSF-1R signaling cascade results in their proliferation, differentiation, and migration to the tumor. Age-related changes occur in monocytes and macrophages in terms of numbers and function, which in turn can impact tumor initiation and progression. Whether this is due to changes in CSF-1R expression with aging is currently unknown and was investigated in this study. We examined monocytes and macrophages in the bone marrow and spleen during healthy aging in young (3-4 months) and elderly (20-24 months) female C57BL/6J mice. Additionally, changes to these tissues and in TAMs were examined during AE17 mesothelioma tumor growth. Healthy aging resulted in an expansion of Ly6C high monocytes and macrophages in the bone marrow and spleen. CSF-1R expression levels were reduced in elderly splenic macrophages only, suggesting differences in CSF-1R signaling between both cell type and tissue site. In tumor-bearing mice, Ly6C high monocytes increased with tumor growth in the spleen in the elderly and increased intracellular CSF-1R expression occurred in bone marrow Ly6C high monocytes in elderly mice bearing large tumors. Age-related changes to bone marrow and splenic Ly6C high monocytes were reflected in the tumor, where we observed increased Ly6C high TAMs earlier and expansion of Ly6C low TAMs later during AE17 tumor growth in the elderly compared to young mice. F4/80 high TAMs increased with tumor growth in both young and elderly mice and were the largest subset of TAMs in the tumor. Together, this suggests there may be a faster transition of Ly6C high towards F4/80 high TAMs with aging. Amongst TAM subsets, expression of CSF-1R was lowest in F4/80 high TAMs, however Ly6C low TAMs had higher intracellular CSF-1R expression. This suggests downstream CSF-1R signaling may vary between macrophage subsets, which can have implications towards CSF-1R blockade therapies targeting macrophages in cancer., Competing Interests: DN acts as a non-salaried Chief Scientific Officer for Selvax. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Duong, Pixley, Nelson and Jackaman.)

Recent studies have shown that the incidence of nephrotoxicity increases when vancomycin is combined with a beta-lactam antibiotic. The objective of this study was to compare the incidence of acute kidney injury (AKI) in adult patients who received vancomycin with either piperacillin-tazobactam (VPT), cefepime (VC), or meropenem (VM). This was a single center retrospective chart review. Patients were included if they were 18 years or older, received 48 hours of combination therapy and antibiotics were started within 24 hours of each other. Exclusion criteria were receiving more than one combination of antibiotics, serum creatinine > 1.2 mg/dL, AKI at the time of inclusion, or any form of renal replacement therapy. Two hundred patients met inclusion criteria. A total of 27 (13%) patients experienced AKI. The incidence of AKI was 21.6%, 9%, and 7.4% in the VPT, VC and VM groups, respectively. A patient who received VPT was 5 times more likely to develop AKI when compared to a patient who received VC (adjusted OR 5.09 95% CI (1.51-17.08), p  = 0.008) and 7 times more likely to develop AKI when compared to VM (adjusted OR 7.03 95% CI (1.97-28.08), p  = 0.002). This study found a statistically significant difference in the incidence of AKI in patient receiving VPT when compared to VC or VM. This finding supports the need for careful monitoring of renal function in patients receiving VPT therapy and routine evaluation for de-escalation of antimicrobial therapy.

Objectives: Tuberculosis (TB) stigma contributes to diagnostic delay, disease concealment, and reduced wellbeing for affected individuals. Despite the availability of several TB stigma scales, most high-TB burden countries do not have a culturally validated version available. This study evaluated the Van Rie TB stigma scale (VTSS) among people with TB in Vietnam., Methods: This study consisted of two phases. In phase 1, the VTSS was culturally and linguistically adapted to the Vietnamese context. In phase 2, people with TB were invited to complete a survey containing the VTSS, a depression scale, and a quality of life scale. The data analysis included confirmatory factor analysis (CFA), exploratory factor analysis (EFA), construct validity, and floor or ceiling effects., Results: In phase 1, items were reworded from the third person to the first person. The TB/HIV co-infection items (items 7 and 11) were the least relevant for people with TB (62% and 73% relevance, respectively). In phase 2, the CFA demonstrated adequate goodness-of-fit indices (GFI = 0.88, CFI = 0.96, RMSEA = 0.058); however several of the item factor loadings were low. The EFA demonstrated good internal consistency (α = 0.85) and revealed one dominant factor. Construct validity was low., Conclusions: The VTSS demonstrated good psychometric properties in Vietnam. Depending on the purpose of the scale, the HIV co-infection items and item 10 could be considered for removal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Ventricular septal defects (VSDs) are common congenital heart malformations. Echocardiography used during VSD hybrid cardiac procedures requires extensive training for image acquisition and interpretation. Cardiac surgery simulators with heart phantoms have shown usefulness for such training, but they are limited in visualization and characterization of complex VSD. This study explores a new method to build patient-specific heart phantoms with VSD, with proper tissue echogenicity for ultrasound imaging., Methods: Heart phantoms were designed from preoperative imaging of three patients with complex VSDs. Each whole heart phantom, including atrial and ventricular septums, was obtained by manual segmentation and by surface reconstruction, then by molding and by casting in different materials. Heart phantoms in silicone and polyvinyl alcohol cryogel (PVA-C) were considered, and they were reconstructed in 3-D using 2-D freehand ultrasound imaging., Results: An electromagnetic measurement system was used to measure the mean VSD diameters from the heart phantoms. Errors were evaluated below 1.0 mm for mean VSD diameters between 6.2 and 7.5 mm., Conclusion: Patient-specific heart phantoms promise for representing complex heart malformations such as VSDs. PVA-C showed better tissue echogenicity than silicone for VSDs visualization and characterization., (© 2021. CARS.)

Background: Research has confirmed a lack of knowledge regarding the risks of unused medications including diversion, misuse, or accidental overdose among health care professionals (Abdulmajeed, 2020). Nurses and pharmacists are often who patients interact with the most regarding medications; therefore, early education on proper storage and disposal is vital (Bowen, Rotz, Patterson, & Sen, 2017; Celio, Ninane, Bugnon, & Schneider, 2018)., Objectives: The study's objective is to explore safe drug storage and disposal knowledge, attitudes, and practices of professional pharmacy (Pharm.D.) and nursing students., Design: This research is an exploratory cross-sectional study from May to September 2019., Methods: An anonymous online survey was administered to a purposive sample of Pharm.D. and nursing students who were 18 years and older and enrolled in the site's accredited Pharm.D. and nursing programs (N = 210). Responses were analyzed using descriptive statistics., Results: Common disposal methods reported by students of their personal medications such as pills and liquids included discarding medications with the household trash (range 30% to 55%) and medication disposal products/bag (range 19% to 28%). More than half of the participants (50.4%) had unused prescription medication at home, 35% kept the medication for later use, and almost 20% of the participants reported sharing personal medications with others., Conclusion: Although the majority of student participants had adequate knowledge of the appropriate methods for safe drug disposal, few reported using them for their own personal medications. The findings suggest there is a disconnect between the participants' knowledge of the appropriate methods of safe drug storage and disposal in a professional setting and their own practices. Further research is needed to explore and address the reasons for this disconnect. Additionally, findings from this research will assist in the development of and/or the improvement of interdisciplinary educational materials among pharmacy and nursing students., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Ketamine is a dissociative anesthetic drug, which has more recently emerged as a rapid-acting antidepressant. When acutely administered at subanesthetic doses, ketamine causes cognitive deficits like those observed in patients with schizophrenia, including impaired working memory. Although these effects have been linked to ketamine's action as an N-methyl-D-aspartate receptor antagonist, it is unclear how synaptic alterations translate into changes in brain microcircuit function that ultimately influence cognition. Here, we administered ketamine to rhesus monkeys during a spatial working memory task set in a naturalistic virtual environment. Ketamine induced transient working memory deficits while sparing perceptual and motor skills. Working memory deficits were accompanied by decreased responses of fast spiking inhibitory interneurons and increased responses of broad spiking excitatory neurons in the lateral prefrontal cortex. This translated into a decrease in neuronal tuning and information encoded by neuronal populations about remembered locations. Our results demonstrate that ketamine differentially affects neuronal types in the neocortex; thus, it perturbs the excitation inhibition balance within prefrontal microcircuits and ultimately leads to selective working memory deficits., (© 2021. Crown.)

Coronary artery disease is the leading cause of mortality worldwide. Almost seven million deaths are reported each year due to coronary disease. Coronary artery events in the adult are primarily due to atherosclerosis with seventy-five percent of the related mortality caused by plaque rupture. Despite significant progress made to improve intravascular imaging of coronary arteries, there is still a large gap between clinical needs and technical developments. The goal of this review is to identify the gap elements between clinical knowledge and recent advances in the domain of medical image analysis. Efficient image analysis computational models should be designed with respect to the exact clinical needs, and detailed features of the tissues under review. In this review, we discuss the detailed clinical features of the intracoronary plaques for mathematical and biomedical researchers. We emphasize the importance of integrating this clinical knowledge validated by clinicians to investigate the potentially effective models for proper features efficiency in the scope of leveraging the state-of-the-art of coronary image analyses., (Copyright © 2021 IPEM. Published by Elsevier Ltd. All rights reserved.)

Adolescent Idiopathic Scoliosis (AIS) is a deformation of the spine and it is routinely diagnosed using posteroanterior and lateral radiographs. The Risser sign used in skeletal maturity assessment is commonly accepted in AIS patient's management. However, the Risser sign is subject to inter-observer variability and it relies mainly on the observation of ossification on the iliac crests. This study proposes a new machine-learning-based approach for Risser sign skeletal maturity assessment using EOS radiographs. Regions of interest including right and left humeral heads; left and right femoral heads; and pelvis are extracted from the radiographs. First, a total of 24 image features is extracted from EOS radiographs using a ResNet101-type convolutional neural network (CNN), pre-trained from the ImageNet database. Then, a support vector machine (SVM) algorithm is used for the final Risser sign classification. The experimental results demonstrate an overall accuracy of 84%, 78%, and 80% respectively for iliac crests, humeral heads, and femoral heads. Class activation maps using Grad-CAM were also investigated to understand the features of our model. In conclusion, our machine learning approach is promising to incorporate a large number of image features for different regions of interest to improve Risser grading for skeletal maturity. Automatic classification could contribute to the management of AIS patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Processes that utilise low-value wastes and convert them to high-value food ingredients systemically add value across commercial operations. Current common disposal options include use as animal feed, anaerobic digestion, composting, incineration, and the worst-case options of landfill and wastewater disposal. The pressure is acute with food manufacturers needing to align with the UN Sustainable Development Goals and reach targets of zero waste to landfill. This research identifies black soldier fly larvae as a bioreactor that converts most food waste into high-value feed materials. Production of larvae and the regulatory framework for their use as animal feed is being assessed in several nations. The requirement to understand the availability of feedstocks for larvae production and the capability to establish feedstock supply chains was tested in this study using geographical information system and life cycle assessment methodologies, providing new research insights for resource utilisation in a circular economy.

Virginia mountain mint ( Pycnanthemum virginianum ) is a peppermint-flavored aromatic herb of the Lamiaceae and is mainly used for culinary, medicinal, aromatic, and ornamental purposes. North Alabama's climate is conducive to growing mint for essential oils used in culinary, confectionery, and medicinal purposes. There is, however, a need for varieties of P. virginianum that can be adapted and easily grown for production in North Alabama. Towards this end, four field-grown varieties with three harvesting times (M1H1, M1H2, M1H3; M2H1, M2H2, M2H3; M3H1, M3H2, M3H3, M4H1, M4H2, M4H3) were evaluated for relative differences in essential oil yield and composition. Thirty-day-old greenhouse-grown plants of the four varieties were transplanted on raised beds in the field at the Alabama A & M University Research Station in North Alabama. The plots were arranged in a randomized complete block with three replications. The study's objective was to compare the four varieties for essential oil yield and their composition at three harvest times, 135, 155, and 170 days after planting (DAP). Essential oils were obtained by hydrodistillation with continuous extraction with dichloromethane using a Likens-Nickerson apparatus and analyzed by gas chromatographic techniques. At the first harvest, the essential oil yield of the four varieties showed that M1H1 had a yield of 1.15%, higher than M2H1, M3H1, and M4H1 with 0.91, 0.76, and 1.03%, respectively. The isomenthone concentrations increased dramatically through the season in M1 (M1H1, M1H2, M1H3) by 19.93, 54.7, and 69.31%, and M3 (M3H1, M3H2, M3H3) by 1.81, 48.02, and 65.83%, respectively. However, it increased only slightly in M2 and M4. The thymol concentration decreased slightly but not significantly in all four varieties; the thymol in M2 and M4 was very high compared with M1 and M3. The study showed that mountain mint offers potential for production in North Alabama. Two varieties, M1 and M3, merit further studies to determine yield stability, essential oil yield, composition, and cultivation development practices.

Purpose: Coronary artery events are mainly associated with atherosclerosis in adult population, which is recognized as accumulation of plaques in arterial wall tissues. Optical Coherence Tomography (OCT) is a light-based imaging system used in cardiology to analyze intracoronary tissue layers and pathological formations including plaque accumulation. This state-of-the-art catheter-based imaging system provides intracoronary cross-sectional images with high resolution of 10-15 µm. But interpretation of the acquired images is operator dependent, which is not only very time-consuming but also highly error prone from one observer to another. An automatic and accurate coronary plaque tagging using OCT image post-processing can contribute to wide adoption of the OCT system and reducing the diagnostic error rate., Method: In this study, we propose a combination of spatial pyramid pooling module with dilated convolutions for semantic segmentation to extract atherosclerotic tissues regardless of their types and training a sparse auto-encoder to reconstruct the input features and enlarge the training data as well as plaque type characterization in OCT images., Results: The results demonstrate high precision of the proposed model with reduced computational complexity, which can be appropriate for real-time analysis of OCT images. At each step of the work, measured accuracy, sensitivity, specificity of more than 93% demonstrate high performance of the model., Conclusion: The main focus of this study is atherosclerotic tissue characterization using OCT imaging. This contributes to wide adoption of the OCT imaging system by providing clinicians with a fully automatic interpretation of various atherosclerotic tissues. Future studies will be focused on analyzing atherosclerotic vulnerable plaques, those coronary plaques which are prone to rupture., (© 2021 American Association of Physicists in Medicine.)