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Purpose: To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm). Methods: OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged ≥18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in BRCA1 or BRCA2 who had received at least one prior systemic regimen for advanced disease were enrolled. Patients received olaparib plus trastuzumab until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was investigator-assessed clinical benefit rate for at least 24 weeks as per RECIST v.1.1. Key secondary endpoints included overall response rate (ORR) and safety profile. Results: A total of 68 pre-treated HER2-positive ABC patients were screened. Due to slow accrual the trial was stopped after enrolling 5 patients instead of the planned sample size of 20. Four patients achieved clinical benefit (80.0 %, 95 % CI; 28.4–99.5, p

Antecedentes: Lobelia villaregalis es una especie endémica y en peligro de extinción en Jalisco, México. Conocer la estructura y diversidad genética de las poblaciones de especies en riesgo puede contribuir a mejorar las estrategias para su conservación. Esta información no se ha generado para L. villaregalis. Preguntas: 1) ¿Presenta L. villaregalis niveles bajos de diversidad genética?, 2) ¿Existen diferencias genéticas entre sus poblaciones? Especies de estudio: Lobelia villaregalis T.J. Ayers (Campanulaceae: Lobelioideae), herbácea perenne. Sitio y años de estudio: Durante 2018-2020 se realizó trabajo de campo en el Área Natural Protegida Bosque La Primavera, Zapopan, Jalisco, para localizar nuevas poblaciones de la especie y recolectar material foliar. Métodos: Se evaluó la diversidad y estructura genética de 87 individuos en cinco poblaciones utilizando marcadores moleculares ISSR. Resultados: La diversidad genética promedio de L. villaregalis es baja (He = 0.057, P = 48.17 %, I = 0.110) así como la diversidad total (HT = 0.069). El análisis de varianza molecular mostró que la mayor parte de la variación genética (92 %) ocurrió dentro de las poblaciones. La prueba de Mantel indica que no hay correlación entre las distancias genéticas y las distancias geográficas para las cinco poblaciones estudiadas (R = 0.64, P = 0.18). Con el análisis de asignación genética se identificaron 4 grupos, sin embargo, no existe estructura genética (GST = 0.060). Conclusiones: Lobelia villaregalis requiere acciones urgentes de conservación para mantener la diversidad genética de todas sus poblaciones, dando máxima prioridad a tres de ellas.

Background: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study. Methods: First-line endocrine-sensitive, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) patients received palbociclib capsules plus fulvestrant or letrozole. The primary endpoint was progression-free survival (PFS). This post-hoc analysis compared PPI use. Patients were PPI-naïve (N-PPI) if not on PPI during the study, and either early (E-PPI) or long-term PPI (LT-PPI) if on PPI at study entry or for at least ≥⅔ of treatment, respectively. PPI groups were not mutually exclusive. Results: Among 486 patients, 66.9 % were N-PPI, 13.2 % E-PPI, 18.7 % LT-PPI, and 11.5 % of the PPI users were defined as neither. Median PFS (mPFS) was 29.6 months in the study population, 28.7 months in N-PPI, 23.0 months in E-PPI (Hazard Ratio [HR] 1.5; 95%Confidence Interval [CI] 1.1–2.2; p = 0.024), and 23.0 months in LT-PPI (HR 1.4; 95%CI 1.0–1.9; p = 0.035). By landmark analysis, PPI use was associated with poorer mPFS at 3 and 12 months. Grade ≥3 hematological adverse events occurred in 71.7 % of N-PPI, 57.8 % of E-PPI (p = 0.021), and 54.9 % of LT-PPI (p = 0.003). Dose reductions and dosing delays due to hematological toxicity occurred in 70.8 % of N-PPI, 56.3 % of E-PPI (p = 0.018), and 52.7 % of LT-PPI (p = 0.002). Conclusions: PPI use may reduce palbociclib capsule toxicity, dose modifications, and clinical activity in HR+/HER2- ABC.

Background: The chloroplast genomes of Cactaceae exhibit boundary modifications in the inverted repeat regions (IRs), gene inversions, and deletions. Among nine Mammillaria species, three distinct chloroplast structures have been identified, although not all of these correspond to the morphology-based classification of the genus. Question: Is there a distinct chloroplast genome structure in the species of Mammillaria series Stylothelae? Studied species: Mammillaria bocasana and M. erythrosperma. Study site and dates: Mexico from 2019 to 2023. Methods: Chloroplast DNA was sequenced, and chloroplast genomes were de novo assembled using the Fast-Plast program. Complete plastome sequences were annotated and verified. The sequences were aligned in MAUVE program to detect possible structural changes. A maximum likelihood phylogeny was executed to evaluate the relationships of the studied species. Results: The plastomes ranged from 107,368 bp in Mammillaria bocasana to 108,069 bp in M. erythrosperma. Both presented a quadripartite structure and contained 108 genes. The IRs were ~ 1,600 bp long and included the genes rpl2, rpl23 (pseudo), and trnI-CAU. MAUVE identified a ~ 21 kb inversion in the large single copy containing a block of genes related to photosynthesis. The phylogenetic analysis placed both species in a single clade separated from the other species within Mammillaria subg. Mammillaria. Conclusions: The studied species of Mammillaria series Stylothelae exhibited a different and synapomorphic chloroplast genome structure. Other Mammillaria chloroplast genome structures have evolved independently in different lineages.

The Mexican Central Pacific (MCP) region has discontinuous coral ecosystems with different protection and anthropogenic disturbance. Characterizing the bacterial assemblage associated with the sea urchin Toxopneustes roseus and its relationship with environmental variables will contribute to understanding the species’ physiology and ecology. We collected sea urchins from coral ecosystems at six sites in the MCP during the summer and winter for two consecutive years. The spatial scale represented the most important variation in the T. roseus bacteriome, particularly because of Isla Isabel National Park (PNII). Likewise, spatial differences correlated with habitat structure variables, mainly the sponge and live coral cover. The PNII exhibited highly diverse bacterial assemblages compared to other sites, characterized by families associated with diseases and environmental stress (Saprospiraceae, Flammeovirgaceae, and Xanthobacteraceae). The remaining five sites presented a constant spatiotemporal pattern, where the predominance of the Campylobacteraceae and Helicobacteraceae families was key to T. roseus’ holobiont. However, the dominance of certain bacterial families, such as Enterobacteriaceae, in the second analyzed year suggests that Punto B and Islas e islotes de Bahía Chamela Sanctuary were exposed to sewage contamination. Overall, our results improve the understanding of host-associated bacterial assemblages in specific time and space and their relationship with the environmental condition.

Abstract Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability

In this study, we sequenced, assembled, and annotated the plastome of Physalis cordata Mill. and compared it with seven species of the genus Physalis sensu stricto. Sequencing, annotating, and comparing plastomes allow us to understand the evolutionary mechanisms associated with physiological functions, select possible molecular markers, and identify the types of selection that have acted in different regions of the genome. The plastome of P. cordata is 157,000 bp long and presents the typical quadripartite structure with a large single-copy (LSC) region of 87,267 bp and a small single-copy (SSC) region of 18,501 bp, which are separated by two inverted repeat (IRs) regions of 25,616 bp each. These values are similar to those found in the other species, except for P. angulata L. and P. pruinosa L., which presented an expansion of the LSC region and a contraction of the IR regions. The plastome in all Physalis species studied shows variation in the boundary of the regions with three distinct types, the percentage of the sequence identity between coding and non-coding regions, and the number of repetitive regions and microsatellites. Four genes and 10 intergenic regions show promise as molecular markers and eight genes were under positive selection. The maximum likelihood analysis showed that the plastome is a good source of information for phylogenetic inference in the genus, given the high support values and absence of polytomies. In the Physalis plastomes analyzed here, the differences found, the positive selection of genes, and the phylogenetic relationships do not show trends that correspond to the biological or ecological characteristics of the species studied.

Physalis (Solanaceae, Solanoideae) is an American genus of ca. 90 species, with its diversity centered on Mexico. We recognize 61 species within the country, for which we provide a generic morphological description, an artificial key to determine species, and brief descriptions. We include distributions, habitats, diagnostic characters, phenology, and uses. Distribution maps and field photographs are also provided. We include conservation status as evaluated by the IUCN.

This corrects the article DOI: 10.1038/ncomms5999.

This corrects the article DOI: 10.1038/ncomms5999.

Con este trabajo se pretende dar a conocer el significado de discapacidad visual, la educación inclusiva y los recursos tiflotecnológicos. Se destaca el papel que desempeñan los recursos materiales especiales, tecnológicos y tiflotecnológicos en la sociedad educativa actual. Puesto que no existe a día de hoydos individuos con características, intereses o habilidades semejantes, la escuela ordinaria debe ser capaz de dotarse de métodos, recursos y estrategias para adaptar el centro a la realidad del alumno, respetando sus ritmos de aprendizaje, así como la realidad individual de cada uno, garantizando de esta forma una formación en todos los ámbitos del desarrollo humano, favoreciendo la igualdad de oportunidades.

Societal Impact Statement Crop wild relatives (CWR) are plant taxa closely related to crops and are a source of high genetic diversity that can help adapt crops to the impacts of global change, particularly to meet increasing consumer demand in the face of the climate crisis. CWR provide vital ecosystem services and are increasingly important for food and nutrition security and sustainable and resilient agriculture. They therefore are of major biological, social, cultural and economic importance. Assessing the extinction risk of CWR is essential to prioritise in situ and ex situ conservation strategies in Mesoamerica to guarantee the long‐term survival and availability of these resources for present and future generations worldwide. Summary Ensuring food security is one of the world's most critical issues as agricultural systems are already being impacted by global change. Crop wild relatives (CWR)—wild plants related to crops—possess genetic variability that can help adapt agriculture to a changing environment and sustainably increase crop yields to meet the food security challenge. Here we report the results of an extinction risk assessment of 224 wild relatives of some of the world's most important crops (i.e. chilli pepper, maize, common bean, avocado, cotton, potato, squash, vanilla and husk tomato) in Mesoamerica—an area of global significance as a centre of crop origin, domestication and of high CWR diversity. We show that 35% of the selected CWR taxa are threatened with extinction according to The International Union for Conservation of Nature (IUCN) Red List demonstrates that these valuable genetic resources are under high anthropogenic threat. The dominant threat processes are land use change for agriculture and farming, invasive and other problematic species (e.g. pests, genetically modified organisms) and use of biological resources, including overcollection and logging. The most significant drivers of extinction relate to smallholder agriculture—given its high incidence and ongoing shifts from traditional agriculture to modern practices (e.g. use of herbicides)—smallholder ranching and housing and urban development and introduced genetic material. There is an urgent need to increase knowledge and research around different aspects of CWR. Policies that support in situ and ex situ conservation of CWR and promote sustainable agriculture are pivotal to secure these resources for the benefit of current and future generations.

Antecedentes: La diversidad topográfica y climática de la Zona de Transición Mexicana (ZTM) favorecieron la riqueza de especies, la disyunción y el endemismo. Tigridia durangensis es una geófita endémica con distribución disyunta en la ZTM. Preguntas y / o Hipótesis: ¿Cuál es la diversidad genética de Tigridia durangensis? ¿Tiene estructura genética y filogeográfica? ¿Hubo cambios en su historia demográfica? ¿Las oscilaciones climáticas del Cuaternario afectaron su área de distribución? Métodos: Las regiones de ADNcp ndhF-rpL32, rpL32-trnL y 3´trnV-ndhC en 55 individuos de 10 poblaciones fueron secuenciadas. La diversidad y estructura genética fueron calculadas con Hd, π y FST. Los parámetros GST y NSTestimaron la estructura filogeográfica. Las relaciones genealógicas fueron estimadas con una red de haplotipos. Hipótesis filogenéticas fueron inferidas con Inferencia bayesiana y Máxima verosimilitud. La demografía histórica fue determinada con pruebas de neutralidad, análisis de distribución de diferencias pareadas (ADDP) y de graficas de líneas de cielo bayesianas. La paleodistribución fue estimada con modelos de nicho ecológico (MNE). Resultados: Tigridia durangensis mostró estructura genética y filogeográfica. Nueve haplotipos fueron identificados, H1 y H2-H9 formaron dos linajes intraespecíficos. Las pruebas de neutralidad no fueron significativas. El gráfico ADDP fue congruente con la red de haplotipos. Tigridia durangensis experimentó un cuello de botella durante el pasado reciente. Los MNE estimaron una distribución disyunta en todos los escenarios. Conclusiones: Un cuello de botella y la interrupción del flujo genético entre los haplogrupos de Tigridia durangensisparecen estar asociados a procesos orogénicos y al volcanismo de la Faja Volcánica Transmexicana.

The triple-negative breast cancer (TNBC) subtype comprises approximately 15% of all breast cancers and is associated with poor long-term outcomes. Classical chemotherapy remains the standard of treatment, with toxicity and resistance being major limitations. TNBC is a high metabolic group, and antimetabolic drugs are effective in inhibiting TNBC cell growth. We analyzed the combined effect of chemotherapy and antimetabolic drug combinations in MDA-MB-231, MDA-MB-468 and HCC1143 human TNBC cell lines. Cells were treated with each drug or with drug combinations at a range of concentrations to establish the half-maximal inhibitory concentrations (IC50). The dose-effects of each drug or drug combination were calculated, and the synergistic or antagonistic effects of drug combinations were defined. Chemotherapy and antimetabolic drugs exhibited growth inhibitory effects on TNBC cell lines. Antimetabolic drugs targeting the glycolysis pathway had a synergistic effect with chemotherapy drugs, and antiglycolysis drug combinations also had a synergistic effect. The use of these drug combinations could lead to new therapeutic strategies that reduce chemotherapy drug doses, decreasing their toxic effect, or that maintain the doses but enhance their efficacy by their synergistic effect with other drugs.

ABSTRACT The aim of this research is to analyze, through a confirmatory factorial design, the relationships between sports practice, interest, frequency and reasons why university students practice sports. In order to respond to this objective, a descriptive, explanatory and correlational research is presented, a Likert scale of own authorship is applied, structured in five dimensions and 28 items, which was validated by an exploratory factor analysis. The research was applied to a sample of 1185 undergraduate university students from first to fourth year, all of them students of an Andalusian university. The results obtained show that sport practices and interest in sport have a strong relationship, as well as this and reasons for practicing a sport, while between frequency with which they practice a sport and the reasons for not practicing have hardly any relationship.

PURPOSE: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. METHODS: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. RESULTS: The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92-0.95, p = 4.13E-13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02-1.06, p = 1.26E-05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95-0.99, p = 8.05E-04). CONCLUSIONS: We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.

Abstract Background Metabolomics has a great potential in the development of new biomarkers in cancer and it has experiment recent technical advances. Methods In this study, metabolomics and gene expression data from 67 localized (stage I to IIIB) breast cancer tumor samples were analyzed, using (1) probabilistic graphical models to define associations using quantitative data without other a priori information; and (2) Flux Balance Analysis and flux activities to characterize differences in metabolic pathways. Results On the one hand, both analyses highlighted the importance of glutamine in breast cancer. Moreover, cell experiments showed that treating breast cancer cells with drugs targeting glutamine metabolism significantly affects cell viability. On the other hand, these computational methods suggested some hypotheses and have demonstrated their utility in the analysis of metabolomics data and in associating metabolomics with patient’s clinical outcome. Conclusions Computational analyses applied to metabolomics data suggested that glutamine metabolism is a relevant process in breast cancer. Cell experiments confirmed this hypothesis. In addition, these computational analyses allow associating metabolomics data with patient prognosis.

Trastuzumab therapy has dramatically changed breast cancer prognosis. Consensus documents recommend a close monitoring during therapy, not always feasible, especially in metastatic breast cancer. The purpose of this study is to describe trastuzumab cardiotoxicity in metastatic breast cancer patients to understand how to improve cardiovascular monitoring. We retrospectively studied metastatic breast cancer patients scheduled for trastuzumab therapy (2001-2018). All patients underwent a baseline evaluation and monitoring during therapy. Cardiotoxicity was defined as symptomatic heart failure or asymptomatic decrease in left ventricular ejection fraction > 10% from baseline and < 53%. Ninety-two women were included, mean age 61 years (±14.43), median follow-up 42.5 months (IQR 26-74). Fourteen percent developed cardiotoxicity: two heart failure with preserved left ventricular ejection fraction, three heart failure with reduced left ventricular ejection fraction, and eight asymptomatic decreased in left ventricular ejection fraction. Eighty-one percent of cardiac dysfunction cases occurred within the first 4 years and on median of 31 months from trastuzumab initiation. Thus, in metastatic breast cancer patients, trastuzumab-mediated cardiotoxicity occurred more frequently during the first 4 years. These data should be considered to optimize follow-up protocols.

Background Pseudalcantarea grandis (Schltdl.) Pinzón & Barfuss is a tank bromeliad that grows on cliffs in the southernmost portion of the Chihuahuan desert. Phytotelmata are water bodies formed by plants that function as micro-ecosystems where bacteria, algae, protists, insects, fungi, and some vertebrates can develop. We hypothesized that the bacterial diversity contained in the phytotelma formed in a bromeliad from an arid zone would differ in sites with and without surrounding vegetation. Our study aimed to characterize the bacterial composition and putative metabolic functions in P. grandis phytotelmata collected in vegetated and non-vegetated sites. Methods Water from 10 individuals was sampled. Five individuals had abundant surrounding vegetation, and five had little or no vegetation. We extracted DNA and amplified seven hypervariable regions of the 16S gene (V2, V4, V8, V3–6, 7–9). Metabarcoding sequencing was performed on the Ion Torrent PGM platform. Taxonomic identity was assigned by the binning reads and coverage between hit and query from the reference database of at least 90%. Putative metabolic functions of the bacterial families were assigned mainly using the FAPROTAX database. The dominance patterns in each site were visualized with rank/abundance curves using the number of Operational Taxonomic Units (OTUs) per family. A percentage similarity analysis (SIMPER) was used to estimate dissimilarity between the sites. Relationships among bacterial families (identified by the dominance analysis and SIMPER), sites, and their respective putative functions were analyzed with shade plots. Results A total of 1.5 million useful bacterial sequences were obtained. Sequences were clustered into OTUs, and taxonomic assignment was conducted using BLAST in the Greengenes databases. Bacterial diversity was 23 phyla, 52 classes, 98 orders, 218 families, and 297 genera. Proteobacteria (37%), Actinobacteria (19%), and Firmicutes (15%) comprised the highest percentage (71%). There was a 68.3% similarity between the two sites at family level, with 149 families shared. Aerobic chemoheterotrophy and fermentation were the main metabolic functions in both sites, followed by ureolysis, nitrate reduction, aromatic compound degradation, and nitrogen fixation. The dominant bacteria shared most of the metabolic functions between sites. Some functions were recorded for one site only and were related to families with the lowest OTUs richness. Bacterial diversity in the P. grandis tanks included dominant phyla and families present at low percentage that could be considered part of a rare biosphere. A rare biosphere can form genetic reservoirs, the local abundance of which depends on external abiotic and biotic factors, while their interactions could favor micro-ecosystem resilience and resistance.

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 × 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 × 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 × 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer.

Breast cancer is a heterogeneous disease. In clinical practice, tumors are classified as hormonal receptor positive, Her2 positive and triple negative tumors. In previous works, our group defined a new hormonal receptor positive subgroup, the TN-like subtype, which had a prognosis and a molecular profile more similar to triple negative tumors. In this study, proteomics and Bayesian networks were used to characterize protein relationships in 96 breast tumor samples. Components obtained by these methods had a clear functional structure. The analysis of these components suggested differences in processes such as mitochondrial function or extracellular matrix between breast cancer subtypes, including our new defined subtype TN-like. In addition, one of the components, mainly related with extracellular matrix processes, had prognostic value in this cohort. Functional approaches allow to build hypotheses about regulatory mechanisms and to establish new relationships among proteins in the breast cancer context.

Physalis philadelphica Lam. has horticultural importance because of its edible fruits. Cultivated and wild populations grow in Mexico. In this study, the complete plastome nucleotide sequence of wild plants was generated using the IonTorrent PGM sequencing technology. The plastome size was 156,804 bp and displayed the typical circular quadripartite structure, consisting of a pair of inverted repeat regions (25,595 bp) separated by a large single copy region (87,131 bp) and a small single copy region (18,483 bp). The chloroplast genome included 80 protein–coding genes, four rRNAs, and 31 tRNAs. The phylogenetic analysis based on 19 Solanaceae chloroplast genomes recovered a clade with all Physalis species. This work revealed the importance of the plastome sequence to solve infrageneric phylogenetic relationships.

Anthracyclines are among the most used chemotherapeutic agents in breast cancer (BC). However their use is hampered by anthracycline-induced cardiotoxicity (AIC). The currently known clinical and genetic risk factors do not fully explain the observed inter-individual variability and only have a limited ability to predict which patients are more likely to develop this severe toxicity. To identify novel predictive genes, we conducted a two-stage genome-wide association study in epirubicin-treated BC patients. In the discovery phase, we genotyped over 700,000 single nucleotide variants in a cohort of 227 patients. The most interesting finding was rs62134260, located 4kb upstream of POLRMT (OR = 5.76, P = 2.23 × 10−5). We replicated this association in a validation cohort of 123 patients (P = 0.021). This variant regulates the expression of POLRMT, a gene that encodes a mitochondrial DNA-directed RNA polymerase, responsible for mitochondrial gene expression. Individuals harbouring the risk allele had a decreased expression of POLRMT in heart tissue that may cause an impaired capacity to maintain a healthy mitochondrial population in cardiomyocytes under stressful conditions, as is treatment with epirubicin. This finding suggests a novel molecular mechanism involved in the development of AIC and may improve our ability to predict patients who are at risk.

Two new species of the family Alpheidae: Alpheus margaritae sp. n. and Leptalpheus melendezensis sp. n. are described from Santa María-La Reforma, coastal lagoon, SE Gulf of California. Alpheus margaritae sp. n. is closely related to A. antepaenultimus and A. mazatlanicus from the Eastern Pacific and to A. chacei from the Western Atlantic, but can be differentiated from these by a combination of characters, especially the morphology of the scaphocerite and the first pereopods. Leptalpheus melendezensis sp. n. resembles L. mexicanus but can be easily differentiated because L. melendezensis sp. n. has the anterior margin of the carapace broadly rounded and has only one spine on the mesial margin of ischium in the major cheliped, versus an acute rostrum and an unarmed major cheliped. Additionally, a phylogenetic analysis was used to explore the relationships of these two new taxa. These results show that Alpheus margaritae sp. n. and Leptalpheus melendezensis sp. n. are indeed related to the species against which we are comparing them, and demonstrate that they can be considered as different species. Additional specimens of Leptalpheus cf. mexicanus, Ambidexter panamensis and A. swifti are recorded for the first time in the Santa María-La Reforma coastal lagoon.

Physalis chenopodifolia is a perennial wild tomatillo with traditional use in central Mexico because of its edible fruits. Due to their agronomic potential and nutraceutical properties, this species is a resource that can be a candidate to plant breeding programs to be included in the Mexican diet. Here, we report the complete chloroplast genome of P. chenopodifolia. Its full size is 156,888 bp, includes a large single-copy (LSC) region of 87,117 bp, a small single-copy (SSC) region of 18,451 bp, and two invert repeat (IR) regions of 25,660 bp each. The plastome contains 113 genes, 79 protein-coding genes, 4 rRNA genes and 30 tRNA genes. The phylogenetic hypothesis supports P. chenopodifolia as a member of Physalis genus. Although relationships within the genus have moderated bootstrap support, the utility of the complete plastome sequence to solve infrageneric phylogenetic relationships is confirmed.

Drug–drug interactions are of significant concern in clinical practice in oncology, particularly in patients receiving Cyclin-dependent kinase (CDK) 4/6 inhibitors, which are typically exposed to long-term regimens. This article presents the highlights from the ‘First Workshop on Pharmacology and Management of CDK4/6 Inhibitors: Consensus about Concomitant Medications’. The article is structured into two modules. The educational module includes background information regarding drug metabolism, corrected QT (QTc) interval abnormalities, management of psychotropic drugs and a comprehensive review of selected adverse effects of palbociclib and ribociclib. The collaborative module presents the conclusions of the five working groups, each of which comprised five experts from different fields. From these conclusions positive lists of drugs for treating common comorbid conditions that can be safely administered concomitantly with palbociclib and/or ribociclib were developed.

Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.