Miracle-dz/UniFAR-FTUs huggingface dataset:
Physical and psychosocial recovery in the year after primary treatment of breast cancer.

PURPOSE The 2000 National Institutes of Health Consensus Conference on Adjuvant Therapy of Breast Cancer recommended chemotherapy for all women with invasive cancer greater than 1 centimeter. Studies of long-term breast cancer survivors have found poorer quality of life (QOL) in women who received adjuvant chemotherapy. The aim of this article is to characterize physical and psychosocial recovery as a function of chemotherapy receipt in the year after medical treatment completion. PATIENTS AND METHODS Prospective longitudinal survey data (RAND SF-36 and Breast Cancer Prevention Trial [BCPT] Symptom Scales) collected from 558 women with breast cancer enrolled on the Moving Beyond Cancer (MBC) psychoeducational intervention trial were compared according to receipt of chemotherapy. MBC study enrollment occurred within 4 weeks after the end of primary treatment (eg, surgery, chemotherapy, radiation). Self-report questionnaire data collected at enrollment and at 2, 6, and 12 months thereafter were examined, controlling for intervention and with propensity score adjustment for imbalance of covariates. Outcome analyses were carried out by fitting linear mixed models by using SAS PROC MIXED. RESULTS Longitudinal SF-36 scale scores did not differ by chemotherapy treatment exposure, and both groups improved significantly (P < .01) in the year after primary treatment ended. However, adjuvant chemotherapy treatment was associated with significantly more severe physical symptoms, including musculoskeletal pain (P = .01), vaginal problems (P < .01), weight problems (P = .01), and nausea (P = .03). CONCLUSION Physical and psychosocial functioning improved significantly after breast cancer treatment, independent of receipt of adjuvant chemotherapy. Women who received chemotherapy experienced more severe and persistent physical symptoms that should be more effectively managed as part of survivorship care.
MPTCP solution for seamless local SIPTO mobility

In this paper, we propose a method to support seamless mobility for sessions carried by SIPTO connections. Session continuity has been considered an issue to be solved within 3GPP, as none of the solutions proposed for Mobile IP directly apply in the context of LTE. As in some cases, typically when SIPTO relies on using Local Gateways (LGW), it is necessary to change the IP address allocated to a User Equipment (UE), an active session may be interrupted. We propose an MPTCP based solution within the LTE architecture to maintain a single session, initially carried over a given SIPTO connection, and then carried over another SIPTO connection initiated due to the mobility of user equipment (UE). We identify how MPTCP operates over the LTE architecture, and estimate whether the corresponding delay is compatible with session continuity.
The role of glia in late-life depression

ABSTRACT Late-life depression (LLD) has a complex and multifactoral etiology. There is growing interest in elucidating how glia, acting alone or as part of a glial–neuronal network, may contribute to the pathophysiology of depression. In this paper, we explore results from neuroimaging studies showing gray-matter volume loss in key frontal and subcortical structures implicated in LLD, and present the few histological studies that have examined neuronal and glial densities in these regions. Compared to results in younger people with depression, there appear to be age-dependent differences in neuronal pathology but the changes in glial pathology may be more subtle, perhaps reflecting a longer-term compensatory gliosis to earlier damage. We then consider the mechanisms by which both astrocytes and microglia may mediate and modulate neuronal dysfunction and possible degeneration in depression. These include a critical role in the response to peripheral inflammation and central microglial activation, as well as a key role in glutamate metabolism. Advances in our understanding of glia are highlighted, including the role of microglia as “electricians” of the brain and astrocytes as key communicating cells, an integral part of the tripartite synapse. Finally, implications for clinicians are discussed, including the consideration of glia as biomarkers for LLD and incorporation of glia into future therapeutic strategies.
Phosphoproteomics of the Arabidopsis Plasma Membrane and a New Phosphorylation Site Databasew⃞

Functional genomic technologies are generating vast amounts of data describing the presence of transcripts or proteins in plant cells. Together with classical genetics, these approaches broaden our understanding of the gene products required for specific responses. Looking to the future, the focus of research must shift to the dynamic aspects of biology: molecular mechanisms of function and regulation. Phosphorylation is a key regulatory factor in all aspects of plant biology; but it is difficult, if not impossible, for most researchers to identify in vivo phosphorylation sites within their proteins of interest. We have developed a large-scale strategy for the isolation of phosphopeptides and identification by mass spectrometry (Nühse et al., 2003b). Here, we describe the identification of more than 300 phosphorylation sites from Arabidopsis thaliana plasma membrane proteins. These data will be a valuable resource for many fields of plant biology and overcome a major impediment to the elucidation of signal transduction pathways. We present an analysis of the characteristics of phosphorylation sites, their conservation among orthologs and paralogs, and the existence of putative motifs surrounding the sites. These analyses yield general principles for predicting other phosphorylation sites in plants and provide indications of specificity determinants for responsible kinases. In addition, more than 50 sites were mapped on receptor-like kinases and revealed an unexpected complexity of regulation. Finally, the data also provide empirical evidence on the topology of transmembrane proteins. This information indicates that prediction programs incorrectly identified the cytosolic portion of the protein in 25% of the transmembrane proteins found in this study. All data are deposited in a new searchable database for plant phosphorylation sites maintained by PlantsP (http://plantsp.sdsc.edu) that will be updated as the project expands to encompass additional tissues and organelles.
Major histocompatibility complex class II+B7-1+ tumor cells are potent vaccines for stimulating tumor rejection in tumor-bearing mice

Mice carrying large established major histocompatibility complex (MHC) class 1+ sarcoma tumors can be successfully treated by immunization with genetically engineered sarcoma cells transfected with syngeneic MHC class II plus B7-1 genes. This approach is significantly more effective than previously described strategies using cytokine- or B7- transduced tumor cells which are only effective against smaller tumor loads, and which cannot mediate regression of longer-term established tumors. The most efficient tumor rejection occurs if both the class II and B7-1 molecules are coexpressed on the same tumor cell. Immunity induced by immunization with class II+B7-1(+)-transfected sarcoma cells involves CD4+ and CD8+ T cells, suggesting that the increased effectiveness of the transfectants is due to their ability to activate both of these T cell populations.
Inducible nitric oxide synthetase is expressed in adult but not fetal pig pancreatic islets

Abstract: Cytokine‐induced expression of inducible nitric oxide synthetase (iNOS) and production of nitric oxide (NO) by pancreatic islet cells has been suggested as one potential mechanism for beta cell destruction. In this study, we investigated the role of iNOS and NO in islet primary non‐function. Islets were assessed for their function, viability and expression of iNOS. Adult rat and pig islets isolated by collagenase digestion and fetal pig pancreas (FPP) grafts isolated by collagenase digestion or high oxygen culture were transplanted into C57BL6 mice and nude mice. iNOS protein was detected by immunohistochemistry. iNOS protein was found in normal rat and pig pancreas and adult rat and pig islets that were isolated by collagenase digestion and transplanted into either C57BL6 mice or nude mice. iNOS was not detected in fetal pig islet grafts, regardless of whether collagenase was used in the isolation process. In adult pig islet grafts, the presence of iNOS protein correlated with high levels of islet cell apoptosis and primary non‐function. Despite the persistent presence of iNOS in rat islets, there was no evidence that it had a deleterious effect on rat islet viability, or function. Therefore, in isolated adult pig islets, there was a correlation between iNOS expression and apoptosis, suggesting that iNOS activation may be deleterious to the adult pig islets. However, other factors such as the fragility of the islet capsule may be equally important. By contrast, fetal pig islets did not express iNOS and this may be an important reason for their enhanced viability when compared with adult islet tissue.
A comparative study of the dentate gyrus in hippocampal sclerosis in epilepsy and dementia

Aims: Hippocampal sclerosis (HS) is long‐recognized in association with epilepsy (HSE) and more recently in the context of cognitive decline or dementia in the elderly (HSD), in some cases as a component of neurodegenerative diseases, including Alzheimer's disease (AD) and fronto‐temporal lobe dementia (FTLD). There is an increased risk of seizures in AD and spontaneous epileptiform discharges in the dentate gyrus of transgenic AD models; epilepsy can be associated with an age‐accelerated increase in AD‐type pathology and cognitive decline. The convergence between these disease processes could be related to hippocampal pathology. HSE typically shows re‐organization of both excitatory and inhibitory neuronal networks in the dentate gyrus, and is considered to be relevant to hippocampal excitability. We sought to compare the pathology of HSE and HSD, focusing on re‐organization in the dentate gyrus. Methods: In nine post mortem cases with HSE and bilateral damage, 18 HSD and 11 controls we carried out immunostaining for mossy fibres (dynorphin), and interneuronal networks (NPY, calbindin and calretinin) on sections from the mid‐hippocampal body. Fibre sprouting (FS) or loss of expression in the dentate gyrus was semi‐quantitatively graded from grade 0 (normal) to grade 3 (marked alteration). Results: Significantly more re‐organization was seen with all four markers in the HSE than HSD group (P < 0.01). Mild alterations were noted in HSD group with dynorphin (FS in 3 cases), calretinin (FS in 6 cases), NPY (FS in 11 cases) and calbindin (loss in 10 cases). In eight HSD cases, alteration was seen with more than one antibody but in no cases were the highest grades seen. We also noted NPY and, to a lesser extent, calretinin labelling of Hirano bodies in CA1 of AD cases and some older controls, but not in HSE. Conclusion: Reorganization of excitatory and inhibitory networks in the dentate gyrus is more typical of HSE. Subtle alterations in HSD may be a result of increased hippocampal excitability, including unrecognized seizure activity. An unexpected finding was the identification of NPY‐positive Hirano bodies in HSD but not HSE, which may be a consequence of the relative vulnerabilities of interneurons in these conditions.
Wearing lower-body compression garment with medium pressure impaired exercise-induced performance decrement during prolonged running

Objective To investigate the effect of wearing a lower body compression garment (CG) exerting different pressure levels during prolonged running on exercise-induced muscle damage and the inflammatory response. Methods Eight male participants completed three exercise trials in a random order. The exercise consisted of 120 min of uphill running at 60% of VO2max. The exercise trials included 1) wearing a lower-body CG with 30 mmHg pressure [HIGH]; 2) wearing a lower-body CG with 15 mmHg pressure [MED]; and 3) wearing a lower-body garment with < 5 mmHg pressure [CON]. Heart rate (HR), and rate of perceived exertion for respiration and legs were monitored continuously during exercise. Time-course change in jump height was evaluated before and immediately after exercise. Blood samples were collected to determine blood glucose, lactate, serum creatine kinase, myoglobin, free fatty acids, glycerol, cortisol, and plasma interleukin-6 (IL-6) concentrations before exercise, 60 min of the 120 min exercise period, immediately after exercise, and 60 min after exercise. Results Jump height was significantly higher immediately after the exercise in the MED trial compared with that in the HIGH trial (P = 0.04). Mean HR during the 120 min exercise was significantly lower in the MED trial (162 ± 4 bpm) than that in the CON trial (170 ± 4 bpm, P = 0.01). Plasma IL-6 concentrations increased significantly with exercise in all trials, but the area under the curve during exercise was significantly lower in the MED trial (397 ± 58 pg/ml·120 min) compared with that in the CON trial (670 ± 86 pg/ml·120 min, P = 0.04). Conclusion Wearing a lower body CG exerting medium pressure (approximately 15 mmHg) significantly attenuated decrease in jump performance than that with wearing a lower body CG exerting high pressure (approximately 30 mmHg). Furthermore, exercise-induced increases in HR and the inflammatory response were significantly smaller with CG exerted 15mmHg than that with garment exerted < 5 mmHg.
Image compression using self-organization networks

A self-organization neural network architecture is used to implement vector quantization for image compression. A modified self-organization algorithm, which is based on the frequency-sensitive cost function and centroid learning rule, is utilized to construct the codebooks. Performances of this frequency-sensitive self-organization network and a conventional algorithm for vector quantization are compared. The proposed method is quite efficient and can achieve near-optimal results. Good adaptivity for different statistics of source data can also be achieved. >
Leptin Stimulates Neuropeptide Y and Cocaine Amphetamine-Regulated Transcript Coexpressing Neuronal Activity in the Dorsomedial Hypothalamus in Diet-Induced Obese Mice

Neuropeptide Y (NPY) neurons in both the arcuate nucleus of the hypothalamus (ARH) and the dorsomedial hypothalamus (DMH) have been implicated in food intake and obesity. However, while ARH NPY is highly expressed in the lean animal, DMH NPY mRNA expression is observed only after diet-induced obesity (DIO). Furthermore, while ARH NPY neurons are inhibited by leptin, the effect of this adipokine on DMH NPY neurons is unknown. In this study we show that in contrast to the consistent expression in the ARH, DMH NPY mRNA expression was undetectable until after 10 weeks in mice fed a high-fat diet, and peaked at 20 weeks. Surprisingly, electrophysiological experiments demonstrated that leptin directly depolarized and increased the firing rate of DMH NPY neurons in DIO mice. To further differentiate the regulation of DMH and ARH NPY populations, fasting decreased expression of DMH NPY expression, while it increased ARH NPY expression. However, treatment with a leptin receptor antagonist failed to alter DMH NPY expression, indicating that leptin may not be the critical factor regulating mRNA expression. Importantly, we also demonstrated that DMH NPY neurons coexpress cocaine amphetamine-regulated transcript (CART); however, CART mRNA expression in the DMH peaked earlier in the progression of DIO. This study demonstrates novel and important findings. First, NPY and CART are coexpressed in the same neurons within the DMH, and second, leptin stimulates DMH NPY neurons. These studies suggest that during the progression of DIO, there is an unknown signal that drives the expression of the orexigenic NPY signal within the DMH, and that the chronic hyperleptinemia increases the activity of these NPY/CART neurons.
Identification of approved and investigational drugs that inhibit hypoxia-inducible factor-1 signaling

One of the requirements for tumor development is blood supply, most often driven by hypoxia-induced angiogenesis. Hypoxia induces the stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), which induces expression of an angiogenic factor, vascular endothelial growth factor (VEGF). The purpose of this study is to validate a new screening platform combined with orthogonal assays to rapidly identify HIF-1 inhibitors and to evaluate the effectiveness of approved drugs on modulating HIF-1 signaling. We generated an endogenous HIF-1α–NanoLuc luciferase reporter allele in the human HCT116 colon cancer cell line using genome editing and screened a panel of small interfering RNAs (siRNAs) to 960 druggable targets and approximately 2,500 drugs on a quantitative high-throughput screening (qHTS) platform. Selected compounds were further investigated with secondary assays to confirm their anti-HIF activity and to study their mode of action. The qHTS assay identified over 300 drugs that inhibited HIF-1α-NanoLuc expression. The siRNA screening results supported the effectiveness of several target-specific inhibitors. Moreover, the identified HIF-1 inhibitors, such as mycophenolate mofetil, niclosamide, and trametinib, were able to suppress cancer cell proliferation and angiogenesis. Our study indicates that blocking the mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K) pathways effectively inhibits hypoxia-induced HIF-1α accumulation and HIF-1α transactivation and that proteasome inhibitors induce accumulation and decrease transcriptional activity of HIF-1α. These findings underline the importance of developing a battery of robust assay platforms and confirmation studies that focus on endogenous protein targets so that only relevant and reliable data will be taken into pre-clinical and clinical studies.
High expression of N-myc (and STAT) interactor predicts poor prognosis and promotes tumor growth in human glioblastoma

Glioma is the most malignant brain tumor and glioblastoma (GBM) is the most aggressive type. The involvement of N-myc (and STAT) interactor (NMI) in tumorigenesis was sporadically reported but far from elucidation. This study aims to investigate roles of NMI in human glioma. Three independent cohorts, the Chinese tissue microarray (TMA) cohort (N = 209), the Repository for Molecular Brain Neoplasia Data (Rembrandt) cohort (N = 371) and The Cancer Genome Atlas (TCGA) cohort (N = 528 or 396) were employed. Transcriptional or protein levels of NMI expression were significantly increased according to tumor grade in all three cohorts. High expression of NMI predicted significantly unfavorable clinical outcome for GBM patients, which was further determined as an independent prognostic factor. Additionally, expression and prognostic value of NMI were associated with molecular features of GBM including PTEN deletion and EGFR amplification in TCGA cohort. Furthermore, overexpression or depletion of NMI revealed its regulation on G1/S progression and cell proliferation (both in vitro and in vivo), and this effect was partially dependent on STAT1, which interacted with and was regulated by NMI. These data demonstrate that NMI may serve as a novel prognostic biomarker and a potential therapeutic target for glioblastoma.
A Placebo-Controlled Randomized Crossover Trial of the N-Methyl-d-Aspartic Acid Receptor Antagonist, Memantine, in Patients with Chronic Phantom Limb Pain

In the present study we investigated the effect of the N-methyl-d-aspartic acid (NMDA) receptor antagonist memantine (30 mg/d) on the intensity of chronic phantom limb pain (PLP) and cortical reorganization. In 8 patients with chronic PLP, memantine was tested in a placebo-controlled double-blinded crossover trial of 4 wk duration per trial. The intensity of PLP was rated hourly by the patients on a visual analog scale during baseline and both treatment periods. At the same time points, the functional organization of the primary somatosensory cortex (SI) was determined by neuromagnetic source imaging. In comparison to baseline and placebo, the NMDA receptor antagonist had no effect on the intensity of chronic PLP. In none of the periods were significant changes in the functional organization of SI observed. Although the conclusions regarding the clinical effect are limited because of the small sample size, the data indicate that in the studied dosage the NMDA receptor antagonist memantine is ineffective in the treatment of chronic PLP and is also ineffective for the reduction of associated neural plasticity in the primary SI.
Special Populations: Adolescents Longitudinal Relations Among Negative Affect, Substance Use, and Peer Deviance During the Transition From Middle to Late Adolescence

The transition from middle to late adolescence brings challenges that increase risk for emotional, behavioral, and social problems. The nature of the associations among these types of problems is poorly understood. This National Institute on Drug Abuse–funded study examined longitudinal relations among negative affect, substance use, and peer deviance from ages 16 to 18 years. Multiwave youth and parent questionnaire data collected from 429 sixth graders (222 girls) and their families residing in the rural Midwestern United States and recruited in 1993 were analyzed via structural equation modeling. Consistent with the self-medication hypothesis, negative affect statistically predicted increased substance use over time. Implications for theory and prevention are discussed and the study’s limitations are noted.
Word and Nonword Repetition Abilities in Spanish Language: Longitudinal Evidence from Typically Developing and Late Talking Children

Abstract This longitudinal study examined the early word and nonword repetition abilities of monolingual Spanish speaking children. We explored the role that word status, word length, and time play in repetition performance of children with different vocabulary levels. We also examined the predictive value of vocabulary level in repetition abilities. Thirty-seven children participated in this study: 15 late talkers and 22 typically developing children. Families completed the Spanish version of the MacArthur Communicative Developmental Inventory (MCDI) at age 2; children performed a word and nonword repetition task at three different moments, with a temporal interval of 6 months between Time 1 and Time 2, and eight months between Time 2 and Time 3, periods during which linguistic development takes place. We found significant effects for word status, word length, vocabulary level and time: words are repeated better than nonwords; one syllable items are easier to repeat than two and three syllable ones; the performance of late talking children is lower compared to typically developing children throughout the study; and repetition abilities improve longitudinally. In addition, early vocabulary level predicts subsequent repetition abilities and early nonword repetition abilities predict future nonword repetition performance.