Summary Primary mammary neuroendocrine carcinoma (NEC) is an uncommon entity that accounts for 2% to 5% of breast carcinomas. Recent reports have shown that NEC of the breast is an aggressive subtype ...of mammary carcinoma that is distinct from invasive ductal carcinoma, not otherwise specified, and have suggested that these tumors have a poorer prognosis than invasive ductal carcinoma, not otherwise specified. In this study, we provide the first cytogenetic characterization of mammary NEC using both conventional G-banding and spectral karyotype on a group of 7 tumors. We identified clonal chromosomal aberrations in 5 (71.4%) cases, with 4 of them showing complex karyotypes. Of these, recurrent numerical aberrations included gain of chromosome 7 (n = 2) and loss of chromosome 15 (n = 2). Recurrent clonal structural chromosomal aberrations involved chromosomes 1 (n = 3), 3 (n = 2), 6q (n = 3), and 17q (n = 3). Of the 4 (57.1%) cases with complex karyotypes, 2 showed evidence of chromothripsis, a phenomenon in which tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. One of these had evidence of chromothripsis involving chromosomes 1, 6, 8, and 15. The other also had evidence of chromosome 8 chromothripsis, making this a recurrent finding shared by both cases. We also found that mammary NEC shared some cytogenetic abnormalities—such as trisomy 7 and 12—with other neuroendocrine tumors in the lung and gastrointestinal tract, suggesting trisomy 7 and 12 as potential common molecular aberrations in neuroendocrine tumors. To our knowledge, this is the first report on molecular cytogenetic characterization of mammary NEC.
Abstract Background: Certain herbal medicines have been reported to be effective in the treatment of psychiatric conditions, and combination treatment with drugs and herbal medicines has been ...reported to be useful in enhancing treatment efficacy and reducing recovery time and adverse events (AEs). Objective: The purpose of this study was to investigate the effectiveness and tolerability of warm-supplementing kidney yang (WSKY) added to risperidone in improving cognitive impairment and negative symptoms (ie, cognitive function) in patients with schizophrenia. Methods: This 8-week, multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in patients who met the clinical classification for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision . Patients were recruited from 3 centers (including inpatient and outpatient clinics) and were evenly randomized to receive WSKY or placebo added to risperidone for 8 weeks. Primary assessments were conducted at weeks 2, 4, and 8. A clinical response was defined as a ≥50% reduction score (from baseline) on the Positive and Negative Syndrome Scale (PANSS), a ≥30% reduction score (from baseline) on the Scale for the Assessment of Negative Symptoms (SANS), or a ≥50% reduction score (from baseline) on the Hamilton Rating Scale for Depression (HAM-D-17). Cognitive function was assessed using the Wisconsin Card Sorting Test (WCST) at baseline and end point. Extrapyramidal AEs were assessed weekly using the Abnormal Involuntary Movement Scale (AIMS) and the Rating Scale for Extrapyramidal Side Effects (RSESE). AEs were assessed by patient interviews conducted at each clinic visit and also by the Treatment Emergent Symptoms Scale (TESS) scores. Results: One-hundred twenty patients (62 males, 58 females; mean SD age, 34.4 9.4 years; range, 18–45 years; baseline mean SD PANSS score, 88.7 12.3) were included in this study. Risperidone- and WSKY-treated patients had statistically significant improvements at end point in the number of completed categories ( P = 0.019), perseverative responses ( P = 0.041), perseverative errors ( P = 0.040), and total errors ( P = 0.049) on the WCST compared with placebo. The improvements in the PANSS, SANS, and HAM-D-17 scores were not significantly different between the 2 groups at week 8 for observed case and last-observation-carried-forward (LOCF) analyses. The response rates (LOCF) for the PANSS scores in the WSKY and placebo groups were 55.0% and 35.0%, respectively ( P = 0.028), while the SANS scores were 63.3% and 45.0% ( P = 0.044) and the HAM-D-17 were 35.0% and 45.0% ( P = 0.264). There were no significant between-group differences in scores on the AIMS, RSESE, or TESS. Conclusions: The results of this study suggest that WSKY added to risperidone significantly improved cognitive function in these patients, as measured by the number of completed categories, perseverative responses, perseverative errors, and total errors on the WCST compared with placebo. The response rates in the WSKY group for the PANSS and SANS scores were significantly higher compared with placebo. All treatments were generally well tolerated.
Coordinating the charging process of a large population of electric vehicles (EV) is promising in increasing power grid flexibility from the demand side, yet requires highly scalable control ...protocols. In contrast to classical decentralized optimization based methods that require approximated distribution network models, this paper frames the EV charging control problem into a multi-agent reinforcement learning (MARL) framework. The MARL-based framework is trained through an actor-critic network and adopts the structure of centralized training and decentralized execution with partial observations. Comparing with model-based approaches, the developed MARL-based approach better captures the attributes of the distribution network, improves grid-level service performance, achieves better network constraints control, reduces the communication load, and achieves a faster response. The efficacy and efficiency of the developed method are verified by simulations on the IEEE 13-bus test feeder.
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