Miracle-dz/UniFAR-FTUs huggingface dataset:
Estrogen‐mediated downregulation of CD24 in breast cancer cells

We have previously reported on the relevance of the prevalence of CD44+/CD24−/low cells in primary breast tumors. To study regulation of CD24, we queried a number of publicly available expression array studies in breast cancer cells and found that CD24 was downregulated upon estrogen treatment. We confirmed this estrogen‐mediated repression of CD24 mRNA by quantitative real‐time PCR in MCF7, T47D and ZR75‐1 cells. Repression was also seen at the protein level as measured by flow cytometry. CD24 was not downregulated in the ERα negative MDA‐MB‐231 cells suggesting that ERα was necessary. This was further confirmed by ERα silencing in MCF7 cells resulting in increased CD24 levels and by reintroduction of ERα into C4‐12 cells resulting in decreased CD24 levels. Estrogen treatment did not alter half‐life of CD24 mRNA and new protein synthesis was not essential for repression, suggesting a primary transcriptional effect. Histone deacetylase inhibition by Trichostatin A completely abolished the repression, but decrease of the ERα corepressors NCoR, LCoR, RIP140, silencing mediator of retinoid and thyroid hormone receptors, SAFB1 and SAFB2 by siRNA or overexpression of SAFB2, NCoR and silencing mediator of retinoid and thyroid hormone receptors had no effect. In silico promoter analyses led to the identification of two estrogen responsive elements in the CD24 promoter, one of which was able to bind ERα as shown by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Together, our results show that CD24 is repressed by estrogen and that this repression is a direct transcriptional effect depending on ERα and histone deacetylases. © 2008 Wiley‐Liss, Inc.
Genetic relatedness in wintering groups of house sparrows (Passer domesticus)

Social behaviour of group‐living animals is often influenced by the relatedness of individuals, thus understanding the genetic structure of groups is important for the interpretation of costs and benefits of social interactions. In this study, we investigated genetic relatedness in feeding aggregations of free‐living house sparrows (Passer domesticus) during the nonbreeding season. This species is a frequent model system for studies of social behaviour (e.g. aggression, social foraging), but we lack adequate information on the kin structure of sparrow flocks. During two winters, we ringed and observed sparrows at feeding stations, and used resightings to identify stable flock‐members and to calculate association indices between birds. We genotyped the birds using seven highly polymorphic microsatellite loci, and estimated pairwise relatedness coefficients and relatedness categories (close kin vs. unrelated) by maximum likelihood method. We found that most birds were unrelated to each other in the flocks (mean ± SE relatedness coefficient: 0.06 ± 0.002), although most individuals had at least a few close relatives in their home flock (14.3 ± 0.6% of flock‐mates). Pairwise association between individuals was not significantly related to their genetic relatedness. Furthermore, there was no difference between within‐flock vs. between‐flock relatedness, and birds had similar proportions of close kin within and outside their home flock. Finally, relatedness among members of different flocks was unrelated to the distance between their flocks. Thus, sparrow flocks were not characterized by association of relatives, nevertheless the presence of some close kin may provide opportunity for kin‐biased behaviours to evolve.
Subpixel subtle motion estimation of micro-expressions multiclass classification

Communication between one individual and another can be delivered in different ways, not only through speech, writing and body motions. Communication can also be delivered through basic emotions one feels through visible facial expressions. Facial expressions displayed in the forms of emotional expressions can be demonstrated briefly or quickly, which is known as micro-expression. The subtle motion of micro facial expression in every exchange makes many people find it difficult to identify and recognize the ongoing emotion. Therefore, this study proposes the recognition of micro-expression emotions with estimated subtle motion in the image sequence based on onset-frame, apex-frame, and offset-frame for feature extraction. The method used for feature extraction are the combination of Block Matching Algorithm with Taylor Series Approximation referred to as Subpixel Subtle Motion Estimation (SME). Multiclass Classification process using Multilayer Perceptron (MLP) Backpropagation and Support Vector Machine (SVM) as a comparison. The evaluation results show the best accuracy 85.07%, with the Mean Absolute Error 0.0597 and Root Mean Square Error 0.2443.
Oral minocycline in the treatment of vitiligo – A preliminary study

For effective treatment of vitiligo, it is as important to arrest the progression of the disease, as it is to induce repigmentation. Epidermal oxidative stress has been documented in vitiligo patients, and there is much support for a free‐radical‐mediated damage as an initial pathogenic event in melanocyte degeneration in vitiligo. Minocycline possesses a wide repertoire of anti‐inflammatory, immunomodulatory, and free‐radical scavenging actions in addition to their well‐characterized antimicrobial effects. Recently, it has been shown that minocycline can rescue melanocytes from oxidative stress in vitro. Minocycline 100 mg was tried in this study to elucidate its role in arresting disease activity. Thirty‐two patients with gradually progressive (slow spreading) vitiligo were enrolled in this study. The patients were advised to take minocycline 100 mg once daily. In 29 patients, the progression of the disease was arrested, and only three patients showed development of new lesions and/or enlargement of existing lesions. Ten patients showed arrest of further depigmentation after 4 weeks of treatment. Thus, minocycline offers a unique and potentially powerful approach to the management of arresting the activity of the disease. The present study showed the effectiveness of minocycline in the treatment of vitiligo. Further controlled studies should be undertaken to confirm its efficacy.
Extreme Obesity and Postcesarean Maternal Complications

OBJECTIVE: To estimate the association of obesity and extreme obesity with maternal complications after cesarean delivery. METHODS: This was a secondary cohort analysis of a randomized controlled trial. The parent study was designed to estimate the effect of supplemental oxygen on postcesarean infectious morbidity. Because the study intervention had no effect, study groups were combined as a cohort. For this secondary analysis, the exposure was obesity, stratified as normal or overweight (body mass index [BMI] less than 30), obese (BMI 30–45), or extremely obese (BMI higher than 45). The primary outcome was a composite of wound infection and endometritis. Secondary outcomes included wound infection, endometritis, wound opening, hematoma or seroma, and emergency department visit. We performed unadjusted and multivariable logistic regression analyses. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) are reported. RESULTS: We included 585 women in the analysis. Eighty-five patients (14.5%) had BMIs higher than 45. Rates of black race, chronic hypertension, diabetes, and gestational diabetes increased and operative duration increased with increasing obesity severity. Obese patients were more likely to have a cesarean delivery after labor and have a vertical skin incision or classical uterine incision. After controlling for confounders, extremely obese patients had a twofold to fourfold increase in postoperative complications, including the primary infectious outcome (18.8%, adjusted OR 2.7, CI 1.2–6.1), wound infection (18.8%, adjusted OR 3.4, CI 1.4–8.0), and emergency department visit (23.1%, adjusted OR 2.2, CI 1.03–4.9). CONCLUSION: Maternal extreme obesity is associated with a considerable increase in postcesarean wound complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials. gov, NCT00602603. LEVEL OF EVIDENCE: II
Genitives in Early English: Typology and Evidence

1. Genitive Case and the Typology of Case Marking 2. Genitive Case and the Germanic Languages: Overview 3. Genitive Case in Old English 4. Genitive Case in Middle English 5. The Possessor Doubling Constructions in the Germanic Languages 6. The Separated Genitive in English 7. Determiners and Possessives 8. Conclusions Appendix References
TNASP: A Transformer-based NAS Predictor with a Self-evolution Framework

Predictor-based Neural Architecture Search (NAS) continues to be an important topic because it aims to mitigate the time-consuming search procedure of traditional NAS methods. A promising performance predictor determines the quality of ﬁnal searched models in predictor-based NAS methods. Most existing predictor-based methodologies train model-based predictors under a proxy dataset setting, which may suffer from the accuracy decline and the generalization problem, mainly due to their poor abilities to represent spatial topology information of the graph structure data. Besides the poor encoding for spatial topology information, these works did not take advantage of the temporal information such as historical evaluations during training. Thus, we propose a Transformer-based NAS performance predictor, associated with a Laplacian matrix based positional encoding strategy, which better represents topology information and achieves better performance than previous state-of-the-art methods on NAS-Bench-101, NAS-Bench-201, and DARTS search space. Furthermore, we also propose a self-evolution framework that can fully utilize temporal information as guidance. This framework iteratively involves previous evaluation information as constraints into current optimization iteration, thus further improving the performance of our predictor. Such framework is model-agnostic, thus can enhance performance on various backbone structures for the prediction task. Our proposed method helped us rank 2nd among all teams in CVPR 2021 NAS Competition Track 2: Performance Prediction Track.
BRCA1 mutation analysis in breast/ovarian cancer families from Greece.

Germline mutations in BRCA1 gene account for varying proportions of breast/ovarian cancer families, and demonstrate considerable variation in mutational spectra coincident with ethnic and geographical diversity. We have screened for mutations the entire coding sequence of BRCA1 in 30 breast/ovarian cancer women with family history of two or more cases of breast cancer under age 50 and/or ovarian cancer at any age. Genomic DNA from patient was initially analyzed for truncating mutations in exon 11 with PTT followed by DNA sequencing. In the cases where no frameshift mutation was observed in exon 11, all other exons were screened with direct sequencing. Two novel (3099delT, 3277insG) and three already described (3741insA, 1623del5-TTAAA, 5382insC-twice) truncating mutations were identified. In addition, 6 point mutations (L771L, P871L, E1038G, K1183R, S1436S, S1613G) which are already classified as polymorphisms were identified. Three unclassified intronic variants (IVS16-68 G>A, IVS16-92 G>A, IVS18+65G>A) were also detected. These results show that BRCA1 deleterious mutations are present in a fraction (20%) of Greek breast/ovarian cancer families similar to other European countries. Mutations were detected in high- (>/=3 members) as well as in moderate-risk (2 members) families. This is the first report of BRCA1 mutation analysis in Greece.
Ubiquitin C-terminal hydrolase-L1 (UCH-L1) as a therapeutic and diagnostic target in neurodegeneration, neurotrauma and neuro-injuries

ABSTRACT Introduction: Since its discovery as a major CNS-abundant protein 25 years ago, Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in regulating brain protein metabolism, by coupling to the proteasome pathway of protein degradation. Areas covered: UCH-L1 is implicated in both familial and sporadic Parkinson disease and other chronic neurodegenerative diseases. Also, UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity coupled with the gain of proteinopathy function are linked to neurodegeneration such as Parkinsonism and Alzheimer’s disease. In addition, certain post-translational modifications of UCH-L1 might promote the conversion of the cytosolic UCH-L1(C) to the membrane-associated UCH-L1(M) form, which seems to play a role in alpha-synucleinopathy formation. Thus, targeting the conversion of UCH-L1(C) to the UCH-L1(M) form might be the key to developing therapies for neurodegenerative diseases linked to UCH-L1. In parallel, UCH-L1 is also emerging as a promising neuron-derived biomarker for traumatic brain injury, ischemic and homographic stroke, pediatric hypoxic-ischemic encephalopathy, spinal cord injury, epileptic seizure and cardiac arrest. This shows that UCH-L1 has strong potential as a robust and universal biomarker target for various forms of CNS injury.
Approaches to isolation and molecular characterization of disseminated tumor cells

Micrometastatic cells in the bone marrow, now usually referred to as “disseminated tumor cells (DTCs)”, can be detected in early stage cancer patients. It has been hypothesized that DTCs represent key intermediates in the metastatic process as possible precursors of bone and visceral metastases, and are indicators of metastatic potential. Indeed, multiple clinical studies have unequivocally demonstrated the prognostic value of these cells in breast and other cancers, as DTCs have been associated with adverse outcomes, including inferior overall and disease-free survival. Despite this established clinical significance, the molecular nature of DTCs remains elusive. The complexity of the bone marrow poses a unique challenge in the isolation and direct characterization of these rare cells. However, recent advances in rare-cell technology along with technical improvements in analyzing limited cell inputs have enabled the molecular profiling of DTCs. In this review, we discuss research featuring the isolation and genomic analysis of DTCs. Emerging work on the molecular characterization of DTCs is now providing new insights into the biology of these cells.
HMO market penetration and hospital cost inflation in California.

UNLABELLED OBJECTIVE--Health maintenance organizations (HMOs) have stimulated price competition in California hospital markets since 1983, when the state legislature eliminated barriers to selective contracting by conventional health insurance plans. This study measures the impact of HMO-induced price competition on the rate of inflation in average cost per admission for 298 private, non-HMO hospitals between 1982 and 1988. DATA--HMO market penetration was calculated using discharge abstract data on insurance coverage, ZIP code of residence, and hospital of choice for 3.35 million patients in 1983 and 3.41 million patients in 1988. Data on hospital characteristics were obtained from the American Hospital Association and other sources. RESULTS -HMO coverage grew from an average of 8.3% of all admissions in local hospital markets in 1983 to 17.0% of all admissions in 1988. The average rate of growth in costs per admission between 1982 and 1988 was 9.4% lower in markets with relatively high HMO penetration compared with markets with relatively low HMO penetration (95% confidence interval, 5.2 to 13.8). Cost savings for these 298 hospitals are estimated at $1.04 billion for 1988. CONCLUSION--Price competition between HMOs and conventional health insurers can significantly reduce hospital cost inflation if legislative barriers to selective contracting are removed. The impact of competition in California was modest, however, when evaluated in terms of the 74.5% average rate of California hospital cost inflation during these years.
Neuroanatomical correlates of happiness, sadness, and disgust.

OBJECTIVE Happiness, sadness, and disgust are three emotions that differ in their valence (positive or negative) and associated action tendencies (approach or withdrawal). This study was designed to investigate the neuroanatomical correlates of these discrete emotions. METHOD Twelve healthy female subjects were studied. Positron emission tomography and [15O]H2O were used to measure regional brain activity. There were 12 conditions per subject: happiness, sadness, and disgust and three control conditions, each induced by film and recall. Emotion and control tasks were alternated throughout. Condition order was pseudo-randomized and counterbalanced across subjects. Analyses focused on brain activity patterns for each emotion when combining film and recall data. RESULTS Happiness, sadness, and disgust were each associated with increases in activity in the thalamus and medial prefrontal cortex (Brodmann's area 9). These three emotions were also associated with activation of anterior and posterior temporal structures, primarily when induced by film. Recalled sadness was associated with increased activation in the anterior insula. Happiness was distinguished from sadness by greater activity in the vicinity of ventral mesial frontal cortex. CONCLUSIONS While this study should be considered preliminary, it identifies regions of the brain that participate in happiness, sadness, and disgust, regions that distinguish between positive and negative emotions, and regions that depend on both the elicitor and valence of emotion or their interaction.
Relation of inflammatory markers with both presence and severity of hyperemesis gravidarum.

OBJECTIVES The aim of our study is to determine the newly introduced systemic inflammation marker, neutrophil lymphocyte ratio (NLR) in hyperemesis gravidarum (HG) patients and to investigate the association between severity of the disease and NLR. METHOD The study population consisted of 55 pregnant patients with HG and 50 pregnant women without complaints matched for gestational age as a control group. The HG patients were grouped as mild (n = 16), moderate (n = 19) and severe (n = 20) according to Modified Pregnancy- Unique Quantification of Emesis and Nausea Scoring Index Questionnaire. Furthermore, hsCRP, neutrophils, lymphocytes, and NLR were evaluated with complete blood count. RESULTS The HG group had significantly higher NLR values compared to the control group (2.69 +/- 1.81 vs 1.97 +/- 1.34, p = 0.004). HsCRP levels were significantly higher among HG patients compared to the control group (1.95 +/- 2.2 vs 0.56 +/- 0.30, p < 0.001). The subgroup analysis revealed statistically significant increases in NLR and hsCRP values with increased HG severity (p < 0.001, p = 0.002). The correlation analysis demonstrated a strong correlation between NLR and hsCRP levels (r: 0.703, p < 0.001). CONCLUSION Our study results showed that NLR and hsCRP levels are increased in HG disease compared to gestational age matched control group subjects. Furthermore, NLR and hsCRP values are correlated with severity of disease. NLR could be used as a marker for both presence and severity of hyperemesis gravidarum.
Folate and long-chain polyunsaturated fatty acid supplementation during pregnancy has long-term effects on the attention system of 8.5-y-old offspring: a randomized controlled trial.

BACKGROUND During fetal and perinatal periods, many nutrients, such as long-chain polyunsaturated fatty acids [contained in fish oil (FO)] and folate, are important in achieving normal brain development. Several studies have shown the benefits of early nutrition on children's neurocognitive development. However, the evidence with regard to the attention system is scarce. OBJECTIVES The aim of this study was to analyze the long-term effects of FO, 5-methyltetrahydrofolate (5-MTHF), or FO+5-MTHF prenatal supplementation on attention networks. DESIGN Participants were 136 children born to mothers from the NUHEAL (Nutraceuticals for a Healthy Life) project (randomly assigned to receive FO and/or 5-MTHF or placebo prenatal supplementation) who were recalled for a new examination 8.5 y later. The response conflict-resolution ability (using congruent and incongruent conditions)), alerting, and spatial orienting of attention were evaluated with behavioral measures (Attention Network Test), electroencephalography/event-related potentials (ERPs), and standardized low-resolution brain electromagnetic tomography (sLORETA). RESULTS Children born to mothers supplemented with 5-MTHF alone solved the response conflict more quickly than did the placebo and the FO+5-MTHF groups (all P < 0.05). Differences between ERP amplitudes for the conflict conditions were also observed. sLORETA analysis showed higher activation of the right midcingulate cortex for the incongruent condition. In addition, a significant slowing down of response speed depending on the warning cue in the 5-MTHF and FO groups was observed. CONCLUSIONS Folate supplementation during pregnancy, rather than FO or FO+5-MTHF supplementation, improves children's ability to solve response conflicts. This advantage seems to be based on the higher activation of the midcingulate cortex, indicating that early nutrition influences the functionality of specific brain areas involved in executive functions. This trial was registered at clinicaltrials.gov as NCT01180933.
Selection Bias and Confounding in Case-Crossover Analyses of Environmental Time-Series Data

The case-crossover study design is a popular analytic tool for estimating the effects of triggers of acute outcomes by environmental exposures. Although this approach controls for time-invariant confounders by design, it may allow for selection bias and confounding by time-varying factors. We conducted a simulation study of the sensitivity of the symmetric bidirectional case-crossover design to time-varying patterns in exposure and outcome. We identified the effects of selection bias and confounding on symmetric bidirectional case-crossover results and offer strategies to eliminate or reduce these biases. Selection bias results when exposure in the reference periods is not identically representative of exposure in the hazard periods, even when the distribution of exposure is stationary. This bias can be estimated and removed. Selection bias also occurs when the distribution of exposure is nonstationary, but the adjusted symmetric bidirectional case-crossover methodology substantially controls for this. Confounding results from a common temporal pattern in the exposure and the outcome time series, but can also be the result of patterns in exposure and outcome that, although asymptotically uncorrelated, are correlated at finite series lengths. All three biases are reduced by choosing shorter referent-spacing lengths. This effect is illustrated using data on air pollution and daily deaths in Chicago.