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Multi-scale computational modeling is a major branch of computational biology as evidenced by the US federal interagency Multi-Scale Modeling Consortium and major international projects. It invariably involves specific and detailed sequences of data analysis and simulation, often with multiple tools and datasets, and the community recognizes improved modularity, reuse, reproducibility, portability and scalability as critical unmet needs in this area. Scientific workflows are a well-recognized strategy for addressing these needs in scientific computing. While there are good examples if the use of scientific workflows in bioinformatics, medical informatics, biomedical imaging and data analysis, there are fewer examples in multi-scale computational modeling in general and cardiac electrophysiology in particular. Cardiac electrophysiology simulation is a mature area of multi-scale computational biology that serves as an excellent use case for developing and testing new scientific workflows. In this article, we develop, describe and test a computational workflow that serves as a proof of concept of a platform for the robust integration and implementation of a reusable and reproducible multi-scale cardiac cell and tissue model that is expandable, modular and portable. The workflow described leverages Python and Kepler-Python actor for plotting and pre/post-processing. During all stages of the workflow design, we rely on freely available open-source tools, to make our workflow freely usable by scientists.

Early identification of younger, non-demented adults at elevated risk for Alzheimer's disease (AD) is crucial because the pathological process begins decades before dementia onset. Toward that end, we showed that an AD polygenic risk score (PRS) could identify mild cognitive impairment (MCI) in adults who were only in their 50s. Participants were 1176 white, non-Hispanic community-dwelling men of European ancestry in the Vietnam Era Twin Study of Aging (VETSA): 7% with amnestic MCI (aMCI); 4% with non-amnestic MCI (naMCI). Mean age was 56 years, with 89%

Monitoring and ensuring the integrity of data within the clinical trial process is currently not always feasible with the current research system. We propose a blockchain-based system to make data collected in the clinical trial process immutable, traceable, and potentially more trustworthy. We use raw data from a real completed clinical trial, simulate the trial onto a proof of concept web portal service, and test its resilience to data tampering. We also assess its prospects to provide a traceable and useful audit trail of trial data for regulators, and a flexible service for all members within the clinical trials network. We also improve the way adverse events are currently reported. In conclusion, we advocate that this service could offer an improvement in clinical trial data management, and could bolster trust in the clinical research process and the ease at which regulators can oversee trials.

Human-milk-targeted metabolomics analysis offers novel insights into milk composition and relationships with maternal and infant phenotypes and nutritional status. The Biocrates AbsoluteIDQ® p180 kit, targeting 40 acylcarnitines, 42 amino acids/biogenic amines, 91 phospholipids, 15 sphingolipids, and sum of hexoses, was evaluated for human milk using the AB Sciex 5500 QTRAP mass-spectrometer in liquid chromatography-tandem mass-spectrometry (LC-MS/MS) and flow-injection analysis (FIA) mode. Milk ( 18.5; n = 12) and (B) Bangladeshi mothers of stunted infants (height-for-age Z (HAZ)-score 18.5 was lower in 6 amino acids/biogenic amines but higher in isovalerylcarnitine, two phospholipids, and one sphingomyelin (p < 0.05 for all). Associations between milk metabolites differed between groups. The AbsoluteIDQ® p180 kit is a rapid analysis tool suitable for human milk analysis and reduces analytical bias by allowing the same technique for different specimens. More research is needed to examine milk metabolite relationships with maternal and infant phenotypes.

PurposeThe National Mammography Database (NMD) contains nearly 20 million examinations from 693 facilities; it is the largest information source for use and effectiveness of breast imaging in the United States. NMD collects demographic, imaging, interpretation, biopsy, and basic pathology results, enabling facility and physician comparison for quality improvement. However, NMD lacks treatment and clinical outcomes data. The network of state cancer registries (CRs) contains detailed pathologic, treatment, and clinical outcomes data. This pilot study assessed electronic linkage of NMD and CR data at a multicenter institution as proof of concept.Materials and methodsWe obtained Quality Oversight Committee approval for this retrospective study. Data of patients diagnosed with breast cancer in 2014 and 2015 were retrieved from our NMD-approved radiology information system (RIS) and matched with reportable patients in our CR using social security number (SSN), first name (fname), last name (lname), and date of birth (DOB). Matching was repeated without SSN. Percentage and reasons for mismatch were evaluated.ResultsThe RIS query identified 1,316 patients. CR linkage was 99.2% successful (n = 1,305 of 1,316) using SSN, fname, lname, and DOB. Eleven mismatches included four CR case-finding failures, one NMD fname error, five nonreportable in the CR, and one with correct identifiers in both databases. Without SSN, linkage was 97.3% successful (n = 1,281 of 1,316); name errors accounted for 19 and DOB accounted for 5 additional mismatches.ConclusionUsing common data elements, linkage between the NMD and state CRs may be feasible and could provide critical outcomes information to advance accurate assessment of breast imaging in the United States.

We describe the observation of stimuli-induced peptide-based nanoscale assemblies by liquid cell transmission electron microscopy (LCTEM). LCTEM offers the opportunity to directly image nanoscale materials in liquid. Despite broad interest in characterizing biological phenomena, electron beam-induced damage remains a significant problem. Concurrently, methods for verifying chemical structure during or following an LCTEM experiment have been few, with key examples limited to electron diffraction or elemental analysis of crystalline materials; this strategy is not translatable to biopolymers observed in nature. In this proof-of-concept study, oligomeric peptides are biologically or chemically stimulated within the liquid cell in a TEM to assemble into nanostructures. The resulting materials are analyzed by MALDI-imaging mass spectrometry (MALDI-IMS) to verify their identity. This approach confirms whether higher-order assemblies observed by LCTEM consist of intact peptides, verifying that observations made during the in situ experiment are because of those same peptides and not aberrant electron beam damage effects.

Spatial mapping is a promising strategy to investigate the mechanisms underlying the incidence of psychosis. We analyzed a case-cohort study (n = 24,028), drawn from the 1.47 million Danish persons born between 1981 and 2005, using a novel framework for decomposing the geospatial risk for schizophrenia based on locale of upbringing and polygenic scores. Upbringing in a high environmental risk locale increases the risk for schizophrenia by 122%. Individuals living in a high gene-by-environmental risk locale have a 78% increased risk compared to those who have the same genetic liability but live in a low-risk locale. Effects of specific locales vary substantially within the most densely populated city of Denmark, with hazard ratios ranging from 0.26 to 9.26 for environment and from 0.20 to 5.95 for gene-by-environment. These findings indicate the critical synergism of gene and environment on the etiology of schizophrenia and demonstrate the potential of incorporating geolocation in genetic studies.

BackgroundAccurate root position is integral for successful orthodontic treatment. Current methods of monitoring root position are either inaccurate, exhibit poor resolution, or use relatively large amount of radiation relative to the benefits for the patient. The purpose of this study was to present an approach that can monitor root position during orthodontic treatment with minimal radiation.MethodsCone-beam computed tomography (CBCT) scans were taken for a patient at pre-treatment and at a dedicated reset appointment. An extra-oral laser scan of a poured up cast was taken at the reset appointment. An expected root position (ERP) setup, an approximation of the root position at the reset appointment, was generated using the pre-treatment CBCT scan and reset appointment cast. The ERP setup was compared to the CBCT scan taken at the reset appointment which served as the control. Color displacement maps were generated to measure any differences between the expected and true root positions.ResultsColor map displacement analysis after indirect superimposition found displacement differences of 0.021 mm ± 0.396 mm for the maxillary roots and 0.079 mm ± 0.499 mm for the mandibular roots.ConclusionsThis approach was demonstrated in a patient at the reset appointment to have the potential to accurately monitor root positions during treatment in three dimensions without the need for additional radiographs.

Objectives: Value-based agreements (VBAs) link access, reimbursement, or price to the realworld usage and impact of a medicine, thereby enabling patient access while reducing clinical or financial uncertainty for the payer. VBAs have the potential to support improved patient outcomes, given the value-oriented approach to care, and lead to overall savings, while enabling payers to share risk and reduce uncertainty. Methods: This commentary outlines the key challenges, enablers, and a framework for successful implementation by comparing the experience of two VBAs for AstraZeneca medicines, aiming to increase confidence in their future use. Results: Engagement by payers, manufacturers, physicians, and provider institutions, and robust data collection systems that are accessible, simple to use, and add little burden to physicians were key to successfully negotiating a VBA that worked for all stakeholders. In both country systems, a legal/policy framework enabled innovative contracting. Conclusions: These examples demonstrate proof of concept for VBA implementation in different settings, and may inform future VBAs. [ABSTRACT FROM AUTHOR]

Purpose: No method is available to systematically study SARS-CoV-2 transmission dynamics using the data that rideshare companies share with government agencies. We developed a proof-of-concept method for the analysis of SARS-CoV-2 transmissions between rideshare passengers and drivers.Method: To assess whether this method could enable hypothesis testing about SARS-CoV-2, we repeated ten 200-day agent-based simulations of SARS-CoV-2 propagation within the Los Angeles County rideshare network. Assuming data access for 25% of infections, we estimated an epidemiologist's ability to analyze the observable infection patterns to correctly identify a baseline viral variant A, as opposed to viral variant A with mask use (50% reduction in viral particle exchange), or a more infectious viral variant B (300% higher cumulative viral load).Results: Simulations had an average of 190,387 potentially infectious rideshare interactions, resulting in 409 average diagnosed infections. Comparison of the number of observed and expected passenger-to-driver infections under each hypothesis demonstrated our method's ability to consistently discern large infectivity differences (viral variant A vs. viral variant B) given partial data from one large city, and to discern smaller infectivity differences (viral variant A vs. viral variant A with masks) given partial data aggregated across multiple cities.Conclusions: This novel statistical method suggests that, for the present and subsequent pandemics, government-facilitated analysis of rideshare data combined with diagnosis records may augment efforts to better understand viral transmission dynamics and to measure changes in infectivity associated with nonpharmaceutical interventions and emergent viral strains. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: Nephrometric scores play an interesting role in nephron sparring surgery (NSS) planning. The aim of this study is to evaluate if R.E.N.A.L. score (RS) is capable to predict the occurrence of adverse events in laparoscopic NSS. Materials and Methods: We prospectively studied 150 laparoscopic NSS between 2015 and 2018 to evaluate the relationship between RS and incidence of adverse events. Clavien 3 or superior complications, warm ischemia time (WIT) over 30 minutes, tumor violation, positive surgical margins (PSM) and necessity of amplification of renal parenchyma during the resection of the masses to obtain free margins were considered as adverse events. We compared each item of the RS isolated and divided the patients between low risk and high risk. Results: Adverse results occurred in 48 cases (32%). Amplification of the margin of resection was observed in 28 cases (19%). WIT exceeded 30 minutes in 9 cases (6.1%), complications Clavien 3 or superior occurred in 13 cases (9%) and PSM were detected en 6 cases (4%). Comparing the patients with adverse outcomes and each item of the RS we did not find any statistical difference, but when divided into high risk and low risk, we found that patients in the high risk group had a higher tendency to present ad-verse results - 25.84% vs. 44.26% (p=0.03). Conclusions: RS system is a good way to predict adverse outcomes in NSS, especially in cases over 7. Further studies should focus on robotic approach and patient's characteristics other than the masses’ aspects.

Previous studies have shown that gut-microbiome is associated with nonalcoholic fatty liver disease (NAFLD). We aimed to examine if serum metabolites, especially those derived from the gut-microbiome, have a shared gene-effect with hepatic steatosis and fibrosis. This is a cross-sectional analysis of a prospective discovery cohort including 156 well-characterized twins and families with untargeted metabolome profiling assessment. Hepatic steatosis was assessed using magnetic-resonance-imaging proton-density-fat-fraction (MRI-PDFF) and fibrosis using MR-elastography (MRE). A twin additive genetics and unique environment effects (AE) model was used to estimate the shared gene-effect between metabolites and hepatic steatosis and fibrosis. The findings were validated in an independent prospective validation cohort of 156 participants with biopsy-proven NAFLD including shotgun metagenomics sequencing assessment in a subgroup of the cohort. In the discovery cohort, 56 metabolites including 6 microbial metabolites had a significant shared gene-effect with both hepatic steatosis and fibrosis after adjustment for age, sex and ethnicity. In the validation cohort, 6 metabolites were associated with advanced fibrosis. Among them, only one microbial metabolite, 3-(4-hydroxyphenyl)lactate, remained consistent and statistically significantly associated with liver fibrosis in the discovery and validation cohort (fold-change of higher-MRE versus lower-MRE: 1.78, P < 0.001 and of advanced versus no advanced fibrosis: 1.26, P = 0.037, respectively). The share genetic determination of 3-(4-hydroxyphenyl)lactate with hepatic steatosis was RG :0.57,95%CI:0.27-0.80, P < 0.001 and with fibrosis was RG :0.54,95%CI:0.036-1, P = 0.036. Pathway reconstruction linked 3-(4-hydroxyphenyl)lactate to several human gut-microbiome species. In the validation cohort, 3-(4-hydroxyphenyl)lactate was significantly correlated with the abundance of several gut-microbiome species, belonging only to Firmicutes, Bacteroidetes and Proteobacteria phyla, previously reported as associated with advanced fibrosis. Conclusion: This proof of concept study provides evidence of a link between the gut-microbiome and 3-(4-hydroxyphenyl)lactate that shares gene-effect with hepatic steatosis and fibrosis. (Hepatology 2018).

Patients with chronic spinal cord injury (SCI) cannot urinate at will and must empty the bladder by self-catheterization. We tested the hypothesis that non-invasive, transcutaneous magnetic spinal cord stimulation (TMSCS) would improve bladder function in individuals with SCI. Five individuals with American Spinal Injury Association Impairment Scale A/B, chronic SCI and detrusor sphincter dyssynergia enrolled in this prospective, interventional study. After a two-week assessment to determine effective stimulation characteristics, each patient received sixteen weekly TMSCS treatments and then received "sham" weekly stimulation for six weeks while bladder function was monitored. Bladder function improved in all five subjects, but only during and after repeated weekly sessions of 1 Hz TMSCS. All subjects achieved volitional urination. The volume of urine produced voluntarily increased from 0 cc/day to 1120 cc/day (p = 0.03); self-catheterization frequency decreased from 6.6/day to 2.4/day (p = 0.04); the capacity of the bladder increased from 244 ml to 404 ml (p = 0.02); and the average quality of life ranking increased significantly (p = 0.007). Volitional bladder function was re-enabled in five individuals with SCI following intermittent, non-invasive TMSCS. We conclude that neuromodulation of spinal micturition circuitry by TMSCS may be used to ameliorate bladder function.

Background and objectivesPercutaneous peripheral nerve stimulation (PNS) is an analgesic modality involving the insertion of a lead through an introducing needle followed by the delivery of electric current. This modality has been reported to treat chronic pain as well as postoperative pain the day following knee surgery. However, it remains unknown if this analgesic technique may be used in ambulatory subjects following foot procedures beginning within the recovery room immediately following surgery, and with only short series of patients reported to date, the only available data are derived from strictly observational studies. The purposes of this proof-of-concept study were to demonstrate the feasibility of using percutaneous sciatic nerve PNS to treat postoperative pain following ambulatory foot surgery in the immediate postoperative period and provide the first available data from a randomized controlled study design to provide evidence of analgesic effect.MethodsPreoperatively, an electrical lead (SPRINT; SPR Therapeutics, Inc, Cleveland, Ohio) was percutaneously inserted posterior to the sciatic nerve between the subgluteal region and bifurcation with ultrasound guidance. Following hallux valgus osteotomy, subjects received 5 minutes of either stimulation or sham in a randomized, double-masked fashion followed by a 5-minute crossover period and then continuous stimulation until lead removal on postoperative days 14 to 28.ResultsDuring the initial 5-minute treatment period, subjects randomized to stimulation (n = 4) experienced a downward trajectory in their pain over the 5 minutes of treatment, whereas those receiving sham (n = 3) reported no such change until their subsequent 5-minute stimulation crossover. During the subsequent 30 minutes of stimulation, pain scores decreased to 52% of baseline (n = 7). Three subjects (43%) used a continuous popliteal nerve block for rescue analgesia during postoperative days 0 to 3. Overall, resting and dynamic pain scores averaged less than 1 on the numeric rating scale, and opioid use averaged less than 1 tablet daily with active stimulation. One lead dislodged, 2 fractured during use, and 1 fractured during intentional withdrawal.ConclusionsThis proof-of-concept study demonstrates that percutaneous sciatic nerve PNS is feasible for ambulatory foot surgery and suggests that this modality provides analgesia and decreases opioid requirements following hallux valgus procedures. However, lead dislodgement and fracture are concerns.Clinical trial registrationThis study was registered at Clinicaltrials.gov, identifier NCT02898103.

Despite great interest in using magnetic resonance imaging (MRI) for studying the effects of genes on brain structure in humans, current approaches have focused almost entirely on predefined regions of interest and had limited success. Here, we used multivariate methods to define a single neuroanatomical score of how William's Syndrome (WS) brains deviate structurally from controls. The score is trained and validated on measures of T1 structural brain imaging in two WS cohorts (training, n = 38; validating, n = 60). We then associated this score with single nucleotide polymorphisms (SNPs) in the WS hemi-deleted region in five cohorts of neurologically and psychiatrically typical individuals (healthy European descendants, n = 1863). Among 110 SNPs within the 7q11.23 WS chromosomal region, we found one associated locus (p = 5e-5) located at GTF2IRD1, which has been implicated in animal models of WS. Furthermore, the genetic signals of neuroanatomical scores are highly enriched locally in the 7q11.23 compared with summary statistics based on regions of interest, such as hippocampal volumes (n = 12,596), and also globally (SNP-heritability = 0.82, se = 0.25, p = 5e-4). The role of genetic variability in GTF2IRD1 during neurodevelopment extends to healthy subjects. Our approach of learning MRI-derived phenotypes from clinical populations with well-established brain abnormalities characterized by known genetic lesions may be a powerful alternative to traditional region of interest-based studies for identifying genetic variants regulating typical brain development.

BackgroundFew effective treatment options exist for cannabis-using youth. This pilot study aimed to test Approach-Avoidance Training to reduce cannabis use with non-treatment-seeking adolescents.MethodsEighty cannabis-using non-treatment-seeking adolescents (average age 19) were recruited from San Diego, California and Charleston, South Carolina, and randomized to complete either six sessions of Cannabis Approach-Avoidance Task Training (CAAT-training) designed to reduce automatic approach biases for cannabis cues or CAAT-sham training. Change in two primary outcome variables was examined: 1) cannabis approach bias and 2) percent cannabis use days over study enrollment. Change in percent alcohol use days over study enrollment was explored as a secondary outcome.ResultsA mixed models repeated measures analysis confirmed the group by time interaction effect for approach bias failed to reach statistical significance (p = .06). Significant group by time interaction effects (ps

OBJECTIVE:We evaluated a novel concept of initiating the etonogestrel implant as a "back-up" method in women who desire using combined oral contraceptives (COC) but want to decrease their risk of unintended pregnancy with a more effective method. STUDY DESIGN:In this prospective cohort study, we planned to include 20 women as a proof-of-concept. We enrolled both new COC starters and continuing COC users and placed an etonogestrel implant. Participants completed daily bleeding diaries and attended follow-up visits at 1, 3, and 6 months. We assessed implant continuation through six months of study participation and side effects with dual hormonal contraceptive use. RESULTS:Between September and December 2016, we enrolled 10 new starters and 10 current COC users. All participants completed 1-month follow-up, and 18 (90%) subjects completed the 3- and 6-month follow-up assessments. Two current COC users had the implant removed for mood changes before 6 months. At the 6-month follow-up visit, 10 women were using both pills and implant, seven relied on the implant only, and one was using a COC only. Three new starters chose implant removal at end of study participation; one for weight gain and acne, another for mood changes, and one for decreased libido. No subjects discontinued the implant for bleeding complaints. CONCLUSION:In this proof-of-concept study, women using COCs were willing to initiate the implant as a "back-up" method to improve pregnancy prevention. Most women continued the implant through 6 months and after completing study participation. IMPLICATIONS:Initiating the etonogestrel implant as a "back-up" method may be an option for women who desire more effective pregnancy prevention while using combined oral contraceptive pills for its bleeding profile or non-contraceptive benefits.

STUDY OBJECTIVES:Longitudinal studies support the usage of positive airway pressure (PAP) therapy in treating obstructive sleep apnea (OSA) to improve cardiovascular disease. However, the anticipated benefit is not ubiquitous. In this study, we elucidate whether PAP therapy leads to immediate improvements on endothelial function, a subclinical marker of cardiovascular status, by examining the effect of circulating exosomes, isolated from patients before and after PAP therapy, on naive endothelial cells. METHODS:We isolated plasma-derived circulating exosomes from 12 patients with severe OSA and obesity hypoventilation syndrome (OHS) before and after 6 weeks of PAP therapy, and examined their effect on cultured endothelial cells using several in vitro reporter assays. RESULTS:We found that circulating exosomes contributed to the induction and propagation of OSA/OHS-related endothelial dysfunction (ie, increased permeability and disruption of tight junctions along with increased adhesion molecule expression, and reduced endothelial nitric oxide synthase expression), and promoted increased monocyte adherence. Further, when comparing exosomes isolated before and after PAP therapy, the disturbances in endothelial cell function were attenuated with treatment, including an overall cumulative decrease in endothelial permeability in all 12 subjects by 10.8% (P = .035), as well as detection of a subset of 4 differentially expressed exosomal miRNAs, even in the absence of parallel changes in systemic blood pressure or metabolic function. CONCLUSIONS:Circulating exosomes facilitate important intercellular signals that modify endothelial phenotype, and thus emerge as potential fundamental contributors in the context of OSA/OHS-related endothelial dysfunction. Exosomes may not only provide candidate biomarkers, but are also a likely and plausible mechanism toward OSA/OHS-induced cardiovascular disease. CLINICAL TRIAL REGISTRATION:Registry: ClinicalTrials.gov, Title: AVAPS-AE Efficacy Study, URL: https://clinicaltrials.gov/ct2/show/NCT01368614, Identifier: NCT01368614.

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Background: Polyomavirus (PyV) nephropathy (PyVN) leads to kidney transplant dysfunction and loss. Since a definitive diagnosis requires an invasive kidney biopsy, a timely diagnosis is often hampered. In this clinical dilemma the PyV haufen-test, centering around the detection of 3-dimensional PyV aggregates in the urine, might provide crucial diagnostic information., Methods: A multistep experimental design was used. The hypothesis was that PyV-haufen form within the kidneys under high concentrations of uromodulin, a kidney-specific protein and that PyV-haufen are, therefore, kidney-specific disease biomarkers., Results: The first investigative step showed colocalization of uromodulin with aggregated PyV (1) in 10 kidneys with PyVN by immunohistochemistry, (2) in urine samples containing PyV-haufen by electron microscopy/immunogold labeling (n = 3), and (3) in urine samples containing PyV-haufen by immunoprecipitation assays (n = 4). In the in vitro experiments of the next step, only high uromodulin concentrations (≥1.25 mg/mL) aggregated PyV, as is expected to occur within injured nephrons. In contrast, in voided urine samples (n = 59) uromodulin concentrations were below aggregation concentrations (1.2-19.6 µg/mL). In the third investigative step, none of 11 uromodulin-/- knockout mice (0%) with histologic signs of PyVN showed urinary PyV-haufen shedding, compared with 10 of 14 uromodulin+/+ wild-type mice (71%)., Conclusions: PyV-haufen form within kidneys under high uromodulin concentrations. Thus, PyV-haufen detected in the urine are specific biomarkers for intrarenal disease (ie, definitive PyVN)., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Choosing between screw-retained and cement-retained restorations in the esthetic zone may significantly impact the restorative contour. This study analyzes the effect of facial-palatal implant positioning on the facial emergence angle of implant restorations in the anterior maxilla. A total of 133 maxillary anterior implant cases were captured with intraoral scans and used to create digital prosthetic designs. The restoration facial emergence angle and the implant depth were determined using images at the midfacial cross section. Simple logistic and linear regression models were used to analyze the interrelation between the emergence angle, depth, and retention methods. The average facial emergence angle for all restorations in this study was 34.4 degrees. A significant difference in emergence angle was found between screw-retained and cement-retained groups, with averages of 37.3 degrees and 27.9 degrees, respectively. There was no difference in the mean depth between the two groups. A strong negative linear relationship between depth and emergence angle was seen for the screw-retained group. Overall, implant positioning in the anterior maxilla has a significant influence on emergence angle. Facial emergence angle is significantly greater for implants in a screw-retained position. This may be partially alleviated by deeper implant placement.

The purpose was to determine whether the benefits of a muscle strength and power training program are superior to those achieved with muscle strength training alone in people with patellofemoral pain (PFP). Thirty-seven individuals with PFP (25.86 ± 7.62 years) were randomly assigned to a strength and power training group (n = 18) or strength training group (n = 19). Primary outcomes were pain intensity and physical functioning. Secondary outcomes were kinesiophobia, quality of life, maximal isometric torque and rate of torque development of the hip and knee and self-perception of recovery. Primary outcomes were measured at baseline, after six weeks, after 12 weeks and at three, six- and 12-months follow-ups. Secondary outcomes were measured at baseline and after 12 weeks. The significance level was 0.05. After interventions, no significant differences were found between groups for primary or secondary outcomes. No difference between groups were found for pain or physical functioning at the other assessment times. Results of this study indicated that addition of power exercises to strength training for hip and knee muscles did not result in superior benefits compared to strength training alone., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Smartphones and wearables are revolutionizing the assessment of cognitive and motor function in neurological disorders, allowing for objective, frequent, and remote data collection. However, these assessments typically provide a plethora of sensor-derived measures (SDMs), and selecting the most suitable measure for a given context of use is a challenging, often overlooked problem., Objective: This analysis aims to develop and apply an SDM selection framework, including automated data quality checks and the evaluation of statistical properties, to identify robust SDMs that describe the cognitive and motor function of people with multiple sclerosis (MS)., Methods: The proposed framework was applied to data from a cross-sectional study involving 85 people with MS and 68 healthy participants who underwent in-clinic supervised and remote unsupervised smartphone-based assessments. The assessment provided high-quality recordings from cognitive, manual dexterity, and mobility tests, from which 47 SDMs, based on established literature, were extracted using previously developed and publicly available algorithms. These SDMs were first separately and then jointly screened for bias and normality by 2 expert assessors. Selected SDMs were then analyzed to establish their reliability, using an intraclass correlation coefficient and minimal detectable change at 95% CI. The convergence of selected SDMs with in-clinic MS functional measures and patient-reported outcomes was also evaluated., Results: A total of 16 (34%) of the 47 SDMs passed the selection framework. All selected SDMs demonstrated moderate-to-good reliability in remote settings (intraclass correlation coefficient 0.5-0.85; minimal detectable change at 95% CI 19%-35%). Selected SDMs extracted from the smartphone-based cognitive test demonstrated good-to-excellent correlation (Spearman correlation coefficient, |ρ|>0.75) with the in-clinic Symbol Digit Modalities Test and fair correlation with Expanded Disability Status Scale (EDSS) scores (0.25≤|ρ|<0.5). SDMs extracted from the manual dexterity tests showed either fair correlation (0.25≤|ρ|<0.5) or were not correlated (|ρ|<0.25) with the in-clinic 9-hole peg test and EDSS scores. Most selected SDMs from mobility tests showed fair correlation with the in-clinic timed 25-foot walk test and fair to moderate-to-good correlation (0.5<|ρ|≤0.75) with EDSS scores. SDM correlations with relevant patient-reported outcomes varied by functional domain, ranging from not correlated (cognitive test SDMs) to good-to-excellent correlation (|ρ|>0.75) for mobility test SDMs. Overall, correlations were similar when smartphone-based tests were performed in a clinic or remotely., Conclusions: Reported results highlight that smartphone-based assessments are suitable tools to remotely obtain high-quality SDMs of cognitive and motor function in people with MS. The presented SDM selection framework promises to increase the interpretability and standardization of smartphone-based SDMs in people with MS, paving the way for their future use in interventional trials., (©Matthew Scaramozza, Aurélie Ruet, Patrizia A Chiesa, Laïtissia Ahamada, Emmanuel Bartholomé, Loïc Carment, Julie Charre-Morin, Gautier Cosne, Léa Diouf, Christine C Guo, Adrien Juraver, Christoph M Kanzler, Angelos Karatsidis, Claudia Mazzà, Joaquin Penalver-Andres, Marta Ruiz, Aurore Saubusse, Gabrielle Simoneau, Alf Scotland, Zhaonan Sun, Minao Tang, Johan van Beek, Lauren Zajac, Shibeshih Belachew, Bruno Brochet, Nolan Campbell. Originally published in JMIR Formative Research (https://formative.jmir.org), 08.11.2024.)

Introduction: No consensus exists on performance standards for evaluation of generative artificial intelligence (AI) to generate medical responses. The purpose of this study was the assessment of Chat Generative Pre-trained Transformer (ChatGPT) to address medical questions in prostate cancer., Methods: A global online survey was conducted from April to June 2023 among > 700 medical oncologists or urologists who treat patients with prostate cancer. Participants were unaware this was a survey evaluating AI. In component 1, responses to 9 questions were written independently by medical writers (MWs; from medical websites) and ChatGPT-4.0 (AI generated from publicly available information). Respondents were randomly exposed and blinded to both AI-generated and MW-curated responses; evaluation criteria and overall preference were recorded. Exploratory component 2 evaluated AI-generated responses to 5 complex questions with nuanced answers in the medical literature. Responses were evaluated on a 5-point Likert scale. Statistical significance was denoted by P < .05., Results: In component 1, respondents (N = 602) consistently preferred the clarity of AI-generated responses over MW-curated responses in 7 of 9 questions ( P < .05). Despite favoring AI-generated responses when blinded to questions/answers, respondents considered medical websites a more credible source (52%-67%) than ChatGPT (14%). Respondents in component 2 (N = 98) also considered medical websites more credible than ChatGPT, but rated AI-generated responses highly for all evaluation criteria, despite nuanced answers in the medical literature., Conclusions: These findings provide insight into how clinicians rate AI-generated and MW-curated responses with evaluation criteria that can be used in future AI validation studies.

Background: the escalating influx of patients with temporomandibular disorders and the challenges associated with accurate diagnosis by non-specialized dental practitioners underscore the integration of artificial intelligence into the diagnostic process of temporomandibular disorders (TMD) as a potential solution to mitigate diagnostic disparities associated with this condition., Objectives: In this study, we evaluated a machine-learning model for classifying TMDs based on the International Classification of Orofacial Pain, using structured data., Methodology: Model construction was performed by the exploration of a dataset comprising patient records from the repository of the Multidisciplinary Orofacial Pain Center (CEMDOR) affiliated with the Federal University of Santa Catarina. Diagnoses of TMD were categorized following the principles established by the International Classification of Orofacial Pain (ICOP-1). Two independent experiments were conducted using the decision tree technique to classify muscular or articular conditions. Both experiments uniformly adopted identical metrics to assess the developed model's performance and efficacy., Results: The classification model for joint pain showed a relevant potential for general practitioners, presenting 84% accuracy and f1-score of 0.85. Thus, myofascial pain was classified with 78% accuracy and an f1-score of 0.76. Both models used from 2 to 5 clinical variables to classify orofacial pain., Conclusion: The use of decision tree-based machine learning holds significant support potential for TMD classification.

Endometrial disorders, such as infertility and endometriosis, significantly impact reproductive health, thus necessitating better models to study endometrial function. Current in vitro models fail to replicate the complexity of the human endometrium throughout the entire menstrual cycle. This study aimed to assess the physiological response of human endometrial organoids (hEOs) to in vitro hormonal treatments designed to mimic the hormonal fluctuations of the menstrual cycle. Endometrial biopsies from three healthy women were used to develop hEOs, which were treated over 28 days with three hormonal stimulation strategies: (1) estrogen only (E) to mimic the proliferative phase, (2) the addition of progesterone (EP) to simulate the secretory phase, and (3) the further addition of cAMP (EPC) to enhance the secretory functions of hEOs. Gene and protein expression were analyzed using qPCR, IHC, and ELISA. The hEOs exhibited proliferation, gland formation, and appropriate expression of markers such as E-cadherin and Ki67. The hormonal treatments induced significant changes in PR , HSD17B1 , PAEP , SPP1 , and other genes relevant to endometrial function, closely mirroring in vivo physiological responses. The prominent changes were observed in EPC-treated hEOs (week 4) with significantly high expression of uterine milk components such as glycodelin (PAEP) and osteopontin (SPP1), reflecting mid- to late-secretory phase physiology. This model successfully recapitulates human menstrual cycle dynamics and offers a promising platform for studying endometrial disorders and advancing personalized treatments in gynecology.

Artificial intelligence (AI) models often face performance drops after deployment to external datasets. This study evaluated the potential of a novel data augmentation framework based on generative adversarial networks (GANs) that creates synthetic patient image data for model training to improve model generalizability. Model development and external testing were performed for a given classification task, namely the detection of new fluid-attenuated inversion recovery lesions at MRI during longitudinal follow-up of patients with multiple sclerosis (MS). An internal dataset of 669 patients with MS ( n = 3083 examinations) was used to develop an attention-based network, trained both with and without the inclusion of the GAN-based synthetic data augmentation framework. External testing was performed on 134 patients with MS from a different institution, with MR images acquired using different scanners and protocols than images used during training. Models trained using synthetic data augmentation showed a significant performance improvement when applied on external data (area under the receiver operating characteristic curve [AUC], 83.6% without synthetic data vs 93.3% with synthetic data augmentation; P = .03), achieving comparable results to the internal test set (AUC, 95.0%; P = .53), whereas models without synthetic data augmentation demonstrated a performance drop upon external testing (AUC, 93.8% on internal dataset vs 83.6% on external data; P = .03). Data augmentation with synthetic patient data substantially improved performance of AI models on unseen MRI data and may be extended to other clinical conditions or tasks to mitigate domain shift, limit class imbalance, and enhance the robustness of AI applications in medical imaging. Keywords: Brain, Brain Stem, Multiple Sclerosis, Synthetic Data Augmentation, Generative Adversarial Network Supplemental material is available for this article. © RSNA, 2024.

Objective: To establish proof-of-concept for the dynamic prediction of adverse pregnancy outcome in women with a history of stillbirth or perinatal death, repeatedly throughout the pregnancy., Methods: A retrospective cohort study of women in a subsequent pregnancy following previous perinatal loss, who received antenatal care at a tertiary hospital between January 2014 and December 2017, was used as the basis for exploratory prognostic model development. Models were developed to repeatedly predict a composite adverse outcome (stillbirth or neonatal death, 5-min Apgar score < 7, umbilical artery pH ≤ 7.05, admission to the neonatal intensive care unit for longer than 24 h, preterm birth (< 37 completed weeks) or birth weight < 10 th centile) using the findings of sequential ultrasound scans for fetal biometry and umbilical and uterine artery Doppler., Results: In total, 506 participants were eligible, of whom 504 were included in the analysis. An adverse pregnancy outcome was experienced by 110 (22%) participants. The ability to predict the composite outcome using repeated head circumference and estimated fetal weight measurements improved as the pregnancy progressed (e.g. area under the receiver-operating-characteristics curve improved from 0.59 at 24 weeks' gestation to 0.74 at 36 weeks' gestation), supporting proof-of-concept. Predictors to include in dynamic prediction models were identified, including ultrasound measurements of fetal biometry, umbilical and uterine artery Doppler and placental size and shape., Conclusion: The present study supports proof-of-concept for dynamic prediction of adverse outcome in pregnancy following prior stillbirth or perinatal death, which could be used to identify risks earlier in pregnancy, while highlighting methodological challenges and requirements for subsequent large-scale model development studies. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To (1) construct a virtual patient (VP) using facial scan, intraoral scan, and low-dose computed tomography scab based on an Artificial intelligence (AI)-approach, (2) quantitatively compare it with AI-refined and semi-automatic registration, and (3) qualitatively evaluate user satisfaction when using virtual patient as a communication tool in clinical practice., Materials and Methods: A dataset of 20 facial scans, intraoral scans, and low-dose computed tomography scans was imported into the Virtual Patient Creator platform to create an automated virtual patient. The accuracy of the virtual patients created using different approaches was further analyzed in the Mimics software. The accuracy (% of corrections required), consistency, and time efficiency of the AI-driven virtual patient registration were then compared with the AI-refined and semi-automatic registration (clinical reference). User satisfaction was assessed through a survey of 35 dentists and 25 laypersons who rated the virtual patient's realism and usefulness for treatment planning and communication on a 5-point scale., Results: The accuracy for AI-driven, AI-refined, and semi-automatic registration virtual patient was 85 %, 85 %, and 100 % for the upper and middle thirds of the face, and 30 %, 30 %, and 35 % for the lower third. Registration consistency was 1, 1 and 0.99, and the average time was 26.5, 30.8, and 385 s, respectively (18-fold time reduction with AI). The inferior facial third exhibited the highest registration mismatch between facial scan and computed tomography. User satisfaction with the virtual patient was consistently high among both dentists and laypersons, with most responses indicating very high satisfaction regarding realism and usefulness as a communication tool., Conclusion: The AI-driven registration can provide clinically accurate, fast, and consistent virtual patient creation using facial scans, intraoral scans, and low-dose computed tomography scans, enabling interpersonal communication., Clinical Significance: Using AI for automated segmentation and registration of maxillofacial structures leads to clinically efficient and accurate VP creation, opening the doors for its widespread use in diagnosis, treatment planning, and interprofessional and professional-patient communication., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Vertebral Body Tethering (VBT), an alternative treatment for adolescent idiopathic scoliosis, shows satisfactory post-operative results. However, the biomechanical quantities and consequences after VBT surgery remain largely unknown. Therefore, the aim of this study is to analyze the spinal biomechanics during different motions using a multibody simulation approach., Methods: The tether and intervertebral compression forces were simulated in a validated spine model during different physiological movements at different pre-tensions and screw positions, while considering the anatomical muscle and ligament properties., Results: The simulations showed that an augmentation of the pre-tension and an alteration of the screw position have both significant impact on the intervertebral compression and tether forces. The forces also vary depending on the movement performed, with the highest tether forces measured during lateral bending. In the upright position, with a pre-tension of 200 N, the maximum compression force increases by up to 157% compared to the untethered maximum compression force. The screw position can lead to large differences in the distribution of forces in the spine., Conclusion: The biomechanical data provide a first impression of the forces that occur along the spine during various physiological movements and are consistent with published clinical data. Forces are not evenly distributed along the spine, with higher lumbar forces. The tether forces reach values during lateral bending that can potentially destroy the tether´s integrity and thus may explain the common post-operative complication, namely tether breakage. The results of the model can therefore have an impact on future directions for improved surgical VBT treatment., (© 2024. The Author(s).)

Background: Acute pancreatitis (AP) is a significant clinical challenge with rising global incidence and substantial mortality rates, necessitating effective treatment strategies. Current guidelines recommend pain and fluid management and early enteral feeding to mitigate complications, yet optimal feeding route remains debated., Methods: We conducted a prospective, randomized, controlled trial at nine centers from October 2020 to May 2023, enrolling 154 patients with moderate to severe AP. Patients were stratified into biliary and non-biliary categories and randomized 1:1 to receive either standard of care (SoC) or SoC plus PandiCath®, a novel catheter enabling selective enteral feeding and duodenal decompression. The primary clinical endpoint (PCE) was a composite of de novo multiple organ dysfunction syndrome (MODS), infectious complications, pancreatic and intestinal fistula formation, bleeding, abdominal compartment syndrome, obstructive jaundice, and AP-related mortality., Results: In the primary modified intention-to-treat analysis, PandiCath® significantly reduced the PCE compared to SoC alone (P = 0.032). The Relative Risk (RR = 0.469, 95 % CI 0.228-0.964) and Number Needed to Treat (NNT = 6.384, 95 % CI 3.349-68.167) indicated its substantial clinical benefit, primarily driven by reduced rates of de novo MODS and infectious complications. These findings were further supported by the evaluation of other populations, including the standard intention-to-treat analysis., Conclusion: PandiCath®, facilitating targeted enteral feeding while isolating and decompressing the duodenum, demonstrates promise in improving outcomes for AP patients at risk of severe complications. Further studies are warranted to validate these findings and explore optimal timing and patient selection for this intervention., Competing Interests: Declaration of competing interest Kunda R. received compensation from PANDICA LTD for consultancy services., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Antibiotic resistance poses a considerable worldwide concern, particularly in clinical environments where drug-resistant Gram-negative bacteria like Klebsiella pneumoniae (K. pneumoniae) present a major challenge. The objective of this research was to investigate the mechanisms by which isobavachalcone (IBC) restores the sensitivity of K. pneumoniae to colistin in vitro and to validate the synergistic therapeutic effect in vivo., Results: The results indicate that the combined administration of colistin and IBC exhibits a potent antibacterial effect both in vitro and in vivo. The in vitro concurrent administration of colistin and IBC resulted in increased membrane permeability, compromised cell integrity, diminished membrane fluidity, and disrupted membrane homeostasis. Additionally, this combination reduced biofilm production, inhibited the synthesis of the autoinducer factor, altered membrane potential, and affected levels of reactive oxygen species and adenosine triphosphate synthesis, ultimately leading to bacterial death. In vivo experiments on Galleria mellonella and mice demonstrated that the co-administration of colistin and IBC increased the survival rate and significantly reduced pathological damage compared to colistin alone., Conclusion: These results suggested that IBC effectively restores the sensitivity of colistin by inducing physical disruption of bacterial membranes and oxidative stress. The combination therapy of colistin and IBC presents a viable and safe strategy to combat drug-resistant K. pneumoniae-associated infections., Competing Interests: Declarations Funding: This study was supported by grants from the National Key R&D Program of China (2021YFD1800900), Natural Science Foundation of Gansu Province (22JR5RA042), and Science-Technology Innovation Engineering of CAAS (25-LZIHPS-02). Declaration of competing interests: The authors declare no conflict of interest. Ethical approval: Animal experiments were approved by the guidelines of the Animal Experimental Ethical Committee of Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS (2023 – 017). Sequence information: Not applicable. Data availability: The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation. Author contributions: Xiang Geng, Xiwang Liu, Jianyong Li, and Wanxia Pu conceived of and proposed the idea, designed the study. Xiang Geng, Yuxi Li, and Ruochen Hao conducted the experiments. Chunyan Xu, Yajun Yang, and Zhun Li performed the acquisition and analysis of data. Xiang Geng and Jianyong Li wrote and revised the manuscript. All authors contributed to the article and approved the submitted version., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objectives: To investigate whether the scanning time, trueness and number of photos are influenced when augmented reality (AR) heads-up display (HUD) is utilized during the intraoral scan of fully dentate mandibular arches., Methods: A total of 10 patients (6 females and 4 males) were included. The mandibular arch of each patient was scanned twice using an intraoral scanner (Trios4 Pod IOS: 3Shape): one with and one without AR-HUD (ML2; Magic Leap). Further, alginate impression was taken, and the cast was digitized to acquire the reference model for trueness comparison (T310, Medit). The scan time and number of photos were recorded. Trueness was evaluated qualitatively and quantitatively using colored heat maps and RMSE values respectively. t-test was used to evaluate the difference in scan time, trueness, and number of photos between the two groups (α = .05)., Results: AR-assisted IOS resulted in significantly faster scan time (44 s) compared to the time consumed following conventional scan method without AR-HUD (63 s) (P = <0.001). The number of photos was also significantly less with AR-assisted IOS (836) compared to IOS using conventional technique without AR-HUD (1209) P = <0.001. No statistical difference was detected in RMSE between the test groups., Conclusions: Integration of AR technology with IOS process represents a promising potential to acquire digital impressions with reduced scan acquisition time and reduced images count while simultaneously maintaining the trueness of the acquired scans., Clinical Significance: Augmented Reality presents an emerging potential in Prosthodontics to acquire digital impressions with decreased number of images and acquisition time., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Metabolomic research involves the comprehensive analysis of metabolites in biological samples and has many applications. Gas chromatography-mass spectrometry (GC-MS) is an established and widely used approach for metabolic profiling. However, sample preparation and metabolite derivatization are time-consuming, and derivatization options are limited. We propose gas-solid phase derivatization (GSPD) as a novel sampling and derivatization method that uses a silica monolith substrate and gaseous derivatization reagents for metabolomics using GC-MS. We developed a method to measure the organic acids and sugar phosphates responsible for glycolysis and the tricarboxylic acid (TCA) cycle. GSPD simplifies the sample preparation and can be applied to derivatization reactions that are difficult to perform in solution owing to solvent limitations. The developed method was applied to human plasma and tomato pulp and was shown to have a higher detection performance than the conventional method. This study provides a strategy to simplify sample preparation and expand derivatization options for GC-MS-based metabolomics., (Copyright © 2024 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

According to the principle of Locard "Every contact leaves a trace", when touching a surface, a bi-directional transfer of self and non-self-DNA residing on the hands and touched objects can occur. Metals are commonly encountered in forensic evidence and, during hand contact with these surfaces, a transfer of metal particles could occur together with the transfer of human DNA. This study proposes a proof-concept approach for the original detection of metal particles and touch DNA to track the activity performed by a donor and particularly to assess the metallic substrate touched before the contact with a subsequent surface. To this scope, a scenario of contact events was simulated by three volunteers, who participated in fingerprint deposition firstly on copper and then on plastic and glass surfaces. Twenty-four stubs were collected on the hands of volunteers and the secondary surfaces and then analyzed by environmental scanning electron microscopy (ESEM). DNA was quantified only from copper and plastic surfaces. Ten additional volunteers followed the same protocol of deposition on copper and then on plastic surfaces to evaluate DNA transfer only. On 20 touch DNA samples, the copper surface yielded significantly lower DNA amounts, ranging from 0.001 to 0.129 ng/μl, compared to the secondary touched plastic surface, ranging from 0.007 to 0.362 ng/μl. ESEM-EDS analysis showed that copper particles could be abundantly detected on the hands of the volunteers after contact with the copper surface. Particles containing silicates with copper were shown on plastic, while they were only found in 1/3 of samples on glass. Our proof-of-concept study has shown that ESEM-EDS analysis has the potential to detect copper particles transferred to the hands of volunteers during contact with a copper metallic surface and deposited on secondarily touched items. The results suggest that this original ESEM-DNA parallel approach could potentially allow the tracking of DNA transfer and metal particles at a crime scene, although this represents only a first step and further research on a wider casuistry could help to address the interpretation of results given activity level propositions., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective(s): Treatment for Zenker's diverticulum and cricopharyngeal dysfunction has evolved to include flexible endoscopic approaches. Currently, no flexible modalities combine the precision cutting of CO 2 laser and the hemostasis of knife electrocautery. We present the first series describing fiber-based 445nm blue light (BL) laser for endoscopic cricopharyngeal myotomy/Zenker's diverticulotomy. We describe usage characteristics and laser parameters with rigid esophagoscopy to determine the feasibility of use with flexible endoscopy., Methods: Retrospective review and literature review., Results: The first nine cases of endoscopic diverticulotomy (n = 5) and cricopharyngeal myotomy (n = 4) with BL were reviewed. Rigid exposure was achieved with the Dohlman Slimline diverticuloscope. Mean age was 75.6 years. Average diverticulum depth was 0.89 cm ±1.0 cm. Pulsed mode was used in seven cases with mean of 6.86 W, 54 ms pulse on, and 286 ms pulse pause and overall mean of 6.00 W and 405 J. Complete myotomy with intact buccopharyngeal fascia and without bleeding limiting view was achieved in all patients. One of two patients in whom continuous wave setting was used developed subcutaneous emphysema following vigorous cough on POD0; this resolved after 7 days nothing per oral (NPO). Eight patients were started on oral intake without evidence for leak. Pulsed mode with fiber-to-tissue contact provided effective muscle cutting without disruption of buccopharyngeal fascia. Literature review yielded three articles examining flexible approach with laser for Zenker's and none with BL., Conclusion: BL provides safe and effective fiber-based cutting and hemostasis in endoscopic cricopharyngeal myotomy/Zenker's diverticulotomy. Future use in flexible endoscopic approaches appears feasible, though continuous wave should be avoided., Level of Evidence: 4 Laryngoscope, 134:4620-4624, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Aim: To assess the possibility of vertical alveolar ridge augmentation by means of activation of the periosteum., Materials and Methods: Six adult male Beagle dogs were used for the study. All premolars and first molars were extracted, and one vertical saucer-shaped bony defect was created on each side of the mandible. After 3 months of healing, full-thickness muco-periosteal flaps were elevated, and one distraction device was placed on each side of the mandible. The distraction plate was left submerged, and the activation mechanism connected to the distraction rod was exposed intra-orally. The protocol of periosteal activation (PP: periosteal 'pumping') was initiated after a latency of 7 days. The alternation of activation and relaxation at the rate of 0.35 mm/12 h during 5 days was followed by the sole activation of 0.35 mm/12 h for 5 days (PP group). Devices were left inactivated on the contralateral control side of the mandible (C group). All animals were euthanized after 8 weeks of consolidation. Samples were analysed histologically and by means of micro-CT., Results: New mature lamellar bone was formed over the pristine bone in all groups. More intensive signs of bone modelling and remodelling were observed in the PP group compared to the C group. Mean new bone, bone marrow, connective tissue and total volumetric densities were greater in the PP group (p < 0.001, p = 0.001, p = 0.003 and p < 0.001, respectively). No differences were observed in the relative area parameters. Total tissue volume and bone volume were higher in the PP group (p = 0.031 and p = 0.076, respectively), while the bone mineral densities were higher in the C group (p = 0.041 and p = 0.003, respectively). Trabecular number, trabecular thickness and trabecular separation values were similar between the two groups., Conclusions: Regeneration of vertical alveolar bone ridge defects may be enhanced by activation of the periosteum, without the application of bone grafting materials., (© 2024 The Author(s). Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: Redo-transcatheter aortic valve replacement (TAVR) is a promising treatment for transcatheter aortic valve degeneration, becoming increasingly relevant with an aging population. In redo-TAVR, the leaflets of the initial (index) transcatheter aortic valve (TAV) are displaced vertically when the second TAV is implanted, creating a cylindrical cage that can impair coronary cannulation and flow. Preventing coronary obstruction and maintaining coronary access is essential, especially in young and low-risk patients undergoing TAVR. This study aimed to develop a new leaflet modification strategy using laser ablation to prevent coronary obstruction and facilitate coronary access after repeat TAVR., Methods: To evaluate the feasibility of the leaflet modification technique using laser ablation, the initial phase of this study involved applying a medical-grade ultraviolet laser for ablation through pericardial tissue. Following this intervention, computational fluid dynamics simulations were utilized to assess the efficacy of the resulting perforations in promoting coronary flow. These simulations played a crucial role in understanding the impact of the modifications on blood flow patterns, ensuring these changes would facilitate the restoration of coronary circulation., Results: Laser ablation of pericardium leaflets was successful, demonstrating the feasibility of creating openings in the TAV leaflets. Flow simulation results show that ablation of index valve leaflets can effectively mitigate the flow obstruction caused by sinus sequestration in redo-TAVR, with the extent of restoration dependent on the number and location of the ablated openings., Conclusions: Laser ablation could be a viable method for leaflet modification in redo-TAVR, serving as a new tool in interventional procedures., (© 2024 Wiley Periodicals LLC.)

Objectives: Objective estimation of minimum hearing levels using auditory brainstem responses (ABRs) elicited by single frequency tone-bursts presented monaurally is currently considered the gold standard. However, the data acquisition time to estimate thresholds (for both ears across four audiometric frequencies) using this method usually exceeds the sleep time (ranging between 35 and 49 minutes) in infants below 4 months, thus providing incomplete information of hearing status which in turn delays timely clinical intervention. Alternate approaches using faster rate, or tone-burst trains have not been readily accepted due to additional hardware and software requirements. We propose here a novel binaural multifrequency stimulation paradigm wherein several stimuli of different frequencies are presented binaurally in an interleaved manner. The rationale here is that the proposed paradigm will increase acquisition efficiency, significantly reduce test time, and improve accuracy by incorporating an automatic wave V detection algorithm. It is important to note that this paradigm can be easily implemented in most commercial ABR systems currently used by most clinicians., Design: Using this binaural multifrequency paradigm, ear specific ABRs were recorded in 30 normal-hearing young adults to both tone-bursts, and narrow-band (NB) iChirps at 500, 1000, 2000, and 4000 Hz. Comparison of ABRs elicited by tone-bursts and narrow-band chirps allowed us to determine if NB iChirps elicited a more robust wave V component compared with the tone-bursts. ABR data were characterized by measures of minimum hearing levels; wave V amplitude; and response detectability for two electrode configurations (high forehead-C7; and high forehead-linked mastoids)., Results: Consistent with the research literature, wave V response amplitudes were relatively more robust for NB iChirp stimuli compared with tone-burst stimuli. The easier identification and better detectability of wave V for the NB iChirps at lower stimulus levels contributed to their better thresholds compared with tone-burst elicited responses. It is important to note that binaural multifrequency hearing levels close to minimum hearing levels were determined in approximately 22 minutes using this paradigm-appreciably quicker than the 45 to 60 minutes or longer time required for threshold determination using the conventional single frequency method., Conclusions: Our novel and simple paradigm using either NB iChirps or tone-bursts provides a reliable method to rapidly estimate the minimum hearing levels across audiometric frequencies for both ears. Incorporation of an automatic wave V detection algorithm increases objectivity and further reduce test time and facilitate early hearing identification and intervention., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To evaluate the performance of vision transformer-derived image embeddings for distinguishing between normal and neoplastic tissues in the oropharynx and to investigate the potential of computer vision (CV) foundation models in medical imaging., Methods: Computational study using endoscopic frames with a focus on the application of a self-supervised vision transformer model (DINOv2) for tissue classification. High-definition endoscopic images were used to extract image patches that were then normalized and processed using the DINOv2 model to obtain embeddings. These embeddings served as input for a standard support vector machine (SVM) to classify the tissues as neoplastic or normal. The model's discriminative performance was validated using an 80-20 train-validation split., Results: From 38 endoscopic NBI videos, 327 image patches were analyzed. The classification results in the validation cohort demonstrated high accuracy (92%) and precision (89%), with a perfect recall (100%) and an F1-score of 94%. The receiver operating characteristic (ROC) curve yielded an area under the curve (AUC) of 0.96., Conclusion: The use of large vision model-derived embeddings effectively differentiated between neoplastic and normal oropharyngeal tissues. This study supports the feasibility of employing CV foundation models like DINOv2 in the endoscopic evaluation of mucosal lesions, potentially augmenting diagnostic precision in Otorhinolaryngology., Level of Evidence: 4 Laryngoscope, 134:4535-4541, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Eumycetoma is an implantation mycosis characterised by a large subcutaneous mass in the extremities commonly caused by the fungus Madurella mycetomatis. Despite the long duration of treatment, commonly a minimum of 12 months, treatment failure is frequent and can lead to amputation. We aimed to compare the efficacy of two doses of fosravuconazole, a synthetic antifungal designed for use in onychomycosis and repurposed for mycetoma, with standard-of-care itraconazole, both in combination with surgery., Methods: This phase 2, randomised, double-blind, active-controlled, superiority trial was conducted in a single centre in Sudan. Patients with eumycetoma caused by M mycetomatis, who were aged 15 years or older, with a set lesion diameter (>2 cm and ≤16 cm) requiring surgery were included. There was a limit of 20 female patients in the initial enrolment, owing to preclinical toxicity concerns. Exclusion criteria included previous surgical or medical treatment for eumycetoma; presence of loco-regional lymphatic extension; osteomyelitis, or other bone involvement; pregnancy or lactation; severe concomitant diseases; a BMI under 16 kg/m 2 ; contraindication to use of the study drugs; pre-existing liver disease; lymphatic extension; osteomyelitis; transaminase levels more than two times the laboratory's upper limit of normal, or elevated levels of alkaline phosphatase or bilirubin; or any history of hypersensitivity to any azole antifungal drug. Patients were randomly allocated in a 1:1:1 ratio to 300 mg fosravuconazole weekly for 12 months (group 1); 200 mg fosravuconazole weekly for 12 months (group 2); or 400 mg itraconazole daily for 12 months (group 3) using a random number list with non-disclosed fixed blocks of size 12, with equal allocation to each of the three arms within a block. To ensure masking between groups, placebo pills were used to disguise the difference in dosing schedules. All groups took pills twice daily with meals. In all groups, surgery was performed at 6 months. The primary outcome was complete cure at end of treatment at the month 12 visit, as evidenced by absence of mycetoma mass, sinuses, and discharge; normal ultrasonography or MRI examination of the eumycetoma site; and, if a mass was present, negative fungal culture from the former mycetoma site. The primary outcome was assessed in the modified intention-to-treat (mITT) population (all patients who received one or more treatment dose with one or more primary efficacy assessment). Safety was assessed in all patients who received one or more doses of the study drug. This study is registered with ClinicalTrials.gov (NCT03086226) and is complete., Findings: Between May 9, 2017, and June 10, 2021, 104 patients were randomly allocated (34 in group 1 and 2, respectively, and 36 in group 3). 86 (83%) of 104 patients were male and 18 (17%) patients were female. After an unplanned second interim analysis, the study was terminated early for futility. Complete cure at 12 months in the mITT population was 17 (50%) of 34 (95% CI 32-68) for group 1, 22 (65%) of 34 (47-80) for group 2, and 27 (75%) of 36 (58-88) in group 3. Neither dose of fosravuconazole was superior to itraconazole (p=0·35 for 200 mg fosravuconazole vs p=0·030 for 300 mg fosravuconazole). 83 patients had a total of 205 treatment-emergent adverse events, and two patients had serious adverse events that led to discontinuation, neither related to treatment., Interpretation: Treatment with either dose of fosravuconazole was not superior to itraconazole, and the two doses had a numerically lower efficacy. However, fosravuconazole presented no new safety signals, and its lower pill burden and reduced risk of drug-drug interactions compared with the relatively expensive and inaccessible itraconazole suggests further research into effective treatments with a shorter duration and higher cure rate, without the need for surgery are warranted., Funding: Drugs for Neglected Diseases initiative., Competing Interests: Declaration of interests BS declares consulting fees and other payments from Drugs for Neglected Diseases initiative (DNDi). KH is employed by the company that invented the study drug. All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Feeling loved by one's parents is critical for children's health and well-being. How can such feelings be fostered? A vital feature of loving interactions is reciprocal self-disclosure, where individuals disclose intimate information about themselves. In a proof-of-concept experiment, we examined whether encouraging reciprocal self-disclosure in parent-child dyads would make children feel more loved during the conversation. Participants were 218 children (ages 8-13, 50% girls, 94% Dutch) and one of their parents (ages 28-56, 62% women, 90% Dutch). Parent-child dyads received a list of 14 questions and took turns asking them each other for 9 min. Dyads were assigned randomly to engage in self-disclosure (questions invoking escalated intimacy) or small talk (questions invoking minimal intimacy). Before and after, children reported how loved they felt by their parent during the conversation. Self-disclosure made children feel more loved during the conversation than did small talk. Compared to small talk, self-disclosure did not instigate conversations that were lengthier or more positive; rather, it instigated conversations that were more emotionally charged (reflecting anger, anxiety, and sadness), social (discussing family and friends), reflective (creating insight), and meaningful (addressing deeply personal topics, including the passing of loved ones). The dyad's gender composition did not significantly moderate these effects. Our research suggests that reciprocal self-disclosure can make children feel more loved in the moment, uncovers linguistic signatures of reciprocal self-disclosure, and offers developmental scientists a tool to examine causal effects of reciprocal self-disclosure in parent-child dyads. Future work should examine long-term effects in everyday parent-child interactions. RESEARCH HIGHLIGHTS: How can parents make children feel more loved by them in the moment? We theorize that these feelings can be cultivated through reciprocal self-disclosure. In a proof-of-concept experiment, we examined effects of reciprocal self-disclosure versus small talk in 218 parent-child dyads, with children aged 8-13. Self-disclosure (vs. small talk) made children feel more loved during the conversation. Linguistically, self-disclosure instigated conversations that were more emotionally charged, social, reflective, and meaningful. This research provides an experimental method to study self-disclosure in parent-child dyads and suggests that self-disclosure can make children feel more loved in the moment., (© 2024 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

Introduction: Prosthetic valve endocarditis (PVE) is a serious complication of prosthetic valve implantation, with an estimated yearly incidence of at least 0.4-1.0%. The Duke criteria and subsequent modifications have been developed as a diagnostic framework for infective endocarditis (IE) in clinical studies. However, their sensitivity and specificity are limited, especially for PVE. Furthermore, their most recent versions (ESC2015 and ESC2023) include advanced imaging modalities, e.g., cardiac CTA and [ 18 F]FDG PET/CT as major criteria. However, despite these significant changes, the weighing system using major and minor criteria has remained unchanged. This may have introduced bias to the diagnostic set of criteria. Here, we aimed to evaluate and improve the predictive value of the modified Duke/ESC 2015 (MDE2015) criteria by using machine learning algorithms., Methods: In this proof-of-concept study, we used data of a well-defined retrospective multicentre cohort of 160 patients evaluated for suspected PVE. Four machine learning algorithms were compared to the prediction of the diagnosis according to the MDE2015 criteria: Lasso logistic regression, decision tree with gradient boosting (XGBoost), decision tree without gradient boosting, and a model combining predictions of these (ensemble learning). All models used the same features that also constitute the MDE2015 criteria. The final diagnosis of PVE, based on endocarditis team consensus using all available clinical information, including surgical findings whenever performed, and with at least 1 year follow up, was used as the composite gold standard., Results: The diagnostic performance of the MDE2015 criteria varied depending on how the category of 'possible' PVE cases were handled. Considering these cases as positive for PVE, sensitivity and specificity were 0.96 and 0.60, respectively. Whereas treating these cases as negative, sensitivity and specificity were 0.74 and 0.98, respectively. Combining the approaches of considering possible endocarditis as positive and as negative for ROC-analysis resulted in an excellent AUC of 0.917. For the machine learning models, the sensitivity and specificity were as follows: logistic regression, 0.92 and 0.85; XGBoost, 0.90 and 0.85; decision trees, 0.88 and 0.86; and ensemble learning, 0.91 and 0.85, respectively. The resulting AUCs were, in the same order: 0.938, 0.937, 0.930, and 0.941, respectively., Discussion: In this proof-of-concept study, machine learning algorithms achieved improved diagnostic performance compared to the major/minor weighing system as used in the MDE2015 criteria. Moreover, these models provide quantifiable certainty levels of the diagnosis, potentially enhancing interpretability for clinicians. Additionally, they allow for easy incorporation of new and/or refined criteria, such as the individual weight of advanced imaging modalities such as CTA or [ 18 F]FDG PET/CT. These promising preliminary findings warrant further studies for validation, ideally in a prospective cohort encompassing the full spectrum of patients with suspected IE., (© 2024. The Author(s).)

Background & Aims: Primary sclerosing cholangitis (PSC), often associated with inflammatory bowel disease (IBD), presents a multifactorial etiology involving genetic, immunologic, and environmental factors. Gut dysbiosis and bacterial translocation have been implicated in PSC-IBD, yet the precise mechanisms underlying their pathogenesis remain elusive. Here, we describe the role of gut pathobionts in promoting liver inflammation and fibrosis due to the release of bacterial outer membrane vesicles (OMVs)., Methods: Preclinical mouse models in addition to ductal organoids were used to acquire mechanistic data. A proof-of-concept study including serum and liver biopsies of a patient cohort of PSC (n = 22), PSC-IBD (n = 45), and control individuals (n = 27) was performed to detect OMVs in the systemic circulation and liver., Results: In both preclinical model systems and in patients with PSC-IBD, the translocation of OMVs to the liver correlated with enhanced bacterial sensing and accumulation of the NLRP3 inflammasome. Using ductal organoids, we were able to precisely attribute the pro-inflammatory and pro-fibrogenic properties of OMVs to signaling pathways dependent on Toll-like receptor 4 and NLRP3-gasdermin-D. The immunostimulatory potential of OMVs could be confirmed in macrophages and hepatic stellate cells. Furthermore, when we administered gut pathobiont-derived OMVs to Mdr2 -/- mice, we observed a significant enhancement in liver inflammation and fibrosis. In a translational approach, we substantiated the presence of OMVs in the systemic circulation and hepatic regions of severe fibrosis using a PSC-IBD patient cohort., Conclusions: This study demonstrates the contribution of gut pathobionts in releasing OMVs that traverse the mucosal barrier and, thus, promote liver inflammation and fibrosis in PSC-IBD. OMVs might represent a critical new environmental factor that interacts with other disease factors to cause inflammation and thus define potential new targets for fibrosis therapy., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Liver transplantation is used for treating end-stage liver disease, fulminant hepatitis, and oncological malignancies and organ shortage is a major limiting factor worldwide. The use of grafts based on extended donor criteria have become internationally accepted. Oxygenated machine perfusion technologies are the most recent advances in organ transplantation; however, it is only applied after a period of cold ischemia. Due to its high cost, we aimed to use a novel device, OxyFlush®, based on oxygenation of the preservation solution, applied during liver procurement targeting the maintenance of ATP during static cold storage (SCS)., Methods: Twenty patients were randomly assigned to the OxyFlush or control group based on a 1:1 ratio. In the OxyFlush group, the perfusion solution was oxygenated with OxyFlush® device while the control group received a non-oxygenated solution. Liver and the common bile duct (CBD) biopsies were obtained at three different time points. The first was at the beginning of the procedure, the second during organ preparation, and the third after total liver reperfusion. Biopsies were analyzed, and adenosine triphosphate (ATP) levels and histological scores of the liver parenchyma and CBD were assessed. Postoperative laboratory tests were performed., Results: OxyFlush® was able to maintain ATP levels during SCS and improved the damage caused by the lack of oxygen in the CBD. However, OxyFlush® did not affect laboratory test results and histological findings of the parenchyma., Conclusion: We present a novel low-cost device that is feasible and could represent a valuable tool in organ preservation during SCS., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: The risk of peritonitis has limited wider adoption of peritoneal dialysis (PD) in the United States. We developed a prototype bedside dialysate turbidity monitoring system, aiming to improve diagnostic accuracy relative to conventional approaches which depend on visual inspection and reporting of insensitive and non-specific symptoms., Methods: The prototype system was tested in a single-centre, proof-of-principle clinical study in patients receiving intermittent PD. We obtained multiple effluent dialysate samples from each consenting participant. We compared turbidity measurements with diagnostic criteria endorsed by the International Society of Peritoneal Dialysis (ISPD)., Results: Overall, we analysed 983 specimens from 65 patients, including 105 samples from patients with peritonitis and 878 samples from patients without peritonitis. An operating point derived from a previous in vitro study yielded an unadjusted sensitivity and specificity of 95.2% and 91.5%, respectively. The majority of samples that did not meet ISPD diagnostic criteria were either cases detected before criteria were met or were related to active peritonitis treatment and resolution., Conclusion: This proof-of-principle study demonstrates the feasibility and diagnostic accuracy of a prototype dialysate turbidity monitoring system for peritonitis surveillance., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BB, GW and GMC are advisors to CloudCath, and receive compensation for their effort. GG, MI and LA received grants from CloudCath to conduct the study. EY, AEB, BF and DW are employees of CloudCath.

Objective: Glucagon-like peptide-1 (GLP-1) analogues are currently the most widely used pharmacotherapies for weight loss. Their primary mechanism of action is attributed to reduction in energy intake. Data from murine studies also support an additional impact of those agents on energy homeostasis through upregulation of visceral adipose tissue (VAT) metabolic activity, but this remains uncertain in humans., Methods: Here, we present data from a proof-of-concept study on 30 individuals with obstructive sleep apnea and obesity who were randomized to a GLP-1 therapy-based weight loss regimen, continuous positive airway pressure, or a combination of both for 24 weeks. At baseline and study completion, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) was performed to evaluate VAT metabolic activity, expressed as VAT target to background ratio., Results: Treatment with GLP-1, but not with continuous positive airway pressure, was associated with a significant increase in VAT target to background ratio. There was a strong correlation between the increase in VAT metabolic activity and the degree of weight loss., Conclusions: These data support the hypothesis that upregulation of VAT metabolic activity by GLP-1 contributes to its weight loss action in humans, and this subject warrants further detailed investigation., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: Current photon-counting computed tomography (CT) systems utilize semiconductor detectors, such as cadmium telluride (CdTe), cadmium zinc telluride (CZT), and silicon (Si), which convert x-ray photons directly into charge pulses. An alternative approach is indirect detection, which involves Yttrium Orthosilicate (YSO) scintillators coupled with silicon photomultipliers (SiPMs). This presents an attractive and cost-effective option due to its low cost, high detection efficiency, low dark count rate, and high sensor gain., Objective: This study aims to establish a comprehensive quantitative imaging framework for three-energy-bin proof-of-concept photon-counting CT based on YSO/SiPM detectors developed in our group using multi-voltage threshold (MVT) digitizers and assess the feasibility of this spectral CT for material identification., Methods: We developed a proof-of-concept YSO/SiPM-based benchtop spectral CT system and established a pipeline for three-energy-bin photon-counting CT projection-domain processing. The empirical A-table method was employed for basis material decomposition, and the quantitative imaging performance of the spectral CT system was assessed. This evaluation included the synthesis errors of virtual monoenergetic images, electron density images, effective atomic number images, and linear attenuation coefficient curves. The validity of employing A-table methods for material identification in three-energy-bin spectral CT was confirmed through both simulations and experimental studies., Results: In both noise-free and noisy simulations, the thickness estimation experiments and quantitative imaging results demonstrated high accuracy. In the thickness estimation experiment using the practical spectral CT system, the mean absolute error for the estimated thickness of the decomposed Al basis material was 0.014 ± 0.010 mm, with a mean relative error of 0.66% ± 0.42%. Similarly, for the decomposed polymethyl methacrylate (PMMA) basis material, the mean absolute error in thickness estimation was 0.064 ± 0.058 mm, with a mean relative error of 0.70% ± 0.38%. Additionally, employing the equivalent thickness of the basis material allowed for accurate synthesis of 70 keV virtual monoenergetic images (relative error 1.85% ± 1.26%), electron density (relative error 1.81% ± 0.97%), and effective atomic number (relative error 2.64% ± 1.26%) of the tested materials. In addition, the average synthesis error of the linear attenuation coefficient curves in the energy range from 40 to 150 keV was 1.89% ± 1.07%., Conclusions: Both simulation and experimental results demonstrate the accurate generation of 70 keV virtual monoenergetic images, electron density, and effective atomic number images using the A-table method. Quantitative imaging results indicate that the YSO/SiPM-based photon-counting detector is capable of accurately reconstructing virtual monoenergetic images, electron density images, effective atomic number images, and linear attenuation coefficient curves, thereby achieving precise material identification., (© 2024 American Association of Physicists in Medicine.)

Introduction: Delays in discharging patients from Acute Medical Units hamper patient flows throughout the hospital. The decision to discharge a patient is mainly based on the patients' physiological condition, but may vary between physicians. An objective decision-support system based on patients' physiological data may help minimizing unnecessary delays in discharge. The aim of this proof-of-concept study is to assess the feasibility of predicting whether patients in an Acute Medical Unit are physiologically fit-for-discharge using machine learning with commonly available hospital data. Furthermore, this study investigated how long before actual time of discharge from the Acute Medical Unit we could predict discharge fitness. Also, the predictive importance of features extracted from these data was assessed., Methods: Electronic Medical Records of patients who participated in a Randomized Controlled Trial conducted in an Acute Medical Unit were used retrospectively (N = 199). Only commonly available hospital data were used. Logistic Regression and Random Forest models were applied to predict every hour whether patients were physiologically fit-for-discharge. Nested 5-fold cross-validation with 5 repeats was used to optimize the model hyperparameters and to estimate the predictive performances., Results: Physiological discharge fitness was predictable with reasonable performance for Logistic Regression (mean AUROC: 0.67) and Random Forest (mean AUROC: 0.69). For an intuitively chosen classification threshold of 0.8, mean specificity was 93.3 % and sensitivity 14.1 %. Models could predict physiological discharge fitness more than 24 h earlier than actual time of discharge for most patients who were correctly predicted to be fit-for-discharge. Patient characteristics, vital signs and laboratory results were shown to be important predictors., Conclusion: This proof-of-concept study showed that it is feasible to predict with machine learning whether patients in an Acute Medical Unit are physiologically fit-for-discharge using commonly available hospital data., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)