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The advent of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) treatment marks a major breakthrough. These therapies have proven safer and more effective than traditional radiotherapy and targeted treatments. Immunotherapies like pembrolizumab, nivolumab, and ipilimumab have pioneered new treatment avenues, potentially improving patient outcomes and quality of life. Additionally, advances in immunotherapy have prompted detailed research into CRC therapies, especially those integrating ICIs with conventional treatments, providing new hope for patients and shaping future research and practice. This review delves into the mechanisms of various ICIs and evaluates their therapeutic potential when combined with radiotherapy, chemotherapy, and targeted therapies in clinical settings. It also sheds light on the current application and research involving ICIs in CRC treatment. [ABSTRACT FROM AUTHOR]

The insolubility and severe self-aggregation tendency of hybridized localized and charge-transfer (HLCT) small molecular emitters have limited their application in solution-processed organic light-emitting diodes (OLEDs), particularly in red OLEDs. Herein, a series of solution-processable novel red hyper-structured molecular (HSM) HLCT emitters, CRA–MTBP(X)–mCP(8−X) (X = 8, 7, 6, 4, 2, 1 or 0), are designed. The benzothiadiazole/triphenylamine-based HLCT unit (MTBP) and the host unit (mCP) at different molar ratios were hooked up to the inactive calix[4]resorcinarene (CRA) core via efficient "Click" reactions, respectively. CRA–MTBP(X)-mCP(8−X) exhibited good thermal stability with a glass transition temperature (Tg) of above 120 °C and a decomposition temperatures (Td) exceeding 363 °C. UV-Vis, PL, and CV results demonstrated that these HSMs inherit the photophysical and electrochemical properties of the corresponding functional units. Spin-coating CRA–MTBP(X)–mCP(8−X) as light-emitting layers, all the non-doped diodes showed orange to red emission. Among them, a CRA–MTBP(8)–mCP(0)-based device emitted red light, with an EL emission peak (λEL) at 651 nm and CIE coordinates of (0.63, 0.36), a maximum external quantum efficiency (EQEmax) of 1.35% with low roll-off and a maximum luminance (Lmax) of 2831 cd m−2. Furthermore, the doped device based on CRA–MTBP(8)–mCP(0) using CBP as the host emitted bright red light with a λEL at 612 nm, an EQEmax of 3.27%, and a Lmax of 4362 cd m−2. These results indicate that the construction of HSMs by introducing red HLCT units could be an effective strategy for structuring solution-processable HLCT red emitters. [ABSTRACT FROM AUTHOR]

Introducing surface defects on molybdenum disulfide (MoS2) crystals plays a crucial role in enhancing the electrocatalytic activity toward the hydrogen evolution reaction (HER). Despite the remarkable progress in this area, the precise control of the size, distance, and defective areas with minimal surface contamination remains unachieved. Conventional microfabrication methods often leave organic residues on the surface that impair electrocatalytic activity and hinder interface elucidation by advanced characterization tools. In this study, we pattern for the first-time arrays of pillars in nanometer-thick MoS2 flakes using a focused ion beam to enhance HER activity. We observe size-dependent stability of the edge-like defects under HER conditions with defective areas. The pillars undergo chemical and structural changes post-patterning due to an amorphization process, unambiguously confirmed by atomic force microscopy, Raman spectroscopy, and synchrotron X-ray photoelectron spectroscopy. Furthermore, the amorphization process is more pronounced in specific in-plane directions, as confirmed by transmission electron microscopy. The electrocatalytic activity of the pillars was measured using a recently reported fabrication method, allowing us to unequivocally correlate defects with HER activity. Microelectrodes with less pillars, i.e. less catalytic sites, demonstrate a lower overpotential of 349 mV at 10 mA cm−2 showcasing a groundbreaking advancement in their fabrication. [ABSTRACT FROM AUTHOR]

Background: Proton beam therapy (PBT) has been gradually introduced for treating choroidal melanoma. This study systematically reviewed clinical reports to evaluate the efficacy and safety of PBT in choroidal melanoma patients. Methods: This systematic review included all the primary studies involving PBT for choroidal melanoma patients through April 2024. Four publicly accessible databases were searched, and the statistical data were analyzed using STATA 15.0. The outcomes of interest included overall survival (OS), metastasis-free survival, local control rate, and adverse reactions. Results: A total of six case series involving 1059 patients with choroidal melanoma were included. The random effect model meta-analysis showed that the 2-, 3-, 5-, and 10-year OS rates of patients with choroidal melanoma treated with PBT were 97%, 92%, 73%, and 39%, respectively. The metastasis-free survival rates at 2, 3, and 5 years were 92%, 89%, and 76%, respectively, and the local control rates at 1, 3, 5, and 10 years were 98%, 92%, 94%, and 88%, respectively. Four studies reported adverse reactions. The most common adverse reactions after PBT were glaucoma, optic neuropathy, and cataracts, with incidence rates ranging from 17.9 to 27%, 12.8–64%, and 29.6–39.8%, respectively. Conclusions: This meta-analysis identified PBT as a vital local treatment strategy against choroidal melanoma. Both OS and local control rates showed excellent results. However, more prospective trials can help compare the efficacy of PBT with typical therapy. [ABSTRACT FROM AUTHOR]

Background: Traditional fish sauce is made from fish that have been coated in 30%–40% sea salt and fermented for up to 2 years. The preparation requires a long time, and the fish source contains considerable biogenic amines. In this report, by measuring the growth curve and identifying the intracellular enzyme and the activity of protease, B. zhangzhouensis with the highest activity of protease production was selected from eight strains, which were applied to the fermentation process of fish sauce. Results: Optimized by response surface methodology, the content of amino nitrogen was taken as the response value, and the best fermentation conditions were 4.15% inocula, pH 9.13, and 36.3°C. Under the optimized conditions, fish sauce samples were obtained by fermentation with B. zhangzhouensis for 15 h, 3 days, 7 days, 15 days, and 30 days, respectively. The contents of amino nitrogen, total nitrogen, biogenic amine, and various flavor substances were determined and compared with the traditional 2‐year‐fermented fish sauce. As a result, the 7‐day‐fermented fish sauce using B. zhangzhouensis had a similar composition of flavor substances to traditional fish sauce, but a much lower level of biogenic amines. Conclusion: The new method of preparing fish sauce with a fermentation condition of 4.15% B. zhangzhouensis, pH 9.13, and 36.3°C can improve the production efficiency of fish sauce, and the flavor is similar to that of traditional fish sauce. [ABSTRACT FROM AUTHOR]

Atypical femoral fractures (AFFs) are rare fractures usually associated with medications that can ultimately alter bone metabolism. Imatinib, a drug prescribed for treatment of chronic myeloid leukemia (CML), has been associated with altered bone homeostasis, however, with unknown clinical significance. Here, we present the case of a 17‐year‐old female, with a diagnosis of CML undergoing chronic imatinib therapy, who developed an AFF treated successfully with prophylactic fixation with intramedullary nailing. Our case underscores the importance of prompt recognition of this entity to allow patients timely appropriate care, even at an early age. [ABSTRACT FROM AUTHOR]

Unlike most plants, members of the genus Solanum produce cholesterol and use this as a precursor for steroidal glycoalkaloids. The production of the compounds begins as a branch from brassinosteroid biosynthesis, which produces cholesterol that is further modified to produce steroidal glycoalkaloids. During the cholesterol biosynthesis pathway, genetic engineering could alter the formation of cholesterol from provitamin D3 (7-dehydrocholesterol) and produce vitamin D3. Cholesterol is a precursor for many steroidal glycoalkaloids, including a-tomatine and esculeoside A. Alpha-tomatine is consumed by mammals and it can reduce cholesterol content and improve LDL:HDL ratio. When there is a high a-tomatine content, the fruit will have a bitter flavor, which together with other steroidal glycoalkaloids serving as protective and defensive compounds for tomato against insect, fungal, and bacterial pests. These compounds also affect the rhizosphere bacteria by recruiting beneficial bacteria. One of the steroidal glycoalkaloids, esculeoside A increases while fruit ripening. This review focuses on recent studies that uncovered key reactions of the production of cholesterol and steroidal glycoalkaloids in tomato connecting to human health, fruit flavor, and plant defense and the potential application for tomato crop improvement. [ABSTRACT FROM AUTHOR]

The wire arc additive manufacturing (WAAM) deposition of Ti–6Al–4V (Ti64) and Ti–6Al–2Sn–2Zr–2Mo–2Cr (Ti62222) alloys produce long columnar grains, indicating tensile anisotropy in various directions. Therefore, this study applied interlayer peening (ILP) during WAAM to modify the solidification morphology. The index of plane anisotropy (IPA) of the as-built Ti64 deposit was 30%, whereas that of the ILP Ti64 alloy was 1%, indicating the significant effect on modifying the solidification morphology and reducing the IPA of the Ti64 deposit. However, the IPA of the as-built Ti62222 alloy was 79%, whereas that of the ILP Ti62222 alloy was 72%, indicating anisotropy in the mechanical properties despite the ILP process. In Ti64 alloy, ILP resulted in larger DILP (3.2 mm) than Dremelt (1.87 mm), which impeded the growth of columnar β grains and nucleated the equiaxed β grains during subsequent layer deposition. However, in Ti62222 alloy, owing to its higher hardness and Yield Strength, DILP (2.2 mm) and Dremelt (1.97 mm) were approximately the same, thus allowing the growth of columnar β grains to continue during subsequent layer deposition. [ABSTRACT FROM AUTHOR]

Two-dimensional material, tellurium, composed of tellurium, has emerged as a promising material for NO2 gas sensing due to its superior intrinsic electrical conductivity and strong affinity to NO2. However, the majority of literature on tellurene-based gas sensors has primarily focused on NO2 detection performances under dry condition, despite the importance of considering humidity-dependent detection properties for practical gas sensing applications. Here, we explore NO2 detection properties of tellurene-based chemiresistive gas sensor devices under humidity environments at room temperature. The resultant tellurene synthesized via a hydrothermal route presents 2D flake-like morphologies with highly crystalline hexagonal structures. The obtained tellurene chemiresistive sensor devices exhibit a good NO2 gas response of 35% with a fast response time of 14 s, under dry conditions. Interestingly, our tellurene-based sensor devices also present the humidity-independent NO2 gas detection performances while achieving a fast response time. These outstanding detection performances are likely due to intrinsically superior electrical conductivity and structural stability of tellurene in air. [ABSTRACT FROM AUTHOR]

Microglia/macrophages participate in the development of and recovery from experimental autoimmune encephalomyelitis (EAE), and the macrophage M1 (pro-inflammatory)/M2 (anti-inflammatory) phase transition is involved in EAE disease progression. We evaluated the efficacy of crisdesalazine (a novel microsomal prostaglandin E2 synthase-1 inhibitor) in an EAE model, including its immune-regulating potency in lipopolysaccharide-stimulated macrophages, and its neuroprotective effects in a macrophage-neuronal co-culture system. Crisdesalazine significantly alleviated clinical symptoms, inhibited inflammatory cell infiltration and demyelination in the spinal cord, and altered the phase of microglial/macrophage and regulatory T cells. Crisdesalazine promoted the M1 to M2 phase transition in macrophages (immunomodulation) and reduced neuronal necrosis (neuroprotection) in vitro. This is the first study to directly demonstrate the therapeutic effects of a microsomal prostaglandin E2 synthase-1 inhibitor in an EAE model and its ability to alter macrophage polarization, suggesting that it may be a new therapeutic option for the treatment of patients affected by multiple sclerosis and other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Climate change is one of the most crucial issues in human society such that if it is not given sufficient attention, it can become a great threat to both humans and the Earth. Due to global warming, soil erosion is increasing in different regions. Therefore, this issue will require further investigation and the use of new tools. In this paper, a portable wind tunnel was designed and built for wind erosion studies using photogrammetry, which is a novel technique. This instrument consists of a working section, a fan, a portable voltage source inverter to control its angular speed, and a honeycomb to straighten the air flow in the working section. The eroded volume of soil is measured using photogrammetry by producing two 3D models and point clouds before and after the soil erosion test and calculating their volume changes. The results show that a 0.175 mm check distance precision is achievable under convergent imaging and with sufficient number of accurate control points which this value indicates the discrepancy between the anticipated and measured lengths of all the check distances. In addition, the features of this portable wind tunnel guarantee its easy portability, and its transparency enables the measurement of the threshold friction velocity. Additionally, this instrument, as an invention, has been registered at the Intellectual Property Center of Iran. [ABSTRACT FROM AUTHOR]

Purpose: Prefabricated construction (PC) can benefit construction industry due to its high efficiency, energy saving, consumption reduction and safety. However, the high capital cost is a critical challenge hindering its development in China. The collaboration of PC stakeholders is conducive to improving cost management efficiency and optimizing resource allocation which has been ignored in previous studies. Therefore, this study aims to explore the collaboration paths of stakeholders in the process of solving critical cost influencing factors (CIFs) of PC to reduce costs. Design/methodology/approach: Firstly, 25 CIFs and five main stakeholders that affect PC capital cost were identified through literature research and expert interviews. Then, questionnaires were used to investigate the relationship between stakeholders and CIFs from the perspectives of three stakeholder attributes of proximity, attitude and power, respectively. Finally, based on the survey data, three stakeholder-CIF networks from three attributes perspective and a comprehensive network were constructed and used for subsequent social network analysis. Findings: (1) Stakeholders mainly show willingness and potential to collaborate on organization and management factors; (2) More stakeholders pay attention to incentive policies and the setting of prefabrication rates and assembly rates, while all stakeholders have the right to facilitate information and resource sharing in the PC supply chain; (3) The comprehensive network shows a core-periphery structure. As core stakeholders, contractor, designer and manufacturer are more likely to actively manage the 14 core CIFs. Originality/value: This paper innovatively combined stakeholder and cost management in PC, and used two-mode network based on three stakeholder perspectives to reveal the collaboration potential and motivation of stakeholders in PC cost management. The findings not only provide guidance for stakeholders to find potential partners and optimize resource allocation in solving specific cost issues, but also facilitate stakeholders' sustainable collaboration to achieve PC's cost performance. [ABSTRACT FROM AUTHOR]

This paper presents a mixed-mode on-chip automatic frequency tuning technique to achieve a process-invariant lowpass cut-off frequency for biopotential amplifiers. It comprises of a sine-like test signal generation circuit, a digital scheme to minimize the deviations in the frequency of the test signal, a programmable switched capacitor array acting as the load of the biopotential amplifier, and a peak detector based digital capacitor selection logic. Results obtained show that the proposed technique curtails the deviation of the cut-off frequency across process (and temperature) variations. The complete scheme implemented in UMC 0.18 μ m CMOS technology consumes only 1.02 μ W average power approximately with 1.8 V supply. Moreover the complete tuning mechanism lasts for less than half a minute only. Its low power consumption and implementation on analog platform makes it integrable with the standard portable biomedical systems intended for remote monitoring. [ABSTRACT FROM AUTHOR]

Neuromorphic computing devices offer promising solutions for next‐generation computing hardware, addressing the high throughput data processing demands of artificial intelligence applications through brain‐mimicking non‐von Neumann architecture. Herein, PEDOT:Tos/PTHF‐based organic electrochemical transistors (OECTs) with dual‐modal memory functions—both short‐term and long‐term—are demonstrated. By characterizing memory levels and relaxation times, the device has been efficiently manipulated and switched between the two modes through coupled control of pulse voltage and duration. Both short‐term and long‐term memory functions are integrated within the same device, enabling its use as artificial neurons for the reservoir unit and synapses in the readout layer to build up a reservoir computing (RC) system. The performance of the dynamic neuron and synaptic weight update are benchmarked with classification tasks on hand‐written digit images, respectively, both attaining accuracies above 90%. Furthermore, by modulating the device as both reservoir mode and synaptic mode, a full‐OECT RC system capable of distinguishing electromyography signals of hand gestures is demonstrated. These results highlight the potential of simplified, homogeneous integration of dual‐modal OECTs to form brain‐like computing hardware systems for efficient biological signal processing across a broad range of applications. [ABSTRACT FROM AUTHOR]

Purpose: The current study developed and tested selected effects of the Together for Life (TFL) program for community-dwelling older adults using an embedded mixed methods design. Method: Nine community volunteers participated in the training program, and 14 people aged ≥65 years, living alone, enrolled in the study. Home visits were conducted by home health nurses every 2 weeks, supplemented by weekly home visits and phone counseling provided by volunteers, for a duration of 20 weeks. This mixed methods study used quantitative and qualitative approaches. Quantitative data were gathered through a questionnaire survey to assess the intervention's effects on health-related quality of life (HRQOL), loneliness, and depression. The qualitative component focused on participants' evaluation of the program. Results: Significant changes were noted in HRQOL scores with an effect size of 0.6 (p = 0.01). Results indicated the positive impact of the TFL program on HRQOL among older adults as their health status was continuously monitored by volunteers who provided care and home health nurses who assisted with health management during the coronavirus disease 2019 (COVID-19) pandemic. Conclusion: In a pandemic, personalized health management, such as regular health check-ins provided by home health nurses and home or phone visits provided by volunteers, is crucial for isolated older adults. This pilot program enhanced participants' HRQOL through continuous health monitoring, volunteer care, and nurse support, even during the COVID-19 pandemic. [Journal of Gerontological Nursing, 51(1), 49–58.] [ABSTRACT FROM AUTHOR]

Analyzing the position time series from the regional global navigation satellite system (GNSS) network can contribute to rationally explaining geophysical phenomena at different spatiotemporal scales. This paper examines the use of machine learning model to reflect the interactions between reference stations from a regional GNSS network. The input and output data to the machine learning algorithm consist of GNSS reference station data. In the forecasting experiments, the Adaptive Boosting (AdaBoost) algorithm is introduced and evaluated with the time series datasets collected from 20 GNSS reference stations over the period of 10 years. The results indicate that the forecasting accuracy of the AdaBoost has improved by 59% compared to the Prophet model using the time variable and show the feature contribution of each GNSS reference station to model the regional GNSS network. Through the modeling of regional GNSS network, interpolation of the GNSS time series can be completed. The interpolation results indicate that the AdaBoost model can capture the trend information and shows better capability than the cubic spline interpolation method. Overall, the AdaBoost model demonstrates superior performance in modeling of GNSS vertical time series, thus impacting the analysis and maintenance of the regional GNSS network. [ABSTRACT FROM AUTHOR]

This study represents the culmination of our efforts to explore the crucial role of polyester composites in the field of biocomposites, highlighting their importance in advanced materials technologies. Our primary objective has been to thoroughly elucidate the significance of polyester composites within biocomposites, with a detailed examination of their impact on advanced material technologies. Through this research, we have meticulously investigated the properties of polyesters derived from biodegradable polymers, analyzing their intricate structure-property relationships and potential applications in bio-based production. To drive the industrial adoption of bio-based polyesters, our work emphasizes the need for developing economically viable production methodologies, exploring ecologically sustainable and effective material designs, and advocating for robust policy support to facilitate the commercialization of bio-based polyesters. We propose that future research should focus on the innovation of novel bio-based monomers as sustainable raw material sources, the design of diverse polyester structures utilizing material genome technology, and a comprehensive understanding of the degradation processes and long-term performance of bio-based polyesters. The advancement in this domain relies on interdisciplinary collaboration across materials science, engineering, and chemistry. Our findings underscore that through such interdisciplinary cooperation, a broader spectrum of bio-based polyester products can be developed, thereby expanding their industrial applications. In this context, our investigation aims to contribute to the advancement of sustainable materials and their more effective integration into future material technologies. [ABSTRACT FROM AUTHOR]

(Al 2 O 3 ) x (HfO 2 ) 1-x films with varying compositions were deposited on silicon substrates via plasma-enhanced atomic layer deposition (PEALD), and metal-oxide-semiconductor (MOS) capacitors were fabricated. The impact of varying induced Al content on the dielectric properties of HfO 2 was examined through electrical measurements. The results showed that increasing Al content raised the flat-band voltage, reduced the interface state density (D it ), and significantly lowered the leakage current at a given voltage. Moreover, room temperature I-V measurements indicated that Schottky emission (~ 0.8-4.8 MV/cm), Poole-Frenkel (PF) emission (~ 4.8-7.3 MV/cm), and Fowler-Nordheim (FN) tunneling (~ 7.3-8.3 MV/cm) were the dominant current mechanisms under varying electric fields. At higher temperatures (75-100 °C), the leakage mechanism in Al-rich samples (50-100%) shifted from FN tunneling to PF emission at high electric fields (~ 3.3-6.87 MV/cm). The composition and energy band alignments of the films were characterized using X-ray photoelectron spectroscopy (XPS) and ultraviolet (UV) spectrophotometry, showing that introducing Al into HfO 2 increases the bandgap, reduces the dielectric constant, and significantly lowers oxygen vacancies. Thus, it is further demonstrated that HfO 2 films with the appropriate Al content can effectively enhance dielectric properties and adjust the material parameters of the dielectric layer., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Alzheimer's disease (AD) consists of two main pathologies, which are the deposition of amyloid plaque as well as tau protein aggregation. Evidence suggests that not everyone who carries the AD-causing genes displays AD-related symptoms; they might never acquire AD as well. These individuals are referred to as non-demented individuals with AD neuropathology (NDAN). Despite the presence of extensive AD pathology in their brain, it was found that NDAN had better cognitive function than was expected, suggesting that they were more resilient (better at coping) to AD due to differences in their brains compared to other demented or cognitively impaired patients. Thus, identification of the mechanisms underlying resilience is crucial since it represents a promising therapeutic strategy for AD. In this review, we will explore the molecular mechanisms underpinning the role of genetic and molecular resilience factors in improving resilience to AD. These include protective genes and proteins such as APOE2, BDNF, RAB10, actin network proteins, scaffolding proteins, and the basal forebrain cholinergic system. A thorough understanding of these resilience mechanisms is crucial for not just comprehending the development of AD but may also open new treatment possibilities for AD by enhancing the neuroprotective pathway and targeting the pathogenic process., Competing Interests: Declarations. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To evaluate the 6-year physiological rates-of-change in ganglion cell inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) thickness measured with optical coherence tomography., Methods: We included 2202 out of 2661 subjects from the population-based Singapore Chinese Eye Study who returned for follow-up 6 years after baseline examination (follow-up rate 87.7%). OCT scans with signal strength (SS) <6, imaging errors, and ocular pathologies were excluded. A linear mixed model was used to measure the rates-of-change in GCIPL and RNFL thickness. Time and difference between baseline and follow-up scan SS were modelled as fixed effect. Baseline age, baseline measurement, gender, hypertensive medication, diabetes status, cardiovascular disease, smoking status, body mass index, spherical equivalent (SE), intraocular pressure and optic disc area were each analysed in an interaction term with time., Results: The adjusted mean rate-of-change in average GCIPL was -0.312 μm/year in males and -0.235 μm/year in females. Older age and thicker GCIPL thickness at baseline were associated with higher rates-of-change while females and more hyperopic SE were associated with lower rates-of-change. The adjusted mean rate-of-change in average RNFL was -0.374 μm, with higher rates-of-change in the vertical quadrants and no differences between genders. Older age and thicker RNFL thickness at baseline were associated with higher rates-of-change in average RNFL and RNFL thickness in the vertical quadrants, and vice versa for each unit increase in scan SS and SE., Conclusion: Our population cohort provides data on physiological thinning of GCIPL and RNFL with age. Differentiating physiological changes in GCIPL and RNFL is important for more accurate clinical assessment., (© 2025 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: Cost-utility analyses examining the value of new vaccines for pneumococcal disease will require health state utilities as inputs. Existing utilities for pneumococcal infections in young children are limited. The purpose of this study was to estimate health state utilities associated with pneumococcal infections in young children., Methods: Six health state vignettes depicting infections due to Streptococcus pneumoniae were drafted based on published literature and clinician interviews. To address methodological challenges in estimating utilities for temporary infections in children 0-5 years of age, several time trade-off approaches were explored in a pilot study (N = 28 participants). In the subsequent utility elicitation study conducted in the UK, health states were valued using the best performing method from the pilot (10-year time horizon, with infections repeated annually) with adult general population respondents imagining a child 2-5 years of age., Results: A total of 208 participants completed interviews (51.9% female; mean [SD] age = 41.0 [14.9] years). Mean (SD) utilities were 0.902 (0.092) for pneumonia requiring hospitalization, 0.901 (0.087) for bacteremia, 0.894 (0.103) for recurrent acute otitis media (AOM), 0.882 (0.107) for recurrent AOM treated with pressure equalization tubes, 0.878 (0.109) for bacteremic pneumonia, and 0.809 (0.145) for meningitis., Conclusion: Lower health state utilities were associated with health states that had longer treatment periods, required more invasive treatment, and described more severe infections. Utilities from this study can be used in models examining cost-effectiveness of pneumococcal vaccines. These results have methodological implications for future research estimating utilities associated with temporary pediatric health conditions., Competing Interests: Declarations. Competing interests: LM, TH, and LH are employed by Evidera, which received funding support from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. Inc., Rahway, NJ, USA to conduct this research. BC, MW, TW, MH, KF, and SM are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. DR consulted on the pediatric utility methodology and received funding for time spent on this consultation. MK, BN, and AH receive consulting fees and grant funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Ethical approval: The study protocol and all study materials were approved by the Salus Institutional Review Board (study 22451), and all participants provided informed consent before participation., (© 2025. Merck & Co., Inc., Rahway, NJ, USA and its affiliates & Imperial College London & Louis S. Matza, Timothy A. Howell, Lucinda Hetherington, Donna Rowen, Tina Tan, Matthew S. Kelly, Alejandro Hoberman.)

Sleep disturbances are increasingly prevalent, significantly impacting physical and mental health. Recent research reveals a bidirectional relationship between gut microbiota and sleep, mediated through the microbiota-gut-brain axis. This review examines the role of gut microbiota in sleep physiology and explores how biotics, including probiotics, prebiotics, synbiotics, postbiotics, and fermented foods, can enhance sleep quality. Drawing from animal and human studies, we discuss neurobiological mechanisms by which biotics may influence sleep, including modulation of neurotransmitters, immune responses, and hormonal regulation. Key microbial metabolites, such as short-chain fatty acids, are highlighted for their role in supporting sleep-related neurochemical processes. Additionally, this review presents dietary strategies and food processing technologies, like fermentation, as innovative approaches for sleep enhancement. Although promising, the available research has limitations, including small sample sizes, variability in biotic strains and dosages, and reliance on subjective sleep assessments. This review underscores the need for standardized protocols, objective assessments such as polysomnography, and personalized biotic interventions. Emerging findings highlight the therapeutic potential of gut microbiota modulation for sleep improvement, though further large-scale human trials are essential to refine strain selection, dosage, and formulation. This interdisciplinary exploration seeks to advance food-based interventions and holistic strategies for managing sleep disorders and improving quality of life., (© 2025 Institute of Food Technologists.)

The development of energy-efficient and high-performance optoelectronic devices is crucial for the advancement of modern optoelectronic and microelectronic systems. Although the self-powered devices and optoelectronic synapses based on 2D heterojunction show great application prospects, the high energy consumption and infrared band detection of self-powered optoelectronic synapses are still an urgent problem to be solved. In this report, a BP/Ta 2 NiS 5 heterojunction is constructed to achieve infrared detection by leveraging differences in Fermi energy levels. This heterojunction exhibits a high specific detectivity of 6.57 × 10 10 , 2.6 × 10 10 , and 1.12 × 10 10 Jones and responsivity of 20, 10.6, and 5.9 mA W -1 for 1064, 1550, and 2200 nm infrared light at 0 bias voltage, respectively. In addition, under the 2200 nm light, by applying an ultra-low bias voltage of 800 µV, the heterojunction exhibits ultra-low power and energy consumption of 28.8 pW and 0.64 pJ, successfully simulates a variety of synaptic behaviors under infrared light, and demonstrates its image perception and image memory capabilities. These findings position the BP/Ta 2 NiS 5 heterojunction as an ideal candidate for a multifunctional optoelectronic device crucial for advanced photodetection, neuromorphic computing, and artificial intelligence., (© 2024 Wiley‐VCH GmbH.)

Vascular smooth muscle cell (vSMC) dysfunction is a critical contributor to cardiovascular diseases, including atherosclerosis, restenosis and vein graft failure. Recent advances have unveiled a fascinating range of non-coding RNAs (ncRNAs) that play a pivotal role in regulating vSMC function. This review aims to provide an in-depth analysis of the mechanisms underlying vSMC dysfunction and the therapeutic potential of various ncRNAs in mitigating this dysfunction, either preventing or reversing it. We explore the intricate interplay of microRNAs, long-non-coding RNAs and circular RNAs, shedding light on their roles in regulating key signalling pathways associated with vSMC dysfunction. We also discuss the prospects and challenges associated with developing ncRNA-based therapies for this prevalent type of cardiovascular pathology. LINKED ARTICLES: This article is part of a themed issue Non-coding RNA Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.2/issuetoc., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Adults with prediabetes are at risk for Alzheimer's Disease and Related Dementia (ADRD). While exercise may lower ADRD risk, the exact mechanism is unclear. We tested the hypothesis that short-term exercise would raise neuronal insulin signaling and pro-BDNF in neuronal extracellular vesicles (nEVs) in prediabetes. Twenty-one older adults (18F, 60.0 ± 8.6 yrs.; BMI: 33.5 ± 1.1 kg/m 2 ) with prediabetes (ADA criteria; 75 g OGTT) were randomized to 12 supervised work-matched continuous (n = 13, 70% HR peak ) or interval (n = 8, 90% HR peak and 50% HR peak for 3 min each) sessions over 2-wks for 60 min/d. Aerobic fitness (VO 2 peak) and body weight were assessed. After an overnight fast, whole-body glucose tolerance (total area under the curve, tAUC) and insulin sensitivity (SIis) were determined from a 120 min 75 g OGTT. nEVs were acquired from 0 and 60 min time-points of the OGTT, and levels of insulin signaling proteins (i.e., p-IRS-1, total-/p-Akt, pERK1/2, pJNK1/2, and pp38) and pro-BNDF were measured. OGTT stimulatory effects were calculated from protein differences (i.e., OGTT 60-0 min). Adults were collapsed into a single group as exercise intensity did not affect nEV outcomes. Exercise raised VO 2 peak (+1.4 ± 2.0 mL/kg/min, p = 0.008) and insulin sensitivity (p = 0.01) as well as decreased weight (-0.4 ± 0.9 kg, p = 0.04) and whole-body glucose tAUC 120min (p = 0.02). Training lowered 0-min pro-BDNF (704.1 ± 1019.0 vs. 414.5 ± 533.5, p = 0.04) and increased OGTT-stimulated tAkt (-51.8 ± 147.2 vs. 95 ± 204.5 a.u., p = 0.01), which was paralleled by reduced pAkt/tAkt at 60 min of the OGTT (1.3 ± 0.2 vs. 1.2 ± 0.1 a.u., p = 0.04). Thus, 2 weeks of exercise altered neuronal insulin signaling responses to glucose ingestion and lowered pro-BNDF among adults with prediabetes, thereby potentially lowering ADRD risk., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Polycrystalline perovskite light-emitting diodes (PeLEDs) have shown great promise with high efficiency and easy processability. However, PeLEDs using single-cation polycrystalline perovskite emitters have demonstrated low efficiency due to defects within the grains and at the interfaces between the perovskite layer and the charge injection contact. Thus, simultaneous defect engineering of perovskites to suppress exciton loss within the grains and at the interfaces is crucial for achieving high efficiency in PeLEDs. Here, 1,8-octanedithiol which is a strong nucleophile, is used to increase the luminescence efficiency of a single-cation perovskite by suppressing non-radiative recombination within the grains of their polycrystalline emitter film as well as at their interface with an anode. The dithiol additive performs a multifunctional role in defect passivation, spatial confinement of excitons, and prevention of exciton quenching at the interface between the perovskite layer and the underlying hole-injection layer. Photoluminescence studies demonstrate that incorporating the dithiol additive significantly enhances the charge carrier dynamics in perovskites, resulting in an external quantum efficiency (EQE) of up to 23.46% even in a simplified PeLED that does not use a hole-injection layer. This represents the highest level of EQE achieved among devices utilizing polycrystalline single-cation perovskites., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)