Brownian Motion Governs the Plasmonic Enhancement of Colloidal Upconverting Nanoparticles.

Upconverting nanoparticles are essential in modern photonics due to their ability to convert infrared light to visible light. Despite their significance, they exhibit limited brightness, a key drawback that can be addressed by combining them with plasmonic nanoparticles. Plasmon-enhanced upconversion has been widely demonstrated in dry environments, where upconverting nanoparticles are immobilized, but constitutes a challenge in liquid media where Brownian motion competes against immobilization. This study employs optical tweezers for the three-dimensional manipulation of an individual upconverting nanoparticle, enabling the exploration of plasmon-enhanced upconversion luminescence in water. Contrary to expectation, experiments reveal a long-range (micrometer scale) and moderate (20%) enhancement in upconversion luminescence due to the plasmonic resonances of gold nanostructures. Comparison between experiments and numerical simulations evidences the key role of Brownian motion. It is demonstrated how the three-dimensional Brownian fluctuations of the upconverting nanoparticle lead to an "average effect" that explains the magnitude and spatial extension of luminescence enhancement.

Electroluminescence as a Probe of Strong Exciton-Plasmon Coupling in Few-Layer WSe2.

The manipulation of coupled quantum excitations is of fundamental importance in realizing novel photonic and optoelectronic devices. We use electroluminescence to probe plasmon-exciton coupling in hybrid structures consisting of a nanoscale plasmonic tunnel junction and few-layer two-dimensional transition-metal dichalcogenide transferred onto the junction. The resulting hybrid states act as a novel dielectric environment that affects the radiative recombination of hot carriers in the plasmonic nanostructure. We determine the plexcitonic spectrum from the electroluminescence and find Rabi splittings exceeding 50 meV in the strong coupling regime. Our experimental findings are supported by electromagnetic simulations that enable us to explore systematically and in detail the emergence of plexciton polaritons as well as the polarization characteristics of their far-field emission. Electroluminescence modulated by plexciton coupling provides potential applications for engineering compact photonic devices with tunable optical and electrical properties.

DNA Origami Assembled Nanoantennas for Manipulating Single-Molecule Spectral Emission.

The emission spectrum of a dye is given by the energy of all of the possible radiative transitions weighted by their probability. This spectrum can be altered with optical nanoantennas that are able to manipulate the decay rate of nearby emitters by modifying the local density of photonic states. Here, we make use of DNA origami to precisely place an individual dye at different positions around a gold nanorod and show how this affects the emission spectrum of the dye. In particular, we observe a strong suppression or enhancement of the transitions to different vibrational levels of the excitonic ground state, depending on the spectral overlap with the nanorod resonance. This reshaping can be used to experimentally extract the spectral dependence of the radiative decay rate enhancement. Furthermore, for some cases, we argue that the drastic alteration of the fluorescence spectrum could arise from the violation of Kasha's rule.

Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer.

Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)-complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease.

Preclinical models in head and neck squamous cell carcinoma.

Head and neck cancer is the sixth most frequent cancer type. Drug resistance and toxicity are common challenges of the existing therapies, making the development of reliable preclinical models essential for the study of the involved molecular mechanisms as well as for eventual intervention approaches that improve the clinical outcome. Preclinical models of head and neck squamous cell carcinoma have been traditionally based on cell lines and murine models. In this review, we will go over the most frequently used preclinical models, from immortalised-cell and primary tumour cultures in monolayer or 3D, to the currently available animal models. We will scrutinise their efficiency in mimicking the molecular and cellular complexity of head and neck squamous cell carcinoma. Finally, the challenges and the opportunities of other envisaged putative approaches, as well as the potential of the preclinical models to further develop personalised therapies will be discussed.

Non-Hermitian Anharmonicity Induces Single-Photon Emission.

Single-photon sources are in high demand for quantum information applications. A paradigmatic way to achieve single-photon emission is through anharmonicity in the energy levels, such that the absorption of a single photon from a coherent drive shifts the system out of resonance and prevents absorption of a second one. We identify a novel mechanism for single-photon emission through non-Hermitian anharmonicity, i.e., anharmonicity in the losses instead of in the energy levels. We demonstrate the mechanism in two types of systems, including a feasible setup consisting of a hybrid metallodielectric cavity weakly coupled to a two-level emitter, and show that it induces high-purity single-photon emission at high repetition rates.

Role of top flat magnetic stimulation for urinary incontinence as a debilitating condition of pelvic floor dysfunction: an observational evaluation of Latin American population.

BACKGROUND: Urinary incontinence (UI) is a common dysfunction of the pelvic floor, affecting 10-20% of all women, and up to 70% in the elderly general prevalence of 17% 20-year-old women and 38% in women over 60 years. It is estimated that only 25% of patients seek treatment for this debilitating condition. AIM: The aim of this study was to evaluate the efficacy of a device based on top flat magnetic stimulation to treat pelvic floor disorders especially female urinary incontinence. METHODS: A total of 33 volunteer patients were divided into 5 groups according to the type of complaint. Subjects received 8 treatment sessions, with a frequency of twice a week with two different settings. Pelvic Floor Bother Questionnaire (PFBQ), Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) and Urinary Incontinence Short Form (ICIQ-UI-SF) were compiled by all patients at the beginning and after 3 months from the end of the last treatment (3MFU). RESULTS: The patient's scores from validated Questionnaires significantly decreased (p < 0.01) from baseline up to 3MFU inside most of the groups. CONCLUSIONS: The noninvasiveness and safety of device make this approach an interesting tool as alternative approach for pelvic floor dysfunctions .

Ethical, legal, organizational and social issues related to the use of scalp cooling for the prevention of chemotherapy-induced alopecia: A systematic review.

INTRODUCTION: Scalp cooling (SC) aims to prevent chemotherapy-induced alopecia. The goal of this systematic review is to tackle ethical, legal, organizational and social issues related to SC. METHODS: A critical appraisal of the literature was carried out using a systematic review design. MEDLINE, Embase and Web of Science databases were searched up until 2 June 2021. Studies addressing these aspects in English or Spanish were considered. Representatives of both patient associations and professional scientific societies related to the topic participated in the design of the protocol and the review of the findings. RESULTS: A total of 17 studies were included. Articles were critically appraised using the MMAT and SANRA. Findings were organized into four categories: (1) ethical aspects focused on equal access, gender equity and doctor-patient communication supported by Patient Decision Aids (PtDAs); (2) patient perspective and acceptability; (3) professional perspective and acceptability; (4) organizational aspects focused on accessibility and feasibility. CONCLUSION: Cancer patients' expectations when using SC need to be adjusted to reduce the potential distress associated with hair loss. PtDAs could help patients clarify their values and preferences regarding SC. Equal access to technology should be guaranteed. PATIENT OR PUBLIC CONTRIBUTION: In this systematic review, the representatives of the patient associations (Ms. María Luz Amador Muñoz of the Spanish Association Against Cancer [AECC] and Ms. Catiana Martinez Cánovas of the Spanish Breast Cancer Federation [FECMA]) participated in the review of the study protocol, as well as in the results, discussion and conclusions, making their contributions. In the type of design of these studies (systematic reviews), it is not usual to have the direct participation of patients, but in this one, we have done so, as it is a systematic review that is part of a report of the Spanish Network of Health Technology Assessment Agencies (ETS).

Plexcitonic Quantum Light Emission from Nanoparticle-on-Mirror Cavities.

We investigate the quantum-optical properties of the light emitted by a nanoparticle-on-mirror cavity filled with a single quantum emitter. Inspired by recent experiments, we model a dark-field setup and explore the photon statistics of the scattered light under grazing laser illumination. Exploiting analytical solutions to Maxwell's equations, we quantize the nanophotonic cavity fields and describe the formation of plasmon-exciton polaritons (or plexcitons) in the system. This way, we reveal that the rich plasmonic spectrum of the nanocavity offers unexplored mechanisms for nonclassical light generation that are more efficient than the resonant interaction between the emitter natural transition and the brightest optical mode. Specifically, we find three different sample configurations in which strongly antibunched light is produced. Finally, we illustrate the power of our approach by showing that the introduction of a second emitter in the platform can enhance photon correlations further.

DNA-Templated Ultracompact Optical Antennas for Unidirectional Single-Molecule Emission.

Optical antennas are nanostructures designed to manipulate light-matter interactions by interfacing propagating light with localized optical fields. In recent years, numerous devices have been realized to efficiently tailor the absorption and/or emission rates of fluorophores. By contrast, modifying the spatial characteristics of their radiation fields remains challenging. Successful phased array nanoantenna designs have required the organization of several elements over a footprint comparable to the operating wavelength. Here, we report unidirectional emission of a single fluorophore using an ultracompact optical antenna. The design consists of two side-by-side gold nanorods self-assembled via DNA origami, which also controls the positioning of the single-fluorophore. Our results show that when a single fluorescent molecule is positioned at the tip of one nanorod and emits at a frequency capable of driving the antenna in the antiphase mode, unidirectional emission with a forward to backward ratio of up to 9.9 dB can be achieved.

Amyotrophic Lateral Sclerosis and Serum Lipid Level Association: A Systematic Review and Meta-Analytic Study.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. Many metabolic alterations occur during ALS progress and can be used as a method of pre-diagnostic and early diagnosis. Dyslipidemia is one of the physiological changes observed in numerous ALS patients. The aim of this study is to analyze the possible relationship between the rate of disease progression (functional rating scale (ALS-FRS)) and the plasma lipid levels at the early stage of ALS. A systematic review was carried out in July 2022. The search equation was "Triglycerides AND amyotrophic lateral sclerosis" and its variants. Four meta-analyses were performed. Four studies were included in the meta-analysis. No significant differences were observed between the lipid levels (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol) and the ALS-FRS score at the onset of the disease. Although the number of studies included in this research was low, the results of this meta-analytic study suggest that there is no clear relationship between the symptoms observed in ALS patients and the plasma lipid levels. An increase in research, as well as an expansion of the geographical area, would be of interest.

Metabolic Disturbance of High-Saturated Fatty Acid Diet in Cognitive Preservation.

Aging continues to be the main cause of the development of Alzheimer's, although it has been described that certain chronic inflammatory pathologies can negatively influence the progress of dementia, including obesity and hyperlipidemia. In this sense, previous studies have shown a relationship between low-density lipoprotein receptor (LDLR) and the amyloid-beta (Aß) binding activity, one of the main neuropathological features of Alzheimer's disease (AD). LDLR is involved in several processes, including lipid transport, regulation of inflammatory response and lipid metabolism. From this perspective, LDLR-/- mice are a widely accepted animal model for the study of pathologies associated with alterations in lipid metabolism, such as familial hypercholesterolemia, cardiovascular diseases, metabolic syndrome, or early cognitive decline. In this context, we induced hyperlipidemia in LDLR-/- mice after feeding with a high-saturated fatty acid diet (HFD) for 44 weeks. LDLR-/--HFD mice exhibited obesity, hypertriglyceridemia, higher glucose levels, and early hepatic steatosis. In addition, HFD increased plasmatic APOE and ubiquitin 60S levels. These proteins are related to neuronal integrity and health maintenance. In agreement, we detected mild cognitive dysfunctions in mice fed with HFD, whereas LDLR-/--HFD mice showed a more severe and evident affectation. Our data suggest central nervous system dysfunction is associated with a well-established metabolic syndrome. As a late consequence, metabolic syndrome boots many behavioral and pathological alterations recognized in dementia, supporting that the control of metabolic parameters could improve cognitive preservation and prognosis.

Gut Microbiota and Therapy in Metastatic Melanoma: Focus on MAPK Pathway Inhibition.

Gut microbiome (GM) and its either pro-tumorigenic or anti-tumorigenic role is intriguing and constitutes an evolving landscape in translational oncology. It has been suggested that these microorganisms may be involved in carcinogenesis, cancer treatment response and resistance, as well as predisposition to adverse effects. In melanoma patients, one of the most immunogenic cancers, immune checkpoint inhibitors (ICI) and MAPK-targeted therapy-BRAF/MEK inhibitors-have revolutionized prognosis, and the study of the microbiome as a modulating factor is thus appealing. Although BRAF/MEK inhibitors constitute one of the main backbones of treatment in melanoma, little is known about their impact on GM and how this might correlate with immune re-induction. On the contrary, ICI and their relationship to GM has become an interesting field of research due to the already-known impact of immunotherapy in modulating the immune system. Immune reprogramming in the tumor microenvironment has been established as one of the main targets of microbiome, since it can induce immunosuppressive phenotypes, promote inflammatory responses or conduct anti-tumor responses. As a result, ongoing clinical trials are evaluating the role of fecal microbiota transplant (FMT), as well as the impact of using dietary supplements, antibiotics and probiotics in the prediction of response to therapy. In this review, we provide an overview of GM's link to cancer, its relationship with the immune system and how this may impact response to treatments in melanoma patients. We also discuss insights about novel therapeutic approaches including FMT, changes in diet and use of probiotics, prebiotics and symbiotics. Finally, we hypothesize on the possible pathways through which GM may impact anti-tumor efficacy in melanoma patients treated with targeted therapy, an appealing subject of which little is known.

Positive Family Environment, General Distress, Subjective Well-Being, and Academic Engagement among High School Students Before and During the COVID-19 Outbreak.

The COVID-19 pandemic has altered the family dynamics of most people worldwide as well as the mode in which students take classes. The impact of such changes on students' well-being, academic engagement, and general distress remains unknown. Therefore, this study aims to test the structural relations among positive family environment (a measure of Positive Home-Based Parent Involvement [HBI]), subjective well-being (SWB), general distress, and academic engagement, focusing on Mexican high school students. A longitudinal study was conducted covering two time points: before (T1) and during (T2) the COVID-19 outbreak. A sample of 502 students answered questionnaires in T1 whereas 111 did so in T2. Analyses were conducted using Mplus software. Principal results showed that the positive and significant association between positive family environment and SWB did not substantially change from T1 to T2, whereas the relation between positive family environment and academic engagement became stronger. Data revealed that a positive family environment can play an important role in promoting academic engagement among adolescent students despite the risks brought about by sanitary lockdowns and the increase of family interactions. Results are discussed highlighting the importance of positive family environments and HBI on academic outcomes for Mexican high school students.

Few-Mode Field Quantization of Arbitrary Electromagnetic Spectral Densities.

We develop a framework that provides a few-mode master equation description of the interaction between a single quantum emitter and an arbitrary electromagnetic environment. The field quantization requires only the fitting of the spectral density, obtained through classical electromagnetic simulations, to a model system involving a small number of lossy and interacting modes. We illustrate the power and validity of our approach by describing the population and electric field spatial dynamics in the spontaneous decay of an emitter placed in a complex hybrid plasmonic-photonic structure.

Impact of weight loss on cancer patients' quality of life at the beginning of the chemotherapy.

PURPOSE: Among the prognostic factors relevant to the condition of oncological patients, nutritional status (NS) has the greatest single impact on quality of life (QL). The goals of our study were to evaluate the influence of NS, weight loss (WL), and the presence of cachexia, prior to the initiation of chemotherapy, on the patient's QL. METHODS: Adult patients (aged ≥ 18 years) diagnosed with solid tumours for whom chemotherapy was started between April 2016 and June 2017 were eligible for inclusion in the study. They were asked to complete a QL questionnaire (Functional Assessment of Cancer Treatment (FACT-G)) at the beginning. The presence or absence of cachexia was evaluated at the outset, following the definition proposed by Fearon and nutritional assessment by the Patient-Generated Subjective Global Assessment (PG-SGA) scale. RESULTS: A total of 177 patients completed the FACT-G, the 60% receiving curative therapy. At the start of the treatment, 58.2% of patients had experienced WL, with an average of 4.4 ± 7.4%, and 19% were at risk of malnutrition. Patient who presented cachexia at diagnosis, were treated with palliative intention, had a Nutriscore ≥ 5 points or presented malnutrition in accordance with PG-SGA had a poorer QL (p < 0.05). Greater WL was associated with a worsened QL (p = 0.001). Breast cancer patients presented an inverse correlation between the %WL and the initial score in the FACT-G (r = - 0.304, p = 0.023), whereas no such correlation was observed for the other types of tumour (r = - 0.012, p = 0.892). CONCLUSIONS: These results underline the relation of NS before starting chemotherapy and QL. Greater WL was associated with a worsened QL, especially in women with breast cancer.

[Health professionals' perception about the socio-educational group intervention with women who present somatic symptoms without organic cause]. / Percepción de profesionales de la salud sobre la intervención grupal socioeducativa con mujeres que presentan síntomas somáticos sin causa orgánica.

OBJECTIVE: To know the perception and opinion of primary care health professionals on the impact of non-medicalizing group educational intervention (GRUSE) with women who present somatic symptoms without organic cause. DESIGN: Qualitative phenomenological study. SETTING: Primary care health centers in Andalusia, during 2017 and 2018. PARTICIPANTS AND/OR CONTEXTS: Twenty-four health professionals, selected according to their level of involvement in the GRUSE strategy (socio-educational groups). METHOD: A qualitative methodology is applied, through the phenomenological method. The technique used to collect the information is the discussion group, and a content analysis is carried out on it. The software Atlas.ti 8.0 is used as a support resource for the analysis. RESULTS: Health professionals highlight group work as a means of achieving change, and point to the importance of intervention as a non-medicalizing strategy. They perceive that the participants obtain some benefits: the improvement of their personal well-being, the increase of their self-esteem and self-determination, and the generation of social networks, benefits that also affect their immediate surroundings. CONCLUSIONS: In the opinion of the professionals, the strategy has positive effects on women and does not mean an increase in resources for the health system. In addition, they express the importance of provide women with tools to cope with daily life problems derivates mostly from gender mandates of a patriarchal society.

On the applicability of quantum-optical concepts in strong-coupling nanophotonics.

Rooted in quantum optics and benefiting from its well-established foundations, strong coupling in nanophotonics has experienced increasing popularity in recent years. With nanophotonics being an experiment-driven field, the absence of appropriate theoretical methods to describe ground-breaking advances has often emerged as an important issue. To address this problem, the temptation to directly transfer and extend concepts already available from quantum optics is strong, even if a rigorous justification is not always available. In this review we discuss situations where, in our view, this strategy has indeed overstepped its bounds. We focus on exciton-plasmon interactions, and particularly on the idea of calculating the number of excitons involved in the coupling. We analyse how, starting from an unfounded interpretation of the term N/V that appears in theoretical descriptions at different levels of complexity, one might be tempted to make independent assumptions for what the number N and the volume V are, and attempt to calculate them separately. Such an approach can lead to different, often contradictory results, depending on the initial assumptions (e.g. through different treatments of V as the-ambiguous in plasmonics-mode volume). We argue that the source of such contradictions is the question itself-How many excitons are coupled?, which disregards the true nature of the coupled components of the system, has no meaning and often not even any practical importance. If one is interested in validating the quantum nature of the system-which appears to be the motivation driving the pursuit of strong coupling with small N-one could instead focus on quantities such as the photon emission rate or the second-order correlation function. While many of the issues discussed here may appear straightforward to specialists, our target audience is predominantly newcomers to the field, either students or scientists specialised in different disciplines. We have thus tried to minimise the occurrence of proofs and overly-technical details, and instead provide a qualitative discussion of analyses that should be avoided, hoping to facilitate further growth of this promising area.

Pronounced Photovoltaic Response from Multilayered Transition-Metal Dichalcogenides PN-Junctions.

Transition metal dichalcogenides (TMDs) are layered semiconductors with indirect band gaps comparable to Si. These compounds can be grown in large area, while their gap(s) can be tuned by changing their chemical composition or by applying a gate voltage. The experimental evidence collected so far points toward a strong interaction with light, which contrasts with the small photovoltaic efficiencies η ≤ 1% extracted from bulk crystals or exfoliated monolayers. Here, we evaluate the potential of these compounds by studying the photovoltaic response of electrostatically generated PN-junctions composed of approximately 10 atomic layers of MoSe2 stacked onto the dielectric h-BN. In addition to ideal diode-like response, we find that these junctions can yield, under AM-1.5 illumination, photovoltaic efficiencies η exceeding 14%, with fill factors of ~70%. Given the available strategies for increasing η such as gap tuning, improving the quality of the electrical contacts, or the fabrication of tandem cells, our study suggests a remarkable potential for photovoltaic applications based on TMDs.

Historical exposure to persistent organic pollutants and risk of incident hypertension.

The aim of this study was to assess the influence of adipose tissue concentrations of a group of persistent organic pollutants (POPs) on the risk of hypertension in an adult cohort of residents of Granada (Southern Spain) over a 10-year follow-up. No chemical was significantly associated with the risk of hypertension in the overall population or when models were stratified by sex or median age. However, we found positive associations between log-transformed POP concentrations and hypertension risk in participants with body mass index (BMI) above the median value of 26.3kg/m(2), which were statistically significant for hexachlorobenzene (HR=1.26, 95% CI=1.03-1.56), ß-hexachlorocyclohexane (HR=1.25, 95% CI=1.03-1.51), and polychlorinated biphenyl congeners -138 (HR=1.32, 95% CI=1.04-1.69) and -153 (HR=1.36, 95% CI=1.00-1.84). Inverse associations were observed in the subgroup with BMI≤26.3kg/m(2), but none was statistically significant. More research and a longer follow-up period are warranted to verify these associations and elucidate the role of obesity as a potential effect modifier. Given the elevated worldwide frequency of POP exposure and hypertension, the public health impact of this relationship may be substantial.