New cytogenetic prognostic markers in breast cancer

Abstract BACKGROUND: The aim of this study was to identify chromosomal imbalances in a series of invasive ductal carcinomas. In order to characterize the prognostic value of the chromosomal aberrations, we determined the association between genetic changes, overall survival, recurrences and some well-known prognostic and diagnostic parameters. MATERIAL AND METHODS: We included in this study 70 ductal invasive carcinomas diagnosed at the Hospital of Navarra during 1991-1994. We used the Comparative Genomic Hybridization Technique (CGH) for the molecular cytogenetic analysis of formalin-fixed, paraffin embedded specimens. RESULTS: We obtained successful results in 57 out of 70 cases (81.4%). The most frequent recurring findings were DNA gains on 8q, 17q, 1q, 20q, 11q and 6q and losses on 16q, Xp, Xq, 13q, 11q and 8p. In the survival study, gains on 1q and 11q13 were more frequent in patients with recurrence (41.3% vs. 18.5% and 50% vs. 23.7%). Loss of 16q appears as a prognostic factor of good outcome because of its association with good pathological prognostic features: 100% of tumors with this aberration showed overexpression of Bcl-2, and 75% of them were node negative. Besides, 46.7% of the positive cases for the expression of estrogen receptors also showed this imbalance. CONCLUSIONS: The CGH is a useful technique for the study of paraffin embedded tumors. Our results confirm that the cytogenetic aberrations of tumors could be considered as prognostic factors contributing to a better knowledge of tumor outcome

Genomic imbalances detected by comparative genomic hybridization are prognostic markers in invasive ductal breast carcinomas

AIMS: The aim of this work is the study of the prognostic significance of the chromosomal aberrations described in a series of invasive ductal breast carcinomas. METHODS AND RESULTS: We analysed by comparative genomic hybridization a group of 70 formalin-fixed paraffin-embedded invasive ductal breast carcinomas. Aberrations showed a frequency similar to previous studies using frozen tumours. Interestingly, we identified gains involving 6q16-q24 more frequently than in other series. We analysed the association among the chromosomal imbalances, 11 histopathological factors, relapse rate and overall survival of patients. Associations showed 16q losses as a potential marker of good prognosis, as they were more frequent in node-negative (P=0.025) and in oestrogen-positive tumours (P < 0.001). Furthermore, 100% of bcl-2+ tumours presented this aberration compared with 29.3% in bcl-2- (P=0.014). 1q, 11q, 17q and 20q gains were associated with poor prognosis: 95% of cases with 1q gains were bigger than 20 mm (P=0.041). Tumours with 1q and 11q gains showed a higher relapse rate (P=0.063; P=0.066). Within the good prognosis group of lymph node-negative patients, 17q and 20q gains identify a subgroup with increased relapse rate (P=0.039). CONCLUSIONS: Chromosomal imbalances, together with histopathological factors, may help to predict outcome in breast cancer patients

Phenolic profile and physicochemical characterization of quince (Cydonia oblonga Mill) fruits at different maturity index

The ripening of fruits is a determinant factor on the composition of phytochemical compounds such as phenolic compounds. In this study the phenolic profile of quince fruits was determined as a function of its maturity index. Based on the total soluble solids (TSS) and the acidity (TA) of the fruits, four maturity indexes were established (12.55, 14.56, 21.86 and 24.77), using the ratio of TSS/TA. The phenolic profile of quince fruits with different maturity indexes were obtained by a reversed-phase HPLC-DAD and HPLC-DAD/MS. A PCA loading plot was generated to explain the relationship between physicochemical parameters and the phenolic compounds. The phenolic compounds identified in the quince fruits were 3-0-caffeoylquinic acid, catechin, 4-0-caffeoylquinic acid, 5-0-caffeoylquinic acid, coumaric acid, quercetin-3-0-rutinoside and quercetin-3-0-glycosides. The maturity index increase caused in general a reduction of phenolic compounds, these compounds were also influenced by pH and acidity of fruits. Quince is a valuable source of natural phenolic antioxidants, and can be used as raw material to elaborate diverse food products, providing important functional properties

Sleep State Modulates Resting-State Functional Connectivity in Neonates.

The spontaneous cerebral activity that gives rise to resting-state networks (RSNs) has been extensively studied in infants in recent years. However, the influence of sleep state on the presence of observable RSNs has yet to be formally investigated in the infant population, despite evidence that sleep modulates resting-state functional connectivity in adults. This effect could be extremely important, as most infant neuroimaging studies rely on the neonate to remain asleep throughout data acquisition. In this study, we combine functional near-infrared spectroscopy with electroencephalography to simultaneously monitor sleep state and investigate RSNs in a cohort of healthy term born neonates. During active sleep (AS) and quiet sleep (QS) our newborn neonates show functional connectivity patterns spatially consistent with previously reported RSN structures. Our three independent functional connectivity analyses revealed stronger interhemispheric connectivity during AS than during QS. In turn, within hemisphere short-range functional connectivity seems to be enhanced during QS. These findings underline the importance of sleep state monitoring in the investigation of RSNs

Seroprevalencija Dirofilaria immitis u pasa iz skloništa za životinje u kolumbijskoj regiji kave (Eje Cafetero)

In Colombia, there are reports of approximately 6.4 million pets, making this the fourth country in Latin America and leading the pet sector with an annual growth of 13%. This study aimed to determine the seroprevalence of Dirofilaria immitis, a parasitic nematode, in 170 canines from the municipalities of Pereira, Santa Rosa de Cabal, and La Virginia, located in the department of Risaralda and the municipalities of Calarca and Armenia in the department of Quindio. A cross-sectional study was carried out on canines from animal shelters during the period 2021–2022. Blood samples were taken, and in vitro immunochromatography was performed to detect specific lesions for Dirofilaria immitis. A peripheral blood smear confirmed positive patients, and a chest x-ray was performed to show changes in the morphology of the heart and blood vessels. Seroprevalence was determined by calculating proportions with the 95% confidence interval determined by the exact or Clopper-Pearson method for a proportion based on sample size and the number of positive cases. The seroprevalence of the test for Dirofilaria immitis was 0.62% (95% CI = 0.016–3.42%). This parasite is a nematode of low distribution in areas of the coffee region. However, surveillance programmes that help control and reduce its transmission should be established.Postoje izvješća o gotovo 6.400.000 kućnih ljubimaca u Kolumbiji i to je četvrta zemlja u Latinskoj Americi u sektoru kućnih ljubimaca, s godišnjim rastom od 13 %. Cilj je ove studije jest utvrditi seroprevalenciju Dirofilaria immitis u 170 pasa iz općina Pereira, Santa Rosa de Cabal i La Virginia, koje se nalaze u departmanu Risaralda i u općinama Calarca i Armenia u departmanu Quindio. Provedena je presječna studija na psima iz skloništa za životinje tijekom godine 2021.-2022. Uzeti su uzorci krvi i obavljena je in vitro imunokromatografija za detekciju lezija specifičnih za Dirofilaria immitis. Razmaz periferne kriv potvrdio je pozitivne pacijente i obavljen je RTG prsnog koša da bi se vidjele promjene u morfologiji srca i krvnih žila. Seroprevalencija je utvrđena izračunom omjera uz interval pouzdanosti od 95% određen preciznom ili Clopper-Pearson metodom za omjer na temelju veličine uzorka i broja pozitivnih slučajeva. Seroprevalencija testa na Dirofilaria immitis bila je 0,62 % (95% CI = 0,016-3,42 %). Ovaj je parazit oblić u područjima regije kave niske rasprostranjenosti, ali predlaže se uspostaviti programe nadzora koji će pomoći kontrolirati i reducirati njegov prijenos

Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration

Aim: To delineate the neurogenetic profiles of brain degeneration patterns in myotonic dystrophy type I (DM1). Methods: In two cohorts of DM1 patients, brain maps of volume loss (VL) and neuropsychological deficits (NDs) were intersected to large-scale transcriptome maps provided by the Allen Human Brain Atlas (AHBA). For validation, neuropathological and RNA analyses were performed in a small series of DM1 brain samples. Results: Twofold: (1) From a list of preselected hypothesis-driven genes, confirmatory analyses found that three genes play a major role in brain degeneration: dystrophin (DMD), alpha-synuclein (SNCA) and the microtubule-associated protein tau (MAPT). Neuropathological analyses confirmed a highly heterogeneous Tau-pathology in DM1, different to the one in Alzheimer's disease. (2) Exploratory analyses revealed gene clusters enriched for key biological processes in the central nervous system, such as synaptic vesicle recycling, localization, endocytosis and exocytosis, and the serotonin and dopamine neurotransmitter pathways. RNA analyses confirmed synaptic vesicle dysfunction. Conclusions: The combination of large-scale transcriptome interactions with brain imaging and cognitive function sheds light on the neurobiological mechanisms of brain degeneration in DM1 that might help define future therapeutic strategies and research into this condition

A neutralizing single-domain antibody that targets the trimer interface of the human metapneumovirus fusion protein

Human metapneumovirus (hMPV) is an important respiratory pathogen for which no licensed antivirals or vaccines exist. Single-domain antibodies represent promising antiviral biologics that can be easily produced and formatted. We describe the isolation and detailed characterization of two hMPV-neutralizing single-domain antibodies that are directed against the fusion protein F. One of these single-domain antibodies broadly neutralizes hMPV A and B strains, can prevent proteolytic maturation of F, and binds to an epitope in the F trimer interface. This suggests that hMPV pre-F undergoes trimer opening or "breathing" on infectious virions, exposing a vulnerable site for neutralizing antibodies. Finally, we show that this single-domain antibody, fused to a human IgG1 Fc, can protect cotton rats against hMPV replication, an important finding for potential future clinical applications.This work was supported by a grant from Janssen Pharmaceuticals Inc. to X.S. and Welch Foundation grant number F-0003-19620604 to J.S.M.S

Machine learning methodologies versus cardiovascular risk scores, in predicting disease risk

BACKGROUND: The use of Cardiovascular Disease (CVD) risk estimation scores in primary prevention has long been established. However, their performance still remains a matter of concern. The aim of this study was to explore the potential of using ML methodologies on CVD prediction, especially compared to established risk tool, the HellenicSCORE. METHODS: Data from the ATTICA prospective study (n = 2020 adults), enrolled during 2001-02 and followed-up in 2011-12 were used. Three different machine-learning classifiers (k-NN, random forest, and decision tree) were trained and evaluated against 10-year CVD incidence, in comparison with the HellenicSCORE tool (a calibration of the ESC SCORE). Training datasets, consisting from 16 variables to only 5 variables, were chosen, with or without bootstrapping, in an attempt to achieve the best overall performance for the machine learning classifiers. RESULTS: Depending on the classifier and the training dataset the outcome varied in efficiency but was comparable between the two methodological approaches. In particular, the HellenicSCORE showed accuracy 85%, specificity 20%, sensitivity 97%, positive predictive value 87%, and negative predictive value 58%, whereas for the machine learning methodologies, accuracy ranged from 65 to 84%, specificity from 46 to 56%, sensitivity from 67 to 89%, positive predictive value from 89 to 91%, and negative predictive value from 24 to 45%; random forest gave the best results, while the k-NN gave the poorest results. CONCLUSIONS: The alternative approach of machine learning classification produced results comparable to that of risk prediction scores and, thus, it can be used as a method of CVD prediction, taking into consideration the advantages that machine learning methodologies may offer

Response to Novel Drugs before and after Allogeneic Stem Cell Transplantation in Patients with Relapsed Multiple Myeloma

Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P <.001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P <.001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment