Transcriptome analysis reveals biosynthesis and regulation of flavonoid in common bean seeds during grain filling.

The Andean domesticated common beans (Phaseolus vulgaris) are significant sources of phenolic compounds associated with health benefits. However, the regulation of biosynthesis of these compounds during bean seed development remains unclear. To elucidate the gene expression patterns involved in the regulation of the flavonoid pathway, we conducted a transcriptome analysis of two contrasting Chilean varieties, Negro Argel (black bean) and Coscorron (white bean), at three developmental stages associated with seed color change, as well as different flavonoid compound accumulations. Our study reveals that phenolic compound synthesis initiates during seed filling, although it exhibits desynchronization between both varieties. We identified 10,153 Differentially Expressed Genes (DEGs) across all comparisons. The KEGG pathway 'Flavonoid biosynthesis' showed enrichment of induced DEGs in Negro Argel (PV172), consistent with the accumulation of delphinidin, petunidin, and malvidin hexosides in their seeds, while catechin glucoside, procyanidin and kaempferol derivatives were predominantly detected in Coscorrón (PV24). Furthermore, while the flavonoid pathway was active in both varieties, our results suggest that enzymes involved in the final steps, such as ANS and UGT, were crucial, inducing anthocyanin formation in Negro Argel. Additionally, during active anthocyanin biosynthesis, the accumulation of reserve proteins or those related to seed protection and germination was induced. These findings provide valuable insights and serve as a guide for plant breeding aimed at enhancing the health and nutritional properties of common beans.

Pre-surgical cryoablation in ≤ 2 cm ER + /HER2-tumors. Prognostic factors for the presence of residual invasive carcinoma.

BACKGROUND: Breast cancer remains the most commonly diagnosed cancer in women. Breast-conserving surgery (BCS) is the standard approach for small low-risk tumors. If the efficacy of cryoablation is demonstrated, it could provide a minimally invasive alternative to surgery. PURPOSE: To determine the success of ultrasound-guided cryoablation in achieving the absence of Residual Invasive Cancer (RIC) for patients with ER + /HER2- tumors ≤ 2cm and sonographically negative axillary nodes. MATERIALS AND METHODS: This prospective study was carried out from April 2021 to June 2023, and involved 60 preoperative cryoablation procedures on ultrasound-visible, node-negative (cN0) infiltrating ductal carcinomas (IDC). Standard diagnostic imaging included mammography and tomosynthesis, supplemented by ultrasound-guided biopsy. MRI was performed in patients with associated intraductal carcinoma (DCIS) and an invasive component on core needle biopsy (18 out of 22 cases). All tumors were tagged with ferromagnetic seeds. A triple-phase protocol (freezing-thawing-freezing) with Argon was used, with an average procedure duration of 40 min. A logistic regression model was applied to determine significant correlation between RIC and the study variables. RESULTS: Fifty-nine women (mean age 63 ± 8 years) with sixty low-risk unifocal IDC underwent cryoablation prior to surgery. Pathological examination of lumpectomy specimens post-cryoablation revealed RIC in only one of 38 patients with pure IDC and in 4 of 22 mixed IDC/DCIS cases. All treated tumors had clear surgical margins, with no significant procedural complications. CONCLUSIONS: Cryoablation was effective in eradicating 97% of pure infiltrating ER + /HER2-tumors ≤ 2cm, demonstrating its potential as a surgical alternative in selected patients.

Survival in pregnancy-associated breast cancer patients compared to non-pregnant controls.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy. METHODS: Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage. RESULTS: Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25). CONCLUSIONS: The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype.

TOPAS-Tissue: A Framework for the Simulation of the Biological Response to Ionizing Radiation at the Multi-Cellular Level.

This work aims to develop and validate a framework for the multiscale simulation of the biological response to ionizing radiation in a population of cells forming a tissue. We present TOPAS-Tissue, a framework to allow coupling two Monte Carlo (MC) codes: TOPAS with the TOPAS-nBio extension, capable of handling the track-structure simulation and subsequent chemistry, and CompuCell3D, an agent-based model simulator for biological and environmental behavior of a population of cells. We verified the implementation by simulating the experimental conditions for a clonogenic survival assay of a 2-D PC-3 cell culture model (10 cells in 10,000 µm2) irradiated by MV X-rays at several absorbed dose values from 0-8 Gy. The simulation considered cell growth and division, irradiation, DSB induction, DNA repair, and cellular response. The survival was obtained by counting the number of colonies, defined as a surviving primary (or seeded) cell with progeny, at 2.7 simulated days after irradiation. DNA repair was simulated with an MC implementation of the two-lesion kinetic model and the cell response with a p53 protein-pulse model. The simulated survival curve followed the theoretical linear-quadratic response with dose. The fitted coefficients α = 0.280 ± 0.025/Gy and ß = 0.042 ± 0.006/Gy2 agreed with published experimental data within two standard deviations. TOPAS-Tissue extends previous works by simulating in an end-to-end way the effects of radiation in a cell population, from irradiation and DNA damage leading to the cell fate. In conclusion, TOPAS-Tissue offers an extensible all-in-one simulation framework that successfully couples Compucell3D and TOPAS for multiscale simulation of the biological response to radiation.

Microdosimetric Analysis for Boron Neutron Capture Therapy via Monte Carlo Track Structure Simulation with Modified Lithium Cross-sections.

Boron neutron capture therapy (BNCT) is a cellular-level hadron therapy achieving therapeutic effects via the synergistic action of multiple particles, including Lithium, alpha, proton, and photon. However, evaluating the relative biological effectiveness (RBE) in BNCT remains challenging. In this research, we performed a microdosimetric calculation for BNCT using the Monte Carlo track structure (MCTS) simulation toolkit, TOPAS-nBio. This paper reports the first attempt to derive the ionization cross-sections of low-energy (>0.025 MeV/u) Lithium for MCTS simulation based on the effective charge cross-section scalation method and phenomenological double-parameter modification. The fitting parameters λ1=1.101,λ2=3.486 were determined to reproduce the range and stopping power data from the ICRU report 73. Besides, the lineal energy spectra of charged particles in BNCT were calculated, and the influence of sensitive volume (SV) size was discussed. Condensed history simulation obtained similar results with MCTS when using Micron-SV while overestimating the lineal energy when using Nano-SV. Furthermore, we found that the microscopic boron distribution can significantly affect the lineal energy for Lithium, while the effect for alpha is minimal. Similar results to the published data by PHITS simulation were observed for the compound particles and monoenergetic protons when using micron-SV. Spectra with nano-SV reflected that the different track densities and absorbed doses in the nucleus together result in the dramatic difference in the macroscopic biological response of BPA and BSH. This work and the developed methodology could impact the research fields in BNCT where understanding radiation effects is crucial, such as the treatment planning system, source evaluation, and new boron drug development.

Laparoscopic adrenalectomy vs. radiofrequency ablation for the treatment of primary aldosteronism. A single center retrospective cohort analysis adjusted with propensity score.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard treatment for unilateral primary aldosteronism. However, satisfactory results have also been published with radiofrequency ablation (RFA). The aim of this study was to compare LA and RFA for the treatment of primary aldosteronism. METHODS: A retrospective cohort study of the patients who underwent LA or RFA in a single center was performed. Morbidity and long-term effectiveness (cure rate and blood pressure control) were analyzed. A multivariate analysis with a propensity score was also performed. RESULTS: Thirty-four patients were included in the study, 24 in the LA group and 10 in the RFA group. Hypertension had been diagnosed a median of 12 years before the intervention. Hypertension was properly controlled before the intervention in 55.9% of the patients. Hypertensive crisis was more common during RFA (4.2% vs. 70.0%, p < 0.001), although no patient suffered any complication because of these crises. LA was longer (174.6 vs. 105.5 min, p = 0.001) and had a longer length of stay (median 2 vs 1 days, p < 0.001). No severe complications were observed in any of the patients. After a median follow-up of 46.2 months, more patients had hypertension cured and blood pressure controlled in the LA group (29.2% vs. 0%, p = 0.078 and 95.5% vs. 50.0%, p = 0.006, respectively). Also, patients in the LA group were taking less antihypertensive drugs (1.8 vs. 3.0, p = 0.054) or mineralocorticoid receptor antagonists (41.7% vs. 90.0%, p = 0.020). Multivariate analysis adjusted by propensity score showed that LA had an OR = 11.3 (p = 0.138) for hypertension cure and an OR = 55.1 (p = 0.040) for blood pressure control. CONCLUSIONS: Although RFA was a less invasive procedure than LA, hypertension was cured and blood pressure was properly controlled in more patients from the LA group. Patients who underwent LA were taking less antihypertensive drugs than patients who had undergone RFA.

Prenatal Diagnosis of Fetal Lymphangioma: A Case Series.

Fetal lymphangioma is an uncommon congenital malformation that is mainly comprised of the subcutaneous tissue of the neck. This malformation can develop in other areas like the thoracic and axillary regions, though rarely. We report 6 consecutive cases of lymphatic malformation in a fetal center in Dominican Republic. In our case series fetal chest lymphangiomas were present in 2 fetuses. In addition, 2 cases of axillary lymphangiomas also involved the thoracic region. Adequate management by a multidiciplinary team is necessary to provide a better approach to delivery.

Atypical image of pneumoperitoneum secondary to colon perforation.

The case was a 66-year-old female with a diagnosis of bilateral ovarian carcinoma with peritoneal carcinomatosis and liver metastases. She had only undergone one cycle of chemotherapy and could not be given other cycles because of her poor general condition. She was admitted due to intermittent vomiting for a week and severe heartburn, with the last stool passed two days before, presenting abdominal distension and lower abdominal pain, without signs of peritonism and no peristaltic sounds. After performing several complementary tests a computed tomography scan showed a large amount of intra-abdominal air, which was thought to be a possible transverse colon volvulus, that caused extrinsic compression on the stomach. A colonoscopy was performed in an attempt to devolvulate, which was unsuccessful.

Effect of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF v600-mutated metastatic colorectal cancer: a real-world study in Spain.

BACKGROUND: Outcomes are poorer in metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations than those without it, but the effect of these mutations on treatment response is unclear. This real-world study assessed the effects of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF V600-mutated mCRC. METHODS: This real-world, multicenter, retrospective, observational study included patients with BRAF V600-mutated mCRC treated in eight hospitals in Spain. The primary endpoints were overall survival (OS) and progression-free survival (PFS); overall response rate (ORR) and disease control rate (DCR) were also assessed. The effect of first- and second-line treatment type on OS, PFS, ORR, and DCR were evaluated, plus the impact of systemic inflammatory markers on these outcomes. A systemic inflammation score (SIS) of 1-3 was assigned based on one point each for platelet-lymphocyte ratio (PLR) ≥200, neutrophil-lymphocyte ratio (NLR) ≥3, and serum albumin < 3.6 g/dL. RESULTS: Of 72 patients, data from 64 were analyzed. After a median of 69.1 months, median OS was 11.9 months and median first-line PFS was 4.4 months. First-line treatment was triplet chemotherapy-antiangiogenic (12.5%), doublet chemotherapy-antiangiogenic (47.2%), doublet chemotherapy-anti-EGFR (11.1%), or doublet chemotherapy (18.1%). Although first-line treatment showed no significant effect on OS, antiangiogenic-based regimens were associated with prolonged median PFS versus non-antiangiogenic regimens. Negative predictors of survival with antiangiogenic-based treatment were NLR, serum albumin, and SIS 1-3, but not PLR. Patients with SIS 1-3 showed significantly prolonged PFS with antiangiogenic-based treatment versus non-antiangiogenic-based treatment, while those with SIS=0 showed no PFS benefit. CONCLUSIONS: Antiangiogenic-based regimens, SIS, NLR, and albumin were predictors of survival in patients with mCRC, while SIS, NLR and serum albumin may predict response to antiangiogenic-based chemotherapy. TRIAL REGISTRATION: GIT-BRAF-2017-01.

Boronated Condensed DNA as a Heterochromatic Radiation Target Model.

The compound 4-dihydroxyboryl-l-phenylalanine (BPA) has found use in clinical trials of boron neutron capture therapy (BNCT). Here, we have examined the interaction with DNA of an amide-blocked BPA derivative of hexa-l-arginine (Ac-BPA-Arg6-NH2). Physical and spectroscopic assays show that this peptide binds to and condenses DNA. The resulting condensates are highly resistant to the effects of nuclease incubation (68-fold) and gamma (38-fold) irradiation. Radioprotection was modeled by Monte Carlo track structure simulations of DNA single strand breaks (SSBs) with TOPAS-nBio. The differences between experimental and simulated SSB yields for uncondensed and condensed DNAs were ca. 2 and 18%, respectively. These observations indicate that the combination of a plasmid DNA target, the BPA-containing peptide, and track structure simulation provides a powerful approach to characterize DNA damage by the high-LET radiation associated with neutron capture on boron.

A Pilot Study Of Aspirin Resistance In Obstructive Sleep Apnea Patients.

Purpose: Obstructive sleep apnea (OSA) leads to endothelial dysfunction and platelet hyperactivity, which are linked to increased risk of cardiovascular disease and implicated in the development of aspirin resistance. We hypothesized that aspirin resistance is prevalent among OSA patients and aimed to explore effects of continuous positive airway pressure (CPAP) therapy on aspirin responsiveness. Methods: In Phase 1, prevalence of aspirin resistance was determined cross-sectionally in a group of OSA patients (n=59) on daily low-dose aspirin (81 mg) taken before entering the study, for primary or secondary prevention. In Phase 2, aspirin responsiveness before and after initiation of CPAP therapy was compared and stratified by endothelial function in a cohort of aspirin-naïve patients with newly diagnosed OSA (n=18). Results: In Phase 1, prevalence of aspirin resistance was 17%; most patients (56%) were on CPAP therapy. In Phase 2, initiation of CPAP therapy was associated with significant improvement in endothelial function (p=0.03). The mean pre-CPAP aspirin resistance units (ARU) was 569 (SD=75). In subjects with endothelial dysfunction (44%), the mean decrease after initiation of CPAP therapy was 43 ARU (SD=81, p=0.18). In contrast, subjects with normal endothelial function experienced the mean decrease of 8 ARU (SD=116, p=0.83). Conclusion: Aspirin resistance may be prevalent among OSA patients. After initiation of CPAP therapy, we observed a trend towards improvement in aspirin responsiveness among patients with endothelial dysfunction. The role of endothelial dysfunction and aspirin resistance should be explored in further studies that focus on the effect of CPAP on cardiovascular outcomes.

Directive Multiband Antenna Based on Rectangular Loop Array and Dumbbell-Shaped Slot Radiator.

In this article, a combination of rectangular loop array and slot radiator for multiband applications is presented. The antenna is configured by arranging, concentrically, a set of rectangular loop radiators excited by electromagnetic coupling provided by a dumbbell slot. The size of the loops is calculated to obtain the desired resonant frequencies, which are almost independent of the adjacent rings. The exciting slot is designed to operate in a wideband frequency range to cover the upper desired resonance. In addition, to obtain directive radiation patterns, a reflector shaped like a box is introduced, giving a stable gain, radiation pattern shape, and port matching at the selected frequencies. The configuration presents great results, since to the authors' knowledge, even a similar configuration given in the open literature presents some disadvantages compared to this one; moreover, not just any structure can be employed as the resonating elements, obtaining multiband behavior at the same time.

External validation of a prognostic model based on total tumor load of sentinel lymph node for early breast cancer patients.

BACKGROUND: A prognostic model based on the results of molecular analysis of sentinel lymph nodes (SLN) is needed to replace the information that staging the entire axilla provided. The aim of the study is to conduct an external validation of a previously developed model for the prediction of 5-year DFS in a group of breast cancer patients that had undergone SLN biopsy assessed by the One Step Nucleic Acid Amplification (OSNA) method. METHODS: We collected retrospective data of 889 patients with breast cancer, who had not received systemic treatment before surgery, and who underwent SLN biopsy and evaluation of all SLN by OSNA. The discrimination ability of the model was assessed by the area under the ROC curve (AUC ROC), and its calibration by comparing 5-years DFS Kaplan-Meier estimates in quartile groups of model predicted probabilities (MPP). RESULTS: The AUC ROC ranged from 0.78 (at 2 years) to 0.73 (at 5 years) in the training set, and from 0.78 to 0.71, respectively, in the validation set. The MPP allowed to distinguish four groups of patients with heterogeneous DFS (log-rank test p < 0.0001). In the highest risk group, the HR were 6.04 [95% CI 2.70, 13.48] in the training set and 4.79 [2.310, 9.93] in the validation set. CONCLUSIONS: The model for the prediction of 5-year DFS was successfully validated using the most stringent form of validation, in centers different from those involved in the development of the model. The external validation of the model confirms its utility for the prediction of 5-year DFS and the usefulness of the TTL value as a prognostic variable.

Photochemical and electrochemical reduction of graphene oxide thin films: tuning the nature of surface defects.

Individual and combined photo(electro)chemical reduction treatments of graphene oxide thin films have been performed to modulate the type of defects introduced into the graphene sheets during the reduction. These were characterized by X-ray photoelectron and Raman spectroscopies, nuclear reaction analysis and electrochemical methods. Illumination of the graphene oxide thin film electrodes with low irradiance simulated solar light provoked the photoassisted reduction of the material with negligible photothermal effects. The photoreduced graphene oxide displayed a fragmented sp2 network due to the formation of a high density of defects (carbon vacancies) and the selective removal of epoxides and hydroxyl groups. In contrast, the electrochemical reduction under mild polarization conditions favored the formation of sp3 defects over vacancies, with a preferential removal of carbonyl and carboxyl groups over hydroxyl/epoxides. Used in conjunction, mild photochemical and electrochemical treatments allowed the obtainment of reduced graphene oxides with varied reduction degrees (ca. C/O ratio ranging from 4.9 to 2.2), and surface defects. Furthermore, the electrochemical reduction prevented the formation of vacancies during the subsequent illumination step. In contrast, both types of defects were accumulated when the GO electrode was first exposed to illumination and then polarized.

Somatic cell counts, reproduction indicators, and technical efficiency in milk production: A stochastic frontier analysis for Spanish dairy farms.

Health and reproductive conditions affect milk yields in dairy cows and may lead to differences in technical efficiency across farms. To investigate this, we created a novel panel data set of 197 dairy farms in northern Spain observed over the period 2006-2014 by combining information from 2 different sources and including data on production variables, somatic cell count, and reproduction indicators, as well as a genetic index. We used these data to estimate a stochastic production frontier where the somatic cell count, age at first calving, and calving interval are included as determinants of technical efficiency. Higher somatic cell count, greater age at first calving, and longer calving intervals were found to decrease technical efficiency, translating into significant losses in profits which we quantify through a simulation exercise. We also quantified the effect of genetic selection on profits, taking into account not only its direct effect on productivity but also its indirect effect through reduced technical efficiency due to the effect of genetic selection on the health and reproduction variables.

Clinical Outcomes in Ring Avulsion Fingers and Systematic Review of the Literature.

Ring avulsions continue to be a challenge in reconstructive surgery. We conducted a retrospective study and reviewed all Urbaniak-Kay type IV degloving injuries replanted at our institution between 2011 and 2018. A systematic review of the literature was also conducted to assess the survival rates, functional, and sensibility outcomes. The results of our systematic review outline a survival rate of 79.50% (101/127). With 1 artery being repaired, 79% of the fingers survived, a value that increased to 87.50% when 2 arteries were anastomosed (P = 0.484). Statistically significant differences (P < 0.001) were found when comparing the survival rates of the fingers with 2 or more veins repaired (87%) with those with only 1 vein anastomosed (51.90%). In terms of nerve reconstruction, there was a significant difference (P < 0.001) with the 2-point discrimination test in favor of the reconstructed group when nerve reparation was done (10.80 mm ± 2.95 mm) versus when digital nerves were not repaired (15.25 mm ± 0.50 mm). Fingers after secondary procedures did not obtain better mobility. The mean total active motion in nonreoperated fingers was 221 degrees (195-270 degrees), whereas the total active motion in the cases who received secondary surgeries was 152 degrees (110-195 degrees), with statistically significant differences (P = 0.02). Therefore, we recommend attempting replantation of degloved fingers. All efforts must be done to carry out 2 vein anastomoses, and our results strongly recommend attempting at least some kind of nerve reconstruction. Secondary surgeries should be reserved for selected cases only, because of the extensive scarring in this kind of injuries. Early mobilization protocols must be encouraged to achieve a good functional result.

DNA Condensation with a Boron-Containing Cationic Peptide for Modeling Boron Neutron Capture Therapy.

The amino acid derivative 4-borono-L-phenylalanine (BPA) has been used in the radiation medicine technique boron neutron capture therapy (BNCT). Here we have characterized its interaction with DNA when incorporated into a positively charged hexa-L-arginine peptide. This ligand binds strongly to DNA and induces its condensation, an effect which is attenuated at higher ionic strengths. The use of an additional tetra-L-arginine ligand enables the preparation of a DNA condensate in the presence of a negligible concentration of unbound boron. Under these conditions, Monte Carlo simulation indicates that >85% of energy deposition events resulting from thermal neutron irradiation derive from boron fission. The combination of experimental model systems and simulations that we describe here provides a valuable tool for accurate track structure modeling of the DNA damage produced by the high LET particles involved in BNCT.

Isolation and Cytotoxic Activity of Phyllocladanes from the Roots of Acacia schaffneri (Leguminosae).

In research on natural molecules with cytotoxic activity that can be used for the development of new anticancer agents, the cytotoxic activity of hexane, chloroform, and methanol extracts from the roots of Acacia schaffneri against colon, lung, and skin cancer cell lines was explored. The hexane extract showed the best activity with an average IC50 of 10.6 µg mL-1. From this extract, three diterpenoids, phyllocladan-16α,19-diol (1), phyllocladan-16α-ol (2), and phylloclad-16-en-3-ol (3), were isolated and characterized by their physical and spectroscopic properties. Diterpenoids 1 and 2 were tested against the same cancer cell lines, as well as their healthy counterparts, CCD841 CoN, MRC5, and VH10, respectively. Compound 1 showed moderate activity (IC50 values between 24 and 70 µg mL-1), although it showed a selective effect against cancer cell lines. Compound 2 was practically inactive. The cytotoxicity mechanism of 1 was analyzed by cell cycle, indicating that the compound induces G0/G1 cell cycle arrest. This effect might be generated by DNA alkylation damage. In addition, compound 1 decreased migration of HT29 cells.