OBJECTIVE: This study aimed to determine the accuracy of detecting ischemic core volume using computed tomography perfusion (CTP) in patients with suspected acute ischemic stroke compared to diffusion-weighted magnetic resonance imaging (DW-MRI) as the reference standard.
METHODS: This retrospective monocentric study included patients who underwent CTP and DW-MRI for suspected acute ischemic stroke. The ischemic core size was measured at DW-MRI. The detectability threshold volume was defined as the lowest volume detected by each method. Clinical data on revascularization therapy, along with the clinical decision that influenced the choice, were collected. Volumes of the ischemic cores were compared using the Mann-Whitney U test.
RESULTS: Of 83 patients who underwent CTP, 52 patients (median age 73 years, IQR 63-80, 36 men) also had DW-MRI and were included, with a total of 70 ischemic cores. Regarding ischemic cores, only 18/70 (26%) were detected by both CTP and DW-MRI, while 52/70 (74%) were detected only by DW-MRI. The median volume of the 52 ischemic cores undetected on CTP (0.6 mL, IQR 0.2-1.3 mL) was significantly lower (p < 0.001) than that of the 18 ischemic cores detected on CTP (14.2 mL, IQR 7.0-18.4 mL). The smallest ischemic core detected on CTP had a volume of 5.0 mL. Among the 20 patients with undetected ischemic core on CTP, only 10% (2/20) received thrombolysis treatment.
CONCLUSIONS: CTP maps failed in detecting ischemic cores smaller than 5 mL. DW-MRI remains essential for suspected small ischemic brain lesions to guide a correct treatment decision-making.

BACKGROUND: The utility of thyroglobulin (Tg) in the follow-up of differentiated thyroid cancer (DTC) patients has been well-documented. Although third-generation immunoassays have improved accuracy, limitations persist (interfering anti-Tg antibodies and measurement variability). Evolving treatment strategies require a reevaluation of Tg thresholds for optimal patient management.
OBJECTIVE: To assess the performance of serum Tg testing in two populations: patients receiving total thyroidectomy and radioiodine remnant ablation (RRA), or treated with thyroidectomy alone.
METHODS: Prospective observational study. Setting. Centers contributing to the Italian Thyroid Cancer Observatory (ITCO) database.
METHODS: We included 540 patients with 5 years of follow-up and negative anti-Tg antibodies.
METHODS: Serum Tg levels assessed at 1-year follow-up visit.
METHODS: Detection of structural disease within 5 years of follow-up.
RESULTS: After excluding 26 patients with structural disease detected at any time point, the median Tg did not differ between patients treated with or without radioiodine. Data-driven Tg thresholds were established based on the 97th percentile of Tg levels in disease-free individuals: 1.97 ng/mL for patients undergoing thyroidectomy alone (lower than proposed by the MSKCC protocol and ESMO Guidelines, yet demonstrating good predictive ability, with a negative predictive value (NPV) of 98%) and 0.84 ng/mL for patients receiving post-surgical RRA. High sensitivity and NPV supported the potential of these thresholds in excluding structural disease.
CONCLUSIONS: This real-world study provides evidence for the continued reliability of 1-year serum Tg levels. The data-driven Tg thresholds proposed offer valuable insights for clinical decision-making in patients undergoing total thyroidectomy with or without RRA.

Recent research has become increasingly interested in the on-linear associations between noise levels and people\'s short-term noise annoyance. However, there has been limited investigation into measuring short-term noise annoyance and how different activity contexts may affect these non-linear associations. To address this research gap, this study measured people\'s short-term noise annoyance using real-time Ecological Momentary Assessment (EMA) data and the Day Reconstruction Method\'s (DRM) recalled data. Corresponding noise levels were captured using Global Positioning Systems and portable noise sensors. Employing the Shapley additive explanations method, we examined the non-linear associations between noise level and people\'s real-time and recalled noise annoyance across different activity contexts. The results indicated that 1) People had greater sensitivity to noise levels in real-time annoyance (non-linear association threshold: 60 dB) compared to recalled annoyance, which had a higher non-linear association threshold of 70 dB. 2) The non-linear associations between noise level and people\'s real-time/recalled noise annoyance varied between different activity contexts. People tended to be more sensitive to noise in real-time annoyance than recalled annoyance on travel routes and at workplaces. 3) Among the factors examined, the contribution of noise level varied across activity contexts. Noise level contributed more significantly to people\'s real-time noise annoyance in outdoor recreational sites and on travel routes. These findings enhance our understanding of the non-linear association between noise level and people\'s short-term noise annoyance, moving beyond the linear paradigm. Policymakers should consider the non-linear relationships and different activity contexts when implementing noise control measures.

Thrombocytopenia is common in preterm neonates and can be associated with hemorrhage. Most platelet transfusions are prophylactic. Previously, higher platelet-count thresholds were recommended for neonates, but this recommendation has been questioned in recent studies. In the PlaNeT2 trial, mortality and serious bleeding were more frequent in neonates with the highest platelet-count threshold than in others. Following this trial, we changed our platelet transfusion practice by lowering the platelet-count threshold for prophylactic transfusion from 50,000 to 25,000/mm3. We conducted a before-after retrospective cohort study to quantify the frequency of platelet transfusions and assess the new protocol by analyzing death and serious hemorrhage events. This retrospective monocentric study included neonates born before 37 weeks of gestation with platelet count < 150,000/mm3 during the 2 years preceding the new platelet transfusion protocol (high prophylactic transfusion threshold, 50,000/mm3) and during the 2 years after the new platelet transfusion protocol (low prophylactic transfusion threshold, 25,000/mm3). The primary outcome was the proportion of neonates receiving at least one platelet transfusion in both groups. We also compared the proportion of deaths and severe hemorrhage events. A total of 707 neonates with thrombocytopenia were identified. In the high-threshold group, 99/360 (27.5%) received at least one platelet transfusion as compared with 56/347 (16.1%) in the low-threshold group (p < 0.001). The groups did not differ in proportion of deaths or severe hemorrhage events.
CONCLUSIONS: A reduced platelet-count threshold for transfusion allowed for a significant reduction in the number of platelet transfusions without increasing severe hemorrhage events.
BACKGROUND: • A recent randomized trial suggested that restrictive platelet-count thresholds for platelet transfusion could be beneficial for preterm neonates.
BACKGROUND: • On lowering the platelet-count threshold for transfusion from 50,000 to 25,000/mm3, the number of transfusions significantly decreased without increasing severe hemorrhage events in a neonatal intensive care unit.

OBJECTIVE: To determine the effect of levomethadone/fenpipramide and metamizole alone and in combination on acute nociception.
METHODS: 8 healthy, adult Beagles were used in 2 separate randomized, complete crossover, experimental trials (threshold testing and determination of minimal alveolar concentration [MAC]) with masked observers. In both trials, treatments were 0.2 mg·kg-1 levomethadone/fenpipramide (L), 75 mg·kg-1 metamizole (M), or their combination (LM). In conscious dogs, mechanical thresholds were determined using constantly rising force. Thermal thresholds were measured via ramped contact heat. The MAC of sevoflurane was determined using the bracketing method with electrical stimulus (50 V, 50 Hz, 10 ms) before and 1 and 4 hours after treatment.
RESULTS: Mechanical thresholds in L and LM were significantly increased above baseline (BL) for 165 minutes and above M for 135 minutes. Percent thermal threshold excursion significantly increased above BL in L for 75 minutes and in LM for 135 minutes. In L and LM, the percent thermal threshold excursion was significantly higher than in M from 15 to 75 or 135 minutes, respectively. In L and LM, the MAC of sevoflurane was significantly reduced at 1 hour compared to BL and M.
CONCLUSIONS: Duration but not the magnitude of thermal antinociception of levomethadone/fenpipramide was increased by metamizole. Mechanical antinociception in awake dogs and anesthetic-sparing effects of levomethadone/fenpipramide were not altered.
CONCLUSIONS: Coadministration of levomethadone/fenpipramide and metamizole to increase antinociception is not justified.

Conserving biodiversity is crucial for maintaining essential ecosystem functions, as indicated by the positive relationships between biodiversity and ecosystem functioning. However, the impacts of declining biodiversity on ecosystem functions in response to mounting human pressures remain uncertain. This uncertainty arises from the complexity of trade-offs among human activities, climate change, river properties, and biodiversity, which have not been comprehensively addressed collectively. Here, we provide evidence that river biodiversity was significantly and positively associated with multifunctionality and contributed to key ecosystem functions such as microbially driven water purification, leaf litter decomposition and pathogen control. However, human pressure led to abrupt changes in microbial diversity and river multifunctionality relationships at a human pressure value of 0.5. In approximately 30 % (N = 58) of countries globally, the ratio of area above this threshold exceeded the global average (~11 %), especially in Europe. Results show that human pressure affected ecosystem functions through direct effects and interactive effects. We provide more direct evidence that the nonadditive effects triggered by prevailing human pressure impact the multifunctionality of rivers globally. Under high levels of human stress, the beneficial effects of biodiversity on nutrient cycling, carbon storage, gross primary productivity, leaf litter decomposition, and pathogen control tend to diminish. Our findings highlight that considering interactions between human pressure and local abiotic and biotic factors is key for understanding the fate of river ecosystems under climate change and increasing human pressure.

Lung images often have the characteristics of strong noise, uneven grayscale distribution, and complex pathological structures, which makes lung image segmentation a challenging task. To solve this problems, this paper proposes an initial lung mask extraction algorithm that combines threshold and gradient. The gradient used in the algorithm is obtained by the time series feature extraction method based on differential memory (TFDM), which is obtained by the grayscale threshold and image grayscale features. At the same time, we also proposed a lung contour repair algorithm based on the improved convex hull method to solve the contour loss caused by solid nodules and other lesions. Experimental results show that on the COVID-19 CT segmentation dataset, the advanced lung segmentation algorithm proposed in this article achieves better segmentation results and greatly improves the consistency and accuracy of lung segmentation. Our method can obtain more lung information, resulting in ideal segmentation effects with improved accuracy and robustness.

According to the sufficiency theory of justice in health, justice requires that people have equal access to adequate health. In this article, I lay out the structure of this view and I assess its distributive implications for setting priority (i) between health needs across persons and (ii) between health care spending and other societal goods. I argue, first, that according to the sufficiency theory, deficiency in health cannot be completely offset by providing other societal goods. And, second, that it can prevent the medicalization of societies by stressing that improvements beyond the level of adequate health have relatively little weight, if any, from the standpoint of justice.

OBJECTIVE: Using data from the National Health and Nutrition Examination Survey (NHANES) and employing Controlled Attenuation Parameter (CAP) measures, this study explores the correlation between vitamin E (VE) intake and hepatic steatosis and its impact on different subsets.
METHODS: We selected 5757 participants with CAP data from the 2017-2020 NHANES dataset. Daily VE intake was assessed by a 24-hour dietary recall. Hepatic fat content was quantified using transient elastography to measure CAP. Stratified multivariable regression analysis investigated relationships in different subsets, and a generalized additive model identified nonlinear relationships and thresholds.
RESULTS: After adjusting for confounders, higher VE intake correlated with lower CAP levels. Subgroup analyses and tests for interaction revealed a significantly stronger negative correlation between VE intake and CAP in obese individuals. Further analysis indicated a curvilinear relationship between VE intake and the severity of liver fat degeneration in both the general study population and the obese subgroup, demonstrating a threshold effect. In the general population, VE intake below the threshold (6.58 mg/day) is positively correlated with CAP levels, whereas intake above this threshold shows a negative correlation. For obese individuals, the threshold is set at 7.37 mg/day, above which the negative correlation with CAP is even more pronounced.
CONCLUSIONS: Our study revealed a negative correlation between VE intake and hepatic fat content, highlighting the potentially crucial role VE plays in obese fatty liver patients. Importantly, we identified threshold effects of VE intake in both general and obese populations. Our results support clinical nutritional interventions, personalized dietary guidance, and the development of drugs to combat fatty liver.

The most widely known pyrogen impurity in vaccines is the Gram-negative bacterial endotoxin lipopolysaccharide (LPS). When administered at toxic doses, endotoxin triggers inflammatory responses, which lead to endotoxic shock. The literature on endotoxic content (EC) for preclinical vaccines\' formulations used in animal studies is very poor, and the recommended thresholds are solely based on commercial vaccine limits set for humans and are, therefore, not connected to the actual impact of EC on animal welfare for species used in preclinical research studies. An extensive study to evaluate the presence of a potential relationship between endotoxin content in formulations administered to mice (the most common species used in preclinical research studies) and their welfare was conducted to calculate an EC threshold for formulations of candidate vaccines. Three years of historical data, from more than 500 formulations of different antigen types (i.e., proteins, glycoconjugates, OMV/GMMA) injected into more than 5000 mice, was evaluated with two alternative statistical methodologies, both demonstrating that there is no significant relationship between actual endotoxin levels and mouse welfare. The calculation of thresholds was, therefore, performed by consistency versus formulations that demonstrated no impact on animal welfare.