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Self-sufficiency, climate change and increasing geopolitical risks have driven energy policies to make renewable energy sources dominant in the power production portfolios. The initial boom in the mid-2000s of global photovoltaic installations demonstrated the feasibility of the ambitious renewable energy targets. However, this rapid scale-up has introduced challenges, including price volatility and system integration issues. This communication calls the attention to these emerging challenges and offers quantitative insights on how rapid adoption of a more diversified photovoltaics deployment strategies can mitigate price volatilities, reduce fossil fuel dependence and steer Europe towards a forward-thinking sustainable energy pathway. The analysis reveals that as innovative bifacial photovoltaic systems are incorporated on a large-scale disruptive scenario, four main patterns emerge: economic value of solar production increases, base-load electricity price decreases, sun-rich countries expand their solar contributions, whereas nations with ample grid interconnections enhance their energy imports from neighbouring countries. It also underscores the importance of maintaining photovoltaics an attractive option for energy investors and traders in the future. Establishing this groundwork is critical since a successful integration of large-scale solar systems contributing to decrease price volatilities in Europe and US will carry significant repercussions for global energy policy formulation., (© 2024. The Author(s).)

The sustainability of social-ecological systems within river deltas globally is in question as rapid development and environmental change trigger "negative" or "positive" tipping points depending on actors' perspectives, e.g. regime shift from abundant sediment deposition to sediment shortage, agricultural sustainability to agricultural collapse or shift from rural to urban land use. Using a systematic review of the literature, we show how cascading effects across anthropogenic, ecological, and geophysical processes have triggered numerous tipping points in the governance, hydrological, and land-use management of the world's river deltas. Crossing tipping points had both positive and negative effects that generally enhanced economic development to the detriment of the environment. Assessment of deltas that featured prominently in the review revealed how outcomes of tipping points can inform the long-term trajectory of deltas towards sustainability or collapse. Management of key drivers at the delta scale can trigger positive tipping points to place social-ecological systems on a pathway towards sustainable development., (© 2024. Crown.)

Objective: Weight loss following vertical sleeve gastrectomy (VSG) in youth can range from 10% to 50%. We examined whether there are differences in demographic or metabolic parameters before VSG in youth who achieve above-average weight loss (AAWL) versus below-average weight loss (BAWL) at 1 year post VSG and if youth with BAWL still achieve metabolic health improvements at 1 year post VSG., Methods: Demographic, anthropometric, and clinical lab data were collected before VSG and at 1, 3, 6, and 12 months after VSG., Results: Forty-three youth with a mean age of 16.9 (SD 1.7) years before VSG were studied; 70% were female, 19% non-Hispanic Black, 58% non-Hispanic White, and 23% mixed/other race. Mean baseline BMI was 51.1 (SD 10.5) kg/m 2 . Average weight loss was 25.8%. The AAWL group lost 18.6 kg/m 2 (35.3%) versus the BAWL group, who lost 8.8 kg/m 2 (17.5%). BMI, age, race, sex, and socioeconomic status at baseline were similar between AAWL and BAWL groups; however, the BAWL group had a higher frequency of pre-VSG dysglycemia, steatotic liver disease, and dyslipidemia. At 1 year post VSG, fewer youth in the BAWL group achieved ideal health parameters, and they had less resolution of comorbidities., Conclusions: The presence of comorbidities before VSG is associated with less weight loss and reduced resolution of metabolic conditions at 1 year post VSG., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

In neurocritical care, the gold standard method is intracranial pressure (ICP) monitoring for the patient's lifesaving. Since it is an invasive method, it is desirable to use an alternative, noninvasive technique. The computerized real-time invasive cerebral blood flow (CBF) autoregulation (AR) monitoring calculates the status of CBF AR, called the pressure reactivity index (PRx). Studies documented that the electrical impedance of the head (Rheoencephalography - REG) can detect the status of CBF AR (REGx) and ICP noninvasively. We aimed to test REG to reflect ICP and CBF AR. For nineteen healthy subjects we recorded bipolar bifrontal and bitemporal REG derivations and arm bioimpedance pulses with a 200 Hz sampling rate. The challenges were a 30-second breath-holding and head-down-tilt (HDT - Trendelenburg) position. Data were stored and processed offline. REG pulse wave morphology and REGx were calculated. The most relevant finding was the significant morphological change of the REG pulse waveform (2 nd peak increase) during the HDT position. Breath-holding caused REG amplitude increase, but it was not significant. REGx in male and female group averages have similar trends during HDT by indicating the active status of CBF AR. The morphological change of REG pulse wave during HDT position was identical to ICP waveform change during increased ICP, reflecting decreased intracranial compliance. A correlation study between ICP and REG was initiated in neurocritical care patients. The noninvasive REG monitoring would also be useful in space research as well as in military medicine during the transport of wounded service members as well as for fighter pilots to indicate the loss of CBF and consciousness., Competing Interests: Conflict of interest The authors state there is no conflict of interest., (© 2024 Sandor Szabo et al., published by Sciendo.)

Plexiform neurofibromas (PNFs) are nerve tumors caused by loss of NF1 and dysregulation of RAS-MAPK signaling in Schwann cells. Most PNFs shrink in response to MEK inhibition, but targets with increased and durable effects are needed. We identified the anaphylatoxin C5a as increased in PNFs and expressed largely by PNF m acrophages. We defined pharmacokinetic and immunomodulatory properties of a C5aR1/2 antagonist and tested if peptide antagonists augment the effects of MEK inhibition. MEK inhibition recruited C5AR1 to the macrophage surface; short-term inhibition of C5aR elevated macrophage apoptosis and Schwann cell death, without affecting MEK-induced tumor shrinkage. PNF macrophages lacking C5aR1 increased the engulfment of dying Schwann cells, allowing their visualization. Halting combination therapy resulted in altered T-cell distribution, elevated Iba1+ and CD169+ immunoreactivity, and profoundly altered cytokine expression, but not sustained trumor shrinkage. Thus, C5aRA inhibition independently induces macrophage cell death and causes sustained and durable effects on the PNF microenvironment., (© 2024 Perrino et al.)

Stress is the nonspecific response of the body to any demand made upon it, as defined by Hans Selye more than 80 years ago, based on his animal experiments at McGill University in Montreal, Canada. By emphasizing 'nonspecificity' he tried to underline that stress response is elicited my several factors, like nowadays in COVID-19, e.g., fear of infection, social isolation, death in family, loss of employment, etc. Thus, COVID-19 has been the largest new human stressor in the twenty-first century. Selye's studies in rats also revealed 3 stages of stress response: the short initial "alarm reaction" is followed by a longer "stage of resistance", associated with increased levels of corticosterone that is often terminated by a "stage of exhaustion", referring to an exhausted adrenal cortex when the secretion of glucocorticoids drops. Fast forward, that is exactly what has been documented in severe cases of infections caused by the SARS-CoV-2 virus: in hospitalized COVID-19 patients initially the blood levels of cortisol not only have been elevated, but only those with high concentration of this natural anti-inflammatory corticosteroid survived vs. those who had low levels of cortisol, suggesting diminished adrenocortical functions. Furthermore, patients with very severe cases of COVID-19 who ended up in intensive care units had significantly low cortisol blood levels, compared to patients with equal severity of diseases due to other causes. Thus, these 'natural phenomena' in clinical medicine, unfortunately confirmed Selye's studies in experimental animals several decades ago. Still, the good news is that astute clinicians empirically recognized this and started to give potent synthetic glucocorticoids such as dexamethasone to severe COVD-19 patients and this beneficial effect of exogenous corticoids has been extensively confirmed in the scientific literature., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Influenza virus-induced respiratory pneumonia remains a major public health concern. Obesity, metabolic diseases, and female sex are viewed as independent risk factors for worsened influenza virus-induced lung disease severity. However, lack of experimental models of severe obesity in female mice limits discovery-based studies. Here, via utility of thermoneutral housing (30 °C) and high-fat diet (HFD) feeding, we induced severe obesity and metabolic disease in female C57BL/6 mice and compared their responses to severely obese male C57BL/6 counterparts during influenza virus infection. We show that lean male and female mice have similar lung edema, inflammation, and immune cell infiltration during influenza virus infection. At standard housing conditions, HFD-fed male, but not female, mice exhibit severe obesity, metabolic disease, and exacerbated influenza disease severity. However, combining thermoneutral housing and HFD feeding in female mice induces severe obesity and metabolic disease, which is sufficient to amplify influenza virus-driven disease severity to a level comparable to severely obese male counterparts. Lastly, increased total body weights of male and female mice at time of infection correlated with worsened influenza virus-driven disease severity metrics. Together, our findings confirm the impact of obesity and metabolic disease as key risk factors to influenza disease severity and present a novel mouse experimental model suitable for future mechanistic interrogation of sex, obesity, and metabolic disease traits in influenza virus-driven disease severity., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study evaluates the precision of a commercially available spine planning software in automatic spine labelling and screw-trajectory proposal., Methods: The software uses automatic segmentation and registration of the vertebra to generate screw proposals. 877 trajectories were compared. Four neurosurgeons assessed suggested trajectories, performed corrections, and manually planned pedicle screws. Additionally, automatic identification/labelling was evaluated., Results: Automatic labelling was correct in 89% of the cases. 92.9% of automatically planned trajectories were in accordance with G&R grade A + B. Automatic mode reduced the time spent planning screw trajectories by 7 s per screw to 20 s per vertebra. Manual mode yielded differences in screw-length between surgeons (largest distribution peak: 5 mm), automatic in contrast at 0 mm. The size of suggested pedicle screws was significantly smaller (largest peaks in difference between 0.5 and 3 mm) than the surgeon's choice., Conclusion: Automatic identification of vertebrae works in most cases and suggested pedicle screw trajectories are acceptable. So far, it does not substitute for an experienced surgeon's assessment., (© 2023 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons Ltd.)

BCOR alterations are described in ultra-rare infantile soft tissue sarcomas including primitive myxoid mesenchymal tumor of infancy and undifferentiated round cell sarcoma (URCS). Previous reports often describe dismal outcomes. Thus, we undertook a retrospective, multi-institutional study of infants with BCOR -rearranged soft tissue sarcomas. Nine patients aged 6 weeks to 15 months were identified. One tumor carried a BCOR :: CCNB3 fusion, whereas 7 tumors harbored internal tandem duplication of BCOR , including 4 cases classified as primitive myxoid mesenchymal tumor of infancy, 1 case as URCS, and 2 cases characterized by a "hybrid morphology" in our evaluation. Four patients underwent upfront surgery with residual disease that progressed locally after a median of 2.5 months. Locoregional recurrences were observed in hybrid patients, and the URCS case recurred with brain metastases. Complete radiographic responses after chemotherapy were achieved in patients treated with vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide, vincristine/doxorubicin/cyclophosphamide alternating with cyclophosphamide/etoposide (regimen I), and ifosfamide/carboplatin/etoposide. Seven patients received radiotherapy. With a median of 23.5 months off therapy, 8 patients are with no evidence of disease. In our study, observation was inadequate for the management of untreated postsurgical residual disease. Tumors demonstrated chemosensitivity with anthracycline-based regimens and ifosfamide/carboplatin/etoposide. Radiotherapy was required to achieve durable response in most patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Asparaginase is a key component of chemotherapy protocols for the treatment of lymphoblastic malignancies among children. Adequate asparagine depletion is an important factor to achieve optimal therapeutic outcomes., Methods: Over a 3.5 year period, 106 patients were monitored for asparaginase activity (329 samples) in a single center of the Hungarian Pediatric Oncology-Hematology Group. In Hungary, three asparaginase products are available: native E. coli ASNase (Kidrolase), a pegylated form of this enzyme (Pegaspargase) and another native product from Erwinia chrysanthemi (Erwinase). A retrospective data analysis was performed., Results: In 81% (268/329) of our patients, AEA levels were in the optimal therapeutic range of over 100 IU/L. Of 106 patients, 13 (12%) were diagnosed with 'silent inactivation'., Conclusions: Monitoring of AEA can help to identify patients with 'silent inactivation' and their asparaginase therapy can thus be optimized.

Background: There are no consensus guidelines regarding the use of percutaneous needle biopsy for the diagnosis of soft tissue and bone tumors. The aim of this study was to understand the efficacy of image-guided percutaneous biopsy for pediatric patients with soft tissue and bony masses, the role of intraoperative image guidance, and diagnostic accuracy., Patients and Methods: A retrospective institutional chart review was performed on patients who underwent percutaneous biopsy of soft tissue or bone tumors between 2007 and 2017. Data collected included preoperative imaging, type of biopsy, demographics, insurance status, number of samples taken, and pathologic results., Results: One hundred forty-one children and young adults underwent 169 biopsies. Female patients received 48.2% of biopsies. The mean age was 14.3 ± 7.0 years. Core needle biopsies made up 89.4% of procedures, while 10.6% were fine needle aspirate. The mean number of samples per patient was 3.6 ± 2.5. All patients had imaging guidance, with computed tomography used in 44.7% of patients, 9.9% using fluoroscopy, 7.1% using ultrasound for guidance, and 53 (37.6%) patients had more than one modality. Diagnostic specimens were obtained in 97.9% of biopsies. The most common overall pathology was osteoid osteoma. The most common malignant tumors were osteosarcoma and Ewing's sarcoma., Conclusion: Image-guided percutaneous biopsy is a safe and effective method of obtaining accurate tissue samples in children and young adults with soft tissue or bone masses., Level of Evidence: Level 4-Study of diagnostic test., (© 2023. Society of Surgical Oncology.)

Clinically significant endemic mycoses (fungal infections) in the United States (U.S.) include Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides immitis/posadasii. While the majority of infections go clinically unnoticed, symptomatic disease can occur in immunocompromised or hospitalized patients, and occasionally in immune-competent individuals. Clinical manifestations vary widely and their diagnosis may require fungal culture, making the rapid diagnosis a challenge. Imaging can be helpful in making a clinical diagnosis prior to laboratory confirmation, as well as assist in characterizing disease extent and severity. In this review, we discuss the three major endemic fungal infections that occur in the U.S., including mycology, epidemiology, clinical presentations, and typical imaging features with an emphasis on the pediatric population., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recent developments in health technology assessment (HTA), including the promotion of a new and internationally accepted definition of HTA, have highlighted the need to go beyond clinical and cost-effectiveness to fully understand the potential value of health technologies. Multidisciplinary efforts to generate patient-focused evidence relevant to HTA, using both quantitative and qualitative approaches, are needed. Although it has been more than 20 years since opportunities for qualitative methods to inform HTA were first discussed, their use remains infrequent. The goal of this article is to resurrect the debate about the value of qualitative research in HTA. Drawing on examples from published literature, we propose five key areas where qualitative methods can contribute to HTA, complementary to studies of clinical and cost-effectiveness: (i) assessing acceptability and subjective value; (ii) understanding perspectives and providing context; (iii) reaching the groups other methods cannot reach; (iv) laying the groundwork for subsequent quantitative exercises; and (v) contributing to economic model development.

Activating non-inherited mutations in the guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) gene family have been identified in childhood vascular tumors. Patients experience extensive disfigurement, chronic pain and severe complications including a potentially lethal coagulopathy termed Kasabach-Merritt phenomenon. Animal models for this class of vascular tumors do not exist. This has severely hindered the discovery of the molecular consequences of GNAQ mutations in the vasculature and, in turn, the preclinical development of effective targeted therapies. Here we report a mouse model expressing hyperactive mutant GNAQ in endothelial cells. Mutant mice develop vascular and coagulopathy phenotypes similar to those seen in patients. Mechanistically, by transcriptomic analysis we demonstrate increased mitogen activated protein kinase signaling in the mutant endothelial cells. Targeting of this pathway with Trametinib suppresses the tumor growth by reducing vascular cell proliferation and permeability. Trametinib also prevents the development of coagulopathy and improves mouse survival., (© 2023. The Author(s).)

The previous acute respiratory diseases caused by viruses originating from China or the middle east (e.g., SARS, MERS) remained fast developing short diseases without major sequalae or any long-lasting complications. The new COVID-19, on the other hand, not only that it rapidly spread over the world, but some patients never fully recovered or even if they did, a few weeks later started to complain not only of shortness of breath, if any, but general weakness, muscle pains and 'brain fog', i.e., fuzzy memories. Thus, these signs and symptoms were eventually labelled 'long COVID', for which the most widely used definition is 'new signs and symptoms occurring 4-8 weeks after recovering from acute stage of COVID-19'. The other most frequent manifestations associated with long COVID include headache, loss of memory, smell and of hair, nausea, and vomiting. Thus, long COVID is not a simple disease, but complex disorder of several organ systems malfunctioning; hence, it is probably more appropriate to call this a syndrome. The pathogenesis of long COVID syndrome is poorly understood, but initial and persistent vascular endothelial injury that often triggers the formation of microthrombi that if dislodged as emboli, damage several organs, especially in the brain, heart and kidney, by creating microinfarcts. The other major contributory mechanistic factor is the persistent cytokine storm that may last longer in long COVID patients than in others, probably triggered by aggregates of SARS-Co-2 discovered recently in the adrenal cortex, kidney and brain. The prevalence of long COVID is relatively high, e.g., initially varied 3-30%, and recent data indicate that 2.5% of UK population suffers from this syndrome, while in the US 14.7% of acute COVID-19 patients continued to have symptoms longer than 2 months. Thus, the long COVID syndrome deserves to be further investigated, both from clinical and basic research perspectives., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Neurofibromatosis type 1 (NF1) patients are predisposed to develop plexiform neurofibromas (PNFs). Three endoplasmic reticulum (ER) stress response pathways restore cellular homeostasis. The unfolded protein response (UPR) sensors contribute to tumor initiation in many cancers. We found that all three UPR pathways were activated in mouse and human PNFs, with protein kinase RNA [PKR]-like ER kinase (PERK) the most highly expressed. We tested if neurofibroma cells adapt to ER stress, leading to their growth. Pharmacological or genetic inhibition of PERK reduced mouse neurofibroma-sphere number, and genetic inhibition in PERK in Schwann cell precursors (SCPs) decreased tumor-like lesion numbers in a cell transplantation model. Further, in a PNF mouse model, deletion of PERK in Schwann cells (SCs) and SCPs reduced tumor size, number, and increased survival. Mechanistically, loss of Nf1 activated PERK-eIF2α-ATF4 signaling and increased ATF4 downstream target gene p21 translocation from nucleus to cytoplasm. This nucleus-cytoplasm translocation was mediated by exportin-1. Runx transcriptionally activated ribosome gene expression and increased protein synthesis to allow SCs to adapt to ER stress and tumor formation. We propose that targeting proteostasis might provide cytotoxic and/or potentially durable novel therapy for PNFs., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Inflammation is a common unifying factor in experimental models of non-alcoholic fatty liver disease (NAFLD) progression. Recent evidence suggests that housing temperature-driven alterations in hepatic inflammation correlate with exacerbated hepatic steatosis, development of hepatic fibrosis, and hepatocellular damage in a model of high fat diet-driven NAFLD. However, the congruency of these findings across other, frequently employed, experimental mouse models of NAFLD has not been studied., Methods: Here, we examine the impact of housing temperature on steatosis, hepatocellular damage, hepatic inflammation, and fibrosis in NASH diet, methionine and choline deficient diet, and western diet + carbon tetrachloride experimental models of NAFLD in C57BL/6 mice., Results: We show that differences relevant to NAFLD pathology uncovered by thermoneutral housing include: (i) augmented NASH diet-driven hepatic immune cell accrual, exacerbated serum alanine transaminase levels and increased liver tissue damage as determined by NAFLD activity score; (ii) augmented methionine choline deficient diet-driven hepatic immune cell accrual and increased liver tissue damage as indicated by amplified hepatocellular ballooning, lobular inflammation, fibrosis and overall NAFLD activity score; and (iii) dampened western diet + carbon tetrachloride driven hepatic immune cell accrual and serum alanine aminotransferase levels but similar NAFLD activity score., Discussion: Collectively, our findings demonstrate that thermoneutral housing has broad but divergent effects on hepatic immune cell inflammation and hepatocellular damage across existing experimental NAFLD models in mice. These insights may serve as a foundation for future mechanistic interrogations focused on immune cell function in shaping NAFLD progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Oates, Sawada, Giles, Alarcon, Damen, Szabo, Stankiewicz, Moreno-Fernandez and Divanovic.)

Results from multiple electrode aggregometry (MEA) may vary according to pre-analytic factors. This study aimed to analyze the association of time from blood draw to MEA in patients undergoing percutaneous coronary intervention (PCI). In this observational single-center cohort study, platelet aggregation (aggregation units, U) was quantified by MEA (Multiplate Analyzer) after stimulation with adenosine diphosphate (ADP; final concentration [Fc] 6.4 μM), thrombin receptor activating peptide (TRAP; Fc 32 μM), or arachidonic acid (AA; Fc 0.5 mM) in patients treated with ASA and clopidogrel following PCI. High on-clopidogrel platelet reactivity (HPR) was defined as ADP-induced platelet aggregation ≥ 46 U. The manufacturer recommends performing the analysis within 30-180 min after blood draw. Patients were grouped according to the time from blood draw to MEA: 30-180 min, < 30 min, or > 180 min. Platelet function of 273 patients with coronary artery disease undergoing PCI with dual antiplatelet therapy was analyzed. The median age was 72 years (interquartile range, IQR 62-79) and 179 (66%) were male. Median ADP-, TRAP-, and AA-induced aggregation was 25 (IQR 18-36) U, 79 (IQR 63-96) U, and 12 (IQR 7-18) U, respectively. For those analyzed within 30-180 min from blood draw, no significant correlation of time from blood draw to MEA was observed 1) ADP (r = - 0.04, p = 0.51); 2) TRAP (r = - 0.06, p = 0.32); 3) AA (r = - 0.03, p = 0.67). In patients undergoing percutaneous coronary intervention and treated with dual antiplatelet therapy, the time from blood draw to multiple electrode aggregometry does not correlate with ADP- induced aggregation when the measurement occurred within the recommended time interval of 30-180 min after blood draw., (© 2022. The Author(s).)

Large publicly funded programmes of research continue to receive increased investment as interventions aiming to produce impact for the world's poorest and most marginalized populations. At this intersection of research and development, research is expected to contribute to complex processes of societal change. Embracing a co-produced view of impact as emerging along uncertain causal pathways often without predefined outcomes calls for innovation in the use of complexity-aware approaches to evaluation. The papers in this special issue present rich experiences of authors working across sectors and geographies, employing methodological innovation and navigating power as they reconcile tensions. They illustrate the challenges with (i) evaluating performance to meet accountability demands while fostering learning for adaptation; (ii) evaluating prospective theories of change while capturing emergent change; (iii) evaluating internal relational dimensions while measuring external development outcomes; (iv) evaluating across scales: from measuring local level end impact to understanding contributions to systems level change. Taken as a whole, the issue illustrates how the research for development evaluation field is maturing through the experiences of a growing and diverse group of researchers and evaluators as they shift from using narrow accountability instruments to appreciating emergent causal pathways within research for development., (© The Author(s) 2023.)

While evaluation of research-to-policy projects is a fundamental aspect of measuring the impact of new knowledge, limited studies have examined evaluation methods in such projects, as well as how the evaluation can generate learning to facilitate the progress towards the Sustainable Development Goals (SDGs). This study conducted a systematic literature review and found that the most commonly used methods for SDG contribution evaluation were Analytical Hierarchy Process (40.4%), Fuzzy TOPSIS (13.2%) and ELECTRE and SPADE Methodology (3.5% each). Ranking analysis was undertaken to determine priorities among the six "Big Wins" as defined for the UKRI-GCRF Trade Hub Project, as a case, where the ranking was exercised by the project partners across the globe. Results revealed that "nature and social factors" was better considered in international trade agreements as the priority (36.4%) among others. Moreover, among the four "mechanisms" of the project, "knowledge, networks, and connectivity" was ranked as the top priority (56.9%), followed by "capacity building" (28.5%), "metrics, tools and models" (7.2%), and "improving the knowledge base" (4.6%). Mapping and evaluation revealed that the Big Wins of the Trade Hub contributed to ten out of the 17 SDGs. The most fulfilled goals were SDG 12 (Sustainable Consumption and Production), SDG 15 (Life on Land), and SDG 2 (Zero Hunger) in descending order. Furthermore, interaction analysis of the core SDGs revealed both synergy and tradeoff between different outputs. The research articles reviewed for this paper showed no gold standard framework for assessing international development projects against the SDGs. Further research should develop a tool to capture holistic and synergistic contributions of the target outcomes of projects to sustainable development., (© The Author(s) 2023.)

Background: Radioiodine therapy for Graves disease can be achieved with dosing based on estimated thyroid gland mass. Thyroid mass can be estimated using linear ultrasound measurements, and conversion factors for volume and density. The choice of conversion factors could impact estimated thyroid mass and thus administered radioiodine dose., Objective: The objective of this study was to define the relationship between thyroid mass estimated by ultrasound and measured thyroid mass following thyroidectomy., Materials and Methods: This was a retrospective, exempt study that included patients < 18 years of age with < 6 months between thyroid ultrasound and thyroidectomy January 2010-June 2020. Thyroid dimensions by ultrasound, thyroid mass at thyroidectomy and histopathological diagnosis were collected. Published conversion factors were used to estimate thyroid volume with conversion to mass using a density of 1.05 g/cm 3 . Pearson correlations and Bland-Altman difference analyses were used to define the relationship between estimated mass and specimen weight. Linear regression was used to calculate an optimal conversion factor for estimating thyroid mass., Results: We included 86 patients, 67 female (78%), with a mean age of 14.5 ± 3.15 years. Mass estimated using all tested conversion factors had similar strong, positive correlation with specimen weight (r = 0.95). The mean difference between thyroid mass estimated by ultrasound and measured mass ranged from - 0.34 g (conversion factor = 0.523) to 1.69 g (conversion factor = 0.554). The optimal simplified factor for estimation of thyroid mass for the study sample was 0.537., Conclusion: All published conversion factors for estimating thyroid mass based on linear ultrasound measurements produce good estimates of thyroid mass. Errors in estimated mass are less than 2 g on average., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Prevalence is reflective of disease incidence and survival, and defined as the number of patients living with active disease. In diseases such as diffuse large B-cell lymphoma (DLBCL) with treatments with curative potential, a proportion of patients are cured, leading to a need for accurate, contemporary estimates of DLBCL prevalence to gauge the impact of the rapidly emerging treatment landscape., Methods: Data from Surveillance, Epidemiology, and End Results (SEER) from 2000-2018 were utilized to develop an epidemiological model of incidence, survival, and cure, to estimate the current prevalent DLBCL population requiring active management in the United States (US). A variety of estimates were explored regarding cure rate and timing, based on a companion analysis of MarketScan data for treatment patterns and survival in incident DLBCL patients, and conditional survival analysis of SEER data., Results: Across scenarios, with estimated cure ranging from 52.8% and 68.9%, and timing of cure ranging from 1 and 20 years post diagnosis, the estimated prevalence ranged from 63,883 to 142,889. With an assumption of no cure, estimated prevalence was 179,475., Discussion: Prevalence estimates of DLBCL varied almost 3-fold, depending on specific cure adjustments made. Further understanding of DLBCL prevalence, for newly diagnosed and relapsed and/or refractory disease, is important to characterize the impact of emerging treatment options and related health care burden., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: 177 Lu-DOTATATE, a radionuclide therapy that binds somatostatin type-2A receptors (SST2A), has demonstrated efficacy in neuroendocrine tumors and evidence of central nervous system (CNS) penetration, supporting potential expansion within pediatric neuro-oncology. Understanding the prevalence of SST2A expression across pediatric CNS tumors is essential to identify patients who may benefit from somatostatin receptor-targeted therapy and to further elucidate the oncogenic role of SST2A., Methods: SST2A immunohistochemistry (IHC) was performed on tumor specimens and interpreted by an experienced pathologist (blinded), utilizing semi-quantitative scoring of membranous expression within viable tumor. Immunoreactive cell percentage was visually scored as 0 (none), 1 (<10%), 2 (10-50%), 3 (51-80%), or 4 (>80%). Staining intensity was scored as 0 (none), 1 (weak), 2 (moderate), or 3 (strong). Combined scores for each specimen were calculated by multiplying percent immunoreactivity and staining intensity values (Range: 0-12)., Results: A total of 120 tumor samples from 114 patients were analyzed. Significant differences in SST2A IHC scores were observed across histopathologic diagnoses, with consistently high scores in medulloblastoma (mean ± SD: 7.5 ± 3.6 [n=38]) and meningioma (5.7 ± 3.4 [n=15]), compared to minimal or absent expression in ATRT (0.3 ± 0.6 [n=3]), ETMR (1.0 ± 0 [n=3]), ependymoma (grades I-III; 0.2 ± 0.7 [n=27]), and high-grade glioma (grades III-IV; 0.4 ± 0.7 [n=23]). Pineoblastoma (3.8 ± 1.5 [n=4]) and other embryonal tumors (2.0 ± 4.0 [n=7]) exhibited intermediate, variable expression. Among medulloblastomas, SST2A IHC scores were higher in non-SHH (8.5 ± 3.1) than SHH (5.0 ± 3.3) molecular subgroups (p=0.033). In a subset of paired primary and recurrent specimens from four patients, SST2A IHC scores remained largely unchanged., Discussion: High membranous SST2A expression was demonstrated in medulloblastoma, meningioma, and some rarer embryonal tumors with potential diagnostic, biologic, and therapeutic implications. Somatostatin receptor-targeted therapy such as 177 Lu-DOTATATE deserves further investigation in these highly SST2A-expressing pediatric CNS tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lazow, Fuller, Trout, Stanek, Reuss, Turpin, Szabo and Salloum.)

Malignant peripheral nerve sheath tumor (MPNST), a highly aggressive Schwann cell (SC)-derived soft tissue sarcoma, arises from benign neurofibroma (NF); however, the identity, heterogeneity and origins of tumor populations remain elusive. Nestin + cells have been implicated as tumor stem cells in MPNST; unexpectedly, single-cell profiling of human NF and MPNST and their animal models reveal a broad range of nestin-expressing SC lineage cells and dynamic acquisition of discrete cancer states during malignant transformation. We uncover a nestin-negative mesenchymal neural crest-like subpopulation as a previously unknown malignant stem-like state common to murine and human MPNSTs, which correlates with clinical severity. Integrative multiomics profiling further identifies unique regulatory networks and druggable targets against the malignant subpopulations in MPNST. Targeting key epithelial-mesenchymal transition and stemness regulators including ZEB1 and ALDH1A1 impedes MPNST growth. Together, our studies reveal the underlying principles of tumor cell-state evolution and their regulatory circuitries during NF-to-MPNST transformation, highlighting a hitherto unrecognized mesenchymal stem-like subpopulation in MPNST disease progression.