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1.
Cureus ; 16(8): e66646, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39258097

RESUMO

Neuroendocrine tumors (NETs) are rare, slow-growing tumors originating from the diffuse neuroendocrine cell system, predominantly affecting the digestive tract. Small bowel neuroendocrine tumors (SBNETs) may present with nonspecific symptoms, such as abdominal pain, or with intermittent intestinal obstruction. This case outlines the diagnostic journey of a septuagenarian male with prolonged abdominal symptoms and weight loss. Despite extensive investigation, a definitive cause remained elusive. Recurrent partial intestinal obstruction led to surgical exploration and segmental resection. Pathology confirmed a NET. The case underscores the importance of considering intestinal neoplasia in older patients with recurrent partial small bowel obstruction.

2.
Molecules ; 29(16)2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39203047

RESUMO

A variational heteroencoder based on recurrent neural networks, trained with SMILES linear notations of molecular structures, was used to derive the following atomic descriptors: delta latent space vectors (DLSVs) obtained from the original SMILES of the whole molecule and the SMILES of the same molecule with the target atom replaced. Different replacements were explored, namely, changing the atomic element, replacement with a character of the model vocabulary not used in the training set, or the removal of the target atom from the SMILES. Unsupervised mapping of the DLSV descriptors with t-distributed stochastic neighbor embedding (t-SNE) revealed a remarkable clustering according to the atomic element, hybridization, atomic type, and aromaticity. Atomic DLSV descriptors were used to train machine learning (ML) models to predict 19F NMR chemical shifts. An R2 of up to 0.89 and mean absolute errors of up to 5.5 ppm were obtained for an independent test set of 1046 molecules with random forests or a gradient-boosting regressor. Intermediate representations from a Transformer model yielded comparable results. Furthermore, DLSVs were applied as molecular operators in the latent space: the DLSV of a halogenation (H→F substitution) was summed to the LSVs of 4135 new molecules with no fluorine atom and decoded into SMILES, yielding 99% of valid SMILES, with 75% of the SMILES incorporating fluorine and 56% of the structures incorporating fluorine with no other structural change.

3.
Cureus ; 16(7): e65329, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39184756

RESUMO

Appendiceal neoplasms are a rare and heterogeneous condition with a non-specific clinical presentation, often concealing intricate predicaments; hence they require complex and diverse management. The present case report aims not only to describe a less usual form of presentation and its orientation but also to provide a modest literature review in a rather demanding pathology.

4.
Front Surg ; 11: 1396432, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39086922

RESUMO

Introduction: Conservative surgery is the gold standard for the treatment of single and small tumors and, combined with the concept of oncoplastic tumors, brings good aesthetic results while maintaining cancer safety. The objective was to comparatively analyze the degree of satisfaction of patients undergoing breast conserving surgery (BCS), with and without oncoplastic surgery (OPS) using level II OPS techniques. Methods: Review with a search in the databases MEDLINE (by PubMed), EMBASE, Clinical Trials, Scopus, Web of Science, BVS and Oppen gray. The meta-analysis of random effects was performed using the Der Simonian-Laird method considering the odds ratio (OR) with a 95% confidence interval (95% CI). Results: There was no statistically significant difference in the aesthetic outcome between women who underwent OPS and BCS (OR 0.90; 95% CI 0.62-1.30). The staging (OR 1.93; 95% CI 0.97-3.84; I 2 = 15.83%); tumor location [central (OR 1.28; 95% CI 0.06-27.49; I 2 = 17.63%); lower (OR 0.75; 95% CI 0.21-2.65; I 2 = 2.21%); superior (OR 0.67; 95% CI 0.26-1.74; I 2 = 0.00%] and tumor size (OR 8.73; 95% CI -11.82-29.28; I 2 = 93.18%) showed no association with the type of BCS performed, with or without OPS. The degree of satisfaction remains even in cases of extreme oncoplasty. Conclusion: The level of patient satisfaction in relation to BCS was similar to that of the group undergoing OPS, highlighting that OPS allows the patient's satisfaction rate to be maintained even in the case of large or multicentric tumors.

5.
Nat Commun ; 15(1): 7567, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217176

RESUMO

Ageing is the accumulation of changes and decline of function of organisms over time. The concept and biomarkers of biological age have been established, notably DNA methylation-based clocks. The emergence of single-cell DNA methylation profiling methods opens the possibility of studying the biological age of individual cells. Here, we generate a large single-cell DNA methylation and transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages. The number of genes expressed increases with age, but gene-specific changes are small. We next develop scEpiAge, a single-cell DNA methylation age predictor, which can accurately predict age in (very sparse) publicly available datasets, and also in single cells. DNA methylation age distribution is wider than technically expected, indicating epigenetic age heterogeneity and functional differences. Our work provides a foundation for single-cell and sparse data epigenetic age predictors, validates their functionality and highlights epigenetic heterogeneity during ageing.


Assuntos
Envelhecimento , Metilação de DNA , Epigênese Genética , Análise de Célula Única , Transcriptoma , Animais , Análise de Célula Única/métodos , Envelhecimento/sangue , Envelhecimento/genética , Camundongos , Senescência Celular/genética , Masculino , Camundongos Endogâmicos C57BL , Feminino , Perfilação da Expressão Gênica/métodos , Epigenômica/métodos
6.
Front Oncol ; 14: 1386697, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974246

RESUMO

Background: Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective: To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods: We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results: Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion: The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern.

7.
Cureus ; 16(5): e60787, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38903319

RESUMO

Synchronous gastric cancer with another neoplasm is a rare condition, with colorectal cancer being the most frequently associated neoplasm. This article presents a case of a 76-year-old male diagnosed with synchronous gastric and rectal cancer with complete remission of gastric and rectal neoplasms after adjuvant therapy. The patient exhibited symptoms prompting upper and lower endoscopies, revealing gastric and rectal adenocarcinomas, respectively. Staging was performed, and due to the locally advanced nature of both malignancies, the patient underwent total neoadjuvant therapy (TNT) for rectal cancer. The treatment consisted of external radiotherapy and neoadjuvant chemotherapy with oxaliplatin, leucovorin, folinic acid, and fluorouracil (FOLFOX). Remarkably, after seven cycles, a complete clinical response of the rectal neoplasm was achieved. Subsequent surgical resection included simultaneous subtotal gastrectomy and rectal anterior resection, resulting in a complete pathological response for both tumors. To the best of our knowledge, it is among the first cases to report a full pathological response in gastric cancer following TNT intended for rectal cancer.

8.
Heart Rhythm ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38848856

RESUMO

BACKGROUND: Recurrent ventricular tachycardia (VT) can be treated by substrate modification of the myocardial scar by catheter ablation during sinus rhythm without VT induction. Better defining this arrhythmic substrate could help improve outcome and reduce ablation burden. OBJECTIVE: The study aimed to limit ablation within postinfarction scar to conduction channels within the scar to reduce VT recurrence. METHODS: Patients undergoing catheter ablation for recurrent implantable cardioverter-defibrillator therapy for postinfarction VT were recruited at 5 centers. Left ventricular maps were collected on CARTO using a Pentaray catheter. Ripple mapping was used to categorize infarct scar potentials (SPs) by timing. Earliest SPs were ablated sequentially until there was loss of the terminal SPs without their direct ablation. The primary outcome measure was sustained VT episodes as documented by device interrogations at 1 year, which was compared with VT episodes in the year before ablation. RESULTS: The study recruited 50 patients (mean left ventricular ejection fraction, 33% ± 9%), and 37 patients (74%) met the channel ablation end point with successful loss of latest SPs without direct ablation. There were 16 recurrences during 1-year follow-up. There was a 90% reduction in VT burden from 30.2 ± 53.9 to 3.1 ± 7.5 (P < .01) per patient, with a concomitant 88% reduction in appropriate shocks from 2.1 ± 2.7 to 0.2 ± 0.9 (P < .01). There were 8 deaths during follow-up. Those who met the channel ablation end point had no significant difference in mortality, recurrence, or VT burden but had a significantly lower ablation burden of 25.7 ± 4.2 minutes vs 39.9 ± 6.1 minutes (P = .001). CONCLUSION: Scar channel ablation is feasible by ripple mapping and can be an alternative to more extensive substrate modification techniques.

9.
Europace ; 26(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38818846

RESUMO

AIMS: We aimed to assess the acute and midterm efficacy of premature ventricular contraction (PVC) ablation guided by multielectrode and point-by-point (PbP) mapping. METHODS AND RESULTS: This is a retrospective, international multicentre study of consecutive patients referred for PVC ablation in 10 hospital centres from January 2017 to December 2021. Based on the mapping approach, two cohorts were identified: the 'Multipolar group', where a dedicated high-density mapping catheter was employed, and the 'PbP group', where mapping was performed with the ablation catheter. Procedural endpoints, safety, and acute (procedural) and midterm efficacies were assessed. Of the 698 patients included in this study, 592 received activation mapping [46% males, median age of 55 (41-65) years]-248 patients in the Multipolar group and 344 patients in the PbP group. A higher number of activation points [432 (217-843) vs. 95 (42-185), P < 0.001], reduced mapping time (40 ± 38 vs. 61 ± 50 min, P < 0.001), and shorter procedure time (124 ± 60 vs. 143 ± 63 min, P < 0.001) were reported in the Multipolar group. Both groups had high acute success rates (84.7% with Multipolar mapping vs. 81.3% with PbP mapping, P = 0.63), as well as midterm efficacy (83.4% vs. 77.4%, P = 0.08), with no significant differences in the risk of adverse events (6.0% vs. 3.5%, P = 0.24). However, for left-sided PVC ablation specifically, there was a higher midterm efficacy in the Multipolar group (80.7% vs. 69.5%, P = 0.04), with multipolar mapping being an independent predictor of success [adjusted OR = 2.231 (95% CI, 1.476-5.108), P = 0.02]. CONCLUSION: The acute and midterm efficacies of PVC ablation are high with both multipolar and PbP mapping, although the former allows for quicker procedures and may potentially improve the outcomes of left-sided PVC ablation.


Assuntos
Ablação por Cateter , Complexos Ventriculares Prematuros , Humanos , Complexos Ventriculares Prematuros/cirurgia , Complexos Ventriculares Prematuros/fisiopatologia , Complexos Ventriculares Prematuros/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Ablação por Cateter/métodos , Estudos Retrospectivos , Idoso , Adulto , Resultado do Tratamento , Técnicas Eletrofisiológicas Cardíacas
10.
Cureus ; 16(3): e55461, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38571850

RESUMO

Intestinal malrotation (IM), a rare congenital anomaly disrupting typical embryonic rotation around the superior mesenteric artery, is exceptionally uncommon in adults, with its link to colon cancer being even rarer. This article presents a case of colonic cancer in conjunction with IM in a 63-year-old male. Image studies and intraoperative findings show signs of IM. Open resection was performed due to concerns about vascular anomalies and abnormal lymphatic drainage. The case underscores the rarity of colon cancer in a malrotated gut, highlighting the necessity of preoperative identification for precise surgical planning and emphasizing the importance of careful dissection to prevent inadvertent vascular injury.

11.
Cureus ; 16(2): e54388, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38505452

RESUMO

BACKGROUND: The use of cervical drains to prevent cervical hematoma or seroma after thyroidectomy remains a controversial issue. OBJECTIVE: Identify clinical and surgical risk factors for hematoma or seroma and evaluate the usefulness of routine use of drains following thyroid surgery. MATERIAL AND METHODS: The authors conducted a retrospective multicentric study related to consecutive patients submitted to thyroid surgery in seven Portuguese hospitals between January 2018 and December 2020 (n=945). The data collected included the following parameters: age and gender of the patients, anticoagulation or anti-aggregating therapy, histological diagnoses, type of surgery, the presence or absence of postoperative drains, thyroid weight, length of hospital stay, postoperative complications, and reinterventions. In this study, surgical complications evaluated were limited to the presence of hematoma or seroma. A total of 945 patients who underwent thyroid surgery were included in the study. Twenty-seven patients (2.9%, n=27) experienced complications classified as hematomas or seromas. In the series, significant differences were observed between the two groups according to hypocoagulation or anti-aggregation status (OR=3.62; 95% CI 1.14-11.4) (p=0.001) and the nature of histological diagnosis (toxic vs. non-toxic benign disease) (OR=6.59; 95% CI 1.83-23.7). Hypocoagulation or anti-aggregation status were independently associated with a higher risk of complications. The presence of drains was associated with longer hospitalization periods (p<0.001) and not a decreased need for reintervention. CONCLUSION: Cervical hematoma or seroma are rare complications associated with both hypocoagulation and anti-aggregation therapy and with the presence of benign toxic pathology. The use of drains does not decrease the need for reintervention and is even associated with a longer length of hospital stay; therefore, their routine use should not be advised.

12.
Commun Biol ; 7(1): 270, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443549

RESUMO

Embryonic diapause in mammals is a temporary developmental delay occurring at the blastocyst stage. In contrast to other diapausing species displaying a full arrest, the blastocyst of the European roe deer (Capreolus capreolus) proliferates continuously and displays considerable morphological changes in the inner cell mass. We hypothesised that developmental progression also continues during this period. Here we evaluate the mRNA abundance of developmental marker genes in embryos during diapause and elongation. Our results show that morphological rearrangements of the epiblast during diapause correlate with gene expression patterns and changes in cell polarity. Immunohistochemical staining further supports these findings. Primitive endoderm formation occurs during diapause in embryos composed of around 3,000 cells. Gastrulation coincides with elongation and thus takes place after embryo reactivation. The slow developmental progression makes the roe deer an interesting model for unravelling the link between proliferation and differentiation and requirements for embryo survival.


Assuntos
Cervos , Diapausa , Animais , Blastocisto , Diferenciação Celular , Polaridade Celular , Diapausa/genética
13.
Cureus ; 16(1): e51536, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38304657

RESUMO

This case report highlights a rare clinical scenario of a 46-year-old male presenting with constipation and fecaloid vomiting due to an impacted chicken bone within an unidentified rectosigmoid neoplasm, leading to acute malignant colonic obstruction. Emergent exploratory laparotomy revealed an impacted chicken bone lodged in a previously unknown rectosigmoid tumor. An anatomopathological examination revealed a mucinous adenocarcinoma with clear margins and one pericolic metastatic lymph node. The postoperative period was uneventful, and the patient was proposed for adjuvant chemotherapy. The abrupt onset of symptoms allowed for an early diagnosis, emphasizing the unexpected association between foreign body impaction and incidental malignant obstruction. This case underscores the complexity of managing foreign body ingestion in the gastrointestinal tract and emphasizes the crucial role of diagnostic imaging in surgical planning. Furthermore, it draws attention to the potential occurrence of colorectal cancer in younger individuals, emphasizing the necessity for clinical vigilance and screening strategies beyond conventional age recommendations.

14.
Open Heart ; 11(1)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316493

RESUMO

OBJECTIVES: Assess safety and performance of novel quadripolar preshaped left ventricular (LV) leads: NAVIGO 4LV 2D ('S shaped') and NAVIGO 4LV ARC ('U shaped'). METHODS: Patients indicated for cardiac resynchronisation therapy were enrolled in a multicentre, prospective, controlled study (NAVIGATOR, NCT03279484). Patients were implanted with either a NAVIGO 4LV 2D or ARC lead, and assessed at 10 weeks, 6, 12 and 24 months post-implant. Co-primary safety and performance endpoints were assessed at 10 weeks. Safety endpoint was the patients' rate free from lead-related complications. Performance endpoint was the rate of patients with successful lead performance, defined as LV pacing threshold ≤2.5 V at 0.5 ms on at least one pacing vector, and the absence of phrenic nerve stimulation at the final programmed configuration. Lead-related complications and electrical parameters were monitored throughout study. RESULTS: A NAVIGO 4LV lead was successfully implanted in 211 out of 217 patients (97.2%). The safety endpoint was met, with 100% and 96.1% of patients free from complications for NAVIGO 4LV 2D and ARC, respectively. The performance endpoint was met with 98.1% and 98.9% of patients with a successful lead performance for NAVIGO 4LV 2D and ARC, respectively. Over 12 months, the global complication-free rate for both leads was 97.1% (95% CI: 93.71% to 98.70%), with a mean pacing capture threshold of 1.23 V±0.73 V and a mean impedance of 951 Ω±300.1 Ω. CONCLUSION: A high implantation success rate and low complication rate was reported for the novel NAVIGO 4LV 2D and ARC leads, along with successful performance up to 12 months.


Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Humanos , Estudos Prospectivos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/etiologia , Terapia de Ressincronização Cardíaca/efeitos adversos , Dispositivos de Terapia de Ressincronização Cardíaca/efeitos adversos , Eletrodos Implantados/efeitos adversos
15.
Heart Rhythm ; 21(5): 571-580, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38286246

RESUMO

BACKGROUND: Three-dimensional (3D) mapping of the ventricular conduction system is challenging. OBJECTIVE: The purpose of this study was to use ripple mapping to distinguish conduction system activation to that of adjacent myocardium in order to characterize the conduction system in the postinfarct left ventricle (LV). METHODS: High-density mapping (PentaRay, CARTO) was performed during normal rhythm in patients undergoing ventricular tachycardia ablation. Ripple maps were viewed from the end of the P wave to QRS onset in 1-ms increments. Clusters of >3 ripple bars were interrogated for the presence of Purkinje potentials, which were tagged on the 3D geometry. Repeating this process allowed conduction system delineation. RESULTS: Maps were reviewed in 24 patients (mean 3112 ± 613 points). There were 150.9 ± 24.5 Purkinje potentials per map, at the left posterior fascicle (LPF) in 22 patients (92%) and at the left anterior fascicle (LAF) in 15 patients (63%). The LAF was shorter (41.4 vs 68.8 mm; P = .0005) and activated for a shorter duration (40.6 vs 64.9 ms; P = .002) than the LPF. Fourteen of 24 patients had left bundle branch block (LBBB), with 11 of 14 (78%) having Purkinje potential-associated breakout. There were fewer breakouts from the conduction system during LBBB (1.8 vs 3.4; 1.6 ± 0.6; P = .039) and an inverse correlation between breakout sites and QRS duration (P = .0035). CONCLUSION: We applied ripple mapping to present a detailed electroanatomic characterization of the conduction system in the postinfarct LV. Patients with broader QRS had fewer LV breakout sites from the conduction system. However, there was 3D mapping evidence of LV breakout from an intact conduction system in the majority of patients with LBBB.


Assuntos
Ablação por Cateter , Sistema de Condução Cardíaco , Ventrículos do Coração , Infarto do Miocárdio , Taquicardia Ventricular , Humanos , Masculino , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Pessoa de Meia-Idade , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Ablação por Cateter/métodos , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/complicações , Eletrocardiografia , Ramos Subendocárdicos/fisiopatologia , Idoso , Imageamento Tridimensional , Mapeamento Potencial de Superfície Corporal/métodos
16.
Spec Care Dentist ; 44(1): 28-39, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36746669

RESUMO

AIM: This systematic review provides a summary of the scientific evidence concerning effects of periodontal treatment on the C-reactive protein (CRP) levels in hemodialysis patients. MATERIAL AND METHODS: Eight databases were accessed until May 2020 for interventional studies which evaluated CRP levels in hemodialysis patients before and after periodontal treatment. Inclusion criteria were studies involving hemodialysis patients with gingivitis or periodontitis, without restriction of year, language, and publication status. Random effects meta-analysis was performed. The risk of bias in eligible studies was assessed using the Joanna Briggs Institute's Critical Appraisal tools for use in systematic reviews. Certainty of evidence was also evaluated using GRADE approach. RESULTS: The search in the databases resulted in 326 records, from which only seven met the eligibility criteria and therefore were submitted to qualitative evaluation. The meta-analysis revealed that, in general, the reduction in CRP levels had moderate and statistically significant effect size (standardized mean difference [SMD] = 0.45; confidence interval [CI] 95% = 0.25, 0.65; p < .001). Statistical heterogeneity was low (I2  = 0.0%; p = .771). Most studies showed moderate risk of bias. CONCLUSION: Based on low certainty of evidence, the results suggest that periodontal treatment can significantly contribute to reduce CRP levels among hemodialysis patients. However, more randomized clinical studies, with follow-up longer than 12 months, using standardized diagnostic methods and controlling confounding factors, should be performed to strengthen the evidence.


Assuntos
Gengivite , Periodontite , Humanos , Proteína C-Reativa , Assistência Odontológica , Diálise Renal
17.
Mol Inform ; 43(1): e202300190, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37885368

RESUMO

GUIDEMOL is a Python computer program based on the RDKit software to process molecular structures and calculate molecular descriptors with a graphical user interface using the tkinter package. It can calculate descriptors already implemented in RDKit as well as grid representations of 3D molecular structures using the electrostatic potential or voxels. The GUIDEMOL app provides easy access to RDKit tools for chemoinformatics users with no programming skills and can be adapted to calculate other descriptors or to trigger other procedures. A command line interface (CLI) is also provided for the calculation of grid representations. The source code is available at https://github.com/jairesdesousa/guidemol.


Assuntos
Quimioinformática , Software , Proteínas Adaptadoras de Transdução de Sinal
18.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; Braz. J. Psychiatry (São Paulo, 1999, Impr.);46: e20233315, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1574153

RESUMO

Objective: To assess nuclear distribution element-like 1 (Ndel1) enzyme activity following acute administration of sodium nitroprusside (sNP) in a rodent model of schizophrenia (SCZ) and in a cohort of chronic SCZ patients. Methods: Ndel1 activity was measured following sNP infusions in spontaneously hypertensive rats (SHR) (2.5 or 5.0 mg/kg) and in a double-blind randomized trial with 15 SCZ patients (0.5 μg/kg/min). Patients were randomized into two groups (group I: n=7; group II: n=8), with one group receiving placebo and the other sNP in phase A. In phase B, the groups switched treatments. sNP was administered as an infusion of 0.5 μg/kg/min, for 4 h, while placebo was a 5% glucose solution infused under the same conditions. The infusions were administered once weekly over 4 weeks. Psychopathology was assessed using the 18-item figure 5 (BPRS-18 - Bech's version) and the negative subscale of the Positive and Negative Syndrome Scale. Results: Ndel1 activity was significantly reduced after sNP infusion in SHR and in patients receiving sNP (t = 7.756, degrees of freedom [df] = 97, p < 0.0001, dcohen=1.44) compared to placebo. Reduced Ndel1 activity from baseline to the end of infusion was only seen in patients after treatment with sNP. Conclusion: SCZ patients may benefit from adjunctive therapy with sNP and that the Ndel1 enzyme is a candidate biomarker of psychopathology in the disorder. Future research should look into the role of Ndel1 in SCZ and the potential effects of sNP and drugs with similar profiles of action in both animals and patients.

19.
Braz J Psychiatry ; 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37994832

RESUMO

OBJECTIVE: Schizophrenia (SCZ) is a disabling disorder that continues to defy clinicians and researchers. We investigated the effects of sodium nitroprusside (sNP) in an animal model of SCZ and as an add-on therapy in patients and the relationship between treatment with sNP and activity of the nDel1 enzyme, whose involvement in the pathophysiology of the disorder has been suggested earlier. METHODS: Ndel1 activity was measured following sNP infusions in spontaneously hypertensive rats (SHR; 2.5 or 5.0 mg/kg) and in a double-blind trial with SCZ patients (0.5 µg/kg/min). RESULTS: Ndel1 activity was significantly reduced after sNP infusion in blood of SHR compared to controls, and in patients receiving sNP (t = 7.756, df = 97, p < 0.0001, dcohen = 1.44) compared to placebo. Reduced Ndel1 activity between baseline and the end of the infusion was only seen in patients after treatment with sNP. CONCLUSION: Our findings suggest that SCZ patients may benefit from adjunctive therapy with sNP and that the Ndel1 enzyme is a candidate biomarker of psychopathology in the disorder. Future research should look into the role of Ndel1 in SCZ and the potential effects of sNP and drugs with similar profiles of action in both animals and patients.

20.
Front Plant Sci ; 14: 1252504, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965018

RESUMO

Introduction: Genomic selection (GS) experiments in forest trees have largely reported estimates of predictive abilities from cross-validation among individuals in the same breeding generation. In such conditions, no effects of recombination, selection, drift, and environmental changes are accounted for. Here, we assessed the effectively realized predictive ability (RPA) for volume growth at harvest age by GS across generations in an operational reciprocal recurrent selection (RRS) program of hybrid Eucalyptus. Methods: Genomic best linear unbiased prediction with additive (GBLUP_G), additive plus dominance (GBLUP_G+D), and additive single-step (HBLUP) models were trained with different combinations of growth data of hybrids and pure species individuals (N = 17,462) of the G1 generation, 1,944 of which were genotyped with ~16,000 SNPs from SNP arrays. The hybrid G2 progeny trial (HPT267) was the GS target, with 1,400 selection candidates, 197 of which were genotyped still at the seedling stage, and genomically predicted for their breeding and genotypic values at the operational harvest age (6 years). Seedlings were then grown to harvest and measured, and their pedigree-based breeding and genotypic values were compared to their originally predicted genomic counterparts. Results: Genomic RPAs ≥0.80 were obtained as the genetic relatedness between G1 and G2 increased, especially when the direct parents of selection candidates were used in training. GBLUP_G+D reached RPAs ≥0.70 only when hybrid or pure species data of G1 were included in training. HBLUP was only marginally better than GBLUP. Correlations ≥0.80 were obtained between pedigree and genomic individual ranks. Rank coincidence of the top 2.5% selections was the highest for GBLUP_G (45% to 60%) compared to GBLUP_G+D. To advance the pure species RRS populations, GS models were best when trained on pure species than hybrid data, and HBLUP yielded ~20% higher predictive abilities than GBLUP, but was not better than ABLUP for ungenotyped trees. Discussion: We demonstrate that genomic data effectively enable accurate ranking of eucalypt hybrid seedlings for their yet-to-be observed volume growth at harvest age. Our results support a two-stage GS approach involving family selection by average genomic breeding value, followed by within-top-families individual GS, significantly increasing selection intensity, optimizing genotyping costs, and accelerating RRS breeding.

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