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A large literature exists on the biochemistry, chemistry, metabolism, and clinical importance of the α-keto acid analogues of many amino acids. However, although glutamine is the most abundant amino acid in human tissues, and transamination of glutamine to its α-keto acid analogue (α-ketoglutaramate; KGM) was described more than seventy years ago, little information is available on the biological importance of KGM. Herein, we summarize the metabolic importance of KGM as an intermediate in the glutamine transaminase – ω-amidase (GTωA) pathway for the conversion of glutamine to anaplerotic α-ketoglutarate. We describe some properties of KGM, notably its occurrence as a lactam (2-hydroxy-5-oxoproline; 99.7% at pH 7.2), and its presence in normal tissues and body fluids. We note that the concentration of KGM is elevated in the cerebrospinal fluid of liver disease patients and that the urinary KGM/creatinine ratio is elevated in patients with an inborn error of the urea cycle and in patients with citrin deficiency. Recently, of the 607 urinary metabolites measured in a kidney disease study, KGM was noted to be one of five metabolites that was most significantly associated with uromodulin (a potential biomarker for tubular functional mass). Finally, we note that KGM is an intermediate in the breakdown of nicotine in certain organisms and is an important factor in nitrogen homeostasis in some microorganisms and plants. In conclusion, we suggest that biochemists and clinicians should consider KGM as (i) a key intermediate in nitrogen metabolism in all branches of life, and (ii) a biomarker, along with ω-amidase, in several diseases. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Level of evidence Establishing the diagnosis of loosening in total or unicondylar knee arthroplasty remains a challenge with different clinical and radiological signs evaluated in study designs with high risk of bias, where few or incomplete criteria are formulated for establishing the diagnosis of implant loosening. This study aimed at evaluating the variability between different clinical and radiological criteria and establish a consensus regarding clinical and radiological criteria for the diagnosis of knee arthroplasty loosening.Highly specialized knee surgeons focusing on revision arthroplasty were invited to take part in an international panel for a Delphi consensus study. In the first round, the participants were asked to state their most important clinical and radiological criteria for implant loosening. In a second round, the panel's agreement with the collected criteria was rated on a 5‐point Likert scale (1–5). High variability was defined by receiving at least one score each indicating complete disagreement and complete agreement. Consensus was established when over 70% of participants rated a criterion as ‘fully agree’ (5) or ‘mostly agree’ (4).High variability was observed in 56% of clinical criteria and 38% of radiological criteria. A consensus was reached on one clinical (weight‐bearing pain [82%]) and four radiological criteria, that is, implant migration, progressive radiolucencies, subsidence and radiolucencies >2 mm on X‐ray or computed tomography (CT) (84%–100%).Amongst specialized knee revision surgeons, there is high variability in clinical and radiological criteria that are seen as important contributing factors to diagnosis of knee implant loosening. A consensus was reached on weight‐bearing pain as clinical criterion and on implant migration, progressive radiolucencies, subsidence and radiolucencies of more than 2 mm on X‐ray or CT as radiological criteria. The variability rates observed, along with the criteria that reached consensus, offer important insights for the standardization of diagnostic protocols.Level V. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate and compare the diagnostic accuracy of modalities used to aid the diagnosis of aseptic knee arthroplasty loosening. Methods: A comparative diagnostic test accuracy systematic review and meta‐analysis was conducted following the Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines. PubMed, EMBASE and Cochrane databases were searched for original articles evaluating diagnostic modalities up to March 2024. Included studies compared the modality (index test) to the intraoperative finding as reference test. The QUADAS‐C (Quality Assessment of Diagnostic Accuracy Studies‐Comparative) tool was used to assess the quality of the included studies. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to evaluate the certainty of evidence. Level of evidence was evaluated using the Oxford Levels of Evidence tool. The primary outcome was the summary of diagnostic accuracy metrics for each modality as demonstrated by a summary receiver‐operating characteristic (SROC) curve. Results: The search yielded 467 articles. Of these, 14 articles were included. These 14 articles evaluated a total of five different diagnostic modalities: bone scintigraphy (three studies, 146 cases), 18‐fluorodeoxyglucose positron emission tomography (two studies, 50 cases), single‐photon emission computed tomography combined with computed tomography (SPECT/CT) (seven studies, 371 cases), radionuclide arthrogram (three studies, 196 cases) and magnetic resonance imaging (MRI) (one study, 116 cases). Nine studies exhibited a high risk of bias in patient selection, and all studies showed a high risk of bias related to the reference test. The majority of the included studies were classified as Level III evidence, leading to an overall low level of certainty in the evidence. The most accurate tests, as demonstrated by the SROC analysis, were MRI and SPECT/CT, with sensitivities ranging from 0.00 to 1.00 and 0.33 to 1.00 and specificities between 0.31–1.00 and 0.00–1.00, respectively. Conclusions: This review and meta‐analysis evaluated available diagnostic modalities to aid the diagnosis of knee arthroplasty loosening and based on a low certainty of evidence suggests that MRI and SPECT/CT are currently the most accurate modalities available to aid the diagnosis of aseptic loosening of knee arthroplasty components. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Level of Evidence There is a lack of a clear, uniform definition for intraoperatively assessed component loosening of a knee arthroplasty component, complicating the interpretation and interchangeability of results of diagnostic studies using an intraoperative observation as the reference test. The purpose of this study was to establish a consensus among specialised knee revision surgeons regarding the definition of intraoperatively determined loosening of total or unicondylar knee arthroplasty components.Utilising the Delphi consensus method, an international panel of highly specialised knee revision surgeons was invited to participate in a three‐round process. The initiation of the first round involved the exploration of possible criteria for intraoperatively determined loosening with open questions. The second round focused on rating these criteria importance on a five‐point Likert scale. For the third round, criteria that reached consensus were summarised in consecutive definitions for intraoperatively determined loosening and proposed to the panel. Consensus was established when over 70% of participants agreed with a definition for intraoperatively determined loosening.The 34 responding panel members described in total 60 different criteria in the first round of which 34 criteria received consensus in the second round. Summarising these criteria resulted in four different definitions as minimal requirements for intraoperatively determined loosening. Eighty‐eight percent of the panel members agreed on defining a component as loose if there is visible fluid motion at the interface observed during specific movements or when gently applying direct force.This study successfully established a consensus using a Delphi method among knee revision surgeons on the definition of intraoperatively determined component loosening. By agreeing on the visibility of fluid motion as new definition, this study provides a standardised reference for future diagnostic research. This definition will enhance the interpretability and interchangeability of future diagnostic studies evaluating knee arthroplasty component loosening.Level V. [ABSTRACT FROM AUTHOR]

Purpose of Review: To provide insights into the role of peptide receptor radionuclide therapy (PRRT) in patients with advanced neuroendocrine tumors (NET) and an overview of possible strategies to combine PRRT with locoregional and systemic anticancer treatments. Recent Findings: Research on combining PRRT with other treatments encompasses a wide variety or treatments, both local (transarterial radioembolization) and systemic therapies, chemotherapy (i.e., capecitabine and temozolomide), targeted therapies (i.e., olaparib, everolimus, and sunitinib), and immunotherapies (e.g., nivolumab and pembrolizumab). Furthermore, PRRT shows promising first results as a treatment prior to surgery. Summary: There is great demand to enhance the efficacy of PRRT through combination with other anticancer treatments. While research in this area is currently limited, the field is rapidly evolving with numerous ongoing clinical trials aiming to address this need and explore novel therapeutic combinations. [ABSTRACT FROM AUTHOR]

Purpose: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([166Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([99mTc]MAA) or [166Ho]-microspheres. The accuracy of eLMD based on [99mTc]MAA (eLMDMAA) was compared to eLMD based on [166Ho]-scout dose (eLMDHo-scout) in two prospective clinical studies. Materials and Methods: Patients were included if they received both scout doses ([99mTc]MAA and [166Ho]-scout), had a posttreatment [166Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMDMAA/eLMDHo-scout and LMDHo-treatment was assessed by Spearman's rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data. Results: Thirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMDMAA (1.53 Gy, range 0.09–21.33 Gy) was significantly higher than median LMDHo-treatment (0.00 Gy, range 0.00–1.20 Gy; p < 0.01). Median eLMDHo-scout (median 0.00 Gy, range 0.00–1.21 Gy) was not significantly different compared to LMDHo-treatment (p > 0.05). In all cases, eLMDMAA was higher than LMDHo-treatment (p < 0.01). While a significant correlation was found between eLMDHo-scout and LMDHo-treatment (r = 0.43, p < 0.01), there was no correlation between eLMDMAA and LMDHo-treatment (r = 0.02, p = 0.90). Conclusion: [166Ho]-scout dose is superior in predicting LMD over [99mTc]MAA, in [166Ho]-radioembolization. Consequently, [166Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization. Trail registration: NCT01031784, registered December 2009. NCT01612325, registered June 2012. [ABSTRACT FROM AUTHOR]

The precise temporal coordination of neural activity is crucial for brain function. In the hippocampus, this precision is reflected in the oscillatory rhythms observed in CA1. While it is known that a balance between excitatory and inhibitory activity is necessary to generate and maintain these oscillations, the differential contribution of feedforward and feedback inhibition remains ambiguous. Here we use conditional genetics to chronically silence CA1 pyramidal cell transmission, ablating the ability of these neurons to recruit feedback inhibition in the local circuit, while recording physiological activity in mice. We find that this intervention leads to local pathophysiological events, with ripple amplitude and intrinsic frequency becoming significantly larger and spatially triggered local population spikes locked to the trough of the theta oscillation appearing during movement. These phenotypes demonstrate that feedback inhibition is crucial in maintaining local sparsity of activation and reveal the key role of lateral inhibition in CA1 in shaping circuit function.Current approaches possibly cannot unambiguously distinguish the unique contributions of feedback inhibition versus feedforward inhibition to oscillatory events. Here authors show that a loss of CA1 pyramidal cell transmission, resulting in feedback inhibition reduction, leads to spatially triggered high-frequency oscillatory events; these events were like place cells in their spatial extent and localized to small regions in CA1. [ABSTRACT FROM AUTHOR]

Placenta accreta spectrum disorder (PASD) encompasses various types of abnormal placentation in which chorionic villi directly adhere to or invade the myometrium. The incidence of PASD has dramatically risen in the US over the past 3 decades owing to the increased rates of patients undergoing cesarean sections. While PASD remains a significant cause of maternal morbidity and mortality, accurate prenatal identification and characterization of PASD is associated with improved outcomes. Although ultrasound is the first-line imaging modality in the evaluation of PASD, with MRI serving as an adjunct, computed tomography angiography (CTA) may also offer unique diagnostic advantages in cases of advanced PASD by providing superior visualization of placental and abdominopelvic vasculature and enabling the creation of comprehensive vascular maps to roadmap complex surgical interventions. This paper represents the first evaluation of CTA as a diagnostic tool and operative planning aid in this context. Appropriate indications and diagnostic advantages of CTA in this setting are reviewed, and key multimodal imaging features of normal and abnormal placentation are highlighted. [ABSTRACT FROM AUTHOR]

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Heterogeneous catalysts are widely used to promote chemical reactions. Although it is known that chemical reactions usually happen on catalyst surfaces, only specific surface sites have high catalytic activity. Thus, identifying active sites and maximizing their presence lies at the heart of catalysis research1–4, in which the classic model is to categorize active sites in terms of distinct surface motifs, such as terraces and steps1,5–10. However, such a simple categorization often leads to orders of magnitude errors in catalyst activity predictions and qualitative uncertainties of active sites7,8,11,12, thus limiting opportunities for catalyst design. Here, using stepped Pt(111) surfaces and the electrochemical oxygen reduction reaction (ORR) as examples, we demonstrate that the root cause of larger errors and uncertainties is a simplified categorization that overlooks atomic site-specific reactivity driven by surface stress release. Specifically, surface stress release at steps introduces inhomogeneous strain fields, with up to 5.5% compression, leading to distinct electronic structures and reactivity for terrace atoms with identical local coordination, and resulting in atomic site-specific enhancement of ORR activity. For the terrace atoms flanking both sides of the step edge, the enhancement is up to 50 times higher than that of the atoms in the middle of the terrace, which permits control of ORR reactivity by either varying terrace widths or controlling external stress. Thus, the discovery of the above synergy provides a new perspective for both fundamental understanding of catalytically active atomic sites and design principles of heterogeneous catalysts. Stress release at stepped platinum surfaces is shown to influence the strain experienced by atoms near the steps, resulting in effects on the catalytic activity of the whole surface. [ABSTRACT FROM AUTHOR]

The conventional process for CO2 conversion requires high energy and expensive catalysts, and shows poor product selectivity. In this study, we address these challenges by investigating an environmentally friendly method for CO production through the variable frequency microwave-driven CO2 Boudouard reaction over biochar. We hypothesized that tuning the microwave frequency to align with the dielectric properties of biochar, and thereby induce a resonance effect, could significantly enhance reaction efficiency. Experiments were conducted to explore the effect of microwave frequency on CO2 conversion efficiency in the variable frequency microwave reactor operating within a frequency range of 2430–6000 MHz. Results reveal a significant resonance effect at 4225 MHz resulting in an outstanding CO2 conversion of 96.3%, in sharp contrast to the complete absence of conversion observed at the conventional 2450 MHz. The resonance frequency not only facilitated exceptional conversion but also remarkably improved energy efficiency, yielding a productivity of 1427.5 µmol/kJ of CO. This represents a remarkable 474-fold increase compared to electrical heating. Furthermore, continuous microwave irradiation at this optimized frequency demonstrated remarkable stability and induced substantial enhancements in the pore structure and surface area of biochar. This innovative approach provides promising insights into sustainable and efficient CO production processes. [ABSTRACT FROM AUTHOR]

Purpose: The literature presents a wide range of success rates for a single surgical intervention of bacterial‐septic‐arthritis, and there is a lack of clear criteria for identifying treatment failure and making decisions about reintervention. This Delphi study aims to establish a consensus among an international panel of experts regarding the definition of treatment failure and the criteria for reintervention in case of bacterial arthritis. Methods: The conducting and reporting Delphi studies (CREDES) criteria were used. Data from a systematic review was provided as the basis for the study. A list of 100 potential experts were identified. The study was designed and conducted as follows: (I) identification and invitation of an expert panel, (II) informing the participating expert panel on the research question and subject, and (III) conducting two or three Delphi rounds to reach consensus on explicit research items. Potential criteria were rated on a five‐point Likert scale. Results: Sixty orthopaedic experts from nine countries participated in this Delphi study, with 55 completing all three rounds. The mean experience as an orthopaedic surgeon was 15 years (SD ± 9). Strong (96%) consensus was reached on the definition of treatment failure: the persistence of physical signs of arthritis (e.g., pain and swelling) and/or systemic inflammation (e.g., fever and no improvement in CRP) despite surgical and antibiotic treatment. Furthermore, consensus (>80%) was reached on six criteria influencing the decision for reintervention; pain (81%), sepsis (98%), fever (88%), serum CRP (93%), blood culture (82%), and synovial fluid culture (84%). Conclusion: The definition of treatment failure for bacterial arthritis after a single surgical intervention was established through a three‐round Delphi study. Additionally, consensus was reached on six criteria that are helpful for determining the need for reintervention. This definition and these criteria may help in the development of clinical guidelines, and will empower physicians to make more precise and consistent decisions regarding reintervention for patients, ultimately aiming to reduce over‐ and undertreatment and improve patient outcomes. Level of Evidence: Level V. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a new quantity called SVD entanglement entropy. This is a generalization of entanglement entropy in that it depends on two different states, as in pre- and post-selection processes. This SVD entanglement entropy takes non-negative real values and is bounded by the logarithm of the Hilbert space dimensions. The SVD entanglement entropy can be interpreted as the average number of Bell pairs distillable from intermediates states. We observe that the SVD entanglement entropy gets enhanced when the two states are in the different quantum phases in an explicit example of the transverse-field Ising model. Moreover, we calculate the Rényi SVD entropy in various field theories and examine holographic calculations using the AdS/CFT correspondence. [ABSTRACT FROM AUTHOR]

Tuta absoluta poses a serious threat to tomato production worldwide as it can cause important yield losses. Its control is currently mainly based on the use of synthetic chemical insecticides, which unfortunately selects resistant populations and entails public health risks. The aim of this study was to evaluate the insecticidal, repellent and sublethal effects of Carapa procera seed oil on all stages of T. absoluta. Larvicidal (by contact and by ingestion), ovicidal and anti-feeding effects were evaluated by testing 1.5%, 3%, 4.5%, 6% and 7.5% concentrations of oil. Larvicidal and ovicidal effects were tested by direct application of Carapa solutions on larvae and eggs but also by feeding the larvae leaves dipped in solutions. The adult repellent effect was investigated by identifying the preferred area on filter paper partly non-treated versus fully treated using LC10, LC50 et LC90 of larvae after ingestion. LC50 was also used on 2-day-old larvae to evaluate the sublethal effects on larval and pupal duration, longevity and adult morphology. Results showed that, regardless of the mode of application, all concentrations had larvicidal effects with a higher dose-response effect and a higher mortality rate via ingestion than via topical application. The ovicidal effect varied with the concentrations tested, the highest mortality rate was obtained at a concentration of 7.5%. At the same dose, Carapa oil reduced large feeding galleries from 92.22 ± 5.02% in controls to 3.33 ± 3.65% at the highest dose and had a repellent effect on 80% of adults. Carapa oil increased larval and pupal duration by 2.14 and 1.35 days, respectively, and reduced adult female longevity by 2.2 days and male longevity by 1.1 days. A deformation rate of 28.33% was observed in newly emerged adults. This study demonstrated insecticidal and insect repellent effects of Carapa oil on different stages of T. absoluta. This botanical oil is a very promising biopesticide to control this major new pest of Solanaceous crops. Its use in an agroecological pest management strategy is discussed. [ABSTRACT FROM AUTHOR]

Identifying locations prone to exporting nitrogen (N), also called export control points, within residential landscapes, is key to determining N mitigation strategies. Within residential landscapes, lawns have the potential to act as either a sink of N via uptake and denitrification, or a source of N via additions such as fertilizer. Lawns draining to impervious surfaces are more likely to be sources of N loading to receiving water bodies through directly connected curb and sewer flow paths. We utilized small-scale rainfall experiments to examine whether hydrobiogeochemical measurements of potential denitrification and saturated infiltration rates were predictive of N mobilization, and how potential export control points (locations within the upper quartile of N mobilization values) varied spatially and temporally on residential lawns in Baltimore, Maryland. We found potential denitrification, but not infiltration, was predictive of N mobilization in runoff and leachate, only on fertilized lawns. Potential export control points occurred more often in the late summer and fall and 85% were on fertilized lawns. Applying fertilizer shortly before a rainfall event increased the N mobilization in runoff and leachate by an order of magnitude. Suburban front yards also had more potential export control points compared to backyards, which is notable as front yards are surrounded by impervious surfaces increasing their vulnerability to transporting N to downstream ecosystems. These findings highlight the spatial and temporal variability of N mobilization on lawns. Targeting locations such as vulnerable front yards, or behaviors, such as timing of fertilizer application, may be useful N mitigation strategies. [ABSTRACT FROM AUTHOR]

Introduction: Most adult cases of bacterial–septic–arthritis of a native joint are effectively managed with a single surgical debridement, but some cases may require more than one debridement to control the infection. Consequently, this study assessed the failure rate of a single surgical debridement in adults with bacterial arthritis of a native joint. Additionally, risk factors for failure were assessed. Materials and Methods: The review protocol was registered on PROSPERO (CRD42021243460) before data collection and conducted in line with the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' (PRISMA) guidelines. Multiple libraries were systematically searched to identify articles including patients reporting on the incidence of failure (i.e. persistence of infection requiring reoperation) of the treatment of bacterial arthritis. The quality of individual evidence were assessed using the Quality in Prognosis Studies (QUIPS) tool. Failure rates were extracted from included studies and pooled. Risk factors for failure were extracted and grouped. Moreover, we evaluated which risk factors were significantly associated with failure. Results: Thirty studies (8,586 native joints) were included in the final analysis. The overall pooled failure rate was 26% (95% CI 20 to 32%). The failure rate of arthroscopy and arthrotomy was 26% (95% CI 19 to 34%) and 24% (95% CI 17 to 33%), respectively. Seventy-nine potential risk factors were extracted and grouped. Moderate evidence was found for one risk factor (synovial white blood cell count), and limited evidence was found for five risk factors (i.e. sepsis, large joint infection, the volume of irrigation, blood urea nitrogen-test, and blood urea nitrogen/creatinine ratio). Conclusion: A single surgical debridement fails to control bacterial arthritis of a native joint in approximately a quarter of all adult cases. Limited to moderate evidence exists that risk factors associated with failure are: synovial white blood cell count, sepsis, large joint infection, and the volume of irrigation. These factors should urge physicians to be especially receptive to signs of an adverse clinical course. [ABSTRACT FROM AUTHOR]

Northward propagating summer monsoon intraseasonal oscillations (MISOs) in the Indian Ocean region remain poorly understood and difficult to predict. Here we examine a free-running high-resolution regional atmospheric model (RegCM4.7 with 25 km resolution), forced distantly at the boundaries by atmospheric observations (ERA-Interim, 0.75 ∘ ) and forced locally by observed sea-surface temperature (SST) over the period 1979–2016, to assess its ability to reproduce key aspects of these MISOs. We find that the model MISO exhibits spatial structures and northward propagation characteristics broadly similar to observed MISO when confining the analysis to the 25–90 day period band. The MISO precipitation anomalies are then shown to be consistent with previously known observed relationships to broad-scale sea-level pressure patterns, Inter-Tropical Convergence Zone (ITCZ) positioning, and changes in the regional Hadley Cell component. The total simulated seasonal (JJAS) rainfall anomalies over India are not significantly correlated with observations, indicating that intrinsic variations in the regional model atmosphere dominate most of the precipitation variability. However, the bandpass-filtered MISO anomalies surprisingly exhibit a significant correlation (0.61) with observations. This suggests that instabilities in the regional broad-scale atmospheric circulation, e.g., linked to the ITCZ position or strength, may be partly controlled by the large-scale atmospheric flows specified at the domain boundaries and/or that specified local SST anomalies may help to guide some fraction of the developing model MISO to follow observations. This result motivates further research on MISO initiation and development using this type of regional atmospheric model. [ABSTRACT FROM AUTHOR]

Seawater intrusion is a growing pressure in coastal communities worldwide, putting millions of people at risk of excess salinity in drinking water. This study examines the impact of saline water on people's health and labor allocation as potential pathways towards chronic poverty. Using a transdisciplinary approach based on a coupled human-water system framework, we test these linkages combining field data on well water salinity levels and rich household survey data in coastal Tanzania. The results suggest that increased salinity levels lead to more time spent collecting drinking water and an increase in illnesses. Moreover, households in poorer villages with weaker public infrastructure have limited access to alternative sources of drinking water, making them more vulnerable to scarce potable water resources stemming from high salinity. To prevent chronic poverty, communities vulnerable to saline drinking water need better adaptation strategies as well as groundwater monitoring and management. [ABSTRACT FROM AUTHOR]

Highly efficient isomerization of glucose to fructose is essential for valorizing cellulose fraction of biomass to value-added chemicals. This work provided an innovative method for preparing Mg-biochar and Mg–K-biochar catalysts by impregnating either MgCl2 alone or in combination with different K compounds (Ding et al. in Bioresour Technol 341:125835, 2021, https://doi.org/10.1016/j.biortech.2021.125835 and KHCO3) on cellulose-derived biochar, followed by hydrothermal carbonization and pyrolysis. Single active substance MgO existing in the 10Mg–C could give better catalytic effect on glucose isomerization than the synergy of MgO and KCl crystalline material present in 10Mg–KCl–C. But the catalytic effect of 10Mg–C was decreased when the basic site of MgO was overloaded. Compared to other carbon-based metal catalysts, 10Mg–KHCO3–C with 10 wt% MgCl2 loading had excellent catalytic performance, which gave a higher fructose yield (36.7%) and selectivity (74.54%), and catalyzed excellent glucose conversion (53.99%) at 100 °C in 30 min. Scanning electron microscope–energy dispersive spectrometer and X-Ray diffraction revealed that the distribution of Mg2+ and K+ in 10Mg–KHCO3–C was uniform and the catalytic active substances (MgO, KCl and K2CO3) were more than 10Mg–C (only MgO). The synergy effects of MgO and K2CO3 active sites enhanced the pH of reaction system and induced H2O ionization to form considerable OH− ions, thus easily realizing a deprotonation of glucose and effectively catalyzing the isomerization of glucose. In this study, we developed a highly efficient Mg–K-biochar bimetallic catalyst for glucose isomerization and provided an efficient method for cellulose valorization. Highlights: The bimetallic Brønsted catalyst designed in this study (10Mg–KHCO3–C) could achieve high fructose yield (36.7%) and selectivity (74.54%). The MgO could give obtain good catalytic effect on glucose isomerization, but the catalytic effect decreased when the Mg+ was overloaded. The synergy effects of MgO and K2CO3 could enhance the pH of reaction system and effectively catalyze the isomerization of glucose. [ABSTRACT FROM AUTHOR]

Purpose: Resecting pineal region tumors in children is often challenging. Several approaches have been proposed and practiced. A personal series of pediatric pineal region tumors resected through craniotomy with posterior interhemispheric occipital transtentorial (OT) approach are reviewed. We present the surgical techniques, pitfalls, and their results. Material and methods: Eighty patients ranging in age from 3 months to 21 years old, and treated over 3 decades were reviewed. Hydrocephalus caused the main presenting symptoms and was noted in 74 patients. It was treated prior to the craniotomy for tumor resection with endoscopic third ventriculostomy (ETV) in 33, external ventricular drainage in 26, and precraniotomy shunt in 15. Nine patients had ETV together with endoscopic biopsy. All patients had a parieto-occipital craniotomy in a prone position. Through a tentorial section, a gross total resection of the tumor was attempted except for germinomas. Results: The tumor pathology showed 32 germ cell tumors (GCT), 22 benign astrocytomas, 13 pineal parenchymal tumors, 5 ATRTs, 3 papillary tumors, and 5 others. Of GCTs, 18 were teratomas. The extent of resection consisted of 55 gross total resections, 13 subtotal resections, 10 partial, and 2 biopsies with one postoperative death. Hemiparesis in 2, cerebellar ataxia in another 2, and hemiballismus in 1 were transient and improved over time. One had permanent hemisensory loss and another patient had bilateral oculomotor palsy. Postoperative homonymous hemianopia occurred in 2 patients but subsided over a short period of time. Parinaud's sign was noted in 24 patients, of which 16 were transient. Conclusion: The posterior interhemispheric OT approach provides a safe route and comfortable access to the pineal region in children. A great majority of postoperative neurological complications are the results of direct manipulations of the midbrain at tumor resection. Identification and preservation of the tumor-brain interface are of paramount importance. GCTs other than teratomas are treated with neoadjuvant chemotherapy and may eliminate the need for craniotomy. Exophytic midbrain JPAs are amenable to resection. [ABSTRACT FROM AUTHOR]

Background: For safe and effective holmium-166 (166Ho) liver radioembolization, dosimetry is crucial and requires accurate healthy liver definition. The current clinical standard relies on manual segmentation and registration of a separately acquired contrast enhanced CT (CECT), a prone-to-error and time-consuming task. An alternative is offered by simultaneous imaging of 166Ho and technetium-99m stannous–phytate accumulating in healthy liver cells (166Ho–99mTc dual-isotope protocol). This study compares healthy liver segmentation performed with an automatic method using 99mTc images derived from a 166Ho–99mTc dual-isotope acquisition to the manual segmentation, focusing on healthy liver dosimetry and corresponding hepatotoxicity. Data from the prospective HEPAR PLuS study were used. Automatic healthy liver segmentation was obtained by thresholding the 99mTc image (no registration step required). Manual segmentation was performed on CECT and then manually registered to the SPECT/CT and subsequently to the corresponding 166Ho SPECT to compute absorbed dose in healthy liver. Results: Thirty-one patients (66 procedures) were assessed. Manual segmentation and registration took a median of 30 min per patient, while automatic segmentation was instantaneous. Mean ± standard deviation of healthy liver absorbed dose was 18 ± 7 Gy and 20 ± 8 Gy for manual and automatic segmentations, respectively. Mean difference ± coefficient of reproducibility between healthy liver absorbed doses using the automatic versus manual segmentation was 2 ± 6 Gy. No correlation was found between mean absorbed dose in the healthy liver and hepatotoxicity. Conclusions: 166Ho–99mTc dual-isotope protocol can automatically segment the healthy liver without hampering the 166Ho dosimetry assessment. Trial registration: ClinicalTrials.gov, NCT02067988. Registered 20 February 2014. https://clinicaltrials.gov/ct2/show/NCT02067988 [ABSTRACT FROM AUTHOR]

Purpose: Riparian zones are important modifiers of nutrient flux between terrestrial and aquatic ecosystems. However, dams alter riparian zones—trapping fine-grained, organic matter-rich sediment and creating poorly mixed, low oxygen conditions—thereby affecting sediment biogeochemistry in poorly understood ways. Methods: We characterized the impact of two relict US mid-Atlantic milldams (one from a primarily agricultural watershed and one from a mixed land use/urban watershed) on spatial patterns of bioavailable element concentrations (Mehlich-3 extractable P, K, Ca, Mg, Mn, Zn, Cu, Fe, B, S, and Na) in sediments upstream and downstream of milldams, with depth, and along transects running parallel and perpendicular to the stream. Results: Element concentrations were not clearly correlated with grain size or organic matter content and, although generally higher, were not significantly more concentrated in upstream riparian sediments when similar (shallow, variably saturated) depths were compared. Pronounced differences were observed: upstream of milldams, sediment concentrations of Ca and Mg were highest in variably saturated shallow sediments, while Fe and Mn were highest in deeper, continuously saturated, low-oxygen sediments. Additionally, data was significantly different by milldam site, a result of differences in land-use histories (e.g., road salt and fertilizer application/runoff) and dominant bedrock geology. Conclusion: Overall, results highlight the combined importance of milldams (and associated influences on groundwater hydrology and sediment redox conditions) and external drivers (other land-use legacies and bedrock geology) in influencing spatial patterns of bioavailable elements in riparian sediments. [ABSTRACT FROM AUTHOR]

Using a dataset consisting of daily vehicle trips, P M 2.5 concentrations, and a host of climactic control variables, we test the hypothesis that "yellow air day advisories" issued by the Utah Division of Air Quality resulted in subsequent reductions in vehicle trips taken during northern Utah's winter-inversion seasons in the early 2000 s. Winter inversions occur in northern Utah when P M 2.5 concentrations (derived mainly from vehicle emissions) become trapped in the lower atmosphere, leading to unhealthy air quality over a span of time known colloquially as "red air day episodes". When concentrations rise above 15 μ g / m 3 toward the National Ambient Air Quality Standard average daily threshold of 35 μ g / m 3 , residents are informed via different media sources and road signage that the region is experiencing a yellow air day, and are urged to reduce their vehicle usage during the day. Our results suggest that the advisories have provided at best weak, at worst perverse, incentives for reducing vehicle usage on yellow air days and ultimately for mitigating the occurrence of red air day episodes during northern Utah's winter inversion seasons. [ABSTRACT FROM AUTHOR]

The correction notice for the article "The extracellular lactate-to-pyruvate ratio modulates the sensitivity to oxidative stress-induced apoptosis via the cytosolic NADH/NAD+ redox state" in the journal Apoptosis addresses an error in Fig. 5C where the labels of the immunoblot were mistakenly swapped. The interpretation of the results and accompanying text and figure legends remain accurate. The correction was made by authors Simei Go, Thorquil T. Kramer, Arthur J. Verhoeven, Ronald P. J. Oude Elferink, and Jung-Chin Chang. The corrected version of the article can be accessed online at the provided DOI link. [Extracted from the article]

Rhabdomyosarcoma, although rare, is the most frequent soft tissue sarcoma in children and adolescents. It can present as a mass at nearly any site in the body, with most common presentations in the head and neck, genitourinary tract and extremities. The optimal diagnostic approach and management of rhabdomyosarcoma require a multidisciplinary team with multimodal treatment, including chemotherapy and local therapy. Survival has improved over the last decades; however, further improvement in management is essential with current 5-year overall survival ranging from 35% to 100%, depending on disease and patient characteristics. In the full patient journey, from diagnosis, staging, management to follow-up after therapy, the paediatric radiologist and nuclear physician are essential members of the multidisciplinary team. Recently, guidelines of the European paediatric Soft tissue sarcoma Study Group, the Cooperative Weichteilsarkom Studiengruppe and the Oncology Task Force of the European Society of Paediatric Radiology (ESPR), in an ongoing collaboration with the International Soft-Tissue Sarcoma Database Consortium, provided guidance for high-quality imaging. In this educational paper, given as a lecture during the 2022 postgraduate ESPR course, the multi-disciplinary team of our national paediatric oncology centre presents the journey of two patients with rhabdomyosarcoma and discusses the impact on and considerations for the clinical (paediatric) radiologist and nuclear physician. The key learning points of the guidelines and their implementation in clinical practice are highlighted and up-to-date insights provided for all aspects from clinical suspicion of rhabdomyosarcoma and its differential diagnosis, to biopsy, staging, risk stratification, treatment response assessment and follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Meta-[18F]fluorobenzylguanidine ([18F]mFBG) is a positron emission tomography (PET) radiotracer that allows for fast and high-resolution imaging of tumours expressing the norepinephrine transporter. This pilot study investigates the feasibility of [18F]mFBG PET-CT for imaging in neuroblastoma. Methods: In a prospective, single-centre study, we recruited children with neuroblastoma, referred for meta-[123I]iodobenzylguanidine ([123I]mIBG) scanning, consisting of total body planar scintigraphy in combination with single-photon emission computed tomography-CT (SPECT-CT). Within two weeks of [123I]mIBG scanning, total body PET-CTs were performed at 1 h and 2 h after injection of [18F]mFBG (2 MBq/kg). Detected tumour localisations on scan pairs were compared. Soft tissue disease was quantified by number of lesions and skeletal disease by SIOPEN score. Results: Twenty paired [123I]mIBG and [18F]mFBG scans were performed in 14 patients (median age 4.9 years, n = 13 stage 4 disease and n = 1 stage 4S). [18F]mFBG injection was well tolerated and no related adverse events occurred in any of the patients. Mean scan time for [18F]mFBG PET-CT (9.0 min, SD 1.9) was significantly shorter than for [123I]mIBG scanning (84.5 min, SD 10.5), p < 0.01. Most tumour localisations were detected on the 1 h versus 2 h post-injection [18F]mFBG PET-CT. Compared to [123I]mIBG scanning, [18F]mFBG PET-CT detected a higher, equal, and lower number of soft tissue lesions in 40%, 55%, and 5% of scan pairs, respectively, and a higher, equal, and lower SIOPEN score in 55%, 30%, and 15% of scan pairs, respectively. On average, two more soft tissue lesions and a 6-point higher SIOPEN score were detected per patient on [18F]mFBG PET-CT compared to [123I]mIBG scanning. Conclusion: Results of this study demonstrate feasibility of [18F]mFBG PET-CT for neuroblastoma imaging. More neuroblastoma localisations were detected on [18F]mFBG PET-CT compared to [123I]mIBG scanning. [18F]mFBG PET-CT shows promise for future staging and response assessment in neuroblastoma. Trial registration: Dutch Trial Register NL8152. [ABSTRACT FROM AUTHOR]

The oceanic South Atlantic Convergence Zone (SACZ) has played a major role during South America's 2021/2022 summer extreme rainy season, being responsible for more than 90% of the precipitation in some regions of Southeast Brazil and in some regions of the Southwestern Atlantic Ocean (SWA). The summer of 2021/2022 was unique and rare and considered an abnormally humid season as verified by official Brazilian Institutes. First, the unusual number of cases of SACZ episodes (seven), was the highest recorded in the last decade. Second, all the cases that occurred were oceanic SACZ that assumed characteristics of an Atmospheric River and produced an excessively anomalous amount of precipitation during this period. Excess precipitation along with the regions located in mountainous and very uneven relief, which by orographic effects favors high precipitation volumes, were responsible for amplifying the observed impacts, such as landslides and floods that caused several losses to society. We also showed the main effects of coupling and interaction between the waters of the surface layer of the SWA and the atmosphere. Our learning from this study ends with the unprecedented results of how the marine atmospheric boundary layer (MABL) is locally modulated by the sea surface temperature (SST) that lies just below it. Until the present moment, we emphasize that this important mechanism has not been widely highlighted in the literature, showing that even though the ocean is colder than before oceanic SACZ is established, it is still warmer than the overlying air, thus, the ocean continues to be an active source of heat and moisture for the atmosphere and enhances the MABL instability process. [ABSTRACT FROM AUTHOR]

The mechanism of symptom amplification, developed in the study of somatization, may be helpful in caring for patients with symptoms that, while they have a demonstrable medical basis, are nonetheless disproportionately severe and distressing. Amplified medical symptoms are marked by disproportionate physical suffering, unduly negative thoughts and concerns about them, and elevated levels of health-related anxiety. They are accompanied by extensive and sustained illness behaviors, disproportionate difficulty compartmentalizing them and circumscribing their impact, and consequent problems and dissatisfaction with their medical care. A distinction has long been made between "medically explained" and "medically unexplained" symptoms. However, a more comprehensive view of symptom phenomenology undermines this distinction and places all symptoms along a smooth continuum regardless of cause: Recent findings in cognitive neuroscience suggest that all symptoms—regardless of origin—are processed through convergent pathways. The complete conscious experience of both medically "explained" and "unexplained" symptoms is an amalgam of a viscerosomatic sensation fused with its ascribed salience and the patient's ideas, expectations, and concerns about the sensation. This emerging empirical evidence furnishes a basis for viewing persistent, disproportionately distressing symptoms of demonstrable disease along a continuum with medically unexplained symptoms. Thus, therapeutic modalities developed for somatization and medically unexplained symptoms can be helpful in the care of seriously ill medical patients with amplified symptoms. These interventions include educational groups for coping with chronic illness, cognitive therapies for dysfunctional thoughts, behavioral strategies for maladaptive illness behaviors, psychotherapy for associated emotional distress, and consultation with mental health professionals to assist the primary care physician with difficulties in medical management. [ABSTRACT FROM AUTHOR]

Objectives: Controversy remains regarding surgical managements of sylvian fissure arachnoid cyst (SFAC). This review presents our experience in the microsurgical fenestration of pediatric patients with SFAC to define surgical indication, and risks and benefits with special emphasis on postoperative subdural fluid collection (SDFC) and cyst size reduction. Methods: Thirty-four children with SFAC who underwent microsurgical cyst fenestration at a single institution over a 10-year period were retrospectively reviewed for their clinical presentation, neuroimaging findings, and postsurgical course. The SFACs were classified by a novel grading system based on the degree of arachnoid cyst extension from the sylvian fissure to the insular cistern shown on MR images: grade 0 — little or no prominence of sylvian fissure, grade I — SFAC confined to the sylvian fissure, grade II — SFAC partially extending to the insular cistern, grade III — SFAC extending to the entire insular cistern. Results: There were 26 males and 8 females. SFAC was present in the left side in 24. Twelve patients presented with cyst rupturing to the subdural space. Cyst grading did not show significant difference compared with rupture status (p > 0.9). All patients underwent microsurgical cyst fenestration. Postoperative SDFC is common but often resolved overtime in two-thirds of the cases with the mean average of 6 months. However, 3 patients had symptomatic postoperative SDFC and needed reoperation shortly after the first operation. Microsurgical cyst fenestrations for SFAC effectively resolved the presenting symptoms and often showed restorations of intracranial structures on follow-up imaging. Cyst resolution or reduction greater than 75% was noted in 61.8% of the patients postoperatively which was noted in a half of the SFAC of children even with age of 11 years or older. During the follow-up, no cyst recurrence or SDFC was noted. Patients with greater surgical reduction of cyst size tended to occur in younger children, and those with lower MR grade. Conclusion: Our results showed a high reduction rate of SFAC and brain re-expansion after microsurgical fenestration together with symptomatic improvements regardless the patient's age. Considering the developing CNS during childhood, reductions of a large space-occupying lesion followed by restorations of the structural integrity of the developing brain are very desirable. However, a multi-center cooperative prospective longitudinal study on long-term comparative data of those treated and untreated of neuro-psychological outcome and cyst rupture incidence is needed. [ABSTRACT FROM AUTHOR]

The physiology of vascular smooth muscle (VSMC) cells is affected by autophagy, a catabolic cellular mechanism responsible for nutrient recycling. Autophagy-inducing compounds may reverse arterial stiffening, whereas congenital VSMC-specific autophagy deficiency promotes arterial stiffening. The elevated aortic stiffness in 3.5-month-old C57Bl/6 mice, in which the essential autophagy-related gene Atg7 was specifically deleted in the VSMCs (Atg7F/F SM22α-Cre+ mice) was mainly due to passive aortic wall remodeling. The present study investigated whether aortic stiffness was also modulated by a shorter duration of autophagy deficiency. Therefore, aortic segments of 2-month-old Atg7F/F SM22α-Cre+ mice were studied. Similarly to the older mice, autophagy deficiency in VSMCs promoted aortic stiffening by elastin degradation and elastin breaks, and increased the expression of the calcium binding protein S100A4 (+ 157%), the aortic wall thickness (+ 27%), the sensitivity of the VSMCs to depolarization and the contribution of VGCC mediated Ca2+ influx to α1 adrenergic contractions. Hence, all these phenomena occurred before the age of 2 months. When compared to autophagy deficiency in VSMCs at 3.5 months, shorter term autophagy deficiency led to higher segment diameter at 80 mmHg (+ 7% versus − 2%), normal baseline tonus (versus increased), unchanged IP3-mediated phasic contractions (versus enhanced), and enhanced endothelial cell function (versus normal). Overall, and because in vivo cardiac parameters or aortic pulse wave velocity were not affected, these observations indicate that congenital autophagy deficiency in VSMCs of Atg7F/F SM22α-Cre+ mice initiates compensatory mechanisms to maintain circulatory homeostasis. [ABSTRACT FROM AUTHOR]

Background: The development of new left bundle branch block (LBBB) is frequently seen post TAVR and is a known risk factor for progression to high degree AV block. The timing and likelihood of progression into complete heart block is variable and can develop after hospital discharge. We sought to determine predictors for the development of high degree AV block in patients who developed LBBB following TAVR. Methods: All patients between 2014 and 2019 underwent electrophysiology study after developing LBBB post TAVR. Data on these patients including baseline characteristics, echo parameters, EKG variables, HV interval, and the need for subsequent pacemaker implantation were extracted. A prolonged HV interval was defined as ≥ 65 ms. Clinically significant conduction abnormality was defined as development of high-degree AV block or clinically significant complete heart block. Results: Thirty-four patients were included in our study of which 10 (29.4%) developed clinically significant heart block, while 24 (70.6%) did not. The mean HV interval for patients with clinically significant heart block was 70.1 ms vs 57.8 ms for those who did not (p = 0.022). Pre-existing first-degree heart block prior to TAVR (p = 0.026), history of AFib (p = 0.05) in addition to STS score (p = 0.037) were predictors of development of high-degree AV block in our patient population. Conclusions: In patients who develop LBBB following TAVR, HV interval, pre-existing first-degree heart block, and STS score predict progression to high-degree AV block. Performance of a routine electrophysiology study should be considered for high-risk patients who develop LBBB following TAVR. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate dosimetry, dose–response and dose-toxicity relationships for holmium-166 (166Ho) radioembolisation in patients with hepatocellular carcinoma (HCC).Thirty-one patients with hepatocellular carcinoma were included in the HEPAR Primary study (NCT03379844, registered on December 20th, 2017) and underwent 166Ho-microspheres radioembolisation. Linear mixed models assessed the association between tumour absorbed doses and response based on mRECIST both on tumour and patient level. Preliminary tumour absorbed dose thresholds were estimated based on predictive value. Linear regression models assessed the association between non-tumour absorbed dose and Common Terminology Criteria for Adverse Events version 4.03.Median tumour absorbed dose (tumour level) was 95.5 Gy (range 44—332 Gy). Median non-tumour absorbed dose based on whole liver volume was 19 Gy (range 3 – 48 Gy) and based on target liver volume was 30 Gy (range 13 – 54 Gy). There was a significant association between non-tumour absorbed dose and toxicity. Tumours with partial response/complete response (PR/CR, responders) received a 41% higher absorbed dose than tumours with progressive disease/stable disease (PD/SD, non-responders) (95%CI: 2%-93%, p = 0.04). A predictive value of 90% for tumour response was observed at a tumour absorbed dose threshold of 155 Gy, 100% predictive value was achieved at 184.5 Gy.This study confirms a positive relationship between tumour absorbed dose and response and between non-tumour absorbed dose and toxicity. Dose thresholds found in this study can serve as a basis for personalized dosimetry in HCC patients treated with 166Ho-microspheres.Methods: To evaluate dosimetry, dose–response and dose-toxicity relationships for holmium-166 (166Ho) radioembolisation in patients with hepatocellular carcinoma (HCC).Thirty-one patients with hepatocellular carcinoma were included in the HEPAR Primary study (NCT03379844, registered on December 20th, 2017) and underwent 166Ho-microspheres radioembolisation. Linear mixed models assessed the association between tumour absorbed doses and response based on mRECIST both on tumour and patient level. Preliminary tumour absorbed dose thresholds were estimated based on predictive value. Linear regression models assessed the association between non-tumour absorbed dose and Common Terminology Criteria for Adverse Events version 4.03.Median tumour absorbed dose (tumour level) was 95.5 Gy (range 44—332 Gy). Median non-tumour absorbed dose based on whole liver volume was 19 Gy (range 3 – 48 Gy) and based on target liver volume was 30 Gy (range 13 – 54 Gy). There was a significant association between non-tumour absorbed dose and toxicity. Tumours with partial response/complete response (PR/CR, responders) received a 41% higher absorbed dose than tumours with progressive disease/stable disease (PD/SD, non-responders) (95%CI: 2%-93%, p = 0.04). A predictive value of 90% for tumour response was observed at a tumour absorbed dose threshold of 155 Gy, 100% predictive value was achieved at 184.5 Gy.This study confirms a positive relationship between tumour absorbed dose and response and between non-tumour absorbed dose and toxicity. Dose thresholds found in this study can serve as a basis for personalized dosimetry in HCC patients treated with 166Ho-microspheres.Results: To evaluate dosimetry, dose–response and dose-toxicity relationships for holmium-166 (166Ho) radioembolisation in patients with hepatocellular carcinoma (HCC).Thirty-one patients with hepatocellular carcinoma were included in the HEPAR Primary study (NCT03379844, registered on December 20th, 2017) and underwent 166Ho-microspheres radioembolisation. Linear mixed models assessed the association between tumour absorbed doses and response based on mRECIST both on tumour and patient level. Preliminary tumour absorbed dose thresholds were estimated based on predictive value. Linear regression models assessed the association between non-tumour absorbed dose and Common Terminology Criteria for Adverse Events version 4.03.Median tumour absorbed dose (tumour level) was 95.5 Gy (range 44—332 Gy). Median non-tumour absorbed dose based on whole liver volume was 19 Gy (range 3 – 48 Gy) and based on target liver volume was 30 Gy (range 13 – 54 Gy). There was a significant association between non-tumour absorbed dose and toxicity. Tumours with partial response/complete response (PR/CR, responders) received a 41% higher absorbed dose than tumours with progressive disease/stable disease (PD/SD, non-responders) (95%CI: 2%-93%, p = 0.04). A predictive value of 90% for tumour response was observed at a tumour absorbed dose threshold of 155 Gy, 100% predictive value was achieved at 184.5 Gy.This study confirms a positive relationship between tumour absorbed dose and response and between non-tumour absorbed dose and toxicity. Dose thresholds found in this study can serve as a basis for personalized dosimetry in HCC patients treated with 166Ho-microspheres.Conclusion: To evaluate dosimetry, dose–response and dose-toxicity relationships for holmium-166 (166Ho) radioembolisation in patients with hepatocellular carcinoma (HCC).Thirty-one patients with hepatocellular carcinoma were included in the HEPAR Primary study (NCT03379844, registered on December 20th, 2017) and underwent 166Ho-microspheres radioembolisation. Linear mixed models assessed the association between tumour absorbed doses and response based on mRECIST both on tumour and patient level. Preliminary tumour absorbed dose thresholds were estimated based on predictive value. Linear regression models assessed the association between non-tumour absorbed dose and Common Terminology Criteria for Adverse Events version 4.03.Median tumour absorbed dose (tumour level) was 95.5 Gy (range 44—332 Gy). Median non-tumour absorbed dose based on whole liver volume was 19 Gy (range 3 – 48 Gy) and based on target liver volume was 30 Gy (range 13 – 54 Gy). There was a significant association between non-tumour absorbed dose and toxicity. Tumours with partial response/complete response (PR/CR, responders) received a 41% higher absorbed dose than tumours with progressive disease/stable disease (PD/SD, non-responders) (95%CI: 2%-93%, p = 0.04). A predictive value of 90% for tumour response was observed at a tumour absorbed dose threshold of 155 Gy, 100% predictive value was achieved at 184.5 Gy.This study confirms a positive relationship between tumour absorbed dose and response and between non-tumour absorbed dose and toxicity. Dose thresholds found in this study can serve as a basis for personalized dosimetry in HCC patients treated with 166Ho-microspheres. [ABSTRACT FROM AUTHOR]

Since its first suggestion as possible option for liver radioembolization treatment, the therapeutic isotope holmium-166 (166Ho) caught the experts' attention due to its imaging possibilities. Being not only a beta, but also a gamma emitter and a lanthanide, 166Ho can be imaged using single-photon emission computed tomography and magnetic resonance imaging, respectively. Another advantage of 166Ho is the possibility to perform the scout and treatment procedure with the same particle. This prospect paves the way to an individualized treatment procedure, gaining more control over dosimetry-based patient selection and treatment planning. In this review, an overview on 166Ho liver radioembolization will be presented. The current clinical workflow, together with the most relevant clinical findings and the future prospective will be provided. [ABSTRACT FROM AUTHOR]

The give-n task is widely used in developmental psychology to indicate young children's knowledge or use of the cardinality principle (CP): the last number word used in the counting process indicates the total number of items in a collection. Fuson (1988) distinguished between the CP, which she called the count-cardinal concept, and the cardinal-count concept, which she argued is a more advanced cardinality concept that underlies the counting-out process required by the give-n task with larger numbers. One aim of the present research was to evaluate Fuson's disputed hypothesis that these two cardinality concepts are distinct and that the count-cardinal concept serves as a developmental prerequisite for constructing the cardinal-count concept. Consistent with Fuson's hypothesis, the present study with twenty-four 3- and 4-year-olds revealed that success on a battery of tests assessing understanding of the count-cardinal concept was significantly and substantially better than that on the give-n task, which she presumed assessed the cardinal-count concept. Specifically, the results indicated that understanding the count-cardinal concept is a necessary condition for understanding the cardinal-count concept. The key methodological implication is that the widely used give-n task may significantly underestimate children's understanding of the CP or count-cardinal concept. The results were also consistent with a second aim, which was to confirm that number constancy concepts develop after the count-cardinal concept but before the cardinal-count concept. [ABSTRACT FROM AUTHOR]

The tropical Pacific exhibits decadal El Niño-Southern Oscillation (ENSO)-like variability, characterized by meridionally broad sea surface temperature anomalies in the eastern Pacific. In this study, we focus on the variability in the equatorial Pacific band (5°S–5°N), termed equatorial Pacific decadal variability (EPDV). While it is known that ocean dynamics plays an essential role in EPDV, the simulations by air-sea thermodynamically coupled slab ocean models (SOM) obscure the nature of the role of ocean dynamics. To confront this issue, we use a mechanically decoupled simulation, which isolates the effects of thermodynamic coupling processes and mean ocean circulation on EPDV. Thus, by comparing the simulation to a SOM, we investigate the role of mean ocean circulation and show that it plays a role in damping EPDV, primarily through mean equatorial Pacific upwelling. By comparing the simulation to a fully coupled dynamic ocean model (DOM), we examine the role of anomalous wind-driven ocean circulation and demonstrate that it plays a role in amplifying EPDV. Further, this amplification strength overwhelms the upwelling damping effect, resulting in the anomalous wind-driven ocean circulation forcing EPDV. Finally, we examine the origin of EPDV in the DOM and show that it originates from a zonal dipole mode in the tropical Pacific, which is strongly associated with decadal modulation of ENSO amplitude. Taking EPDV as an example, our study advances the understanding of the two distinct dynamical systems (SOM and DOM), benefiting the physical interpretation of other climate variabilities. [ABSTRACT FROM AUTHOR]

The South Atlantic Convergence Zone (SACZ) is an atmospheric system occurring in austral summer on the South America continent and sometimes extending over the adjacent South Atlantic. It is characterized by a persistent and very large, northwest-southeast-oriented, cloud band. Its presence over the ocean causes sea surface cooling that some past studies indicated as being produced by a decrease of incoming solar heat flux induced by the extensive cloud cover. Here we investigate ocean–atmosphere interaction processes in the Southwestern Atlantic Ocean (SWA) during SACZ oceanic episodes, as well as the resulting modulations occurring in the oceanic mixed layer and their possible feedbacks on the marine atmospheric boundary layer. Our main interests and novel results are on verifying how the oceanic SACZ acts on dynamic and thermodynamic mechanisms and contributes to the sea surface thermal balance in that region. In our oceanic SACZ episodes simulations we confirm an ocean surface cooling. Model results indicate that surface atmospheric circulation and the presence of an extensive cloud cover band over the SWA promote sea surface cooling via a combined effect of dynamic and thermodynamic mechanisms, which are of the same order of magnitude. The sea surface temperature (SST) decreases in regions underneath oceanic SACZ positions, near Southeast Brazilian coast, in the South Brazil Bight (SBB) and offshore. This cooling is the result of a complex combination of factors caused by the decrease of solar shortwave radiation reaching the sea surface and the reduction of horizontal heat advection in the Brazil Current (BC) region. The weakened southward BC and adjacent offshore region heat advection seems to be associated with the surface atmospheric circulation caused by oceanic SACZ episodes, which rotate the surface wind and strengthen cyclonic oceanic mesoscale eddy. Another singular feature found in this study is the presence of an atmospheric cyclonic vortex Southwest of the SACZ (CVSS), both at the surface and aloft at 850 hPa near 24°S and 45°W. The CVSS induces an SST decrease southwestward from the SACZ position by inducing divergent Ekman transport and consequent offshore upwelling. This shows that the dynamical effects of atmospheric surface circulation associated with the oceanic SACZ are not restricted only to the region underneath the cloud band, but that they extend southwestward where the CVSS presence supports the oceanic SACZ convective activity and concomitantly modifies the ocean dynamics. Therefore, the changes produced in the oceanic dynamics by these SACZ events may be important to many areas of scientific and applied climate research. For example, episodes of oceanic SACZ may influence the pathways of pollutants as well as fish larvae dispersion in the region. [ABSTRACT FROM AUTHOR]

Previous toxicity assessments of heavy metals on Drosophila are limited to investigating the survival, development rate, and climbing behaviour by oral administration while cardiac toxicity of these elements have not been investigated. We utilized a microfluidic device to inject known dosages of zinc (Zn) or cadmium (Cd) into the larvae's hemolymph to expose their heart directly and study their heart rate and arrhythmicity. The effect of heart-specific overexpression of metal responsive transcription factor (MTF-1) on different heartbeat parameters and survival of Drosophila larvae was investigated. The heart rate of wild-type larvae decreased by 24.8% or increased by 11.9%, 15 min after injection of 40 nL of 100 mM Zn or 10 mM Cd solution, respectively. The arrhythmicity index of wild-type larvae increased by 58.2% or 76.8%, after injection of Zn or Cd, respectively. MTF-1 heart overexpression ameliorated these effects completely. Moreover, it increased larvae's survival to pupal and adulthood stages and prolonged the longevity of flies injected with Zn and Cd. Our microfluidic-based cardiac toxicity assay illustrated that heart is an acute target of heavy metals toxicity, and MTF-1 overexpression in this tissue can ameliorate cardiac toxicity of Zn and Cd. The method can be used for cardiotoxicity assays with other pollutants in the future. [ABSTRACT FROM AUTHOR]

Telomeres, the natural ends of linear chromosomes, comprise repeat-sequence DNA and associated proteins1. Replication of telomeres allows continued proliferation of human stem cells and immortality of cancer cells2. This replication requires telomerase3 extension of the single-stranded DNA (ssDNA) of the telomeric G-strand ((TTAGGG)n); the synthesis of the complementary C-strand ((CCCTAA)n) is much less well characterized. The CST (CTC1–STN1–TEN1) protein complex, a DNA polymerase α-primase accessory factor4,5, is known to be required for telomere replication in vivo6–9, and the molecular analysis presented here reveals key features of its mechanism. We find that human CST uses its ssDNA-binding activity to specify the origins for telomeric C-strand synthesis by bound Polα-primase. CST-organized DNA polymerization can copy a telomeric DNA template that folds into G-quadruplex structures, but the challenges presented by this template probably contribute to telomere replication problems observed in vivo. Combining telomerase, a short telomeric ssDNA primer and CST–Polα–primase gives complete telomeric DNA replication, resulting in the same sort of ssDNA 3′ overhang found naturally on human telomeres. We conclude that the CST complex not only terminates telomerase extension10,11 and recruits Polα–primase to telomeric ssDNA4,12,13 but also orchestrates C-strand synthesis. Because replication of the telomere has features distinct from replication of the rest of the genome, targeting telomere-replication components including CST holds promise for cancer therapeutics.The Polα–primase-associated CST complex organizes telomeric C-strand DNA synthesis, and, in combination with telomerase, it carries out complete replication of the single-stranded DNA overhang found at human telomeres. [ABSTRACT FROM AUTHOR]

Background: Despite its high specificity, PSMA PET/CT has a moderate to low sensitivity of 40–50% for pelvic lymph node detection, implicating that a negative PSMA PET/CT cannot rule out lymph node metastases. This study investigates a strategy of implementing PSMA PET/CT for initial prostate cancer staging and treatment planning compared to conventional diagnostics. In this PSMA PET/CT strategy, a bilateral extended pelvic lymph node dissection (ePLND) is only performed in case of a negative PSMA PET/CT; in case of a positive scan treatment planning is solely based on PSMA PET/CT results. Method: A decision table and lifetime state transition model were created. Quality-adjusted life years and health care costs were modelled over lifetime. Results: The PSMA PET/CT strategy of treatment planning based on initial staging with [68Ga]Ga-PSMA-11 PET/CT results in cost-savings of €674 and a small loss in quality of life (QoL), 0.011 QALY per patient. The positive effect of [68Ga]Ga-PSMA-11 PET/CT was caused by abandoning both an ePLND and unnecessary treatment in iM1 patients, saving costs and resulting in higher QoL. The negative effect was caused by lower QoL and high costs in the false palliative state, due to pN1lim patients (≤ 4 pelvic lymph node metastases) being falsely diagnosed as iN1ext (> 4 pelvic lymph node metastases). These patients received subsequently palliative treatment instead of potentially curative therapy. Conclusion: Initial staging and treatment planning based on [68Ga]Ga-PSMA-11 PET/CT saves cost but results in small QALY loss due to the rate of false positive findings. [ABSTRACT FROM AUTHOR]

Programmable photonic integrated circuits (PICs) are dense assemblies of tunable elements that provide flexible reconfigurability to enable different functions to be selected; however, due to manufacturing variations and thermal gradients that affect the optical phases of the elements, it is difficult to guarantee a stable correspondence between the electrical commands to the chip, and the function that it provides. Here we demonstrate a self-calibrating programmable PIC with full control over its complex impulse response, in the presence of thermal cross-talk between phase-tuning elements. Self-calibration is achieved by: (1) incorporating an optical reference path into the PIC; (2) using the Kramers–Kronig relationship to recover the phase response from amplitude measurements; and (3) applying a fast-converging self-calibration algorithm. We demonstrate dial-up signal processing functions with complex impulse responses using only 25 training iterations. This approach offers stable and accurate control of large-scale PICs, for demanding applications such as communications network reconfiguration, neuromorphic hardware accelerators and quantum computers. Researchers demonstrate a self-calibrating programmable photonic integrated circuit. The findings may be useful for the accurate control of large-scale photonic integrated circuits in applications such as light-based machine learning. [ABSTRACT FROM AUTHOR]