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Abstract Tyrosine hydroxylase deficiency (THD) is a rare genetic disorder leading to dopaminergic depletion and early‐onset Parkinsonism. Affected children present with either a severe form that does not respond to L‐Dopa treatment (THD‐B) or a milder L‐Dopa responsive form (THD‐A). We generated induced pluripotent stem cells (iPSCs) from THD patients that were differentiated into dopaminergic neurons (DAn) and compared with control‐DAn from healthy individuals and gene‐corrected isogenic controls. Consistent with patients, THD iPSC‐DAn displayed lower levels of DA metabolites and reduced TH expression, when compared to controls. Moreover, THD iPSC‐DAn showed abnormal morphology, including reduced total neurite length and neurite arborization defects, which were not evident in DAn differentiated from control‐iPSC. Treatment of THD‐iPSC‐DAn with L‐Dopa rescued the neuronal defects and disease phenotype only in THDA‐DAn. Interestingly, L‐Dopa treatment at the stage of neuronal precursors could prevent the alterations in THDB‐iPSC‐DAn, thus suggesting the existence of a critical developmental window in THD. Our iPSC‐based model recapitulates THD disease phenotypes and response to treatment, representing a promising tool for investigating pathogenic mechanisms, drug screening, and personalized management.

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Hyperglycemia during early brain injury (EBI) period after spontaneous subarachnoid hemorrhage (SAH) is associated with poor outcome, but the underlying physiopathology is unknown. This study assessed if hyperglycemia during EBI is associated with markers of neuroaxonal injury and whether these biomarkers partially account for the association between hyperglycemia and poor clinical outcome. Ninety-two SAH patients admitted within 24 h of bleeding onset were prospectively included. Glucose levels were measured at arrival and every 6 h for 72 h. Serum neurofilament light chain (NFL) levels were measured at 72 h. Functional outcome was assessed with the modified Rankin Scale (mRS) at 90 days (poor outcome, mRS > 2). The association between glucose metrics, NFL levels, and clinical outcome was assessed with univariate and multivariate analyses. Mediation analysis was performed to examine the potential chain in which NFL may mediate the relationship between glucose and functional outcome. Higher glucose and NFL levels during EBI were associated with poor clinical outcome in adjusted analysis. NFL levels were associated with older age, higher initial severity, and higher glucose levels during EBI period. In adjusted mediation analyses, the association between glucose and clinical outcome was significantly mediated by NFL levels. The mediator NFL explained 25% of the association between glucose during EBI period and poor functional outcome at 90 days. In SAH, the association between glucose levels during EBI and poor clinical outcome might be significantly mediated by NFL levels. The link between hyperglycemia and poor clinical outcome might be explained in part through secondary neuroaxonal injury. [ABSTRACT FROM AUTHOR]

Mountain environments pose challenges for accurately assessing the population size of ungulates, which may hamper confidence in using abundance estimates for decision-making. Thus, evaluations of the accuracy of methods using known-size populations are valuable. Here, we tested the accuracy of direct counts and distance sampling to assess the size of a fenced population of Iberian ibex (Capra pyrenaica) of known size. We evaluated the influence of observer expertise (beginners and experts) on the detection error of female and male ibexes and whether training improved accuracy. The ibex population comprised 18 individuals (ten males and eight females) living in a 17-ha enclosure in northeastern Spain. After 27 surveys, experts detected 16% more ibexes than beginners. Male ibexes were ~ 13% easier to detect than females, and experts were more accurate than beginners in sexing individuals. Additionally, the detection error in absolute counts was similar among beginners but different among experts (> 10%). Despite reducing detection error over subsequent surveys, under-detection was > 50% in all events (> 85% and > 67% for beginners and experts, respectively). Our data indicate a systematic underestimation of direct counts of our mountain ungulate populations and the contribution of expertise to improving accuracy. Our results show that managers assessing mountain ungulate populations for management purposes should consider alternative methods. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of isolated REM sleep behavior disorder (IRBD) requires video polysomnography (V-PSG) showing increased muscle activity and abnormal behaviors in REM sleep. Objective: To describe in IRBD the behavioral manifestations occurring during REM sleep in the diagnostic V-PSG. Methods: This is a systematic audiovisual V-PSG analysis of consecutive IRBD patients. According to the International RBD Study Group recommendations, REM sleep movements and vocalizations were classified into categories and severity. Results: We analyzed the V-PSG of 62 IRBD patients with a mean age of 67.6 ± 8.1 years. Of 6,330 30-s epochs of REM sleep, 55.1% epochs exhibited motor events, 5.5% contained vocalizations and 39.4% were silent. Among the epochs with motor manifestations, 66.1% contained simple minor movements, 25.0% simple major and 8.9% complex movements. Motor severity of the epochs was mild in 82.2%, moderate in 13.2% and severe in 4.6%. Most movements were bilateral (62.4%) and located in the upper limbs (42.5%). Of the epochs with vocalizations, 61.5% were simple minor, 20.7% complex and 17.8% simple major of mild (72.7%), moderate (23.0%) and severe (4.3%) severity. Complex movements occurred in 87.1% of the patients and complex vocalizations in 38.7%. Conclusions: In IRBD, the most common manifestations in REM sleep are simple minor movements and vocalizations of mild intensity. Complex movements are observed during REM sleep in most patients but are much less frequent than simple minor and major motor events. These findings should be considered for the routine diagnosis of IRBD when reviewing the V-PSG studies. [ABSTRACT FROM AUTHOR]

Introduction: Open ureteroenteric reimplantation (OUER) of ureteroenteric strictures (UESs) is related to important morbidity. Robot-assisted ureteroenteric reimplantation (RUER) has been proposed to provide similar outcomes with lower morbidity. We aimed to compare perioperative and functional outcomes between RUER and OUER. Methods: A retrospective multicenter study of 80 patients, who underwent 82 ureteroenteric reimplantations (17 OUER vs 65 RUER) at 8 institutions between 2009–2021 for benign UESs after radical cystectomy. All the open procedures were performed by the same center in order to compare the robotic approach with a standardized technique. Data were reviewed for demographics, stricture characteristics, and perioperative outcomes. Complication and stricture recurrence rates were compared between both groups. Results: Among 82 reimplantations, 44 were left sided (54%) and 12 bilateral (14%). Median time from cystectomy to diagnosis of stricture was 6 months (range 3–18). Baseline characteristics (gender, age, BMI, side, type of urinary diversion and previous abdominal radiotherapy) were comparable between RUER and OUER groups, except for ASA score and rates of prior robotic cystectomy. The 30-day overall postoperative complication rate was 37% in RUER compared to 70.6% in OUER (p = 0.026). Patients who underwent a RUER had statistically significant lower rate of intraoperative blood transfusion (0% vs 12%, p = 0.041), urinary tract infection (12% vs 53%, p < 0.001), bowel injury (0% vs 12%, p = 0.041) and high-grade complications (Clavien III-IV) (4.6% vs 23.5%, p = 0.031). RUER patients had shorter median length of hospital stay (3 days IQR[1–6] vs 6 IQR[3–9], p = 0.018) and lower readmission rate (4.6% vs 29.4%, p = 0.008). After a median follow-up of 23.5 months (8.7–43), 80% of RUER cases were stricture free compared to 90% of OUER (p = 0.42). Conclusions: RUER achieved a success rate comparable to that of open revisions and may provide some advantages in terms of perioperative outcomes. Prospective and larger studies are warranted to prove its superiority compared to the standard open technique. [ABSTRACT FROM AUTHOR]

Introduction: Unicompartmental knee arthroplasty (UKA) treats osteoarthritis in one knee compartment, while total knee arthroplasty (TKA) addresses all compartments. The debate focuses on UKA's advantages of quicker recovery and fewer complications versus TKA's lower long-term revision rates, emphasizing the need for thorough outcome evaluations. The aim of the present study is to describe and compare the pain, functional and psychological trajectories during a 6-month postoperative rehabilitation period between total and unicompartmental knee arthroplasties. Materials and Methods: 115 participants who had undergone either TKA or UKA were recruited. Outcome measurements were performed at 1, 4, 12 and 24 weeks post-surgery. Measurements included pain intensity (Visual Analog Scale), range of motion, walking speed (4 m walking test), physical performance (30-s chair stand test), health functioning (Western Ontario and McMaster Universities Osteoarthritis Index), pain catastrophizing (pain catastrophizing scale), fear of movement (Tampa Scale of Kinesiophobia), anxiety and depression (Hospital Anxiety and Depression Scale). A mixed-effects model was used to estimate the influence of type of surgery (either unicompartmental or total knee arthroplasty) to pain, function, and psychological trajectories. Results: Both TKA and UKA groups showed significant improvements across the six-month rehabilitation period except for anxiety symptoms in the TKA group, and fear of movement and depression in the UKA group. Between group analysis revealed that in the acute phase UKA patients showed improved range of motion and TKA patients displayed faster walking speed but higher fear of movement. Overall, the type of surgery does not significantly influence the overall rehabilitation pain, functional and psychological trajectories. Conclusions: Despite differences in the acute phase, there are no differences in pain, functional and psychological trajectories throughout the six-month rehabilitation period. These results should be acknowledged to better inform patients and to improve patient education during the perioperative period. Trial registration number: NCT03378440 (2017-12-18), retrospectively registered. Level of evidence: Level II. [ABSTRACT FROM AUTHOR]

Neural networks are widely used in critical environments such as healthcare, autonomous vehicles, or video surveillance. To ensure the safety of the systems that rely on their functionality, it is essential to validate their correct behaviour in the presence of faults. This paper studies the behaviour of state-of-the-art neural network models with fault injection in their weights. For this purpose, we analyse the sensitivity of these models and identify the impact of bit flips on their accuracy. To mitigate the effects of faults, we introduce two mechanisms that leverage bit-level redundancy for protection. The first mechanism, Fixed Protection, safeguards consecutive sets of bits, while the second, Variable Protection, targets non-consecutive bits. Our findings demonstrate that, on average, random bit flip faults cause the accuracy of the original models to drop by 1.3% to over 3%. However, with our protection mechanisms in place, accuracy reductions are significantly minimised, ranging from only 0.0001% to 0.4%. [ABSTRACT FROM AUTHOR]

Isolated rapid-eye-movement sleep behavior disorder (iRBD) is a strong predictor of Parkinson’s disease and Dementia with Lewy bodies. Previous studies indicate that cortical atrophy in iRBD patients may be linked to cognitive impairment, but the pattern of atrophy is inconsistently reported. This study aimed to elucidate cortical atrophy patterns in a cognitively unimpaired iRBD cohort, focusing on regions associated with cognitive functions, particularly the cuneus/precuneus, and evaluated the predictive value for future phenoconversion. We conducted voxel-based morphometry and region of interest (ROI) analysis of structural MRI scans of 36 healthy controls and 19 iRBD patients, nine of whom also received a 3-year follow-up MRI scan. The iRBD patients were followed clinically for 8 years, and time-to-event analyses, using Cox regression, were performed based on baseline ROI volumes. The iRBD patients had lower gray-matter volume in the cuneus/precuneus region as well as in subcortical structures (caudate nuclei and putamen) compared to controls. Eight iRBD patients developed either Parkinson’s disease (N = 4) or Dementia with Lewy bodies (N = 4) during the follow-up period. Time-to-event analyses showed that lower right cuneus volume was associated with a higher risk of phenoconversion to alpha-synuclein-linked Parkinsonism in the iRBD patients (Hazard ratio = 13.0, CI: 1.53–110), and correlated with shorter time to conversion. In addition, lower volumes of the bilateral precuneus trended to indicate a higher risk of phenoconversion. These findings suggest a potential predictive value of cuneus and precuneus volumes in identifying iRBD patients at risk of disease progression, even before the onset of cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption is popular among adolescents and young people and adolescent non-drinkers may be socially excluded and/or stigmatized. The aim of this qualitative study was to explore the social life of young non-drinkers (14–20 years old), to understand how they live their non-drinking and how they are perceived by their drinking peers. Methods: We conducted a qualitative research on non-consumption of alcohol in the French-speaking region of Switzerland. Our study included 63 young people divided into 12 focus groups aged 14 to 20 years. Results: Overall, young non-drinkers would be a minority in their peer groups, leading some of them to feel out of the norm. Participants reported that not drinking alcohol is generally questioned and non-drinkers are almost always asked to justify their non-consumption. Finally, non-drinkers are sometimes automatically designated as resources who have to control the drinking of others and/or are the ones who help their drinking-peers if they are drunk and need help, a status that can put them under pressure. Conclusions: It is important to normalize the non-consumption of alcohol and make non-drinkers visible by including them in school-based prevention interventions. [ABSTRACT FROM AUTHOR]

Orchard and tree-child networks share an important property with phylogenetic trees: they can be completely reduced to a single node by iteratively deleting cherries and reticulated cherries. As it is the case with phylogenetic trees, the number of ways in which this can be done gives information about the topology of the network. Here, we show that the problem of computing this number in tree-child networks is akin to that of finding the number of linear extensions of the poset induced by each network, and give an algorithm based on this reduction whose complexity is bounded in terms of the level of the network. [ABSTRACT FROM AUTHOR]

Positron Emission Tomography (PET) imaging after 90 Y liver radioembolization is used for both lesion identification and dosimetry. Bayesian penalized likelihood (BPL) reconstruction algorithms are an alternative to ordered subset expectation maximization (OSEM) with improved image quality and lesion detectability. The investigation of optimal parameters for 90 Y image reconstruction of Q.Clear, a commercial BPL algorithm developed by General Electric (GE), in PET/MR is a field of interest and the subject of this study. The NEMA phantom was filled at an 8:1 sphere-to-background ratio. Acquisitions were performed on a PET/MR scanner for clinically relevant activities between 0.7 and 3.3 MBq/ml. Reconstructions with Q.Clear were performed varying the β penalty parameter between 20 and 6000, the acquisition time between 5 and 20 min and pixel size between 1.56 and 4.69 mm. OSEM reconstructions of 28 subsets with 2 and 4 iterations with and without Time-of-Flight (TOF) were compared to Q.Clear with β = 4000. Recovery coefficients (RC), their coefficient of variation (COV), background variability (BV), contrast-to-noise ratio (CNR) and residual activity in the cold insert were evaluated. Increasing β parameter lowered RC, COV and BV, while CNR was maximized at β = 4000; further increase resulted in oversmoothing. For quantification purposes, β = 1000–2000 could be more appropriate. Longer acquisition times resulted in larger CNR due to reduced image noise. Q.Clear reconstructions led to higher CNR than OSEM. A β of 4000 was obtained for optimal image quality, although lower values could be considered for quantification purposes. An optimal acquisition time of 15 min was proposed considering its clinical use. [ABSTRACT FROM AUTHOR]

A Multi-Channel Man-in-the-Middle (MC-MitM) attack is an advanced form of MitM attack, characterized by its ability to manipulate encrypted wireless communications between the Access Point (AP) and clients within a WiFi network. MC-MitM attacks can target any Wi-Fi client, regardless of the authentication method used with the AP. Notable examples of such attacks include Key Reinstallation Attacks and FragAttacks, which have impacted millions of WiFi systems worldwide, especially those involving Internet of Things devices. Current defense mechanisms are inadequate against these attacks due to interoperability challenges and the need for modifications to devices or protocols within the targeted Wi-Fi networks. This paper introduces a distributed and cooperative signature-based wireless intrusion detection mechanism designed for online passive monitoring to detect malicious traffic patterns during MC-MitM attacks in any environment, from apartments and houses to large areas like hotels, offices or industrial sites. We implemented the proposed framework on Raspberry Pis and evaluated it in real-world settings. Our evaluation demonstrates that this framework can effectively identify MC-MitM attacks with an average accuracy of 98% when deployed across different locations within our experimental testbed. [ABSTRACT FROM AUTHOR]

The article discusses the outcomes of using a cemented modular rotational-hinge design in a two-stage replacement for chronic knee periprosthetic joint infection. The study found an infection control rate of 87.2% and an implant survival rate of 92.3% after a mean follow-up of 4.3 years. Factors associated with increased risk of infection control failure included obesity, history of cancer, and the need for debridement after the second stage. The study suggests that the use of a cemented modular rotational-hinge design may be associated with high rates of infection control and low incidence of aseptic loosening or modular component failure. [Extracted from the article]

We consider a hierarchically structured population in which the amount of resources an individual has access to is affected by individuals that are larger, and that the intake of resources by an individual only affects directly the growth rate of the individual. We formulate a deterministic model, which takes the form of a delay equation for the population birth rate. We also formulate an individual based stochastic model, and study the relationship between the two models. In particular the stationary birth rate of the deterministic model is compared to that of the quasi-stationary birth rate of the stochastic model. Since the quasi-stationary birth rate cannot be obtained explicitly, we derive a formula to approximate it. We show that the stationary birth rate of the deterministic model can be obtained as the large population limit of the quasi-stationary birth rate of the stochastic model. This relation suggests that the deterministic model is a good approximation of the stochastic model when the number of individuals is sufficiently large. [ABSTRACT FROM AUTHOR]

In the R 2 plane, the simplest non-linear differential systems are the quadratic polynomial differential systems. This type of differential systems have been studied intensively because of its non-linearity and wide range of applications. These systems have been classified into ten classes. In this article, we characterize in the Poincarè disk all topologically different phase portraits for one of these classes. Concretely we provide the complete study of the geometry of family IV. The family IV is six-dimensional and is reduced to several subfamilies which are three-dimensional. We give the bifurcation diagram of each specific normal form using invariant polynomials. The split of all quadratic systems in ten subfamilies could have been a good way to find all possible phase portraits of quadratic systems, if all ten families could have been studied completely. All families are six-dimensional and some of them can even be divided in several subfamilies with fewer parameters. However, certain families (I, II, and III) are too generic and cannot be reduced enough to allow its complete study. Regardless, this division of quadratic systems has been useful to study several families of quadratic systems having some other properties, and it is worth trying to get as many of them as possible studied in a complete way. [ABSTRACT FROM AUTHOR]

Chronic sexual abuse in childhood can be directly associated with the formation of personality disorders such as BPD, with the majority of this abuse occurring in the family context. The objective of this article is to reference the importance of clinical and psychotherapeutic intervention from a systemic approach, prioritizing the analysis of interpersonal relationships, behavioral patterns repeated during the patient's history and the adaptation of family roles learned during childhood to adulthood, obtaining extremely positive results in terms of remission of symptoms and general recovery of the patient. [ABSTRACT FROM AUTHOR]

Animated films are highly popular in society, particularly among children and adolescents. During film production, selecting an adequate colour palette and scene dynamism is crucial for creating a visual impact on the audience. However, the influence of visual aesthetics, such as colour and scene dynamism on visual fatigue remains unexplored. In the present study, visual fatigue was assessed and compared in 30 young participants after viewing two popular films: Spider-Man: Across the Spider-Verse, an active, fast-paced film, and My Neighbour Totoro, a more relaxed film. Both films were viewed twice, once with the original colour palette and once in greyscale. Watching Spider-Man film induced a greater degree of visual fatigue than My Neighbour Totoro in two subjective questionnaires evaluating visual fatigue, and in the vergence facility and binocular accommodative facility tests. Moreover, important differences in the visual dynamics and colour aspects between both films were found. These results demonstrate that the high-paced and high-colour aspects of films directly affect visual fatigue. Future animated film producers should consider these factors that are relevant to their audiences. [ABSTRACT FROM AUTHOR]

The promotion of healthy aging has become a priority in most parts of the world and should be promoted at all ages. However, the baseline training of health and social professionals is currently not adequately tailored to these challenges. This paper reports the results of a Delphi study conducted to reach expert agreement about health and social professionals' competencies to promote healthy aging throughout the lifespan within the SIENHA project. Materials and methods: This study was developed following the CREDES standards. The initial version of the competence framework was based on the results of a scoping review and following the CanMEDS model. The expert panel consisted of a purposive sample of twenty-two experts in healthy aging with diverse academic and clinical backgrounds, fields and years of expertise from seven European countries. Agreement was reached after three rounds. The final framework consisted of a set of 18 key competencies and 80 enabling competencies distributed across six domains. The SIENHA competence framework for healthy aging may help students and educators enrich their learning and the academic content of their subjects and/or programs and incentivize innovation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) has a 5-year overall survival rate of over 60%. The decrease in the rate of metastatic disease is due to screening programs and the population's awareness of healthy lifestyle. Similarly, advancements in surgical methods and the use of adjuvant chemotherapy have contributed to a decrease in the recurrence of resected disease. Before evaluating a patient's treatment, it is recommended to be discussed in a multidisciplinary tumor board. In stage II tumors, the pathologic characteristics of poor prognosis must be known (T4, number of lymph nodes analyzed less than 12, lymphovascular or perineural invasion, obstruction or perforation, poor histologic grade, presence of tumor budding) and it is mandatory to determine the MSI/MMR status for avoiding administering fluoropyridimidines in monotherapy to patients with MSI-H/dMMR tumors. In stage III tumors, the standard treatment consists of a combination of fluoropyrimidine (oral or intravenous) with oxaliplatin for 6 months although the administration of CAPOX can be considered for 3 months in low-risk tumors. Neoadjuvant treatment is not consolidated yet although immunotherapy is achieving very good preliminary results in MSI-H patients. The use of ctDNA to define the treatment and monitoring of resected tumors is only recommended within studies. These guidelines are intended to help decision-making to offer the best management of patients with non-metastatic colon cancer. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint pain and disability. The connection between RA and cardiovascular (CV) disease is still being studied. This research aims to explore the relationship between CV-related microRNAs, inflammation, and glycosylated proteins to understand RA's inflammatory pathophysiology concerning CV disease. The study included 219 RA patients, 82 with metabolic disorders, and 64 controls. Clinical evaluations and blood samples were collected. Quantification of microRNAs (Let7a, 24, 96, 103, 125a, 125b, 132, 146, 191, 223, 425, 451) and measurement of glycoproteins (GlycA, GlycB, GlycF) using proton nuclear magnetic resonance (1 H-NMR) were performed. Multivariate linear models were applied. RA patients showed higher glycoprotein levels than those with metabolic disorders and controls. Significant associations between miRNAs 24, 451, Let7a and glycoprotein levels were found in RA patients, particularly in women. Glycoprotein levels were positively correlated with inflammatory markers, highlighting their role in indicating RA severity. This study highlights elevated glycoprotein levels in RA patients, indicating a severe inflammatory pattern. Moreover, glycoproteins were highly associated with CV-disease-related miRNAs, indicating that glycoproteins are involved in both inflammation and CV disease. Finally, the inflammatory profile of glycoproteins was validated as they were highly associated with inflammatory markers of RA. [ABSTRACT FROM AUTHOR]

Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers. In 15 patients (68%), we observed a hypothalamic and brainstem-predominant tauopathy of varying severity in which the original research neuropathological criteria were readily applicable. This pathology was observed in younger patients (median age at onset 61 years) with a long disease duration (median 9 years). In contrast, in 7 (32%) patients, the originally described brainstem tauopathy was nearly absent or only minimal in the form of delicate threads, despite mild-to-moderate neurodegenerative features, consistent clinical symptoms and the presence of anti-IgLON5 antibodies in CSF and serum. These patients were older at onset (median 79 years) and had shorter disease duration (median < 1 year). Overall, about one-third of the patients showed concomitant TDP-43 pathology within the regions affected by tau pathology and/or neurodegeneration. Based on these observations and in view of the spectrum of the tau burden in the core regions involved in the disease, we propose a simple staging system: stage 1 mild neurodegeneration without overt or only minimal tau pathology, stage 2 moderate neurodegeneration and mild/ moderate tauopathy and stage 3 prominent neurodegeneration and tau pathology. This staging intends to reflect a potential (age- and time-dependent) progression of tau pathology, supporting the current notion that tau accumulation is a secondary phenomenon related to the presence of anti-IgLON5 antibodies in the CNS. Finally, we adapt the original research criteria of the anti-IgLON5 disease-related tauopathy to include the spectrum of pathologies observed in this larger postmortem series. [ABSTRACT FROM AUTHOR]

Objectives: In lung cancer, one of the main limitations for the optimal integration of the biological and anatomical information derived from Positron Emission Tomography (PET) and Computed Tomography (CT) is the time and expertise required for the evaluation of the different respiratory phases. In this study, we present two open-source models able to automatically segment lung tumors on PET and CT, with and without motion compensation. Materials and methods: This study involved time-bin gated (4D) and non-gated (3D) PET/CT images from two prospective lung cancer cohorts (Trials 108237 and 108472) and one retrospective. For model construction, the ground truth (GT) was defined by consensus of two experts, and the nnU-Net with 5-fold cross-validation was applied to 560 4D-images for PET and 100 3D-images for CT. The test sets included 270 4D- images and 19 3D-images for PET and 80 4D-images and 27 3D-images for CT, recruited at 10 different centres. Results: In the performance evaluation with the multicentre test sets, the Dice Similarity Coefficients (DSC) obtained for our PET model were DSC(4D-PET) = 0.74 ± 0.06, improving 19% relative to the DSC between experts and DSC(3D-PET) = 0.82 ± 0.11. The performance for CT was DSC(4D-CT) = 0.61 ± 0.28 and DSC(3D-CT) = 0.63 ± 0.34, improving 4% and 15% relative to DSC between experts. Conclusions: Performance evaluation demonstrated that the automatic segmentation models have the potential to achieve accuracy comparable to manual segmentation and thus hold promise for clinical application. The resulting models can be freely downloaded and employed to support the integration of 3D- or 4D- PET/CT and to facilitate the evaluation of its impact on lung cancer clinical practice. Clinical relevance statement: We provide two open-source nnU-Net models for the automatic segmentation of lung tumors on PET/CT to facilitate the optimal integration of biological and anatomical information in clinical practice. The models have superior performance compared to the variability observed in manual segmentations by the different experts for images with and without motion compensation, allowing to take advantage in the clinical practice of the more accurate and robust 4D-quantification. Key Points: Lung tumor segmentation on PET/CT imaging is limited by respiratory motion and manual delineation is time consuming and suffer from inter- and intra-variability. Our segmentation models had superior performance compared to the manual segmentations by different experts. Automating PET image segmentation allows for easier clinical implementation of biological information. [ABSTRACT FROM AUTHOR]

Pseudomonas luteola (P.luteola), formerly called Chryseomonas luteola, is a strict aerobic gram-negative bacillus, 0.8 to 1.0 µm wide and 1.5 to 2.5 µm long, considered an opportunistic pathogen found ubiquitously in humid environments, both in soil and water. It sporadically causes disease in animals and immunosuppressed humans or those subjected to invasive procedures such us peritoneal dialysis or catheterization. In ferrets, this infection was first described in Spain in 2012 and since then, cases have appeared occasionally in Finland, Austria, Australia, France, the United States and also in Spain. This pathogen is considered an emerging zoonotic disease in ferrets, causing respiratory disease, panniculitis, and abscesses due to pyogranulomatous or suppurative inflammation predominantly of the pleura, lung, mediastinum, panniculus or salivary glands, frequently with lethal consequences. The clinical case of a ferret, infected by Pseudomona luteola, presenting with ulcerative suppurative pododermatitis and ipsilateral popliteal purulent lymphadenitis, is described. Together with a complete resolution of the clinical case by means of a non-invasive medical management likely due to the rapid detection, identification, and treatment of the infection. [ABSTRACT FROM AUTHOR]

Aim: To assess the appropriateness of systemic oncological treatments (SOT) provided to patients diagnosed with advanced esophageal cancer (EC) across a group of participating hospitals. Methods: Multicenter, retrospective cohort study in five Spanish hospitals including newly confirmed advanced EC cases between July 1, 2014, and June 30, 2016, with a 5-year follow-up. Results: We identified 157 patients fulfilling the inclusion criteria (median age: 65 years, 85.9% males). Most patients, 125 (79.6%) were treated at least with one active treatment, and 33% received two or more lines of SOT. The 1-, 2- and 5-year overall survival rates were 30.3% [95%CI: 23.8, 38.7], 14.0% [95%CI: 9.3, 21.0], and 7.1% [95% CI: 3.8, 13.1] respectively, and the median survival time 8 months (95% CI: 6, 19) for stages IIIb IIIc and 7 months (95% CI: 5, 9) for stage IV. Clinical stage, receiving more than one line of SOT, and treatment with radiotherapy accelerated the time to death (0.4, 0.9-, and 0.8-times shorter survival respectively, p < 0.05). Better performance status (ECOG < 2) extended survival time by 2.2 times (p = 0.04). Age < 65 years (OR 9.4, 95% CI 3.2, 31.4, p < 0.001), and being treated in one particular hospital (OR 0.2, 95% CI 0.0, 0.8, p < 0.01) were associated with the administration of two or more lines of SOT. Altogether, 18.9% and 9.0% of patients received chemotherapy in the last four and two weeks of life, respectively. Moreover, 2.5% of patients were prescribed a new line of chemotherapy during the last month of life. The proportion of all patients who did not have access to palliative care reached 29.3%, and among those who had access to it, 34.2% initiated it in the last month of life. Conclusion: A high proportion of advanced EC patients receive many treatments not based on sound evidence and they do not benefit enough from palliative care services. The most accepted appropriateness indicators point out that some of the analyzed patients could have been overtreated. This study provides important insights into the quality of care provided to advanced EC, and furthermore, for giving valuable insight and opportunities for improvement. [ABSTRACT FROM AUTHOR]

Cellular senescence is a hallmark of advanced age and a major instigator of numerous inflammatory pathologies. While endothelial cell (EC) senescence is aligned with defective vascular functionality, its impact on fundamental inflammatory responses in vivo at single-cell level remain unclear. To directly investigate the role of EC senescence on dynamics of neutrophil-venular wall interactions, we applied high resolution confocal intravital microscopy to inflamed tissues of an EC-specific progeroid mouse model, characterized by profound indicators of EC senescence. Progerin-expressing ECs supported prolonged neutrophil adhesion and crawling in a cell autonomous manner that additionally mediated neutrophil-dependent microvascular leakage. Transcriptomic and immunofluorescence analysis of inflamed tissues identified elevated levels of EC CXCL1 on progerin-expressing ECs and functional blockade of CXCL1 suppressed the dysregulated neutrophil responses elicited by senescent ECs. Similarly, cultured progerin-expressing human ECs exhibited a senescent phenotype, were pro-inflammatory and prompted increased neutrophil attachment and activation. Collectively, our findings support the concept that senescent ECs drive excessive inflammation and provide new insights into the mode, dynamics, and mechanisms of this response at single-cell level. Synopsis: A murine model of endothelial cell (EC) senescence reveals that exacerbated generation of EC-derived CXCL1 is a driver of pathogenic neutrophil interactions with senescent endothelium at sites of inflammation. Senescent progerin-expressing ECs support aberrant neutrophil adhesion in inflamed tissues. Senescent ECs promote neutrophil-dependent vascular leakage. The pro-inflammatory effects of senescent ECs is mediated by excessive EC production of CXCL1. A murine model of endothelial cell (EC) senescence reveals that exacerbated generation of EC-derived CXCL1 is a driver of pathogenic neutrophil interactions with senescent endothelium at sites of inflammation. [ABSTRACT FROM AUTHOR]

Intracranial tumors present a significant therapeutic challenge due to their physiological location. Immunotherapy presents an attractive method for targeting these intracranial tumors due to relatively low toxicity and tumor specificity. Here we show that SCIB1, a TRP-2 and gp100 directed ImmunoBody® DNA vaccine, generates a strong TRP-2 specific immune response, as demonstrated by the high number of TRP2-specific IFNγ spots produced and the detection of a significant number of pentamer positive T cells in the spleen of vaccinated mice. Furthermore, vaccine-induced T cells were able to recognize and kill B16HHDII/DR1 cells after a short in vitro culture. Having found that glioblastoma multiforme (GBM) expresses significant levels of PD-L1 and IDO1, with PD-L1 correlating with poorer survival in patients with the mesenchymal subtype of GBM, we decided to combine SCIB1 ImmunoBody® with PD-1 immune checkpoint blockade to treat mice harboring intracranial tumors expressing TRP-2 and gp100. Time-to-death was significantly prolonged, and this correlated with increased CD4+ and CD8+ T cell infiltration in the tissue microenvironment (TME). However, in addition to PD-L1 and IDO, the GBM TME was found to contain a significant number of immunoregulatory T (Treg) cell-associated transcripts, and the presence of such cells is likely to significantly affect clinical outcome unless also tackled. [ABSTRACT FROM AUTHOR]

Increasing seawater influence in coastal areas is an ongoing environmental issue. Gardening is a widespread activity mainly in touristic areas such as the Mediterranean coasts. However, the use of exotic species well adapted to salinity encompasses the risk of invasive species introduction. This study aimed to evaluate salinity tolerance of native geophytes, Pancratium maritimum L. and Eryngium maritimum L., to assess their use as ornamental species in salt affected coastal areas. Experiments were conducted using cultivated plants for flowering response and physiological and enzymatic antioxidant response. Six treatments were applied for two months, exposing plants to seawater (SW) dilutions (Tap-Water, 6.25%SW, 12.5%SW, 25%SW, 50%SW and 100%SW). Taxa decreased inflorescence production being this effect more architectonical in E. maritimum and affecting all inflorescence integrity in P. maritimum. Flowering time was strongly delayed and reduced in P. maritimum, while E. maritimum showed smaller effects among treatments. Physiological and biochemical response showed at moderate salinity levels (1/4SW) variation concomitant with late stress response and senescence in P. maritimum, with decreased water use efficiency, NPQ values, and enzymatic activity, and increased malondialdehyde (MDA) levels. In contrast, E. maritimum showed early stress response with steady gas exchange response, increasing NPQ values and catalase (CAT) and superoxide dimutase (SOD) activity, and decreasing MDA levels with salinity. Glutathione enzymes showed limited participation in both species. The results of this study suggest that neither species can be classified as halophytes, but they exhibit tolerance to low and moderate salinity levels, making them suitable for ornamental use. [ABSTRACT FROM AUTHOR]

The article discusses the need to diversify voices in the field of philosophy of science by including perspectives from across the globe. The edited collection, "Global Epistemologies and Philosophies of Science," aims to move beyond the traditional Western philosophical canon to showcase different visions on epistemology and philosophy of science. The volume is directed towards specialized academic communities of philosophers of science and undergraduate and graduate students in history and philosophy of science, offering a broad overview of epistemologies from different cultural and geographical areas. The book challenges traditional curricula by providing entry points into philosophy of science along paths that were previously less explored, such as decolonial philosophy and feminist epistemology. [Extracted from the article]

Abstract The consequence of a mutation can be influenced by the context in which it operates. For example, loss of gene function may be tolerated in one genetic background, and lethal in another. The extent to which mutant phenotypes are malleable, the architecture of modifiers and the identities of causal genes remain largely unknown. Here, we measure the fitness effects of ~ 1,100 temperature‐sensitive alleles of yeast essential genes in the context of variation from ten different natural genetic backgrounds and map the modifiers for 19 combinations. Altogether, fitness defects for 149 of the 580 tested genes (26%) could be suppressed by genetic variation in at least one yeast strain. Suppression was generally driven by gain‐of‐function of a single, strong modifier gene, and involved both genes encoding complex or pathway partners suppressing specific temperature‐sensitive alleles, as well as general modifiers altering the effect of many alleles. The emerging frequency of suppression and range of possible mechanisms suggest that a substantial fraction of monogenic diseases could be managed by modulating other gene products.

Abstract The importance of skeletal muscle tissue is undoubted being the controller of several vital functions including respiration and all voluntary locomotion activities. However, its regenerative capability is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. Here, we propose a biofabrication approach to rapidly restore skeletal muscle mass, 3D histoarchitecture, and functionality. By recapitulating muscle anisotropic organization at the microscale level, we demonstrate to efficiently guide cell differentiation and myobundle formation both in vitro and in vivo. Of note, upon implantation, the biofabricated myo‐substitutes support the formation of new blood vessels and neuromuscular junctions—pivotal aspects for cell survival and muscle contractile functionalities—together with an advanced muscle mass and force recovery. Altogether, these data represent a solid base for further testing the myo‐substitutes in large animal size and a promising platform to be eventually translated into clinical scenarios.

Abstract In Alzheimer’s disease (AD), tau phosphorylation in the brain and its subsequent release into cerebrospinal fluid (CSF) and blood is a dynamic process that changes during disease evolution. The main aim of our study was to characterize the pattern of changes in phosphorylated tau (p‐tau) in the preclinical stage of the Alzheimer’s continuum. We measured three novel CSF p‐tau biomarkers, phosphorylated at threonine‐181 and threonine‐217 with an N‐terminal partner antibody and at threonine‐231 with a mid‐region partner antibody. These were compared with an automated mid‐region p‐tau181 assay (Elecsys) as the gold standard p‐tau measure. We demonstrate that these novel p‐tau biomarkers increase more prominently in preclinical Alzheimer, when only subtle changes of amyloid‐β (Aβ) pathology are detected, and can accurately differentiate Aβ‐positive from Aβ‐negative cognitively unimpaired individuals. Moreover, we show that the novel plasma N‐terminal p‐tau181 biomarker is mildly but significantly increased in the preclinical stage. Our results support the idea that early changes in neuronal tau metabolism in preclinical Alzheimer, likely in response to Aβ exposure, can be detected with these novel p‐tau assays.

Abstract An open debate in antiangiogenic therapies is about their consequence on tumor invasiveness and metastasis, which is undoubtedly relevant for patients currently treated with antiangiogenics, such as renal cell carcinoma patients. To address, this we developed an extensive series of 27 patient biopsy‐derived orthotopic xenograft models (Ren‐PDOX) that represent inter‐patient heterogeneity. In specific tumors, antiangiogenics produced increased invasiveness and metastatic dissemination, while in others aggressiveness remained unchanged. Mechanistically, species‐discriminative RNA sequencing identified a tumor cell‐specific differential expression profile associated with tumor progression and aggressivity in TCGA RCC patients. Gene filtering using an invasion‐annotated patient series pinpointed two candidate genes, of which ALDH1A3 differentiated the pro‐invasive subtype of Ren‐PDOXs. Validation in an independent series of 15 antiangiogenic‐treated patients confirmed that pre‐treatment ALDH1A3 can significantly discriminate patients with pro‐aggressive response upon treatment. Overall, results confirm that effects of antiangiogenic drugs on tumor invasion and metastasis are heterogeneous and may profoundly affect the natural progression of tumors and promote malignancy. Furthermore, we identify a specific molecular biomarker that could be used to select patients that better benefit from treatment.

Abstract Essential genes tend to be highly conserved across eukaryotes, but, in some cases, their critical roles can be bypassed through genetic rewiring. From a systematic analysis of 728 different essential yeast genes, we discovered that 124 (17%) were dispensable essential genes. Through whole‐genome sequencing and detailed genetic analysis, we investigated the genetic interactions and genome alterations underlying bypass suppression. Dispensable essential genes often had paralogs, were enriched for genes encoding membrane‐associated proteins, and were depleted for members of protein complexes. Functionally related genes frequently drove the bypass suppression interactions. These gene properties were predictive of essential gene dispensability and of specific suppressors among hundreds of genes on aneuploid chromosomes. Our findings identify yeast's core essential gene set and reveal that the properties of dispensable essential genes are conserved from yeast to human cells, correlating with human genes that display cell line‐specific essentiality in the Cancer Dependency Map (DepMap) project.

Abstract Our ability to understand the genotype‐to‐phenotype relationship is hindered by the lack of detailed understanding of phenotypes at a single‐cell level. To systematically assess cell‐to‐cell phenotypic variability, we combined automated yeast genetics, high‐content screening and neural network‐based image analysis of single cells, focussing on genes that influence the architecture of four subcellular compartments of the endocytic pathway as a model system. Our unbiased assessment of the morphology of these compartments—endocytic patch, actin patch, late endosome and vacuole—identified 17 distinct mutant phenotypes associated with ~1,600 genes (~30% of all yeast genes). Approximately half of these mutants exhibited multiple phenotypes, highlighting the extent of morphological pleiotropy. Quantitative analysis also revealed that incomplete penetrance was prevalent, with the majority of mutants exhibiting substantial variability in phenotype at the single‐cell level. Our single‐cell analysis enabled exploration of factors that contribute to incomplete penetrance and cellular heterogeneity, including replicative age, organelle inheritance and response to stress.

Alzheimer’s disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood1–3. Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1.3 million cells from 283 post-mortem human brain samples across 48 individuals with and without Alzheimer’s disease. We identify 76 cell types, including region-specific subtypes of astrocytes and excitatory neurons and an inhibitory interneuron population unique to the thalamus and distinct from canonical inhibitory subclasses. We identify vulnerable populations of excitatory and inhibitory neurons that are depleted in specific brain regions in Alzheimer’s disease, and provide evidence that the Reelin signalling pathway is involved in modulating the vulnerability of these neurons. We develop a scalable method for discovering gene modules, which we use to identify cell-type-specific and region-specific modules that are altered in Alzheimer’s disease and to annotate transcriptomic differences associated with diverse pathological variables. We identify an astrocyte program that is associated with cognitive resilience to Alzheimer’s disease pathology, tying choline metabolism and polyamine biosynthesis in astrocytes to preserved cognitive function late in life. Together, our study develops a regional atlas of the ageing human brain and provides insights into cellular vulnerability, response and resilience to Alzheimer’s disease pathology.A regional atlas of the ageing human brain—spanning six distinct anatomical regions from individuals with and without Alzheimer’s dementia—provides insights into cellular vulnerability, response and resilience to Alzheimer’s disease pathology [ABSTRACT FROM AUTHOR]

In this paper, we discuss the requirements and technical challenges within the EHEM project, Enhancement of Heritage Experiences: The Middle Ages, an ongoing research program for the acquisition, analysis, documentation, interpretation, digital restoration, and communication of medieval artistic heritage. The project involves multidisciplinary teams comprising art historians and visual computing experts. Despite the vast literature on digital 3D models in support of Cultural Heritage, the field is so rich and diverse that specific projects often imply distinct, unique requirements which often challenge the computational technologies and suggest new research opportunities. As good representatives of such diversity, we describe the three monuments that serve as test cases for the project, all of them with a rich history of architecture and paintings. We discuss the art historians' view of how digital models can support their research, the expertise and technological solutions adopted so far, as well as the technical challenges in multiple areas spanning geometry and appearance acquisition, color analysis and digital restitution, as well as the representation of the profound transformations due to the alterations suffered over the centuries. [ABSTRACT FROM AUTHOR]

Purpose: This study compared the results of the new Sysmex PA-100 AST System, a point-of-care analyser, with routine microbiology for the detection of urinary tract infections (UTI) and performance of antimicrobial susceptibility tests (AST) directly from urine. Methods: Native urine samples from 278 female patients with suspected uncomplicated UTI were tested in the Sysmex PA-100 and with reference methods of routine microbiology: urine culture for bacteriuria and disc diffusion for AST. Results: The analyser delivered bacteriuria results in 15 min and AST results within 45 min. Sensitivity and specificity for detection of microbiologically confirmed bacteriuria were 84.0% (89/106; 95% CI: 75.6–90.4%) and 99.4% (155/156; 95% CI: 96.5–100%), respectively, for bacterial species within the analyser specifications. These are Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus, which are common species causing uncomplicated UTI. Overall categorical agreement (OCA) for AST results for the five antimicrobials tested in the Sysmex PA-100 (amoxicillin/clavulanic acid, ciprofloxacin, fosfomycin, nitrofurantoin and trimethoprim) ranged from 85.4% (70/82; 95%CI: 75.9–92.2%) for ciprofloxacin to 96.4% (81/84; 95% CI: 89.9–99.3%) for trimethoprim. The Sysmex PA-100 provided an optimal treatment recommendation in 218/278 cases (78.4%), against 162/278 (58.3%) of clinical decisions. Conclusion: This first clinical evaluation of the Sysmex PA-100 in a near-patient setting demonstrated that the analyser delivers phenotypic AST results within 45 min, which could enable rapid initiation of the correct targeted treatment with no further adjustment needed. The Sysmex PA-100 has the potential to significantly reduce ineffective or unnecessary antibiotic prescription in patients with UTI symptoms. [ABSTRACT FROM AUTHOR]

Torsional disorders of the lower limb are common in childhood, and they are one of the primary reasons parents seek consultation with healthcare providers. While clinical manoeuvres can assess femoral and tibial torsion, their reliability is medium to low. Various imaging-based techniques, including computed tomography, magnetic resonance imaging, fluoroscopy, biplanar radiology and ultrasonography, have been used to evaluate torsional alterations of the lower extremity. Among these, ultrasound assessment offers certain advantages: it is a low-cost, non-irradiating technique, which allows the follow-up of children's torsional development. However, to the best of the authors' knowledge, its validity and reliability have not been summarised in a systematic review. This study aims to analyse the validity and reliability of ultrasonography in determining femoral and tibial torsion in children and adolescents. A search from Medline (via PubMed), Web of Science, Scopus and CINAHL databases were performed from inception to 16 March 2023. No restrictions were placed on the publication year or language. The methodological quality of all eligible studies was independently reviewed by two authors using QUADAS and STARD checklists. Overall, 1546 articles were identified through the searches; 30 were considered eligible for full-text screening; and 8 studies were finally included in this review. The included studies were conducted in Germany, Norway and the UK. Among them, 7 studies analysed the validity of ultrasonography compared with other imaging techniques such as computed tomography, magnetic resonance imaging and biplanar X-ray, and 4 studies assessed intra- and inter-observer reliability. All the studies assessed femoral torsion, but only one of them also included tibial torsion. Conclusion: Ultrasound is a good alternative for routine evaluation and follow-up of femoral torsional alterations in children and adolescents due to its safety, accessibility and immediate results in the clinical examination room. Although ultrasound has good accuracy and reliability for routine evaluations, there is controversy about whether it is sufficient for surgical planning. In cases where greater accuracy is required, magnetic resonance imaging and biplanar radiography are the preferred imaging techniques. What is Known: • Several imaging-based techniques have been described for the assessment of torsional alterations of the lower extremity. • Computed tomography, magnetic resonance imaging, biplanar radiology and ultrasonography are the most used and studied methods. What is New: • Ultrasonography represents a good alternative for the assessment of femoral and tibial torsional alterations in children and adolescents, given its safety, accessibility and immediacy of results in the consultation room. • Its accuracy and reliability are good but not sufficient for surgical planning, in which case MRI and biplanar X-ray will be the preferred choices. [ABSTRACT FROM AUTHOR]

Purpose: The presurgical discrimination of IDH-mutant astrocytoma grade 4 from IDH-wildtype glioblastoma is crucial for patient management, especially in younger adults, aiding in prognostic assessment, guiding molecular diagnostics and surgical planning, and identifying candidates for IDH-targeted trials. Despite its potential, the full capabilities of DSC-PWI remain underexplored. This research evaluates the differentiation ability of relative-cerebral-blood-volume (rCBV) percentile values for the enhancing and non-enhancing tumor regions compared to the more commonly used mean or maximum preselected rCBV values. Methods: This retrospective study, spanning 2016–2023, included patients under 55 years (age threshold based on World Health Organization recommendations) with grade 4 astrocytic tumors and known IDH status, who underwent presurgical MR with DSC-PWI. Enhancing and non-enhancing regions were 3D-segmented to calculate voxel-level rCBV, deriving mean, maximum, and percentile values. Statistical analyses were conducted using the Mann-Whitney U test and AUC-ROC. Results: The cohort consisted of 59 patients (mean age 46; 34 male): 11 astrocytoma-4 and 48 glioblastoma. While glioblastoma showed higher rCBV in enhancing regions, the differences were not significant. However, non-enhancing astrocytoma-4 regions displayed notably higher rCBV, particularly in lower percentiles. The 30th rCBV percentile for non-enhancing regions was 0.705 in astrocytoma-4, compared to 0.458 in glioblastoma (p = 0.001, AUC-ROC = 0.811), outperforming standard mean and maximum values. Conclusion: Employing an automated percentile-based approach for rCBV selection enhances differentiation capabilities, with non-enhancing regions providing more insightful data. Elevated rCBV in lower percentiles of non-enhancing astrocytoma-4 is the most distinguishable characteristic and may indicate lowly vascularized infiltrated edema, contrasting with glioblastoma's pure edema. [ABSTRACT FROM AUTHOR]

Purpose of Review: Diuretics are the cornerstone therapy for acute heart failure (HF) and congestion. Patients chronically exposed to loop diuretics may develop diuretic resistance as a consequence of nephron remodelling, and the combination of diuretics will be necessary to improve diuretic response and achieve decongestion. This review integrates data from recent research and offers a practical approach to current pharmacologic therapies to manage congestion in HF with a focus on combinational therapy. Recent Findings: Until recently, combined diuretic treatment was based on observational studies and expert opinion. Recent evidence from clinical trials has shown that combined diuretic treatment can be started earlier without escalating the doses of loop diuretics with an adequate safety profile. Summary: Diuretic combination is a promising strategy for overcoming diuretic resistance in HF. Further studies aiming to get more insights into the pathophysiology of diuretic resistance and large clinical trials confirming the safety and efficacy over standard diuretics regimens are warranted. [ABSTRACT FROM AUTHOR]

Objective: Presurgical differentiation between astrocytomas and oligodendrogliomas remains an unresolved challenge in neuro-oncology. This research aims to provide a comprehensive understanding of each tumor's DSC-PWI signatures, evaluate the discriminative capacity of cerebral blood volume (CBV) and percentage of signal recovery (PSR) percentile values, and explore the synergy of CBV and PSR combination for pre-surgical differentiation. Methods: Patients diagnosed with grade 2 and 3 IDH-mutant astrocytomas and IDH-mutant 1p19q-codeleted oligodendrogliomas were retrospectively retrieved (2010–2022). 3D segmentations of each tumor were conducted, and voxel-level CBV and PSR were extracted to compute mean, minimum, maximum, and percentile values. Statistical comparisons were performed using the Mann-Whitney U test and the area under the receiver operating characteristic curve (AUC-ROC). Lastly, the five most discriminative variables were combined for classification with internal cross-validation. Results: The study enrolled 52 patients (mean age 45-year-old, 28 men): 28 astrocytomas and 24 oligodendrogliomas. Oligodendrogliomas exhibited higher CBV and lower PSR than astrocytomas across all metrics (e.g., mean CBV = 2.05 and 1.55, PSR = 0.68 and 0.81 respectively). The highest AUC-ROCs and the smallest p values originated from CBV and PSR percentiles (e.g., PSRp70 AUC-ROC = 0.84 and p value = 0.0005, CBVp75 AUC-ROC = 0.8 and p value = 0.0006). The mean, minimum, and maximum values yielded lower results. Combining the best five variables (PSRp65, CBVp70, PSRp60, CBVp75, and PSRp40) achieved a mean AUC-ROC of 0.87 for differentiation. Conclusions: Oligodendrogliomas exhibit higher CBV and lower PSR than astrocytomas, traits that are emphasized when considering percentiles rather than mean or extreme values. The combination of CBV and PSR percentiles results in promising classification outcomes. Clinical relevance statement: The combination of histogram-derived percentile values of cerebral blood volume and percentage of signal recovery from DSC-PWI enhances the presurgical differentiation between astrocytomas and oligodendrogliomas, suggesting that incorporating these metrics into clinical practice could be beneficial. Key Points: • The unsupervised selection of percentile values for cerebral blood volume and percentage of signal recovery enhances presurgical differentiation of astrocytomas and oligodendrogliomas. • Oligodendrogliomas exhibit higher cerebral blood volume and lower percentage of signal recovery than astrocytomas. • Cerebral blood volume and percentage of signal recovery combined provide a broader perspective on tumor vasculature and yield promising results for this preoperative classification. [ABSTRACT FROM AUTHOR]

Aims: To determine the prevalence and the impact on prognosis of metabolic alkalosis (MA) in patients admitted for acute heart failure (AHF). Methods and results: The ALCALOTIC is a multicenter, observational cohort study that prospectively included patients admitted for AHF. Patients were classified into four groups according to their acid–base status on admission: acidosis, MA, respiratory alkalosis, and normal pH (reference group for comparison). Primary endpoint was all-cause in-hospital mortality, and secondary endpoints included 30/90-day all-cause mortality, all-cause readmission, and readmission for HF. Associations between endpoints and acid–base alterations were estimated in a multivariate Cox regression model including sex, age, comorbidities, and Barthel index and expressed as hazard ratio (HR) with 95% confidence interval (95% CI). Six hundred sixty-five patients were included (84 years and 57% women), and 40% had acid–base alterations on admission: 188 (28%) acidosis and 78 (12%) alkalosis. The prevalence (95% CI) of MA was 9% (6.8–11.2%). Patients with MA were more women; had fewer comorbidities, better renal function, and higher left ventricle ejection fraction values; and received more treatment with oral acetazolamide during hospitalization and at discharge. MA was not associated with a higher risk of in-hospital mortality and 30/90-day all-cause mortality or readmissions but was associated with a significant increase in readmissions for HF at 30 and 90 days (adjusted HR [95% CI] 3.294 [1.397–7.767], p = 0.006 and 2.314 [1.075–4.978], p = 0.032). Conclusion: The prevalence of MA in patients admitted for AHF was 9%, and its presence was associated with more readmissions for HF but not with all-cause mortality. [ABSTRACT FROM AUTHOR]

This study explores the characteristics of young female and male adults (mean age 26.3 years) reporting a low sexual desire. A 2017 Swiss national survey was carried out among young adults. Participants were divided into two groups based on their level of sexual desire: Low and High. Overall, 17.2% of females and 5.7% of males reported a low sexual desire. At the multivariate level, compared to females in the High group, females in the Low group had higher odds of being dissatisfied with their social life and with their sexual life in the past 4 weeks, having no current relationship and having accepted several times sexual intercourse without really wanting. Compared to males in the High group, males in the Low group had higher odds of reporting a non-heterosexual attraction (trend), having no current relationship and having accepted several times sexual intercourse without really wanting. The prevailing idea that young people, particularly males, always have high levels of sexual desire may not be accurate and warrants further consideration. These results show that sexual desire encompasses social aspects and underscore importance of addressing how stereotypes and social norms may influence our sexuality. [ABSTRACT FROM AUTHOR]

We consider a population organised hierarchically with respect to size in such a way that the growth rate of each individual depends only on the presence of larger individuals. As a concrete example one might think of a forest, in which the incidence of light on a tree (and hence how fast it grows) is affected by shading by taller trees. The classic formulation of a model for such a size-structured population employs a first order quasi-linear partial differential equation equipped with a non-local boundary condition. However, the model can also be formulated as a delay equation, more specifically a scalar renewal equation, for the population birth rate. After discussing the well-posedness of the delay formulation, we analyse how many stationary birth rates the equation can have in terms of the functional parameters of the model. In particular we show that, under reasonable and rather general assumptions, only one stationary birth rate can exist besides the trivial one (associated to the state in which there are no individuals and the population birth rate is zero). We give conditions for this non-trivial stationary birth rate to exist and analyse its stability using the principle of linearised stability for delay equations. Finally, we relate the results to the alternative, partial differential equation formulation of the model. [ABSTRACT FROM AUTHOR]

Background: Variant transthyretin amyloidosis (ATTRv) can cause sensorimotor and autonomic neuropathy. Objective quantification of sudomotor function may be essential for early diagnosis and early initiation of treatment. The aim of this study is to evaluate the diagnostic value of the Sudoscan® in ATTRv. Methods: Electrochemical skin conductance (ESC) was measured in V30M ATTRv patients, asymtomatic V30M carriers and healthy controls. Comparisons between the three groups were made using the Kruskal-Wallis test, and ROC curves were used to estimate the discriminatory power of ESC values between groups. Results: ESC was measured in 52 ATTRv patients, 107 asymptomatic carriers and 40 healthy controls. ESC was significantly lower in ATTRv patients compared to asymptomatic carriers and healthy controls in both feet and hands; median values are as follows: 40 µS, 78 µS and 81 µS, respectively (p < 0.001), and 53 µS, 69 µS and 74 µS, respectively (p < 0.001). ESC in feet < 70.5 µS had a sensitivity of 89.7% and specificity of 84.6% to discriminate asymptomatic carriers from patients with ATTRv. Conclusion: The determination of ESC by Sudoscan® is a rapid, noninvasive and easily reproducible technique capable of discriminating patients with ATTRv from asymptomatic carriers and healthy controls with adequate sensitivity and specificity. [ABSTRACT FROM AUTHOR]