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Aim: Metal nanoclusters are emerging nanomaterials applicable for drug delivery. Here, the toxicity and oxidative stress induction of divalent cationic cadmium (Cd2+) was compared with a Cd in the form of nanocluster. Then, it was used for targeted drug delivery into breast cancer cell lines. Methods: Using a green chemistry route, a Cd nanocluster (Cd-NC) was synthesized based on bovine serum albumin. After characterization, its genotoxicity and oxidative stress induction were studied in both in vitro and in vivo. After that, it was conjugated with hyaluronic acid (HA). The efficiency of hyaloronized-Cd-CN (HA-Cd-NC) for loading and releasing crocin (Cro), an anticancer phytochemical, was studied. Finally, it was applied for cell death induction in a panel of breast cancer cell lines. Results: The comet assay results indicated that, unlike Cd2+ and potassium permanganate (KMnO4), no genotoxicity and oxidative stress was induced by Cd-NC in vitro. Then, the pharmacokinetics of this Cd-NC was studied in vivo. The data showed that Cd-NC has accumulated in the liver and excreted from the feces of mice. Unlike Cd2+, no toxicity and oxidative stress were induced by this Cd-NC in animal tissues. Then, the Cd-NC was targeted toward breast cancer cells by adding HA, a ligand for the CD44 cell surface receptor. After that, Cro was loaded on HA-Cd-NC and it was used for the treatment of a panel of human breast cancer cell lines with varying degrees of CD44. The half-maximal drug inhibitory concentration (IC50) of Cro was significantly decreased when it was loaded on HA-Cd-NC, especially in MDA-MB-468 with a higher degree of CD44 at the surface. These results indicate the higher toxicity of Cro toward breast cancers when carried out by HA-Cd-NC. Conclusions: The Cd-NC was completely safe and is a promising candidate for delivering anticancer drugs/phytochemicals into the targeted breast tumors.

Abstract A common feature of collapse models and an expected signature of the quantization of gravity at energies well below the Planck scale is the deviation from ordinary quantum-mechanical behavior. Here, we analyze the general consequences of such modifications from the point of view of quantum information theory and we anticipate applications to different quantum systems. We show that quantum systems undergo corrections to the quantum speed limit which, in turn, imply the modification of the Heisenberg limit for parameter estimation. Our results hold for a wide class of scenarios beyond ordinary quantum mechanics. For some nonlocal models inspired by quantum gravity, the bounds are found to oscillate in time, an effect that could be tested in future high-precision quantum experiments.

Abstract In this work, we show that quantum state discrimination can be modified due to a change in the underlying topology of a system. In particular, we explicitly demonstrate that the quantum state discrimination of systems with underlying discrete topology differs from that of systems with underlying continuous topology. Such changes in the topology of a spacetime can occur in certain quantum gravity approaches. In fact, all approaches to quantum gravity can be classified into two types: those with underlying continuous topology (such as string theory) and those with an underlying discrete topology (such as loop quantum gravity). We demonstrate that the topology of these two types of quantum gravity approaches has different effects on the quantum state discrimination of low-energy quantum systems. We also show that any modification of quantum mechanics, which does not change the underlying topology, does not modify quantum state discrimination.

Abstract Assuming that Quantum Mechanics is universal and that it can be applied over all scales, then the Universe is allowed to be in a quantum superposition of states, where each of them can correspond to a different space-time geometry. How can one then describe the emergence of the classical, well-defined geometry that we observe? Considering that the decoherence-driven quantum-to-classical transition relies on external physical entities, this process cannot account for the emergence of the classical behaviour of the Universe. Here, we show how models of spontaneous collapse of the wavefunction can offer a viable mechanism for explaining such an emergence. We apply it to a simple General Relativity dynamical model for gravity and a perfect fluid. We show that, by starting from a general quantum superposition of different geometries, the collapse dynamics leads to a single geometry, thus providing a possible mechanism for the quantum-to-classical transition of the Universe. Similarly, when applying our dynamics to the physically-equivalent Parametrised Unimodular gravity model, we obtain a collapse on the basis of the cosmological constant, where eventually one precise value is selected, thus providing also a viable explanation for the cosmological constant problem. Our formalism can be easily applied to other quantum cosmological models where we can choose a well-defined clock variable.

Abstract Background The COVID-19 pandemic had socioeconomic effects in Africa. This study assessed the social and economic determinants of healthcare utilization during the first wave of COVID-19 among adults in Ghana. Methods Information about individuals residing in Ghana was derived from a survey conducted across multiple countries, aiming to evaluate the impact of the COVID-19 pandemic on the mental health and overall well-being of adults aged 18 and above. The dependent variable for the study was healthcare utilization (categorized as low or high). The independent variables were economic (such as financial loss, job loss, diminished wages, investment/retirement setbacks, and non-refunded travel cancellations) and social (including food scarcity, loss of financial support sources, housing instability, challenges affording food, clothing, shelter, electricity, utilities, and increased caregiving responsibilities for partners) determinants of health. A multinomial logistic regression was conducted to identify factors associated with healthcare utilization after adjusting for confounders (age, gender, access to medical insurance, COVID-19 status, educational background, employment, and marital status of the participants). Results The analysis included 364 responses. Individuals who encountered a loss of financial support (AOR: 9.58; 95% CI: 3.44–26.73; p

Collaborative multitarget search and navigation (CMTSN) is highly demanded in complex missions such as rescue and warehouse management. Traditional centralized and decentralized approaches fall short in terms of scalability and adaptability to real‐world complexities such as unknown targets and large‐scale missions. This article addresses this challenging CMTSN problem in three‐dimensional spaces, specifically for agents with local visual observation operating in obstacle‐rich environments. To overcome these challenges, this work presents the POsthumous Mix‐credit assignment with Attention (POMA) framework. POMA integrates adaptive curriculum learning and mixed individual‐group credit assignments to efficiently balance individual and group contributions in a sparse reward environment. It also leverages an attention mechanism to manage variable local observations, enhancing the framework's scalability. Extensive simulations demonstrate that POMA outperforms a variety of baseline methods. Furthermore, the trained model is deployed over a physical visual drone swarm, demonstrating the effectiveness and generalization of our approach in real‐world autonomous flight.

To investigate factors associated with healthcare utilization by adults in the Kingdom of Saudi Arabia (KSA) during the COVID-19 pandemic. Based on Andersen’s Behavioral Model of Health Services utilization, we conducted logistic regressions to determine the relationship between predisposing factors (age, gender, education, employment status), need factors (critical medical needs), and enabling factors (insurance coverage, financial loss) on healthcare utilization (challenges accessing medical health care needs, resorting to alternative care, unable to attend medical appointments) as the main outcome. Data of 958 adults residing in KSA were extracted. Financial loss increased the odds of challenges in accessing healthcare (OR: 1.73) and lowered the odds of resorting to alternative medical care (OR: 0.63) and inability to attend healthcare appointments (OR: 0.55). Public insurance increased the odds of skipping healthcare appointments (OR: 1.62). Need factors were associated with lower odds of facing challenges accessing healthcare (OR: 0.37), higher odds of resorting to alternative medical care (OR: 5.65), and failure to attend healthcare appointments (OR: 1.92) respectively. Factors known to enable healthcare utilization should be continuously evaluated during emergency situations. Alternative routes of health provision, along with proper health education, should be accessible to all socioeconomic groups.

Background: This study aimed to assess the longevity of serologic response and seroconversion rates at several time points following TCV vaccination among children living with HIV aged 6 months to 15 years in Pakistan., Methods: From November 20, 2020, to January 2, 2021; 336 children were enrolled and followed up prospectively for 12 months. Blood samples were collected before the administration of TCV and at 4-6 weeks, 6 months, and 1 year after administration of a single dose (0.5 ml) of intramuscular Typbar TCV®. Samples were analyzed for anti-Vi-IgG antibodies using ELISA. Geometric mean titers (GMTs), seroconversion rates (fourfold rise in anti-Vi-IgG from baseline) were assessed, and factors associated with sustained seroconversion at 1 year were evaluated using generalized linear mixed models., Findings: The seroconversion rates were significantly lower in children aged 6 months to 5 years compared to children > 5 years; (127/216 (58·8%)) versus (81/111 (73·0%)) at 6 months and (110/217 (50·7%)) versus (78/109 (71·6%)) at 1 year, only two-third; 188/326 (57·7%) remained seroconverted at 1 year. The GMTs (95 % CI) were significantly lower in children aged 6 months to 5 years compared to children > 5 years, 9·6 (7·6, 12·0) versus 28·9 (20·2, 41·4) at 6 months, and 6·6 (5·4, 8·0) versus 23·1 (16·4, 32·5) at 1 year time point. The odds of sustained seroconversion significantly decreased with time (adjusted odds ratio (aOR): 0.23; 95 % CI: 0.14, 0.40). The odds of sustained seroconversion following 1 year of TCV vaccination were significantly higher among children with non-severe HIV clinical disease (aOR: 10·61; 95% CI: 1·52, 73·98) and children in elder age group (aOR: 7·45; 95% CI: 1·18, 47·03)., Conclusions: A significant decrease in seroconversion rates was observed among children living with HIV following one year of TCV administration. The decline was significantly higher in children with severe or advanced HIV clinical disease and children younger than five years of age., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Abstract: Orthostatic hypotension is a prevalent clinical condition, caused by heterogenous etiologies and associated with significant morbidity and mortality. Management is particularly challenging in patients with uncontrolled hypertension. A thorough assessment is needed to draw an appropriate management plan. The treatment aims to improve postural symptoms while minimizing side effects and reducing iatrogenic exacerbation of supine hypertension. A personalized management plan including rationalizing medications, patient education, identification, and avoidance of triggers, as well as nonpharmacological therapies such as compression devices, dietary modifications, and postural aids, make the first steps. Among pharmacological therapies, midodrine and fludrocortisone are the most prescribed and best studied; pyridostigmine, atomoxetine, and droxidopa are considered next. Yohimbine remains an investigational agent. A multidisciplinary team may be required in some patients with multiple comorbidities and polypharmacy. However, there is a lack of robust efficacy and safety evidence for all therapies. Building robust real-world and stratified clinical trials based on underlying pathophysiology may pave the way for further drug development and better clinical strategies and in this challenging unmet medical need., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

NiFe-based nanomaterials are extensively studied as one of the promising candidates for the oxygen evolution reaction (OER). However, their practical application is still largely impeded by the unsatisfied activity and poor durability caused by the severe leaching of active species. Herein, a rapid and facile combustion method is developed to synthesize the vertical graphene (VG) supported N-doped carbon modified (Ni x Fe 1-x )Se composites (NC@(Ni x Fe 1-x )Se/VG). The interconnected heterostructure of obtained materials plays a vital role in boosting the catalytic performance, offering rich active sites and convenient pathways for rapid electron and ion transport. The incorporation of Se into NiFe facilitates the formation of active species via in situ surface reconstruction. According to density functional theory (DFT) calculations, the in situ formation of a Ni 0.75 Fe 0.25 Se/Ni 0.75 Fe 0.25 OOH layer significantly enhances the catalytic activity of NC@(Ni x Fe 1-x )Se/VG. Furthermore, the surface-adsorbed selenoxide species contribute to the stabilization of the catalytic active phase and increase the overall stability. The obtained NC@(Ni x Fe 1-x )Se/VG exhibits a low overpotential of 220 mV at 20 mA cm -2 and long-term stability over 300 h. This work offers a novel perspective on the design and fabrication of OER electrocatalysts with high activity and stability., (© 2024 Wiley‐VCH GmbH.)

Introduction: Kartagener syndrome is rare, with an incidence of 1 in 32,000 live births. It consists of a triad of bronchiectasis, situs inversus, and sinusitis. Normally, the middle lobe is part of the right lung, but due to situs inversus, the middle lobe is part of the left lung, making it prone to bronchiectasis and infections., Case Report: We present a unique case of a 16-year-old adolescent with a known history of Kartagener syndrome who presented with recurrent chest infections and hemoptysis refractory to conservative management. He was diagnosed with bronchiectasis of the left middle lobe through a computed tomography (CT) scan and subsequently underwent a posterolateral thoracotomy and left middle lobectomy. This is a rare finding with limited literature available on such cases, to the best of our knowledge., Discussion: Conservative treatment is usually the first line of approach. However, in cases of recurrent chest infections and hemoptysis, surgical management is considered to prevent the infection from spreading to the healthy lung and to avoid life-threatening complications when medical therapy fails. Surgical intervention, while more invasive, can provide a definitive solution and improve the patient's quality of life., Conclusion: Early diagnosis of Kartagener syndrome is crucial for determining the appropriate management course. In patients presenting with recurrent hemoptysis and chest infections, surgical resection is an effective treatment approach to prevent complications and enhance long-term outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Interictal spikes are electroencephalographic discharges that occur at or near brain regions that produce epileptic seizures. While their role in generating seizures is not well understood, spikes have profound effects on cognition and behaviour, depending on where and when they occur. We previously demonstrated that spiking areas of human neocortex show sustained MAPK activation in superficial cortical Layers I-III and are associated with microlesions in deeper cortical areas characterized by reduced neuronal nuclear protein staining and increased microglial infiltration. Based on these findings, we chose to investigate additional neuronal populations within microlesions, specifically inhibitory interneurons. Additionally, we hypothesized that spiking would be sufficient to induce similar cytoarchitectonic changes within the rat cortex and that inhibition of MAPK signalling, using a MAP2K inhibitor, would not only inhibit spike formation but also reduce these cytoarchitectonic changes and improve behavioural outcomes. To test these hypotheses, we analysed tissue samples from 16 patients with intractable epilepsy who required cortical resections. We also utilized a tetanus toxin-induced animal model of interictal spiking, designed to produce spikes without seizures in male Sprague-Dawley rats. Rats were fitted with epidural electrodes, to permit EEG recording for the duration of the study, and automated algorithms were implemented to quantify spikes. After 6 months, animals were sacrificed to assess the effects of chronic spiking on cortical cytoarchitecture. Here, we show that microlesions may promote excitability due to a significant reduction of inhibitory neurons that could be responsible for promoting interictal spikes in superficial layers. Similarly, we found that the induction of epileptic spikes in the rat model produced analogous changes, including reduced neuronal nuclear protein, calbindin and parvalbumin-positive neurons and increased microglia, suggesting that spikes are sufficient for inducing these cytoarchitectonic changes in humans. Finally, we implicated MAPK signalling as a driving force producing these pathological changes. Using CI-1040 to inhibit MAP2K, both acutely and after spikes developed, resulting in fewer interictal spikes, reduced microglial activation and less inhibitory neuron loss. Treated animals had significantly fewer high-amplitude, short-duration spikes, which correlated with improved spatial memory performance on the Barnes maze. Together, our results provide evidence for a cytoarchitectonic pathogenesis underlying epileptic cortex, which can be ameliorated through both early and delayed MAP2K inhibition. These findings highlight the potential role for CI-1040 as a pharmacological treatment that could prevent the development of epileptic activity and reduce cognitive impairment in both patients with epilepsy and those with non-epileptic spike-associated neurobehavioural disorders., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Exaggerated lung strain and stress could damage lungs in anesthetized children. The authors hypothesized that the association of capnoperitoneum and lung collapse in anesthetized children increases lung strain-stress. Their primary aim was to describe the impact of capnoperitoneum on lung strain-stress and the effects of an individualized protective ventilation during laparoscopic surgery in children., Methods: The authors performed an observational cohort study in healthy children aged 3 to 7 yr scheduled for laparoscopic surgery in a community hospital. All received standard protective ventilation with 5 cm H2O of positive end-expiratory pressure (PEEP). Children were evaluated before capnoperitoneum, during capnoperitoneum before and after lung recruitment and optimized PEEP (PEEP adjusted to get end-expiratory transpulmonary pressure of 0), and after capnoperitoneum with optimized PEEP. The presence of lung collapse was evaluated by lung ultrasound, positive Air-Test (oxygen saturation measured by pulse oximetry 96% or less breathing 21% O2 for 5 min), and negative end-expiratory transpulmonary pressure. Lung strain was calculated as tidal volume/end-expiratory lung volume measured by capnodynamics, and lung stress as the end-inspiratory transpulmonary pressure., Results: The authors studied 20 children. Before capnoperitoneum, mean lung strain was 0.20 ± 0.07 (95% CI, 0.17 to 0.23), and stress was 5.68 ± 2.83 (95% CI, 4.44 to 6.92) cm H2O. During capnoperitoneum, 18 patients presented lung collapse and strain (0.29 ± 0.13; 95% CI, 0.23 to 0.35; P < 0.001) and stress (5.92 ± 3.18; 95% CI, 4.53 to 7.31 cm H2O; P = 0.374) increased compared to before capnoperitoneum. During capnoperitoneum and optimized PEEP, children presenting lung collapse were recruited and optimized PEEP was 8.3 ± 2.2 (95% CI, 7.3 to 9.3) cm H2O. Strain returned to values before capnoperitoneum (0.20 ± 0.07; 95% CI, 0.17 to 0.22; P = 0.318), but lung stress increased (7.29 ± 2.67; 95% CI, 6.12 to 8.46 cm H2O; P = 0.020). After capnoperitoneum, strain decreased (0.18 ± 0.04; 95% CI, 0.16 to 0.20; P = 0.090), but stress remained higher (7.25 ± 3.01; 95% CI, 5.92 to 8.57 cm H2O; P = 0.024) compared to before capnoperitoneum., Conclusions: Capnoperitoneum increased lung strain in healthy children undergoing laparoscopy. Lung recruitment and optimized PEEP during capnoperitoneum decreased lung strain but slightly increased lung stress. This little rise in pulmonary stress was maintained within safe, lung-protective, and clinically acceptable limits., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Background Teledentistry, defined as the use of telecommunication technologies for dental care, has emerged as a transformative approach to oral health services. This prospective observational analysis aims to comprehensively assess the impact of teledentistry on patient outcomes and satisfaction, addressing key aspects such as diagnostic accuracy, longitudinal treatment outcomes, and economic and logistical considerations. Methods The study involved 242 participants selected from diverse dental clinics offering teledentistry services. Participants could choose between traditional in-person visits and teledentistry consultations. The teledentistry interventions included remote consultations, diagnostic evaluations, and treatment planning facilitated through virtual communication tools. Baseline assessments captured initial dental conditions, and follow-up assessments were conducted at three, six, and 12 months. Outcome measures included diagnostic accuracy, patient satisfaction, changes in dental conditions over time, and economic and logistical feedback. Results Descriptive statistics revealed baseline characteristics, with participants evenly distributed between in-person and teledentistry groups. However, the overall satisfaction with diagnoses was significantly lower in the teledentistry group as compared to the in-person group (p < 0.001). Longitudinal assessments demonstrated comparable changes in dental conditions between the two groups. Economic feedback highlighted a cost-saving advantage for teledentistry users, with 80% reporting reduced expenses. Conclusion This study highlights the transformative potential of teledentistry in expanding access to oral health services, reducing costs, and providing comparable treatment outcomes to traditional in-person care. Future efforts should focus on enhancing the teledentistry experience, addressing patient satisfaction concerns, and refining the delivery of remote dental care to maximize its benefits for both patients and healthcare systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Chatterjee et al.)

The design and experimental verification of a deeply implanted conformal printed antenna is presented. The hip implant acts as the ground plane for a coaxial-cable-fed trapezoidal radiator designed to transmit biological signals collected within the body by proper biosensors. The arrangement, consisting of a metallic (or equivalent) hip implant, bio-compatible gypsum-based dielectric, and conformal radiator, was tested when the hosting 3D-printed plastic bone was immersed in tissue-like liquid contained in a plastic bucket. The dimensions of the set-up are similar to a human leg. Matching and radiation characteristics are presented in the industrial, scientific, and medical (ISM) frequency band (2.4-2.5 GHz), showing the feasibility of the proposed arrangement.