Scalable stable comb-to-tone integrated RF photonic drive for superconducting qubits.

The recent advent of quantum computing has the potential to overhaul security, communications, and scientific modeling. Superconducting qubits are a leading platform that is advancing noise-tolerant intermediate-scale quantum processors. The implementation requires scaling to large numbers of superconducting qubits, circuit depths, and gate speeds, wherein high-purity RF signal generation and effective cabling transport are desirable. Fiber photonic-enhanced RF signal generation has demonstrated the principle of addressing both signal generation and transport requirements, supporting intermediate qubit numbers and robust packaging efforts; however, fiber-based approaches to RF signal distribution are often bounded by their phase instability. Here, we present a silicon photonic integrated circuit-based version of a photonic-enhanced RF signal generator that demonstrates the requisite stability, as well as a path towards the necessary signal fidelity.

Predictive factors of osteoporotic hip fracture in octogenarians.

OBJECTIVE: This study aims to identify the risk factors associated with osteoporotic hip fractures in octogenarians and seeks to refine primary prevention strategies for these fractures. MATERIAL AND METHODS: We conducted a case-control study involving individuals aged 79 years and older with hip fractures, comparing them to age- and sex-matched controls without a history of hip fractures. We collected epidemiological, clinical, anthropometric, and analytical factors. We evaluated the presence of osteoporosis using bone densitometry. We defined sarcopenia according the European Working Group on Sarcopenia in Older People criteria (EWGSOP2). RESULTS: Ninety-five patients per group were analyzed, with a mean age of 82 years, of which 74% were women. The multivariate analysis included statistically significant factors found in the univariate analysis (p < 0.05). These factors included the Barthel Index, nutritional assessment using the CONUT tool, folic acid, vitamin D deficiency, presence of previous fractures, loss of visual acuity, bicipital circumference, sarcopenia, and osteoporosis (densitometry in the neck of the femur). The Nutritional state (OR: 0.08 [0.01-0.61]), the folic acid levels (OR 0.32 [0.1-1]), and a loss of visual acuity (OR 33.16 [2.91-377.87]) were the independent risk factors associated with hip fracture. CONCLUSIONS: The assessment of nutritional status in elderly patients, coupled with a comprehensive geriatric assessment, represents easily reproducible and cost-effective tools. These tools can effectively aid in identifying individuals at risk of hip fractures, thereby contributing to more targeted and efficient preventive measures.

Perioperative stress and anxiety in parents of children operated on for congenital heart disease.

INTRODUCTION: Levels of stress and anxiety suffered by parents of children with congenital heart disease (PCUCS) during their children's admission for cardiac surgery may be higher than those suffered by other parents who go through the same experience. OBJECTIVE: General objective of this study was to measure the stress and anxiety suffered by PCUCS and parents of children undergoing renal surgery (PCURS) in relation to the intervention of their children. The specific objective of the quantitative study was to compare global stress and anxiety according to sex, time of the perioperative period, and cohort. The general objective of the qualitative section is to explore the experience that PCUCS and PCURS have during their hospital stay and to identify the specific factors that influence the genesis of stress and anxiety. METHOD: A cohort study was carried out in which PCURS and PCUCS were included. The quantitative part was performed by comparing the scores of three questionnaires that measure stress levels (PSS-14), state anxiety (STAIE) and trait anxiety (STAIR) throughout three perioperative moments. At the same time, a qualitative study was carried out with semi-structured interviews and collection of diaries on which a descriptive phenomenological analysis was carried out, according to Munhall. The analysis of the text was carried out according to Colaizzi. RESULTS: Stress and anxiety levels were significantly higher in PCUCS compared to PCURS. Mothers in the cardiac cohort were those with the highest scores on all scales. In the qualitative study, four themes emerged: "stress and anxiety from the moment of diagnosis", "surgical intervention as a critical moment", "harshness of the postoperative period in the Intensive Care Unit" and "joy and gratitude versus dependence and fear for the future". CONCLUSIONS: PCUCS suffer higher levels of stress and anxiety than PCURS, being the mothers of the cardiac cohort those who suffer these disorders with greater intensity. This study can constitute a starting point to develop strategies that cover these parental needs.

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study.

BACKGROUND: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. METHODS: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. RESULTS: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. CONCLUSION: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. TRIAL REGISTRATION: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

Hyper-Reflective Outer Nuclear Layer (HONL) in Vogt-Koyanagi-Harada Disease and Sympathetic Ophthalmia.

PURPOSE: To describe the optical coherence tomography (OCT) findings of hyper-reflective outer nuclear layer (HONL) in two cases of stromal choroiditis (Vogt-Koyanagi-Harada disease - VKH, and sympathetic ophthalmia - SO). METHODS: Case report. RESULTS: Clinical and imaging findings of two patients (37-year-old female with VKH and 34-year-old male with SO) have been described. Both patients showed typical features of the disease with subretinal fluid accumulation and choroidal thickening on OCT. However, OCT of both patients at the initial visit revealed HONL, which was unusual in these conditions. During follow-up, OCT scans revealed thinning and atrophy of the outer retinal layers, irregular thickening of the retinal pigment epithelium, and irregular autofluorescence pattern on autofluorescence imaging. CONCLUSIONS: The presence of HONL may serve as a poor prognostic factor in VKH and SO, resulting in thinning and atrophy of the outer retinal layers.

Modified videoendoscopic inguinal lymphadenectomy through suprafascial approach: Technical description and preliminary surgical outcomes.

INTRODUCTION: The videoendoscopic approach to inguinal lymph node dissection (VEIL) has been suggested as an excellent alternative carrying lower morbidity but equivalent oncological control. One of its most difficult steps is the development of an appropriate plane of dissection. A suprafascial approach would allow for better exposure. The objective of this study is to determine the feasibility, in terms of safety and oncological control, of a technical modification to the classical VEIL technique using a suprafascial plane of dissection in an initial series of patients. PATIENTS AND METHODS: A single institution retrospective review of patients undergoing VEIL technique using our modified suprafascial approach was conducted. A step-by-step surgical description is provided. Data collected included demographics; comorbid conditions; disease characteristics; intraoperative factors; and postoperative factors. RESULTS: A total of 7 patients (12 procedures) were included. Average age was 64.42 years old, and 71.42% of the patients were male. The procedure was performed bilaterally in 71.4% of the cases. Median estimated blood loss was 10 mL (range 10-25). Mean operative time was 185 min (range 120-170). Median number of nodes removed was 10.25 nodes (range 7-11). Only one of the patients (8.3%) experienced a Clavien-Dindo grade IIIa complication requiring delayed percutaneous drainage replacement. Median time until drainage removal was 13 days (range 10-16). Median length of stay was 48 hours but ranged from 24-96 hours within the series. CONCLUSIONS: The modified VEIL technique using a suprafascial plane of the dissection, allows a bilateral ILND in highly competitive operative times and with limited morbidity, without compromising its oncological efficacy.

Tau Appearance from High-Energy Neutrino Interactions.

High-energy muon and electron neutrinos yield a non-negligible flux of tau neutrinos as they propagate through Earth. In this Letter, we address the impact of this additional component in the PeV and EeV energy regimes for the first time. Above 300 TeV, this contribution is predicted to be significantly larger than the atmospheric background, and it alters current and future neutrino telescopes' capabilities to discover a cosmic tau-neutrino flux. Further, we demonstrate that Earth-skimming neutrino experiments, designed to observe tau neutrinos, will be sensitive to cosmogenic neutrinos even in extreme scenarios without a primary tau-neutrino component.

Non-metastatic castration-resistant prostate cancer: management recommendations.

INTRODUCTION AND OBJECTIVE: Survival and quality of life (QoL) of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) deteriorate significantly when they develop metastases. New generation antiandrogens (apalutamide, enzalutamide and darolutamide) can prolong metastasis-free survival (MFS) and overall survival (OS) in these patients, maintaining their QoL. MATERIAL AND METHODS: After the performance of a systematic review of the literature, a scientific committee reached a consensus on simple and practical recommendations to consolidate and improve the management of patients with nmCRPC in urology consultations. RESULTS: Recommendations are made on the frequency of PSA determination and imaging tests in patients with nmCRPC. The importance of co-morbidities in patients with nmCRPC is also highlighted, and recommendations are also made on functional and QoL assessment that can be carried out during urology consultations. The efficacy, safety, and effects on QoL of new generation antiandrogens are reviewed. CONCLUSIONS: To evaluate treatment of patients with nmCRPC, it is necessary to consider co-morbidities and QoL, in addition to age. New generation antiandrogens are a safe and effective treatment option for patients with nmCRPC. The recommendations of this review can be helpful in optimizing the management of nmCRPC patients in urology consultations.

[Prevalence and incidence of ictus in Europe: systematic review and meta-analysis].

BACKGROUND: Stroke is the second cause of death and the first cause of disability in Europe. The number of stroke patients shows a rapidly increasing due to the increase in the elderly population. The aim of this meta-analysis is to evaluate the prevalence and incidence of stroke in Europe. METHOD: We conducted a literature search in MEDLINE, SCOPUS, CINAHL Complete and EMBASE, using the keywords "stroke", "cerebrovascular accident", "epidemiology", "prevalence", "incidence" and "Europe". In order to evaluate the quality and risk of bias, we used the Hoy's modified scale for prevalence studies and the Newcastle Ottawa Scale for incidence studies. A random effects model with 95% confidence intervals (95%CI) was used for the meta-analysis. The I2 statistic was applied to assess heterogeneity. RESULTS: The prevalence of stroke in Europe adjusted for sex was estimated at 9.2% (95%CI: 4.4-14.0). The prevalence was 9.1% (95%CI: 4.7-13.6) in men and 9.2% (95%CI: 4.1-14.4) in women, and increased with age. The incidence of stroke in Europe adjusted for sex was 191.9 per 100,000 person-years (95%CI: 156.4-227.3); it was 195.7 per 100,000 person-years (95%CI: 142.4-249.0) in men and 188.1 per 100,000 person-years (95%CI: 138.6-237.7) in women. Again, these rates increased with age. CONCLUSION: The prevalence of stroke in Europe is 9.2%. The incidence of stroke in Europe is 191.9 per 100,000 person-years. The prevalence of stroke has increased, whereas the incidence of stroke is stable in comparison with studies conducted at the beginning of the 21st century.

The interaction of deep convection with the general circulation in Titan's atmosphere. Part 1: Cloud Resolving Simulations.

The deep convective cloud-environment feedback loop is likely important to Titan's global methane, energy, and momentum cycles, just as it is for Earth's global water, energy, and momentum budgets. General circulation models of Titan's atmosphere are unable to explicitly simulate deep convection and must instead parameterize the impact of this important subgrid-scale phenomenon on the model-resolved atmospheric state. The goal of this study is to better quantify through cloud resolving modeling the effects of deep convective methane storms on their environment and to feed that information forward to improve parameterizations in global models. Dozens of atmospheric profiles unstable with respect to deep moist convection are extracted from the global Titan Atmospheric Model (TAM) and used to initialize the cloud-resolving Titan Regional Atmospheric Modeling System (TRAMS). Mean profiles of heating/cooling and moistening/drying of the large-scale environment in TRAMS indicate that Titan's deep convection forces the environment in a manner analogous to Earth: Large-scale subsidence of the environmental air warms and dries the environment, but clouds can also moisten the environment through the detrainment and evaporation of condensate near cloud top. Relative humidity profiles and characteristic convective time scales are derived to guide the tuning of the deep convective parameterization implemented in TAM, as described in a companion paper. The triggering of convection, the dry convective mixing of the planetary boundary layer, and the entrainment of environmental air into rising air parcels are found to be critical to determining whether a deep convective cloud will form. Only profiles with relatively large convective available potential energy (CAPE) and well mixed planetary boundary layers with high relative humidity were found to produce storms. Environments with low level thermal inversions and planetary boundary layers with low relative humidity or rapidly decreasing moisture with height failed to generate deep convection in TRAMS despite positive CAPE.

A TLR4 agonist improves immune checkpoint blockade treatment by increasing the ratio of effector to regulatory cells within the tumor microenvironment.

Brucella lumazine synthase (BLS) is a homodecameric protein that activates dendritic cells via toll like receptor 4, inducing the secretion of pro-inflammatory cytokines and chemokines. We have previously shown that BLS has a therapeutic effect in B16 melanoma-bearing mice only when administered at early stages of tumor growth. In this work, we study the mechanisms underlying the therapeutic effect of BLS, by analyzing the tumor microenvironment. Administration of BLS at early stages of tumor growth induces high levels of serum IFN-γ, as well as an increment of hematopoietic immune cells within the tumor. Moreover, BLS-treatment increases the ratio of effector to regulatory cells. However, all treated mice eventually succumb to the tumors. Therefore, we combined BLS administration with anti-PD-1 treatment. Combined treatment increases the outcome of both monotherapies. In conclusion, we show that the absence of the therapeutic effect at late stages of tumor growth correlates with low levels of serum IFN-γ and lower infiltration of immune cells in the tumor, both of which are essential to delay tumor growth. Furthermore, the combined treatment of BLS and PD-1 blockade shows that BLS could be exploited as an essential immunomodulator in combination therapy with an immune checkpoint blockade to treat skin cancer.

Osteoporotic vertebral fractures: A diagnostic challenge in the 21st century.

Vertebral fractures are the most prevalent osteoporotic fractures and are paradoxically the most underdiagnosed. While only one-third of patients have acute pain, they can present other associated chronic complications. Vertrebal fractures are associated with the onset of new fractures, both vertebral and nonvertebral. Radiography of the dorsal-lumbar spine is a useful tool for detecting them but depends on the subjective interpretation of the physician conducting the assessment. New techniques, such as vertebral morphometry, have recently demonstrated greater efficacy in detecting v vertebral fractures and are performed concomitantly with bone densitometry. Knowing how to identify vertebral fractures is essential for the secondary prevention of new fractures and improving our patients' quality of life.

Clinical drivers for imaging testing in non-metastatic castration-resistant prostate cancer in clinical practice: Results of the IDENTIFICA study. / Factores clínicos determinantes para la realización de pruebas de imagen en cáncer de próstata resistente a la castración no metastásico en la práctica clínica: resultados del estudio IDENTIFICA.

INTRODUCTION: The aim of the study was to describe the clinical drivers that lead physicians to perform imaging tests in search of metastasis in non-metastasic castration prostate resistant cancer (nmCRPC) patients. METHODS: Observational, cross-sectional study conducted at the Departments of Urology of 38 Spanish hospitals. The study included 188 patients diagnosed with nmCRPC who underwent an imaging test for the assessment of metástasis. In one study visit, physicians were requested to specify the clinical factors that led them to perform these tests. The results of the imaging tests and the clinical characteristics of the patients since the time of prostate cancer (PC) diagnosis, were reported. Regression analyses were used to determine predictors of imaging test results. RESULTS: Prostate-specific antigen (PSA) level was the most important driver to order imaging tests (57.1%), followed by regular follow-up (16.5%) and PSA doubling time (PSADT) (12.0%). Although these drivers were not associated to detection of metastasis, patients with PSA levels ≥20 ng/mL had a greater risk of metastasis than patients with PSA levels <4ng/mL (P=.004) and CRPC patients diagnosed with metastasis (mCRPC) had higher median PSA levels (20.9; interquartile range [IQR]: 6.7-38.6) than nmCRPC (9.1; IQR: 5.0-18.0) (P=.005). Sixty-six percent of the patients did not undergo any imaging test after CRPC diagnosis until the study visit (10.6, IQR: 4.0-19.5 months). Curative-intent treatment at PC diagnosis and Gleason score predicted longer time from PC to CRPC diagnosis. CONCLUSIONS: Physicians based their decisions to order imaging tests for metastasis detection in nmCRPC patients mainly on PSA and PSA kinetics, including the regular follow-up stated by guideline recommendations.

Trends in mortality from stroke in the European Union, 1996-2015.

BACKGROUND AND PURPOSE: Stroke is the second largest single cause of death in Europe, responsible for 9% and 13% of all deaths in men and women, respectively. There have been large overall declines in stroke mortality rates in the majority of European countries in recent decades. The aim of this study was to analyse trends in mortality caused by stroke in the 28 member countries of the European Union (EU) over the last two decades. METHODS: We extracted data for age-standardized stroke mortality rates per 100 000 in the EU for the period 1996-2015 from the World Health Organization database. Joinpoint regression analysis was used to analyse the trends and compute the annual percent change (APC) in the EU as a whole and by country. Analyses were conducted by gender and by European region. RESULTS: Mortality from stroke has decreased in the EU over the study period by an average APC of 4.2%. All countries showed downward trends, with the sharpest decreases in Estonia, Portugal and Austria. We recorded statistically significant decreases of 4.2% and 4.3% in mortality rates in men and women, respectively, in the whole EU. Southern and western countries showed the steepest decreases, whereas mortality has increased in northern countries in recent years. CONCLUSIONS: Stroke mortality has decreased in the EU, in both sexes, especially in southern and western European countries. Our results could be a reference for the development of primary prevention and acute management of stroke policies focused on countries with higher mortality.

Cross-modality and in-vivo validation of 4D flow MRI evaluation of uterine artery blood flow in human pregnancy.

OBJECTIVES: Clinical assessment of uterine artery (UtA) hemodynamics is currently limited to Doppler ultrasound (US) velocimetry. We have demonstrated previously the feasibility of applying four-dimensional (4D) flow magnetic resonance imaging (MRI) to evaluate UtA hemodynamics during pregnancy, allowing flow quantification of the entire course of the vessel. In this study, we sought to further validate the physiological relevance of 4D flow MRI measurement of UtA blood flow by exploring its association with pregnancy outcome relative to US-based metrics. METHODS: Recruited into this prospective, cross-sectional study were 87 women with a singleton pregnancy who underwent 4D flow MRI between May 2016 and April 2019 to measure the UtA pulsatility index (MRI-PI) and blood flow rate (MRI-flow, in mL/min). UtA-PI was also measured using US (US-PI). The primary outcome was a composite (COMP) of pre-eclampsia (PE) and/or small-for-gestational-age (SGA) neonate, and secondary outcomes were PE and SGA neonate individually. We assessed the ability of MRI-flow, MRI-PI and US-PI to distinguish between outcomes, and evaluated whether MRI-flow changed as gestation progressed. RESULTS: Following 4D flow postprocessing and exclusions from the analysis, 74 women had 4D flow MRI data analyzed for both UtAs. Of these, 18 developed a COMP outcome: three developed PE only, 11 had a SGA neonate only and four had both. A comparison of the COMP group vs the no-COMP group found no differences in maternal age, body mass index, nulliparity, gravidity or race. For 66 of the 74 subjects, US data were also available. In these subjects, both median MRI-PI (0.95 vs 0.70; P < 0.01) and median US-PI (0.95 vs 0.73; P < 0.01) were significantly increased in subjects in the COMP group compared with those in the no-COMP group. The UtA blood-flow rate, as measured by MRI, did not increase significantly from the second to the third trimester (median flow (interquartile range (IQR)), 543 (419-698) vs 575 (440-746) mL/min; P = 0.77), but it was significantly lower overall in the COMP compared with the no-COMP group (median flow (IQR), 486 (366-598) vs 624 (457-749) mL/min; P = 0.04). The areas under the receiver-operating-characteristics curves for MRI-flow, MRI-PI and US-PI in predicting COMP were not significantly different (0.694, 0.737 and 0.731, respectively; P = 0.87). CONCLUSIONS: 4D flow MRI can yield physiological measures of UtA blood-flow rate and PI that are associated with adverse pregnancy outcome. This may open up new avenues in the future to expand the potential of this technique as a robust tool with which to evaluate UtA hemodynamics in pregnancy. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Wood development regulators involved in apical growth in Pinus canariensis.

The shoot apical meristem is responsible of seasonal length increase in plants. In woody plants transition from primary to secondary growth is also produced during seasonal apical growth. These processes are controlled by different families of transcription factors. Levels of transcriptomic activity during apical growth were measured by means of a cDNA microarray designed from sequences related to meristematic activity in Pinus canariensis. The identification of differentially expressed genes was performed using a time-course analysis. A total of 7170 genes were differentially expressed and grouped in six clusters according to their expression profiles. We identified master regulators, such as WUSCHEL-like HOMEOBOX (WOX), to be involved in the first stages of apical development, i.e. growth of primary tissues, while other transcription factors, such as Class III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIP III) and KNOTTED-like (KNOX) and BEL1-like (BELL) HOMEODOMAIN proteins, were found to be induced during last stages of apical seasonal development, already with secondary growth. Our results reveal the main expression patterns of these genes during apical development and the transition from primary to secondary stem growth. In particular, the regulatory factors identified play key roles in controlling stem architecture and constitute candidate genes for the study of other development processes in conifers.