bluuebunny/crossref_metadata_2025 huggingface dataset:
Eco-tourism as a reflection of sustainable living: Insights from Uzbekistan’s unique landscapes
Authors: Sakhibov Akram , Shonazarov Jamshid
Published: November 2024

This study examines eco-tourism as a reflection of sustainable living, focusing on its conceptual foundations and role in promoting environmental awareness and conservation. With a growing global interest in sustainable practices, eco-tourism offers a unique approach to experiencing nature while supporting ecological balance. The research highlights Uzbekistan's diverse landscapes, ranging from arid deserts to lush valleys and rugged mountains, as ideal settings for eco-tourism. These natural features provide immersive experiences for tourists and foster a deeper appreciation for environmental stewardship. The study also discusses recent reforms and developments in Uzbekistan aimed at enhancing ecotourism, demonstrating the country’s commitment to sustainable tourism practices. Findings indicate that eco-tourism can significantly contribute to sustainable development by promoting a green lifestyle and preserving natural heritage. The insights gained underscore the potential of eco-tourism in Uzbekistan to serve as a model for integrating ecological awareness into everyday life.
Processes of management of competitiveness of ecotourism destinations and methodology of its assessment
Authors: Hamidov Saidjon , Tokhirov Javlon , Adizov Bakhtiyor
Published: November 2024

Assessment of the competitiveness of existing tourist destinations in the regions requires the improvement of a comprehensive analysis methodology. As a result of this, in the future, the possibility of positive implementation of the measures developed to minimize risks in business activities in the destination area will increase. At the same time, issues of increasing the competitiveness of products and services created in tourist destinations are important in the development of the industry based on market laws and are considered one of the most important factors of economic stability. The article contains the opinions, conclusions and suggestions of the authors on the topic.
The relation of cluster headache to alexithymia, depression, and anxiety
Authors: İşcan Dilek , Dal Cansu
Published: November 2024

Background The pathophysiology of cluster headaches (CHs) involves the trigeminovascular system, the parasympathetic nervous system, and the hypothalamus. Because of the affected hypothalamus, there may be limbic system involvement in CH.

Objective To investigate the relationship between depression, anxiety, and alexithymia in CH, to demonstrate that the limbic system is affected.

Methods A total of 18 patients with CHs who were outside of cluster period and 18 healthy controls were included. Participants were administered the Beck depression inventory (BDI), Beck anxiety inventory (BAI), and Toronto alexithymia scale-20 (TAS-20).

Results Patients with CHs had significantly higher rates of alexithymia (p = 0.003) and depression (p = 0.014) than controls. There was no significant difference in anxiety levels (p = 0.297) between groups.

Conclusion It was shown that, in addition to previously identified psychiatric disorders, alexithymia can accompany CHs in patients.
Association of hyperventilation-induced heart rate variability and sudden unexpected death in epilepsy in drug-resistant epilepsy
Authors: Algin Demet Ilhan , Erdinc Oguz
Published: November 2024

Background Within the general epilepsy population, the incidence of Sudden Unexpected Death in Epilepsy (SUDEP) ranges from approximately 0.35 to 2.3 per 1,000 individuals per year.

Objective We aimed to evaluate the relationship between SUDEP risk factors and heart rate variability (HRV) parameters as a potential biomarker of SUDEP in patients with drug-resistant epilepsy (DRE).

Methods There were 52 patients diagnosed with DRE and under follow-up, and controls including 45 healthy subjects, included in the study. Hyperventilation-induced HRV (HRVHV) parameters, including the standard deviation of all RR intervals (SDRR), mean heart rate (HR), root mean squares of successive differences (RMSSD), SD of mean NN intervals recordings (SDANN), and HRV triangular index, were assessed during resting. To predict the risk of SUDEP, the relationship between HRV parameters and SUDEP risks was evaluated using the Risk Assessment for Sudden Death in Epilepsy (SUDEP-7) Risk Inventory.

Results No statistically significant difference was found in sympathetic skin response (SSR) latency and amplitudes between the patient and control groups. In comparing healthy control subjects with patients experiencing DRE, we observed significant decreases in SDRRHV and hyperventilation-induced RMSSD (RMSSDHV) values, specifically within HRVHV. Notably, a significant correlation emerged concerning the RMSSDHV values (p < 0.01), when examining the correlation between the SUDEP-7 inventory and HRVHV parameters.

Conclusion This correlation between RMSSDHV and the SUDEP-7 Risk Inventory in patients with DRE represents a novel and consequential finding, suggesting its potential as an indicator of SUDEP risk.
Efficacy and Safety Profile of Different Schedules of Adjuvant Trastuzumab Therapy among Patients with HER2-Positive Breast Cancer: Real-World Experience from a Tertiary Cancer Center in South India
Authors: Rajan Nandini Devi , Menon Abhilash , Shenoy Praveen Kumar , Avaronnan Manuprasad , Shahana Sherin , Therayangalath Bindu
Published: November 2024

One year of adjuvant trastuzumab is the standard of care for HER2-positive breast cancer. In low–middle income countries, delivery of 1-year trastuzumab is challenging due to significant financial burden. Evidence for shorter durations of adjuvant trastuzumab is gaining popularity in this regard. In this study, we compared the effectiveness and safety of 1 year versus shorter durations of adjuvant trastuzumab practiced in our center. In total, 312 patients were included in this analysis. The median age was 52 years. More than two-thirds of patients (67.6%) had stage 2 disease and majority were hormone-receptor-positive (62.5%). The median follow-up duration was 50 months. The 4-year disease-free survival was 97.3%. The 4-year disease-free survival for shorter durations of adjuvant trastuzumab was 98% compared with 96.7% in 1-year trastuzumab therapy group. In univariate analysis, stage at diagnosis was the only factor which had statistically significant association with disease-free survival. In multivariate analysis, none of the variables were found to be predictive of survival. Two patients (0.6%) had significant left ventricular ejection fraction decline.

Shorter durations of adjuvant trastuzumab have comparable 4-year disease-free survival to standard 1-year therapy and is an alternative adjuvant treatment option for HER2-positive breast cancer patients in resource-limited settings.
Enhanced oxygen evolution reaction in flexoelectric thin-film heterostructures
Authors: Xu Jibo , Zhang Xiaoyan , Liu Xia , Wu Ming , Liu Junzhe , Liu Zhiyu , Li Meiyue , Yue Yuhao , Xu Yawen , Dong Chenyu , Zheng Weijie , Zhu Lin , Cao Yanqiang , Zheng Chunyan , Liu Jianyi , Li Aidong , Wu Di , Zhang Lixue , Wen Zheng
Published: November 2024

Recently, the flexoelectric effect has triggered considerable interest in energy-related applications, such as flexo-actuation, flexo-photovoltaic, and flexo-catalysis, because of its ubiquitous feature allowing the creation of electric polarity, i.e., the flexoelectric polarization (Pflexo), in non-polar materials by strain gradient. Here, we show a flexoelectric strategy in electrocatalytic water splitting. Remarkably enhanced oxygen evolution reaction (OER) properties are achieved in strain-gradient LaFeO3 (LFO) thin-film heterostructures owing to the promotion of kinetic processes by Pflexo. The improved OER is demonstrated by increased current density of ∼300% in linear sweep voltammetry and lowered charge transfer resistance by two orders of magnitude in electrochemical impedance spectroscopy. These are ascribed to the flexoelectric-induced downward bending of the LFO band, as revealed by density functional theory calculations and band structure measurements. With Pflexo in the thin-film heterostructure catalysts, the adsorption of hydroxyl ions is strengthened on the polar LFO surface, and the transfer of electrons is accelerated from the reactants/key intermediates to the catalyst across the band-tilted LFO layer. These findings indicate the significance of flexoelectric effect in OER kinetics and open a new perspective for exploiting catalytic mechanisms and performances in water splitting.
Generation of 10 kT axial magnetic fields using multiple conventional laser beams: A sensitivity study for kJ PW-class laser facilities
Authors: Hao Jue Xuan , Tang Xiang , Arefiev Alexey , Kingham Robert J. , Zhu Ping , Shi Yin , Zheng Jian
Published: November 2024

Strong multi-kilotesla magnetic fields have various applications in high-energy density science and laboratory astrophysics, but they are not readily available. In our previous work [Y. Shi et al., Phys. Rev. Lett. 130, 155101 (2023)], we developed a novel approach for generating such fields using multiple conventional laser beams with a twist in the pointing direction. This method is particularly well-suited for multi-kilojoule petawatt-class laser systems like SG-II UP, which are designed with multiple linearly polarized beamlets. Utilizing three-dimensional kinetic particle-in-cell simulations, we examine critical factors for a proof-of-principle experiment, such as laser polarization, relative pulse delay, phase offset, pointing stability, and target configuration, and their impact on magnetic field generation. Our general conclusion is that the approach is very robust and can be realized under a wide range of laser parameters and plasma conditions. We also provide an in-depth analysis of the axial magnetic field configuration, azimuthal electron current, and electron and ion orbital angular momentum densities. Supported by a simple model, our analysis shows that the axial magnetic field decays owing to the expansion of hot electrons.
eIF5A controls mitoprotein import by relieving ribosome stalling at TIM50 translocase mRNA
Authors: Barba-Aliaga Marina , Bernal Vanessa , Rong Cynthia , Volfbeyn Madeleine E. , Zhang Keguang , Zid Brian M. , Alepuz Paula
Published: November 2024

Efficient import of nuclear-encoded proteins into mitochondria is crucial for proper mitochondrial function. The conserved translation factor eIF5A binds ribosomes, alleviating stalling at polyproline-encoding sequences. eIF5A impacts mitochondrial function across species, though the precise molecular mechanism is unclear. We found that eIF5A depletion in yeast reduces the translation and levels of the TCA cycle and oxidative phosphorylation proteins. Loss of eIF5A causes mitoprotein precursors to accumulate in the cytosol and triggers a mitochondrial import stress response. We identify an essential polyproline protein as a direct target of eIF5A: the mitochondrial inner membrane protein and translocase component Tim50. Thus, eIF5A controls mitochondrial protein import by alleviating ribosome stalling along Tim50 mRNA at the mitochondrial surface. Removal of polyprolines from Tim50 partially rescues the mitochondrial import stress response and translation of oxidative phosphorylation genes. Overall, our findings elucidate how eIF5A impacts the mitochondrial function by promoting efficient translation and reducing ribosome stalling of co-translationally imported proteins, thereby positively impacting the mitochondrial import process.
A new approach of generalized shifted Vieta-Fibonacci polynomials to solve nonlinear variable order time fractional Burgers-Huxley equations
Authors: Avazzadeh Zakieh , Hassani Hossein , Ebadi Mohammad Javad , Eshkaftaki Ali Bayati
Published: November 2024

In recent years, advancements in optimization techniques and the widespread availability of high-performance computing have made it increasingly feasible to study and develop approximation strategies for nonlinear models. This progress has empowered researchers to address more intricate and realistic challenges associated with these models. This paper introduces the application of a novel polynomial, the generalized shifted Vieta-Fibonacci polynomials (GSVFPs), in solving nonlinear variable order time fractional Burgers-Huxley equations. To mitigate storage and computational costs, new operational matrices (OMs) are devised. The proposed algorithm integrates GSVFPs, OMs, and Lagrange multipliers to achieve optimal approximations. Through convergence analysis and numerical examples, the effectiveness and accuracy of the proposed algorithm in solving these equations are demonstrated. The provided numerical illustrations further bolster this assertion.
Constraining the average magnetic field in galaxy clusters with current and upcoming CMB surveys
Authors: Muralidhara Vyoma , Basu Kaustuv
Published: November 2024

Galaxy clusters that host radio halos indicate the presence of population(s) of non-thermal electrons. These electrons can scatter low-energy photons of the Cosmic Microwave Background, resulting in the non-thermal Sunyaev-Zeldovich (ntSZ) effect. We measure the average ntSZ signal from 62 radio-halo hosting clusters using the Planck multi-frequency all-sky maps. We find no direct evidence of the ntSZ signal in the Planck data. Combining the upper limits on the non-thermal electron density with the average measured synchrotron power collected from the literature, we place lower limits on the average magnetic field strength in our sample. The lower limit on the volume-averaged magnetic field is 0.01–0.24 μG, depending on the assumed power-law distribution of electron energies. We further explore the potential improvement of these constraints from the upcoming Simons Observatory and Fred Young Submillimeter Telescope (FYST) of the CCAT-prime collaboration. We find that combining these two experiments, the constraints will improve by a factor of

two, which can be sufficient to rule out some power-law models.
High-count-rate particle tracking in proton and carbon radiotherapy with Timepix2 operated in ultra-short acquisition time
Authors: Oancea C. , Resch A. , Barna S. , Magrin G. , Grevillot L. , Hladik D. , Marek L. , Jakubek J. , Granja C.
Published: November 2024

This work investigates the operational acquisition time limits of Timepix3 and Timepix2
detectors operated in frame mode for high-count rate of high deposited energy transfer
particles. Measurements were performed using alpha particles from a 241Am laboratory source
and proton and carbon ion beams from a synchrotron accelerator. The particle count rate upper
limit is determined by overlapping per-pixel particle signals, identifiable by the hits per pixel
counter > 2, indicating the need to decrease acquisition time. On the other hand, the lower
limit is the time required to collect the particle deposited charge while maintaining spectral
properties. Different acquisition times were evaluated for an AdvaPIX Timepix3 detector (500 μm Silicon sensor) with standard per-pixel

Digital to Analog Converter (DAC)
settings and a Minipix Timepix2 detector (300 μm Silicon sensor) with standard and customized settings the pulse shaping parameter and
threshold. For AdvaPIX Timepix3, spectra remained accurate down to 100 μs frame acquisition
time; at 10 μs, loss of collected charge occurred, suggesting either avoiding this acquisition
time or applying a correction. Timepix2 allowed acquisition times down to 100 ns for single
particle track measurements even for high energy loss, enabled by a new Timepix2 feature delaying
shutter closure until full particle charge collection. This work represents the first measurement
utilizing Timepix-chips pixel detectors in an accelerator beam of clinical energy and intensity
without the need to decrease the beam current. This is made possible by exploiting the short
shutter feature in Timepix2 and a customized per-pixel energy calibration of the Timepix2 detector
with a larger discharging signal value which allowed for shorter

Time-over-Threshold (ToT)
signal. These customized
settings extend the operation of the pixel detectors to higher event rates up to 109
particles/cm2/s.
High-resolution geophysical monitoring of moisture accumulation preceding slope movement—a path to improved early warning
Authors: Watlet Arnaud , Wilkinson Paul , Whiteley Jim , White Adrian , Uhlemann Sebastian , Swift Russell , Ouellet Susanne , Minto Chris , Meldrum Philip , Jones Lee , Gunn David , Godfrey Alastair , Dashwood Ben , Crickmore Roger , Clarkson Paul , Boyd James , Chambers Jonathan
Published: November 2024

Slope failures are an ongoing global threat leading to significant numbers of fatalities and infrastructure damage. Landslide impact on communities can be reduced using efficient early warning systems to plan mitigation measures and protect elements at risk. This manuscript presents an innovative geophysical approach to monitoring landslide dynamics, which combines electrical resistivity tomography (ERT) and low-frequency distributed acoustic sensing (DAS), and was deployed on a slope representative of many landslides in clay rich lowland slopes. ERT is used to create detailed, dynamic moisture maps that highlight zones of moisture accumulation leading to slope instability. The link between ERT derived soil moisture and the subsequent initiation of slope deformation is confirmed by low-frequency DAS measurements, which were collocated with the ERT measurements and provide changes in strain at unprecedented spatiotemporal resolution. Auxiliary hydrological and slope displacement data support the geophysical interpretation. By revealing critical zones prone to failure, this combined ERT and DAS monitoring approach sheds new light on landslide mechanisms. This study demonstrates the advantage of including subsurface geophysical monitoring techniques to improve landslide early warning approaches, and highlights the importance of relying on observations from different sources to build effective landslide risk management strategies.
Nanoscale sintering of zinc micropowders for high conductivity and sensing applications of transient electronics
Authors: Pamuła Zuzanna , Słoma Marcin
Published: November 2024

In the face of new social and environmental challenges, there is a need for an alternative approach to the fabrication of electronics. Increasing demand for smart healthcare applications or the growing e-waste problems inspired the work on new adaptations and materials for biodegradable, bioresorbable or even edible electronics. Such a trend is called transient electronics, which is a response to the mentioned problems, yet efficient and affordable fabrication of such elements is challenging. We report a broader approach to the application of zinc inks for printed electronics and a nanochemical sintering approach with several types of organic acids. Selectively spray-printed fine zinc microparticles subjected to acetic, lactic, malonic, ethylmalonic and citric acids were evaluated for obtaining the lowest electrical resistivity and its variations induced by the amount of applied acids. Resulting sintered Zn patterns exhibited sheet resistivity values as low as 15 · 10−2 Ω sq−1. Not all acids are suitable for fabricating stable, conductive paths, as in the case of citric and ethylmalonic acids. On the other hand, with malonic acid, there was a wide range of resistance changes in the function of applied acid doses (from one to fifteen), suggesting application as a chemical sensor for acid concentration. Such results suggest that with a low-cost zinc powder, absorbable by living organisms and disintegrating in the natural environment, using common organic acids, we can efficiently fabricate printed electronic circuits and sensors for transient electronics applications.
The development of paliperidone nanocrystals for the treatment of schizophrenia
Authors: Lhaglham Phattalapol , Jiramonai Luksika , Liang Xing-Jie , Liu Bingchuan , Li Fangzhou
Published: November 2024

Schizophrenia is a complex and chronic psychiatric disorder that significantly impacts patients’ quality of life. Ranking 12th among 310 diseases and injuries that result in disability, the number of patients suffering from schizophrenia continues to rise, emphasizing the urgent need for developing effective treatments. Despite the availability of effective antipsychotic drugs, over 80% of patients taking oral antipsychotics experience relapses, primarily caused by non-adherence as the high dosing frequency is required. In this review, we discuss about schizophrenia, its incidence, pathological causes, influencing factors, and the challenges of the current medications. Specifically, we explore nanocrystal technology and its application to paliperidone, making it one of the most successful long-acting antipsychotic drugs introduced to the market. We highlight the clinical advantages of paliperidone nanocrystals, including improved adherence, efficacy, long-term outcomes, patient satisfaction, safety, and cost-effectiveness. Additionally, we address the physicochemical factors influencing the drug’s half-life, which crucially contribute to long-acting medications. Further studies on nanocrystal-based long-acting medications are crucial for enhancing their effectiveness and reliability. The successful development of paliperidone nanocrystals holds great promise as a significant approach for drug development, with potential applications for other chronic disease management.
The Impact of the Number and Duration of Treatments With a 1064 nm Diode Laser on Adipocyte Apoptosis: Implications for Noninvasive Fat Reduction Strategies
Authors: Salameh Fares , Lazzarini Ariane , Kenkel Jeffrey , Akgul Yucel
Published: November 2024

Background

Noninvasive treatment with a 1064 nm diode laser, generating hypodermal temperatures between 42 and 47 °C, induces adipocyte cell death, offering a solution to reduce fat in problematic areas.

Objectives

The objective of the authors of this study is to determine whether a 15 min treatment provides similar efficacy as the standard 25 min treatment.

Methods

Pigs underwent a 15 or 25 min 1064 nm laser treatment on 6 × 6 cm areas of abdominal skin. Single treatments were administered 14 or 28 days before biopsy, whereas dual treatments were performed at both 14 and 28 days prebiopsy. Hematoxylin and TUNEL staining were used to detect histological changes and apoptosis in harvested skin tissue.

Results

Pig skin subjected to a 25 min diode laser treatment exhibited nearly twice the apoptotic counts in the hypodermis compared with the 15 min treatment (10.5 vs 5.7) at 28 days following treatment. The degree of apoptosis increased with time following the treatment, with nearly twice the apoptosis counts at 28 days than at 14 days following a single 25 min treatment (10.5 vs 5.8). When testing 1 vs 2 treatments, 2 treatments (28 and 14 days before harvesting the tissue) did not result in significantly higher apoptosis than 1 treatment 28 days before harvesting. Apoptosis was primarily localized to adipocytes in the hypodermis and the dermis/hypodermis junction. There were no adverse side effects in the animals.

Conclusions

The degree of apoptosis following a 1064 nm laser treatment was proportional to the treatment duration. The 25 min treatment produced significantly more apoptosis than the 15 min treatment. The process of apoptosis continued over several weeks.

Level of Evidence: 4 (Therapeutic)
Maternal undernutrition in the first eighty days of gestation negatively programs ovarian development in dairy calves
Authors: Frau Adele , Edache David , Sale Sebastiano , Gallo Antonio , Miragliotta Vincenzo , Lazzarini Giulia , Corda Andrea , Corda Francesca , Barbato Olimpia , Succu Sara , Bebbere Daniela , Franciosi Federica , Atzori Alberto S , Mossa Francesca
Published: November 2024

We hypothesized that in dairy cattle maternal energy restriction applied during two gestational windows (up to day 80 or 120 of gestation) impairs ovarian and cardiovascular development in juvenile female offspring. We also investigated the role of maternal leptin and testosterone in developmental programming in calves. Holstein-Friesian heifers were randomly assigned to one of three experimental groups; starting 10 days before artificial insemination, they were individually fed at (i) 0.6 of their maintenance energy requirements (M) up to day 80 (Nutrient Restricted, NR80) or (ii) day 120 of gestation (NR120); (iii) 1.8 M until day 120 of pregnancy (Control). Plasma leptin concentrations increased transiently in nutritionally restricted heifers pregnant with a single female calf, but maternal testosterone concentrations were not influenced by diet. Calves had similar body growth, but daughters of NR80 and NR120 had impaired ovarian development, as assessed by reduced gonadal weight, fewer surface antral and primary follicles, and recovered cumulus-oocyte complexes, as well as lower circulating anti-Müllerian hormone concentrations. Cardiovascular morphology and function in the offspring were not influenced by maternal diet, as determined by peripheral arterial blood pressure, echocardiography, post-mortem heart weight, and aortic circumference. Regardless of its duration (until day 80 or 120 of gestation), nutritional restriction resulted in a similar alteration of ovarian development in juvenile progeny, but cardiovascular development was unaltered. Evidence suggests that the window of development that encompasses the peri-ovulatory period to the first 2.6 months of gestation is critical in ovarian programming and that maternal leptin may be involved.
Management of knee osteoarthritis using bone marrow aspirate concentrate: a systematic review
Authors: Migliorini Filippo , Pilone Marco , Ascani Jacopo , Schäfer Luise , Jeyaraman Madhan , Maffulli Nicola
Published: November 2024

Introduction

Knee osteoarthritis (OA) is a common degenerative joint condition and a major cause of disability in the general population.

Source of data

Recent published literature identified from PubMed, EMBASE, Google Scholar, and Scopus.

Areas of agreement

Orthobiological therapies try to regenerate articular cartilage and stop the progression of the degenerative lesion. Intra-articular injections of biological derivates have been increasingly used in the last decade.

Areas of controversy

The indications for the use of bone marrow aspirate concentrate (BMAC) are still unclear.

Growing points

We systematically reviewed the current literature on BMAC in the management of knee OA, giving an update on the current indications for the selection of the ideal patient and the preparations and efficacy of BMAC compared to other biological alternatives.

Areas timely for developing research

BMAC is a valuable source of mesenchymal stem cells, offering potential benefits in attenuating the inflammatory pathway associated with knee OA. Intra-articular injection of BMAC has shown effectiveness in clinical trials improving functional outcomes of knee OA patients. The superiority of BMAC over other orthobiological treatments cannot be assessed because of conflicting results.
Online transcranial magnetic stimulation reveals dynamic interactions between language control and processing in bilingual language production
Authors: Wu Junjie , Ji Yannan , Cai Chuyao , Pu Xinping , Wang Qiping , Yan Guoli , Wang Qiang , Wang Xin
Published: November 2024

Language production in bilinguals relies on the collaborative interaction between two neural systems: the language control system (e.g. the right inferior frontal gyrus) and the language processing system (e.g. the left superior temporal gyrus). However, the causal mapping between these brain systems and their cognitive functions, as well as the temporal dynamics between these two systems during bilingual language production, remain unclear. To investigate this, our study applied online transcranial magnetic stimulation to the right inferior frontal gyrus and left superior temporal gyrus in Chinese–English bilinguals performing a language-switching task. Transcranial magnetic stimulation was administered within seven 100 ms time windows (TW1 to TW7) following the picture onset. We observed time window–specific enhancements of language control, as shown by a significant reduction in switching costs upon the stimulations on both sites relative to the sham stimulation: specifically, the right inferior frontal gyrus at TW1, TW2, TW4, and TW5 and the left superior temporal gyrus at TW2 and TW5. These findings indicate a double-strike top–down control mechanism underpinned by the pathway from the right inferior frontal gyrus to the right inferior frontal gyrus, potentially during both stages during production: the language task schema and the lemma selection. Our study provides the first evidence of the dynamic interactions between language control and processing systems causally underpinning bilingual language production.
Survival after extracorporeal cardiopulmonary resuscitation for adolescent arrhythmogenic arrest: ECPella (extracorporeal membrane oxygenation with Impella®)—a case report
Authors: Lerner Anouska , Desai Ajay , Trimlett Richard , Till Janice , Chan-Dominy Amy
Published: November 2024

Background

The combined therapy with venoarterial extracorporeal membrane oxygenation and Impella (ECPella) has been shown to improve survival in acute cardiogenic shock (CS) in adult patient. Only three paediatric cases have been reported in a multicentre study.

Case summary

We present our case, the first described to our knowledge in the UK, of a 15-year-old adolescent of Afro-Caribbean descent, weight 75 kg, who received extracorporeal cardiopulmonary resuscitation (E-CPR) and ECPella implantation. The patient suffered a sudden cardiac arrest at home; his mother called for an ambulance that arrived within 10 min and commenced life support with a LUCAS device. He received three doses of adrenaline and three desynchronized shocks for an underlying rhythm of ventricular fibrillation (VF) after which return of spontaneous circulation was achieved. He was then transferred to his local hospital where he had another VF arrest with successful cardioversion and was then transferred to our institution where on arrival he had another VF arrest and received E-CPR and ECPella implantation under the institutional adult shock programme within 3 h of in-hospital cardiac arrest. Following weaning from ECPella, the patient underwent cardiac and brain magnetic resonance imaging and serial echocardiograms with complete recovery of ventricular function. After implantation of cardiac defibrillator, he was discharged home without neurological sequelae. He remains asymptomatic from a cardiac perspective, with a normal cardiac examination and with no neurological sequelae at 2-year follow-up.

Discussion

This is the first case description of ECPella use in a child in the UK and highlighted the importance of timely institution of E-CPR on survival benefit in fatal CS. The outcome success of post-resuscitation ECPella strategy in this adolescent was through collaborative interprofessional engagement of multiple supra-specialists within acute cardiology and critical care across paediatric and adult services and alignment with the institutional adult shock programme.
Tracking the uptake of labelled host-derived extracellular vesicles by the human fungal pathogen Aspergillus fumigatus
Authors: Visser Corissa , Rivieccio Flora , Krüger Thomas , Schmidt Franziska , Cseresnyés Zoltán , Rohde Manfred , Figge Marc Thilo , Kniemeyer Olaf , Blango Matthew G , Brakhage Axel A
Published: November 2024

Extracellular vesicles (EVs) have gained attention as facilitators of intercellular as well as interkingdom communication during host–microbe interactions. Recently we showed that upon infection, host polymorphonuclear leukocytes produce antifungal EVs targeting the clinically important fungal pathogen Aspergillus fumigatus; however, the small size of EVs (<1 µm) complicates their functional analysis. Here, we employed a more tractable, reporter-based system to label host alveolar epithelial cell-derived EVs and enable their visualization during in vitro A. fumigatus interaction. Fusion of EV marker proteins (CD63, CD9, and CD81) with a Nanoluciferase (NLuc) and a green fluorescent protein (GFP) facilitated their relative quantification by luminescence and visualization by a fluorescence signal. The use of an NLuc fused with a GFP is advantageous as it allows for quantification and visualization of EVs simultaneously without additional external manipulation and to distinguish subpopulations of EVs. Using this system, visualization and tracking of EVs was possible using confocal laser scanning microscopy and advanced imaging analysis. These experiments revealed the propensity of host cell-derived EVs to associate with the fungal cell wall and ultimately colocalize with the cell membrane of A. fumigatus hyphae in large numbers. In conclusion, we have created a series of tools to better define the complex interplay of host-derived EVs with microbial pathogens.
Hyperactivation of the PI3K pathway in inborn errors of immunity: current understanding and therapeutic perspectives
Authors: IJspeert Hanna , Dalm Virgil A S H , van Zelm Menno C , Edwards Emily S J
Published: November 2024

The phosphoinositide-3-kinase (PI3K) pathway function is crucial to the normal development, differentiation, and function of immune cells including B, T, and NK cells. Following the description of two cohorts of patients with an inboirn error of immunity (also known as primary immunodeficiency) with gain-of-function variants in the PIK3CD gene a decade ago, the disease entity activated PI3K delta syndrome (APDS) was named. Since then, many more patients with PIK3CD variants have been described, and loss-of-function variants in PIK3R1 and PTEN have also been linked to APDS. Importantly, the availability of small molecules that inhibit the PI3K pathway has enabled targeted treatment of APDS patients. In this review, we define (i) the PI3K pathway and its role in inborn errors of immunity; (ii) the clinical and immunological presentation of APDS1 (PIK3CD GOF), APDS2 (PIK3R1 LOF), and related disorders; (iii) Diagnostic approaches to identify and functionally validate the genetic causes of disease; (iv) therapeutic interventions to target PI3K hyperactivation; and finally (v) current challenges and future perspectives that require attention for the optimal treatment of patients with APDS and APDS-L diseases.
Saccharomyces boulardii enhances anti-inflammatory effectors and AhR activation via metabolic interactions in probiotic communities
Authors: Hedin Karl Alex , Mirhakkak Mohammad H , Vaaben Troels Holger , Sands Carmen , Pedersen Mikael , Baker Adam , Vazquez-Uribe Ruben , Schäuble Sascha , Panagiotou Gianni , Wellejus Anja , Sommer Morten Otto Alexander
Published: November 2024

Metabolic exchanges between strains in gut microbial communities shape their composition and interactions with the host. This study investigates the metabolic synergy between potential probiotic bacteria and Saccharomyces boulardii, aiming to enhance anti-inflammatory effects within a multi-species probiotic community. By screening a collection of 85 potential probiotic bacterial strains, we identified two strains that demonstrated a synergistic relationship with S. boulardii in pairwise co-cultivation. Furthermore, we computationally predicted cooperative communities with symbiotic relationships between S. boulardii and these bacteria. Experimental validation of 28 communities highlighted the role of S. boulardii as a key player in microbial communities, significantly boosting the community’s cell number and production of anti-inflammatory effectors, thereby affirming its essential role in improving symbiotic dynamics. Based on our observation, one defined community significantly activated the aryl hydrocarbon receptor—a key regulator of immune response—280-fold more effectively than the community without S. boulardii. This study underscores the potential of microbial communities for the design of more effective probiotic formulations.
Dose-efficient phase-contrast imaging of thick weak phase objects via OBF STEM using a pixelated detector
Authors: Ooe Kousuke , Seki Takehito , Nogami Mitsuru , Ikuhara Yuichi , Shibata Naoya
Published: November 2024

Optimum bright-field scanning transmission electron microscopy (OBF STEM) is a recently developed low-dose imaging technique that uses a segmented or pixelated detector. While we previously reported that OBF STEM with a segmented detector has a higher efficiency than conventional STEM techniques such as annular bright field (ABF), the imaging efficiency is expected to be further improved by using a pixelated detector. In this study, we adopted a pixelated detector for the OBF technique and investigated the imaging characteristics. Because OBF imaging is based on the thick weak phase object approximation (tWPOA), a non-zero crystalline sample thickness is considered in addition to the conventional WPOA, where the pixelated OBF method can be regarded as the theoretical extension of single side band (SSB) ptychography. Thus, we compared these two techniques via signal-to-noise ratio transfer functions (SNRTFs), multi-slice image simulations, and experiments, showing how the OBF technique can improve dose efficiency from the conventional WPOA-based ptychographic imaging.
Detection of Gram-positive and Gram-negative bacteria in brain abscesses by 16S rRNA in situ hybridization
Authors: Mbongo William , Laga Alvaro C , Solomon Isaac H
Published: November 2024

In situ hybridization (ISH) staining of bacterial 16S ribosomal RNA (rRNA) is an alternative to standard histological stains (eg, Gram, Warthin-Starry), and may improve the diagnosis of bacterial brain abscesses. To evaluate the utility of 16S rRNA ISH, a 10-year retrospective cohort was assembled from a large academic medical center. Results of histological stains, cultures, and 16S rRNA sequencing were extracted from reports, and new Gram and 16S rRNA ISH stains were performed. Histologically identifiable bacteria were present in 40/63 (63%) cases and 38/57 (67%) were associated with positive cultures. Overall, 16S rRNA ISH was positive in 18/63 (29%) cases, including 16/37 (43%) with positive Gram stains, 12/38 (32%) positive by culture, and 4/8 (50%) positive by sequencing. 16S rRNA ISH highlighted bacteria in 14/40 (35%) cases with Gram-positive organisms and 9/17 (53%) with Gram-negative organisms (including 6 polymicrobial cases). Compared to a composite gold standard of Gram stain and culture, the sensitivity and specificity of 16S rRNA ISH were 35% and 93%, respectively. While sensitivity is relatively low, 16S rRNA ISH may be useful for distinguishing real organisms from artifacts and for identifying brain abscess cases suitable for 16S rRNA sequencing.
Case report: Migratory biliary stent resulting in sigmoid colon perforation
Authors: Beloy Jasmine B , Lund Nicholas P , Van Hell Annika M , Allamaneni Shyam
Published: November 2024

Biliary stent insertion during endoscopic retrograde cholangiopancreatography is a therapeutic intervention to relieve obstruction and facilitate flow through the biliary tree. In rare circumstances, these stents can migrate and result in distal gastrointestinal perforation, which may necessitate endoscopic or surgical intervention. We report a case involving a 79-year-old female who presented with peritonitis due to sigmoid colon perforation following biliary stent migration. The stent was placed to treat acute cholangitis with choledocholithiasis. Two weeks following stent placement, gastroenterology attempted scheduled stent removal, but was unable to visualize the stent on endoscopy. Eleven days later, the patient was emergently taken to the operating room for an exploratory laparotomy and a Hartmann’s procedure for stent migration and subsequent sigmoid perforation. No established protocol exists for managing migratory biliary stents to avoid perforations. We emphasize the need for follow-up imaging and individualized clinical decision-making based on patient stability.
Nash meets Łukasiewicz: computing equilibria through logic
Authors: Preto Sandro , Finger Marcelo
Published: November 2024

A Nash equilibrium is a strategy profile of a game in which none of the players involved has any gain by changing alone his/her own strategy. Given a two-player game, we show a codification of all of its Nash equilibria into Łukasiewicz infinitely-valued logic, that is, we derive a propositional theory in this logic whose models codify all the Nash equilibria. Based on such propositional theory, we derive a polynomial reduction from the problem of computing a Nash equilibrium to the problem of satisfiability of (sets of) formulas of Łukasiewicz infinitely-valued logic. These applications of logic to game theory lead to new methods for computing Nash equilibria.
Combat-Relevant Anesthesia Fellowships Help Sustain the Army’s Multidomain Medical Force
Authors: Custer Jonathan
Published: November 2024

In the community of Army Nurse Anesthetists, there is an underutilized potential for Combat-Relevant Fellowship training that, if enthusiastically encouraged and taken advantage of, would proffer many benefits to the Military Health System and the beneficiaries of its care. Most importantly, increased access to and encouragement for participation in these fellowships for Nurse Anesthetists would act as a tool for skill sustainment, denying any potential for skill degradation or readiness gaps in preparation for the next-generation war. These fellowships would also augment the already robust breadth, quality, and safety of Army Nurse Anesthetists’ combat and noncombat anesthesia care, potentially increase Return-To-Duty rates, potentially expedite casualty clearance of the battlefield, increase the often-limited access to advanced pain management care for chronic pain patients in Military Treatment Facilities, increase the retention rates of Nurse Anesthetists, augment the military anesthesia community’s knowledge-base, and help to advance the art of anesthesia as a whole. To triumph against the anticipated rigors of the future war’s multidomain operational environment, we are duty bound to continually improve and strive to be the best versions of ourselves as soldiers, as professionals, and as communities. This paper will explore the untapped utility of Combat-Relevant Fellowships for Army Nurse Anesthetists.
Preparing Military Interprofessional Health Care Teams for Effective Collaboration
Authors: Barry Erin S , Varpio Lara , Teunissen Pim , Vietor Robert , Kiger Michelle
Published: November 2024

Introduction

Military Interprofessional Health care Teams (MIHTs) are the backbone of modern military medicine. However, these teams face distinct operational challenges, including frequent personnel rotation, diverse work environments, and the constant possibility of rapid deployment. Serving in dynamic teams that deploy for both military and humanitarian missions, MIHTs face the unique challenge of constant restructuring and reorganization. Consequently, preparing MIHT members to function effectively as a team presents a significant hurdle. This difficulty highlights the limited applicability of existing literature focused on training civilian interprofessional health care teams. To address this gap, we conducted interviews with MIHT members to understand specific training elements that equip MIHT members to effectively collaborate. By gaining a deeper understanding of their needs, we can improve training programs and ultimately optimize MIHT performance, readiness, and patient care.

Methods

We conducted individual semi-structured interviews with military health care professionals. We employed purposeful sampling to ensure a diverse range of perspectives from individuals with direct experience working in or leading MIHTs. The 30 participants interviewed represented a broad spectrum of MIHT professions. The data used for this study stems from a broader research program on MIHTs conducted between 2017 and 2019. We conducted a secondary analysis focusing specifically on interview data related to education and training. Using Braun and Clarke’s 6-step approach to Thematic Analysis, we identified themes from the data to build an understanding of MIHT perspectives on training effectiveness.

Results

The participants’ insights allowed us to identify 3 critical themes related to the training elements they considered most beneficial for fostering collaboration within MIHTs: (1) MIHT members rely on their own predeployment readiness; (2) MIHT contexts require unique, adaptive communication skills; and (3) MIHT training is an ongoing endeavor.

Discussion

We need our MIHTs to be ready to deploy and effectively collaborate, which involves being clinically, emotionally, physically, and operationally ready. MIHT members describe 3 aspects of specific training elements as having significant potential to equip them to effectively collaborate: (1) MIHT members rely on their own predeployment readiness; (2) MIHT contexts require unique, adaptive communication skills; and (3) MIHT training is an ongoing endeavor at both the individual and team levels. By investing in tailored training programs that address these areas, we can empower MIHTs to continuously adapt, excel, and ultimately, positively impact patient outcomes in diverse military health care settings.
The X-ray re-brightening of GRB afterglow revisited: a possible signature from activity of the central engine
Authors: Yang Zhe , Lü Hou-Jun , Yang Xing , Shen Jun , Yi Shuang-Xi
Published: November 2024

Long-duration gamma-ray bursts (GRBs) are thought to be from core collapse of massive stars, and a rapidly spinning magnetar or black hole may be formed as the central engine. The extended emission in the prompt emission, flares, and plateaus in X-ray afterglow, are proposed to be as the signature of central engine re-activity. However, the direct evidence from observations of identifying the central engines remains an open question. In this paper, we systemically search for long-duration GRBs that consist of bumps in X-ray afterglow detected by Swift/XRT and find that the peak time of the X-ray bumps exhibit bimodal distribution (defined as ‘early’ and ‘late’ bumps) with division line at $t=7190$ s. Although we cannot rule out that such a bimodality arises from selection effects. We proposed that the long-duration GRBs with an early (or late) bumps may be originated from the fall-back accretion onto a new-born magnetar (or black hole). By adopting Monte Carlo Markov Chain (MCMC) method to fit the early (or late) bumps of X-ray afterglow with the fall-back accretion of magnetar (or black hole), it is found that the initial surface magnetic field and period of magnetars for most early bumps are clustered around $5.88\times 10^{13}$ G and 1.04 ms, respectively. Meanwhile, the derived accretion mass of black hole for late bumps is in the range of $[4\times 10^{-4}, 1.8\times 10^{-2}]\,{\rm M}_{\odot }$, and the typical fall-back radius is distributed range of $[1.04, 4.23]\times 10^{11}$ cm, which is consistent with the typical radius of a Wolf–Rayet star. However, we also find that the fall-back accretion magnetar model is disfavoured by the late bumps, but the fall-back accretion of black hole model cannot be ruled out to interpret the early bumps of X-ray afterglow.