Melatonin alleviates endoplasmic reticulum stress to improve ovarian function by regulating the mTOR pathway in aged laying hens.

Granular cell apoptosis is a key factor leading to follicular atresia and decreased laying rate in aged laying hens. Endoplasmic reticulum stress (ERS) induced cell apoptosis is a new type of apoptosis pathway. Previous studies have shown that the ERS pathway is involved in the regulation of follicular development and atresia, and can be regulated by mTOR. Melatonin (MEL) can protect the normal development of follicles, but the precise mechanism by which MEL regulates follicular development is not yet clear. So, we investigated the potential relationship between MEL and ERS and mTOR signaling pathway in vivo through intraperitoneal injection of MEL in aged laying hens. The results show that the laying rate, ovarian follicle number, plasma MEL, E2, LH, FSH concentrations, as well as the mRNA expression of mTOR signaling-associated genes TSC1, TSC2, mTOR, 4E-BP1, and S6K in old later-period chicken control (Old-CN) group was significantly decreased (P < 0.01). In contrast, the ERS-related of plasma and granular cell layer mRNA expression of Grp78, CHOP, and Caspase-3 was significantly increased (P < 0.01). While both of the effects were reversed by MEL. Then, aging granulosa cells were treated with MEL in vitro, followed by RNA seq analysis, and it was found that 259 and 322 genes were upregulated and downregulated. After performing GO enrichment analysis, it was found that DEGs significantly contribute to the biological processes including cell growth and apoptosis. Using pathway enrichment analysis, we found significant overrepresentation of cellular processes related to mTOR signaling and endoplasmic reticulum (ER) stress, involving genes such as GRB10, SGK1, PRKCA, RPS6KA2, RAF1, PIK3R3, FOXO1, DERL3, HMOX1, TLR7, VAMP7 and INSIG2. The obtained results of RT-PCR showed consistency with the RNA-Seq data. In summary, the underlined results revealed that MEL has significantly contributed to follicular development via activating the mTOR signaling pathway-related genes and alleviating ERS-related genes in laying hens. The current study provides a theoretical background for enhancing the egg-laying capability of hens and also providing a basis for elucidating the molecular mechanism of follicular selection.

Mitochondrial Signaling, the Mechanisms of AKI-to-CKD Transition and Potential Treatment Targets.

Acute kidney injury (AKI) is increasing in prevalence and causes a global health burden. AKI is associated with significant mortality and can subsequently develop into chronic kidney disease (CKD). The kidney is one of the most energy-demanding organs in the human body and has a role in active solute transport, maintenance of electrochemical gradients, and regulation of fluid balance. Renal proximal tubular cells (PTCs) are the primary segment to reabsorb and secrete various solutes and take part in AKI initiation. Mitochondria, which are enriched in PTCs, are the main source of adenosine triphosphate (ATP) in cells as generated through oxidative phosphorylation. Mitochondrial dysfunction may result in reactive oxygen species (ROS) production, impaired biogenesis, oxidative stress multiplication, and ultimately leading to cell death. Even though mitochondrial damage and malfunction have been observed in both human kidney disease and animal models of AKI and CKD, the mechanism of mitochondrial signaling in PTC for AKI-to-CKD transition remains unknown. We review the recent findings of the development of AKI-to-CKD transition with a focus on mitochondrial disorders in PTCs. We propose that mitochondrial signaling is a key mechanism of the progression of AKI to CKD and potential targeting for treatment.

Assessing Continuous Epidural Infusion and Programmed Intermittent Epidural Bolus for Their Effectiveness in Providing Labor Analgesia: A Mono-Centric Retrospective Comparative Study.

Background and Objectives: Local anesthetics administered via epidural catheters have evolved from intermittent top-ups to simultaneous administration of continuous epidural infusion (CEI) and patient-controlled epidural analgesia (PCEA) using the same device. The latest programmed intermittent epidural bolus (PIEB) model is believed to create a wider and more even distribution of analgesia inside the epidural space. The switch from CEI + PCEA to PIEB + PCEA in our department began in 2018; however, we received conflicting feedback regarding workload from the quality assurance team. This study aimed to investigate the benefits and drawbacks of this conversion, including the differences in acute pain service (APS) staff workload, maternal satisfaction, side effects, and complications before and after the changeover. Materials and Methods: Items from the APS records included total delivery time, average local anesthetic dosage, and the formerly mentioned items. The incidence of side effects, the association between the duration of delivery and total dosage, and hourly medication usage in the time subgroups of the CEI and PIEB groups were compared. The staff workload incurred from rescue bolus injection, catheter adjustment, and dosage adjustment was also analyzed. Results: The final analysis included 214 and 272 cases of CEI + PCEA and PIEB + PCEA for labor analgesia, respectively. The total amount of medication and average hourly dosage were significantly lower in the PIEB + PCEA group. The incidences of dosage change, manual bolus, extra visits per patient, and lidocaine use for rescue bolus were greater in the PIEB + PCEA group, indicating an increased staff workload. However, the two groups did not differ in CS rates, labor time, maternal satisfaction, and side effects. Conclusions: This study revealed that while PIEB + PCEA maintained the advantage of decreasing total drug doses, it inadvertently increased the staff burden. Increased workload might be a consideration in clinical settings when choosing between different methods of PCEA.

Chronic Kidney Disease-How Does It Go, and What Can We Do and Expect?

Chronic kidney disease (CKD), as a worldwide threat to public health, is a key determinant of poor health outcomes, but the severity of the problem is probably not fully appreciated [...].

High risk of renal outcome of metabolic syndrome independent of diabetes in patients with CKD stage 1-4: The ICKD database.

AIMS: To investigate whether metabolic syndrome (MetS) could predict renal outcome in patients with established chronic kidney disease (CKD). MATERIALS AND METHODS: We enroled 2500 patients with CKD stage 1-4 from the Integrated CKD care programme, Kaohsiung for delaying Dialysis (ICKD) prospective observational study. 66.9% and 49.2% patients had MetS and diabetes (DM), respectively. We accessed three clinical outcomes, including all-cause mortality, RRT, and 50% decline in estimated glomerular filtration rate events. RESULTS: The MetS score was positively associated with proteinuria, inflammation, and nutrition markers. In fully adjusted Cox regression, the hazard ratio (HR) (95% confidence interval) of MetS for composite renal outcome (renal replacement therapy, and 50% decline of renal function) in the DM and non-DM subgroups was 1.56 (1.15-2.12) and 1.31 (1.02-1.70), respectively, while that for all-cause mortality was 1.00 (0.71-1.40) and 1.27 (0.92-1.74). Blood pressure is the most important component of MetS for renal outcomes. In the 2 by 2 matrix, compared with the non-DM/non-MetS group, the DM/MetS group (HR: 1.62 (1.31-2.02)) and the non-DM/MetS group (HR: 1.33 (1.05-1.69)) had higher risks for composite renal outcome, whereas the DM/MetS group had higher risk for all-cause mortality (HR: 1.43 (1.09-1.88)). CONCLUSIONS: MetS could predict renal outcome in patients with CKD stage 1-4 independent of DM.

Learning to read Chinese: the roles of phonological awareness, paired-associate learning, and phonetic radical awareness.

This study aimed to determine how Chinese children adapt to Chinese orthography-phonology correspondence by acquiring phonetic radical awareness (PRA). This study used two important Chinese encoding approaches (rote and orthographic approaches) as the developmental trajectory, in which the present study hypothesized that phonological awareness (PA) exerts not only a direct influence on PRA but also an indirect influence through paired- associate learning (PAL). We also explored whether the association between PA and PAL is affected by the complexity of visual stimuli embedded in PAL. This study recruited 70 s-grade students to participate in various tests, which assessed (a) PA (measured by onset and rhyme awareness), (b) PRA (measured by regularity and consistency of phonetic radicals), (c) PAL (measured by learning performance on strokes; pattern-object and strokes pattern-syllable mapping), and (d) Chinese character recognition ability. Path analyses indicated that (1) character size had a significant positive correlation with PRA but not with PAL, (2) PAL fully mediated the association between PA and PRA, and (3) compared with PAL with a low stroke count, PA had a stronger relationship with PAL with a high stroke count. The results of this study were consistent with previous studies and suggest that PRA is the most important literacy skill for children in the middle of their learning-to-read stage. The results also augment existing literature by revealing that PRA acquisition is increased by PAL supported by PA, rather than by PA alone. Moreover, when the visual complexity of PAL increases, the support of PA to PAL would increase to make up for the working memory shortage.

The Effect of Visual Mnemonics and the Presentation of Character Pairs on Learning Visually Similar Characters for Chinese-As-Second-Language Learners.

This study investigates the effects of visual mnemonics and the methods of presenting learning materials on learning visually similar characters for Chinese-as-second-language (CSL) learners. In supporting CSL learners to build robust orthographic representations in Chinese, addressing the challenges of visual similarity of characters (e.g., and ) is an important issue. Based on prior research on perceptual learning, we tested three strategies that differ in the extent to which they promote interrelated attention to the form and meaning of characters: (1) Stroke Sequence, a form-emphasis strategy, (2) Key-images, a form + meaning strategy utilizing visual code, (3) Pithy Formulas with Key-images, a form + meaning strategy combining visual and verbal codes. A pretest-posttest equivalent-group design was adopted. The independent variables were the learning strategy, the method of presenting character pairs (visually similar vs. dissimilar), and testing time. The dependent variables were learners' proportions of accurate responses to reading and writing Chinese characters through a posttest (immediately performed after learning) and a delayed posttest (1 week after learning); a learner experience survey was also administered to investigate learners' opinions on each strategy. Sixty-six non-beginning learners of Chinese participated; they were randomly assigned to one of the two groups in which participants learned ten characters via the three strategies, respectively, differing between whether the characters were presented in similar pairs or dissimilar pairs. Data were analyzed via three-way ANCOVAs. The Pithy Formulas with Key-images and the Key-images generally yielded higher writing accuracy than Stroke Sequence immediately after learning. Notably, the advantage of the Pithy Formulas with Key-images (verbal and visual) over the Key-images (visual) on writing was specific to the participants that learned with visually similar pairs rather than those that learned with dissimilar pairs. All strategies were effective for reading, yet learners' experience ratings favored the two form + meaning strategies over the strategy that focused primarily on form. Suggestions for future research and pedagogical implications on learning visually similar characters were offered.

Development and validation of a Chinese pseudo-character/non-character producing system.

This study developed and validated a Chinese pseudo-character/non-character producing system (CPN system) that can assist researchers in creating experimental materials using Chinese characters. Based on a large-scale dataset of 6097 characters, the CPN system provides researchers with precise Chinese orthographic information (structures and positions, radical frequency, number of strokes, number of radical-sharing neighbors, and position-based regularity) to create three types of experimental stimuli: pseudo-characters, semi non-characters, and whole non-characters. Featuring the position-based regularity of 446 radicals, the CPN system helps researchers to manipulate, or to control for, orthographic characteristics of radicals to study Chinese lexical processing. In two empirical validations for stimuli created by the system, Chinese-as-second-language learners (n = 79) and first-language users (n = 41), respectively, participated in a Chinese orthographic choice task in which participants compared two artificial characters and chose the one that more closely resembled a real Chinese character. Both validations demonstrate that highly proficient Chinese readers are better able to identify pseudo-characters, suggesting that the radical's position-based information impacts Chinese character identification to different extents. With the empirical support for the created stimuli, the system further affords researchers auto-generated outcomes with downloadable images and Excel sheets for creating customized stimuli, making material selection easy, efficient, and effective. This CPN system is the first large-scale, data-driven tool free for researchers who are interested in studies of written Chinese. CPN should benefit the field of Chinese orthographic processing, Chinese instruction, and cross-linguistic comparisons, providing a useful tool for studying Chinese lexical processing.

Serotonin Signals Modulate Mushroom Body Output Neurons for Sustaining Water-Reward Long-Term Memory in Drosophila.

Memory consolidation is a time-dependent process through which an unstable learned experience is transformed into a stable long-term memory; however, the circuit and molecular mechanisms underlying this process are poorly understood. The Drosophila mushroom body (MB) is a huge brain neuropil that plays a crucial role in olfactory memory. The MB neurons can be generally classified into three subsets: γ, αß, and α'ß'. Here, we report that water-reward long-term memory (wLTM) consolidation requires activity from α'ß'-related mushroom body output neurons (MBONs) in a specific time window. wLTM consolidation requires neurotransmission in MBON-γ3ß'1 during the 0-2 h period after training, and neurotransmission in MBON-α'2 is required during the 2-4 h period after training. Moreover, neurotransmission in MBON-α'1α'3 is required during the 0-4 h period after training. Intriguingly, blocking neurotransmission during consolidation or inhibiting serotonin biosynthesis in serotoninergic dorsal paired medial (DPM) neurons also disrupted the wLTM, suggesting that wLTM consolidation requires serotonin signals from DPM neurons. The GFP Reconstitution Across Synaptic Partners (GRASP) data showed the connectivity between DPM neurons and MBON-γ3ß'1, MBON-α'2, and MBON-α'1α'3, and RNAi-mediated silencing of serotonin receptors in MBON-γ3ß'1, MBON-α'2, or MBON-α'1α'3 disrupted wLTM. Taken together, our results suggest that serotonin released from DPM neurons modulates neuronal activity in MBON-γ3ß'1, MBON-α'2, and MBON-α'1α'3 at specific time windows, which is critical for the consolidation of wLTM in Drosophila.

Effect of natural garlic essential oil on chickens with artificially infected Eimeria tenella.

Chicken coccidiosis is a kind of parasitic protozoosis caused by Eimeria parasitizing in the chicken intestinal epithelial cells. Eimeria tenella is considered as a significantly virulent and harmful parasite. At present, drug resistance remains a major problem and a large number of drug residues have been found to be produced in the treatment of the disease. Hence, novel strategies are needed to avoid the harmful effects caused by the generation of various chemical drug residues to the human body and also reduce the economic loss caused by coccidiosis to the chicken industry. In this study, natural garlic essential oil was used to control Eimeria tenella infection. The anticoccidial index (ACI) was calculated according to the clinical symptoms, body weight gain, oocyst excretion and cecal lesions. The immune organ index and serum biochemical indexes were measured to verify the possible anticoccidial effects. The results showed that: compared with the infected group, continuous feeding of different doses of natural garlic essential oil could significantly reduce the clinical symptoms, cecal lesions, the number of oocysts, but increase the weight of sick chickens, and effectively improve the intestinal functions. Moreover, compared with diclazuril control group, 0.06 mL/L garlic essential oil exhibited similar anticoccidial index. The content of immune organ index, serum biochemical index IgM, IgG and IgA in 0.06 mL/L garlic essential oil group was the highest, which indicated that garlic essential oil had a significant tendency to improve the immune function of the chickens. This study also showed that the natural garlic essential oil exhibited the same beneficial effects as that of diclazuril on chicken coccidiosis, and the anti-coccidiosis index of 0.06 mL/L garlic essential oil was favorable. Thus based on the above evidences and its relatively low cost, garlic essential oil can be potentially be used as an efficient anti parasitic drug.

Melatonin regulates chicken granulosa cell proliferation and apoptosis by activating the mTOR signaling pathway via its receptors.

Melatonin is a key regulator of follicle granular cell maturation and ovulation. The mammalian target of rapamycin (mTOR) pathway plays an important role in cell growth regulation. Therefore, our aim was to investigate whether the mTOR signaling pathway is involved in the regulation of melatonin-mediated proliferation and apoptotic mechanisms in granulosa cells. Chicken follicle granular cells were cultured with melatonin (0, 2, 20, or 200 µmol/L) for 48 h. The results showed that melatonin treatment enhanced proliferation and suppressed apoptosis in granular cells at 20 µmol/L and 200 µmol/L (P < 0.05) by upregulation of cyclin D1 (P < 0.01) and Bcl-2 (P < 0.01) and downregulation of P21, caspase-3, Beclin1, and LC3-II (P < 0.01). The effects resulted in the activation of the mTOR signaling pathway by increasing the expression of avTOR, PKC, 4E-BP1, S6K (P < 0.05), p-mTOR, and p-S6K. We added an mTOR activator and inhibitor to the cells and identified the optimal dose (10 µmol/L MHY1485 and 100 nmol/L rapamycin) for subsequent experiments. The combination of 20 µmol/L melatonin and 10 µmol/L MHY1485 significantly enhanced granulosa cell proliferation (P < 0.05), while 100 nmol/L rapamycin significantly inhibited proliferation and enhanced apoptosis (P < 0.05), but this action was reversed in the 20-µmol/L melatonin and 100-nmol/L rapamycin cotreatment groups (P < 0.05). This was confirmed by mRNA and protein expression that was associated with proliferation, apoptosis, and autophagy (P < 0.05). The combination of 20 µmol/L melatonin and 10 µmol/L MHY1485 also activated the mTOR pathway upstream genes PI3K, AKT1, and AKT2 and downstream genes PKC, 4E-BP1, and S6K (P < 0.05), as well as protein expression of p-mTOR and p-S6K. Rapamycin significantly inhibited the mTOR pathway-related genes mRNA levels (P < 0.05). In addition, activation of the mTOR pathway increased melatonin receptor mRNA levels (P < 0.05). In conclusion, these findings demonstrate that melatonin regulates chicken granulosa cell proliferation and apoptosis by activating the mTOR signaling pathway via its receptor.

Mushroom body subsets encode CREB2-dependent water-reward long-term memory in Drosophila.

Long-term memory (LTM) formation depends on the conversed cAMP response element-binding protein (CREB)-dependent gene transcription followed by de novo protein synthesis. Thirsty fruit flies can be trained to associate an odor with water reward to form water-reward LTM (wLTM), which can last for over 24 hours without a significant decline. The role of de novo protein synthesis and CREB-regulated gene expression changes in neural circuits that contribute to wLTM remains unclear. Here, we show that acute inhibition of protein synthesis in the mushroom body (MB) αß or γ neurons during memory formation using a cold-sensitive ribosome-inactivating toxin disrupts wLTM. Furthermore, adult stage-specific expression of dCREB2b in αß or γ neurons also disrupts wLTM. The MB αß and γ neurons can be further classified into five different neuronal subsets including αß core, αß surface, αß posterior, γ main, and γ dorsal. We observed that the neurotransmission from αß surface and γ dorsal neuron subsets is required for wLTM retrieval, whereas the αß core, αß posterior, and γ main are dispensable. Adult stage-specific expression of dCREB2b in αß surface and γ dorsal neurons inhibits wLTM formation. In vivo calcium imaging revealed that αß surface and γ dorsal neurons form wLTM traces with different dynamic properties, and these memory traces are abolished by dCREB2b expression. Our results suggest that a small population of neurons within the MB circuits support long-term storage of water-reward memory in Drosophila.

ARC 118925XX stimulates cation influx in bEND.3 endothelial cells.

In a previous publication when we studied the purinergic receptor with which ATP interacted in mouse brain bEND.3 endothelial cells, we observed addition of 3 µm ARC 118925XX (ARC; selective P2Y2 antagonist) strongly suppressed ATP-triggered Ca2+ release, suggesting the response was mediated via P2Y2 receptors. We here report ARC unexpectedly promoted substantial Ca2+ influx even when ATP-triggered Ca2+ release was largely inhibited. Since this large Ca2+ influx may have important pharmacological significance, we proceeded to investigate its mechanism. ARC did not trigger intracellular Ca2+ release thus suggesting Ca2+ influx triggered by ARC was not store-operated. ARC-triggered Ca2+ influx could be blocked by 1 mm Ni2+ , a general Ca2+ channel blocker, but not by SK&F 96365, a nonselective TRP channel blocker. Unexpectedly, ARC promoted influx of Na+ and La3+ , but not Mn2+ . This is a surprising finding, since Mn2+ is conventionally used as a Ca2+ surrogate ion (as it permeates Ca2+ channel), and La3+ is classically used as a potent Ca2+ channel antagonist. Electrophysiological examination showed ARC did not stimulate any cation currents. Therefore, ARC opened, rather than a cation channel pore, an unidentified Ca2+ influx pathway which was Na+ - and La3+ -permeable but Mn2+ -impermeable.

Reading Pinyin activates sublexcial character orthography for skilled Chinese readers.

How do skilled Chinese readers, accustomed to characters, process Pinyin, a phonemic transcription of Chinese? Does the orthography of Chinese characters become activated? In four experiments, native speakers first made a meaning judgment on a two-syllable word written in Pinyin. Immediately following, they responded to a character whose orthography sometimes was related to the character corresponding to the Pinyin. In Experiments 1 and 3, participant named the color of the presented characters; there was an interference effect when the presented characters included phonetic radicals that were part of the character corresponding to the Pinyin. In Experiments 2 and 4, participants named the character; naming times were affected if either the semantic or phonetic radical was shared with the character corresponding to the Pinyin. The results indicate that access to lexical representations in Chinese is centered on the orthographic character, even when the input is Pinyin.

GraphCom: A multidimensional measure of graphic complexity applied to 131 written languages.

We report a new multidimensional measure of visual complexity (GraphCom) that captures variability in the complexity of graphs within and across writing systems. We applied the measure to 131 written languages, allowing comparisons of complexity and providing a basis for empirical testing of GraphCom. The measure includes four dimensions whose value in capturing the different visual properties of graphs had been demonstrated in prior reading research-(1) perimetric complexity, sensitive to the ratio of a written form to its surrounding white space (Pelli, Burns, Farell, & Moore-Page, 2006); (2) number of disconnected components, sensitive to discontinuity (Gibson, 1969); (3) number of connected points, sensitive to continuity (Lanthier, Risko, Stolz, & Besner, 2009); and (4) number of simple features, sensitive to the strokes that compose graphs (Wu, Zhou, & Shu, 1999). In our analysis of the complexity of 21,550 graphs, we (a) determined the complexity variation across writing systems along each dimension, (b) examined the relationships among complexity patterns within and across writing systems, and (c) compared the dimensions in their abilities to differentiate the graphs from different writing systems, in order to predict human perceptual judgments (n = 180) of graphs with varying complexity. The results from the computational and experimental comparisons showed that GraphCom provides a measure of graphic complexity that exceeds previous measures in its empirical validation. The measure can be universally applied across writing systems, providing a research tool for studies of reading and writing.

Carbon Nanodots with Sub-Nanosecond Spontaneous Emission Lifetime.

Compared with most mature cadmium-containing quantum dots (QDs), carbon nanodots (CNDs) are a new class of colloidal nanomaterials that exhibit unique photoluminescence (PL) properties while being nontoxic and easily manufactured using low-cost precursor materials. However, solid-state CNDs exhibit poor PL quantum yields (PL-QYs) and inefficient radiative transition, which significantly hinders their practical use in optoelectronic devices. To address this issue, plasmonic nanoantennas consisting of Au nanorods (Au-NRs) deposited on a flat Au film with inserted dielectric layers were used to enhance the spontaneous emission of solid-state CNDs with broad spectral linewidth. Using steady-state, time-resolved, and spatial-resolved PL measurements, we found that after coupling to plasmonic nanogaps (PNGs), the PL emission was significantly enhanced, accompanied by a PL lifetime shortening to the sub-nanosecond range (≈140 ps). According to the experimental data, the radiative transition is strongly accelerated and can thus overcome the metal loss, leading to a large PL enhancement. Our demonstration can pave the way to the design of eco-friendly nanoemitters with sub-nanosecond PL lifetime for promising applications in light-emitting devices.

Synthesis of vibroarthrographic signals in knee osteoarthritis diagnosis training.

BACKGROUND: Vibroarthrographic (VAG) signals are used as useful indicators of knee osteoarthritis (OA) status. The objective was to build a template database of knee crepitus sounds. Internships can practice in the template database to shorten the time of training for diagnosis of OA. METHODS: A knee sound signal was obtained using an innovative stethoscope device with a goniometer. Each knee sound signal was recorded with a Kellgren-Lawrence (KL) grade. The sound signal was segmented according to the goniometer data. The signal was Fourier transformed on the correlated frequency segment. An inverse Fourier transform was performed to obtain the time-domain signal. Haar wavelet transform was then done. The median and mean of the wavelet coefficients were chosen to inverse transform the synthesized signal in each KL category. The quality of the synthesized signal was assessed by a clinician. RESULTS: The sample signals were evaluated using different algorithms (median and mean). The accuracy rate of the median coefficient algorithm (93 %) was better than the mean coefficient algorithm (88 %) for cross-validation by a clinician using synthesis of VAG. CONCLUSIONS: The artificial signal we synthesized has the potential to build a learning system for medical students, internships and para-medical personnel for the diagnosis of OA. Therefore, our method provides a feasible way to evaluate crepitus sounds that may assist in the diagnosis of knee OA.

The Major Prognostic Features of Nuclear Receptor NR5A2 in Infiltrating Ductal Breast Carcinomas.

Background. Gene expression profiles of 181 breast cancer samples were analyzed to identify prognostic features of nuclear receptors NR5A1 and NR5A2 based upon their associated transcriptional networks. Methods. A supervised network analysis approach was used to build the NR5A-mediated transcriptional regulatory network. Other bioinformatic tools and statistical methods were utilized to confirm and extend results from the network analysis methodology. Results. NR5A2 expression is a negative factor in breast cancer prognosis in both ER(-) and ER(-)/ER(+) mixed cohorts. The clinical and cohort significance of NR5A2-mediated transcriptional activities indicates that it may have a significant role in attenuating grade development and cancer related signal transduction pathways. NR5A2 signature that conditions poor prognosis was identified based upon results from 15 distinct probes. Alternatively, the expression of NR5A1 predicts favorable prognosis when concurrent NR5A2 expression is low. A favorable signature of eight transcription factors mediated by NR5A1 was also identified. Conclusions. Correlation of poor prognosis and NR5A2 activity is identified by NR5A2-mediated 15-gene signature. NR5A2 may be a potential drug target for treating a subset of breast cancer tumors across breast cancer subtypes, especially ER(-) breast tumors. The favorable prognostic feature of NR5A1 is predicted by NR5A1-mediated 8-gene signature.

Correction to: Prognostic Features of Signal Transducer and Activator of Transcription 3 in an ER(+) Breast Cancer Model System.

[This corrects the article on p. 21 in vol. 13, PMID: 24526833.].

Pregnancy-associated breast cancer in Taiwanese women: potential treatment delay and impact on survival.

This study investigated the clinicopathologic characteristics and survival of women diagnosed with pregnancy-associated breast cancer (PABC) in Taiwan. PABC is defined as breast cancer diagnosed during pregnancy or within 1 year after obstetric delivery. Our sample of PABC patients (N = 26) included all patients diagnosed at a major medical center in northern Taiwan from 1984 through 2009. Among these patients, 15 were diagnosed during pregnancy and 11 were diagnosed within 1 year after delivery. The comparison group included 104 patients within the same age range as the PABC patients and diagnosed with breast cancer not associated with pregnancy from 2004 through 2009 at the same hospital. Patients' initiating treatment delayed, 5-year and 10-year overall survival were delineated by stratified Kaplan-Meier estimates. Patients' characteristics were associated with initiating treatment delayed was evaluated with multivariate proportional hazards modeling. Antepartum PABC patients were younger and had longer time between diagnosis and treatment initiation than postpartum PABC patients. The predictor of treatment delayed was including birth parity, cancer stage, and pregnancy. The PABC group had larger tumors, more advanced cancer stage, and tumors with less progesterone receptor than the comparison group. The antepartum PABC patients had higher mortality than postpartum PABC and comparison groups within 5 years after diagnosis. Based on these results, we confirmed that pregnant women with breast cancer were more likely to delay treatment. Therefore, we recommend that breast cancer screening should be integrated into the prenatal and postnatal routine visits for early detection of the women's breast problems.