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Background: The primary aim of this proof-of-concept study was to investigate whether the Cardiac Power Index (CPI) could be a novel alternative method to assess fluid responsiveness in the prone position., Methods: Patients undergoing scheduled elective lumbar spine surgery in the prone position under general anesthesia were enrolled in the criteria of patients aged 19-75 years with American Society of Anesthesiologists (ASA) physical status I-II. The hemodynamic variables were evaluated before and after changes in posture after administering a colloid bolus (5 mL.kg -1 ) in the prone position. Fluid responsiveness was defined as an increase in the Stroke Volume Index (SVI) ≥ 10%., Results: A total of 28 patients were enrolled. In responders, the CPI (median [1/4Q-3/4Q]) decreased to 0.34 [0.28-0.39] W.m -2 (p = 0.035) after the prone position. After following fluid loading, CPI increased to 0.48 [0.37-0.52] W.m -2 (p < 0.008), and decreased SVI (median [1/4Q-3/4Q]) after prone increased from 26.0 [24.5-28.0] mL.m -2 to 33.0 [31.0-37.5] mL.m -2 (p = 0.014). Among non-responders, CPI decreased to 0.43 [0.28-0.53] W.m -2 (p = 0.011), and SVI decreased to 29.0 [23.5-34.8] mL.m -2 (p < 0.009). CPI exhibited predictive capabilities for fluid responsiveness as a receiver operating characteristic curve of 0.78 [95% Confidence Interval, 0.60-0.95; p = 0.025]., Conclusion: This study suggests the potential of CPI as an alternative method to existing preload indices in assessing fluid responsiveness in clinical scenarios, offering potential benefits for responders and non-responders., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Anestesiologia. Published by Elsevier España S.L.U. All rights reserved.)

Background: A noninvasive, wearable continuous glucose monitor would be a major advancement in diabetes therapy. This trial investigated a novel noninvasive glucose monitor which analyzes spectral variations in radio frequency/microwave signals reflected from the wrist., Methods: A single-arm, open-label, experimental study compared glucose values from a prototype investigational device with laboratory glucose measurements from venous blood samples (Super GL Glucose Analyzer, Dr. Müller Gerätebau GmbH) at varying levels of glycemia. The study included 29 male participants with type 1 diabetes (age range = 19-56 years). The study comprised three stages with the following aims: (1) demonstrate initial proof-of-principle, (2) test an improved device design, and (3) test performance on two consecutive days without device recalibration. The co-primary endpoints in all trial stages were median and mean absolute relative difference (ARD) calculated across all data points., Results: In stage 1, the median and mean ARDs were 30% and 46%, respectively. Stage 2 produced marked performance improvements with a median and mean ARD of 22% and 28%, respectively. Stage 3 showed that, without recalibration, the device performed as well as the initial prototype (stage 1) with a median and mean ARD of 35% and 44%, respectively., Conclusion: This proof-of-concept study shows that a novel noninvasive continuous glucose monitor was capable of detecting glucose levels. Furthermore, the ARD results are comparable to first models of commercially available minimally invasive products without the need to insert a needle. The prototype has been further developed and is being tested in subsequent studies., Trial Registration Number: NCT05023798., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Although a majority of patients in the U.S. receive post-acute care in skilled nursing facilities (SNFs) following hip fracture, large-sample observational studies of analgesic prescribing and use in SNFs have not been possible due to limitations in available data sources. We conducted a proof-of-concept federated analysis of electronic health records (EHRs) from 11 SNF chains to describe analgesic use during hip fracture post-acute care., Methods: We included residents with a diagnosis of hip fracture between January 1, 2018 and June 30, 2021 who had at least one administration of an analgesic. Use of analgesics was ascertained from EHR medication orders and medication administration records. We quantified the proportion of residents receiving analgesic regimens based on the medications that were administered up to 100 days after hip fracture diagnosis. Plots visualizing trends in analgesic use were stratified by multiple resident characteristics including age and Alzheimer's Disease and Related Dementias (ADRD) diagnosis., Results: The study included 23,706 residents (mean age 80.5 years, 68.6% female, 87.7% White). Most (~ 60%) residents received opioids + APAP. Monotherapy with APAP or opioids was also common. The most prevalent regimens were oxycodone + APAP (20.1%), hydrocodone + APAP (15.8%), APAP only (15.1%), tramadol + APAP (10.4%), and oxycodone only (4.3%). During the study period, use of APAP-only increased, opioids-only decreased, and opioids + APAP remained stable. Use of APAP-only appeared to be more prevalent among individuals aged > 75 years (versus ≤ 75 years) and those with ADRD (versus without)., Conclusions: We successfully leveraged federated SNF EHR data to describe analgesic use among residents receiving hip fracture post-acute care., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Bimolecular fluorescence complementation (BiFC) methodology uses split fluorescent proteins to detect interactions between proteins in living cells. To date, BiFC has been used to investigate receptor dimerization by splitting the fluorescent protein between the intracellular portions of different receptor components. We reasoned that attaching these split proteins to the extracellular N-terminus instead may improve the flexibility of this methodology and reduce the likelihood of impaired intracellular signal transduction. As a proof-of-concept, we used receptors for calcitonin gene-related peptide, which comprise heterodimers of either the calcitonin or calcitonin receptor-like receptor in complex with an accessory protein (receptor activity-modifying protein 1). We created fusion constructs in which split mVenus fragments were attached to either the C-termini or N-termini of receptor subunits. The resulting constructs were transfected into Cos7 and HEK293S cells, where we measured cAMP production in response to ligand stimulation, cell surface expression of receptor complexes, and BiFC fluorescence. Additionally, we investigated ligand-dependent internalization in HEK293S cells. We found N-terminal fusions were better tolerated with regards to cAMP signaling and receptor internalization. N-terminal fusions also allowed reconstitution of functional fluorescent mVenus proteins; however, fluorescence yields were lower than with C-terminal fusion. Our results suggest that BiFC methodologies can be applied to the receptor N-terminus, thereby increasing the flexibility of this approach, and enabling further insights into receptor dimerization., (© 2024 The Author(s).)

This study aims to develop explainable AI methods for matching patients with phase 1 oncology clinical trials using Natural Language Processing (NLP) techniques to address challenges in patient recruitment for improved efficiency in drug development. A prototype system based on modern NLP techniques has been developed to match patient records with phase 1 oncology clinical trial protocols. Four criteria are considered for the matching: cancer type, performance status, genetic mutation, and measurable disease. The system outputs a summary matching score along with explanations of the evidence. The outputs of the AI system were evaluated against the ground truth matching results provided by the domain expert on a dataset of twelve synthesized dummy patient records and six clinical trial protocols. The system achieved a precision of 73.68%, sensitivity/recall of 56%, accuracy of 77.78%, and specificity of 89.36%. Further investigation into the misclassified cases indicated that ambiguity of abbreviation and misunderstanding of context are significant contributors to errors. The system found evidence of no matching for all false positive cases. To the best of our knowledge, no system in the public domain currently deploys an explainable AI-based approach to identify optimal patients for phase 1 oncology trials. This initial attempt to develop an AI system for patients and clinical trial matching in the context of phase 1 oncology trials showed promising results that are set to increase efficiency without sacrificing quality in patient-trial matching., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ghosh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The growing concern on adolescent mental health calls for proactive early detection and intervention strategies. There is a recognition of the link between digital phenotypes and mental health, drawing attention to their potential use. However, the process of collecting digital phenotype data presents challenges despite its promising prospects., Objective: This study aims to develop and validate system concepts for collecting adolescent digital phenotypes that effectively manage inherent challenges in the process., Methods: In a formative investigation (N=34), we observed adolescent self-recording behaviors and conducted interviews to develop design goals. These goals were then translated into system concepts, which included planners resembling interfaces, simplified data input with tags, visual reports on behaviors and moods, and supportive ecological momentary assessment (EMA) prompts. A proof-of-concept study was conducted over 2 weeks (n=16), using tools that simulated the concepts to record daily activities and complete EMA surveys. The effectiveness of the system was evaluated through semistructured interviews, supplemented by an analysis of the frequency of records and responses., Results: The interview findings revealed overall satisfaction with the system concepts, emphasizing strong support for self-recording. Participants consistently maintained daily records throughout the study period, with no missing data. They particularly valued the recording procedures that aligned well with their self-recording goal of time management, facilitated by the interface design and simplified recording procedures. Visualizations during recording and subsequent report viewing further enhanced engagement by identifying missing data and encouraging deeper self-reflection. The average EMA compliance reached 72%, attributed to a design that faithfully reflected adolescents' lives, with surveys scheduled at convenient times and supportive messages tailored to their daily routines. The high compliance rates observed and positive feedback from participants underscore the potential of our approach in addressing the challenges of collecting digital phenotypes among adolescents., Conclusions: Integrating observations of adolescents' recording behavior into the design process proved to be beneficial for developing an effective and highly compliant digital phenotype collection system., (©Minseo Cho, Doeun Park, Myounglee Choo, Jinwoo Kim, Doug Hyun Han. Originally published in JMIR Formative Research (https://formative.jmir.org), 24.10.2024.)

The development of effective vaccines against Hepatitis C Virus (HCV) remains a global health priority and challenge. In this study, we employed an integrative approach combining computational epitope prediction with experimental validation to identify immunogenic peptides targeting the E1 glycoprotein of HCV. In the present report, computational data from various epitope prediction algorithms such as IEDB and SYFPEITHI, followed by molecular dynamics (MD) simulations and immuno-informatics analysis is presented. Through computational screening, we identified potential epitope candidates, with QVRNSSGLY (P3) and QLFTFSPRH (P7) emerging as promising candidates. MD simulations revealed stable interactions between these epitopes and MHC molecule, further validated by free energy estimations using MMPBSA method. Immuno-informatics analysis supported these findings, showing high binding potential and immunogenicity scores for the selected peptides. Subsequent synthesis and characterization of epitope peptides confirmed their structural integrity and purity required for conducting immune activation assays. Experimental immunological assays carried out in this study involved epitope peptide induced activation of CD8 + and CD4 + T cells from healthy human subjects and HCV- recovered patients. Data from experimental validation revealed significant cytokine release upon exposure to epitope peptides, particularly TNF-a, IL-6, and GM-CSF, indicative of robust immune responses. Notably, peptides P3 and P7 exhibited the most pronounced cytokine induction profiles, underscoring their potential as vaccine candidates. Further investigations addressing the mechanism of action of these epitope peptides under preclinical and clinical settings may help in developing effective vaccine against HCV., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [All the methods involving the ethical concerns were performed in accordance with the relevant guidelines and regulations of Institutional Ethical Committee of Savitribai Phule Pune University, Pune, India]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Emerging evidence suggests that cancer stemness plays a crucial role in tumor progression, metastasis, and chemoresistance. Upon exposure to internal or external stress, ribosomes stand sentinel and facilitate diverse biological processes, including oncological responses. In the present study, ribosome-inactivating stress (RIS) was evaluated for its modulation of cancer cell stemness as a pivotal factor of tumor cell reprogramming. Based on the concept of stress-responsive cancer cell stemness, we addressed human intestinal cancer cell line-based off-the-shelf spheroid cultures. Intestinal cancer cell line-based spheroids exhibited heightened levels of CD44 + CD133 + cancer stemness, which was improved by chemical-induced RIS. Further evaluations revealed the potential of these stress-imprinted spheroids as a platform for chemoresistance screening. Compared to adherent cells, stemness-improved spheroid cultures displayed reduced apoptosis in response to 5-fluorouracil (5-FU), a frontline chemotherapeutic agent against colorectal cancer. Moreover, serial subcultures with repeated RIS exposure maintained and even enhanced cancer stemness and chemoresistance patterns. In particular, isolated CD44 + CD133 + cancer stem cells exhibited higher chemoresistance compared to unsorted cells. To elucidate the mechanisms underlying RIS-induced stemness, RNA-seq analysis identified Wnt signaling pathways and stemness-associated signals as notable features in spheroids exposed to RIS. Loss-of-function studies targeting connective tissue growth factor (CTGF), a negative regulator of Wnt signaling, revealed that CTGF-deficient spheroids exhibited improved cancer stemness and resistance to 5-FU, with RIS further enhancing these effects. In conclusion, this proof-of-concept study demonstrates the feasibility of leveraging stress-responsive cancer stemness for the development of spheroid-based platforms for chemoresistance evaluation and elucidation of pathophysiological processes of colorectal tumorigenesis under environmental stress.

Background: Despite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment options. Adenoviral vascular endothelial growth factor-D ΔNΔC (AdVEGF-D)-encoding gene therapy (GT) holds promise for the treatment of refractory angina., Methods: ReGenHeart is an investigator-initiated, multicentre, randomised, placebo-controlled and double-blinded phase 2 clinical trial that aims to study the safety and efficacy of intramyocardially administered angiogenic AdVEGF-D GT for refractory angina. Patients will be randomised in a 2:1 ratio and blocks of six to receive either AdVEGF-D or placebo. Primary endpoints are improvements in functional capacity assessed with the 6 min walking test and angina symptoms with Canadian Cardiovascular Society class after 6 month follow-up. Secondary endpoints are improvements in myocardial perfusion assessed with either positron emission tomography or single-photon emission CT after 6 month follow-up and functional capacity and angina symptoms after 12 months. In addition, changes in the quality of life, the use of angina medication and the incidence of major adverse cardiac and cerebrovascular events will be evaluated., Conclusions: The phase 2 ReGenHeart trial will provide knowledge of the safety and efficacy of AdVEGF-D GT to ameliorate symptoms in refractory angina patients, extending and further testing positive results from the preceding phase 1/2a trial., Competing Interests: Competing interests: JEKH received consultancy fees from Novo Nordisk and speaker fees from the BMS-Pfizer alliance. JK received consultancy fees from GE Healthcare and Synektik and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer-Ingelheim, Pfizer, Siemens Healthineers and Merck, outside of the submitted work. AS received consultancy fees from Amgen, Astra Zeneca, Boehringer Ingelheim and Pfizer, and speaker fees from Abbott, Astra Zeneca and Bayer. Other authors declare that they have no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments., Objectives: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids., Methods: PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomized to either secukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W) or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤ 2 at week 16., Results: Overall, 111 patients were randomized (n = 37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the three cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤ 2 response at week 16 with SECQ4W vs. placebo in the MLP {37.5% [95% credibility interval (Crl) 20.3-57.2] vs. 23.1% (95% Crl 6.5-49.2)} and LPP cohorts [37.5% (95% Crl 20.2-57.3) vs. 30.8% (95% Crl 10.8-57.6)]. In the LPP cohort, a sustained response for IGA ≤ 2 from week 16 to week 32 was achieved with SECQ4W (week 16, 37.5%; week 32, 45.8%), and a substantial improvement was observed in IGA ≤ 2 response in patients from this cohort who switched from placebo (week 16, 30.8%) to SECQ2W after week 16 (week 32, 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals., Conclusions: PRELUDE is the first randomized controlled basket trial evaluating interleukin (IL)-17A inhibition with secukinumab across three subtypes of LP. Secukinumab was well tolerated and safe, showing different response rates across the three subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of IL-17A across LP subtypes. The novel IGA score showed significant correlation with both patient- and physician-reported outcome measurements., Competing Interests: Conflicts of interest T.P. has received honoraria and/or consultation fees from AbbVie, Almirall, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, UCB Pharma and Vyne Therapeutics. He is a cofounder of YUKIN Therapeutics. B.E. has served as a consultant and/or clinical study investigator for AbbVie, Acelyrin, Aclaris, Allakos, Almirall, Alumis, Amgen, AnaptysBio, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert Pharma, Dermavant Sciences, Dermira Inc., Eli Lilly, Evelo Biosciences, Evommune, Incyte, Janssen, Kymab, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Priovant, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma and Ventyx, and as a paid speaker for Dermavant, Incyte, LEO Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Regeneron and Sanofi Genzyme. J.W. has served as an investigator/advisor and/or speaker for AbbVie, Aclaris, Almirall, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dr Reddy’s, EPI Health, Foamix/Vyne, Galderma, Incyte, Janssen, LEO Pharma, Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB Pharma and Verrica. M.S. is an investigator, speaker, consultant/advisory board member, and participated in clinical trials with the following companies: AbbVie, Amgen, BMS, Celgene, Galderma, GSK, Janssen Cilag, Leo, Lilly, MSD, Mundipharma, Novartis, Regeneron, Pfizer, Sanofi, and UCB. P.R. has been an investigator, speaker, or member of an advisory board for Bristol Myers Squibb, Concert Pharmaceutical, Ducray, Legacy Healthcare, LEO Pharma, Lilly, L’Oreal Research, Novartis, Pfizer, Pierre Fabre Dermatologie and Vichy Laboratories. J.W. has received grants for scientific projects, clinical studies, lectures or consultancy from the following companies in the last 5 years: Abbott, AbbVie, Actelion, Allergika, Almirall, Aristo, BayPharma, Beiersdorf, Biogen, BMS, Boehringer Ingelheim, Celltrion, Dermapharm, Evolva, Galderma, GSK, Helm, Hexal, Incyte, Infectopharm, Janssen-Cilag, Jenapharm, Johnson & Johnson, Klinge, LEO, Lilly, L’Oréal, Medac, Medice, Mibe, MSD, Mylan, Novaliq, Novartis, Pierre Fabre, Pfizer, Regeneron, Rigi, Skinomics and Wolff. M.H. has received honoraria and/or consultation fees from AbbVie, Argenx, Biotest, Janssen, Novartis, Pfizer, Sanofi Genzyme and Topas Therapeutics. M.R., E.M., H.F., and I.H. are employees and stockholders of Novartis. N.C. was an employee of Novartis Pharma AG at the time of the study and is a stockholder of Novartis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

A machine learning-assisted 3D-printed conducting microneedle-based electrochemical sensing platform was developed for wireless, efficient, economical, and selective determination of buprenorphine. The developed microneedle array-based sensing platform used 3D printing and air spray coating technologies for rapid and scalable manufacturing of a conducting microneedle surface. Upon optimization and understanding of the electrode stability, redox behavior, and electrochemical characteristics of as-prepared conducting microneedle array, the developed electrochemical platform was investigated for monitoring different levels of buprenorphine in the artificial intestinal fluid and found to be highly sensitive and selective towards buprenorphine for a wide detection range from 2 to 140 μM, with a low limit of detection of 0.129 μM. Furthermore, to make the sensing platform user accessible, the experimentally recorded sensing data was used to train a machine learning model and develop a web application for the numerical demonstration of buprenorphine levels at the point of site. Finally, the proof-of-concept study demonstrated that by advancing our prevailing 3D printing and additive manufacturing techniques, a low-cost, user-accessible, and compelling wearable electrochemical sensor could be manufactured for minimally invasive determination of buprenorphine in interstitial fluid., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Misfolding and aggregation of amyloid β (Aβ), along with neurofibrillary tangles consisting of aggregated Tau species, are pathological hallmarks of Alzheimer's disease (AD) onset and progression. In this study, we hypothesized the clearance of Aβ aggregates from the brain and body into the gut., Methods: To investigate this, we used surface-based fluorescence intensity distribution analysis (sFIDA) to determine the Aβ aggregate concentrations in feces from 26 AD patients and 31 healthy controls (HC)., Results: Aβ aggregates were detectable in human feces and their concentrations were elevated in AD patients compared to HC (specificity 90.3%, sensitivity 53.8%)., Conclusion: Thus, fecal Aβ aggregates constitute a non-invasive biomarker candidate for diagnosing AD. Whether digestion-resistant Aβ aggregates in feces are secreted via the liver and bile or directly from the enteric neuronal system remains to be elucidated., (© 2024. The Author(s).)

Objective. Cavitation dose monitoring plays a key role in ultrasound drug delivery to the brain. The use of capacitive micromachined ultrasonic transducer (CMUT) technology has a great potential for passive cavitation detection (PCD). Approach. Here, a circular (diameter 7 mm) CMUT centered at 5 MHz was designed to be inserted into a therapeutic transducer (1.5 MHz) used for ultrasound-induced blood-brain barrier (BBB) disruption on mice. CMUT-based real-time cavitation detection was performed during the ultrasound procedure (50 μ l intravenous injection of SonoVue microbubbles, frequency 1.5 MHz, PNP 480 kPa, duty Cycle 10%, PRF 10 Hz, duration 60 s). BBB disruption were confirmed by contrast-enhanced 7T-MRI. Main results. The CMUT device has a fractional bandwidth of 140%, almost twice a conventional piezocomposite PCD transducer. As expected, the CMUT device was able to detect the occurrence of harmonic, subharmonic and ultraharmonic frequencies as well as the increase of broadband signal indicating inertial cavitation in a wide frequency range (from 0.75 to 6 MHz). Signal-to-noise ratio was high enough (>40 dB) to perform ultrafast monitoring and follow the subtle intrapulse variations of frequency components at a rate of 10 kHz. Significance . This first in vivo proof of concept demonstrates the interest of CMUT for PCD and encourages us to develop devices for PCD in larger animals by integrating an amplifier directly to the CMUT front-end to considerably increase the signal-to-noise ratio., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objective: To determine the safety and proof of concept of a parcel-guided, repetitive Transcranial Magnetic Stimulation (rTMS) in patients who develop a heterogeneous array of symptoms, known collectively as post-concussive syndrome (PCS), following traumatic brain injury (TBI)., Methods: We performed a retrospective review of off-label, individualized, parcel-guided rTMS in 19 patients from December 2020 to May 2023. Patients had at least one instance of mild, moderate, or severe TBI and developed symptoms not present prior to injury. rTMS targets were identified based on machine learning connectomic software using functional connectivity anomaly matrices compared to healthy controls. EuroQol (EQ-5D), as a measurement of quality of life, and additional questionnaires dependent on individual's symptoms were submitted prior to, after, and during follow-up from rTMS., Results: Nineteen patients showed improvement in EQ-5D and Rivermead Post Concussion Symptoms Questionnaires - 3 after treatment and follow-up. For nine patients who developed depression, five (55%) attained response and remission based on the Beck Depression Inventory after treatment. Eight of ten patients with anxiety had a clinically significant reduction in Generalized Anxiety Disorder-7 scores during follow-up., Conclusion: Parcel-guided rTMS is safe and may be effective in reducing PCS symptoms following TBI and should incite further controlled studies.

Binaural beat (BB) has been investigated as a potential modality to enhance sleep quality. In this study, we introduce a new form of BB, referred to as dynamic BB (DBB), which incorporates dynamically changing carrier frequency differences between the left and right ears. Specifically, the carrier frequency of the right ear varied between 100 and 103 Hz over a period, while the left ear remained fixed at 100 Hz, yielding a frequency difference range of 0 to 3 Hz. The objective of this study was to examine the effect of DBB on sleep quality. Ten healthy participants were included in a cross-over design, where they experienced both DBB and a SHAM (absence of sound) condition across two consecutive nights, with polysomnography evaluation. DBB was administrated during pre-sleep initiation, sleep onset, and transition from rapid eye movement (REM) to non-REM stage. DBB significantly reduced sleep latency compared to the SHAM condition. Electrocardiogram analysis revealed that exposure to DBB led to diminished heart rate variability during the pre-sleep initiation and sleep onset periods, accompanied by a decrease in low-frequency power of heart rate during the sleep onset period. DBB might be effective in improving sleep quality, suggesting its possible application in insomnia treatments., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The emergence of hitherto unknown viral pathogens presents a great challenge for researchers to develop effective therapeutics and vaccines within a short time to avoid an uncontrolled global spread, as seen during the coronavirus disease 2019 (COVID-19) pandemic. Therefore, rapid and simple methods to identify immunogenic antigens as potential therapeutical targets are urgently needed for a better pandemic preparedness. To address this problem, we chose the well-characterized Modified Vaccinia virus Ankara (MVA)-T7pol expression system to establish a workflow to identify immunogens when a new pathogen emerges, generate candidate vaccines, and test their immunogenicity in an animal model. By using this system, we detected severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) nucleoprotein (N)-, and spike (S)-specific antibodies in COVID-19 patient sera, which is in line with the current literature and our observations from previous immunogenicity studies. Furthermore, we detected antibodies directed against the SARS-CoV-2-membrane (M) and -ORF3a proteins in COVID-19 patient sera and aimed to generate recombinant MVA candidate vaccines expressing either the M or ORF3a protein. When testing our candidate vaccines in a prime-boost immunization regimen in humanized HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II -knockout mice, we were able to demonstrate M- and ORF3a-specific cellular and humoral immune responses. Hence, the established workflow using the MVA-T7pol expression system represents a rapid and efficient tool to identify potential immunogenic antigens and provides a basis for future development of candidate vaccines.

Background: Digital interventions hold promise for improving physical activity in adolescents. However, a lack of empirical decision points (eg, timing of intervention prompts) is an evidence gap in the optimization of digital physical activity interventions., Objective: The study examined the feasibility and acceptability, as well as the technical and functional reliability, of and participant engagement with a digital intervention that aligned its decision points to occur during times when adolescents typically exercise. This study also explored the impact of the intervention on adolescents' moderate to vigorous physical activity (MVPA) levels. Consistent with the Obesity-Related Behavioral Interventions Trials (ORBIT) model, the primary goal of the study was to identify opportunities to refine the intervention for preparation for future trials., Methods: Ten adolescents completed a 7-day baseline monitoring period and Temporally Augmented Goal Setting (TAGS), a 20-day digital physical activity intervention that included a midday self-monitoring message that occurred when adolescents typically start to exercise (3 PM). Participants wore an accelerometer to measure their MVPA during the intervention. Participants completed questionnaires about the acceptability of the platform. Rates of recruitment and attrition (feasibility), user and technological errors (reliability), and engagement (average number of text message responses to the midday self-monitoring message) were calculated. The investigation team performed multilevel models to explore the effect of TAGS on MVPA levels from preintervention to intervention. In addition, as exploratory analyses, participants were matched to adolescents who previously completed a similar intervention, Network Underwritten Dynamic Goals Engine (NUDGE), without the midday self-monitoring message, to explore differences in MVPA between interventions., Results: The TAGS intervention was mostly feasible, acceptable, and technically and functionally reliable. Adolescents showed adequate levels of engagement. Preintervention to intervention changes in MVPA were small (approximately a 2-minute change). Exploratory analyses revealed no greater benefit of TAGS on MVPA compared with NUDGE., Conclusions: TAGS shows promise for future trials with additional refinements given its feasibility, acceptability, technical and functional reliability, participants' rates of engagement, and the relative MVPA improvements. Opportunities to strengthen TAGS include reducing the burden of wearing devices and incorporating of other strategies at the 3 PM decision point. Further optimization of TAGS will inform the design of a Just-in-Time Adaptive Intervention for adolescent physical activity and prepare the intervention for more rigorous testing., (©Adrian Ortega, Christopher C Cushing. Originally published in JMIR Formative Research (https://formative.jmir.org), 10.10.2024.)

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by the predisposition to develop tumors such as malignant peripheral nerve sheath tumors (MPNSTs) which represents the primary cause of death for NF1-affected patients. Regardless of the high incidence and mortality, the molecular mechanisms underneath MPNST growth and metastatic progression remain poorly understood. In this proof-of-concept study, we performed somatic whole-exome sequencing (WES) to profile the genomic alterations in four samples from a patient with NF1-associated MPNST, consisting of a benign plexiform neurofibroma, a primary MPNST, and metastases from lung and skin tissues. By comparing genomic patterns, we identified a high level of variability across samples with distinctive genetic changes which allow for the definition of profiles of the early phase with respect to the late metastatic stages. Pathogenic and likely pathogenic variants were abundant in the primary tumor, whereas the metastatic samples exhibited a high level of copy-number variations (CNVs), highlighting a possible genomic instability in the late phases. The most known MPNST-related genes, such as TP53 and SUZ12 , were identified in CNVs observed within the primary tumor. Pathway analysis of altered early genes in MPNST pointed to a potential role in cell motility, division and metabolism. Moreover, we employed survival analysis with the TCGA sarcoma genomic dataset on 262 affected patients, in order to corroborate the predictive significance of the identified early and metastatic MPNST driver genes. Specifically, the expression changes related to the mutated genes, such as in RBMX , PNPLA6 and AGAP2 , were associated with reduced patient survival, distinguishing them as potential prognostic biomarkers. This study underlines the relevance of integrating genomic results with clinical information for early diagnosis and prognostic understanding of tumor aggressiveness.

Purpose: Large language models (LLM) show potential for decision support in breast cancer care. Their use in clinical care is currently prohibited by lack of control over sources used for decision-making, explainability of the decision-making process and health data security issues. Recent development of Small Language Models (SLM) is discussed to address these challenges. This preclinical proof-of-concept study tailors an open-source SLM to the German breast cancer guideline (BC-SLM) to evaluate initial clinical accuracy and technical functionality in a preclinical simulation., Methods: A multidisciplinary tumor board (MTB) is used as the gold-standard to assess the initial clinical accuracy in terms of concordance of the BC-SLM with MTB and comparing it to two publicly available LLM, ChatGPT3.5 and 4. The study includes 20 fictional patient profiles and recommendations for 5 treatment modalities, resulting in 100 binary treatment recommendations (recommended or not recommended). Statistical evaluation includes concordance with MTB in % including Cohen's Kappa statistic (κ). Technical functionality is assessed qualitatively in terms of local hosting, adherence to the guideline and information retrieval., Results: The overall concordance amounts to 86% for BC-SLM (κ = 0.721, p < 0.001), 90% for ChatGPT4 (κ = 0.820, p < 0.001) and 83% for ChatGPT3.5 (κ = 0.661, p < 0.001). Specific concordance for each treatment modality ranges from 65 to 100% for BC-SLM, 85-100% for ChatGPT4, and 55-95% for ChatGPT3.5. The BC-SLM is locally functional, adheres to the standards of the German breast cancer guideline and provides referenced sections for its decision-making., Conclusion: The tailored BC-SLM shows initial clinical accuracy and technical functionality, with concordance to the MTB that is comparable to publicly-available LLMs like ChatGPT4 and 3.5. This serves as a proof-of-concept for adapting a SLM to an oncological disease and its guideline to address prevailing issues with LLM by ensuring decision transparency, explainability, source control, and data security, which represents a necessary step towards clinical validation and safe use of language models in clinical oncology., (© 2024. The Author(s).)

Background: Longitudinal T1 relaxation time is a key imaging biomarker. In addition, T1 values are modulated by the administration of T1 contrast agents used in patients with tumors and metastases. However, in clinical practice, dedicated T1 mapping sequences are often not included in brain MRI protocols. The aim of this study is to address the absence of dedicated T1 mapping sequences in imaging protocol by deriving T1 maps from standard T1-weighted sequences., Methods: A phantom, composed of 144 solutions of paramagnetic agents at different concentrations, was imaged with a three-dimensional (3D) T1-weighed turbo spin-echo (TSE) sequence designed for brain imaging. The relationship between the T1 values and the signal intensities was established using this phantom acquisition. T1 mapping derived from 3D T1-weighted TSE acquisitions in four healthy volunteers and one patient with brain metastases were established and compared to reference T1 mapping technique. The concentration of Gd-based contrast agents in brain metastases were assessed from the derived T1 maps., Results: Based on the phantom acquisition, the relationship between T1 values and signal intensity (SI) was found equal to T1 = 0.35 × SI - 1.11 (R 2  = 0.97). TSE-derived T1 values measured in white matter and gray matter in healthy volunteers were equal to 0.997 ± 0.096 s and 1.358 ± 0.056 s (mean ± standard deviation), respectively. Mean Gd 3+ concentration value in brain metastases was 94.7 ± 30.0 μM., Conclusion: The in vivo results support the relevance of the phantom-based approach: brain T1 maps can be derived from T1-weighted acquisitions., Relevance Statement: High-resolution brain T1 maps can be generated, and contrast agent concentration can be quantified and imaged in brain metastases using routine 3D T1-weighted TSE acquisitions., Key Points: Quantitative T1 mapping adds significant value to MRI diagnostics. T1 measurement sequences are rarely included in routine protocols. T1 mapping and concentration of contrast agents can be derived from routine standard scans. The diagnostic value of MRI can be improved without additional scan time., (© 2024. The Author(s).)

Metabolic conditions, such as gout, can result from elevated uric acid (UA) levels. Consuming high-purine meals increases UA levels. Therefore, people with hyperuricemia typically must avoid ingesting such foods. Polyphenols have been shown to reduce uric acid levels and tart cherries (TCs) are a rich source of phenolic and anthocyanin compounds. This proof-of-concept study evaluated whether ingesting TCs with a purine-rich meal affects the uricemic response. Methods: A total of 25 adults (15 males and 10 females, 85.0 ± 17 kg, 40.6 ± 9 years, 29.1 ± 4.9 kg/m 2 ) with elevated fasting UA levels (5.8 ± 1.3 mg/dL) donated a fasting blood sample. In a randomized, double-blind, crossover, placebo-controlled, counterbalanced manner, participants ingested capsules containing 960 mg of a placebo (PLA) or concentrated TC powder containing 20.7 mg of proanthocyanins with a serving of hot soup (10 g of carbohydrate, 2 g protein, and 1 g fat) containing 3 g of purines (1 g of adenosine 5'-monophosphate, 1 g of disodium 5'-guanylate, and 1 g of disodium 5'-inosinate). Blood samples were obtained at 0, 60, 120, 180, and 240 min after ingestion to assess changes in uric acid levels and pharmacokinetic profiles. Cell blood counts, a comprehensive metabolic panel, cytokines, inflammatory markers, and subjective side effects ratings were analyzed on baseline (0 min) and post-treatment (240 min) samples. Participants continued consuming two capsules/day of the assigned treatment for one week and then repeated the experiment. Participants observed a 14-day washout and then repeated the experiment while ingesting the alternate treatment. Data were analyzed using general linear model (GLM) statistics with repeated measures, pairwise comparisons, and percentage change from baseline with 95% confidence intervals (CIs). Results: No statistically significant interaction effects or differences between treatments were seen in uric acid levels or PK profiles. Analysis of percent changes from baseline revealed that TC ingestion reduced the blood glucose levels following the ingestion of the high-purine meal (-4.2% [-7.7, -0.7], p = 0017). Additionally, there was some evidence that TC ingestion attenuated the increase from baseline in IL-1β and IL-10 and increased INF-γ. No significant differences were seen in the remaining health markers or subjective side effects ratings. Conclusions: Acute and one-week TC supplementation did not affect the uricemic response to ingesting a high-purine meal in individuals with mildly elevated UA levels. However, there was some evidence that TC supplementation may blunt the glycemic response to ingesting a meal and influence some inflammatory cytokines. Registered clinical trial NCT04837274.

Background and Purpose: The circle of Willis (COW) is a crucial mechanism for cerebral collateral circulation. This proof-of-concept study aims to develop and assess an analysis method to characterize the hemodynamics of the arterial segments in the COW by using arterial spin-labeling (ASL) based non-contrast-enhanced dynamic MR angiography (dMRA)., Materials and Methods: The developed analysis method uses a graph model, bootstrap strategy, and ensemble learning methodologies to determine the time curve shift from ASL dMRA to estimate the flow direction within the COW. The performance of the method was assessed on 52 subjects, by using the flow direction, either antegrade or retrograde, derived from 3D phase-contrast MR imaging as the reference., Results: A total of 340 arterial segments in the COW were evaluated, among which 30 (8.8%) had retrograde flow according to 3D phase-contrast MRI. The ASL dMRA-based flow direction estimation has an accuracy, sensitivity, and specificity of 95.47%, 80%, and 96.34%, respectively., Conclusions: Using ASL dMRA and the developed image analysis method to estimate the flow direction in COW is feasible. This study provides a new method to assess the hemodynamics of the COW, which could be useful for the diagnosis and study of cerebrovascular diseases., (© 2024 by American Journal of Neuroradiology.)

Background: Detecting peripheral neuropathy (PNP) is crucial in preventing complications such as foot ulceration. Clinical examinations for PNP are infrequently provided to patients at high risk due to restrictions on facilities, care providers, or time. A gamified health assessment approach combining wearable sensors holds the potential to address these challenges and provide individuals with instantaneous feedback on their health status., Objective: We aimed to develop and evaluate an application that assesses PNP through video games controlled by pressure sensor-equipped insoles., Methods: In the proof-of-concept exploratory cohort study, a complete game-based framework that allowed the study participant to play 4 video games solely by modulating plantar pressure values was established in an outpatient clinic setting. Foot plantar pressures were measured by the sensor-equipped insole and transferred via Bluetooth to an Android tablet for game control in real time. Game results and sensor data were delivered to the study server for visualization and analysis. Each session lasted about 15 minutes. In total, 299 patients with diabetes mellitus and 30 with metabolic syndrome were tested using the game application. Patients' game performance was initially assessed by hypothesis-driven key capabilities that consisted of reaction time, sensation, skillfulness, balance, endurance, and muscle strength. Subsequently, specific game features were extracted from gaming data sets and compared with nerve conduction study findings, neuropathy symptoms, or disability scores. Multiple machine learning algorithms were applied to 70% (n=122) of acquired data to train predictive models for PNP, while the remaining data were held out for final model evaluation., Results: Overall, clinically evident PNP was present in 247 of 329 (75.1%) participants, with 88 (26.7%) individuals showing asymmetric nerve deficits. In a subcohort (n=37) undergoing nerve conduction study as the gold standard, sensory and motor nerve conduction velocities and nerve amplitudes in lower extremities significantly correlated with 79 game features (|R|>0.4, highest R value +0.65; P<.001; adjusted R 2 =0.36). Within another subcohort (n=173) with normal cognition and matched covariates (age, sex, BMI, etc), hypothesis-driven key capabilities and specific game features were significantly correlated with the presence of PNP. Predictive models using selected game features achieved 76.1% (left) and 81.7% (right foot) accuracy for PNP detection. Multiclass models yielded an area under the receiver operating characteristic curve of 0.76 (left foot) and 0.72 (right foot) for assessing nerve damage patterns (small, large, or mixed nerve fiber damage)., Conclusions: The game-based application presents a promising avenue for PNP screening and classification. Evaluation in expanded cohorts may iteratively optimize artificial intelligence model efficacy. The integration of engaging motivational elements and automated data interpretation will support acceptance as a telemedical application., (©Antao Ming, Vera Clemens, Elisabeth Lorek, Janina Wall, Ahmad Alhajjar, Imke Galazky, Anne-Katrin Baum, Yang Li, Meng Li, Sebastian Stober, Nils David Mertens, Peter Rene Mertens. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 01.10.2024.)

Background: Effective rehabilitation following total knee arthroplasty (TKA) is crucial for enhancing both range of motion (ROM) and functional outcomes. While robotics has demonstrated its potential in various medical contexts, the evidence on its application in TKA rehabilitation is still scarce. The marsi active knee (MAK), a robotic device that has already proven to be safe and beneficial in people with neurological disease, has been tested to facilitate the rehabilitation of TKA patients., Objective: This study aims to evaluate the safety, patient satisfaction, and clinical impact of integrating the MAK into an early rehabilitation regimen for TKA patients., Methods: The intervention comprised 14 one-hour sessions administered thrice a week, utilizing the MAK within 48 h post-TKA surgery. The rehabilitation sessions incorporated exercises involving passive mobilizations, sit-to-stand transitions, and gait training. Comprehensive data encompassing safety parameters, patient satisfaction, and clinical outcomes were meticulously collected and analyzed., Results: Six participants successfully completed the rehabilitation protocol with the MAK device. Notably, no significant adverse events were documented. Application of the device corresponded to perceptible reductions in self-reported pain levels. Vital signs remained within minimal variance pre- and post-rehabilitation. Participants proficiently engaged in all assisted exercises facilitated by the device, culminating in a high overall satisfaction rating of 4.6 ± 0.5 out of 5., Conclusion: The findings indicate that the MAK device exhibits a commendable level of safety while obtaining considerable patient satisfaction during the early rehabilitation phase following TKA, suggesting this device may be a reliable adjunct to TKA protocols., (© 2024 The Author(s). Physiotherapy Research International published by John Wiley & Sons Ltd.)

C-X-C motif chemokine receptor 4 (CXCR4)-directed imaging has gained clinical interest in aiding clinical diagnostics in primary aldosteronism (PA). We retrospectively evaluated the feasibility of CXCR4-directed scintigraphy using the novel CXCR-4 ligand [ 99m Tc]Tc-pentixatec in patients with PA. Methods: Six patients (mean age ± SD, 49 ± 15 y) underwent CXCR4-directed scintigraphy (including planar imaging and SPECT/CT) 30, 120, and 240 min after injection of 435 ± 50 MBq of [ 99m Tc]Tc-pentixatec. Adrenal CXCR4 expression was analyzed by calculating lesion-to-contralateral ratios (LCRs). Imaging results were correlated to clinical information. Histopathology and clinical follow-up served as the standard of reference. Results: Three subjects showed lateralization of adrenal tracer accumulation, with a mean maximum lesion-to-contralateral ratio of 1.65 (range, 1.52-1.70), which correlated with morphologic findings on CT. One individual underwent adrenalectomy and presented with complete biochemical and clinical remission at follow-up. Histopathologic workup confirmed unilateral aldosterone-producing adenoma. Conclusion: [ 99m Tc]Tc-pentixatec scintigraphy with SPECT in patients with PA is feasible and might offer a valuable alternative to CXCR4-directed imaging with [ 68 Ga]Ga-pentixafor PET., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Broken screw removal from the implant connection is a common but challenging process. Several proposed methods and technical solutions may result in unsuccessful removal; thus, a novel, more conservative, risk-free method is proposed as a first attempt. The proposal is to use a silicon restoration holder to be twisted counterclockwise on the dried surface of the broken fragment inside the implant connection. This method, within the limitations of a minimal case series, yielded 100% results; however, despite previous attempts with less conservative techniques, this approach showed no efficacy. This article aims to promote the use of silicon restoration holders as a minimally invasive first attempt at broken screw retrieval treatment before considering other options.

Background: Hypothermic liver perfusion decreases ischemia/reperfusion injury during hepatectomy under standard total vascular exclusion (TVE) of the liver. This surgery needs venovenous bypass and is hampered by high morbi-mortality. TVE preserving the inferior vena cava (IVC) flow is hemodynamically well tolerated but remains limited in duration when performed under liver normothermia. The objective of this study was to report the results of TVE preserving the caval flow, modified to allow hypothermic liver perfusion and obviate splanchnic congestion., Patients and Methods: The technique, indicated for tumors abutting large tributaries of the hepatic veins but sparing their roots in IVC and the latter, was applied when TVE was anticipated to last for ≥ 60 min. It combines continuous TVE preserving the IVC flow with hypothermic liver perfusion and temporary portacaval shunt (PCS). Results are given as median (range)., Results: Vascular control was achieved in 13 patients with excellent hemodynamical tolerance. PCS was direct or via an interposed synthetic graft (five and eight cases, respectively). Liver temperature dropped to 16.5 (6-24) °C under perfusion of 2 (2-4) L of cold perfusate. TVE lasted 67 (54-125) min and 4.5 (0-8) blood units were transfused. Resection was major in nine cases and was complete in all cases. Five complications occurred in four patients, and the 90-day mortality rate was zero., Conclusions: This technique maintains stable hemodynamics and combines the advantages of in situ or ex situ standard TVE with hypothermic liver perfusion, without their inherent prolongation of ischemia time and need for venovenous bypass., (© 2024. Society of Surgical Oncology.)

Background: Functional Electrical Stimulation (FES) represents a promising technique for promoting functional recovery in individuals with neuromuscular diseases. Traditionally, current pulses are delivered through self-adhesive hydrogel Ag/AgCl electrodes, which allow a good contact with the skin, are easy-to-use and have a moderate cost. However, skin adherence decreases after a few uses and skin irritations can originate. Recently, textile electrodes have become an attractive alternative as they assure increased durability, easy integration into clothes and can be conveniently cleaned, improving the wearability of FES. However, as various manufacture processes were attempted, their clear validation is lacking. This proof-of-concept study proposes a novel set of ink-based printed textile electrodes and compares them to adhesive hydrogel electrodes in terms of impedance, stimulation performance and perceived comfort., Methods: The skin-electrode impedance was evaluated for both types of electrodes under different conditions. These electrodes were then used to deliver FES to the Rectus Femoris of 14 healthy subjects to induce its contraction in both isometric and dynamic conditions. This allowed to compare the two types of electrodes in terms of sensory, motor, maximum and pain thresholds, FES-induced range of motion during dynamic tests, FES-induced torque during isometric tests and perceived stimulation comfort., Results: No statistically significant differences were found both in terms of stimulation performance (Wilcoxon test) and comfort (Generalized Linear Mixed Model)., Conclusion: The results showed that the proposed ink-based printed textile electrodes can be effectively used as alternative to hydrogel ones. Further experiments are needed to evaluate their durability and their response to sterilizability and stretching tests., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Respiratory diseases, claim over eight million lives annually. However, the transition from preclinical to clinical phases in research studies is often hindered, partly due to inadequate representation of preclinical models in clinical trials. To address this, we conducted a proof-of-concept study using an ex vivo model to identify lung pathologies and to screen therapeutics in a humanized rodent model. We extracted and decellularized mouse heart-lung tissues using a detergent-based technique. The lungs were then seeded and cultured with human cell lines (BEAS-2B, A549, and Calu3) for 6-10 days, representing healthy lungs, cancerous states, and congenital pathologies, respectively. By manipulating cultural conditions and leveraging the unique characteristics of the cell lines, we successfully modeled various pathologies, including advanced-stage solid tumors and the primary phase of SARS-CoV-2 infection. Validation was conducted through histology, immunofluorescence staining, and pathology analysis. Additionally, our study involved pathological screening of the efficacy and impact of key anti-neoplastic therapeutics (Cisplatin and Wogonin) in cancer models. The results highlight the versatility and strength of the ex vivo model in representing crucial lung pathologies and screening therapeutics during the preclinical phase. This approach holds promise for bridging the gap between preclinical and clinical research, aiding in the development of effective treatments for respiratory diseases, including lung cancer., (© 2024 The Author(s). Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Pentraxin 3 (PTX3) is an acute phase protein produced in various tissues in response to microbial and sterile stimuli, which regulates the inflammation outcomes. PTX3 has not been investigated in myocarditis. Our aim was to assess circulating and cardiac tissue expression of PTX3 in 55 patients with myocarditis proven by magnetic resonance and/or endomyocardial biopsy. A major proportion of patients with myocarditis displayed significantly increased plasma PTX3 levels as compared with controls (26/30 vs. 0/10), with higher diagnostic yield than conventional biomarkers in the study group. Cardiac tissue analysis revealed PTX3 expression in all patients (40/40), with viral myocarditis exhibiting higher signal intensity than autoimmune myocarditis, and with a predominant localization in cardiomyocytes. Abnormal plasma PTX3 was associated with systolic dysfunction and heart failure at presentation. Interestingly, patients who recovered by 12 months had higher baseline PTX3 levels. Our preliminary data support the potential use of PTX3 as a biomarker in myocarditis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Forests face many threats. While traditional breeding may be too slow to deliver well-adapted trees, genomic selection (GS) can accelerate the process. We describe a comprehensive study of GS from proof of concept to operational application in western redcedar (WRC, Thuja plicata). Using genomic data, we developed models on a training population (TrP) of trees to predict breeding values (BVs) in a target seedling population (TaP) for growth, heartwood chemistry, and foliar chemistry traits. We used cross-validation to assess prediction accuracy (PACC) in the TrP; we also validated models for early-expressed foliar traits in the TaP. Prediction accuracy was high across generations, environments, and ages. PACC was not reduced to zero among unrelated individuals in TrP and was only slightly reduced in the TaP, confirming strong linkage disequilibrium and the ability of the model to generate accurate predictions across breeding generations. Genomic BV predictions were correlated with those from pedigree but displayed a wider range of within-family variation due to the ability of GS to capture the Mendelian sampling term. Using predicted TaP BVs in multi-trait selection, we functionally implemented and integrated GS into an operational tree-breeding program., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

For many years, noninvasive methods to measure intracranial pressure (ICP) have been unsuccessful. However, such methods are crucial for the assessment of patients with nonpenetrating traumatic brain injuries (TBIs) who are unconscious. In this study, we explored the use of transcranial transmission ultrasound (TTUS) to gather experimental data through brain pulsatility, assessing its effectiveness in detecting high ICP using machine learning analysis. We included patients with severe TBI under invasive ICP monitoring in our intensive care unit. During periods of both normal and elevated ICP, we simultaneously recorded ICP, arterial blood pressure, heart rate, and TTUS measurements. Our classification model was based on data from 9 patients, encompassing 387 instances of elevated ICP (>15 mmHg) and 345 instances of normal ICP (<10 mmHg), and validated through a leave-one-subject-out method. The study, conducted from October 2021 to October 2022, involved 25 patients with an average age of 61.6 ± 17.6 years, producing 279 datasets with an average ICP of 11.3 mmHg (1st quartile 6.1 mmHg; 3rd quartile 14.8 mmHg). The automated TTUS analysis effectively identified ICP values over 15 mmHg with 100% sensitivity and 47% specificity. It achieved a 100% negative predictive value and a 14% positive predictive value. This suggests that TTUS can accurately rule out high ICP above 15 mmHg in TBI patients, indicating patients who may need immediate imaging or intervention. These promising results, if confirmed and expanded in larger studies, could lead to the first reliable, noninvasive screening tool for detecting elevated ICP.

Objectives: To present the first clinical application of a novel mixed reality-based dynamic navigation (MR-DN) system in the rehabilitation of a single tooth gap., Methods: The protocol consisted of the following: (1) three-dimensional patient data acquisition using intraoral scanning (IOS) and cone-beam computed tomography (CBCT), (2) implant planning using guided surgery software, (3) holography-guided implant placement using the novel MR-DN system (ANNA®, MARS Dental, Haifa, Israel) and (4) placement accuracy verification., Results: The novel MR-DN system was safe and time-efficient, as the surgery took 30 min from anaesthesia to suturing. The accuracy of implant placement was high with minimal deviations recorded in the three planes of space compared to the presurgical planning: the error at the entry point planar distance (XY) was 0.381 mm, and the entry point planar distance (Z) was 0.173 mm, for a 3D entry point distance (En) of 0.417 mm. A 3D apex deviation (An) of 0.193 mm was registered, with an angle difference of 1.852° Conclusions: This proof-of-concept study demonstrated the clinical feasibility of MR-DN for guided implant placement in single tooth gaps. Further clinical studies on a large sample of patients are needed to confirm these positive preliminary results. Statement of clinical relevance: The use of MR-DN can change the perspectives of guided dental implant surgery as a possible alternative to the classic static and dynamic guided surgical techniques for the rehabilitation of single tooth gaps., Competing Interests: Declaration of competing interest The authors report no conflict of interest related to the present in vitro study. Dr. Ariel Shusterman is an employee of MARS, but the materials presented in the study belong to all the authors, who have not received any grant or financial support for the preparation of the present research., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Pain is a common non-motor symptom in patients with cervical dystonia (CD), severely impacting their quality of life. The pathophysiology of CD is incompletely understood but it involves altered processing of proprioceptive and pain signals., Objectives: The purpose of this proof-of-concept study was to determine if vibro-tactile stimulation (VTS)-a non-invasive form of neuromodulation targeting the somatosensory system-can modulate neck pain in people with CD., Methods: In a multi-center study, 44 CD patients received VTS to sternocleidomastoid and/or trapezius muscles for up to 45 min under 9 different stimulation conditions that either targeted a single or a pair of muscles. The primary outcome measure was a perceived pain score (PPS) rated by participants on a 100-point analogue scale., Results: During VTS, 29/44 (66%) of participants experienced a reduction in PPS of at least 10% with 17/44 (39%) reporting a reduction in pain of 50% or higher. After VTS cessation, 57% of participants still reported a 10% or higher reduction in PPS. Effects were significant at the group level and persisted for up to 20 min post-treatment. No distinct optimal stimulation profiles were identified for specific CD phenotypes. Clinical markers of disease severity or duration did not predict the degree of VTS-induced pain reduction., Conclusion: This proof-of-concept study demonstrates the potential of VTS as a new non-invasive therapeutic option for treating neck pain associated with CD. Further research needs to delineate optimal dosage and long-term effects., (© 2024. The Author(s).)

Purpose: To evaluate safety and impact of particle embolization on pancreatic function in a pig model., Materials and Methods: Embolization of the dorsal pancreatic artery using 100-300-μm particles was performed on 14 Yorkshire pigs. Baseline and post-embolization glucose tolerance testing results and serum amylase/lipase levels were obtained. Pigs were observed for 2 weeks to assess for behavioral signs of pain/distress, bowel changes, and changes to intake/output. After 2 weeks, euthanasia and necropsy with gross and histopathologic assessment of the pancreas were performed., Results: Embolization was technically successful in all pigs. All animals survived the 2-week follow-up without evidence of pain/distress. There were significant increases in amylase and lipase at 24 and 48 hours (P < .001), which normalized by 2 weeks. There was minimal change in glucose tolerance testing at 2 weeks. Bowel habits were unchanged without diarrhea. At necropsy, all examined pancreases had fibrosis in the distal body and tail, without gross evidence of ongoing inflammation. On histopathologic evaluation, all pancreases demonstrated fibrosis in the embolized portions without evidence of active inflammation in treated or adjacent pancreatic tissue., Conclusions: Particle embolization of the pancreas was feasible and tolerated by all tested pigs with transient amylasemia, lipasemia, and mildly impaired glucose tolerance but without clinical or histopathologic evidence of acute pancreatitis and no evident impact on pancreatic endocrine or exocrine function., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Immune dysregulation can play a role in depression pathophysiology, and immunological antagonists can improve depressive symptoms in treatment-resistant bipolar depression (TRD) patients according to studies., Objective: To evaluate the anti-depressant effects of the anti-inflammatory drug, pentoxifylline (PTX) in TRD bipolar I/II adult subjects., Methods: This 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at Hawler Psychiatric Hospital and Private Clinic in Erbil, Iraq. Participants were confirmed as being qualified for bipolar I/II depression based on DSM-5 criteria. Data were analyzed using modified intent-to-treat analysis., Results: There were no significant differences between the two groups in Hamilton Rating Scale for Depression-17 (HAM-D-17) scores (χ 2 =1.9, P =.48) or a significant time × treatment interaction (χ 2 =7.1, P=.54). Nevertheless, a significant effect of time was observed with both groups' reduction in HAM-D-17 scores from the start to the endpoint (χ 2 = 2.11, P=.002). Besides, a significant time × treatment × CRP interaction was found (χ 2 =3.1, P=0.016), where there was more reduction in HAM-D-17 score in PTX-treated subjects with CRP> 7.1 mg/L. The response rate difference between PTX and the placebo group did not reach a significance level (χ 2 =0.84, p=0.43). Furthermore, serum concentrations of TNF-α, CRP, and IL-6 significantly reduced at week 12 in the PTX group (P=.007,.04, and <.001, respectively)., Conclusion: The current proof of concept study found that in terms of overall anti-depressant effectiveness in bipolar patients with TRD, PTX is not superior to placebo. However, it may improve depressive mood in a subpopulation of subjects with a higher pretreatment inflammatory profile., 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 Inc. All rights reserved.)

Starches-rich and protein-rich cereal samples commonly need tedious sample preparation steps before instrumental analysis. This study developed a miniaturized centrifugal integrated cold-induced phase separation (CIPS) method for convenient sample preparation. A small-sized centrifuge tube (2 mL) and a low-temperature centrifuge, both of which are easily accessible, make up the basic components of the system. Unlike conventional sample preparation methods that need a step-by-step extraction, enrichment, purification, and centrifugation, this centrifugal integrated CIPS method can be performed by a one-step combination protocol under a low-temperature centrifuge. As a proof-of-concept study, satisfactory recoveries and enrichment factors were demonstrated for the extraction of fumonisins and ochratoxins from cereals. A sensitive and selective quantification method was yielded by combining LC-HRMS using tSIM acquisition mode, with good linearity (R 2  > 0.998), accuracy (82.9-106.5%), and precision (<13.4%). This strategy is convenient, low-cost, repeatable, and easy to semi-automate, further expanding the extraction potential for other acidic mycotoxins., 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 Elsevier Ltd. All rights reserved.)

Objectives: To demonstrate the potential application of mixed reality (MR) holographic imaging technology in subgingival scaling and root planing (SRP) for patient with advanced periodontitis., Methods: This case series comprised the analysis of 1566 sites from 261 teeth of 10 patients with advanced periodontitis. Digital CBCT scans and intraoral scans of the patients were digitally acquired preoperatively and aligned to create a three-dimensional periodontal visualization model. Through rendering, interactive holographic images were displayed using MR. The surgeon first used MR images to communicate with the patients, and then facilitated SRP under their guidance. Probing pocket depth (PPD), clinical attachment loss (CAL), Plaque index (PI), and bleeding on probing (BOP) parameters were recorded at baseline and at 8-week postoperatively. Patient-reported outcome indicator questionnaires on self-efficacy were also collected., Results: PPD, CAL, PI, and BOP significantly decreased at 8-week following MR hologram-assisted SRP (p<0.001). For sites with PPD≥4 mm, PPD and CAL declined by 2.33±1.23 mm and 0.69±1.07 mm, respectively. PI significantly decreased from 1.94±0.61 to 0.82±0.58 (p < 0.001) and BOP sites decreased significantly from 84.11% to 40.25%. After receiving MR holograms for condition communication, most patients had a better perception of the effectiveness of SRP treatment and the benefits it brings. 80% of the subjects expressed their willingness to undergo MR-assisted periodontal treatment in the future., Conclusion: These results provide preliminary support for MR hologram-assisted digital SRP. With this technology, images of the gingiva and alveolar bone can be displayed in real time, accurately and three-dimensionally. This improves SRP effectiveness, diminishes complications, and enhances patients' confidence in the treatment., Clinical Significance: MR holographic imaging-based digital SRP is a clinically feasible and promising adjunctive periodontal treatment option. It may contribute to improved non-surgical treatment efficacy in patients with severe periodontitis., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interests., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: To evaluate if acute intermittent hypoxia (AIH) coupled with transcutaneous spinal cord stimulation (tSCS) enhances task-specific training and leads to superior and more sustained gait improvements as compared with each of these strategies used in isolation in persons with chronic, incomplete spinal cord injury., Design: Proof of concept, randomized crossover trial., Setting: Outpatient, rehabilitation hospital., Interventions: Ten participants completed 3 intervention arms: (1) AIH, tSCS, and gait training (AIH + tSCS); (2) tSCS plus gait training (SHAM AIH + tSCS); and (3) gait training alone (SHAM + SHAM). Each arm consisted of 5 consecutive days of intervention with a minimum of a 4-week washout between arms. The order of arms was randomized. The study took place from December 3, 2020, to January 4, 2023., Main Outcome Measures: 10-meter walk test at self-selected velocity (SSV) and fast velocity, 6-minute walk test, timed Up and Go (TUG) and secondary outcome measures included isometric ankle plantarflexion and dorsiflexion torque RESULTS: TUG improvements were 3.44 seconds (95% CI: 1.24-5.65) significantly greater in the AIH + tSCS arm than the SHAM AIH + tSCS arm at post-intervention (POST), and 3.31 seconds (95% CI: 1.03-5.58) greater than the SHAM + SHAM arm at 1-week follow up (1WK). SSV was 0.08 m/s (95% CI: 0.02-0.14) significantly greater following the AIH + tSCS arm than the SHAM AIH + tSCS at POST. Although not significant, the AIH + tSCS arm also demonstrated the greatest average improvements compared with the other 2 arms at POST and 1WK for the 6-minute walk test, fast velocity, and ankle plantarflexion torque., Conclusions: This pilot study is the first to demonstrate that combining these 3 neuromodulation strategies leads to superior improvements in the TUG and SSV for individuals with chronic incomplete spinal cord injury and warrants further investigation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: In this proof-of-concept study, we propose a new method for automated digital quantification of PRAME (PReferentially expressed Antigen of MElanoma) as a diagnostic aid to distinguish between benign and malignant melanocytic lesions. The proposed method utilizes immunohistochemical virtual double nuclear staining for PRAME and SOX10 to precisely identify the melanocytic cells of interest, which is combined with digital image analyse to quantify a PRAME-index., Methods: Our study included 10 compound nevi, 3 halo nevi, and 10 melanomas. Tissue slides were stained with PRAME, scanned, the cover glass removed, stained with SOX10, scanned again, and finally analysed digitally. The digitally quantified PRAME-index was compared with a manual qualitative assessment by a dermatopathologist using the standard PRAME-scoring system., Results: The digitally quantified PRAME-index showed a sensitivity of 70 % and a specificity of 100 % for separating melanomas from benign lesions. The manual qualitative PRAME-score showed a sensitivity of 60 % and a specificity of 100 %. Comparing the two methods using ROC-analyses, our digital quantitative method (AUC: 0.931, 95 % CI: 0.834;1.00, SD: 0.050) remains on par with the manual qualitative method (AUC: 0.877, 95 % CI: 0.725;1.00, SD: 0.078)., Conclusion: We found our novel digital quantitative method was at least as precise at classifying lesions as benign or malignant as the current manual qualitative assessment. Our method has the advantages of being operator-independent, objective, and replicable. Furthermore, our method can easily be implemented in an already digitalized pathology department. Given the small cohort size, more studies are to be done to validate our findings., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mette Bak Brogard reports financial support was provided by Harboefonden. Mette Bak Brogard reports financial support was provided by Torben and Alice Frimodts Fund. If there are other authors, they 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 GmbH.. All rights reserved.)

Background and Purpose: Radiotherapy for bulky tumors often results in palliation with suboptimal outcomes. The prognosis is worsened by immunosuppression caused by radio-chemotherapy, negatively impacting on survival. Novel Partial Tumor Irradiation (PTI) was designed to spare the Peritumoral Immune Microenvironment (PIM) and to be delivered synchronously with immune activity peaks, thus enhancing both local and distant tumor control through immunostimulation., Materials and Methods: Present proof-of-principle trial enrolled 26 patients with bulky tumors, comparing outcomes between treatments administered at immune activity peaks versus troughs. The primary endpoint was local-bystander and distal-abscopal response-rate. Secondary endpoints included overall-, progression-free-, cancer-specific survival, neoadjuvant and immunomodulatory potential., Results: All measured outcomes were significantly influenced by treatment-timing. The bystander and abscopal response rates were 77% and 41%, respectively. PTI significantly upregulated pro-inflammatory and cell-death-inducing pathways improving the efficacy of radiotherapy by highly complex tumors., Conclusions: This study highlights the profound impact PTI can have on a highly palliative patient cohort previously deemed beyond therapeutic hope. With 41 % of these patients still alive after a median follow-up of 50 months, PTI offers a potential lifeline for those facing advanced, treatment-resistant cancers. This approach generated also distant immunogenic anti-tumor responses, offering a promising new avenue for the treatment of advanced cancers., 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 Elsevier B.V. All rights reserved.)

Background: Endometriosis of the distal segment of the uterosacral ligament may lead to a displaced ureter in the surgical field and must be identified before safe disease excision can be carried out. The aim of this study is to investigate the benefit of the systematic use of preoperative intraureteral indocyanine green (ICG) fluorescence injection in patients undergoing endometriosis surgery., Method: In this proof-of-concept, monocentric, observational, cohort study data were prospectively collected and retrospectively analyzed. Patients underwent laparoscopic surgery for deep infiltrating endometriosis with suspected ureteral involvement between January 2022 and December 2023. Using the propensity score matching (PSM) in a 1:1 matching ratio, patients who underwent preoperative ICG injection were compared with those who did not in terms of ureterolysis length and duration, and operative time., Results: The mean length of ureterolysis was shorter in the ICG group compared to the non-ICG group ( p  < 0.001). The ICG group also had shorter ureterolysis duration ( p  < 0.001) and operative time ( p  = 0.02). No complications were reported at mean 6.8-month follow-up visit., Conclusions: The systematic use of intraureteral ICG prior to uterosacral ligaments endometriosis surgery may be safe and could assist in reducing the length of ureterolysis and operative time. Larger prospective studies are needed to confirm our findings.

Background: Chronic pain involves communication between neural and immune systems. Recent data suggest localization of glial (brain immune cells) activation to the sensorimotor regions of the brain cortex (S1/M1) in chronic low back pain (LBP). As glia perform diverse functions that impact neural function, activation might contribute to sensorimotor changes, particularly in LBP maintained by increased nervous system sensitivity (i.e., nociplastic pain). This preliminary proof-of-concept study aimed to: (i) compare evidence of neuroinflammatory activation in S1/M1 between individuals with and without LBP (and between nociceptive and nociplastic LBP phenotypes), and (ii) evaluate relationships between neuroinflammatory activation and sensorimotor function., Methods: Simultaneous PET-fMRI measured neuroinflammatory activation in functionally defined S1/M1 in pain-free individuals (n = 8) and individuals with chronic LBP (n = 9; nociceptive: n = 4, nociplastic: n = 5). Regions of S1/M1 related to the back were identified using fMRI during motor tasks and thermal stimuli. Sensorimotor measures included single and paired-pulse transcranial magnetic stimulation (TMS) and quantitative sensory testing (QST). Sleep, depression, disability and pain questionnaires were administered., Results: Neuroinflammatory activation was greater in the lower back cortical representation of S1/M1 of the nociplastic LBP group than both nociceptive LBP and pain-free groups. Neuroinflammatory activation in S1/M1 was positively correlated with sensitivity to hot (r = 0.52) and cold (r = 0.55) pain stimuli, poor sleep, depression, disability and BMI, and negatively correlated with intracortical facilitation (r = -0.41)., Conclusion: This preliminary proof-of-concept study suggests that neuroinflammation in back regions of S1/M1 in individuals with nociplastic LBP could plausibly explain some characteristic features of this LBP phenotype., Significance Statement: Neuroinflammatory activation localized to sensorimotor areas of the brain in individuals with nociplastic pain might contribute to changes in sensory and motor function and aspects of central sensitization. If cause-effect relationships are established in longitudinal studies, this may direct development of therapies that target neuroinflammatory activation., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Objectives: In this study, we used atomic force microscopy (AFM) to quantify the size of surface pore apertures of enamel white spot lesions and then demonstrated the penetration of fluorapatite nanocrystals (nFA) into the subsurface of these lesions., Methods: For the porosity study, enamel lesions were created on three sound human teeth using a demineralizing gel for 8 days. The interface between sound enamel and the artificial lesion was analyzed by AFM. To visualize the penetration of nFA tagged with a calcium-binding fluorophore (Fluo-4) into the subsurface of white spot lesions, we used two-photon microscopy. Sixteen extracted human teeth with either active, natural, or in vitro-created carious lesions in enamel were randomly divided into three groups. The teeth were treated for 2 min with either a suspension of tagged nFA crystals, Fluo-4 alone, or deionized water, and left for 30 min before being washed with distilled water and examined microscopically., Results: A greater concentration of surface pores with larger areas was observed on the in vitro demineralized enamel (29 % of pores greater than 1.0 µm 2 ) when compared with the adjacent sound enamel (8 % of pores greater than 1.0 µm 2 ) (p=0.012, Fisher exact test). In vitro and natural lesions treated with tagged nFA showed fluorescence at depths ranging from 50 to 170 µm, demonstrating penetration of the nFA into the lesion subsurface. The lesions treated with Fluo-4 alone with no crystals showed mostly surface fluorescence (restricted to the outer 25 µm), while those treated with deionized water showed minimal (restricted to the outer 20 µm) to no fluorescence., Conclusion: We have demonstrated the use of AFM to quantify the surface pore apertures and two-photon microscopy to visualize nFA crystals in the subsurface of non-cavitated enamel lesions., Clinical Significance: The restoration of the subsurface of non-cavitated caries lesions is a clinical challenge. This study demonstrated that a 2 min application of nFA could penetrate through the surface apertures of non-cavitated enamel lesions into their subsurface., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

FTIR spectroscopy is well known for its molecule fingerprinting capability but is also able to differentiate classes in complex biological systems. This includes strain typing and species level identification of bacterial, yeast or fungal cells, as well as distinguishing between cell layers in eukaryotic tissues. However, its use for the identification of macromolecules such as proteins remains underexplored and rarely used in practice. Here we demonstrate the efficacy of FTIR microspectroscopy coupled with machine learning methods for rapid and accurate identification of proteins in their dry state within minutes, from very small quantities of material, if they are obtained in a pure aqueous solution. FTIR microspectroscopy can provide additional information beside identification: it can detect small differences among different purification batches potentially originating from post-translational modifications or distinct folding states. Moreover, it distinguishes glycoproteins and evaluate glycosylation while detecting contaminants. This methodology presents itself as a valuable quality control tool in protein purification processes or any process requiring the utilization of precisely identified, pure proteins., 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. Published by Elsevier B.V.)

Purpose: To evaluate effectiveness of pulmonary arteriovenous malformation (PAVM) embolization using dual-energy computed tomography (CT) and spectral curve analysis by characterizing contrast enhancement and vascular perfusion as a surrogate of the degree of vascular occlusion after embolotherapy., Materials and Methods: Nine consecutive adult patients underwent embolization for 21 PAVMs (size range, 0.4-2.0 cm; 15/21 simple angioarchitecture) and subsequent postembolization chest dual-energy CT angiography. Twelve PAVMs were treated with vascular plugs with or without coils, whereas 9 PAVMs were treated with coils alone. Virtual spectral curves were generated using dual-energy image postprocessing in order to measure embolization effectiveness., Results: Complete occlusion of target PAVM was achieved in all cases on digital subtraction angiography (DSA) at the end of the embolization procedure. With a median follow-up of 12.7 months, the vascular plug group demonstrated significantly less vascular opacification compared with the coils-only group, as measured by opacification between upstream feeding artery and different downstream vasculature locations (Δslope1: median 79.1 vs 28.6; P = .003; Δslope2: 76.4 vs 28.6; P = .0197; Δslope3: 78.9 vs 28.6; P = .004). Persistence occurred in 3 PAVMs based on size criteria, which demonstrated higher vascular opacification by dual-energy CT (Δslope1: 72 vs 28.6; P = .253; Δslope2: 65.1 vs 32.7; P = .326; Δslope3: 72.9 vs 53.5; P = .733), although statistical significance was not reached., Conclusions: Similar to emerging literature, dual-energy CT showed improved occlusion in PAVMs treated with vascular plugs compared with those treated with coils alone., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Objective:  This proof-of-concept study assessed how confidently an artificial intelligence (AI) model can determine the sex of a fetus from an ultrasound image., Study Design:  Analysis was performed using 19,212 ultrasound image slices from a high-volume fetal sex determination practice. This dataset was split into a training set (11,769) and test set (7,443). A computer vision model was trained using a transfer learning approach with EfficientNetB4 architecture as base. The performance of the computer vision model was evaluated on the hold out test set. Accuracy, Cohen's Kappa and Multiclass Receiver Operating Characteristic area under the curve (AUC) were used to evaluate the performance of the model., Results:  The AI model achieved an Accuracy of 88.27% on the holdout test set and a Cohen's Kappa score 0.843. The ROC AUC score for Male was calculated to be 0.896, for Female a score of 0.897, for Unable to Assess a score of 0.916, and for Text Added a score of 0.981 was achieved., Conclusion:  This novel AI model proved to have a high rate of fetal sex capture that could be of significant use in areas where ultrasound expertise is not readily available., Key Points: · This is the first proof-of-concept AI model to determine fetal sex.. · This study adds to the growing research in ultrasound AI.. · Our findings demonstrate AI integration into obstetric care.., Competing Interests: None declared., (Thieme. All rights reserved.)

The current study trains, tests, and evaluates a deep learning algorithm to detect subglottic stenosis (SGS) on endoscopy. A retrospective review of patients undergoing microlaryngoscopy-bronchoscopy was performed. A pretrained image classifier (Resnet50) was retrained and tested on 159 images of airways taken at the glottis, 106 normal-sized airways, and 122 with SGS. Data augmentation was performed given the small sample size to prevent overfitting. Overall model accuracy was 73.3% (SD: 3.8). Precision and recall for stenosis were 77.3% (SD: 4.0) and 72.7 (SD: 4.0). F1 score for the detection of stenosis was 0.75 (SD: 0.04). Precision and recall for normal-sized images were lower at 69% (SD: 4.35) and 74% (SD: 4), with an F1 score of 0.71 (SD: 0.04). This study demonstrates that an image classification algorithm can identify SGS on endoscopic images. Work is needed to improve diagnostic accuracy for eventual deployment of the algorithm into clinical care., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Releasing large numbers of Aedes albopictus males, carrying the artificially introduced Wolbachia 'wPip' strain, results in a decrease in the reproductive capacity of wild females due to a phenomenon known as cytoplasmic incompatibility (CI). This vector control strategy is referred to as the incompatible insect technique (IIT). However, its widespread implementation faces various challenges, including the complexity of removing fertile females from the males intended for release. Here, we present the results of semi-field experiments comparing the impact of minimal female co-release on two IIT modes: unidirectional CI-based (UnCI IIT) and bidirectional CI-based (BiCI IIT), specifically targeting Ae. albopictus., Results: The contamination of 'wPip' infected females (2%) during male releases significantly weakened the overall effectiveness of IIT, emphasizing the need for thorough sex separation. Specifically, with UnCI IIT, despite the low rate of co-released females, there was a gradual rise in 'wPip' infection frequency, resulting in more compatible mating and subsequently higher rates of egg hatching. Conversely, this pattern was effectively mitigated in BiCI IIT owing to the reciprocal sterility between the wild-type and the 'wPip' infected populations., Conclusion: Through an experimental approach, conducted in a semi-field setting, we have contributed to advancing scientific understanding regarding the potential outcomes of implementing the IIT strategy in the absence of a complete sexing system. The results suggest that safety measures for mitigating the potential impacts of co-released females can be tailored according to the specific type of IIT being utilized. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)