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Background: Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort., Methods: The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (n = 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers., Results: Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction P = .0200 and .0510, respectively)., Conclusion: In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC)., Patients and Methods: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery., Results: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%)., Conclusion: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region., (© 2023. The Author(s).)

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 de Almeida, Cortés, Vilensky, Valenzuela, Cortes-Sanabria, de Souza, Barbeito, Abdelhay, Artagaveytia, Daneri-Navarro, Llera, Müller, Podhajcer, Velazquez, Alcoba, Alonso, Bravo, Camejo, Carraro, Castro, Cataldi, Cayota, Cerda, Colombo, Crocamo, Del Toro-Arreola, Delgadillo-Cristerna, Delgado, Breitenbach, Fernández, Fernández, Fernández, Franco-Topete, Gaete, Gómez, Gonzalez-Ramirez, Guerrero, Gutierrez-Rubio, Jalfin, Lopez-Vazquez, Loria, Míguez, Moran-Mendoza, Morgan-Villela, Mussetti, Nagai, Oceguera-Villanueva, Reis, Retamales, Rodriguez, Rosales, Salas-Gonzalez, Segovia, Sendoya, Silva-Garcia, Viña, Zagame, Jones, Szklo and United States-Latin American Cancer Research Network (US-LACRN).)

Traditionally, beers are made with gluten-containing cereals. It is crucial to have rapid analytical methodologies that allow gluten content control of the beers for celiac consumers. We assess the content of gluten in 65 conventional and 41 gluten-free labeled beers commercialized in Europe and compare the results in a subgroup of 71 beers with three ELISA kits. This research allows gathering information on the potential complementary utility of NIR analysis applied to gluten analysis of gluten-free beers in terms of time saving. Results obtained with the ELISA technique identified competitive R5 to be the most sensitive in detecting the prolamins, by eliciting a higher number of beers containing gluten above 20 mg/kg. The gluten content in conventional beers tested increased with the presence of wheat as raw material and with the use of ale-type yeasts. By using competitive R5, 3 out of the 41 gluten-free labeled beers appeared to contain gluten above 20 mg/kg, and conversely, 15 out of 65 of the conventional beers showed a gluten content below this threshold. According to our approaches, NIR did not achieve a suitable correlation with ELISA results, neither for gluten quantification nor for discrimination, and therefore, it cannot be proposed as a complementary technique.

Objective: To determine the feasibility of performing neoadjuvant chemotherapy (NCH) followed by radical surgery in patients with locally advanced squamous cell carcinoma of the vulva., Methods: Prospective and multicenter trial. Thirty-five patients with a diagnosis of previously untreated locally advanced squamous cell carcinoma of the vulva were given 4 schemes of cisplatin-based NCH and 1 NCH regimen with single bleomycin. Then, they underwent radical surgery of the vulva if clinical response was 50% or more. Age, NCH schemes used, toxicity, response to treatment, type of radical surgery performed, and clinical outcome were evaluated., Results: Thirty-three patients completed the proposed schemes, and 30 were assessed for radical surgery. Finally, 27 patients underwent radical surgery (radical vulvectomy or radical local excision plus bilateral inguinofemoral lymphadenectomy). In 2 cases of persistent rectal involvement, posterior pelvic exenteration was performed. Moreover, 24 of 27 patients remain with no evidence of disease to date. Toxicity was acceptable. Median age was 62 years (range, 54-72 years). Median follow-up was 49 months (range, 4-155 months)., Conclusions: The use of NCH in selected groups may increase surgical feasibility in initially inoperable patients, thus favoring organ preservation and less extensive resections. Adverse reactions were acceptable, and vulvoperineal deleterious effects that may occur after radiotherapy were consequently avoided.

Background. Breast cancer is an important cause of cancer‐related death in women worldwide and represents the second most frequent cause of brain metastases after lung cancer. The aim of this study was to determine the characteristics and outcomes of triple‐negative breast cancer (TNBC) patients with brain metastasis (BM). Methods. We retrospectively reviewed a cohort of patients diagnosed with TNBC at the "Instituto Nacional de Enfermedades Neoplasicas" (period 2000–2014) to evaluate patients who developed BM. Survival rates were assessed by the Kaplan–Meier method, and prognostic factors were identified with the Cox regression analysis. Results. Of a total of 2007 TNBC patients, 193 (9.62%) developed BM. Of these, 169 stages I–III patients with a median age of 45 years (range:21–78) were included. The stage in this cohort was 4 (2.4%) clinical stage (CS) I, 23 (13.6%) with CS II and 142 (84.0%) with CS III. Most of these patients presented ECOG ≥2 (68.6%). The most common symptom was headache (74.0%), followed by nausea‐vomiting (46.7%). Imaging showed that 80 patients (53.0%) had ≥1 metastatic brain lesion. Regarding the treatment of BM in this cohort, 132 patients (84.6%) received radiotherapy (RT), 2 (1.5%) surgery, and 6 (4.5%) surgery plus RT. The overall survival (OS) rate of BM was 59.8%, 37.3%, and 15.0% at 3, 6, and 12 months, respectively. A multivariate analysis showed RT to be the only factor with a positive impact on the OS of BM (hazard ratio (HR) = 0.48, 95% confidence interval (CI):0.30‐0.77, and p = 0.002), while ECOG ≥2 was associated with a worse OS (HR = 1.69, 95%CI:1.15–2.48, and p = 0.007). Conclusion. Despite the poor prognosis of TNBC patients who develop BM, RT showed a benefit in OS rates, while ECOG ≥2 was the only prognostic factor associated with a worse OS. These results may be useful for multidisciplinary teams for treatment planning in patients with TNBC and BM. [ABSTRACT FROM AUTHOR]

We report the first isolation of Histoplasma capsulatum var. capsulatum from a male bat Eumops bonariensis captured in Buenos Aires city in 2003. The pathogen was recovered from spleen and liver specimens, and was identified by its phenotypic characteristics. PCR with primers 1283, (GTG)5, (GACA)4 and M13 was used to compare both bat isolates with 17 human isolates, 12 from patients residing in Buenos Aires city, and 5 from other countries of the Americas. The profiles obtained with the four primers showed that both bat isolates were identical to each other and closer to Buenos Aires patients than to the other isolates (similarity percentage: 91-100% and 55-97%, respectively). The high genetic relationship between bat isolates and those from patients living in Buenos Aires suggests a common source of infection. This is the first record of E. bonariensis infected with H. capsulatum in the world, and the first isolation of the fungus in the Argentinean Chiroptera population. In the same way as these wild mammals act as reservoir and spread the fungus in the natural environment, infection in urban bats could well be associated with the increase in histoplasmosis clinical cases among immunosuppressed hosts in Buenos Aires city.

The peptidomes from the literature of 24 prolyl-endopeptidase-treated beers during fermentation, declared gluten-free, and 13 untreated beers have been characterised and subjected to an extensive study to investigate their safety for celiac patients. The analysis contains 1996 gluten peptides, ascribed to the treated beers, and 1804 to the untreated beers. The prolyl-endopeptidase-untreated malt beers are hazardous for celiac patients. Peptides of most of these beers showed matches with complete celiac immunogenic motifs, and an additional 28% of the peptides have partial matches with complete immunogenic motifs. On the other hand, after the enzyme treatment during fermentation no celiac hazardous gluten peptides are identified in the treated beers. Due to partial matches with complete celiac immunogenic motifs, 11% potentially hazardous gluten peptides are still identified in the treated beers. Only a maximum of 17% of these peptides can be detected by ELISA analysis. A mass spectrometry analysis or the recently developed method based on G12/A1 monoclonal antibody lateral flow immunochromatographic assay seems necessary to thoroughly reveal the potential risk of the treated beers. The actual immune response of treated beer, described in the literature by the response of the serum antibodies of celiac disease (CD)-active patients and by in vitro immune response, could not be related to the presence of known (partial) CD-immunogenic motifs in the gluten peptides. [ABSTRACT FROM AUTHOR]

In this work, we perform variational calculations of two-electron reduced density matrices corresponding to open-shell N-electron systems within the framework of the doubly occupied configuration interaction treatment, traditionally limited to studies of closed-shell systems. This has allowed us to provide a satisfactory description of molecular systems in triplet states following two methods. One of them adds hydrogen atoms at an infinite distance of the triplet system studied, constituting a singlet supersystem. The energies and reduced density matrices of the triplet system are obtained by removing the contributions of the added atoms from the singlet supersystem results. The second procedure involves variational determination of the two-electron reduced density matrices corresponding to the triplet systems by means of adequate couplings of basis-set functions. Both models have been studied by imposing N-representability conditions on the reduced density matrix calculations. Results obtained from these methods for molecular systems in triplet ground states are reported and compared with those provided by benchmark methods. [ABSTRACT FROM AUTHOR]

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This work implements a variational determination of the elements of two-electron reduced density matrices corresponding to the ground and excited states of N-electron interacting systems based on the dispersion operator technique. The procedure extends the previously reported proposal [Nakata et al., J. Chem. Phys. 125, 244109 (2006)] to two-particle interaction Hamiltonians and N-representability conditions for the two-, three-, and four-particle reduced density matrices in the doubly occupied configuration interaction space. The treatment has been applied to describe electronic spectra using two benchmark exactly solvable pairing models: reduced Bardeen–Cooper–Schrieffer and Richardson–Gaudin–Kitaev Hamiltonians. The dispersion operator combined with N-representability conditions up to the four-particle reduced density matrices provides excellent results. [ABSTRACT FROM AUTHOR]

This work studies the performance of doubly occupied configuration interaction treatments based on the determination of wave functions and on the direct variational evaluation of two‐electron reduced density matrices in both, restricted and unrestricted approaches. We describe potential energy curves and spin contamination curves predicted by these methods for N‐electron molecular systems in their electronic ground states, at internuclear distances lying in intervals from near equilibrium geometries to dissociation limits. The corresponding numerical determinations in terms of energies, expectation values of the N‐electron spin‐squared operator, local spins, and electronic populations of the dissociation products are compared with those provided by the full configuration interaction procedure. An analysis of these results allows us to assess the abilities of the restricted and unrestricted methodologies and to illuminate the advantages and shortcomings of each of these treatments. [ABSTRACT FROM AUTHOR]

This work extends to the unrestricted orbital approach the procedure described in our previous report [Alcoba et al., J. Chem. Phys. 148, 024105 (2018)] for determining variationally the two-electron reduced density matrix arising from doubly occupied-configuration-interaction wave functions by imposing two- and three-index N-representability conditions. An analysis of the numerical results obtained in selected systems, from both restricted and unrestricted treatments, allows one to assess the performance of these methodologies as well as to show the influence of the P, Q, G, T1, and T2 positivity conditions. We highlight the satisfactory results obtained within the unrestricted scheme. [ABSTRACT FROM AUTHOR]

Most gluten analysis methods have been developed to detect intact gluten, but they have shown limitations in certain foods and beverages in which gluten proteins are hydrolyzed. Methods based on G12/A1 moAbs detect the sequences of gluten immunogenic peptides (GIP), which are the main contributors to the immune response of celiac disease (CD). Immunogenic sequences with tandem epitopes for G12/A1 have been found in beers with <20 mg/kg gluten, which could be consumed by CD patients according to the Codex Alimentarius. Therefore, an accurate method for the estimation of the immunogenicity of a beer is to use two moAbs that can recognize celiac T cell epitopes comprising most of the immunogenic response. Here, a specific and sensitive method based on G12/A1 LFIA was developed to detect GIP in beers labeled gluten-free or with low gluten content, with an LOD of 0.5 mg/kg. A total of 107 beers were analyzed, of those 6.5% showed levels higher than 20 mg/kg gluten and 29% showed levels above the LOD. In addition, G12/A1 LFIA detected gluten in 15 more beer samples than competitive ELISA with another antibody. Despite their labeling, these beers contained GIP which may cause symptoms and/or intestinal damage in CD patients. [ABSTRACT FROM AUTHOR]

This work exploits the Kohn nearsightedness principle in the algorithms arising from the anti‐Hermitian contracted Schrödinger equation. The procedure provides the implementation of approximations yielding a considerable saving of computational costs in descriptions of N‐electron molecular systems by means of that technique. We report energies, at correlated level, of linear hydrogen chains designed at different geometries, so that we can analyze the strength of the interactions between first‐, second‐, third‐, fourth‐, and so forth neighbor atoms. Using localized molecular orbital basis sets, we observe rapid decays in the values of the elements of the reduced‐density‐matrix cumulant matrices, beyond a cut‐off radius, which justify the proposed approximations. The results, in terms of energies and reduced density matrices, have been compared with those obtained from the full configuration interaction method, showing the usefulness of the nearsightedness principle in this methodology. [ABSTRACT FROM AUTHOR]

Objective: To determine the feasibility and overall survival (OS) outcome of utilizing neoadjuvant chemotherapy (NACT) followed by wide local excision (WLE) in women with sphincter-threatening locally advanced squamous cell carcinoma (SCC) of the vulva. Methods: The electronic chemotherapy prescribing system was used to iden-tify patients from the West of Scotland Cancer Network (WoSCAN) who received NACT over a 5 year period, January 2012 to December 2016 inclusive. Baseline characteristics and treatment details were collected. Association of treatment type and other variables with OS were analysed using Cox proportional hazards model. Results: 57 patients with newly diagnosed SCC of the vulva were identified; recurrences were excluded. 25 patients proceeded to WLE following NACT. No permanent stomas were required. 4% of patients had a complete response with NACT alone, not undergoing surgery, and remained disease free at the study end. OS was 39.3 months (95%Confidence Interval (CI) 32.5 -- Not reached (NR)) for the entire cohort and 40.1 months (95% CI 39.3 -- NR) in the surgical group following median follow up of 27 months. Local recurrence was the predominant cause of failure. Conclusions: NACT followed by WLE is effective in a subgroup of patients with locally advanced vulval cancer and can minimize the extent of surgery necessary, but close monitoring is required to identify and manage relapse early. [ABSTRACT FROM AUTHOR]

Convectively generated cold pools are important to the Earth system as they exert strong controls on deep convective-storm initiation, intensity, and life cycle. Despite their importance, efforts to introduce such cold pool controls into weather and climate models lack guidance and/or physical constraints from cold pool observations. This work presents a detailed, purely observational analysis of a cold pool event that took place on 23–24 May 2011 in north-central Oklahoma. The characteristics of the cold pool, and the spatiotemporal evolution of the hydrometeors and dynamics in the proximity of the cold pool, are studied with high-resolution observations. The unprecedented dataset used in this work to study cold pool characteristics includes an enhanced network of surface weather stations, a high-temporal-frequency sounding array, and the NEXRAD and Atmospheric Radiation Measurement (ARM) Southern Great Plains radar networks. The potential use of NEXRAD surveillance scans to estimate height and propagation speed of the leading edge of the cold pool (LECP) is presented in this work. Manual identification and tracking of the LECP from NEXRAD imagery shows a spatial and temporal heterogeneity of the LECP properties. Surprisingly, over its detected life cycle, the LECP speed remains almost constant, even though the strength of the cold pool diminishes in time and its height varies. Radar analysis shows that pulses of graupel and hail within downdrafts in the convective system generating the cold pool appeared to be related to temporary increases in the LECP height. [ABSTRACT FROM AUTHOR]

Some formal requirements for the second-order reduced density matrix are discussed in the context of density matrix functional theory. They serve as a basis for the ad hoc construction of the second-order reduced density matrix in terms of the first-order reduced density matrix and lead to implicit functionals where the occupation numbers of the natural orbitals are obtained as diagonal elements of an idempotent matrix the elements of which represent the variational parameters to be optimized. The numerical results obtained from a first realization of such an implicit density matrix functional give excellent agreement with the results of full configuration interaction calculations for four-electron systems like LiH and Be. Results for H[sub 2]O taken as an example for a somewhat larger molecule are numerically less satisfactory but still give reasonable occupation numbers of the natural orbitals and indicate the capability of density matrix functional theory to cope with static electron correlation. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

In this brief report, we present our experience with 3-weekly paclitaxel-carboplatin chemotherapy for patients with vulvar cancer. Two patients with locally advanced disease had an impressive response allowing standard vulvar cancer surgery. One patient with metastatic disease had local stable disease though it was progressive in the lymph nodes. The available literature is sparse and retrospective. Based on promising results, however, a prospective multicenter study is mandatory in order to obtain full data in a larger series of patients in order to learn the benefits of neoadjuvant paclitaxel-carboplatin and compare the results with chemoradiation. [ABSTRACT FROM AUTHOR]

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Objective: To evaluate factors associated with an increased risk of local recurrence of squamous cell carcinoma (SCCA) of the vulva. Materials and Methods: Sixty-seven pathologic specimens of vulvar SCCA from 1991-2010 were retrospectively reviewed by a gynecologic pathologist. Medical records were reviewed for demographic, treatment, disease, and follow-up information. Risk of local recurrence was analyzed using Wilcoxon rank sum test and Fisher's analysis. Recurrence-free survival (RFS) was calculated with the Log Rank test and Cox regression. Results: Stage distribution in the 67 patients was: four (6.0%) Stage IA, 48 (77.6%) Stage IB, three (4.5%) Stage II, 11 (16.4%) Stage III, and one (1.5%) Stage IV. Overall five-year survival was 84% and median RFS was 84.8 months. Thirty-seven percent of patients (25/67) presented with a local recurrence at their initial re-presentation after initial treatment, accounting for 92.6% of initial recurrences. Rates of local recurrence were lower in non-Caucasians (p = 0.047) and when carcinoma in situ was present at the margin (p = 0.03). RFS was not affected by stage (p = 0.60), lymph node status (p = 0.55), tumor size (p=0.45), or pathologic factors. In particular, tumor distance from the surgical margins as a continuous variable or at any cut-off was not associated with either risk of local recurrence or shortened recurrence-free survival; however, there was a trend between prolonged RFS with increasing disease-free pathologic margin (p = 0.09). Conclusion: Risk of local recurrence and RFS of vulvar SCCA following surgical excision were not affected significantly by most clinical or pathologic variables, including lymph node status, and disease-free margin size. [ABSTRACT FROM AUTHOR]

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Copyright of Nexus (1900-9909) is the property of Universidad del Valle and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Key content: This article reviews the changing role of adjuvant radiation therapy in gynaecological cancer, with emphasis on data from recent clinical trials. The evolution of practice with modern technology is improving the delivery of radiation, which has the potential to escalate doses, reduce toxicity and improve outcome. Radiation is infrequently used in ovarian cancer but in selected patients may provide good palliation. Late toxicity and survivorship issues are now recognised as important factors and there is a need to modify treatments to improve this. Learning objectives: To learn and understand the changing uses of adjuvant radiation therapy in gynaecological cancer. To understand the changing practice of brachytherapy, especially with the use of imaging to allow adaptive therapy. To understand the use of high technology to improve the delivery of radiation therapy in gynaecological cancers with potential for dose escalation with improved outcome and reduced toxicities. To understand the developments in brachytherapy and the use of computerised technologies and adaptive treatments. [ABSTRACT FROM AUTHOR]

Background/Aims: Extensive studies have demonstrated that Bleomycin (BLM) is a glycopeptide antibiotic that has been used as an anticancer chemotherapeutic reagent. It can induce both single- and double-strand DNA damage, inhibit synthesis of DNA, suppress proliferation, and induce apoptosis in cancer cells. Smad signaling transducers are considered as important molecules in tumor development and progression, and may closely be related to the biological behaviors of some malignant carcinomas, including gastric cancer. Methods: The effects of different concentrations of BLM on the proliferation, cell cycle, apoptosis, migration, and invasion on gastric cancer cell lines MKN45 and AGS were assayed by using CCK-8 assay, Annexin V/PI double staining, PI staining, and transwell assay. Western blot and Immunohistochemistry were applied to analyze the potential mechanism(s). Results: BLM treatment resulted in a low proliferation, high apoptosis, low migration and invasion in MKN45 and AGS cells. Furthermore, the possible mechanisms underlying that Smad3 activity could be changed after binding with BLM, and subsequently the Smad signaling pathway had a cascade response. Conclusion: These results highlight BLM as an exciting theme for gastric cancer treatment, which may represent an effective clinical therapeutic reagent for gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Extensive studies have demonstrated that Bleomycin (BLM) is a glycopeptide antibiotic that has been used as an anticancer chemotherapeutic reagent. It can induce both single- and double-strand DNA damage, inhibit synthesis of DNA, suppress proliferation, and induce apoptosis in cancer cells. Smad signaling transducers are considered as important molecules in tumor development and progression, and may closely be related to the biological behaviors of some malignant carcinomas, including gastric cancer. Methods: The effects of different concentrations of BLM on the proliferation, cell cycle, apoptosis, migration, and invasion on gastric cancer cell lines MKN45 and AGS were assayed by using CCK-8 assay, Annexin V/PI double staining, PI staining, and transwell assay. Western blot and Immunohistochemistry were applied to analyze the potential mechanism(s). Results: BLM treatment resulted in a low proliferation, high apoptosis, low migration and invasion in MKN45 and AGS cells. Furthermore, the possible mechanisms underlying that Smad3 activity could be changed after binding with BLM, and subsequently the Smad signaling pathway had a cascade response. Conclusion: These results highlight BLM as an exciting theme for gastric cancer treatment, which may represent an effective clinical therapeutic reagent for gastric cancer patients. [ABSTRACT FROM AUTHOR]

The treatment of patients with vulvar cancer remains challenging for gynecologic oncologists. Up to 30 % of the cases are diagnosed in a clinical condition of irresectability, and some kind of strategy has to be taken into account beyond surgery. In this regard, a common and standard definition is critical to maximize oncological results and minimize complications after treatments. Each patient treatment must be tailored individually according to their clinical and biological features and to the setting in which they are dealing with. [ABSTRACT FROM AUTHOR]

Key content: Ovarian cancer requires multidisciplinary management, usually with postoperative adjuvant chemotherapy. In some cases, however, neo‐adjuvant chemotherapy and delayed surgery may be offered.Recurrent ovarian cancer management is usually treated with chemotherapy, with drug choice often influenced by the platinum‐free interval.The role of adjuvant chemotherapy for endometrial cancer remains open to debate. Adjuvant chemotherapy is increasingly offered for high‐risk cases with lymphovascular space invasion. Carboplatin and paclitaxel are the most effective drugs in adjuvant and recurrent settings.Concomitant cisplatin with radiation therapy is the standard of care for locally advanced cervical cancer; recent studies have shown that the addition of bevacizumab to carboplatin and paclitaxel leads to improved response rates in the recurrent, metastatic setting.There are many rare gynaecological cancers that require multidisciplinary management, and entry into clinical trials should be strongly supported. Learning objectives: To understand the role and scheduling of chemotherapy in both newly diagnosed and recurrent epithelial ovarian cancer.To understand when chemotherapy should be offered in cervical and endometrial cancers.To be able to seek information sources for the management of rare and uncommon gynaecological cancers. Ethical issues: The question of systemic lymphadenectomy remains controversial and should be carefully discussed with the patient.Women should be encouraged to participate in clinical trials to help address some of the controversies in endometrial cancer management. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a systemic mycosis caused by Histoplasma capsulatum, a dimorphic fungal pathogen that can infect both humans and animals. This disease has worldwide distribution and affects mainly immunocompromised individuals. In the environment, H. capsulatum grows as mold but undergoes a morphologic transition to the yeast morphotype under special conditions. Molecular techniques are important tools to conduct epidemiologic investigations for fungal detection, identification of infection sources, and determination of different fungal genotypes associated to a particular disease symptom. In this study, we performed a systematic review in the PubMed database to improve the understanding about the molecular epidemiology of histoplasmosis. This search was restricted to English and Spanish articles. We included a combination of specific keywords: molecular typing [OR] genetic diversity [OR] polymorphism [AND] H. capsulatum; molecular epidemiology [AND] histoplasmosis; and molecular epidemiology [AND] Histoplasma. In addition, we used the specific terms: histoplasmosis [AND] outbreaks. Non-English or non-Spanish articles, dead links, and duplicate results were excluded from the review. The results reached show that the main methods used for molecular typing of H. capsulatum were: restriction fragment length polymorphism, random amplified polymorphic DNA, microsatellites polymorphism, sequencing of internal transcribed spacers region, and multilocus sequence typing. Different genetic profiles were identified among H. capsulatum isolates, which can be grouped according to their source, geographical origin, and clinical manifestations. [ABSTRACT FROM AUTHOR]

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Mitochondria contain multiple copies of their own 16.6 kb circular genome. To explore the impact of mitochondrial DNA (mtDNA) damage on mitochondrial (mt) function and viability of AML cells, we screened a panel of DNA damaging chemotherapeutic agents to identify drugs that could damage mtDNA. We identified bleomycin as an agent that damaged mtDNA in AML cells at concentrations that induced cell death. Bleomycin also induced mtDNA damage in primary AML samples. Consistent with the observed mtDNA damage, bleomycin reduced mt mass and basal oxygen consumption in AML cells. We also demonstrated that the observed mtDNA damage was functionally important for bleomycin-induced cell death. Finally, bleomycin delayed tumor growth in xenograft mouse models of AML and anti-leukemic concentrations of the drug induced mtDNA damage in AML cells preferentially over normal lung tissue. Taken together, mtDNA-targeted therapy may be an effective strategy to target AML cells and bleomycin could be useful in the treatment of this disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the clinical, therapeutic, laboratory, and radiological differences between respiratory syncytial virus (RSV) and non-RSV bronchiolitis in order to assess if the prior knowledge of viral etiology changed management decisions and would be able to predict outcomes. Medical charts of children <1 year admitted to the emergency department with bronchiolitis during two RSV seasons (2010-2012) were reviewed. We analyzed 221 episodes of bronchiolitis. The percentage of exams performed (95 % confidence interval (CI) 0.74-2.52), abnormal laboratory and radiological findings (95 % CI 0.53-16.89) did not differ between groups. RSV bronchiolitis had a more severe clinical course. However, virologic testing for RSV had low specificity in identifying at-risk patients for hospitalization, longer hospital length of stay, and need of oxygen therapy and nasogastric tube (44, 40, 42, and 35 %, respectively), and while statistically significant, the positive likelihood ratios were only slightly greater than 1. Conclusion: Although RSV bronchiolitis has a more severe clinical course, virologic testing does not help in management decisions, and at an individual level, as a performance test, it seems insufficient to precisely predict outcomes. [ABSTRACT FROM AUTHOR]

The phrase "locally advanced carcinoma of the vulva" has often been mentioned in the literature, though not accurately defined, or even leading to the interpretation overlapping. Grounded on cervical cancer experience, we are able to state that designing a tailored primary strategy based on clinically measurable adverse prognostic factors represents the cornerstone of therapy. This fact urged us to rethink about the real usefulness of the concept of locally advanced squamous cell carcinoma of the vulva. We will refer to this concept as a clinical entity emerging from a rigorous workup which is a valuable guiding tool in the context of a thorough debate about the best primary treatment approach to be used. Furthermore, bulky tumors of the vulva have been associated with a worse prognosis on several occasions. Some authors have questioned the fact that tumor size has not been considered in the staging system. Finally, a standardized definition will help us compare the results obtained, which is extremely necessary given the worldwide low prevalence of this disease. [ABSTRACT FROM AUTHOR]

Objective: The therapeutic outcomes of patients with advanced vulvar cancer are poor. Multi-modality treatments including concurrent chemoradiation or different regimens of neoadjuvant chemotherapy (NACT), and surgery have been explored to reduce the extent of surgery and morbidity. The present single-institution trial aimed to evaluate the efficacy and toxicity of paclitaxel and cisplatin in locally advanced vulvar cancer. Methods: From 2002 to 2009, 10 patients with stage III-IV locally advanced squamous cell carcinoma of the vulva were prospectively treated with 3 courses of paclitaxel-ifosfamide-cisplatin or paclitaxel-cisplatin. Nine of them subsequently underwent radical local excision or radical partial vulvectomy and bilateral inguino-femoral lymphadenectomy. Results: The clinical response rate of all enrolled patients was 80%, whereas the pathological responses included 1 case with complete remission, 2 with persistent carcinoma in situ, and 6 invasive cancer cases with tumor shrinkage of more than 50%. Four patients had positive nodes. Forty percent of patients experienced grade 3-4 bone marrow toxicity, which was successfully managed with granulocyte-colony stimulating factor, even in cases of elderly patients. Median progression-free survival after surgery was 14 months (range, 5 to 44 months). Six of the 7 recurrent cases were local, and 3 of them were treated with salvage surgery while the other 3 received radiation with or without chemotherapy. After a median follow-up period of 40 months (range, 5 to 112 months), 55.5% of patients remained alive with no evidence of disease, including 2 long-term survivors after recurrence at 5 and 9 years. Conclusion: Based on the high response rate and manageable toxicity, NACT with paclitaxel and cisplatin with or without ifosfamide followed by surgery could be considered as a therapeutic option for locally advanced vulvar cancer. [ABSTRACT FROM AUTHOR]

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Very recently, we have shown the suitability to combine the G-particle-hole Hypervirial (GHV) equation method (Alcoba et al. in Int J Quantum Chem 109:3178, ) with the Hermitian Operator (HO) method (Bouten et al. in Nucl Phys A 202:127, ) for computing various energy differences of an electronic system spectrum (Valdemoro et al. in J Math Chem 50:492, ). The purpose of this paper is to extend our preliminary studies by applying the combined GHV-HO method to obtain the set of ground and low-lying excited states potential energy curves of several selected electronic systems. The calculations confirm the reliability of the method. [ABSTRACT FROM AUTHOR]

Recently, through the use of one-electron excitation operators, the set of low-lying excited states of several electronic systems was obtained within the framework of the Hermitian Operator method combined with the G-particle-hole Hypervirial equation method [Valdemoro et al., J. Math. Chem. 2012, 50, 492]. The main aim of this article is to extend our study by including higher-order excitations as well as extended ionization and electron affinity operators. Several examples show the convenience of this extension to improve the accuracy of the results in some relevant cases. Through the use of geminal excitations, the algebra of the formal derivations is considerably simplified. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]