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Abstract Background Two-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States. Methods Virologically suppressed (viral load [VL]

Abstract Introduction The first complete long-acting antiretroviral therapy (ART) regimen, cabotegravir + rilpivirine long-acting (CAB + RPV LA) injectable, was approved in the US for HIV-1 treatment in individuals on a stable antiretroviral regimen with a viral load

Background We evaluated the impact of the CHORUS™ app on adherence to the cabotegravir and rilpivirine long-acting injectable (CAB + RPV LAI) monthly injections schedule. Methods Healthcare centers (HCCs) were randomized to access CHORUS™ CAB + RPV LAI features (intervention) or not (control) from 01OCT2021-31JAN2022. Target window adherence (maintenance injections ≤7 days before/after target day) was assessed with multivariate logistic regression (generalized estimating equations). Results CAB + RPV LAI was administered to 188 and 79 individuals at intervention and control HCCs, respectively. Intervention was not associated with improved target window adherence (adjusted odds ratio: 0.61 [95% CI: 0.30-1.25]). However, app use was associated with increased odds of adherence compared to no app use among all intervention HCCs (2.98 [1.26-7.06]) and at smaller HCCs (3.58 [1.31-9.80]). Conclusions While access to CHORUS™ CAB + RPV LAI features did not improve target window adherence, app use did, especially at smaller HCCs which may not have established LAI management procedures. Trial registration https://clinicaltrials.gov/show/NCT04863261.

We present an analysis of the pitch angle distribution function (PADF) for nearby galaxies and its resulting black hole mass function (BHMF) via the well-known relationship between pitch angle and black hole mass. Our sample consists of a subset of 74 spiral galaxies from the Carnegie-Irvine Galaxy Survey with absolute B-band magnitude MB>−19.12 mag and luminosity distance DL≤25.4 Mpc, which is an extension of a complementary set of 140 more luminous (MB≤−19.12 mag) late-type galaxies. We find the PADFs of the two samples are, somewhat surprisingly, not strongly dissimilar; a result that may hold important implications for spiral formation theories. Our data show a distinct bimodal population manifest in the pitch angles of the Sa–Sc types and separately the Scd–Sm types, with Sa–Sc types having tighter spiral arms on average. Importantly, we uncover a distinct bifurcation of the BHMF, such that the Sa–Sc galaxies typically host so-called “supermassive” black holes (M•≳106M⊙), whereas Scd–Sm galaxies accordingly harbor black holes that are “less-than-supermassive” (M•≲106M⊙). It is amongst this latter population of galaxies where we expect fruitful bounties of elusive intermediate-mass black holes (IMBHs), through which a better understanding will help form more precise benchmarks for future generations of gravitational wave detectors.

Entrapment neuropathies at the elbow are common in clinical practice and require an accurate diagnosis for effective management. Understanding the imaging characteristics of these conditions is essential for confirming diagnoses and identifying underlying causes. Ultrasound serves as the primary imaging modality for evaluating nerve structure and movement, while MRI is superior for detecting muscle denervation. Plain radiography and CT play a minor role and can be used for the evaluation of bony structures and calcifications/ossifications. Comprehensive knowledge of anatomical landmarks, nerve pathways, and compression sites is crucial for clinicians to accurately interpret imaging and guide appropriate treatment strategies for entrapments of ulnar, median, and radial nerves, and their branches. CRITICAL RELEVANCE STATEMENT: Accurate imaging and anatomical knowledge are essential for diagnosing elbow entrapment neuropathies. Ultrasound is the preferred modality for assessing nerve structure and motion, while MRI excels in detecting muscle denervation and guiding effective management of ulnar, median, and radial nerve entrapments. KEY POINTS: Ultrasound is the primary modality for assessing nerve structure and stability. Findings include nerve structural loss, isoechogenicity, thickening, and hyper-vascularization. MRI provides a comprehensive evaluation of the elbow and accurate muscle assessment. Imaging allows the identification of compressive causes, including anatomical variants, masses, or osseous anomalies. Awareness of anatomical landmarks, nerve pathways, and compression sites is essential., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable Consent for publication: Not applicable Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: This study aimed to assess the posterior cruciate ligament (PCL) angle in anterior cruciate ligament (ACL) deficient knees and correlate it with anatomical and demographic factors such as tibial slope, anterior tibial translation, age, gender, and time of injury., Material and Methods: Patients were eligible for inclusion if they were clinically diagnosed with an ACL tear confirmed by MRI. For each patient, the following parameters were evaluated: PCL angle (PCLA), medial tibial slope (MTS), lateral tibial slope (LTS), medial anterior tibial translation (MATT), and lateral anterior tibial translation (LATT)., Results: A total of 193 patients were included in the study, comprising 91 (47.2%) females and 102 (52.8%) males, with a mean age of 30.27 ± 12.54 years. The mean time from injury to MRI was 14.18 ± 55.77 days. In the overall population, the mean PCL angle was 128.72 ± 10.33°, the mean medial tibial slope was 3.57 ± 2.33°, and the mean lateral tibial slope was 6.07 ± 3.52°. The mean medial and lateral anterior tibial translations were 4.76 ± 2.02 mm and 7.01 ± 2.48 mm, respectively. In 190 cases (98.4%), the PCL angle was ≥ 105°. The PCL angle negatively correlated with medial and lateral anterior tibial translation (p < 0.05). Females exhibited a higher PCL angle compared to males (p = 0.019)., Conclusion: In the context of ACL lesions, the PCL angle has a normal value in acute injuries (> 105°) and decreases over time. The PCL angle is negatively correlated with anterior tibial translation, and females have a higher PCL angle compared to males., Level of Evidence Iv: Retrospective Cohort., Competing Interests: Declarations. Ethical approval: Ethical approval was appropriately obtained ACL-L2104. Consent to participate: All patients signed an informed to consent for the study. Consent to publish: All authors consent to the publication of the manuscript., (© 2025. The Author(s).)

Glycoside hydrolases (GHs) are enzymes involved in the degradation of oligosaccharides and polysaccharides. The sequence space of GHs is rapidly expanding due to the increasing number of available sequences. This expansion paves the way for the discovery of novel enzymes with peculiar structural and functional properties. This work is focused on two GHs, Ps&#95;GH5 and Ps&#95;GH50, from the genome of the Antarctic bacterium Pseudomonas sp. ef1. These enzymes are in an unexplored region of the sequence space of their respective GH families, not allowing a reliable sequence-based function prediction. For this reason, a computational pipeline was developed that combines deep learning "dynamic docking" on AlphaFold 3D models with physics-based molecular dynamics simulations to infer their substrate specificity. From in silico screening of a repertoire of potential oligosaccharides, only xylooligosaccharides for Ps&#95;GH5 and galactooligosaccharides for Ps&#95;GH50 emerged as catalytically competent substrates. Biochemical characterization agrees with computational simulations indicating that Ps&#95;GH5 is an endo-β-xylanase, and Ps&#95;GH50 is active mainly on small galactooligosaccharides. In conclusion, this study identifies two novel GHs subfamilies placed in remote regions of the sequence space and highlights the efficacy of substrate specificity prediction by computational approaches in the discovery of new enzymes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco Mangiagalli reports financial support was provided by University of Milan-Bicocca. Marina Lotti reports financial support was provided by University of Milan-Bicocca. Salvatore Fusco reports was provided by Ministero dell'Università e della Ricerca (MUR). 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 © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Surfactin is a biosurfactant produced by many B. subtilis strains with a wide variety of functions from lowering surface tension to allowing motility of bacterial swarms, acting as a signaling molecule, and even exhibiting antimicrobial activities. However, the impact of surfactin during biofilm formation has been debated with variable findings between studies depending on the experimental conditions. B. subtilis is known to form biofilms at the solid-air, the solid-medium, and the liquid-air interfaces, the latter of which is known as a pellicle biofilm. Pellicle formation is a complex process requiring coordinated movement to the liquid-air interface and subsequent cooperative production of biofilm matrix components to allow robust pellicle biofilm formation. This makes pellicle formation a promising model system for assaying factors in biofilm formation and regulation. Here, we assayed the influence of surfactin and additional metabolites on the timing of pellicle biofilm formation. Using time-lapse imaging, we assayed pellicle formation timing in 12  B. subtilis isolates and found that one, MB9&#95;B4, was significantly delayed in pellicle formation by approximately 10 h. MB9&#95;B4 was previously noted to lack robust surfactin production. Indeed, deletion of surfactin synthesis in the other isolates delayed pellicle formation. Further, pellicle delay was rescued by addition of exogeneous surfactin. Testing reporters of biofilm-related gene expression revealed that induction of pellicle formation was caused by a combination of increased gene expression of one of the biofilm components and promotion of growth., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Protein post-translational modifications (PTM) play a crucial role in the modulation of synaptic function and their alterations are involved in the onset and progression of neurodegenerative disorders. S-palmitoylation is a PTM catalyzed by zinc finger DHHC domain containing (zDHHC) S-acyltransferases that affects both localization and activity of proteins regulating synaptic plasticity and amyloid-β (Aβ) metabolism. Here, we found significant increases of both zDHHC7 expression and protein S-palmitoylation in hippocampi of both 3×Tg-AD mice and post-mortem Alzheimer's disease (AD) patients. Chronic intranasal administration of the S-palmitoylation inhibitor 2-bromopalmitate counteracted synaptic plasticity and cognitive deficits, reduced the Aβ deposition in the hippocampus and extended the lifespan of both male and female 3×Tg-AD mice. Moreover, hippocampal silencing of zDHHC7 prevented the onset of cognitive deficits in the same experimental model. We also identified a FoxO1-mediated epigenetic mechanism inducing zDHHC7 expression, which was triggered by brain insulin resistance in 3×Tg-AD mice. Finally, in hippocampi of AD patients S-palmitoylation levels of Beta-Secretase 1 were associated with Aβ 1 to 42 load and they inversely correlated with Mini Mental State Examination scores. Our data reveal a key role of both zDHHC7 overexpression and protein hyperpalmitoylation in the onset and progression of AD-related alterations of synaptic plasticity and memory., Competing Interests: Competing interests statement:The authors declare no competing interest.

Purpose: The aim of this study was to systematically review the use of automated detection systems for identifying bone lesions based on CT and MRI, focusing on advancements in artificial intelligence (AI) applications., Materials and Methods: A literature search was conducted on PubMed and MEDLINE. Data were extracted and grouped into three main categories, namely baseline study characteristics, model validation strategies, and the type of AI algorithms., Results: A total of 10 studies were selected and analyzed, including 2,768 patients overall with a median of 187 per study. These studies utilized various AI algorithms, predominantly deep learning models (6 studies) such as Convolutional Neural Networks. Among machine learning validation strategies, K-fold cross-validation was the mostly used (5 studies). Clinical validation was performed using data from the same institution (internal testing) in 8 studies and from both the same and different (external testing) institutions in 1 study, respectively., Conclusion: AI, particularly deep learning, holds significant promise in enhancing diagnostic accuracy and efficiency. However, the review highlights several limitations, such as the lack of standardized validation methods and the limited use of external datasets for testing. Future research should address these gaps to ensure the reliability and applicability of AI-based detection systems in clinical settings., Competing Interests: Declarations. Conflict of interest: D. Albano is a Scientific Editorial Board Member, C. Messina is a Junior Deputy Editor, and L.M. Sconfienza is a Consultant to the Editor of La Radiologia Medica. They have not taken part in the review or selection process of this article. The remaining authors declare that they have no competing interests related to this article. Ethical approval: This is a systematic review of the literature. All studies included contain a statement that approval from the local ethics committee and informed consent from each patient or a waiver for it was obtained. The manuscript does not contain new clinical studies or patient data., (© 2024. Italian Society of Medical Radiology.)

Plastic waste pollution has become a global crisis, with millions of tons of plastic expected to accumulate in landfills and in natural environments, posing a serious threat to wildlife and human health. As current recycling methods remain inefficient, there is an urgent need for innovative enzymatic solutions to break down plastics and enable a circular economy approach. In this study, we explore the plastic-degrading potential of microorganisms enriched from activated sludge (AS) sourced from a municipal wastewater treatment plant (WWTP)-a known microplastic-contaminated industrial niche. Five microbial consortia (i.e., microbiomes) were enriched under selective pressure using low-carbon conditions and high concentrations of polyester polymers, including post-consumer PET, post-consumer PLA, and virgin PLA. Enrichment was performed for 100 days at 37 °C and 50 °C, followed by microbiomes isolation and metagenomic analysis to identify plastic-active bacteria and their enzymes. The results revealed that PLA polymers, but not post-consumer PET, were effectively degraded by the microbiomes, as confirmed by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC), showing significant molecular weight reduction compared to the abiotic controls. Microbial community analysis highlighted a distinct enrichment profile driven by the polymer composition and the temperature. At 50 °C, the Bacillales order became the predominant population, whereas at 37 °C, a more diverse community within the Proteobacteria and Actinobacteria phyla were selected. Nonetheless, the enriched microbial communities at both temperatures included phyla with members known for polyester degradation. Moreover, at 50 °C, enrichment of putative PET/PLA hydrolases was also observed. These findings suggest that AS microorganisms are a reservoir of polyester-active enzymes, particularly PLA-depolymerases, and hold promise for advancing biotechnological strategies to mitigate plastic pollution through re- and up-cycling.

Background: The acute and chronic pancreatitis (CP) can lead to severe complications like walled-off necrosis, large symptomatic pseudocyst or multiorgan failure. The treatment of these complications is multivariate and can differ from conservative, symptomatic treatment or minimal-invasive, endoscopic transgastral stenting to transgastral necrosectomy., Objectives: This study aims to analyse the clinical course for patients that develop local complications of severe pancreatitis., Design: This is a retrospective observational single-centre study on 46 patients with severe pancreatitis., Methods: In this retrospective single-centre study, 46 out of 474 inpatients from January 2014 to December 2020, who were treated because of an acute or CP, developed acute pancreatitis complications and could be included. We analysed and compared the clinical course of different treatments (lumen apposing metal stents, transgastral double pigtail stent, endoscopic retrograde cholangiopancreatography, operation, conservative treatment) and different complications (walled-off necrosis (WON), pancreatic pseudocyst (PPC))., Results: Forty-six patients developed an acute complication due to severe pancreatitis. Twenty-seven patients developed a WON, while 19 patients suffered from PPC. 48% of the whole cohort had an alcoholic aetiology of pancreatitis. 78% were treated with antibiotics, 48% suffered from infected pancreatitis and 22% needed intensive care treatment. WON patients more often had a longer hospitalization of more than 21 days. PPC patients were correlated with an alcoholic aetiology, whereas WON patients were inversely correlated with an alcoholic aetiology. Increased lactate dehydrogenase, lipase, and C-reactive protein levels as well as leucocyte count could be associated with a higher probability to exhibit a WON instead of another local complication. The mortality rate was low with 7% in our study., Conclusion: WON and PPC differ in certain patients and laboratory characteristics such as aetiology, elevated laboratory values, antibiotic treatment or the duration of hospitalization. Invasive treatment is not required in all severe pancreatitis cases., (© The Author(s), 2024.)

In the central nervous system, cell-to-cell interaction is essential for brain plasticity and repair, and its alteration is critically involved in the development of neurodegenerative diseases. Neural stem cells are a plentiful source of biological signals promoting neuroplasticity and the maintenance of cognitive functions. Extracellular vesicles (EVs) represent an additional strategy for cells to release signals in the surrounding cellular environment or to exchange information among both neighboring and distant cells. In the last years, rising attention has been devoted to the ability of stem cell (SC)-derived EVs to counteract inflammatory and degenerative brain disorders taking advantage of their immunomodulatory capacities and regenerative potential. Here, we review the role of adult neurogenesis impairment in the cognitive decline associated with neurodegenerative diseases and describe the beneficial effects of SC-derived EVs on brain plasticity and repair also discussing the advantages of SC-derived EV administration versus SC transplantation in the treatment of neurodegenerative disorders., (© The Author(s) 2024. Published by Oxford University Press. 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.)

Acute and chronic stress markedly affects behavior by triggering sympathetic nervous system activation and several hypothalamus-pituitary-adrenal-dependent responses. Brain regions of the limbic system are responsible for the regulation of stress response, and different reports have demonstrated that their activity can be influenced by olfactory stimuli. Here we report that, in mice exposed to acute restraint stress, olfactory stimulation employing a combination of three odorants, i.e. vanillin, limonene and green odor (trans-2-hexenal and cis-3-hexenol) decreased anxiety behavior, assessed in the elevated plus maze, and halted recognition and spatial memory deficits, as appraised in two different object recognition tasks. Of note, when applied singularly, the same odorants were unable to block the detrimental effects of stress. We also found that the multiple odorants stimulation prevented the development of depressive symptoms assessed by the sucrose splash test and forced swim test in an experimental model of depression, i.e. mice exposed to a chronic unpredictable stress paradigm, and reduced interleukin 1β levels in the prefrontal cortex of depressed mice. Collectively, our data indicate that olfactory stimulation counteracts the detrimental effects of acute and chronic stress on mood regulation and cognitive functions, thus representing a potential tool for the treatment of stress-induced disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Surgical resection is the consistent component of curative treatment strategies for primary malignant diseases of the stomach and the esophagus. The placement of anastomoses for the necessary reconstruction still accounts for substantial morbidity and in the case of a failure to rescue also for mortality, especially for esophagojejunostomy and esophagogastrostomy. The diagnostics of anastomotic leakage routinely involve computed tomography and endoscopy and timely performance appears to be essential. Endoscopy can simultaneously initiate the essential treatment step. A major reason for the improvement of postoperative outcomes after resection in the upper gastrointestinal tract in the last decades is the successful and mostly endoscopically performed management of anastomotic leakage, whereby different endoscopic treatment options are now available. Endoscopic vacuum therapy has become established as the standard, normally with an endoscopic vacuum sponge technique but is also now supplemented by a combination system of vacuum sponge and stent. Furthermore, a foil-coated multiple lumen nasogastric tube represents another available option, which can possibly especially be used as a prophylactic measure. The longest established endoscopic therapy option for anastomotic leaks, the endoluminal metal stent, has been replaced as the standard by the vacuum treatment but is still used in suitable situations. Additionally, there are endoscopic suture devices that are currently only used very occasionally. Surgical revision is always available as treatment escalation but is only recommended for very early occurrences and possibly technically related anastomotic leakage and in the case of failure of endoscopic treatment. This article describes and summarizes the diagnostics and treatment of anastomotic leakages after surgical procedures of the upper gastrointestinal tract., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Carbon nanomaterials have been widely applied for cutting edge therapeutic applications as they offer tunable physio-chemical properties with economic scale-up options. Nuclear delivery of cancer drugs has been of prime focus since it controls important cellular signaling functions leading to greater anti-cancer drug efficacies. Better cellular drug uptake per unit drug injection drastically reduces severe side-effects of cancer therapies. Similarly, carbon dots (CDs) uptaken by the nucleus can also be used to set-up cutting edge nano delivery systems. In an earlier paper, we showed the cellular uptake and plasma membrane impact of combustion generated yellow luminescing CDs produced by our group from fuel rich combustion reactors in a one-step tunable production. In this paper, we aim to specifically study the nucleus by establishing the uptake kinetics of these combustion-generated yellow luminescing CDs. At sub-lethal doses, after crossing the plasma membrane, they impact the actin and microtubule mesh, affecting cell adhesion and migration; enter nucleus by diffusion processes; modify the overall appearance of the nucleus in terms of morphology; and alter chromatin condensation. We thus establish how this one-step produced, cost and bulk production friendly carbon dots from fuel rich combustion flames can be innovatively repurposed as potential nano delivery agents in cancer cells.

Objective: To investigate the association between sarcopenia, as appraised with CT-derived muscle metrics, and cardiovascular status, as assessed via coronary CT angiography (CCTA) using the Coronary Artery Disease-Reporting and Data System (CAD-RADS) and with pericoronary adipose tissue (pCAT) metrics., Methods: A retrospective observational study conducted on patients who underwent CCTA. The cross-sectional area (CSA) and attenuation values of the paravertebral muscles at the T8 level and the pectoralis major muscles at the T6 level were measured. The patient height was employed for the normalization of the skeletal muscle CSA. The pCAT attenuation around the coronary arteries was assessed, and the CAD severity was graded using the CAD-RADS reporting system. Regression analyses were performed to assess the impact of demographics, clinical factors, and CT variables on the CAD-RADS and pCAT., Results: A total of 220 patients were included (132 males, median age 65 years). Regression analyses showed the associations of CAD with age and sex ( p < 0.001). Familiarity with CAD was related to the left anterior descending artery pCAT ( p = 0.002) and circumflex artery pCAT ( p = 0.018), whereas age was related to the left anterior descending artery pCAT ( p = 0.032). Weak positive correlations were found between the lower muscle density and lower pCAT attenuation (ρ = 0.144-0.240, p < 0.039)., Conclusions: This study demonstrated weak associations between the sarcopenia indicators and the cardiovascular risk, as assessed by the CAD severity and pCAT inflammation. However, these correlations were not strong predictors of CAD severity, as age and traditional cardiovascular risk factors overshadowed the impact of sarcopenia in the cardiovascular risk assessment.

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form of sensorimotor behavioral tests, or in combination with an intranasal treatment of EVs restored neurological function and ischemic damage. Handled rats were exposed to a battery of sensorimotor tests, including the modified Neurological Severity Score (mNSS), beam balance, corner, grid walking, forelimb placement, and cylinder tests, together with Magnetic Resonance Imaging (MRI) at 2, 7, 14, 21, and 28 days post-stroke (dps). Handled MCAO rats were also exposed to an intranasal multidose or single dose of EVs. Non-handled rats were evaluated only by mNSS and MRI at 2, 28, and 56 dps and were treated with a single intranasal dose of EVs. Our results showed that handling animals after MCAO is necessary for EVs to work at the tested dose and frequency, and that a single cumulative dose of EVs further improves the neurological function recovered during handling. These results show the importance of rehabilitation in combination with other treatments such as EVs, and highlight how extensive behavioral testing might influence functional recovery after stroke., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gomez-Galvez 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: Endoscopic retrograde cholangiopancreaticography (ERCP) is the standard endoscopic procedure for the diagnosis and treatment of diseases of the pancreas and bile ducts. Cholangioscopy provides direct visualization of the bile ducts. It offers the possibility of more detailed diagnostic and therapeutic indications. Today, cholangioscopy is often performed as a single-operator (SOC) procedure., Objectives: We were interested in the clinical efficacy of our SOC procedure in comparison with published studies, and performed this retrospective data analysis of all our consecutive patients from 2016 to 2022 to analyze the feasibility, safety, and efficacy of SOC., Design and Methods: A retrospective single-center analysis of patients undergoing SOC at a tertiary center from 2016 to 2022 ( N  = 196) was performed. Demographic data, indication for SOC, exam-specific data, efficacy, and complications were included. Sensitivity and specificity for diagnosing indeterminate biliary strictures were calculated., Results: The most common indications for SOC were indeterminate biliary strictures ( n  = 117; 60%), treatment of biliary stones ( n  = 45; 23%), and other indications ( n  = 34; 17%), for example, foreign body removal or intraoperative SOC. In 97% of the SOC ( n  = 191), the procedure was technically successful. The diagnostic or therapeutic goal was achieved in 91% of SOC ( n  = 173). In the subgroup where the SOC result was confirmed by subsequent surgery ( n  = 93), sensitivity was 86%, specificity 99%, and SOC treatment of stones was successful in 89%. Complications occurred in (20%; n  = 37). The majority of these patients ( n  = 18; 10%) had minor bleeding requiring no intervention., Conclusion: SOC is an effective and safe procedure that should be the standard of care when primary diagnostic and/or therapeutic ERCP has failed. The sensitivity and specificity for determining the dignity of biliary strictures and the efficacy for the treatment of difficult-to-treat stones are reproducibly very high., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

The rise of agro-industrial activities over recent decades has exponentially increased lignocellulose biomasses (LCB) production. LCB serves as a cost-effective source for fermentable sugars and other renewable chemicals. This study explores the use of microbial consortia, particularly thermophilic consortia, for LCB deconstruction. Thermophiles produce stable enzymes that retain activity under industrial conditions, presenting a promising approach for LCB conversion. This research focused on two microbial consortia (i.e., microbiomes) that were analyzed for enzyme production using a cheap medium, i.e., a mixture of spent mushroom substrate (SMS) and digestate. The secreted xylanolytic enzymes were characterized in terms of temperature and pH optima, thermal stability, and hydrolysis products from LCB-derived polysaccharides. These enzymes showed optimal activity aligning with common biorefinery conditions and outperformed a formulated enzyme mixture in thermostability tests in the digestate. Phylogenetic and genomic analyses highlighted the genetic diversity and metabolic potential of these microbiomes. Bacillus licheniformis was identified as a key species, with two distinct strains contributing to enzyme production. The presence of specific glycoside hydrolases involved in the cellulose and hemicellulose degradation underscores these consortia's capacity for efficient LCB conversion. These findings highlight the potential of thermophilic microbiomes, isolated from an industrial environment, as a robust source of robust enzymes, paving the way for more sustainable and cost-effective bioconversion processes in biofuel and biochemical production and other biotechnological applications.

The placenta is crucial to fetal development and performs vital functions such as nutrient exchange, waste removal and hormone regulation. Abnormal placental development can lead to conditions such as fetal growth restriction, pre-eclampsia and stillbirth, affecting both immediate and long-term fetal health. Placental development is a highly complex process involving interactions between maternal and fetal components, imprinted genes, signaling pathways, mitochondria, fetal sexomes and environmental factors such as diet, supplementation and exercise. Probiotics have been shown to make a significant contribution to prenatal health, placental health and fetal development, with associations with reduced risk of preterm birth and pre-eclampsia, as well as improvements in maternal health through effects on gut microbiota, lipid metabolism, vaginal infections, gestational diabetes, allergic diseases and inflammation. This review summarizes key studies on the influence of dietary supplementation on placental development, with a focus on the role of probiotics in prenatal health and fetal development.

Production of the high industrial value cis,cis-muconic acid (ccMA) from renewable biomasses is of main interest especially when biological (green) processes are used. We recently generated a E. coli strain expressing five recombinant enzymes to convert vanillin (VA, from lignin) into ccMA. Here, we optimized a growing cell approach in bioreactor for the ccMA production. The medium composition, fermentation conditions, and VA addition were tuned: pulse-feeding VA at 1 mmol/h allowed to reach 5.2 g/L of ccMA in 48 h (0.86 g ccMA/g VA), with a productivity 4-fold higher compared to the resting cells approach, thus resulting in significantly lower E-factor and Process Mass Intensity green metric parameters. The recovered ccMA has been used as building block to produce a fully bioderived polymer with rubber-like properties. The sustainable optimized bioprocess can be considered an integrated approach to develop a platform for bio-based polymers production from renewable feedstocks., 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 Ltd.. All rights reserved.)

Metabolic disorders such as insulin resistance and type 2 diabetes are associated with brain dysfunction and cognitive deficits, although the underpinning molecular mechanisms remain elusive. Epigenetic factors, such as non-coding RNAs, have been reported to mediate the molecular effects of nutrient-related signals. Here, we investigated the changes of miRNA expression profile in the hippocampus of a well-established experimental model of metabolic disease induced by high fat diet (HFD). In comparison to the control group fed with standard diet, we observed 69 miRNAs exhibiting increased expression and 63 showing decreased expression in the HFD mice's hippocampus. Through bioinformatics analysis, we identified numerous potential targets of the dysregulated miRNAs, pinpointing a subset of genes regulating neuroplasticity that were targeted by multiple differentially modulated miRNAs. We also validated the expression of these synaptic and non-synaptic proteins, confirming the downregulation of Synaptotagmin 1 (SYT1), calcium/calmodulin dependent protein kinase I delta (CaMK1D), 2B subunit of N-methyl-D-aspartate glutamate receptor (GRIN2B), the DNA-binding protein Special AT-Rich Sequence-Binding Protein 2 (SATB2), and RNA-binding proteins Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) and Neuro-oncological ventral antigen 1 (NOVA1) in the hippocampus of HFD mice. In summary, our study offers a snapshot of the HFD-related miRNA landscape potentially involved in the alterations of brain functions associated with metabolic disorders. By shedding light on the specific miRNA-mRNA interactions, our research contributes to a deeper understanding of the molecular mechanisms underlying the effects of HFD on the synaptic function., (© 2024. The Author(s).)

Osteoporosis is the most prevalent skeletal disorder, a condition that is associated with significant social and healthcare burden. In the elderly, osteoporosis is commonly associated with sarcopenia, further increasing the risk of fracture. Several imaging techniques are available for a non-invasive evaluation of osteoporosis and sarcopenia. This review focuses on dual-energy X-ray absorptiometry (DXA), as this technique offers the possibility to evaluate bone mineral density and body composition parameters with good precision and accuracy. DXA is also able to evaluate the amount of aortic calcification for cardiovascular risk estimation. Additionally, new DXA-based parameters have been developed in recent years to further refine fracture risk estimation, such as the Trabecular Bone Score and the Bone Strain Index. Finally, we describe the recent advances of a newly developed ultrasound-based technology known as Radiofrequency Echographic Multi-Spectrometry, which represent the latest non-ionizing approach for osteoporosis evaluation at central sites., (© 2024. The Author(s).)

Glycoside hydrolases (GHs) are pivotal in the hydrolysis of the glycosidic bonds of sugars, which are the main carbon and energy sources. The genome of Marinomonas sp. ef1, an Antarctic bacterium, contains three GHs belonging to family 3. These enzymes have distinct architectures and low sequence identity, suggesting that they originated from separate horizontal gene transfer events. M-GH3&#95;A and M-GH3&#95;B, were found to differ in cold adaptation and substrate specificity. M-GH3&#95;A is a bona fide cold-active enzyme since it retains 20 % activity at 10 °C and exhibits poor long-term thermal stability. On the other hand, M-GH3&#95;B shows mesophilic traits with very low activity at 10 °C (< 5 %) and higher long-term thermal stability. Substrate specificity assays highlight that M-GH3&#95;A is a promiscuous β-glucosidase mainly active on cellobiose and cellotetraose, whereas M-GH3&#95;B is a β-xylosidase active on xylan and arabinoxylan. Structural analysis suggests that such functional differences are due to their differently shaped active sites. The active site of M-GH3&#95;A is wider but has a narrower entrance compared to that of M-GH3&#95;B. Genome-based prediction of metabolic pathways suggests that Marinomonas sp. ef1 can use monosaccharides derived from the GH3-catalyzed hydrolysis of oligosaccharides either as a carbon source or for producing osmolytes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Marco Mangiagalli reports financial support was provided by University of Milano-Bicocca. Marina Lotti reports financial support was provided by University of Milano-Bicocca. Salvatore Fusco reports financial support was provided by University of Verona. 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 B.V. All rights reserved.)

Over the past few decades, there has been a notable increase in the global burden of central nervous system (CNS) diseases. Despite advances in technology and therapeutic options, neurological and neurodegenerative disorders persist as significant challenges in treatment and cure. Recently, there has been a remarkable surge of interest in extracellular vesicles (EVs) as pivotal mediators of intercellular communication. As carriers of molecular cargo, EVs demonstrate the ability to traverse the blood-brain barrier, enabling bidirectional communication. As a result, they have garnered attention as potential biomarkers and therapeutic agents, whether in their natural form or after being engineered for use in the CNS. This review article aims to provide a comprehensive introduction to EVs, encompassing various aspects such as their diverse isolation methods, characterization, handling, storage, and different routes for EV administration. Additionally, it underscores the recent advances in their potential applications in neurodegenerative disorder therapeutics. By exploring their unique capabilities, this study sheds light on the promising future of EVs in clinical research. It considers the inherent challenges and limitations of these emerging applications while incorporating the most recent updates in the field., (© 2024 The Authors. Medicinal Research Reviews published by Wiley Periodicals LLC.)

Dual-energy CT stands out as a robust and innovative imaging modality, which has shown impressive advancements and increasing applications in musculoskeletal imaging. It allows to obtain detailed images with novel insights that were once the exclusive prerogative of magnetic resonance imaging. Attenuation data obtained by using different energy spectra enable to provide unique information about tissue characterization in addition to the well-established strengths of CT in the evaluation of bony structures. To understand clearly the potential of this imaging modality, radiologists must be aware of the technical complexity of this imaging tool, the different ways to acquire images and the several algorithms that can be applied in daily clinical practice and for research. Concerning musculoskeletal imaging, dual-energy CT has gained more and more space for evaluating crystal arthropathy, bone marrow edema, and soft tissue structures, including tendons and ligaments. This article aims to analyze and discuss the role of dual-energy CT in musculoskeletal imaging, exploring technical aspects, applications and clinical implications and possible perspectives of this technique., (© 2024. The Author(s).)

This review examines the latest advancements in compositional and quantitative cartilage MRI techniques, addressing both their potential and challenges. The integration of these advancements promises to improve disease detection, treatment monitoring, and overall patient care. We want to highlight the pivotal task of translating these techniques into widespread clinical use, the transition of cartilage MRI from technical validation to clinical application, emphasizing its critical role in identifying early signs of degenerative and inflammatory joint diseases. Recognizing these changes early may enable informed treatment decisions, thereby facilitating personalized medicine approaches. The evolving landscape of cartilage MRI underscores its increasing importance in clinical practice, offering valuable insights for patient management and therapeutic interventions. This review aims to discuss the old evidence and new insights about the evaluation of articular cartilage through MRI, with an update on the most recent literature published on novel quantitative sequences.

Total hip arthroplasty (THA) is the best surgical approach for treating advanced hip degeneration, providing pain relief, and improved function in most cases. In the past, MR imaging quality has been highly compromised by in-plane distortions, inadequate fat saturation, and other artifacts due to metal components of THA. Technological advancements have made pathologic conditions, which were previously hidden by periprosthetic artifacts, outstanding features due to the optimization of several sequences. To date, several short and long-term complications involving bony and soft-tissue structures may be detected through magnetic resonance imaging (MRI). The use of MRI with adapted sequences and protocols may drastically reduce artifacts thereby providing essential pre-operative elements for planning revision surgery of failed THA. This review has the purpose of conveying new insights to musculoskeletal radiologists about the techniques to suppress metal-related artifacts and the hallmark MRI findings of painful THA. CRITICAL RELEVANCE STATEMENT: Advancements in metal-suppression have given radiologists the opportunity to play an emerging role in THA management. This article provides technical and imaging insights into challenges that can be encountered in cases of THA, which may present complications and characteristic imaging findings. KEY POINTS: Imaging total hip arthroplasty requires adapted MRI protocol and awareness of the common complications. We have reported the available metal-suppression sequences for evaluating total hip arthroplasty. Many structures and conditions should be considered when dealing with painful aseptic or septic arthroplasty., (© 2024. The Author(s).)

Biocatalysis, a cornerstone of modern biotechnology, is poised to revolutionize industrial processes across diverse sectors [...]., Competing Interests: The authors declare no conflicts of interest.

The stiffness of the extracellular matrix plays a crucial role in cell motility and spreading, influencing cell morphology through cytoskeleton organization and transmembrane proteins' expression. In this context, mechanical characterization of both cells and the extracellular matrix gains prominence for enhanced diagnostics and clinical decision-making. Here, we investigate the combined effect of mechanotransduction and ionizing radiations on altering cells' mechanical properties, analysing mammary cell lines (MCF10A and MDA-MB-231) after X-ray radiotherapy (2 and 10 Gy). We found that ionizing radiations sensitively affect adenocarcinoma cells cultured on substrates mimicking cancerous tissue stiffness (15 kPa), inducing an increased structuration of paxillin-rich focal adhesions and cytoskeleton: this process translates in the augmentation of tension at the actin filaments level, causing cellular stiffness and consequently affecting cytoplasmatic/nuclear morphologies. Deeper exploration of the intricate interplay between mechanical factors and radiation should provide novel strategies to orient clinical outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mottareale, Frascogna, La Verde, Arrichiello, Muto, Netti, Fusco, Panzetta and Pugliese.)

Segmentation and image intensity discretization impact on radiomics workflow. The aim of this study is to investigate the influence of interobserver segmentation variability and intensity discretization methods on the reproducibility of MRI-based radiomic features in lipoma and atypical lipomatous tumor (ALT). Thirty patients with lipoma or ALT were retrospectively included. Three readers independently performed manual contour-focused segmentation on T1-weighted and T2-weighted sequences, including the whole tumor volume. Additionally, a marginal erosion was applied to segmentations to evaluate its influence on feature reproducibility. After image pre-processing, with included intensity discretization employing both fixed bin number and width approaches, 1106 radiomic features were extracted from each sequence. Intraclass correlation coefficient (ICC) 95% confidence interval lower bound ≥ 0.75 defined feature stability. In contour-focused vs. margin shrinkage segmentation, the rates of stable features extracted from T1-weighted and T2-weighted images ranged from 92.68 to 95.21% vs. 90.69 to 95.66% after fixed bin number discretization and from 95.75 to 97.65% vs. 95.39 to 96.47% after fixed bin width discretization, respectively, with no difference between the two segmentation approaches (p ≥ 0.175). Higher stable feature rates and higher feature ICC values were found when implementing discretization with fixed bin width compared to fixed bin number, regardless of the segmentation approach (p < 0.001). In conclusion, MRI radiomic features of lipoma and ALT are reproducible regardless of the segmentation approach and intensity discretization method, although a certain degree of interobserver variability highlights the need for a preliminary reliability analysis in future studies., (© 2024. The Author(s).)

Purpose: To test the feasibility of US/CT fusion imaging to guide lumbar intradiscal O 2 /O 3 therapy to treat discogenic degenerative low back pain due to lumbar disc herniation (LDH)., Methods: We retrospectively included consecutive patients affected by low back pain and/or sciatica due to LDH resistant to conservative therapies, who underwent to lumbar intradiscal O 2 /O 3 injection under CT/US fusion imaging guidance (Fusion Group) and standard CT guidance (Control Group). For each procedure, we collected procedure operative time, room utilization time, number of CT passes, complications, and O 2 /O 3 intradiscal diffusion adequacy. Technical success was defined as the ability to complete the procedure as initially planned to reach the disc. Technical efficacy was based on O 2 /O 3 intradiscal diffusion adequacy, as demonstrated by the last CT scan., Results: Six patients (4 males; mean age: 68 ± 15 years) were included in the Fusion group, six (4 males; mean age: 66 ± 12 years) in Control group. No complications were observed in both groups. In Fusion group we found significantly lower room utilization time (30 ± 6 min vs. 46 ± 10 min, p = 0.008), procedure operative time (14 ± 3 min vs. 24 ± 6 min, p = 0.008), and number of CT passes (2 [2,2] vs. 3 [3,3], p = 0.006) than in Control Group, respectively. Technical success and efficacy were 100% in both Groups., Conclusion: CT/US fusion imaging seems to be a feasible and safe guidance for intradiscal O 2 /O 3 injections, allowing decrease of procedure time and number of CT passes., (© 2023. The Author(s).)

The posteromedial corner (PMC) of the knee is an anatomical region formed by ligamentous structures (medial collateral ligament, posterior oblique ligament, oblique popliteal ligament), the semimembranosus tendon and its expansions, the posteromedial joint capsule, and the posterior horn of the medial meniscus. Injuries to the structures of the PMC frequently occur in acute knee trauma in association with other ligamentous or meniscal tears. The correct assessment of PMC injuries is crucial because the deficiency of these supporting structures can lead to anteromedial rotation instability or the failure of cruciate ligaments grafts. This article reviews the anatomy and biomechanics of the PMC to aid radiologists in identifying injuries potentially involving PMC components., Competing Interests: None declared., (Thieme. All rights reserved.)