Feasibility study of a SiPM-fiber detector for non-invasive measurement of arterial input function for preclinical and clinical positron emission tomography.

Pharmacokinetic positron emission tomography (PET) studies rely on the measurement of the arterial input function (AIF), which represents the time-activity curve of the radiotracer concentration in the blood plasma. Traditionally, obtaining the AIF requires invasive procedures, such as arterial catheterization, which can be challenging, time-consuming, and associated with potential risks. Therefore, the development of non-invasive techniques for AIF measurement is highly desirable. This study presents a detector for the non-invasive measurement of the AIF in PET studies. The detector is based on the combination of scintillation fibers and silicon photomultipliers (SiPMs) which leads to a very compact and rugged device. The feasibility of the detector was assessed through Monte Carlo simulations conducted on mouse tail and human wrist anatomies studying relevant parameters such as energy spectrum, detector efficiency and minimum detectable activity (MDA). The simulations involved the use of 18F and 68Ga isotopes, which exhibit significantly different positron ranges. In addition, several prototypes were built in order to study the different components of the detector including the scintillation fiber, the coating of the fiber, the SiPMs, and the operating configuration. Finally, the simulations were compared with experimental measurements conducted using a tube filled with both 18F and 68Ga to validate the obtained results. The MDA achieved for both anatomies (approximately 1000 kBq/mL for mice and 1 kBq/mL for humans) falls below the peak radiotracer concentrations typically found in PET studies, affirming the feasibility of conducting non-invasive AIF measurements with the fiber detector. The sensitivity for measurements with a tube filled with 18F (68Ga) was 1.2 (2.07) cps/(kBq/mL), while for simulations, it was 2.81 (6.23) cps/(kBq/mL). Further studies are needed to validate these results in pharmacokinetic PET studies.

Feeding neurons integrate metabolic and reproductive states in mice.

Balance between metabolic and reproductive processes is important for survival, particularly in mammals that gestate their young. How the nervous system coordinates this balance is an active area of study. Herein, we demonstrate that somatostatin (SST) neurons of the tuberal hypothalamus alter feeding in a manner sensitive to metabolic and reproductive states in mice. Whereas chemogenetic activation of SST neurons increased food intake across sexes, ablation decreased food intake only in female mice during proestrus. This ablation effect was only apparent in animals with low body mass. Fat transplantation and bioinformatics analysis of SST neuronal transcriptomes revealed white adipose as a key modulator of these effects. These studies indicate that SST hypothalamic neurons integrate metabolic and reproductive cues by responding to varying levels of circulating estrogens to modulate feeding differentially based on energy stores. Thus, gonadal steroid modulation of neuronal circuits can be context dependent and gated by metabolic status.

Feeding Neurons Integrate Metabolic and Reproductive States in Mice.

Trade-offs between metabolic and reproductive processes are important for survival, particularly in mammals that gestate their young. Puberty and reproduction, as energetically taxing life stages, are often gated by metabolic availability in animals with ovaries. How the nervous system coordinates these trade-offs is an active area of study. We identify somatostatin neurons of the tuberal nucleus (TNSST) as a node of the feeding circuit that alters feeding in a manner sensitive to metabolic and reproductive states in mice. Whereas chemogenetic activation of TNSST neurons increased food intake across sexes, selective ablation decreased food intake only in female mice during proestrus. Interestingly, this ablation effect was only apparent in animals with a low body mass. Fat transplantation and bioinformatics analysis of TNSST neuronal transcriptomes revealed white adipose as a key modulator of the effects of TNSST neurons on food intake. Together, these studies point to a mechanism whereby TNSST hypothalamic neurons modulate feeding by responding to varying levels of circulating estrogens differentially based on energy stores. This research provides insight into how neural circuits integrate reproductive and metabolic signals, and illustrates how gonadal steroid modulation of neuronal circuits can be context-dependent and gated by metabolic status.

Genomic prediction of tocochromanols in exotic-derived maize.

Tocochromanols (vitamin E) are an essential part of the human diet. Plant products, including maize (Zea mays L.) grain, are the major dietary source of tocochromanols; therefore, breeding maize with higher vitamin content (biofortification) could improve human nutrition. Incorporating exotic germplasm in maize breeding for trait improvement including biofortification is a promising approach and an important research topic. However, information about genomic prediction of exotic-derived lines using available training data from adapted germplasm is limited. In this study, genomic prediction was systematically investigated for nine tocochromanol traits within both an adapted (Ames Diversity Panel [AP]) and an exotic-derived (Backcrossed Germplasm Enhancement of Maize [BGEM]) maize population. Although prediction accuracies up to 0.79 were achieved using genomic best linear unbiased prediction (gBLUP) when predicting within each population, genomic prediction of BGEM based on an AP training set resulted in low prediction accuracies. Optimal training population (OTP) design methods fast and unique representative subset selection (FURS), maximization of connectedness and diversity (MaxCD), and partitioning around medoids (PAM) were adapted for inbreds and, along with the methods mean coefficient of determination (CDmean) and mean prediction error variance (PEVmean), often improved prediction accuracies compared with random training sets of the same size. When applied to the combined population, OTP designs enabled successful prediction of the rest of the exotic-derived population. Our findings highlight the importance of leveraging genotype data in training set design to efficiently incorporate new exotic germplasm into a plant breeding program.

Leveraging prior biological knowledge improves prediction of tocochromanols in maize grain.

With an essential role in human health, tocochromanols are mostly obtained by consuming seed oils; however, the vitamin E content of the most abundant tocochromanols in maize (Zea mays L.) grain is low. Several large-effect genes with cis-acting variants affecting messenger RNA (mRNA) expression are mostly responsible for tocochromanol variation in maize grain, with other relevant associated quantitative trait loci (QTL) yet to be fully resolved. Leveraging existing genomic and transcriptomic information for maize inbreds could improve prediction when selecting for higher vitamin E content. Here, we first evaluated a multikernel genomic best linear unbiased prediction (MK-GBLUP) approach for modeling known QTL in the prediction of nine tocochromanol grain phenotypes (12-21 QTL per trait) within and between two panels of 1,462 and 242 maize inbred lines. On average, MK-GBLUP models improved predictive abilities by 7.0-13.6% when compared with GBLUP. In a second approach with a subset of 545 lines from the larger panel, the highest average improvement in predictive ability relative to GBLUP was achieved with a multi-trait GBLUP model (15.4%) that had a tocochromanol phenotype and transcript abundances in developing grain for a few large-effect candidate causal genes (1-3 genes per trait) as multiple response variables. Taken together, our study illustrates the enhancement of prediction models when informed by existing biological knowledge pertaining to QTL and candidate causal genes.

Tardigrade Community Microbiomes in North American Orchards Include Putative Endosymbionts and Plant Pathogens.

The microbiome of tardigrades, a phylum of microscopic animals best known for their ability to survive extreme conditions, is poorly studied worldwide and completely unknown in North America. An improved understanding of tardigrade-associated bacteria is particularly important because tardigrades have been shown to act as vectors of the plant pathogen Xanthomonas campestris in the laboratory. However, the potential role of tardigrades as reservoirs and vectors of phytopathogens has not been investigated further. This study analyzed the microbiota of tardigrades from six apple orchards in central Iowa, United States, and is the first analysis of the microbiota of North American tardigrades. It is also the first ever study of the tardigrade microbiome in an agricultural setting. We utilized 16S rRNA gene amplicon sequencing to characterize the tardigrade community microbiome across four contrasts: location, substrate type (moss or lichen), collection year, and tardigrades vs. their substrate. Alpha diversity of the tardigrade community microbiome differed significantly by location and year of collection but not by substrate type. Our work also corroborated earlier findings, demonstrating that tardigrades harbor a distinct microbiota from their environment. We also identified tardigrade-associated taxa that belong to genera known to contain phytopathogens (Pseudomonas, Ralstonia, and the Pantoea/Erwinia complex). Finally, we observed members of the genera Rickettsia and Wolbachia in the tardigrade microbiome; because these are obligate intracellular genera, we consider these taxa to be putative endosymbionts of tardigrades. These results suggest the presence of putative endosymbionts and phytopathogens in the microbiota of wild tardigrades in North America.

Combining GWAS and TWAS to identify candidate causal genes for tocochromanol levels in maize grain.

Tocochromanols (tocopherols and tocotrienols, collectively vitamin E) are lipid-soluble antioxidants important for both plant fitness and human health. The main dietary sources of vitamin E are seed oils that often accumulate high levels of tocopherol isoforms with lower vitamin E activity. The tocochromanol biosynthetic pathway is conserved across plant species but an integrated view of the genes and mechanisms underlying natural variation of tocochromanol levels in seed of most cereal crops remains limited. To address this issue, we utilized the high mapping resolution of the maize Ames panel of ∼1,500 inbred lines scored with 12.2 million single-nucleotide polymorphisms to generate metabolomic (mature grain tocochromanols) and transcriptomic (developing grain) data sets for genetic mapping. By combining results from genome- and transcriptome-wide association studies, we identified a total of 13 candidate causal gene loci, including 5 that had not been previously associated with maize grain tocochromanols: 4 biosynthetic genes (arodeH2 paralog, dxs1, vte5, and vte7) and a plastid S-adenosyl methionine transporter (samt1). Expression quantitative trait locus (eQTL) mapping of these 13 gene loci revealed that they are predominantly regulated by cis-eQTL. Through a joint statistical analysis, we implicated cis-acting variants as responsible for colocalized eQTL and GWAS association signals. Our multiomics approach provided increased statistical power and mapping resolution to enable a detailed characterization of the genetic and regulatory architecture underlying tocochromanol accumulation in maize grain and provided insights for ongoing biofortification efforts to breed and/or engineer vitamin E and antioxidant levels in maize and other cereals.

Inter-sectorial network for assisting women in situations of violence: handicraft work built by the people.

OBJECTIVES: to discuss the meanings attributed by professionals to the construction of the service network for women in situations of violence. METHODS: Convergent Care Research developed with the application of a convergence group with 32 participants from the health, social assistance, or public security sectors, in Santa Maria, Rio Grande do Sul. The data was produced during ten meetings, based on the problematization methodology, and submitted to analysis of thematic content and interpreted with the referential of networks. RESULTS: the construction of the network is an artisanal work carried out by people continuously, permeated by bonds, communication and partnerships between services and knowledge of work processes. Lashings require permanent movement. FINAL CONSIDERATIONS: building a network implies defining intertwining lines; form nodes that create cross-sector connections. There is a need to institutionalize processes through care continuity protocols, associated with an efficient communication system between sectors.

Association Between Unbalanced Solutions and Acute Kidney Injury During Fluid Resuscitation in Children With Sepsis.

OBJECTIVE: To evaluate the outcomes of patients with sepsis-associated organ dysfunction and septic shock who receive fluid resuscitation with balanced and unbalanced solutions in a middle-income country. DESIGN: An observational, analytical cohort study with propensity score matching (PSM) in children admitted to a pediatric intensive care unit (PICU). Patients from one month to 17 years old who required fluid boluses due to hemodynamic instability were included. The primary outcome was the presence of acute kidney injury and the secondary outcomes were the need to begin continuous renal replacement therapy (CRRT), metabolic acidosis, PICU length of stay and mortality. MEASUREMENTS AND MAIN RESULTS: Out of the 1,074 admissions to the PICU during the study period, 99 patients had sepsis-associated organ dysfunction and septic shock. Propensity score matching was performed including each patient´s baseline characteristics. The median age was 9.9 months (IQR 4.9-22.2) with 55.5% of the patients being male. Acute kidney injury was seen less frequently in children who received a balanced solution than in those who received an unbalanced solution (20.3% vs 25.7% P = 0.006 ORa, 0.75; 95% CI, 0.65-0.87), adjusted for disease severity. In addition, the group that received balanced solutions had less need for CRRT (3.3 % vs 6.5%; P = 0.02 ORa 0.48; 95% CI, 0.36-0.64) and a shorter PICU stay (6 days IQR 4.4-20.2 vs 10.2 days IQR 4.7-26; P < 0.001) than the group with unbalanced solutions. We found no difference in the frequency of metabolic acidosis (P = 0.37), hyperchloremia (P = 0.11) and mortality (P = 0.25) between the 2 groups. CONCLUSION: In children with sepsis-associated organ dysfunction and septic shock, the use of unbalanced solutions for fluid resuscitation is associated with a higher frequency of acute kidney injury, a greater need for continuous renal support and a longer PICU stay compared to the use of balanced solutions, in a middle-income country.

DNA Methylation and Demethylation Underlie the Sex Difference in Estrogen Receptor Alpha in the Arcuate Nucleus.

INTRODUCTION: Neurons expressing estrogen receptor (ER) ɑ in the arcuate (ARC) and ventromedial (VMH) nuclei of the hypothalamus sex-specifically control energy homeostasis, sexual behavior, and bone density. Females have more ERɑ neurons in the VMH and ARC than males, and the sex difference in the VMH is eliminated by neonatal treatment with testosterone or a DNA methylation inhibitor. OBJECTIVE: Here, we tested the roles of testosterone and DNA methylation/demethylation in development of ERɑ in the ARC. METHODS: ERɑ was examined at birth and weaning in mice that received vehicle or testosterone subcutaneously, and vehicle or DNA methyltransferase inhibitor intracerebroventricularly, as neonates. To examine effects of DNA demethylation on the ERɑ cell number in the ARC, mice were treated neonatally with small interfering RNAs against ten-eleven translocase enzymes. The methylation status of the ERɑ gene (Esr1) was determined in the ARC and VMH using pyrosequencing of bisulfite-converted DNA. RESULTS: A sex difference in ERɑ in the ARC, favoring females, developed between birth and weaning and was due to programming effects of testosterone. Neonatal inhibition of DNA methylation decreased ERɑ in the ARC of females, and an inhibition of demethylation increased ERɑ in the ARC of males. The promoter region of Esr1 exhibited a small sex difference in percent of total methylation in the ARC (females > males) that was opposite to that in the VMH (males > females). CONCLUSION: DNA methylation and demethylation regulate ERɑ cell number in the ARC, and methylation correlates with activation of Esr1 in this region.

Inter-sectorial network for assisting women in situations of violence: handicraft work built by the people / Red intersectorial de atención a mujeres en situación de violencia: trabajo artesanal construido por las personas / Rede intersetorial de atendimento às mulheres em situação de violência: trabalho artesanal construído pelas pessoas

ABSTRACT Objectives: to discuss the meanings attributed by professionals to the construction of the service network for women in situations of violence. Methods: Convergent Care Research developed with the application of a convergence group with 32 participants from the health, social assistance, or public security sectors, in Santa Maria, Rio Grande do Sul. The data was produced during ten meetings, based on the problematization methodology, and submitted to analysis of thematic content and interpreted with the referential of networks. Results: the construction of the network is an artisanal work carried out by people continuously, permeated by bonds, communication and partnerships between services and knowledge of work processes. Lashings require permanent movement. Final Considerations: building a network implies defining intertwining lines; form nodes that create cross-sector connections. There is a need to institutionalize processes through care continuity protocols, associated with an efficient communication system between sectors.

RESUMEN Objetivos: discutir los sentidos atribuidos por profesionales a construcción de la red de atención a mujeres en situación de violencia. Métodos: Investigación Convergente Asistencial desarrollada con aplicación de grupo de convergencia con 32 participantes de sectores de salud, asistencia social o seguridad pública, en Santa Maria, Rio Grande do Sul. Datos fueron producidos durante diez encuentros, pautados en la metodología de la problematización, sometidos al análisis de contenido temático e interpretados con el referencial de redes. Resultados: la construcción de la red es un trabajo artesanal realizado por personas continuamente, permeado por vínculo, comunicación y colaboraciones entre los servicios y conocimiento de los procesos de trabajo. Las amarraduras demandan movimiento permanente. Consideraciones Finales: construir red implica definir líneas que se entrelazan; formar nudos que crean conexiones intersectoriales. Hay necesidad de institucionalización de los procesos mediante protocolos de continuidad del cuidado, asociados a un sistema de comunicación eficiente entre los sectores.

RESUMO Objetivos: discutir os sentidos atribuídos por profissionais à construção da rede de atendimento às mulheres em situação de violência. Métodos: Pesquisa Convergente Assistencial desenvolvida com aplicação de grupo de convergência com 32 participantes de setores da saúde, assistência social ou segurança pública, em Santa Maria, Rio Grande do Sul. Os dados foram produzidos durante dez encontros, pautados na metodologia da problematização, submetidos à análise de conteúdo temática e interpretados com o referencial de redes. Resultados: a construção da rede é um trabalho artesanal realizado pelas pessoas continuamente, permeado por vínculo, comunicação e parcerias entre os serviços e conhecimento dos processos de trabalho. As amarrações exigem movimento permanente. Considerações Finais: construir rede implica definir linhas que se entrelaçam; formar nós que criam conexões intersetoriais. Há necessidade de institucionalização dos processos por meio de protocolos de continuidade do cuidado, associados a um sistema de comunicação eficiente entre os setores.

Immunotherapy in non-small cell lung cancer: Update and new insights.

BACKGROUND: The treatment of non-small-cell lung carcinoma (NSCLC) has changed markedly in recent years as a result of two major treatment milestones: Targeted therapy and immunotherapy. Since 2015, immunotherapy has been changing the paradigm of NSCLC treatment in different settings and has contributed to improve the quality of life of these patients. The most widely used immunotherapy strategy in clinical practice is currently PD-1 and CTLA-4 immune checkpoint inhibition-based immunotherapy. Initial successful results came from an improvement in overall survival for pretreated patients, and immunotherapy subsequently moved to a first-line palliative setting as monotherapy, in combination with chemotherapy or as double-checkpoint inhibition. With regard to earlier stages, consolidation immunotherapy after chemoradiation has also changed the paradigm of unresectable NSCLC, with marked benefits in terms of disease-free and overall survival. During the last few years, efforts have focused on the introduction of immunotherapy in earlier stages as neoadjuvant treatment for potentially resectable tumors and in an adjuvant setting, with some very promising results. AIM: In this manuscript, we provide both an agile and thorough review of the role of immunotherapy in non-small cell lung cancer, a critical analysis of the most important studies, current indications, the role of biomarkers, new insights, and future challenges. RELEVANCE FOR PATIENTS: Immunotherapy has revolutionized the treatment of non-small cell lung cancer patients reaching better survival outcomes in first and second palliative setting and in unresectable stage III tumors. Next year's immunotherapy will also introduce in earlier stages. Through an extensive knowledge of the mechanisms of action and of immunotherapy-based studies, the best treatment alternative can be offered to patients, helping to improve their survival and cure rates.

An integrated framework reinstating the environmental dimension for GWAS and genomic selection in crops.

Identifying mechanisms and pathways involved in gene-environment interplay and phenotypic plasticity is a long-standing challenge. It is highly desirable to establish an integrated framework with an environmental dimension for complex trait dissection and prediction. A critical step is to identify an environmental index that is both biologically relevant and estimable for new environments. With extensive field-observed complex traits, environmental profiles, and genome-wide single nucleotide polymorphisms for three major crops (maize, wheat, and oat), we demonstrated that identifying such an environmental index (i.e., a combination of environmental parameter and growth window) enables genome-wide association studies and genomic selection of complex traits to be conducted with an explicit environmental dimension. Interestingly, genes identified for two reaction-norm parameters (i.e., intercept and slope) derived from flowering time values along the environmental index were less colocalized for a diverse maize panel than for wheat and oat breeding panels, agreeing with the different diversity levels and genetic constitutions of the panels. In addition, we showcased the usefulness of this framework for systematically forecasting the performance of diverse germplasm panels in new environments. This general framework and the companion CERIS-JGRA analytical package should facilitate biologically informed dissection of complex traits, enhanced performance prediction in breeding for future climates, and coordinated efforts to enrich our understanding of mechanisms underlying phenotypic variation.

Adolescent stress during, but not after, pubertal onset impairs indices of prepulse inhibition in adult rats.

Exposure to stress during adolescence is a risk factor for developing several psychiatric disorders, many of which involve prefrontal cortex (PFC) dysfunction. The human PFC and analogous rodent medial prefrontal cortex (mPFC) continue to mature functionally and anatomically during adolescence, and some of these maturational events coincide with pubertal onset. As developing brain regions are more susceptible to the negative effects of stress, this may make puberty especially vulnerable. To test this, we exposed male and female rats to isolation and restraint stress during the onset of puberty or during the post-pubertal period of adolescence. In young adulthood, both stressed groups and an unstressed control group underwent testing on a battery of tasks to assess emotional and cognitive behaviors, and the volume of the mPFC was quantified postmortem. Factor analysis revealed only subjects stressed peri-pubertally showed a long-term deficiency compared to controls in prepulse inhibition. Additionally, both sexes showed volumetric mPFC decreases following adolescent stress, and these losses were most pronounced in females. Our findings suggest that pubertal onset may be a vulnerable window wherein adolescents are most susceptible to the negative consequences of stress exposure. Furthermore, it highlights the importance of accounting for pubertal status when studying adolescents.

Birth elicits a conserved neuroendocrine response with implications for perinatal osmoregulation and neuronal cell death.

Long-standing clinical findings report a dramatic surge of vasopressin in umbilical cord blood of the human neonate, but the neural underpinnings and function(s) of this phenomenon remain obscure. We studied neural activation in perinatal mice and rats, and found that birth triggers activation of the suprachiasmatic, supraoptic, and paraventricular nuclei of the hypothalamus. This was seen whether mice were born vaginally or via Cesarean section (C-section), and when birth timing was experimentally manipulated. Neuronal phenotyping showed that the activated neurons were predominantly vasopressinergic, and vasopressin mRNA increased fivefold in the hypothalamus during the 2-3 days before birth. Copeptin, a surrogate marker of vasopressin, was elevated 30-to 50-fold in plasma of perinatal mice, with higher levels after a vaginal than a C-section birth. We also found an acute decrease in plasma osmolality after a vaginal, but not C-section birth, suggesting that the difference in vasopressin release between birth modes is functionally meaningful. When vasopressin was administered centrally to newborns, we found an ~ 50% reduction in neuronal cell death in specific brain areas. Collectively, our results identify a conserved neuroendocrine response to birth that is sensitive to birth mode, and influences peripheral physiology and neurodevelopment.

Deformations and Ruptures in Human Lenses With Cortical Cataract Subjected to Ex Vivo Simulated Accommodation.

Purpose: Human cortical opacities are most commonly accompanied by changes in lens fiber structure in the equatorial region at the lens nucleus-cortex interface. Cortex and nucleus have different elastic properties, which change with age. We therefore subjected ex vivo lenses to simulated accommodation and studied the internal deformations to better understand the mechanism of cortical cataract formation. Methods: Nine human donor lenses (33-88 years old) were tested using a bespoke radial stretching device for anterior eye segments. Seven of the lenses exhibited cortical cataracts. The other two lenses, without cataract, were used as controls. Frontal and cross-sectional images of the lens obtained during stretching facilitated measurements on equatorial lens diameter and central lens thickness in the stretched and unstretched states. Results: Stretching caused the lens equatorial diameter to increase in all cases. Conversely, the lens central thickness showed no systematic variation during stretching. For four of the lenses with cortical cataract, ruptures were observed during stretching at the nucleus-cortex boundary adjacent to the cortical cataracts. Ruptures were not observed in the control lenses or in the three other lenses with cortical cataract. Conclusions: Internal ruptures can occur in aged ex vivo lenses subjected to simulated disaccommodation. These ruptures occur at the nucleus-cortex interface; at this location, a significant stiffness discontinuity is expected to develop with age. It is hypothesized that ruptures occur in in vivo lenses during accommodation-or attempted accommodation.

Status and prospects of genome-wide association studies in plants.

Genome-wide association studies (GWAS) have developed into a powerful and ubiquitous tool for the investigation of complex traits. In large part, this was fueled by advances in genomic technology, enabling us to examine genome-wide genetic variants across diverse genetic materials. The development of the mixed model framework for GWAS dramatically reduced the number of false positives compared with naïve methods. Building on this foundation, many methods have since been developed to increase computational speed or improve statistical power in GWAS. These methods have allowed the detection of genomic variants associated with either traditional agronomic phenotypes or biochemical and molecular phenotypes. In turn, these associations enable applications in gene cloning and in accelerated crop breeding through marker assisted selection or genetic engineering. Current topics of investigation include rare-variant analysis, synthetic associations, optimizing the choice of GWAS model, and utilizing GWAS results to advance knowledge of biological processes. Ongoing research in these areas will facilitate further advances in GWAS methods and their applications.

Prognostic value of the TGFß1 rs4803455 single nucleotide polymorphism in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein ß1 (HSPB1) and transforming growth factor ß1 (TGFß1) and survival have been investigated. METHODS: A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFß1 gene and 5 of HSPB1 gene) variables were analyzed. RESULTS: The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFß1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19-8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37-10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98-3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p < 0.001) and DFS (p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. CONCLUSIONS: Genetic analysis showed the CA genotype of TGFß1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.