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

Background and purpose: Most patients with isolated rapid eye movement sleep behaviour disorder (iRBD) progress to a parkinsonian alpha‐synucleinopathy. However, time to phenoconversion shows great variation. The aim of this study was to investigate whether cholinergic and dopaminergic dysfunction in iRBD patients was associated with impending phenoconversion. Methods: Twenty‐one polysomnography‐confirmed iRBD patients underwent baseline 11C‐donepezil and 6‐Fluoro‐(18F)‐l‐3,4‐dihydroxyphenylalanine (18F‐DOPA) positron emission tomography (PET). Potential phenoconversion was monitored for up to 8 years. PET images were analysed according to patients' diagnoses after 3 and 8 years using linear regression. Time‐to‐event analysis was made with Cox regression, dividing patients into low and high tracer uptake groups. Results: Follow‐up was accomplished in 17 patients. Eight patients progressed to either Parkinson's disease (n = 4) or dementia with Lewy bodies (n = 4), while nine remained non‐phenoconverters. Compared with non‐phenoconverters, 8‐year phenoconverters had lower mean 11C‐donepezil uptake in the parietal (p = 0.032) and frontal cortex (p = 0.042), whereas mean 11C‐donepezil uptake in 3‐year phenoconverters was lower in the parietal cortex (p = 0.005), frontal cortex (p = 0.025), thalamus (p = 0.043) and putamen (p = 0.049). Phenoconverters within 3 years and 8 years had lower 18F‐DOPA uptake in the putamen (p < 0.001). iRBD patients with low parietal 11C‐donepezil uptake had a 13.46 (95% confidence interval 1.42;127.21) times higher rate of phenoconversion compared with those with higher uptake (p = 0.023). iRBD patients with low 18F‐DOPA uptake in the most affected putamen were all phenoconverters with higher rate of phenoconversion (p = 0.0002). Conclusions: These findings suggest that cortical cholinergic dysfunction, particularly within the parietal cortex, could be a biomarker candidate for predicting short‐term phenoconversion in iRBD patients. This study aligns with previous reports suggesting dopaminergic dysfunction is associated with forthcoming phenoconversion. [ABSTRACT FROM AUTHOR]

The article focuses on the use of SGLT2 inhibitors in patients with HNF1A-MODY, a type of monogenic diabetes. Topics include the typical treatment regimen for HNF1A-MODY, the observed clinical outcomes from adding SGLT2 inhibitors to existing therapies, and the specific HNF1A genetic variants found in the study participants.

Purpose: Children with surgically corrected nonsyndromic craniosynostosis have been previously found to have neurocognitive and behavioral difficulties. Children with metopic synostosis have been described to have more difficulties than children with sagittal synostosis. This study aims to characterize the behavioral differences between children with metopic and sagittal synostosis. Methods: Children with metopic and sagittal synostosis were recruited at school age. Parents completed four separated behavioral assessments: Conners-3 (evaluation of ADHD), Social Responsiveness Scale-2 (SRS-2: evaluation of autism), Behavior Rating Inventory of Executive Function-2 (BRIEF-2: evaluation of executive function), and Child Behavior Checklist (CBCL: evaluation of overall behavioral problems). Children underwent intelligence quotient (IQ) testing using the Wechsler Abbreviated Scale of Intelligence (WASI-II). Results: There were 91 children (45 with metopic and 46 with sagittal synostosis). More children with metopic synostosis reported requiring supportive services (57.7% vs 34.7%, p = 0.02) and more reached or exceeded borderline clinical levels of two executive function subscales of the BRIEF-2 (emotion regulation index: 33.3% vs 17.4%, p = 0.05; global executive composite: 33.3% vs 17.4%, p = 0.05). Children with sagittal synostosis had higher scores on the rule-breaking and externalizing problem subscales of the CBCL. Increasing age at surgery was associated with worse executive function scores. Conclusions: A relationship between suture subtype and behavioral outcomes exists at school age. More children with metopic synostosis required social services indicating more overall difficulties. Children with metopic synostosis have more specific problems with executive function, while children with sagittal synostosis had more difficulties with externalizing behaviors. [ABSTRACT FROM AUTHOR]

Educational theology provides the basis for religious education by integrating religious values into the curriculum and teaching methods. Through the authors' literature research, it was determined that the biblical concept of Christian religious education for children has significant value. This discipline is steeped in Bible teachings and aims to cultivate a personal relationship with God, which ultimately glorifies His name. Those who are responsible for teaching in the field of Christian religious education play an important role. The Israel Shema, or Jewish Creed, found in Deuteronomy 6:4-5, serves as the basis for teaching God's teachings to children. The authors provide a qualitative analysis of the text and its contextual background, which is closely related to Israeli beliefs and their relationship to educational theology. Shema, as a declaration of faith for the nation of Israel, is a manifestation of personal commitment and determination to the one true God and is used in the practice of teaching faith education in both the family and church circles. [ABSTRACT FROM AUTHOR]

Greenlit in 1956, opened in 1961, Hotel Phoenicia in Beirut marked the arrival of the United States to the Lebanese hotel industry. Most telling, it was the first Middle East holding of the U.S-owned Intercontinental Hotel Corporation – a subsidiary of Pan American Airways – signaling growing U.S. capital interest, and influence, in Beirut and Lebanon. This article explores the history of Hotel Phoenicia through primary sources on its genesis, building, marketing, and sustaining. It argues that the hotel represented an American attempt at empire, through tourism, in the Middle East. This form of empire during the Cold War was distinct from earlier, European colonialism in its reliance on commercial airpower, corporate branding, and governmental investment in the absence of territorial annexation. Pan Am's global reach and vision for American influence, backed by the U.S. government, sought to make an American enclave and closed tourist loop, from U.S. marketing to U.S. air travel to U.S. hotel and pro-U.S. business practices in Beirut. Nonetheless, this process was contentious and multi-directional. Accordingly, the article emphasises how local businessmen, tourism promoters, and popular culture surrounding the hotel leveraged U.S. interest, setting the Phoenicia as an indigenous, modern hotel in an outward looking country. [ABSTRACT FROM AUTHOR]

Introduction: Ear molding is a safe, non-surgical approach to treat newborns with congenital ear anomalies. In this study, we aimed to investigate long-term aesthetic outcomes and caretaker satisfaction from ear molding therapy. Methods: A retrospective chart review from 2018 to 2020 was conducted for infants who underwent ear molding treatment at our institution. Patient demographics and treatment related variables were collected. Caretakers were surveyed regarding their experience, expectations, and aesthetic outcome at 1 year (short-term) and 3 years (long-term) from treatment. Independent physicians evaluated treatment efficacy. Responses were converted to a Likert scale (1–5), with 5 representing most desirable. Results: Overall, 38 of 42 patients participated in our long-term study (90%) for a total of 62 ears. Average follow-up was 3.31 ± 0.50 years after completion of treatment. Mean age at treatment was 23.2 ± 19.7 days with a mean treatment duration of 21.7 ± 7.7 days. Caretakers' satisfaction regarding auricular appearance remained high (short-term: 4.18 vs. long-term: 4.17, p = 0.54) and anticipated social distress decreased over time. Physician aesthetic evaluations were favorable between "somewhat effective" and "very effective" and remained consistent over time (short term: 3.46 vs. long-term: 3.31, p = 0.31). Furthermore, physician evaluations were higher for deformations than malformations (p = 0.04) and in children who began treatment by 30 days old (p = 0.04). Conclusion: Caretaker satisfaction from ear molding therapy remained high after long-term follow up, and social distress from the perception of their child's ears decreased with time. Physician aesthetic ratings confirmed efficacy, with better outcomes seen in deformations than in malformations. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Copyright of Informatik Spektrum is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Two different media platforms played a key role in keeping Tema Port in Ghana afloat during the period immediately leading up to and during the three-week COVID-19 pandemic-related lockdown in late March–April of 2020. The one media platform, Eye on Port, is a weekly broadcast television show by the port's authorities, which caters primarily to external commercial stakeholders of the port. The other platform is a closed WhatsApp forum used by stakeholders working at the operational level of the port. Both platforms served specific needs among their users, who had been restricted in their mobility but had to keep the port operational. Combining 'scalable sociality' with the concept of polymedia, we identify how the two media functioned to meet the different informational and conversational needs of their respective users. We argue that either medium alone could not fulfil the communicative needs necessary to keep the port operational during the early stage of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Heart failure due to myocardial infarction (MI) involves fibrosis driven by epicardium‐derived cells (EPDCs) and cardiac fibroblasts, but strategies to inhibit and provide cardio‐protection remains poor. The imprinted gene, non‐canonical NOTCH ligand 1 (Dlk1), has previously been shown to mediate fibrosis in the skin, lung and liver, but very little is known on its effect in the heart. Methods: Herein, human pericardial fluid/plasma and tissue biopsies were assessed for DLK1, whereas the spatiotemporal expression of Dlk1 was determined in mouse hearts. The Dlk1 heart phenotype in normal and MI hearts was assessed in transgenic mice either lacking or overexpressing Dlk1. Finally, in/ex vivo cell studies provided knowledge on the molecular mechanism. Results: Dlk1 was demonstrated in non‐myocytes of the developing human myocardium but exhibited a restricted pericardial expression in adulthood. Soluble DLK1 was twofold higher in pericardial fluid (median 45.7 [34.7 (IQR)) μg/L] from cardiovascular patients (n = 127) than in plasma (median 26.1 μg/L [11.1 (IQR)]. The spatial and temporal expression pattern of Dlk1 was recapitulated in mouse and rat hearts. Similar to humans lacking Dlk1, adult Dlk1−/− mice exhibited a relatively mild developmental, although consistent cardiac phenotype with some abnormalities in heart size, shape, thorax orientation and non‐myocyte number, but were functionally normal. However, after MI, scar size was substantially reduced in Dlk1−/− hearts as compared with Dlk1+/+ littermates. In line, high levels of Dlk1 in transgenic mice Dlk1fl/flxWT1GFPCre and Dlk1fl/flxαMHCCre/+Tam increased scar size following MI. Further mechanistic and cellular insight demonstrated that pericardial Dlk1 mediates cardiac fibrosis through epithelial to mesenchymal transition (EMT) of the EPDC lineage by maintaining Integrin β8 (Itgb8), a major activator of transforming growth factor β and EMT. Conclusions: Our results suggest that pericardial Dlk1 embraces a, so far, unnoticed role in the heart augmenting cardiac fibrosis through EMT. Monitoring DLK1 levels as well as targeting pericardial DLK1 may thus offer new venues for cardio‐protection. [ABSTRACT FROM AUTHOR]

Real-time monitoring of output electrical parameters of the transmitted signals in a capacitive resistivity underground imaging system is necessary because these are significant in the calculation of underground resistivity, however, machine learning has not yet been applied in this application to improve the accuracy of measurement. This study aims to develop and select the best prediction models that can be implemented for a digital measuring unit suitable for capacitive resistivity underground imaging. Three deep neural network models namely Elman recurrent neural network (ERNN), long short-term memory (LSTM), and gated recurrent unit (GRU) were explored to build prediction models for the current and voltage of the transmitter circuit. The prediction models' performance was assessed using mean squared error (MSE), which is reduced to its absolute lowest value. The result shows that the best-trained models for current and voltage prediction are the ERNN models with configurations of 900-600-500 hidden neurons network with training MSE of 9.82 X 10-9 and the configured 1300-1000-900 hidden neurons with training MSE of 0.465, respectively. With the help of the prediction models, it would be possible to measure current and voltage output accurately, allowing simultaneous data acquisition while avoiding the need for a separate measuring device. [ABSTRACT FROM AUTHOR]

Abrasion of tire tread, caused by friction between vehicle tires and road surfaces, causes release of tire wear particles (TWPs) into various environmental compartments. These TWPs contribute to chemical, microplastic, and particulate matter pollution. Their fate remains largely unknown, especially regarding the extent and form in which they persist in the environment. The present study investigated (1) the biodegradability of tread particles (TPs) in the form of ground tire tread, (2) how accelerated ultraviolet (UV) weathering affects their biodegradability, and (3) which TP constituents are likely contributors to TP biodegradability based on their individual biodegradability. A series of closed‐bottle tests, with aerobic aqueous medium inoculated with activated sludge, were carried out for pristine TPs, UV‐weathered TPs, and selected TP constituents; natural rubber (NR), isoprene rubber (IR), butadiene rubber (BR), and treated distillate aromatic extracts (TDAE). Biodegradation was monitored by manometric respirometry, quantifying biological oxygen consumption over 28 days. Pristine TP biodegradability was found to be 4.5%; UV‐weathered TPs showed higher biodegradability of 6.7% and 8.0% with similar and increased inoculum concentrations, respectively. The observed TP biodegradation was mainly attributed to biodegradation of NR and TDAE, with individual biodegradability of 35.4% and 8.0%, respectively; IR and BR showed negligible biodegradability. These findings indicate that biodegradability of individual constituents is decreased by a factor of 2 to 5 when compounded into TPs. Through scanning electron microscopy analysis, biodegradation was found to cause surface erosion. Processes of TP biodegradation are expected to change throughout their lifetime as new constituents are incorporated from the road and others degrade and/or leach out. Tire emissions likely persist as particles with an increased fraction of synthetic rubbers and carbon black. Environ Toxicol Chem 2024;43:31–41. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA), highly expressed in prostate cancer, is a promising target for radionuclide therapy. Auger electron-emitting radionuclides are well suited for targeted radionuclide therapy if they can be delivered close to the DNA of the targeted cells. This preclinical study evaluated the theranostic pair [55/58mCo]Co-DOTA-PSMA-617 for PET imaging and Auger electron therapy of prostate cancer. [58mCo]Co-DOTA-PSMA-617 was successfully prepared with > 99% radiochemical yield and purity. In vitro, uptake and subcellular distribution assays in PSMA-positive prostate cancer cells showed PSMA-specific uptake with high cell-associated activity in the nucleus. Incubation with [58mCo]Co-DOTA-PSMA-617 reduced cell viability and clonogenic survival in a significant dose-dependent manner (p < 0.05). Biodistribution of xenografted mice showed high specific tumor uptake of the cobalt-labeled PSMA ligand for all time points with rapid clearance from normal tissues, which PET imaging confirmed. In vivo, therapy with [58mCo]Co-DOTA-PSMA-617 in tumor-bearing mice demonstrated significantly increased median survival for treated mice compared to control animals (p = 0.0014). In conclusion, [55/58mCo]Co-DOTA-PSMA-617 displayed excellent in vitro and in vivo properties, offering significant survival benefits in mice with no observed toxicities. [ABSTRACT FROM AUTHOR]

Rationale: The psychedelic effects of the traditional Amazonian botanical decoction known as ayahuasca are often attributed to agonism at brain serotonin 5-HT2A receptors by N,N-dimethyltryptamine (DMT). To reduce first pass metabolism of oral DMT, ayahuasca preparations additionally contain reversible monoamine oxidase A (MAO-A) inhibitors, namely β-carboline alkaloids such as harmine. However, there is lacking biochemical evidence to substantiate this pharmacokinetic potentiation of DMT in brain via systemic MAOA inhibition. Objectives: We measured the pharmacokinetic profile of harmine and/or DMT in rat brain, and tested for pharmacodynamic effects on brain glucose metabolism and DMT occupancy at brain serotonin 5-HT2A receptors. Methods: We first measured brain concentrations of harmine and DMT after treatment with harmine and/or DMT at low sub-cutaneous doses (1 mg/kg each) or harmine plus DMT at moderate doses (3 mg/kg each). In the same groups of rats, we also measured ex vivo the effects of these treatments on the availability of serotonin 5-HT2A receptors in frontal cortex. Finally, we explored effects of DMT and/or harmine (1 mg/kg each) on brain glucose metabolism with [18F]FDG-PET. Results: Results confirmed that co-administration of harmine inhibited the formation of the DMT metabolite indole-3-acetic acid (3-IAA) in brain, while correspondingly increasing the cerebral availability of DMT. However, we were unable to detect any significant occupancy by DMT at 5-HT2A receptors measured ex vivo, despite brain DMT concentrations as high as 11.3 μM. We did not observe significant effects of low dose DMT and/or harmine on cerebral [18F]FDG-PET uptake. Conclusion: These preliminary results call for further experiments to establish the dose-dependent effects of harmine/DMT on serotonin receptor occupancy and cerebral metabolism. [ABSTRACT FROM AUTHOR]

Potential evapotranspiration (PET) indicates if a cultivation area is suitable for planting. Currently, site-specific PET models that are based on large geographic regions are vulnerable to inaccurate predictions as a result of climate change and sudden changes in the environmental abiotic stressors that affect plant growth. For the aim of promoting the papaya Sinta F1 cultivar, the study optimized the standard Thornthwaite PET model by integrating three advanced physics-based metaheuristics and evolutionary computing, namely atom search (ASO), differential evolution (DE), and multiverse (MVO) optimizers. The PET value was optimized through minimization as a function of air temperature, light intensity, heat index, and extended heat index. As the PET value approaches 0, it indicates that there is more soil-water content that can be absorbed by plants. Based on the four cultivation treatments (uncontrolled, ASO, DE, and MVO) exposed in three replicates within 90 days, the ASO-optimized Thornthwaite PET-treated (ASOTh) papaya plants resulted in the highest chlorophyll a and b concentrations, densest stomatal density, concentrated root and stem xylem and phloem vessels, considerable root and stem length, most formed leaf count, and strongest action potentials coming from stem membrane for both light and dark periods. This proves the applicability of the intelligent process in modifying the Thornthwaite model for plant growth promotion. Also, through the developed ASOTh, the stem length and thickness ratio was improved for mechanical stability to facilitate more branching leaves and potential fruits during the fruiting stage, and the chlorophyll a and b ratio was enhanced, which naturally extended the light energy band for photosynthesis. Overall, the newly developed ASOTh model may be used to grow papaya seedlings year-round anywhere on Earth if there is a control system to regulate the environmental setting inside the growth chamber. [ABSTRACT FROM AUTHOR]

The management of produced water (PW) discharges from offshore oil and gas installations in the North Atlantic is under the auspices of OSPAR (Oslo/Paris convention for Protection of the Marine Environment of the North‐East Atlantic). In 2010, OSPAR introduced the risk‐based approach (RBA) for PW management. The RBA includes a hazard assessment estimating PW ecotoxicity using two approaches: whole‐effluent toxicity (WET) and substance‐based (SB). Set against the framework of the WET and SB approach, we conducted a literature review on the magnitude and cause of PW ecotoxicity, respectively, and on the challenges of estimating these. A large variability in the reported magnitude of PW WET was found, with EC50 or LC50 values ranging from <1% to >100%, and a median of 11% (n = 301). Across the literature, metals, hydrocarbons, and production chemicals were identified as causing ecotoxicity. However, this review reveals how knowledge gaps on PW composition and high sample and species dependency of PW ecotoxicity make clear identification and generalization difficult. It also highlights how limitations regarding the availability and reliability of ecotoxicity data result in large uncertainties in the subsequent risk estimates, which is not adequately reflected in the RBA output (e.g., environmental impact factors). Thus, it is recommended to increase the focus on improving ecotoxicity data quality before further use in the RBA, and that WET should play a more pronounced role in the testing strategy. To increase the reliability of the SB approach, more attention should be paid to the actual composition of PW. Bioassay‐directed chemical analysis, combining outcomes of WET and SB in toxicity identification evaluations, may hold the key to identifying drivers of ecotoxicity in PW. Finally, an uncertainty appraisal must be an integrated part of all reporting of risk estimates in the RBA, to avoid mitigation actions based on uncertainties rather than reliable ecotoxicity estimations. Integr Environ Assess Manag 2023;19:1172–1187. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Key Points: The whole‐effluent toxicity and substance‐based approaches to toxicity estimation provide complementary information, with the former assessing if the sample is toxic and the latter identifying drivers of toxicity as targets for treatment or chemical substitution.The experimental protocols of whole‐effluent toxicity testing should be optimized for handling the complex physicochemical characteristics of produced water.The chemical analysis of produced water composition should be improved, targeting the unresolved complex mixture, and the array of compounds included in the substance‐based approach should be expanded accordingly.The quality and quantity of ecotoxicity data underlying predicted no‐effect concentration and species sensitivity distribution calculations should be increased, focusing on chemicals with high assessment factors. [ABSTRACT FROM AUTHOR]

The increasing release of engineered nanoparticles (NPs) into aquatic ecosystems makes it crucial to understand the interactions of NPs with aquatic organisms, such as algae. In this study, the association of CeO2 NPs with unicellular algae (Raphidocelis subcapitata) and changes to the cellular elemental profile were investigated using three exposure concentrations (1, 50, and 1000 µg CeO2/L) at two different algal growth conditions—exponential and inhibited growth (1% glutaraldehyde). After a 24 h-exposure, algal suspensions were settled by gravity and CeO2-NP/algae association was analyzed by single-cell inductively coupled plasma quadrupole mass spectrometry (sc-ICP-QMS) and ICP time-of-flight MS (sc-ICP-TOFMS). Concurrent detection of the cellular fingerprint with cerium indicated NP association with algae (adsorption/uptake) and changes in the cellular elemental profiles. Less than 5% of cells were associated with NPs when exposed to 1 µg/L. For 50 µg/L exposures in growing and inhibited cell treatments, 4% and 16% of cells were associated with CeO2 NPs, respectively. ICP-TOFMS analysis made it possible to exclude cellular exudates associated with CeO2 NPs due to the cellular fingerprint. Growing and inhibited cells had different elemental profile changes following exposure to CeO2 NPs—e.g., growing cells had higher Mg and lower P contents independent of CeO2 concentration compared to inhibited cells. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is associated with a poor prognosis, which calls for earlier diagnosis. This study aimed to analyse the health care use in primary care and at hospitals among women with OC compared to non-cancerous women to identify a window of opportunity for earlier diagnosis. Methods: This nationwide register-based observational cohort study included all Danish women aged ≥ 40 years who were diagnosed with a first-time OC or borderline ovarian tumour in 2012–2018 and with no previous cancer diagnosis (n = 4,255). For each case, ten non-cancerous women were identified (n = 42,550). We estimated monthly incidence rate ratios using a negative binomial regression model to assess the use of health care services. We calculated risk ratios of having multiple contacts to general practice before a diagnosis using a binary regression model. Results: Cases had statistically significantly higher contact rates to general practice from five months prior to the diagnosis compared to references. From six to eight months prior to diagnosis, an increased use of transvaginal ultrasound and gynaecologist was seen for cases compared to references. Conclusions: Increased healthcare use was seen relatively closely to the time of diagnosis for women with OC. This indicates a narrow window of opportunity for a timelier diagnosis. Still, the use of specialised assessment increased at six to eight months before the diagnosis. When women present unspecific symptoms, awareness of potential ovarian malignancies and safety-netting by the general practitioner may be pivotal. Trial registration: Not relevant. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is associated with a poor prognosis, which calls for earlier diagnosis. This study aimed to analyse the health care use in primary care and at hospitals among women with OC compared to non-cancerous women to identify a window of opportunity for earlier diagnosis. Methods: This nationwide register-based observational cohort study included all Danish women aged ≥ 40 years who were diagnosed with a first-time OC or borderline ovarian tumour in 2012–2018 and with no previous cancer diagnosis (n = 4,255). For each case, ten non-cancerous women were identified (n = 42,550). We estimated monthly incidence rate ratios using a negative binomial regression model to assess the use of health care services. We calculated risk ratios of having multiple contacts to general practice before a diagnosis using a binary regression model. Results: Cases had statistically significantly higher contact rates to general practice from five months prior to the diagnosis compared to references. From six to eight months prior to diagnosis, an increased use of transvaginal ultrasound and gynaecologist was seen for cases compared to references. Conclusions: Increased healthcare use was seen relatively closely to the time of diagnosis for women with OC. This indicates a narrow window of opportunity for a timelier diagnosis. Still, the use of specialised assessment increased at six to eight months before the diagnosis. When women present unspecific symptoms, awareness of potential ovarian malignancies and safety-netting by the general practitioner may be pivotal. Trial registration: Not relevant. [ABSTRACT FROM AUTHOR]

Lymphedema is a common complication following breast cancer treatment with axillary lymphadenectomy and radiotherapy. Currently, there is no curative treatment for this disease, hence there is a need for new therapeutic suggestions. The aim of this study was to investigate the effect of hyaluronidase (HYAL) injections after inducing hindlimb lymphedema in 36 female C57BL/6 mice. HYAL injections were administered every second day for 14 days in three groups: (1) HYAL for 1 week followed by saline for 1 week, (2) HYAL for 2 weeks, and (3) saline injections for 2 weeks. Volume of the lymphedema limb was weekly assessed with micro-computed tomography (µ-CT) scans for a total course of 6 weeks. Lymph vessel morphometry was assessed in the end of the study after staining cross-sections of the hindlimb for anti-LYVE-1 blindly. Lymphatic function was assessed by lymphoscintigraphy to assess lymphatic clearance. There was a significant reduction of the volume of lymphedema in mice treated with HYAL-7 compared with mice treated with HYAL-14 (p < 0.05) and saline (p < 0.05). No differences were detected in lymph vessel morphometry and the lymphoscintigraphy between groups. Short-term treatment with HYAL-7 might be a potential therapeutic suggestion for secondary lymphedema induced in mouse hindlimbs. In the future, clinical studies are needed to investigate the potential of HYAL treatment in human beings. [ABSTRACT FROM AUTHOR]

This study serves to provide evidence on how the increase in people working from home due to government induced social distancing measures is contributing to the frequency of individuals suffering from depression or anxiety. Using a compilation of datasets from the NHIS, Household Pulse Survey, and the Oxford Covid-19 Response Tracker, we find a general trend of increased rates of depression and anxiety in those who moved to a remote working format. However, while all regions have an increased frequency in anxiety for those who switched to telework, those in the Northeast and West (that also have implemented strict lockdown measures related to social distancing) have slightly higher rates of anxiety compared to those in the South and Midwest. [ABSTRACT FROM AUTHOR]

Land surveying has been one of the core operations in performing underground imaging. It is known that dynamic and continuous resistivity readings were employed through this technique using the array of capacitive electrodes being towed with a light vehicle. However, the main challenge in doing subsurface surveying is the change in speed of the system when there are inevitable obstacles and sloping road surfaces. To address it, this study will develop prediction models using different computational intelligence such as multigene symbolic regression genetic programming (MSRGP), regression-based decision tree (RTree), and feed forward neural network (FFNN) that will result in a smart speed controller system that can maintain the constant speed of the towed subterranean system. The best performing prediction model will be considered as the SpeedX. The expected output is a correction factor that will signal the speed controller in slow down or inclined plane road environment to maintain a constant speed of 1.6667 m/s for avoidance of data distortion on land surveying. Thus, the MSEs for MSRGP, FFNN, and RTree are 0.00163, 0.00178, and 0.00240, respectively. This results in MSRGP as the best performing model and was considered as the SpeedX model. Other evaluation metrics were employed such as the MAE and R2 which signify the advantage of SpeedX. Furthermore, the comparison between the CI-controlled and uncontrolled towed subterranean imaging trailer system, as well as its advantages clearly highlight the advantage of embedded SpeedX in the system. [ABSTRACT FROM AUTHOR]

In performing underground imaging surveying, applying a coating in the antenna dipole plates with robust and durable material to stay protected against rough road features is vital to consider. By doing this, the mechanical properties of the metallic antenna dipole can be improved and be shielded from deterioration. With that, this study has developed an indentation-flexure algorithm optimized using a hybrid Lichtenberg algorithm (LA) and artificial neural network (ANN) that can predict the indentation-flexure as a function of the coating material's elastic modulus, Poisson ratio, and thickness as well as the load antenna weight. Acrylic, epoxy, nylon 101, high-density polyethylene, and polyvinyl chloride were chosen as the top five most popular coating materials. A 120° titanium cone indenter with a 0.5-inch-diameter, slightly rounded point, and a constant compressive force of 200 N in the center was employed to plot and use a nonlinear mechanical finite element analysis on an antenna dipole plate using SolidWorks. Nature-inspired and evolutionary metaheuristics such as African vultures, Lichtenberg, and gorilla troop optimization algorithm including genetic algorithm (GA) were employed as optimized models for the hardness indentation for capacitively coupled antenna dipoles. Based on the results, the hybrid LA-ANN solution with a hidden neurons of 3000 and a sigmoid activation function is the best performing model as it acquired a MSE score of 0.0061 in validation and 0.1478 in testing compare to the other model with 0.1610 for GA with 100 hidden neurons with sigmoid activation function. Thus, LA-ANN model is considered as the optIFnet as it exhibited the best prediction performance and fastest convergence among all optimizers used. [ABSTRACT FROM AUTHOR]

Genetic programming (GP) is an evolutionary algorithm used to produce high-quality solutions to various problems. It has seen few claims in circuitry and the development of antenna designs. The application of GP in the model of embedded digital systems on multi-channel antenna arrays of subsurface imaging equipment has not yet been investigated. This study focuses on designing and developing a digital multimeter embedded with a multigene genetic programming (MGGP) model for multi-array transmitter antenna used for subsurface imaging operating at a low frequency of 3.5 kHz to 18.5 kHz using Arduino microcontroller for prototyping. The electrical outputs of a transmitter antenna system employed in a subsurface imaging device require live measurement and monitoring during operation for data logging purposes. The amount of transmitted voltage, produced current, and operating frequency are significant parameters for mapping the underground resistivity, thus the produced GP models are functions of the three parameters. GP fitness function was determined through MATLAB software. The output current signal from the transmitter were imitated in Proteus simulation software using a current source in the designed current measuring circuit. This produced linear and nonlinear relationships of the electrical outputs where GP modeling was beneficially applied. The application of GP in with the microcontroller provided an accurate reading of frequency, current and voltage produced by the multi-array transmitter antenna. These measurements were displayed using LM016L LCD display. Moreover, this embedded digital multimeter on transmitter antenna avoids utilizing costly high voltage measuring devices. [ABSTRACT FROM AUTHOR]

Electrical resistivity tomography (ERT) has been seen as an appropriate instrument in several works to monitor and aid in the control of seawater intrusion (SWI) in coastal groundwater systems. This study seeks to discuss the synthesis of a digital twin that couples information between the physical space through ERT as a monitoring sensor and the digital space using SWI simulations to accurately model the behavior of SWI in the present and future settings. To showcase the concept, a Python-based simulation was presented that shows (a) the joint forward modeling-simulation scheme for calculating expected ERT apparent resistivity values from simulated SWI and (b) the calibration of the digital coastal aquifer system through genetic algorithm to accurately match the outputs of the SWI simulations with the ERT measurements. [ABSTRACT FROM AUTHOR]

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Introduction: A severe side effect of cancer chemotherapy is the development of gastrointestinal mucositis, characterised by mucosal inflammation. We investigated if 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography combined with computed tomography (2-[18F]FDG-PET/CT) could visualise gastrointestinal mucositis in mice treated with the chemotherapeutic agent doxorubicin. Methods: In this study, gastrointestinal inflammation was longitudinally evaluated by 2-[18F]FDG-PET/CT scans before and 1, 3, 6, and 10 days after treatment with doxorubicin. Doxorubicin-treated mice were compared to saline-treated littermates using the abdominal standard uptake value of 2- [ 18F]FDG corrected for body weight (SUVBW). Results: Abdominal SUVBW was significantly increased on day 1 (p < 0.0001), day 3 (p < 0.0001), and day 6 (p < 0.05) in the doxorubicin-treated group compared to controls. Abdominal SUVBW returned to baseline levels on day 10. In the doxorubicin group, the largest weight loss was observed on day 3 (control vs doxorubicin, mean percent of baseline weight: (98.5 ± 3.2% vs 87.9 ± 4.6%, p < 0.0001). Moreover, in the doxorubicin-treated group, villus lengths were decreased by 23-28% on days 1 and 3 in the small intestine (p < 0.05), and jejunal levels of tumour necrosis factor and interleukin-1b were significantly increased on day 3 (p < 0.05). Discussion: Together, these findings indicate that sequential 2-[18F]FDG-PET/CT scans can objectively quantify and evaluate the development and resolution of intestinal inflammation over time in a mouse model of doxorubicin-induced mucositis. [ABSTRACT FROM AUTHOR]

In early 2021, the new definition of the term "nanomaterial" proposed by the European Commission (EC) was subject to a stakeholder consultation and in June 2022, the EC published its updated definition. Based on an independent analysis of the different versions of the definition and the results of the stakeholder consultation, the aim of this paper is to identify key aspects to be considered when deciding whether a material should be regarded as a nanomaterial. More than 130 comments submitted during the stakeholder consultation by various organizations, companies, citizens, and authorities were analyzed. We find that the introduction of new terms such as "solid particles" has added clarity to terms used in the former definition. Our analysis shows that stakeholders seemed inclined to maintain the default number-based 50% threshold value, but were opposed to (1) the possible flexibility of varying the threshold in specific sectorial legislation, (2) the default inclusion of carbonaceous materials < 1 nm, and (3) the use of volume specific surface area (VSSA) other than for excluding materials from being defined as nanomaterials. Overall, we find that the updated definition addresses many of the limitations of the former definition. However, the updated definition also creates new challenges that will have to be addressed via development of new regulatory guidance. Apart from the relatively minor change of the VSSA threshold from 5 to 6 m2/cm3, it generally seems that no arguments from the stakeholder consultation made the EC reconsider its position. [ABSTRACT FROM AUTHOR]

Background: A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence of diverse obligate or facultative anaerobic bacteria and a paucity in Lactobacillus species, similar to communities found in bacterial vaginosis (BV), is considered non-optimal and associated with adverse health outcomes. Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human model that faithfully reproduces the vaginal epithelial microenvironment for preclinical validation of potential therapeutics or testing hypotheses about vaginal epithelium-microbiome interactions. Results: Here, we describe an organ-on-a-chip (organ chip) microfluidic culture model of the human vaginal mucosa (vagina chip) that is lined by hormone-sensitive, primary vaginal epithelium interfaced with underlying stromal fibroblasts, which sustains a low physiological oxygen concentration in the epithelial lumen. We show that the Vagina Chip can be used to assess colonization by optimal L. crispatus consortia as well as non-optimal Gardnerella vaginalis-containing consortia, and to measure associated host innate immune responses. Co-culture and growth of the L. crispatus consortia on-chip was accompanied by maintenance of epithelial cell viability, accumulation of D- and L-lactic acid, maintenance of a physiologically relevant low pH, and down regulation of proinflammatory cytokines. In contrast, co-culture of G. vaginalis-containing consortia in the vagina chip resulted in epithelial cell injury, a rise in pH, and upregulation of proinflammatory cytokines. Conclusion: This study demonstrates the potential of applying human organ chip technology to create a preclinical model of the human vaginal mucosa that can be used to better understand interactions between the vaginal microbiome and host tissues, as well as to evaluate the safety and efficacy of live biotherapeutics products. AsSRkJhp7GmswS9e3XcXgr Video Abstract [ABSTRACT FROM AUTHOR]

Background: The somatostatin receptors 1–5 are overexpressed on neuroendocrine neoplasms and, as such, represent a favorable target for molecular imaging. This study investigates the potential of [18F]AlF-NOTA-[1-Nal3]-Octreotide and compares it in vivo to DOTA- and NOTA-[1-Nal3]-Octreotide radiolabeled with gallium-68. Methods: DOTA- and NOTA-NOC were radiolabeled with gallium-68 and NOTA-NOC with [18F]AlF. Biodistributions of the three radioligands were evaluated in AR42J xenografted mice at 1 h p.i and for [18F]AlF at 3 h p.i. Preclinical PET/CT was applied to confirm the general uptake pattern. Results: Gallium-68 was incorporated into DOTA- and NOTA-NOC in yields and radiochemical purities greater than 96.5%. NOTA-NOC was radiolabeled with [18F]AlF in yields of 38 ± 8% and radiochemical purity above 99% after purification. The biodistribution in tumor-bearing mice showed a high uptake in tumors of 26.4 ± 10.8 %ID/g for [68Ga]Ga-DOTA-NOC and 25.7 ± 5.8 %ID/g for [68Ga]Ga-NOTA-NOC. Additionally, [18F]AlF-NOTA-NOC exhibited a tumor uptake of 37.3 ± 10.5 %ID/g for [18F]AlF-NOTA-NOC, which further increased to 42.1 ± 5.3 %ID/g at 3 h p.i. Conclusions: The high tumor uptake of all radioligands was observed. However, [18F]AlF-NOTA-NOC surpassed the other clinically well-established radiotracers in vivo, especially at 3 h p.i. The tumor-to-blood and -liver ratios increased significantly over three hours for [18F]AlF-NOTA-NOC, making it possible to detect liver metastases. Therefore, [18F]AlF demonstrates promise as a surrogate pseudo-radiometal to gallium-68. [ABSTRACT FROM AUTHOR]

Drug-induced cytopenias are a prevalent and significant issue that worsens clinical outcomes and hinders the effective treatment of cancer. While reductions in blood cell numbers are classically associated with traditional cytotoxic chemotherapies, they also occur with newer targeted small molecules and the factors that determine the hematotoxicity profiles of oncologic drugs are not fully understood. Here, we explore why some Aurora kinase inhibitors cause preferential neutropenia. By studying drug responses of healthy human hematopoietic cells in vitro and analyzing existing gene expression datasets, we provide evidence that the enhanced vulnerability of neutrophil-lineage cells to Aurora kinase inhibition is caused by early developmental changes in ATP-binding cassette (ABC) transporter expression. These data show that hematopoietic cell-intrinsic expression of ABC transporters may be an important factor that determines how some Aurora kinase inhibitors affect the bone marrow. Patients treated with Aurora kinase inhibitors experience dose-limiting neutropenia while other cytopenias are rare. Here, Chou et al. show that this cell-type specific side effect is partly explained by loss of drug efflux pump expression during neutrophil differentiation. [ABSTRACT FROM AUTHOR]

This article investigates far-right conceptions of history and memory through the case of Christchurch shooter. Scholarly work on far-right memory practices is still in its infancy, and research into the Christchurch shooter in particular has underplayed this crucial aspect of his ideological drive for violence. By investigating the narrative elements of his historiography, the article argues that far-right extremism taps into a range of historical templates to structure a trajectory of time and historical development that seeks to legitimize present violence in relation to the legacies and exemplary instances of the past as well as historically contingent aspirations for the future. The danger of this memory working is its utility—through the channels of digital culture and communication—in promising to canonize the terrorist as a historicized object in a chronicle of ancient struggle, providing temporalized purpose to his violence in both a retrospective and prospective manner. [ABSTRACT FROM AUTHOR]

Lymphoid follicles (LFs) are responsible for generation of adaptive immune responses in secondary lymphoid organs and form ectopically during chronic inflammation. A human model of ectopic LF formation will provide a tool to understand LF development and an alternative to non-human primates for preclinical evaluation of vaccines. Here, it is shown that primary human blood B- and T-lymphocytes autonomously assemble into ectopic LFs when cultured in a 3D extracellular matrix gel within one channel of a two-channel organ-on-a-chip microfluidic device. Superfusion via a parallel channel separated by a microporous membrane is required for LF formation and prevents lymphocyte autoactivation. These germinal center-like LFs contain B cells expressing Activation-Induced Cytidine Deaminase and exhibit plasma cell differentiation upon activation. To explore their utility for seasonal vaccine testing, autologous monocyte-derived dendritic cells are integrated into LF Chips. The human LF chips demonstrate improved antibody responses to split virion influenza vaccination compared to 2D cultures, which are enhanced by a squalene-in-water emulsion adjuvant, and this is accompanied by increases in LF size and number. When inoculated with commercial influenza vaccine, plasma cell formation and production of anti-hemagglutinin IgG are observed, as well as secretion of cytokines similar to vaccinated humans over clinically relevant timescales. [ABSTRACT FROM AUTHOR]

Objective: To assess the feasibility and reliability of incorporating quantitative shear wave elastography (SWE) data as an additional means of characterizing focal atheromata during routine carotid sonographic examinations when compared with conventional gray-scale Gray-Weale (GW) methods. Methods: Inpatients and outpatients undergoing routine carotid examinations at a medical center were included in the pilot study. Patients with prior history of endarterectomy, interventional therapeutic procedures, or absence of plaque formation were excluded. All examinations were performed by registered vascular technologist using a Mindray Resona 7 ultrasound equipment system with an L9-3U transducer in a carotid examination mode. The images were later reviewed by two independent, blinded observers and correlated to GW characterization. Results: There were 41 atheromatous lesions evaluated during the pilot study. The range of absolute (low to high) average and median Young's modulus (YM) kPa values vary widely across each plaque type; they nonetheless still exhibit evidence of increasing stiffness as the gray-scale sonographic appearance becomes denser. The same observation is true of the average kPa and median kPa values as increasing YM values indicate increasing stiffness of interrogated tissues. Conclusion: This pilot study affirms the feasibility and reliability of incorporating quantitative SWE data as an additional means of characterizing focal atheromata during routine carotid sonographic examinations; further large-scale studies are needed to determine the sensitivity and specificity of individual kPa values associated with specific plaque types. [ABSTRACT FROM AUTHOR]