Intracellular Synthesis of Indoles Enabled by Visible-Light Photocatalysis.

Performing abiotic synthetic transformations in live cell environments represents a new, promising approach to interrogate and manipulate biology and to uncover new types of biomedical tools. We now found that photocatalytic bond-forming reactions can be added to the toolbox of bioorthogonal synthetic chemistry. Specifically, we demonstrate that exogenous styryl aryl azides can be converted into indoles inside living mammalian cells under photocatalytic conditions.

Polarization calibration assessment for a broadband imaging polarimeter based on a division of aperture architecture.

This article intends to provide all the experimental insights and analyze the best polarimetric calibration method for a division of aperture polarimetric imager considering the different implications it has on the experimental set-up and its performance. Polarimetric cameras require careful calibration for the correct measurement of polarization information. The calibration methods are introduced, intermediate results are presented, and the ability of the set-up to estimate Stokes vectors and Mueller matrices of the samples in passive and active imaging modes is evaluated. Polarization information recovery achieves accuracy errors below the 10% for all polarization modes when the Data Reduction Matrix or the Eigenvalue Calibration Method are used. Such performance, however, degrades significantly when using the Polarizer Calibration Method. To the best of our knowledge, this is the first time such a detailed comparison of calibration methods is presented in the literature, and it is also the first time the Polarizer Calibration Method is applied to a division of aperture polarimeter.

DNA polymorphisms associated with lactase persistence, self-perceived symptoms of lactose intolerance, milk and dairy consumption, and ancestry, in the Uruguayan population.

Uruguay has one of the highest per capita milk intakes worldwide, even with a limited supply of lactose-free products; furthermore, the admixed nature of its population is well known, and various frequencies of lactase persistence (LP) are observed in the source populations. We aimed to contribute to the understanding of the relation between allelic variants associated with LP, milk consumption, digestive symptoms, and genetic ancestry in the Uruguayan population. Samples of saliva or peripheral blood were collected from 190 unrelated individuals from two regions of Uruguay, genotypes for polymorphic sites in a fragment within the LCT enhancer were determined and allelic frequencies calculated in all of them. Data were collected on frequency of milk and dairy consumption and self-reported symptoms in a subsample of 153 individuals. Biparental and maternal ancestry was determined by analyzing individual ancestry markers and mitochondrial DNA. Twenty-nine percentage of individuals reported symptoms attributed to the ingestion of fresh milk, with abdominal pain, bloating and flatulence being the most frequent. European LP-associated allele T-13910 showed a frequency of 33%, while other LP-associated alleles like G-13915 and T-14011 were observed in very low frequencies. Associations between self-reported symptoms, fresh milk intake, and C/T-13910 genotype were statistically significant. No evidence of association between genetic ancestry and C/T-13910 was found, although individuals carrying one T-13910 allele appeared to have more European ancestry. In conclusion, the main polymorphism capable of predicting lactose intolerance in Uruguayans is C/T-13910, although more studies are required to unravel the relation between genotype and lactase activity, especially in heterozygotes.

Effects of exercise interventions to reduce chemotherapy-induced peripheral neuropathy severity: A meta-analysis.

OBJECTIVES: The two aims of this systematic review and meta-analysis were to (1) analyze the effect of exercise on chemotherapy-induced peripheral neuropathy (CIPN) severity and (2) determine the best type of exercise for the management of CIPN. METHODS: We systematically searched the MEDLINE, WOS, Sportdiscus, Scopus, and Cochrane databases from inception to December 2020 for experimental studies addressing the effect of exercise on CIPN severity, as measured by symptom severity (SSS) and peripheral deep sensitivity (PDS). The DerSimonian and Laird method was used to compute pooled estimates of the standardized mean differences (SMDs) and its respective 95% confidence intervals (CIs). Subgroup analyses were performed based on the types of exercise and the frequency and length of the interventions. RESULTS: Thirteen studies were included in this meta-analysis. In the analyses comparing exercise interventions versus controls, there was an improvement in the SSS (SMD = -0.21; 95% CI: -0.40 to -0.01; %change: -20.34%) and the PDS (SMD = 0.49; 95% CI: 0.06 to 0.91; %change: 31.64%) in favor of the intervention group. In the pre-post analyses, there was an improvement in the SSS (SMD = -0.72; 95% CI: -1.10 to -0.34; %change: -15.65%) and the PDS (SMD = 0.47; 95% CI: 0.15 to 0.79; %change:18.98%). CONCLUSIONS: This meta-analysis provides an overview of the evidence supporting exercise as a suitable intervention to reduce the severity of CIPN by reducing the severity of the symptoms and the peripheral deep sensitivity among patients with cancer or cancer survivors. Furthermore, sensoriomotor training and mind-body exercises appear to be more effective in reducing symptom severity, and active nerve-specific exercises and mind-body exercises seem to be more effective in improving peripheral deep sensitivity.

Effect of different types of exercise on fitness in people with multiple sclerosis: A network meta-analysis.

BACKGROUND: It is assumed that people with multiple sclerosis (MS) who participate in programs of physical exercise improve their physical fitness. OBJECTIVE: The aim of this network meta-analysis (NMA) was to analyze the effect of different types of exercise on muscular fitness and cardiorespiratory fitness (CRF) among people with MS and to determine the best type of exercise according to disease severity. METHODS: MEDLINE, the Physiotherapy Evidence Database, the Cochrane Library, SPORTDiscus, Scopus, and Web of Science were searched from inception to April 2022 to identify randomized controlled trials (RCTs) concerning the effect of physical exercise on fitness in people with MS. We ranked the types of physical exercise by calculating the surface under the cumulative ranking (SUCRA). RESULTS: We included 72 RCTs involving 2543 MS patients in this NMA. A ranking of five types of physical exercise (aerobic, resistance, combined [aerobic and resistance], sensorimotor training, and mind-body exercises) was achieved. Combined and resistance training had the highest effect sizes (0.94, 95% CI 0.47, 1.41, and 0.93, 95% CI 0.57, 1.29, respectively) and the highest SUCRA (86.2% and 87.0%, respectively) for muscular fitness. The highest effect size (0.66, 95% CI 0.34, 0.99) and SUCRA (86.9%) for CRF was for aerobic exercise. CONCLUSIONS: Combined and resistance training seem to be the most effective exercises to improve muscular fitness and aerobic exercise for CRF in people with MS.

Experimental Characterization of Polarized Light Backscattering in Fog Environments.

This paper focuses on the experimental characterization of the polarization behavior of light backscattered through fog. A polarimetric orthogonal state contrast imager and an active, purely polarized white illuminator system are used to evaluate both linear and circular polarization signals. The experiments are carried out in a macro-scale fog chamber under controlled artificial fog conditions. We explore the effect of backscattering in each imaging channel, and the persistence of both polarization signals as a function of meteorological visibility. We confirm the presence of the polarization memory effect with circularly polarized light, and, as a consequence, the maintenance of helicity in backscattering. Moreover, the circular cross-polarized channel is found to be the imaging channel less affected by fog backscattering. These results are useful and should be taken into account when considering active polarimetric imaging techniques for outdoor applications under foggy conditions.

Analysis of the performance of a polarized LiDAR imager in fog.

This paper focuses on exploring ways to improve the performance of LiDAR imagers through fog. One of the known weaknesses of LiDAR technology is the lack of tolerance to adverse environmental conditions, such as the presence of fog, which hampers the future development of LiDAR in several markets. Within this paper, a LiDAR unit is designed and constructed to be able to apply temporal and polarimetric discrimination for detecting the number of signal photons received with detailed control of its temporal and spatial distribution under co-polarized and cross-polarized configurations. The system is evaluated using different experiments in a macro-scale fog chamber under controlled fog conditions. Using the complete digitization of the acquired signals, we analyze the natural light media response, to see that due to its characteristics it could be directly filtered out. Moreover, we confirm that there exists a polarization memory effect, which, by using a polarimetric cross-configuration detector, allows improvement of object detection in point clouds. These results are useful for applications related to computer vision, in fields like autonomous vehicles or outdoor surveillance where many variable types of environmental conditions may be present.

Quantitative demonstration of the superiority of circularly polarized light in fog environments.

The polarization behavior of light transmitted through scattering media is studied quantitatively. A division of focal plane (DOFP) imaging polarimeter modified with a wideband quarter-wave plate (QWP) is used to evaluate the linear and circular depolarization signals. This system allows the measurement of the linear and circular co-polarization and cross-polarization channels simultaneously. The experiments are carried out at CEREMA's 30 m fog chamber under controlled fog density conditions. The polarization memory effect with circularly polarized light is demonstrated to be superior in forward transmission compared to the same phenomena with linearly polarized light when imaging inside a scattering medium. This paves the way for its use in imaging through scattering media for hazard detection in different applications.

Effect of Manual Therapy Interventions on Range of Motion Among Individuals with Myofascial Trigger Points: A Systematic Review and Meta-Analysis.

OBJECTIVE: Patients with myofascial trigger points (MTPs) frequently manifest restricted range of motion (ROM) during physical evaluation. Multiple manual therapy interventions have been developed for the treatment of MTPs, but their effect on ROM has not been clarified through a systematic review and meta-analysis. Thus, this systematic review aimed to assess the effect of manual therapy interventions on ROM among individuals with MTPs. METHODS: A systematic search was conducted in PubMed, Web of Science, Cochrane, Scopus, and Clinical Trials.gov. Articles analyzing the effect of manual therapy interventions on ROM were included. The risk of bias was assessed with the Cochrane Risk of Bias (RoB) 2 tool. The DerSimonian-Laird method was used to compute the pooled effect size (ES) and its 95% confidence interval (95% CI) for ROM. RESULTS: A total of 13 randomized controlled trials were included in this systematic review and meta-analysis. The pooled ES for ROM was 0.52 (95% CI: 0.42-0.63). The pooled ES for ROM evaluated in centimeters was 0.36 (95% CI: 0.14-0.59), and the pooled ES for ROM evaluated in degrees was 0.57 (95% CI: 0.47-0.68). CONCLUSION: Manual therapy interventions may be an effective approach for improving ROM among individuals with MTPs.

Prevalence of Neuropsychiatric Disorders in Duchenne and Becker Muscular Dystrophies: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the prevalence of neuropsychiatric disorders, including autism spectrum disorders (ASDs), attention-deficit hyperactivity disorder (ADHD), depression, anxiety disorders, and obsessive-compulsive disorder (OCD), in populations with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DATA SOURCES: MEDLINE (via PubMed), Scopus, Web of Science, and Cochrane Library from inception to November 2021. STUDY SELECTION: Observational studies of individuals with DMD or BMD that estimated the prevalence of ASDs, ADHD, depression, anxiety disorders, and OCD in each population. DATA EXTRACTION: A random-effects meta-analysis was performed on each outcome and each population (ie, DMD, BMD). DATA SYNTHESIS: Twenty-three studies were included in the meta-analysis. In DMD, there was a prevalence of 7.0% of ASDs, 18.0% of ADHD, 11.0% of depression, 24.0% of anxiety disorders, and 12.0% of OCD. Furthermore, in BMD, there was a prevalence of 6.0% of ASDs, 28.0% of ADHD, 7.0% of depression, 25.0% of anxiety disorders, and 7.0% of OCD. CONCLUSIONS: The prevalence of these neuropsychiatric disorders is higher among patients with DMD or BMD than among the general population, and the presence of these disorders may negatively influence optimal medical management.

Effect of Exercise on Fatigue in Multiple Sclerosis: A Network Meta-analysis Comparing Different Types of Exercise.

OBJECTIVE: A network meta-analysis (NMA) of current evidence was conducted to determine if physical exercise has a positive influence on multiple sclerosis (MS) fatigue and type of exercise with the largest effect on fatigue also according to disease severity. DATA SOURCES: MEDLINE, Embase, SPORTDiscus, Physiotherapy Evidence Database, Cochrane Library, and Web of Science. The search strategy combined relevant terms related to (1) MS; (2) clinical trials; (3) exercise; and (4) fatigue from inception to February 2021. STUDY SELECTION: Randomized controlled trials concerning the effectiveness of different types of exercise on total and physical fatigue in people with MS were included. DATA EXTRACTION: The data were extracted into predesigned data extraction tables. Risk of bias was evaluated with the Cochrane Risk of Bias tool (RoB 2.0), and the Grading of Recommendations, Assessment, Development, and Evaluation tool was used to evaluate the quality of the evidence. DATA SYNTHESIS: A total of 58 studies were examined. Data were pooled using a random-effects model. A ranking of 7 and 8 different exercise interventions for physical and total fatigue scores, respectively, was achieved. The highest effects for pairwise comparisons were for combined exercise and resistance training vs control (ranging between -0.74 and -1.24). In the NMA, combined exercise (-1.51; 95% confidence interval [CI], -2.01 to -1.01) and resistance training (-1.15; 95% CI, -1.81 to -0.49) compared with the control group achieved the highest effects for physical and total fatigue, respectively. CONCLUSIONS: Exercise should be considered an effective fatigue management strategy. Among the different exercise modalities, combined exercise is the most effective exercise modality for improving both physical and total fatigue. Resistance training is also an effective exercise for total fatigue among people diagnosed with MS.

Napping and cognitive decline: a systematic review and meta-analysis of observational studies.

BACKGROUND: No clear evidence is available for the influence of napping on cognitive function in older adults. This systematic review and meta-analysis aimed to elucidate the cross-sectional and longitudinal relationships between napping and cognitive function (global cognition and memory) and to explore whether some individual characteristics and sleep characteristics can modify this relationship. METHODS: We systematically searched Medline (via PubMed), Web of Science, and Scopus. DerSimonian and Lair and Hartung-Knapp-Sidik-Jonkman random effects methods were used to compute pooled estimates of odds ratios (ORs) and their respective 95% confidence intervals (95% CIs) for the association of global cognition and memory with napping. The mean age, the night sleep time (hours), and the percentage of women, no nappers, and people in the less night-time sleep duration category were used for meta-regressions. RESULTS: Twenty-five studies were included in this systematic review and meta-analysis, 18 cross-sectional and seven longitudinal studies, including 95,719 participants older than 60 years. The pooled ORs from the cross-sectional analyses were 1.03 (95% CI: 1.01 to 1.06) for global cognition and 1.06 (95%: 0.90 to 1.26) for memory. The pooled ORs from the longitudinal analyses were 1.00 (95% 0.85 to 1.18) for global cognition and 1.08 (95% 0.98 to 1.19) for memory. These associations were not modified by individual or sleep characteristics. CONCLUSION: Our data confirm the absence of association between napping and global cognition and memory regardless of the characteristics of the population. This information might be considered when providing lifestyle recommendations to adults with and without cognitive complaints.

Telomere Length, SIRT1, and Insulin in Male Master Athletes: The Path to Healthy Longevity?

Lower SIRT1 and insulin resistance are associated with accelerated telomere shortening. This study investigated whether the lifestyle of master athletes can attenuate these age-related changes and thereby slow aging. We compared insulin, SIRT1, and telomere length in highly trained male master athletes (n=52; aged 49.9±7.2 yrs) and age-matched non-athletes (n=19; aged 47.3±8.9 yrs). This is a cross-sectional study, in which all data were collected in one visit. Overnight fasted SIRT1 and insulin levels in whole blood were assessed using commercial kits. Relative telomere length was determined in leukocytes through qPCR analyses. Master athletes had higher SIRT1, lower insulin, and longer telomere length than age-matched non-athletes (p<0.05 for all). Insulin was inversely associated with SIRT1 (r=-0.38; p=0.001). Telomere length correlated positively with SIRT1 (r=0.65; p=0.001), whereas telomere length and insulin were not correlated (r=0.03; p=0.87). In conclusion, master athletes have higher SIRT1, lower insulin, and longer telomeres than age-matched non-athletes. Furthermore, SIRT1 was negatively associated with insulin and positively associated with telomere length. These findings suggest that in this sample of middle-aged participants reduced insulin, increased SIRT1 activity, and attenuation of biological aging are connected.

Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge.

Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4+ and CD4-), and, to a lower extent, in B-cells from healthy controls. Notably, IDE's surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE's surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4+ T-cells, and CD4- T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4+ T-cells and CD4- T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients.

Maternal Education and Academic Achievement in Schoolchildren: The Role of Cardiorespiratory Fitness.

OBJECTIVES: To examine the relationship between maternal education, cardiorespiratory fitness, and academic achievement in schoolchildren, specifically whether the association between maternal education and academic achievement is mediated by cardiorespiratory fitness. STUDY DESIGN: This is a secondary analysis of a cross-sectional study including 478 Spanish schoolchildren aged 8-11 years. ANOVA was used to test differences in cardiorespiratory fitness by maternal education level. ANCOVA was used to test the differences in academic achievement by the educational level of mothers and the cardiorespiratory fitness of children, controlling for each other. A mediation analysis was used to test if the relationship between maternal education and academic achievement was explained by cardiorespiratory fitness. RESULTS: A higher level of maternal education was associated with a higher cardiorespiratory fitness level and academic achievement in children; moreover, the cardiorespiratory fitness level in children was associated with better academic achievement (P < .05). Finally, cardiorespiratory fitness acted as a partial mediator of the relationship between maternal education and academic achievement in boys (z = 1.81; P = .03) but not in girls (z = 0.86; P = .19), explaining 6.54% of this relationship for the total sample and 6.67% for boys. CONCLUSIONS: This study suggests that the benefits of maternal education on academic achievement are partially explained by the mediating role of cardiorespiratory fitness.

The effect of hallux valgus open and percutaneous surgery on AOFAS scale: a systematic review and meta-analysis.

PURPOSE: To estimate the comparative effect of open and percutaneous hallux valgus (HV) surgery on patients' quality of life (QoL) using the American Orthopedic Foot and Ankle Society (AOFAS) scale including total score and individual domains (pain, function, and alignment). METHODS: MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched from inception to March 2020 for studies on the effect of HV surgery on patients' QoL using the AOFAS score. A standardized mean difference score was calculated on the total AOFAS score and on each AOFAS domain (pain, function, and alignment) using Cohen's d index. RESULTS: Considering the 53 published studies included, the pooled effect size (ES) estimates for the AOFAS total score were 3.69 (95% CI 3.37-4.01; I2 = 95.5%) for open surgery and 3.40 (95% CI 2.99-3.80, I2 = 88.2%) for percutaneous surgery. The total pooled ES estimate was 3.61 (95% CI 3.35-3.87, I2 = 94.5%). Considering the pain domain, the pooled ES estimates were 2.21 (95% CI 1.98-2.43, I2 = 64%) for open surgery and 2.52 (95% CI 1.83-3.20, I2 = 92.6%) for percutaneous surgery. For the function domain, the pooled ES estimates were 1.37 (95% CI 0.93-1.81, I2 = 91%) for open surgery and 2.28 (95% CI 1.10-3.47, I2 = 96.8%) for percutaneous surgery. Finally, the pooled ES estimates for the alignment domain were 3.99 (95% CI 3.51-4.47, I2 = 85.7%) for open surgery and 2.66 (95% CI 2.23-3.09, I2 = 78.5%) for percutaneous surgery. CONCLUSION: Our data support that HV surgery increases the total AOFAS score as well as the AOFAS scores by domain (pain, function, and alignment). Furthermore, our data show that HV surgery increases patients' QoL, after both open and percutaneous surgery, without differences between them.

Effectiveness of Pulmonary Rehabilitation in Interstitial Lung Disease, Including Coronavirus Diseases: A Systematic Review and Meta-analysis.

OBJECTIVE: A meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effect of pulmonary rehabilitation on functional capacity and quality of life in interstitial lung diseases, including those caused by coronaviruses. DATA SOURCES: MEDLINE, EMBASE, SPORTDiscus, Cochrane Library, Web of Science, and MedRxiv from inception to November 2020 were searched to identify documents. STUDY SELECTION: Publications investigating the effect of pulmonary rehabilitation on lung function (forced vital capacity [FVC]), exercise capacity (6-minute walk distance [6MWD]), health related quality of life (HRQOL), and dyspnea were searched. DATA EXTRACTION: The data were extracted into predesigned data extraction tables. Risk of bias was evaluated with the Cochrane Risk of Bias tool (RoB 2.0). DATA SYNTHESIS: A total of 11 RCTs with 637 interstitial lung disease patients were eligible for analyses. The pooled effect sizes of the association for pulmonary rehabilitation were 0.37 (95% confidence interval [CI], 0.02-0.71) for FVC, 44.55 (95% CI, 32.46-56.64) for 6MWD, 0.52 (95% CI, 0.22-0.82) for HRQOL, and 0.39 (95% CI, -0.08 to 0.87) for dyspnea. After translating these findings considering clinical improvements, pulmonary rehabilitation intervention increased predicted FVC by 5.5%, the 6MWD test improved by 44.55 m, and HRQOL improved by 3.9 points compared with baseline values. Results remained similar in sensitivity analyses. CONCLUSIONS: Although specific evidence for pulmonary rehabilitation of coronavirus disease 2019 patients has emerged, our data support that interstitial lung disease rehabilitation could be considered as an effective therapeutic strategy to improve the functional capacity and quality of life in this group of patients.

Effect of eHealth to increase physical activity in healthy adults over 55 years: A systematic review and meta-analysis.

To estimate the effect of eHealth interventions on increasing physical activity (PA) in healthy adults over 55 years, a systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. MEDLINE, Cochrane, Web of Science, SPORTDiscus, and Scopus databases were searched, from inception to February 2020, for experimental studies reporting the effect of eHealth interventions on steps/day, daily moderate-to-vigorous physical activity (MVPA min/day), PA min/week, and MVPA min/week among adults over 55 years. The DerSimonian and Laird method was used to compute a pooled effect size (ES) estimate and the respective 95% confidence interval (95% CI). Eighteen studies were included in this meta-analysis with adults whose age ranged from 58 to 74.2 years. The interventions lasted between four and 52 weeks. The ES estimates of eHealth interventions on increasing PA were 0.59 (95% CI: 0.15-1.02) for steps/day, 0.49 (95% CI: 0.17-0.80) for daily MVPA, 0.13 (95% CI: 0.01-0.24) for total weekly PA and 0.31 (95% CI: 0.13-0.48) for weekly MVPA. Considering clinical improvements, the mean change difference estimates were an increase of 1616.28 steps/day (95% CI: 386.25-2846.31), 7.41 minutes of daily MVPA (95% CI: 3.24-11.57), 40.54 minutes of total weekly PA (95% CI: -8.71 to 89.79) and 56.35 minutes of weekly MVPA (95% CI: 17.43-95.27). In conclusion, eHealth interventions are effective in increasing PA levels among adults over 55 years, resulting in increased steps/day, MVPA min/day, PA min/week and MVPA min/week.

Optical Technologies for the Improvement of Skin Cancer Diagnosis: A Review.

The worldwide incidence of skin cancer has risen rapidly in the last decades, becoming one in three cancers nowadays. Currently, a person has a 4% chance of developing melanoma, the most aggressive form of skin cancer, which causes the greatest number of deaths. In the context of increasing incidence and mortality, skin cancer bears a heavy health and economic burden. Nevertheless, the 5-year survival rate for people with skin cancer significantly improves if the disease is detected and treated early. Accordingly, large research efforts have been devoted to achieve early detection and better understanding of the disease, with the aim of reversing the progressive trend of rising incidence and mortality, especially regarding melanoma. This paper reviews a variety of the optical modalities that have been used in the last years in order to improve non-invasive diagnosis of skin cancer, including confocal microscopy, multispectral imaging, three-dimensional topography, optical coherence tomography, polarimetry, self-mixing interferometry, and machine learning algorithms. The basics of each of these technologies together with the most relevant achievements obtained are described, as well as some of the obstacles still to be resolved and milestones to be met.

Exporting Metal-Carbene Chemistry to Live Mammalian Cells: Copper-Catalyzed Intracellular Synthesis of Quinoxalines Enabled by N-H Carbene Insertions.

Implementing catalytic organometallic transformations in living settings can offer unprecedented opportunities in chemical biology and medicine. Unfortunately, the number of biocompatible reactions so far discovered is very limited, and essentially restricted to uncaging processes. Here, we demonstrate the viability of performing metal carbene transfer reactions in live mammalian cells. In particular, we show that copper (II) catalysts can promote the intracellular annulation of alpha-keto diazocarbenes with ortho-amino arylamines, in a process that is initiated by an N-H carbene insertion. The potential of this transformation is underscored by the in cellulo synthesis of a product that alters mitochondrial functions, and by demonstrating cell selective biological responses using targeted copper catalysts. Considering the wide reactivity spectrum of metal carbenes, this work opens the door to significantly expanding the repertoire of life-compatible abiotic reactions.