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Recently, phytochemicals play an important role in cancer management. Curcumin (CUR), a natural phytochemical, has been co-administered with widespread chemotherapeutic agents such as doxorubicin (DOX) due to its excellent antitumor activity and the ability to lower the adverse reactions and drug resistance cells associated with DOX use. The present study aims to determine DOX and CUR utilizing a label-free, selective, sensitive, and precise synchronous spectrofluorimetric method. The obvious overlap between the emission spectra of DOX and CUR prevents simultaneous estimation of both analytes by conventional spectrofluorimetry. To solve such a problem, synchronous spectrofluorimetric measurements were recorded at Δλ = 20 nm, utilizing ethanol as a diluting solvent. Curcumin was recorded at 442.5 nm, whereas DOX was estimated at 571.5 nm, each at the zero-crossing point of the other one. The developed method exhibited linearity over a concentration range of 0.04–0.40 μg/mL for CUR and 0.05–0.50 μg/mL for DOX, respectively. The values of limit of detection (LOD) were 0.009 and 0.012 µg/mL, while the values of limit of quantitation (LOQ) were 0.028 and 0.037 µg/mL for CUR and DOX, respectively. The adopted approach was carefully validated according to the guidelines of ICH Q2R1. The method was utilized to estimate CUR and DOX in laboratory-prepared mixtures and human biological matrices. It showed a high percentage of recoveries with minimal RSD values. Additionally, three different tools were utilized to evaluate the greenness of the proposed approach. [ABSTRACT FROM AUTHOR]

Background: Since the advent of laparoscopic hysterectomy, several studies have described artefacts, such as vascular pseudoinvasion, constituting potential pitfalls in the histological evaluation of these specimens. The use of an intrauterine manipulator is often suggested as the factor creating these artefacts. Objectives: To describe possible artefacts, such as vascular pseudoinvasion, myometrial clefts, and tumor cells in the lumen of the cervix, on the serosa, and in the tubal lumen, and to correlate them with clinical and pathological characteristics. Material and Methods: This is a retrospective monocentric study of 60 patients having been treated for benign (n = 27, 45%) or malignant (n = 33, 55%) uterine pathologies. Results: Vascular pseudoinvasion was found in 13 (22%) adenocarcinomas and in one (2%) benign uterine pathology. Clefts within the myometrium were observed in 16 (27%) uteri. Cells in the tubal lumen were observed in six (10%) hysterectomies. True vascular emboli were not correlated with the use of an intrauterine manipulator (p = 0.47) or the type of surgery (p = 0.21). Vascular pseudoinvasion was correlated with the presence of tumor cells in the lumen of the cervix (p = 0.013) and the presence of clefts in the myometrium (p < 0.001), but not with the other factors studied. Conclusions: Overall, in our series, we did not observe any statistical association between the use of an intrauterine manipulator and the presence of true emboli or vascular pseudoinvasion during hysterectomy in women with malignant or benign uterine pathologies. Vascular pseudoinvasion was also associated with the presence of other artefacts. [ABSTRACT FROM AUTHOR]

Background: The Nightmare Distress Questionnaire (NDQ), known and commonly used for its adequate psychometric properties, is the most widely used instrument for the measurement of nightmare distress. This study aimed to assess the psychometric properties of a newly translated Arabic version of the Nightmare Distress Questionnaire (NDQ-AV). Methods: A total of 546 Lebanese adolescents was recruited for this study and completed the NDQ-AV, the Insomnia Severity Index (ISI), and the eight-item Depression, Anxiety and Stress Scale (DASS-8). Results: The results of the exploratory factor analysis (EFA) and the confirmatory factor analysis (CFA) supported both a one-factor model and a two-factor model of the NDQ-AV, with the latter consisting of seven items within both factors. The first factor was referred to as the "general nightmare distress and coping" while the second was named "nightmare impact and perception". The reliability of the scale was excellent (α = 0.930 and ω = 0.915). Moreover, measurement invariance was shown across gender, demonstrating that this measure performs consistently for both men and women. Additionally, the NDQ-AV scores exhibited excellent reliability alongside factorial and concurrent validity. Conclusion: In conclusion, these results support the psychometric validity of the Arabic version of the NDQ. The availability of the NDQ-AV is expected to facilitate the understanding of nightmare distress within the Lebanese context. [ABSTRACT FROM AUTHOR]

In the era of digitization and technical breakthroughs, artificial intelligence (AI) has progressively found its way into the field of customer relationship management (CRM), bringing benefits as well as difficulties to businesses. AI, particularly in the context of CRM, employs machine learning (ML) and deep learning (DL) techniques to extract knowledge from data, recognize trends, make decisions, and learn from mistakes with minimal human intervention. Successful firms have effectively integrated AI into CRM for predictive analytics, computer vision, sentiment analysis, personalized recommendations, chatbots and virtual assistants, and voice and speech recognition. AI-driven chatbots, one of the AI-powered CRM systems, arose as a disruptive approach to customer service, and as such, unfolded with economic and managerial ramifications in CRM. Given the literature's focus on other AI-driven systems, there is an obvious need for an investigation of industry applications and the implications of AI-driven chatbots in CRM. The purpose of this study is to explore and elucidate the economic and managerial implications of AI-powered chatbots within CRM systems. This investigation aims to provide a comprehensive understanding of how these technologies can enhance customer interactions, streamline business processes, and impact organizational strategies. To reach this goal, this study conducts a comparative qualitative analysis based on many interviews with experts and contributors in the field. Interviews with CRM specialists yielded insights into the use of AI-driven chatbots in CRM and their impact on the industry. The primary advantages identified in this study were the impact of AI-powered chatbots on cost, efficiency, and human performance. In addition, AI chatbots have proven useful in a variety of industries, including retail and tourism. Nonetheless, there were limitations to its usage in the healthcare system, particularly in terms of ethical problems. [ABSTRACT FROM AUTHOR]

In the setting of Carnot groups, we propose an approach of taming singularities to get coercive inequalities. To this end, we develop a technique to introduce natural singularities in the energy function U in order to force one of the coercivity conditions. In particular, we explore explicit constructions of probability measures on Carnot groups which secure Poincaré and even Logarithmic Sobolev inequalities. As applications, we get analogues of the Dyson–Ornstein–Uhlenbeck model on the Heisenberg group and obtain results on the discreteness of the spectrum of related Markov generators. [ABSTRACT FROM AUTHOR]

Floating offshore wind is a promising renewable energy source, as 60% of the wind resources globally are found at depths requiring floating technologies, it minimizes construction at sea, and provides opportunities for industrialization given a lower site dependency. While floating offshore wind has numerous advantages, a current obstacle is its cost in comparison to more established energy sources. One cost-reduction approach for floating wind is increasing turbine capacities, which minimizes the amount of foundations, moorings, cables, and O&M equipment. This work presents trends in mass-optimized VolturnUS hull designs as turbine capacity increases for various wave environments. To do this, a novel rapid hull optimization framework is presented that employs frequency domain modeling, estimations of statistical extreme responses, industry constructability requirements, and genetic algorithm optimization to generate preliminary mass-optimal VolturnUS hull designs for a given turbine design and set of site conditions. Using this framework, mass-optimized VolturnUS hull designs were generated for 10–30 MW turbines for wave environments of varying severities. These design studies show that scaling up turbine capacities increases the mass efficiency of substructure designs, with decreasing returns, throughout the examined turbine capacity range. Additionally, increased wave environment severity is shown to increase the required mass of a given substructure design. [ABSTRACT FROM AUTHOR]

The principle of modal continuity has become an increasingly popular bit of modal epistemology, featuring prominently in debates about mereology, value, causation, and theism. It claims, roughly, that degreed properties are modally unified. So, if the property of being three inches tall is exemplifiable, so is the property of being four inches tall, and five inches tall, etc. Despite its plausibility, in this paper I show that there is a class of counterexamples to modal continuity: what I call ‘powered properties.’ More surprisingly, I show that an instance of these powered properties is entailed by another widely popular family of modal principles: the Lewisian patchwork principles, also known as cut-and-paste, or recombination, principles. Thus, despite appearing to be similar, and motivated by plenitudinous intuitions about the nature of modality, it turns out that the continuity and recombination approaches to modality rely on crucially different pictures of plenitude. [ABSTRACT FROM AUTHOR]

The T2-Fluid-Attenuated Inversion Recovery (T2-FLAIR) mismatch sign is a radiogenomic marker that is easily discernible on preoperative conventional MR imaging. Application of strict criteria (adult population, cerebral hemisphere location, and classic imaging morphology) permits the noninvasive preoperative diagnosis of isocitrate dehydrogenase (IDH)-mutant 1p/19q-non-codeleted diffuse astrocytoma with near-perfect specificity, albeit with variably low sensitivity. This leads to improved preoperative planning and patient counseling. More recent research has shown that the application of less strict criteria compromises the near-perfect specificity of the sign but remains adequate for ruling out IDH-wildtype (glioblastoma) phenotype, which bears a far grimmer prognosis compared to IDH-mutant diffuse astrocytic disease. In this review, we elaborate on the various definitions of the T2-FLAIR mismatch sign present in the literature, illustrate these with images obtained at a comprehensive cancer center, discuss the potential of the mismatch sign for application to certain pediatric-type brain tumors, namely dysembryoplastic neuroepithelial tumor and diffuse midline glioma, and elaborate upon the clinical, histologic, and molecular associations of the T2-FLAIR mismatch sign as recognized to date. Finally, the sign's correlates in diffusion- and perfusion-weighted imaging are presented, and opportunities to further maximize the diagnostic and prognostic applications of the sign in the context of the 2021 revision of the WHO Classification of Central Nervous System Tumors are discussed. [ABSTRACT FROM AUTHOR]

A large body of work has highlighted the role of disgust in contamination-related OCD. However, there appears to be a lack of research examining the potential cognitive mechanisms through which disgust may potentiate symptoms of contamination fear. Research has shown that the "feared self" may be a cognitive factor involved in the development of OCD symptoms. The aim of this study was to assess the potential mediating effects of feared possible selves in the associations between disgust propensity (DP), disgust sensitivity (DS) and symptoms of contamination fear. A sample of 412 undergraduate participants completed measures of DP and DS, feared possible selves, and symptoms of both contact and mental contamination. Using path analysis, the results indicated that while DP was a significant predictor of contact and mental contamination, DS predicted both contamination symptom domains via the mediating effect of the "feared corrupted self". Notably, the association between DS and mental contamination was fully mediated by the "feared corrupted self". These findings highlight the role of the "feared corrupted self" in misappraisals of disgust and shed light on the relevance of assessing and targeting feared possible selves in the treatment of disgust in contamination fear. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases (BMs), the most common type of cerebral tumor, are primarily associated with lung cancer, breast cancer, and melanoma. Patients typically present to the emergency department (ED) with insidious symptoms such as headaches, focal neurological deficits, seizures, and signs of increased intracranial pressure. Key symptomatic treatment in the ED includes corticosteroids to manage peritumoral edema, and carefully selected antiepileptic medications for tumor-related epileptic conditions. After stabilization, the treatment philosophy for BMs should prioritize effective yet minimally toxic options to maximize quality of life. Surgery is recommended for accessible BMs in patients with good performance status. Radiation therapy and systemic treatments, including chemotherapy, targeted therapy, and immunotherapy, are available options for managing disease progression. Given that over half of patients with BMs in the ED are admitted, a better understanding of avoidable hospitalizations is essential to differentiate those who can be safely discharged from those needing observation or hospitalization. Brain metastases (BMs) are the most prevalent type of cerebral tumor, significantly affecting survival. In adults, lung cancer, breast cancer, and melanoma are the primary cancers associated with BMs. Symptoms often result from brain compression, and patients may present to the emergency department (ED) with life-threatening conditions. The goal of treatment of BMs is to maximize survival and quality of life by choosing the least toxic therapy. Surgical resection followed by cavity radiation or definitive stereotactic radiosurgery remains the standard approach, depending on the patient's condition. Conversely, whole brain radiation therapy is becoming more limited to cases with multiple inoperable BMs and is less frequently used for postoperative control. BMs often signal advanced systemic disease, and patients usually present to the ED with poorly controlled symptoms, justifying hospitalization. Over half of patients with BMs in the ED are admitted, making effective ED-based management a challenge. This article reviews the epidemiology, clinical manifestations, and current treatment options of patients with BMs. Additionally, it provides an overview of ED management and highlights the challenges faced in this setting. An improved understanding of the reasons for potentially avoidable hospitalizations in cancer patients with BMs is needed and could help emergency physicians distinguish patients who can be safely discharged from those who require observation or hospitalization. [ABSTRACT FROM AUTHOR]

The limitation of conventional visual acuity assessment, which primarily focuses on individual eye performance (monocular visual acuity tests). This study addresses this limitation by emphasizing the importance of binocular vision, where both eyes work together. Binocular vision provides numerous advantages, such as improved depth perception, a wider field of view, reduced visual fatigue, and binocular summation. The article introduces a new mathematical model based on the physics of constructive interference in light waves and the anatomy of visual nerves. This model yields an equation that quantifies how weakness in one eye affects the visual acuity of the other. By analyzing the correlation between the rates of visual weakness in each eye and the corresponding distances, utilizing the Snellen 6-meter test, valuable insights are gained into the complex interplay between eye deficiencies and their collective impact on overall visual acuity. The equations derived from this study can have significant implications for eye care professionals, clinicians, and patients, contributing to a more comprehensive understanding of visual impairments and enriching the field of optics and vision science. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Inferior vena cava atresia is a rare condition with highly variable anatomy due to the complexity of caval embryology. When endovascular venovenous reconstruction is considered for severe persistent sequelae, multimodality imaging with CT and invasive venography is used to determine the appropriateness of intervention and for procedural planning. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common type of cancer of the female gender. A rare subtype of breast cancer is the invasive breast carcinoma (IBC) with neuroendocrine (NE) differentiation. Its incident is believed to be 0.1% to 5% of all breast cancers. We report a rare case of a 66-year old woman who presented with an isolated nodule of the left breast. The patient underwent modified radical mastectomy. Pathology revealed invasive breast carcinoma with neuroendocrine differentiation. Invasive breast carcinoma is an extremely rare group of neoplasms, the exact frequency of which cannot be determined with current data. Therefore, it is necessary for future studies to focus on the pathophysiology of this subtype of breast cancer and on the potential therapeutic approaches. [ABSTRACT FROM AUTHOR]

Cutaneous fungal infections affect millions around the world. However, severe, multi‐resistant fungal infections are increasingly being reported over the past years. As a result of the high rate of resistance which urged for drug repurposing, statins were studied and found to have multiple pleiotropic effects, especially when combined with other already‐existing drugs. An example of this is the synergism found between several typical antifungals and statins, such as antifungals Imidazole and Triazole with a wide range of statins shown in this review. The main mechanisms in which they exert an antifungal effect are ergosterol inhibition, protein prenylation, mitochondrial disruption, and morphogenesis/mating inhibition. This article discusses multiple in vitro studies that have proven the antifungal effect of systemic statins against many fungal species, whether used alone or in combination with other typical antifungals. However, as a result of the high rate of drug–drug interactions and the well‐known side effects of systemic statins, topical statins have become of increasing interest. Furthermore, patients with dyslipidemia treated with systemic statins who have a new topical fungal infection could benefit from the antifungal effect of their statin. However, it is still not indicated to initiate systemic statins in patients with topical mycotic infections if they do not have another indication for statin use, which raises the interest in using topical statins for fungal infections. This article also tackles the different formulations that have been studied to enhance topical statins' efficacy, as well as the effect of different topical statins on distinct dermatologic fungal diseases. [ABSTRACT FROM AUTHOR]

Spirulina (Arthrospira platensis) is reported to play a role in improving nonalcoholic fatty liver disease (NAFLD) and intestinal microbiota (IM). To study spirulina's effects in the improvement of NAFLD characteristics, IM, and pancreatic–renal lesions induced by a fructose-enriched diet, 40 Wistar healthy male rats, weighing 200–250 g, were randomly divided into four groups of 10, and each rat per group was assigned a diet of equal quantities (20 g/day) for 18 weeks. The first control group (CT) was fed a standardized diet, the second group received a 40% fructose-enriched diet (HFr), and the third (HFr-S5) and fourth groups (HFr-S10) were assigned the same diet composition as the second group but enriched with 5% and 10% spirulina, respectively. At week 18, the HFr-S10 group maintained its level of serum triglycerides and had the lowest liver fat between the groups. At the phylae and family level, and for the same period, the HFr-S10 group had the lowest increase in the Firmicutes/Bacteroidetes ratio and the Ruminococcaceae and the highest fecal alpha diversity compared to all other groups (p < 0.05). These findings suggest that at a 10% concentration, spirulina could be used in nutritional intervention to improve IM, fatty liver, metabolic, and inflammatory parameters associated with NAFLD. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Biomarkers have shown promise in amyotrophic lateral sclerosis (ALS) research, but the quest for reliable biomarkers remains active. This study evaluates the effect of debamestrocel on cerebrospinal fluid (CSF) biomarkers, an exploratory endpoint. Methods: A total of 196 participants randomly received debamestrocel or placebo. Seven CSF samples were to be collected from all participants. Forty‐five biomarkers were analyzed in the overall study and by two subgroups characterized by the ALS Functional Rating Scale‐Revised (ALSFRS‐R). A prespecified model was employed to predict clinical outcomes leveraging biomarkers and disease characteristics. Causal inference was used to analyze relationships between neurofilament light chain (NfL) and ALSFRS‐R. Results: We observed significant changes with debamestrocel in 64% of the biomarkers studied, spanning pathways implicated in ALS pathology (63% neuroinflammation, 50% neurodegeneration, and 89% neuroprotection). Biomarker changes with debamestrocel show biological activity in trial participants, including those with advanced ALS. CSF biomarkers were predictive of clinical outcomes in debamestrocel‐treated participants (baseline NfL, baseline latency‐associated peptide/transforming growth factor beta1 [LAP/TGFβ1], change galectin‐1, all p <.01), with baseline NfL and LAP/TGFβ1 remaining (p <.05) when disease characteristics (p <.005) were incorporated. Change from baseline to the last measurement showed debamestrocel‐driven reductions in NfL were associated with less decline in ALSFRS‐R. Debamestrocel significantly reduced NfL from baseline compared with placebo (11% vs. 1.6%, p =.037). Discussion: Following debamestrocel treatment, many biomarkers showed increases (anti‐inflammatory/neuroprotective) or decreases (inflammatory/neurodegenerative) suggesting a possible treatment effect. Neuroinflammatory and neuroprotective biomarkers were predictive of clinical response, suggesting a potential multimodal mechanism of action. These results offer preliminary insights that need to be confirmed. [ABSTRACT FROM AUTHOR]

Associations between brain and obesity are bidirectional: changes in brain structure and function underpin over-eating, while chronic adiposity leads to brain atrophy. Investigating brain-obesity interactions across the lifespan can help better understand these relationships. This study explores the interaction between obesity and cortical morphometry in children, young adults, adults, and older adults. We also investigate the genetic, neurochemical, and cognitive correlates of the brain-obesity associations. Our findings reveal a pattern of lower cortical thickness in fronto-temporal brain regions associated with obesity across all age cohorts and varying age-dependent patterns in the remaining brain regions. In adults and older adults, obesity correlates with neurochemical changes and expression of inflammatory and mitochondrial genes. In children and older adults, adiposity is associated with modifications in brain regions involved in emotional and attentional processes. Thus, obesity might originate from cognitive changes during early adolescence, leading to neurodegeneration in later life through mitochondrial and inflammatory mechanisms. This study reveals that obesity-related brain changes evolve across the lifespan and involve mitochondrial and inflammatory genes, as well as neurochemical and cognitive alterations. [ABSTRACT FROM AUTHOR]

Over 50 million Americans endure chronic pain where many do not receive adequate treatment and self-medicate to manage their pain by taking substances like opioids and cannabis. Research has shown high comorbidity between chronic pain and substance use disorders (SUD) and these disorders share many common neurobiological underpinnings, including hypodopaminergic transmission. Drugs commonly used for self-medication such as opioids and cannabis relieve emotional, bothersome components of pain as well as negative emotional affect that perpetuates misuse and increases the risk of progressing towards drug abuse. However, the causal effect between chronic pain and the development of SUDs has not been clearly established. In this review, we discuss evidence that affirms the proposition that chronic pain is a risk factor for the development of opioid and cannabis use disorders by outlining the clinical evidence and detailing neurobiological mechanisms that link pain and drug misuse. Central to the link between chronic pain and opioid and cannabis misuse is hypodopaminergic transmission and the modulation of dopamine signaling in the mesolimbic pathway by opioids and cannabis. Moreover, we discuss the role of kappa opioid receptor activation and neuroinflammation in the context of dopamine transmission, their contribution to opioid and cannabis withdrawal, along with potential new treatments. [ABSTRACT FROM AUTHOR]

Background: Following marketing authorization in Japan, for almost all new drugs or new indications, postmarketing studies (PMS) are a regulatory requirement. These PMS focus on accrual of a defined number of cases with data being collected for a predetermined period after approval to confirm efficacy/effectiveness, safety, and quality in the Japanese population. In contrast to other regions where PMS are only required to address a specific scientific uncertainty, in Japan, PMS are often required regardless of any specific scientific uncertainty, and therefore, their scientific value is unclear. Objectives: To determine the contribution to the understanding of benefit/risk of PMS conducted by Pfizer in Japan over 2000–2020 for Pharmaceuticals and Medical Devices Agency (PMDA) reexamination. Methods: A retrospective analysis of all Pfizer Japan postmarketing studies (PMS) during 2000–2020 was performed. Available Pfizer clinical study reports (CSRs) and PMDA reexamination reports (RERs) were reviewed for key safety findings. The primary analysis was conducted on the subset of PMS that had both an English CSR and a discussion of that PMS in the relevant RER issued by the PMDA, which was subsequently translated into English by a professional translation vendor. Reexamination outcome is included in each RER and served to demonstrate the impact of the study of the benefit/risk profile of the drug. Results: A total of 79 PMS for 43 different drug products across therapy areas enrolled a total of 98,035 patients. The 79 PMS comprised 34 general drug use investigation (GDUI) studies and 45 special investigation (SI) studies. The primary analysis involved 37 PMS with a CSR and RER available in English (40,470 patients); all of which were observational in design. For 31 of 37 PMS, the RER concluded the overall adverse drug reaction (ADR) rate in the PMS was nominally lower than in the phase 3 program. Unlabeled ADRs were reported in 28 of 37 PMS; however, no new safety concerns requiring regulatory action arose from any PMS. The PMDA did not require additional risk minimization measures for any of the 43 drug products studied in any of the 79 PMS assessed. Japan PMS data were consistent with prior global data with no evidence of clinically meaningful differences in safety in Japanese patients. In all cases, the reexamination outcome was category 1 ("usefulness is confirmed"). Conclusions: The reexamination process did not result in regulatory changes for any of the examined drugs. The Japan new-drug application (J-NDA) review and approval process, including implementation of the initial Japan product label, assures acceptable benefit/risk at the time of approval such that mandatory GDUI or SI studies for all products should be reconsidered. In the case of genuine scientific uncertainty to the extent that the benefit/risk of the product is not clear, a PMS is warranted. [ABSTRACT FROM AUTHOR]

This paper presents an adaptive neural network acting like a proportional-integral-derivative (PID) controller that uses an intelligent meta-heuristic technique to improve the drug infusion rate (propofol) as a manipulated variable in closed-loop control of anesthesia systems using the Bispectral Index (BIS) as the primary controlled variable. The effect of propofol on the human body is modelled using the pharmacokinetic (PK) and pharmacodynamics (PD) models. A physiological dataset of patients, including gender, weight, height, age, and the like, determines the parameters of the PK/PD mathematical model. The proposed controller seeks to provide the optimal propofol control action, which is in charge of swiftly, precisely, and accurately maintaining a triad of hypnosis, analgesia, and neuromuscular blockade by infusing several drugs that are specific to each state. To train this neural network like a PID controller with the radial basis function (RBF) in a neuron, the meta-heuristic method is employed. The first technique is particle swarm optimization (PSO), which has been widely used in both data estimation and training because of its quick computing speed, while the second technique is the chaotic PSO algorithm, and the third technique is the modified CPSO algorithm (MCPSO). The fundamental proposed procedures of the MCPSO algorithm use the chaos method, including the coefficients of acceleration, and remove the two random parameters from the velocity update equation to generate more randomness in the search space to quickly solve the local minima problem. The PSO, CPSO, and MCPSO meta-heuristic algorithms use the mean square error (MSE) performance index to find and optimize the optimal or the nearly ideal gain parameters of the nonlinear neural network to function like a PID controller. The simulation results show that the proposed controller for different physiological dataset patients is characterized by its efficacy and resilience in terms of controlling the depth of the hypnosis state and the infusion rate of the anesthetic drug during surgery in order to avoid under- or over-dosing of the drug for the patient through the desired value of BIS (50) with minimizing the steady-state error, which is equal to zero without any oscillation. Moreover, the comparison results showed that the proposed RBF-NN-PID controller enhanced the time in one minute to reach the depth of anesthesia at the moderate hypnotic state when compared to the fractional-order adaptive high-gain controller, in which the time to reach the depth of anesthesia is two minutes. In contrast, the adaptive neuro-fuzzy controller reached the depth of anesthesia in three minutes. Therefore, the time was improved by 50% and 67%, respectively. In particular, the surgery BIS index was kept at the BIS desired 50 at the moderate hypnotic state without any error and with no oscillation at steady-state. [ABSTRACT FROM AUTHOR]

This work proposes an intelligent method that uses an adaptive auto-tuned proportional-integral-derivative (PID) controller to track and regulate the blood glucose level of diabetic patients. The suggested controller seeks to provide the optimal insulin control action, which is in charge of swiftly, precisely, and accurately managing the blood glucose level. To train this controller, two meta-heuristic techniques are employed. The first technique is the particle swarm optimization (PSO), which has been widely used in both data estimation and training because of its quick computing speed, while the second one is an intrusion detection technique called grey wolf optimization (GWO), which was created to categorize data and effectively find multiple intrusions. The mean square error performance index is used in the two distinct meta-heuristic algorithm types to determine and optimize the optimal or nearly optimal gain parameters of the adaptive PID controller. The results of the MATLAB simulations for three different patients demonstrated the efficacy and resilience of the proposed control algorithm in tracking the dynamic behaviour of the diabetic patients' blood glucose levels by minimizing overshoot in the transient state to zero value, maintaining the steady-state blood glucose level in the normal physiological level of (60-120) mg/dl. These characteristics were particularly evident when we added a meal as a disturbance effect. Moreover, the comparison results showed that the proposed PID-GWO and PID-PSO algorithms enhanced the time (96 and 88) minutes to reach the blood glucose level at a normal physiological level by 4% and 12%, respectively, when compared to the fractional order PID and fuzzy logic control algorithms that the blood glucose level reached at a normal physiological level at 100 minutes and improved the time by 20% and 27%, respectively, when compared to the type-2 fuzzy control algorithm that the blood glucose level reached at a normal level at 120 minutes. In particular, the blood glucose level was kept at the desired normal physiological level without any oscillation. [ABSTRACT FROM AUTHOR]

At theoretical model of three levels describing Holmium-doped fiber lasers (HDFL) pumped by Laser-diodes 1.15 µm is presented. Based on the model, each of the efficiency, output power depending on fiber core radius, fiber length, and ion concentration of active media were investigated, using the MATLAB program (R 2019 a). The results show that at a doped fiber core radius, 2, 5 & 10 µm pumped with a power range of 10 - 100 W got an output power ranging from 5 to 55 W, respectively, while slope efficiency (η) was 31.3%. Output power was 2.7 - 4 W, η = 50% at a fiber length of 0.01 m, and 81.7 - 83 W, η = 19.6% at a fiber length of 0.5 m. The output power ranged from 107.8 to 109 W & η = 4.7% for 3 m fiber length. The threshold power value of Pth = 0.05 W at fiber core radius 2 µm and Pth = 0.006 W at 3 µm was then gradually slightly increased from 4 to 10 µm. As a result, the output power and efficiency are no longer reliant on the diameter of the fiber core. [ABSTRACT FROM AUTHOR]

Background and Purpose: We aimed to predict the functional outcome of acute ischemic stroke patients with anterior circulation large vessel occlusions (LVOs), irrespective of how they were treated or the severity of the stroke at admission, by only using imaging parameters in machine learning models. Methods: Consecutive adult patients with anterior circulation LVOs who were scanned with CT angiography (CTA) and CT perfusion were queried in this single‐center, retrospective study. The favorable outcome was defined as a modified Rankin score (mRS) of 0‐2 at 90 days. Predictor variables included only imaging parameters. CatBoost, XGBoost, and Random Forest were employed. Algorithms were evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision‐recall curve (AUPRC), accuracy, Brier score, recall, and precision. SHapley Additive exPlanations were implemented. Results: A total of 180 patients (102 female) were included, with a median age of 69.5. Ninety‐two patients had an mRS between 0 and 2. The best algorithm in terms of AUROC was XGBoost (0.91). Furthermore, the XGBoost model exhibited a precision of 0.72, a recall of 0.81, an AUPRC of 0.83, an accuracy of 0.78, and a Brier score of 0.17. Multiphase CTA collateral score was the most significant feature in predicting the outcome. Conclusions: Using only imaging parameters, our model had an AUROC of 0.91 which was superior to most previous studies, indicating that imaging parameters may be as accurate as conventional predictors. The multiphase CTA collateral score was the most predictive variable, highlighting the importance of collaterals. [ABSTRACT FROM AUTHOR]

Background: Individuals experiencing homelessness face unique physical and mental health challenges, increased morbidity, and premature mortality. COVID -19 creates a significant heightened risk for those living in congregate sheltering spaces. In March 2020, the COVID-19 Community Response Team formed at Women’s College Hospital, to support Toronto shelters and congregate living sites to manage and prevent outbreaks of SARS-CoV-2 using a collaborative model of onsite mobile testing and infection prevention. From this, the Women’s College COVID-19 vaccine program emerged, where 14 shelters were identified to co-design and support the administration of vaccine clinics within each shelter. This research seeks to evaluate the impact of this partnership model and its future potential in community-centered integrated care through three areas of inquiry: (1) vaccine program evaluation and lessons learned; (2) perceptions on hospital/community partnership; (3) opportunities to advance hospital-community partnerships. Methods: Constructivist grounded theory was used to explore perceptions and experiences of this partnership from the voices of shelter administrators. Semi-structured interviews were conducted with administrators from 10 shelters using maximum variation purposive sampling. A constructivist-interpretive paradigm was used to determine coding and formation of themes: initial, focused, and theoretical. Results: Data analysis revealed five main categories, 16 subcategories, and one core category. The core category “access to healthcare is a human right; understand our communities” emphasizes access to healthcare is a consistent barrier for the homeless population. The main categories revealed during a time of confusion, the hospital was seen as credible and trustworthy. However, the primary focus of many shelters lies in housing, and attention is often not placed on health resourcing, solidifying partnerships, accountability, and governance structures therein. Health advocacy, information sharing tables, formalized partnerships and educating health professionals were identified by shelter administrators as avenues to advance intersectoral relationship building. Conclusion: Hospital-community programs can alleviate some of the ongoing health concerns faced by shelters – during a time of COVID-19 or not. In preparation for future pandemics, access to care and cohesion within the health system requires the continuous engagement in relationship-building between hospitals and communities to support co-creation of innovative models of care, to promote health for all. [ABSTRACT FROM AUTHOR]

Tickling is commonly perceived as juvenile play associated with laughter. However, its potential connection to adult sexual behavior has largely remained unexplored. Our online survey, primarily distributed among individuals interested in tickle fetishism, explored tickling and its association with sexual behavior. Ticklishness types, tools, preferred body parts, and partner preferences, were examined. Results revealed diverse patterns of ticklishness changes over time and distinct body-part preferences for different types of tickling. Childhood experiences and exposure to tickling content in television were found to shape individuals’ affinity for tickle fetishism. A quarter of respondents reported experiencing orgasms exclusively from tickling, while around 88% expressed sexual satisfaction through tickling alone, indicating its sufficiency as a sexual stimulus among fetishists. Tickling desire decreased after orgasm, indicating an association between tickling and sexual activity. Moreover, ticklishness degree predicted preferences for being tickled rather than tickling others. Exploratory factor analysis identified three factors underlying tickling and sexual experiences: enjoyment and frequency of tickling during sexual activity; preference for intense sexual experiences; age of becoming sexually active. In conclusion, this study provides unique insights into tickling and its connections to sexual context, enhancing our understanding of diverse human sexual behavior and tickle fetishism as a distinct preference. [ABSTRACT FROM AUTHOR]

This research investigates the intricacies of motivation and job satisfaction among military service members within the Lebanese Armed Forces (LAF) amidst various challenges. Employing an intrinsic–extrinsic framework, the study adopts a sequential mixed-method design. Interviews were conducted with 42 LAF service members, a Focus Group was convened with 12 LAF subject matter experts, and a survey was administered to 3880 LAF service members across the country. The findings underscore the significance of monetary rewards and praise as primary motivators. Notably, the expectation of rewards emerges as a crucial motivating factor closely linked to job satisfaction, while intrinsic factors exhibit comparatively lesser influence. Salary emerges as the foremost determinant of job satisfaction. Moreover, economic challenges, particularly the drastic decline in purchasing power, serve as a significant moderating factor, adversely impacting the relationship between motivation and job satisfaction. Health challenges, such as the scarcity and increased prices of medical supplies, also exert a negative moderating influence. Conversely, security challenges demonstrate no significant moderating impact. Insights gleaned from the Lebanese context emphasize the importance of offering competitive salaries and recognition programs, ensuring equitable compensation, designing reward systems aligned with performance expectations, regularly reviewing, and adjusting salary structures, providing comprehensive support for employees' physical and mental well-being, and fostering a secure work environment. [ABSTRACT FROM AUTHOR]

Extensive research into mRNA vaccines for cancer therapy in preclinical and clinical trials has prepared the ground for the quick development of immune-specific mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and are an attractive choice for future cancer immunotherapy. Ideal personalized tumor-dependent mRNA vaccines could stimulate both humoral and cellular immunity by overcoming cancer-induced immune suppression and tumor relapse. The stability, structure, and distribution strategies of mRNA-based vaccines have been improved by technological innovations, and patients with diverse tumor types are now being enrolled in numerous clinical trials investigating mRNA vaccine therapy. Despite the fact that therapeutic mRNA-based cancer vaccines have not yet received clinical approval, early clinical trials with mRNA vaccines as monotherapy and in conjunction with checkpoint inhibitors have shown promising results. In this review, we analyze the most recent clinical developments in mRNA-based cancer vaccines and discuss the optimal platforms for the creation of mRNA vaccines. We also discuss the development of the cancer vaccines' clinical research, paying particular attention to their clinical use and therapeutic efficacy, which could facilitate the design of mRNA-based vaccines in the near future. [ABSTRACT FROM AUTHOR]

In the setting of Carnot groups, we prove the q -logarithmic Sobolev inequality for probability measures as a function of the Carnot–Carathéodory distance. As an application, we use the Hamilton–Jacobi equation in the setting of Carnot groups to prove the p -Talagrand inequality and hypercontractivity. [ABSTRACT FROM AUTHOR]

This is a study of Norway's sustainable environment development amidst the interactions of natural resources, external investment (FDI) and economic development. Much has been done with respect to the study of Norway's economic performance in relation to the link between the natural resources and FDI with little emphasis on the environmental performance of the resource‐based economy. Also, Norway is classified as among the top countries in Europe with a greater percentage of adopting renewable energy, and no study has done a critical review of the impact of natural resources and FDI which are part of drivers of carbon emission that can counter the positive impact of renewable energy towards the Norway's sustainable environment. On this basis, this study adopts a time series data of Norway, 1970 to 2018 to study its environmental performance. Approaches such as structural break analysis, Autoregressive Distributed Lag (ARDL)‐bound testing and Granger causality estimations are utilised in this study for in‐depth analysis of the subject. Findings from ARDL confirmed a positive association between fuels and carbon emission, other indicators (economic growth and natural resources) are improving the quality of the country's environment. FDI even though shows positive sign remains insignificant in impacting the environmental performance in the short run reverted to a significant negative relationship with carbon emissions. This confirms the pollution halo hypothesis and rejects the pollution haven hypothesis (PHH) for Norway, and this trend can be sustained with the constant implementation of environmental rules in the country. Granger test confirms, a one‐way transition from fossil fuels to carbon emission, from carbon emission to growth, and from economic growth to fossil fuels. Also, a two‐way transmission is found between fossil fuels and FDI. These findings from Granger causality are consistent with the findings from ARDL, hence, two ways interactions between FDI and fossil fuel energy source consumption from Granger causality and the two variables (fossil fuels and FDI) are seen impacting on Norway's environmental performance. Findings from the estimates suggest that natural resources and FDI are mitigating pollution, hence, Norway's policy is expected to be resources and FDI driven in sustainable environment development. [ABSTRACT FROM AUTHOR]

Chronic liver diseases are a major global health concern. Aims: this study investigated the links between medical, clinical, anthropometric, and dietary factors with dysfunction-associated steatotic liver disease (MASLD) in the Lebanese population using a case-control approach to uncover factors influencing visceral obesity, sarcopenia, and sarcopenic obesity. Methods and Materials: a total of 120 participants (20–70 years old) were divided into case and control groups based on liver disease diagnosis. Patient information was gathered through a questionnaire encompassing demographics, medical history, and beverage consumption. Anthropometric and body composition data were collected in a clinical setting. Results: our findings indicated a clear association between the presence of MASLD and obesity, hypertension, and diabetes. The positive association with higher body mass index and all three conditions remained consistent even when data was stratified by case and control groups. A greater proportion of MASLD patients exhibited sarcopenic obesity. Furthermore, MASLD cases showed higher consumption of sugary beverages and a reduced intake of milk and water in their diets. Conclusions: this study shed light on the health attributes and diets of the Lebanese population with liver diseases and suggested more research in this area and in a more ethnically diverse population. [ABSTRACT FROM AUTHOR]

A 40-year-old female patient presented to a secondary facility with dull lower abdominal pain and a persistent low-grade fever. Her laboratory results showed elevated inflammation markers. A CT scan revealed two abscesses in the lesser pelvic region in direct contact with the apex of the appendix, the posterior wall of the uterus, and the right-side appendages. The patient responded well to intravenous antibiotics, and an MRI scan revealed the cause to be an appendiceal rupture. The patient was scheduled for an appendectomy. The procedure started laparoscopically but had to be converted to an open one with a midline infra-umbilical incision in order to protect the right appendages. A standard appendectomy was conducted, and the histology report revealed rupture of the appendix with concomitant wall inversion in the context of fibrous adhesions as well as obstruction due to a fecalith. Patient recovery and follow-up were excellent. Acute appendicitis, while frequently encountered in surgical practice, can present a diagnostic conundrum when it manifests in an atypical manner. This unique form of inversion appeared to confer a protective role against peritonitis, primarily through the mechanism of obstruction occurring centrally to the rupture. We suggest that this case should be included in current classifications as a partial inversion of the appendix after rupture and inflammation. [ABSTRACT FROM AUTHOR]

One of William Lane Craig's key arguments for the finitude of the past is the Successive Addition Argument (SAA). Malpass (2021) has recently developed a novel challenge to the SAA, utilising a thought experiment from the work of Fred Dretske, which is meant to show that it is possible to count to infinity, to argue that there is a counterexample to the SAA's second premise. In this paper, I contend that the Malpass‐Dretske counterexample should not worry advocates of the SAA. First, I argue that one objection Malpass considers—the Potential Infinite Objection—reveals an interesting fact: the SAA's second premise is unnecessarily strong and can be weakened whilst still yielding the same conclusion. Second, I show how another one of the objections considered by Malpass—the Accumulation Objection—is successful, provided some clarification to the SAA's premises. The upshot of both analyses is that we generate two 'new' Successive Addition arguments that not only move the dialectic forward, but shed light on deeper assumptions and motivating intuitions concerning the Kalām. [ABSTRACT FROM AUTHOR]

Chronic inflammation and dysregulated repair mechanisms after epithelial damage have been implicated in chronic obstructive pulmonary disease (COPD). However, the lack of ex vivo-models that accurately reflect multicellular lung tissue hinders our understanding of epithelial-mesenchymal interactions in COPD. Through a combination of transcriptomic and proteomic approaches applied to a sophisticated in vitro iPSC-alveolosphere with fibroblasts model, epithelial-mesenchymal crosstalk was explored in COPD and following SARS-CoV-2 infection. These experiments profiled dynamic changes at single-cell level of the SARS-CoV-2-infected alveolar niche that unveiled the complexity of aberrant inflammatory responses, mitochondrial dysfunction, and cell death in COPD, which provides deeper insights into the accentuated tissue damage/inflammation/remodeling observed in patients with SARS-CoV-2 infection. Importantly, this 3D system allowed for the evaluation of ACE2-neutralizing antibodies and confirmed the potency of this therapy to prevent SARS-CoV-2 infection in the alveolar niche. Thus, iPSC-alveolosphere cultured with fibroblasts provides a promising model to investigate disease-specific mechanisms and to develop novel therapeutics. [ABSTRACT FROM AUTHOR]

Simple Summary: The results of previous studies may suggest that Nirmatrelvir/Ritonavir, when evaluated against placebo controls, could potentially be more effective than Molnupiravir in reducing COVID-19 progression. While Nirmatrelvir/Ritonavir reduced COVID-19 progression risk by 88% versus placebo, Molnupiravir reduced it by 31%. However, there has been no direct head-to-head comparison between the two drugs in a prospective randomized trial. This study compared the safety and effectiveness of Nirmatrelvir/Ritonavir versus Molnupiravir in the treatment of mild-to-moderate COVID-19 in 240 immunocompromised cancer patients who received one of the two drugs. The results showed no significant differences in the rate of disease progression between the treatments. Nevertheless, those treated with Nirmatrelvir/Ritonavir reported a higher incidence of drug interactions and adverse events. Therefore, although both medications are effective in preventing severe disease or death in cancer patients with COVID-19, Molnupiravir could be safer than Nirmatrelvir/Ritonavir in terms of drug interactions and adverse effects. Background: Nirmatrelvir/Ritonavir has been shown to reduce the risk of COVID-19 progression by 88% compared to placebo, while Molnupiravir reduced it by 31%. However, these two agents have not been compared head-to-head. We therefore compared the safety and efficacy of both agents for the treatment of mild-to-moderate COVID-19 in immunocompromised cancer patients. Methods: We identified 240 cancer patients diagnosed with COVID-19 and treated with Molnupiravir or Nirmatrelvir/Ritonavir. Patients were matched using a 1:2 ratio based on age group (18–64 years vs. ≥65) and type of cancer. The collected data included demographics, comorbidities, and treatment outcome. Results: Both groups had comparable characteristics and presenting symptoms. However, dyspnea was more prevalent in the Molnupiravir group, while sore throat was more prevalent in the Nirmatrelvir/Ritonavir group. The rate of disease progression was comparable in both groups by univariate and multivariable analysis. Treatment with Molnupiravir versus Nirmatrelvir/Ritonavir revealed no significant difference in disease progression by multivariable analysis (adjusted OR = 1.31, 95% CI: 0.56–3.14, p = 0.70). Patients who received Nirmatrelvir/Ritonavir, however, were significantly more prone to having drug–drug interactions/adverse events (30% vs. 0%, p < 0.0001). Conclusions: In the treatment of mild-to-moderate COVID-19 in cancer patients, Molnupiravir was comparable to Nirmatrelvir/Ritonavir in preventing progression to severe disease/death and rebound events, and it had a superior safety profile. [ABSTRACT FROM AUTHOR]

There is heterogeneity across studies and a lack of knowledge about recovery of EFs over time following traumatic brain injury (TBI). Also, EFs are associated with functional outcome, but there is still a gap in knowledge concerning the association between EFs and social participation following TBI. For this reason, we aim to (1) measure the recovery of the three executive function subcomponents of Miyake's model, namely flexibility, updating and inhibition between the acute phase (T1) and 6 months post TBI (T2) and (2) measure the relationship between EFs and social participation after TBI. Thus, a prospective longitudinal study that included 75 patients with TBI (mild and moderate-severe) and 50 patients with orthopedic injuries (controls) without brain damage was carried out. An extensive EFs test battery was administered at T1 and T2 whereas the Mayo-Portland Adaptability Inventory-4 (MPAI-4) was administered only at T2. In contrast with the controls, both TBI groups improved significantly between T1 and T2 on WMS-III Mental Control test (MC) and the D-KEFS Category Switching Condition of the Verbal Fluency task (SVF). Results also showed a simple time effect for the WAIS-IV Digit span and the Hayling tests. Moreover, there was an association between the SVF test and social participation (MPAI-4) at T2. In conclusion, the MC and SVF tests were found to be the best tools for measuring recovery of EFs following TBI. The SVF test was the most likely measure of EFs to give the neuropsychologist an idea of the patient's social participation. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to validate a scale that could help surgeons evaluate patients' psychological readiness to return to sport (RTS) after peroneal tendon pathology surgery. Methods: The Ankle Ligament Reconstruction‐Return to Sport after Injury (ALR‐RSI) scale, which had previously been validated in ankle ligament reconstruction patients, was adapted to evaluate the psychological preparedness for RTS in athletic patients who underwent peroneal tendinopathy surgery. The Foot and Ankle Outcome Score (FAOS) and Foot Ankle Ability Measurement (FAAM) scores were employed as patient‐related outcome measurement (PROM) instruments. Results: This study included 57 patients. There was a strong correlation between ALR‐RSI and both FAOS and FAAM (r = −0.68 and 0.74, respectively). ALR‐RSI was considerably higher in patients who returned to sports than in those who did not. The mean score was 72.9 ± 19.0 in patients who returned to the same preinjury level, 48.5 ± 24.0 in those who returned to a lower level and 53.6 ± 31.1 in patients who changed their athletic activity (p < 0.0001). Furthermore, ALR‐RSI showed at least a similar discrimination ability when compared to FAOS and FAAM. The test–retest intraclass correlation coefficient was 0.95. The Cronbach's α statistic used to measure the internal consistency was high (0.95). A Youden index of 0.65 was observed for a cut‐off score of 68 points. Conclusion: ALR‐RSI is a valid instrument for assessing psychological readiness to RTS in an athletic population following peroneal tendon surgery. When compared to the most commonly used PROMs, it was strongly correlated and demonstrated at least similar discrimination capacity. This could assist surgeons in identifying athletes who will have poor postoperative results and advising them on their capability to RTS. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

There is no clear census as to which operative technique provides better recovery for radial nerve injuries. Therefore, in this systematic review, we examined the functional recovery, patient-reported outcomes, and complications of tendon transfer (TT) and nerve transfer (NT). Five electronic databases were searched for studies (>10 cases per study) comparing NT and TT regardless of the study design (observational or experimental). Manual search was also conducted. The quality was assessed by the NIH tool. Outcomes included functional recovery, patient-reported outcomes (DASH score, satisfaction, and inability to return to work), and complications. The prevalence was pooled across studies using STATA software, and then, a subgroup analysis based on the intervention type. Twenty-one studies (542 patients) were analyzed. Excellent recovery, assessed by the Bincaz scale, was higher in the TT group (29 % vs. 11 %) as well as failure to extend the fingers (49 % vs. 9 %). No significant difference was noted between both groups regarding DASH score (mean difference = −2.76; 95 % CI: −12.66: 6.93). Satisfaction was great in the TT group (89 %) with a limited proportion of patients unable to return to work (7 %). Complications were slightly higher in the TT group (8 % vs. 7 %) while 18 % of patients undergoing TT requiring revision surgery. Radial deviation was encountered in 18 % of patients in the TT group and 0 % in the NT group. The quality was good, fair, and poor in 2, 13, and 6, respectively. In radial nerve injuries, although tendon transfer may seem to provide better functional motor recovery than nerve transfer, it is associated with a higher rate of failure to extend the finger. Given the large confidence interval, the accuracy of this finding is questioned. However, a great proportion of those patients require revision surgery afterward. Additionally, tendon transfer is associated with a greater complication rate than nerve transfer, particularly radial deviation. [ABSTRACT FROM AUTHOR]

Adoptive cell therapy (ACT) using ex vivo–expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell–intrinsic immunogenicity and mutational burden. Compared with nonresponders, CD8+ TILs exhibited increased cytotoxicity, exhaustion, and costimulation, whereas myeloid cells had increased type I interferon signaling in responders. Cell-cell interaction prediction analyses corroborated by spatial neighborhood analyses revealed that responders had rich baseline intratumoral and stromal tumor–reactive T cell networks with activated myeloid populations. Successful TIL-ACT therapy further reprogrammed the myeloid compartment and increased TIL-myeloid networks. Our systematic target discovery study identifies potential T-myeloid cell network–based biomarkers that could improve patient selection and guide the design of ACT clinical trials. Editor's summary: Adoptive cellular therapy with tumor-infiltrating lymphocytes (TIL-ACT) represents a promising immunotherapy alternative to immune checkpoint blockade, particularly in certain patients with advanced melanoma. Using single-cell transcriptomics and spatial proteomics, Barras et al. analyzed tumor specimens from patients with metastatic melanoma receiving ex vivo–expanded TIL-ACT through a phase 1 clinical trial. At baseline, tumors responding to TIL-ACT had more activated T cells, macrophages, and dendritic cells, which formed strong stimulatory interactions in responding tumors. After TIL-ACT, responders showed reprograming of myeloid cells including toward CXCL9+ macrophages and further expansion of T-myeloid cell networks. Together, these findings demonstrate that robust baseline supporting networks between intratumoral immune cells are strongly associated with response to TIL-ACT in metastatic melanoma. —Claire Olingy [ABSTRACT FROM AUTHOR]

Language barriers (LB) contribute to coronavirus disease 2019 (COVID-19) health inequities. People with LB were more likely to be SARS-CoV-2 positive despite lower testing and had higher rates of hospitalization. Data on hospital outcomes among immigrants with LB, however, are limited. We aimed to investigate the clinical outcomes of hospitalized COVID-19 cases by LB, immigration status, ethnicity, and access to COVID-19 health information and services prior to admission. Adults with laboratory-confirmed community-acquired COVID-19 hospitalized from March 1 to June 30, 2020, at four tertiary-care hospitals in Montréal, Quebec, Canada were included. Demographics, comorbidities, immigration status, country of birth, ethnicity, presence of LB, and hospital outcomes (ICU admission and death) were obtained through a chart review. Additional socio-economic and access to care questions were obtained through a phone survey. A Fine-Gray competing risk subdistribution hazards model was used to estimate the risk of ICU admission and in-hospital death by immigrant status, region of birth and LB Among 1093 patients, 622 (56.9%) were immigrants and 101 (16.2%) of them had a LB. One third (36%) of immigrants with LB did not have access to an interpreter during hospitalization. Admission to ICU and in-hospital mortality were not significantly different between groups. Prior to admission, one third (14/41) of immigrants with LB had difficulties accessing COVID-19 information in their mother tongue and one third (9/27) of non-white immigrants with a LB had difficulties accessing COVID-19 services. Immigrants with LB were inequitably affected by the first wave of the pandemic in Quebec, Canada. In our study, a large proportion had difficulties accessing information and services related to COVID-19 prior to admission, which may have increased SARS-CoV-2 exposure and hospitalizations. After hospitalization, a large proportion did not have access to interpreters. Providing medical information and care in the language of preference of increasing diverse populations in Canada is important for promoting health equity. [ABSTRACT FROM AUTHOR]

A significant factor in the antitumor immune response is the increased metabolic reprogramming of immunological and malignant cells. Increasing data points to the fact that cancer metabolism affects not just cancer signaling, which is essential for maintaining carcinogenesis and survival, but also the expression of immune cells and immune-related factors such as lactate, PGE2, arginine, IDO, which regulate the antitumor immune signaling mechanism. In reality, this energetic interaction between the immune system and the tumor results in metabolic competition in the tumor ecosystem, limiting the amount of nutrients available and causing microenvironmental acidosis, which impairs the ability of immune cells to operate. More intriguingly, different types of immune cells use metabolic reprogramming to keep the body and self in a state of homeostasis. The process of immune cell proliferation, differentiation, and performance of effector functions, which is crucial to the immune response, are currently being linked to metabolic reprogramming. Here, we cover the regulation of the antitumor immune response by metabolic reprogramming in cancer cells and immune cells as well as potential strategies for metabolic pathway targeting in the context of anticancer immunotherapy. We also discuss prospective immunotherapy-metabolic intervention combinations that might be utilized to maximize the effectiveness of current immunotherapy regimes. [ABSTRACT FROM AUTHOR]

Purpose: In this study we gathered and analyzed the available evidence regarding 17 different imaging modalities and performed network meta-analysis to find the most effective modality for the differentiation between brain tumor recurrence and post-treatment radiation effects. Methods: We conducted a comprehensive systematic search on PubMed and Embase. The quality of eligible studies was assessed using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. For each meta-analysis, we recalculated the effect size, sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio from the individual study data provided in the original meta-analysis using a random-effects model. Imaging technique comparisons were then assessed using NMA. Ranking was assessed using the multidimensional scaling approach and by visually assessing surface under the cumulative ranking curves. Results: We identified 32 eligible studies. High confidence in the results was found in only one of them, with a substantial heterogeneity and small study effect in 21% and 9% of included meta-analysis respectively. Comparisons between MRS Cho/NAA, Cho/Cr, DWI, and DSC were most studied. Our analysis showed MRS (Cho/NAA) and 18F-DOPA PET displayed the highest sensitivity and negative likelihood ratios. 18-FET PET was ranked highest among the 17 studied techniques with statistical significance. APT MRI was the only non-nuclear imaging modality to rank higher than DSC, with statistical insignificance, however. Conclusion: The evidence regarding which imaging modality is best for the differentiation between radiation necrosis and post-treatment radiation effects is still inconclusive. Using NMA, our analysis ranked FET PET to be the best for such a task based on the available evidence. APT MRI showed promising results as a non-nuclear alternative. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this trial is to (1) determine the best exercise modality to improve sleep quality and sleep architecture in people with Parkinson disease (PD); (2) investigate whether exercise-induced improvements in sleep mediate enhancements in motor and cognitive function as well as other non-motor symptoms of PD; and (3) explore if changes in systemic inflammation after exercise mediate improvements in sleep. Methods This is a multi-site, superiority, single-blinded randomized controlled trial. One hundred fifty persons with PD and sleep problems will be recruited and randomly allocated into 4 intervention arms. Participants will be allocated into 12 weeks of either cardiovascular training, resistance training, multimodal training, or a waiting list control intervention. Assessments will be conducted at baseline, immediately after each intervention, and 8 weeks after each intervention by blinded assessors. Objective sleep quality and sleep architecture will be measured with polysomnography and electroencephalography. Motor and cognitive function will be assessed with the Unified PD Rating Scale and the Scale for Outcomes in PD-Cognition, respectively. Subjective sleep quality, fatigue, psychosocial functioning, and quality of life will be assessed with questionnaires. The concentration of inflammatory biomarkers in blood serum will be assessed with enzyme-linked immunosorbent assays. Impact This study will investigate the effect of different types of exercise on sleep quality and architecture in PD, exploring interactions between changes in sleep quality and architecture with motor and cognitive function and other non-motor symptoms of the disease as well as mechanistic interactions between systemic inflammation and sleep. The results will provide important practical information to guide physical therapists and other rehabilitation professionals in the selection of exercise and the design of more personalized exercise–based treatments aimed at optimizing sleep, motor, and cognitive function in people with PD. [ABSTRACT FROM AUTHOR]

This study aims to investigate the spillover effects from geopolitical risks (proxied by the geopolitical risk index) and cryptocurrencies-related uncertainty (proxied by the Cryptocurrency Uncertainty Index) to cryptocurrencies. We utilise the Baruník and Křehlík (2018) framework to detect timefrequency connectedness. Our investigation for the period 2017 to 2022 discovers significant spillover effects from both indices to cryptocurrencies. Utilising the information transmission theory and network graphs, our findings reveal that some cryptocurrencies function as net receivers of spillovers from geopolitical risks and uncertainty in the short-term, while over longer time horizons they transform into net transmitters of spillovers to uncertainty. The study contributes to better understanding how uncertainty due to various factors (geopolitical, policy changes, regulatory changes, etc.) could affect the cryptocurrencies' markets. [ABSTRACT FROM AUTHOR]