Neural correlates of decisions under risk and under ambiguity have been examined for several decades. In the current study, we focus on a neglected aspect that is a potential confounding of the average risk of alternatives in a trial, the average magnitude of the outcomes, and the difference in risk between the two alternatives. We present an experimental approach to solve this problem here and explicitly separate risk and ambiguity. In the present fMRI-study with 20 participants, we created different levels of risk and ambiguity to investigate their effects on behavior and brain activation. In a first experimental block, decisions with mixed-risk options (one high-risk option paired with one low-risk option) were compared to decisions with two high-risk or two low-risk options in terms of the effects on decision-making and neural activity. The second block consisted of the same risk levels crossed with high and low ambiguity by withholding information about the probabilities of the outcomes. During mixed-risk trials participants made cautious decision significantly more often. This effect was strongest during mixed trials with high ambiguity in the second block. In addition, risk behavior of subjects was correlated with the subjective importance of the amount of potential monetary losses or wins and the related probabilities. The fMRI results revealed activation of the dorsal anterior cingulate cortex (dACC), the insula, and the orbitofrontal cortex (OFC) during mixed risk trials without ambiguity. In contrast, activation of the amygdala was specifically present during mixed-risk trials with high ambiguity.

In this article, we attempt to provide a more general method based on Petryshyn’s fixed-point theorem to ensure the existence of solutions to implicit functional equations. These implicit functional equations include fractional, non-fractional, (fractional) stochastic integral equations, etc., and any combination of them in C( I). Some results regarding the existence of fixed points in implicit functional integral equations will be reviewed in the literature. We show that this general result unifies and improves many of the main results in the literature. To illustrate that our approach is more general than other methods, we present some concrete examples. Also, we apply our method to create new functional equations in practice and check the existence of solutions.

UMA FESTA CARNAVALESCA DE SABERES: ATRAVESSANDO FRONTEIRAS CULTURAIS POR MEIO DO LETRAMENTO EM PROGRAMAÇÃO

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. The prevalence of AF is known to be constantly rising due to an overall increased ageing population with multiple co-morbidities in the Western world, predisposing to debilitating complications such as stroke and coronary artery disease (CAD). Therefore, there has been a great interest in improving clinical outcomes for these patients. Hence, various screening strategies have come into guidelines in order to identify individuals at an increased risk of AF and its complications. It is speculated that assessment of risk factors using various screening tools will aid in improving outcomes and reducing AF-related complications. Thereby, there has been a recognised need for investigating the diagnostic accuracy of key index tests in the diagnosis and management of AF.

An 80-year-old man had a secondary prevention defibrillator in place for treatment of sustained ventricular tachycardia. After a generator replacement several years later, he developed a series of apparent pulse generator infections requiring extraction. Each purulent appearing pocket eruption was culture negative. Eventually, he was diagnosed with a delayed hypersensitivity reaction to triclosan, an antibacterial that is commonly impregnated in surgical sutures. The evaluation for this is difficult and can be misleading. This entity should be considered in the differential diagnosis of patients with culture negative CIED infections.

Objective：Cholinesterase inhibitor (ChEIs) is the first-line drug for Alzheimer’s disease (AD). Understanding torsade de pointes (TdP)/QT prolongation with different ChEIs is essential for its safe and rational administration. This study aimed to evaluate the correlation between different ChEIs and TdP/QT prolongation. Methods：All ChEIs related TdP/QT prolongation cases were retrieved from the FAERS database using standard MedDRA query (SMQ) from the first quarter of 2004 to the third quarter of 2022. Disproportionality and sensitivity analysis were used to determine the signal of TdP/QT prolongation related to ChEIs. Results：557 cases of TdP/QT prolongation related to 3 ChEIs were searched by SMQ. The patients were mostly elderly people, with markedly more female than male. The signals of TdP/QT prolongation for ChEIs were detected by disproportionality analysis, and the signal of Donepezil was the strongest. The sensitivity analysis results indicate a robust and stable correlation between these signals with ChEIs. TdP/QT prolongation usually occurs within one month after taking ChEIs. Conclusion：The signals of TdP/QT prolongation related to ChEIs were strong and stable. It is necessary to be vigilant about the TdP/QT prolongation of various ChEIs, especially in the initial stage after taking ChEIs.

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the emerging role of psychedelics in the management of chronic pain and opioid use disorder (OUD), two critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy (LTOT) who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and opioid use disorder, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective, and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.

The progression of tumors is heavily influenced by mechanical properties of their microenvironment. In this work, we designed micropatterned models with varying distances and shapes to investigate the differences between metastatic breast cancer cells MDA-MB-231 and non-metastatic MCF-7 in reconfiguring the extracellular matrix to promote cell migration induced by long-distance cell mechanics. Both cancer cells were able to rearrange type I collagen fibres to form collagen threads, in which MDA-MB-231 consistently migrated more rapidly than MCF-7, ranging from matrix model with differently arrayed spacings to complex polygonal models. MDA-MB-231 displayed higher capability of reorganizing fibre bundles at longer distance (800 μm). Further looking for differences in cellular mechanical mechanisms, siRNA knockdown inhibiting either integrin β1 or Piezo1 decreased fibre assembly. Metastatic MDA-MB-231 showed inhibited migration with integrin knockdown, whereas scattered migration with Piezo1 knockdown indicating cells losing distant mechanosensation. MCF-7 with reduced E-cadherin by siRNA transfection showed less significant differences in migration compared to MDA-MB-231 that didn’t express E-cadherin. MDA-MB-231 expressed little E-cadherin mRNA indicating mutagenetic change in genome. In summary this work has explored the differences between malignant and benign breast cancer cells, particularly in terms of fibre matrix remodelling and cell migrations, along with significant differences in E-cadherin expressions, of which had an important effect on cell migration. The results of this study provide new research approaches for therapeutic advances in breast cancer.

The focus of this research is to investigate the relationship between lactate induced by exercise and inhibition, a key element of executive functions. Lactate is vital for neuronal function as both an energy source and a signalling molecule. The increase in lactate production during exercise is linked to heightened brain uptake, potentially impacting cognitive performance. Through a systematic search, 16 relevant studies were identified. Three, employing cognitive tasks akin to ours, suggested a positive correlation between the changes in cognitive performance and peripheral lactate. However, these studies suffered from methodological limitations such as not having proper non-exercise controls, not manipulating exercise intensity, and having limited analytical robustness. The current study aims to address these gaps by analysing the data from a four-arm randomized crossover trial, incorporating three distinct exercise intensities alongside a control group, focusing on the potential role of lactate in modulating inhibition post-exercise.

Abstract Background: Currently, there is no consensus on the effect of 24-h and 36-h acute total sleep deprivation (ATSD) on human attention. This activation likelihood estimation (ALE) meta-analysis aimed to compare the different patterns of functional magnetic resonance imaging (fMRI activation) between 24-h and 36-h ATSD across attention tasks. Methods: We used GingerALE 2.3.6 software to conduct coordinate-based ALE meta-analysis. The literature related to sleep deprivation, attention, and neuroimaging was searched in four databases: CNKI, PubMed, Web of Science, and PsycINFO from November 1980 to March 2023. Results: We included 16 fMRI-related articles, with 383 participants and 95 foci. The findings revealed that 24-h ATSD and 36-h ATSD may impair different brain areas. After 24-h ATSD, there was significantly reduced brain activation in the parietal-occipital attention lobes and the salience network, including the bilateral superior parietal lobule, right inferior occipital gyrus, and left insula. Increased activation was observed in the sub-lobar regions, including the bilateral thalamus. After 36-h ATSD, there was significantly reduced activation in the frontoparietal attention network, including the left middle frontal gyrus and the right inferior frontal gyrus. Conclusions: This ALE meta-analysis revealed that prolonged ATSD leads to more severe temporary brain damage and a cumulative decrease in the external stimuli captured by humans. This primarily affects the frontal-parietal-occipital attention network and the salience network. Thalamic activation may compensate for dysfunction in the parietal-occipital attention network after 24-h ATSD. Sleep deprivation duration plays a crucial role in the extent of attention impairment.

Generalists are thought to adapt to a broader breadth of ecological conditions compared to less flexible specialists. However, few studies have systematically tested what ecological or life-history traits are associated with organisms' ecological flexibility. Here, we used stony corals to test the relative effects of host traits and ecological factors on corals' flexibility to form photosymbioses with algae. We analyzed data from 211 stony coral species to test if coral's geographic distribution, depth range, symbiont transmission mode, or colony morphology predict coral-algal flexibility. We report a novel positive correlation between coral-algal flexibility and coral species' geographic range. Symbiont transmission mode is also a predictor of flexibility, albeit the result is less robust against sampling bias. Coral depth range and morphology did not show significant effects. We discuss how host-symbiont dispersal abilities, interactions, and evolutionary history could contribute to the observed patterns and how this finding could inform conservation efforts.

The publish-or-perish culture in academia has catalysed the development of an unethical publishing system. This system is characterised by the proliferation of journals and publishers—unaffiliated with learned societies or universities—that maintain extremely large revenues and profit margins diverting funds away from the academic community. Early career researchers (ECRs) are particularly vulnerable to the consequences of this publishing system because of intersecting factors, including pressure to pursue high impact publications, rising publication costs and job insecurity. Moving towards a more ethical system requires that scientists advocate for structural change by making career choices that come with risks, many of which disproportionately impact ECRs. We illuminate major issues facing ECRs in Ecology and Evolution under the current publishing system, and propose a portfolio of actions to promote systemic change that can be implemented by ECRs and established researchers.

The well-posedness and regularity properties of diffusion-aggregation equations, emerging from interacting particle systems, are established on the whole space for bounded interaction force kernels by utilizing a compactness convergence argument to treat the non-linearity as well as a Moser iteration. Moreover, we prove a quantitative estimate in probability with arbitrary algebraic rate between the approximative interacting particle systems and the approximative McKean--Vlasov SDEs, which implies propagation of chaos for the interacting particle systems.

Objective To explore the association of clinical and subclinical bacterial vaginosis before conception with the risk of spontaneous abortion. Design Retrospective cohort study. Setting Mainland China. Population This study included women who enrolled in and completed the National Free Pre-Pregnancy Checkups Project between January 1, 2014 and December 31, 2018. Methods Clinical bacterial vaginosis before conception was diagnosed according to the Amsel criteria, and subclinical bacterial vaginosis before conception was defined as any indicators in the Amsel Criteria being positive but not meeting the diagnostic criteria. Analyses were performed by multivaribale-adjusted logistic models with crude and multivaribale-adjusted odds ratios including 95% confidence interval. Main outcome measures Spontaneous abortion was defined as fetal death occurring spontaneously before the 28th week of gestation. Results Of the included participants, 0.27% and 6.97% of them had clinical and subclinical bacterial vaginosis before conception respectively. A significantly increased risk of spontaneous abortion was observed for women with preconception bacterial vaginosis (OR: 1.19, 95% CI: 1.06-1.34). After excluding participants with preconception bacterial vaginosis, subclinical bacterial vaginosis was associated with a 15% (13%-18%) increased risk of spontaneous abortion. And the corresponding multivariable-adjusted ORs of exposure to abnormal vaginal discharge characteristics, vaginal pH value ≥4.5, positive clue cell test, and positive Whiff test for spontaneous abortion were 1.20 (1.03-1.39), 1.15 (1.12-1.18), 1.08 (0.97-1.19), and 1.24 (1.11-1.38). Conclusion Both clinical and subclinical bacterial vaginosis before conception were prospectively associated with an increased risk of spontaneous abortion.

A document by Andrew D Weeks. Click on the document to view its contents.

Objectives Maternal and Child Health Outcomes have been considered a serious global concern in recent times, especially for low to middle-income countries like Nigeria. The aim of the study was to identify factors associated with the choice of obstetric delivery among pregnant women in a local community of Ikenne LG, Nigeria. Design The study used a validated 32-item questionnaire to gather demographic information, knowledge about obstetric care, and participants’ experiences. It involved 200 pregnant women from Ikenne LG and collected data through an Interviewer-Administered method. Setting A health education sensitization program and administration of questionnaires were conducted at the health facilities. Population or Sample Methods Pregnant women in Ikenne local government, Ogun state, Nigeria, are surveyed on demographic characteristics, pregnancy outcomes, personal risk choice, knowledge of OB delivery services, and obstetric history. Main outcome They are classified into two independent variables and dependent variables. Measures The researcher reviewed and edited questionnaires, with a trained assistant available for completeness. The SPSS Package was used for data analysis. Results The study revealed that 73% of participants had their last deliveries in a hospital, with factors like previous deliveries, recommendations, government approval, and proximity influencing birthplace choices. Conclusions In conclusion, factors associated with the choice of delivery facilities included knowledge, recommendation, proximity, and perception of risk involved.

Background Little is known about the oncologic results of patients with low-grade endometrial stromal sarcoma (LGESS) with fertility preservation. This study was to investigate the prognosis of fertility-sparing surgeries and relevant obstetrical outcomes. Methods All eligible patients in the study center were retrospectively reviewed if they consented to surgical treatment for primary LGESS from February 2012 to June 2019 in the study center. Follow-up of fertility and oncologic outcomes was carried out until June 1, 2020. Results Among 135 patients accepted surgical therapy for primary uterine LGESS, 21 (15.6%) and 42 (31.1%) had fertility-sparing surgery and ovarian preservation, respectively. After a median follow-up of 38.5 (range 5-98) months, differences existed in the recurrent rates among patients with and without fertility-sparing surgery (47.6% versus 15.8%, p=0.002), or with and without ovarian preservation (42.9% versus 10.8%, p<0.001). Fertility-sparing surgery and ovarian preservation significantly increased the recurrent risks in the whole cohort (hazard ratio [HR] 3.5 and 5.2, 95% confidential interval [CI] 1.6-7.6 and 2.4-11.3, p=0.002 and <0.001) and in stage I patients (HR 2.6 and 3.1, 95% CI 1.0-6.4 and 1.3-7.4, p=0.041 and 0.011). No factor was found to be associated with increased mortality risk. Among 9 patients attempting pregnancy, 7 (77.8%) achieved 8 live births. Three advanced stage patients with fertility-sparing surgery all experienced recurrence without successful conception. Conclusion Fertility-sparing surgery for LGESS results in a significantly increased risk of recurrence but not of mortality, and has promising results in terms of live births in stage I patients.

This study, investigates the goal setting and goal optimization using machine learning techniques. Goal setting assesses whether a goal is achievable; if so, it helps define the main goals, sub-goals, and establish a plan. During the study, we analyzed a three-year sales dataset and predicted prices that would achieve a 20% revenue increase goal for the year following the last day of the dataset. We implemented the time series forecasting models for this study and applied the goal optimization methods. We tested six different time series models, and based on accuracy values, we benchmarked the Seasonal Autoregressive Integrated Moving Average (SARIMAX) model with the highest success rate. Goal optimization is implemented using the Python programming language with time series and optimization libraries. While departments within companies typically spend days working on pricing issues to reach the target revenue, this study offers a rapid and smooth solution for the goal optimization. In addition to saving time for companies, it also helps save money and prevents excessive risk-taking beyond the target goal, ultimately enhancing customer satisfaction and ensuring the company’s sustainability. From a broader perspective, it contributes to supporting sustainable economic growth, thereby assisting in achieving long-term economic development.

The global pandemic of coronavirus disease is attributable to a newly emerged coronavirus targeting the respiratory system. A pivotal approach in addressing this pandemic involves the search for pharmaceutical compounds capable of impeding the essential viral proteins necessary for viral replication and infection. Since ACE2 enzyme acts as the primary cellular entry point for certain coronaviruses, inhibiting it can play a crucial role in our efforts to combat these viruses. In this study, we employed a range of ACE2 inhibitors to conduct quantitative structure-activity relationship (QSAR) analyses, molecular docking analysis, and molecular dynamics simulations. The QSAR investigation, which relies on the Stepwise-MLR model developed in this study, provides a conceptual framework for improving the effectiveness of ACE2 inhibitor compounds. The molecular docking analysis revealed possible binding locations of the compounds within the ACE2 (PDB ID=6m0j). A 150-ns molecular dynamics simulation was conducted to validate the conformational stability of the top three promising compounds when bound to SARS-CoV-2-ACE2 complex. The findings indicated that all three compounds consistently occupied the specific binding pocket of the target and established numerous hydrogen bonds throughout the simulation, aligning with the results of the molecular docking studies. This research could help identify new leads for the development of novel anti-viral drugs against SARS-CoV-2.

Purpose: The first clinical biology-guided radiation therapy (BgRT) system – RefleXion TM X1 - was installed and commissioned for clinical use at our institution. This study aims at evaluating X1 treatment planning feasibility of complex craniospinal targets for pediatric medulloblastoma patients and comparing plan quality to multi-isocenter linac-based VMAT plans. Methods: Five pediatric patients treated with multi-isocenter craniospinal irradiation (CSI), planned using Eclipse VMAT and delivered using Varian Trilogy C-arm linac, were selected for this retrospective study. All PTV targets had a craniocaudal length<50cm (current X1 TPS limit) and received 36 Gy in 20 fractions. The target volumes and organs-at-risk (OARs) used for VMAT plans were used to generate plans using RefleXion X1. The near maximum dose to PTV (PTV D2%), OARs Dmean and Dmax, and treatment times were collected for analysis. A paired-sample t-test was performed to detect significance at p <0.05. Results: All five RefleXion X1 CSI plans were successfully generated and were clinically acceptable for treatment. PTV D2% was higher for X1 compared to VMAT plans at 41.3 Gy and 39.2 Gy, respectively, (p = 0.08). For the X1 plans, the average Dmean to the bowel, cochleas, heart, kidneys, lungs, and oral cavity were 10.4 Gy, 38.5 Gy, 12.5 Gy, 18.2 Gy, 13.7 Gy, and 16.0 Gy, respectively. The difference was not found to be statistically significant (p>0.05) compared to VMAT plans which showed Dmean to the bowel, heart, kidneys, lungs, and oral cavity at 11.7 Gy, 38.4 Gy, 11.6 Gy, 15.6 Gy, 13.3 Gy, and 15.0 Gy, respectively. The average treatment beam-on time for X1 plans was 16.7 min versus 3.6 min for VMAT plans (p<0.01). However, RefleXion X1 platform enabling one-isocenter treatment and 90 cm long kVCT scan has a potential to decrease the setup/imaging time, and thus the total treatment time compared to multi-isocenter linac-based VMAT where the total treatment time up to 43.5 min was observed. Conclusion: Apart from a higher maximum dose to PTV, X1 plans showed comparable dosimetry to multi-isocenter VMAT plans. Although the average beam-on time with X1 was longer, there is a potential for a more streamlined setup and IGRT using a single-isocenter plans.

Neuroblastoma is the most common extracranial tumor in children, and some children have already metastasized throughout the body when diagnosed, rapidly progressing to death. This article summarizes existing research findings and indicators for predicting poor prognosis, aiming to provide reference for clinical treatment and promote the research development.

A document by Takeru Okouchi. Click on the document to view its contents.

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopamine neurons and aberrant deposits of alpha-synuclein (a-syn) in the brain. The symptomatic treatment is started after the onset of motor manifestations in a late stage of the disease. Preclinical studies show promising results of disease-modifying neuroprotective or even neurorestorative therapies with neurotrophic factors (NTFs). Three NTFs have entered phase I-II clinical trials with inconclusive outcomes. This is not surprising since the preclinical evidence is from acute early-stage disease models but the clinical trials included advanced PD patients. In order to conclude the value of NTF therapies, clinical studies should be performed in early-stage patients with prodromal symptoms, i.e. before motor manifestations. In this review, we summarize currently available diagnostic and prognostic biomarkers that could help identify at-risk patients benefiting from NTF therapies. Focus is on biochemical and imaging biomarkers, but also other modalities are discussed. Neuroimaging is the most important diagnostic tool today, but a-syn imaging is not yet viable. Modern techniques allow measuring various forms of a-syn in cerebrospinal fluid, blood, saliva and skin. Digital biomarkers and artificial intelligence offer new means for early diagnosis and longitudinal follow-up of degenerative brain diseases.

Initiated in 1966, the Breeding Bird Survey (BBS) has gathered a large collection of data on 800 avian species from 300,000 sites across North America. Managed collaboratively by the United States Geological Survey (USGS) and the Geological Survey of Canada (GSC), this dataset helps in the ecological assessment of 40,000 protected areas (PAs) in the region. To unlock this data’s full potential, we present the SaveBirds.app—a specialized web application designed to explore the extensive BBS dataset. The platform empowers various stakeholders, including ecologists, wildlife managers, and policymakers, by providing them with custom analytical tools to address critical conservation questions. SaveBirds.app offers three core functionalities: 1) Metrics, for calculating species-specific Rarity Scores and route-based Species Richness (SR), Rarity-Weighted Richness (RWR), and Shannon diversity ( H ′ ) based on customizable parameters; 2) Presence/Absence Data, for mapping the spatio-temporal distribution of selected bird species; and 3) Bird Atlas Generator, the first publicly available tool equipped with a pre-built ArcGIS model, enabling users to create customized bird atlases. SaveBirds.app represents a pivotal advancement in using long-term ecological datasets, providing strong analytics to inform and prioritize conservation initiatives in North America.