A massive galaxy that formed its stars at z ≈ 11.

The formation of galaxies by gradual hierarchical co-assembly of baryons and cold dark matter halos is a fundamental paradigm underpinning modern astrophysics1,2 and predicts a strong decline in the number of massive galaxies at early cosmic times3-5. Extremely massive quiescent galaxies (stellar masses of more than 1011 M⊙) have now been observed as early as 1-2 billion years after the Big Bang6-13. These galaxies are extremely constraining on theoretical models, as they had formed 300-500 Myr earlier, and only some models can form massive galaxies this early12,14. Here we report on the spectroscopic observations with the JWST of a massive quiescent galaxy ZF-UDS-7329 at redshift 3.205 ± 0.005. It has eluded deep ground-based spectroscopy8, it is significantly redder than is typical and its spectrum reveals features typical of much older stellar populations. Detailed modelling shows that its stellar population formed around 1.5 billion years earlier in time (z ≈ 11) at an epoch when dark matter halos of sufficient hosting mass had not yet assembled in the standard scenario4,5. This observation may indicate the presence of undetected populations of early galaxies and the possibility of significant gaps in our understanding of early stellar populations, galaxy formation and the nature of dark matter.

Transcultural pathways to the will to fight.

In 2022, the "Will to Fight Act" was referred to the US Congress urging attention to measuring and assessing will to fight. That Bill was not enacted, and evaluation efforts within the political and military establishment remain contentious, fragmented, and meager. This likely will persist, along with attendant policy failures and grievous costs, without awareness of research that the social and psychological sciences reveal on the will to fight [S. Atran, Science 373, 1063 (2021)]. We illustrate such research using converging data from a multimethod and multicultural approach, including field and online studies from the Middle East, North Africa, and Europe. These studies reveal specific psychosocial pathways, within a general causal framework, that predict willingness to make costly sacrifices, including to cooperate, fight, and die in war and sustained conflict. From the continuing strife in Iraq to embattled Ukraine, 31 studies were conducted in 9 countries with nearly 12,000 participants. These include people in longstanding conflicts, refugees, imprisoned jihadists and gangs, US military, studies in Ukraine before and during the current war, and rolling studies with a European ally of Ukraine. Results provide evidence for a mediation model of transcultural pathways to the will to fight. Building on our previous behavioral and brain research, on the battlefield in Iraq, with violent extremists, and with US military, the linear mediation yielding the will to fight involves identity fusion, perceived spiritual formidability, and trust. The model, a variation on "The Devoted Actor Framework," applies to primary reference groups, core cultural values, and leaders.

Spiritual over physical formidability determines willingness to fight and sacrifice through loyalty in cross-cultural populations.

Across 11 studies involving six countries from four continents (n = 3,285), we extend insights from field investigations in conflict zones to offline and online surveys to show that personal spiritual formidability-the conviction and immaterial resources (values, strengths of beliefs, character) of a person to fight-is positively associated with the will to fight and sacrifice for others. The physical formidability of groups in conflict has long been promoted as the primary factor in human decisions to fight or flee in times of conflict. Here, studies in Spain, Iraq, Lebanon, Palestine, and Morocco reveal that personal spiritual formidability, a construct distinct from religiosity, is more strongly associated with the willingness to fight and make costly self-sacrifices for the group than physical formidability. A follow-on study among cadets of the US Air Force Academy further indicates that this effect is mediated by a stronger loyalty to the group, a finding replicated in a separate study with a European sample. The results demonstrate that personal spiritual formidability is a primary determinant of the will to fight across cultures, and this individual-level factor, propelled by loyal bonds made with others, disposes citizens and combatants to fight at great personal risk.

γ-Amino Alcohols via Energy Transfer Enabled Brook Rearrangement.

In the long-standing quest to synthesize fundamental building blocks with key functional group motifs, photochemistry in the recent past has comprehensively established its attractiveness. Amino alcohols are not only functionally diverse but are ubiquitous in the biologically active realm of compounds. We developed bench-stable bifunctional reagents that could then access the sparsely reported γ-amino alcohols directly from feedstock alkenes through energy transfer (EnT) photocatalysis. A designed 1,3-linkage across alkenes is made possible by the intervention of a radical Brook rearrangement that takes place downstream to the EnT-mediated homolysis of our reagent(s). A combination of experimental mechanistic investigations and detailed computational studies (DFT) indicates a radical chain propagated reaction pathway.

An analysis of protein language model embeddings for fold prediction.

The identification of the protein fold class is a challenging problem in structural biology. Recent computational methods for fold prediction leverage deep learning techniques to extract protein fold-representative embeddings mainly using evolutionary information in the form of multiple sequence alignment (MSA) as input source. In contrast, protein language models (LM) have reshaped the field thanks to their ability to learn efficient protein representations (protein-LM embeddings) from purely sequential information in a self-supervised manner. In this paper, we analyze a framework for protein fold prediction using pre-trained protein-LM embeddings as input to several fine-tuning neural network models, which are supervisedly trained with fold labels. In particular, we compare the performance of six protein-LM embeddings: the long short-term memory-based UniRep and SeqVec, and the transformer-based ESM-1b, ESM-MSA, ProtBERT and ProtT5; as well as three neural networks: Multi-Layer Perceptron, ResCNN-BGRU (RBG) and Light-Attention (LAT). We separately evaluated the pairwise fold recognition (PFR) and direct fold classification (DFC) tasks on well-known benchmark datasets. The results indicate that the combination of transformer-based embeddings, particularly those obtained at amino acid level, with the RBG and LAT fine-tuning models performs remarkably well in both tasks. To further increase prediction accuracy, we propose several ensemble strategies for PFR and DFC, which provide a significant performance boost over the current state-of-the-art results. All this suggests that moving from traditional protein representations to protein-LM embeddings is a very promising approach to protein fold-related tasks.

Coronavirus disease 2019 is associated with long-term depressive symptoms in Spanish older adults with overweight/obesity and metabolic syndrome.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort. METHODS: Participants (n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology. RESULTS: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted ß = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women (ß = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008). CONCLUSIONS: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

Ultrasound-assisted diastereoselective green synthesis of spiro-fused-γ-lactams functionalized with an amide bond heterocyclic bioisostere via the Ugi azide/domino process coupled strategy.

A series of linked-type 1,5-disubstituted tetrazoles (1,5-DS-Ts) were synthesised via an isocyanide-based multicomponent reaction (IMCR) and used as synthetic platforms to access bound-type polyheterocycles containing an epoxyisoindol-1(6H)-one scaffold under green conditions. This rapid sonochemical synthetic strategy includes a double domino process using an orthogonal heterocyclic input in the Ugi-azide (UA) reaction. DFT calculations and NBO analysis were performed to understand the pseudopericyclic reaction involved in the 1,5-electrocyclization of the UA mechanism.

Novel vaccine candidates of Bordetella pertussis identified by reverse vaccinology.

Whooping cough is a disease caused by Bordetella pertussis, whose morbidity has increased, motivating the improvement of current vaccines. Reverse vaccinology is a strategy that helps identify proteins with good characteristics fast and with fewer resources. In this work, we applied reverse vaccinology to study the B. pertussis proteome and pangenome with several in-silico tools. We analyzed the B. pertussis Tohama I proteome with NERVE software and compared 234 proteins with B. parapertussis, B. bronchiseptica, and B. holmessi. VaxiJen was used to calculate an antigenicity value; our threshold was 0.6, selecting 84 proteins. The candidates were depurated and grouped in eight family proteins to select representative candidates, according to bibliographic information and their immunological response predicted with ABCpred, Bcepred, IgPred, and C-ImmSim. Additionally, a pangenome study was conducted with 603 B. pertussis strains and PanRV software, identifying 3421 core proteins that were analyzed to select the best candidates. Finally, we selected 15 proteins from the proteome study and seven proteins from the pangenome analysis as good vaccine candidates.

Selective 1,2-Hydroarylation(Alkenylation) of gem-Difluoroalkenes to Access (-CF2 H) Motifs.

An emerging class of C-C coupling transformations that furnish drug-like building blocks involves catalytic hydrocarbonation of alkenes. However, despite notable advances in the field, hydrocarbon addition to gem-difluoroalkenes without additional electronic activation remains largely unsuccessful. This owes partly to poor reactivity and the propensity of difluoroalkenes to undergo defluorinative side reactions. Here, we report a nickel catalytic system that promotes efficient 1,2-selective hydroarylation and hydroalkenylation, suppressing defluorination and providing straightforward access to a diverse assortment of prized organofluorides bearing difluoromethyl-substituted carbon centers. In contrast to radical-based pathways and reactions triggered by hydrometallation via a nickel-hydride complex, our experimental and computational studies support a mechanism in which a catalytically active nickel-bromide species promotes selective carbonickelation with difluoroalkenes followed by alkoxide exchange and hydride transfer, effectively overcoming the difluoroalkene's intrinsic electronic bias.

Photoinduced Acylations Via Azolium-Promoted Intermolecular Hydrogen Atom Transfer.

Photoinduced hydrogen atom transfer (HAT) has been developed as a powerful tool to generate synthetically valuable radical species. The direct photoexcitation of ketones has been known to promote HAT or to generate acyl radicals through Norrish-type pathways, but these modalities remain severely limited by radical side reactions. We report herein a catalyst- and transition metal-free method for the acylation of C-H bonds that leverages the unique properties of stable, isolable acyl azolium species. Specifically, acyl azolium salts are shown to undergo an intermolecular and regioselective HAT upon LED irradiation with a range of substrates bearing active C-H bonds followed by C-C bond formation to afford ketones. Experimental and computational studies support photoexcitation of the acyl azolium followed by facile intersystem crossing to access triplet diradical species that promote selective HAT and radical-radical cross-coupling.

Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort.

BACKGROUND: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. METHODS: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. RESULTS: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. CONCLUSIONS: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19. TRIAL REGISTRATION: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 ).

Effects of Supplemented Mediterranean Diets on Plasma-Phospholipid Fatty Acid Profiles and Risk of Cardiovascular Disease after 1 Year of Intervention in the PREDIMED Trial.

BACKGROUND: Plasma fatty acids (FAs) have been associated with cardiovascular disease (CVD) risk. Diet and endogenous metabolism influence the FA profile of the plasma phospholipid (PL) fraction. In the PREDIMED trial, we examined 1-year changes in the FA profile of plasma PL according to a nutritional intervention with Mediterranean diets, either supplemented with extra-virgin olive oil (MedDiet + EVOO) or mixed nuts (MedDiet + nuts), in a high cardiovascular risk population. We also analyzed if 1-year changes in PL FAs were associated with subsequent cardiovascular risk. METHODS: We included 779 participants in our case-cohort study: 185 incident cases and 594 participants in the subcohort (including 31 overlapping cases). The end point was the incidence of CVD. We measured the FAs of plasma PL at baseline and after 1 year of intervention. RESULTS: MedDiet + EVOO increased C17:0 and C20:3n9 in linear regression models [ß coefficientperSD : 0.215 (95% CI, 0.032-0.399) and 0.271 (0.107-0.434), respectively] and decreased 16:1n7 and C22:4n6 [ßperSD: -0.239 (95% CI, -0.416 to -0.061) and -0.287 (95% CI, -0.460 to -0.113), respectively] vs the control group. MedDiet + nuts increased C18:3n3 [ßperSD: 0.382 (95% CI, 0.225 - 0.539)], C18:2n6 [ßper SD: 0.250 (95% CI, 0.073 - 0.428)], C18:0 [ßperSD: 0.268 (95% CI, 0.085-0.452)], and C22:0 [ßper SD: 0.216 (95% CI, 0.031-0.402)]; and decreased the sum of six n6 FAs [ßper SD: -0.147 (95% CI, -0.268 to -0.027)] vs the control group. The 1-year increase in C18:2n6 was inversely associated with the subsequent CVD risk (HRperSD: 0.64 (95% CI, 0.44-0.92)). CONCLUSIONS: MedDiet interventions changed n6 FAs and C16:1n7c; other changes were specific for each group: MedDiet + EVOO increased C17:0 and C20:3n9, and MedDiet + Nuts C18:3n3, C18:2n6, C18:0, and C22:0 FAs.

Dietary intake of polychlorinated dibenzo-p-dioxins and furans, adiposity and obesity status.

INTRODUCTION: The principal source of exposure to Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) in humans comes from food intake. PCDD/Fs, are a family of potential endocrine disruptors and have been associated with different chronic diseases such as diabetes and hypertension. However, studies assessing the relationship between dietary exposure to PCDD/Fs and adiposity or obesity status in a middle-aged population are limited. OBJECTIVE: To assess cross-sectionally and longitudinally the associations between estimated dietary intake (DI) of PCDD/Fs and body mass index (BMI), waist circumference, and the prevalence/incidence of obesity and abdominal obesity in a middle-aged population. METHODS: In 5899 participants aged 55-75 years (48% women) living with overweight/obesity from the PREDIMED-plus cohort, PCDD/Fs DI was estimated using a 143-item validated food-frequency questionnaire, and the levels of food PCDD/F expressed as Toxic Equivalents (TEQ). Consequently, cross-sectional and prospective associations between baseline PCDD/Fs DI (in pgTEQ/week) and adiposity or obesity status were assessed at baseline and after 1-year follow-up using multivariable cox, logistic or linear regression models. RESULTS: Compared to participants in the first PCDD/F DI tertile, those in the highest tertile presented a higher BMI (ß-coefficient [confidence interval]) (0.43kg/m2 [0.22; 0.64]; P-trend <0.001), a higher waist circumference (1.11 cm [0.55; 1.66]; P-trend <0.001), and a higher prevalence of obesity and abdominal obesity (1.05 [1.01; 1.09] and 1.02 [1.00; 1.03]; P-trend = 0.09 and 0.027, respectively). In the prospective analysis, participants in the top PCDD/F DI baseline tertile showed an increase in waist circumference compared with those in the first tertile after 1-year of follow-up (ß-coefficient 0.37 cm [0.06; 0.70]; P-trend = 0.015). CONCLUSION: Higher DI of PCDD/Fs was positively associated with adiposity parameters and obesity status at baseline and with changes in waist circumference after 1-year of follow-up in subjects living with overweight/obesity. Further large prospective studies using a different population with longer follow-up periods are warranted in the future to strengthen our results.

Carbon dioxide (CO2) emissions and adherence to Mediterranean diet in an adult population: the Mediterranean diet index as a pollution level index.

BACKGROUND: Research related to sustainable diets is is highly relevant to provide better understanding of the impact of dietary intake on the health and the environment. AIM: To assess the association between the adherence to an energy-restricted Mediterranean diet and the amount of CO2 emitted in an older adult population. DESIGN AND POPULATION: Using a cross-sectional design, the association between the adherence to an energy-reduced Mediterranean Diet (erMedDiet) score and dietary CO2 emissions in 6646 participants was assessed. METHODS: Food intake and adherence to the erMedDiet was assessed using validated food frequency questionnaire and 17-item Mediterranean questionnaire. Sociodemographic characteristics were documented. Environmental impact was calculated through greenhouse gas emissions estimations, specifically CO2 emissions of each participant diet per day, using a European database. Participants were distributed in quartiles according to their estimated CO2 emissions expressed in kg/day: Q1 (≤2.01 kg CO2), Q2 (2.02-2.34 kg CO2), Q3 (2.35-2.79 kg CO2) and Q4 (≥2.80 kg CO2). RESULTS: More men than women induced higher dietary levels of CO2 emissions. Participants reporting higher consumption of vegetables, fruits, legumes, nuts, whole cereals, preferring white meat, and having less consumption of red meat were mostly emitting less kg of CO2 through diet. Participants with higher adherence to the Mediterranean Diet showed lower odds for dietary CO2 emissions: Q2 (OR 0.87; 95%CI: 0.76-1.00), Q3 (OR 0.69; 95%CI: 0.69-0.79) and Q4 (OR 0.48; 95%CI: 0.42-0.55) vs Q1 (reference). CONCLUSIONS: The Mediterranean diet can be environmentally protective since the higher the adherence to the Mediterranean diet, the lower total dietary CO2 emissions. Mediterranean Diet index may be used as a pollution level index.

Metabolic syndrome criteria and severity and carbon dioxide (CO2) emissions in an adult population.

BACKGROUND: Metabolic syndrome (MetS) has become a growing risk factor of some non-communicable diseases. Increase of greenhouse gas emissions affects the planet. AIMS: To assess the association between MetS severity and amount of carbon dioxide (CO2) emitted in an adult population. DESIGN: Cross-sectional study (n = 6646; 55-76-year-old-men; 60-75-year-old-women with MetS). METHODS: Dietary habits were assessed using a pre-validated semi quantitative 143-item food frequency questionnaire. The amount of CO2 emitted due to the production of food consumed by person and day was calculated using a European database, and the severity of the MetS was calculated with the MetS Severity Score. RESULTS: Higher glycaemia levels were found in people with higher CO2 emissions. The risk of having high severe MetS was related to high CO2 emissions. CONCLUSIONS: Low CO2 emissions diet would help to reduce MetS severity. Advantages for both health and the environment were found following a more sustainable diet. TRIAL REGISTRATION: ISRCTN, ISRCTN89898870 . Registered 05 September 2013.

Intentions to be Vaccinated Against COVID-19: The Role of Prosociality and Conspiracy Beliefs across 20 Countries.

Understanding the determinants of COVID-19 vaccine uptake is important to inform policy decisions and plan vaccination campaigns. The aims of this research were to: (1) explore the individual- and country-level determinants of intentions to be vaccinated against SARS-CoV-2, and (2) examine worldwide variation in vaccination intentions. This cross-sectional online survey was conducted during the first wave of the pandemic, involving 6697 respondents across 20 countries. Results showed that 72.9% of participants reported positive intentions to be vaccinated against COVID-19, whereas 16.8% were undecided, and 10.3% reported they would not be vaccinated. At the individual level, prosociality was a significant positive predictor of vaccination intentions, whereas generic beliefs in conspiracy theories and religiosity were negative predictors. Country-level determinants, including cultural dimensions of individualism/collectivism and power distance, were not significant predictors of vaccination intentions. Altogether, this study identifies individual-level predictors that are common across multiple countries, provides further evidence on the importance of combating conspiracy theories, involving religious institutions in vaccination campaigns, and stimulating prosocial motives to encourage vaccine uptake.

Fatty Acid Sensing in the Gastrointestinal Tract of Rainbow Trout: Different to Mammalian Model?

It is well established in mammals that the gastrointestinal tract (GIT) senses the luminal presence of nutrients and responds to such information by releasing signaling molecules that ultimately regulate feeding. However, gut nutrient sensing mechanisms are poorly known in fish. This research characterized fatty acid (FA) sensing mechanisms in the GIT of a fish species with great interest in aquaculture: the rainbow trout (Oncorhynchus mykiss). Main results showed that: (i) the trout GIT has mRNAs encoding numerous key FA transporters characterized in mammals (FA transporter CD36 -FAT/CD36-, FA transport protein 4 -FATP4-, and monocarboxylate transporter isoform-1 -MCT-1-) and receptors (several free FA receptor -Ffar- isoforms, and G protein-coupled receptors 84 and 119 -Gpr84 and Gpr119-), and (ii) intragastrically-administered FAs differing in their length and degree of unsaturation (i.e., medium-chain (octanoate), long-chain (oleate), long-chain polyunsaturated (α-linolenate), and short-chain (butyrate) FAs) exert a differential modulation of the gastrointestinal abundance of mRNAs encoding the identified transporters and receptors and intracellular signaling elements, as well as gastrointestinal appetite-regulatory hormone mRNAs and proteins. Together, results from this study offer the first set of evidence supporting the existence of FA sensing mechanisms n the fish GIT. Additionally, we detected several differences in FA sensing mechanisms of rainbow trout vs. mammals, which may suggest evolutionary divergence between fish and mammals.

Gene Characterization of Nocturnin Paralogues in Goldfish: Full Coding Sequences, Structure, Phylogeny and Tissue Expression.

The aim of this work is the full characterization of all the nocturnin (noc) paralogues expressed in a teleost, the goldfish. An in silico analysis of the evolutive origin of noc in Osteichthyes is performed, including the splicing variants and new paralogues appearing after teleostean 3R genomic duplication and the cyprinine 4Rc. After sequencing the full-length mRNA of goldfish, we obtained two isoforms for noc-a (noc-aa and noc-ab) with two splice variants (I and II), and only one for noc-b (noc-bb) with two transcripts (II and III). Using the splicing variant II, the prediction of the secondary and tertiary structures renders a well-conserved 3D distribution of four α-helices and nine ß-sheets in the three noc isoforms. A synteny analysis based on the localization of noc genes in the patrilineal or matrilineal subgenomes and a phylogenetic tree of protein sequences were accomplished to stablish a classification and a long-lasting nomenclature of noc in goldfish, and valid to be extrapolated to allotetraploid Cyprininae. Finally, both goldfish and zebrafish showed a broad tissue expression of all the noc paralogues. Moreover, the enriched expression of specific paralogues in some tissues argues in favour of neo- or subfunctionalization.

Recurrence rate and survival implications of surgical margins in patients with acral melanoma. Is a wide margin necessary?

INTRODUCTION: Appropriate size of resection margins in acral melanoma is not clearly established. OBJECTIVE: To investigate whether narrow-margin excision is appropriate for thick acral melanoma. METHODS: Three-hundred and six patients with acral melanoma were examined. Factors associated with recurrence and survival were analyzed according to surgical margin size (1 to 2 cm and > 2 cm). RESULTS: Out of 306 patients, 183 were women (59.8%). Median Breslow thickness was 6 mm; 224 cases (73.2%) were ulcerated, 154 patients (50.3%) had clinical stage III disease, while 137 were at stage II (44.8%) and 15 at stage IV (4.9%). All cases had negative margins, with a median of 31.5 mm. A Breslow thickness of 7 mm (p = 0.001) and clinical stage III (p = 0.031) were associated with recurrence; the factors associated with survival were Breslow index (p = 0.047), ulceration (p = 0.003), advanced clinical stage (p < 0.001), and use of adjuvant therapy (p = 0.003). CONCLUSION: A resection margin of 1 to 2 cm did not affect tumor recurrence or survival in patients with acral melanoma.

INTRODUCCIÓN: La extensión apropiada de los márgenes de resección en el melanoma acral no está claramente establecida. OBJETIVO: Investigar si la escisión con margen estrecho es adecuada en el melanoma acral grueso. MÉTODOS: Se estudiaron 306 pacientes con melanoma acral. Conforme a la extensión del margen quirúrgico (de 1 a 2 cm y > 2 cm), se analizaron los factores asociados a la recurrencia y la supervivencia. RESULTADOS: De 306 pacientes, 183 fueron mujeres (59.8 %). La mediana del grosor de Breslow fue 6 mm; 224 casos (73.2 %) fueron de tipo ulcerados, 154 pacientes (50.3 %) tenían enfermedad en estadio clínico III, 137 en II (44.8 %) y 15 en IV (4.9 %). Todos los casos presentaron margen negativo, con una mediana de 31.5 mm. Un grosor de Breslow de 7 mm (p = 0.001) y la etapa clínica III (p = 0.031) se asociaron a recurrencia; los factores asociados a la supervivencia fueron el índice de Breslow (p = 0.047), la ulceración (p = 0.003), la etapa clínica avanzada (p < 0.001) y el uso de adyuvancia (p = 0.003). CONCLUSIÓN: Un margen de resección de 1 a 2 cm no afectó la recurrencia tumoral ni la supervivencia en los pacientes con melanoma acral.

Experimental and Computational Studies on Cobalt(I)-Catalyzed Regioselective Allylic Alkylation Reactions.

Here, we report the development of cobalt(I)-catalyzed regioselective allylic alkylation reactions of tertiary allyl carbonates with 1,3-dicarbonyl compounds. A family of well-defined tetrahedral cobalt(I) complexes bearing commercially available bidentate bis(phosphine) ligands [(P,P)Co(PPh3 )Cl] are synthesized and explored as catalysts in allylic alkylation reactions. The catalyst [(dppp)Co(PPh3 )Cl] (dppp=1,3-Bis(diphenylphosphino)propane) enables the alkylation of a large variety of tertiary allyl carbonates with high yields and excellent regioselectivity for the branched product. Remarkably, this methodology is selective for the activation of tertiary allyl carbonates even in the presence of secondary allyl carbonates. This contrasts with the selectivity observed in cobalt-catalyzed allylic alkylations enabled by visible light photocatalysis. Mechanistic insights by means of experimental and computational investigations support a Co(I)/Co(III) catalytic cycle.