Miracle-dz/UniFAR-FTUs huggingface dataset:
Progression of lumbar disc degeneration over a decade: a heritability study

Objectives Lumbar disc degeneration (LDD) is prevalent, age-related and contributes to low back pain. Cross-sectional LDD as determined by MRI scan is known to be highly heritable. The authors postulated that the rate of progression might also be controlled by genetic factors. Methods A 10-year follow-up of MRI-determined LDD was performed in 234 pairs of twin volunteers in the UK and Australia, comprising 90 monozygotic pairs and 144 dizygotic same-sex twin pairs. Of the total sample, 95% were female. The mean age at baseline was 53.3 years (range 32.3–69.5). The rate of progression was calculated and, because the effect of age was non-linear, the sample was divided into age strata and heritability estimated for each trait's progression. Results All MRI-determined traits worsened significantly over the period of follow-up (p<0.0001 for each). Change in disc height was not heritable at any age while posterior disc bulge was heritable across all age categories (range 28–53%), with higher heritability in those over 60 years. Change in disc signal intensity and anterior osteophytes were found to be heritable only in those aged under 50 years at baseline (heritability estimates 76% (95% CI 44% to 100%) and 74% (42% to 100%), respectively). Conclusions Longitudinal change in LDD traits is heritable for all traits except disc height, but there is a significant influence of age, which varies across traits. Future studies to define the genetic variants influencing LDD progression should examine MRI traits individually and in women should focus on those under 50 years of age.
Genome Streamlining Results in Loss of Robustness of the Circadian Clock in the Marine Cyanobacterium Prochlorococcus marinus PCC 9511

The core oscillator of the circadian clock in cyanobacteria consists of 3 proteins, KaiA, KaiB, and KaiC. All 3 have previously been shown to be essential for clock function. Accordingly, most cyanobacteria possess at least 1 copy of each kai gene. One exception is the marine genus Prochlorococcus, which we suggest here has suffered a stepwise deletion of the kaiA gene, together with significant genome streamlining. Nevertheless, natural Prochlorococcus populations and laboratory cultures are strongly synchronized by the alternation of day and night, displaying 24-h rhythms in DNA replication, with a temporal succession of G1, S, and G2-like cell cycle phases. Using quantitative real-time PCR, we show here that in Prochlorococcus marinus PCC 9511, the mRNA levels of the clock genes kaiB and kaiC, as well as a few other selected genes including psbA, also displayed marked diel variations when cultures were kept under a light-dark rhythm. However, both cell cycle and psbA gene expression rhythms damped very rapidly under continuous light. In the closely related Synechococcus sp. WH8102, which possesses all 3 kai genes, cell cycle rhythms persisted over several days, in agreement with established cyanobacterial models. These data indicate a correlation between the loss of kaiA and a loss of robustness in the endogenous oscillator of Prochlorococcus and raise questions about how a basic KaiBC system may function and through which mechanism the daily “lights-on” and “lights-off” signal could be mediated.
A Modified Efficient Certificateless Signature Scheme without Bilinear Pairings

Certificateless public key cryptography was proposed to solve the key escrow problem in identity-based public key cryptography. Namely, a user's full private key must be comprised of a partial private key which is provided by the key generation center and a secret value which is chosen by the user. Thus the key generation center can no longer acquire each user's full private key by itself. In 2014, Yeh et al. proposed an efficient certificateless public key signature scheme without bilinear pairings. They also showed their scheme is secure against super adversary under the hardness of breaking discrete logarithm problem in the random model. In this paper, we modify Yeh et al.'s scheme to obtain a new scheme which is more practical than theirs. And our modified scheme can achieve the same security level as Yeh et al.'s scheme under the hardness of breaking discrete logarithm problem in the random model.
Neuroendocrine-Immune Surveillance of Osteosarcoma: Emerging Hypothesis

Osteosarcoma is a bone-forming cancer predominantly found in children and adolescents more often than in adults. Osteosarcoma of the gnathic apparatus is relatively rare in the young population, and this condition becomes a concern of clinical dentists for predominantly the middle-aged and aging patient groups. Osteosarcomas are invaded by lymphocytes, which exhibit signs of activation. The immune processes that are engaged within the malignant bone matrix involve the production of cytokines, which regulate the process of apoptotic programed cell death. This paper discusses the mechanisms by which apoptosis of osteosarcoma cells is modulated by the neuroendocrine-immune system, and potential physiological implications.
Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer.

CONTEXT Adjuvant chemotherapy improves survival for patients with local-regional breast cancer, but healthy older patients at high risk of recurrence are frequently not offered adjuvant chemotherapy, and the benefit of adjuvant chemotherapy in older patients is uncertain. OBJECTIVE To compare the benefits and toxic effects of adjuvant chemotherapy among breast cancer patients in age groups of 50 years or younger, 51 to 64 years, and 65 years or older. DESIGN AND SETTING Retrospective review of data from 4 randomized trials that accrued patients from academic and community medical centers between 1975 and 1999. Median follow-up for all patients was 9.6 years. All trials randomized patients to different regimens, doses, schedules, and durations of chemotherapy and all had a treatment arm with doses or schedules that were regarded to be "high" and potentially more toxic. PATIENTS A total of 6487 women with lymph node-positive breast cancer; 542 (8%) patients were 65 years or older and 159 (2%) were 70 years or older. MAIN OUTCOME MEASURE Comparison of disease-free survival, overall survival, and treatment-related mortality among different age groups. RESULTS Multivariate analysis showed that smaller tumor size, fewer positive lymph nodes, more chemotherapy, and tamoxifen use were all significantly (P<.001) related to longer disease-free and overall survival. There was no association between age and disease-free survival. Overall survival was significantly (P<.001) worse for patients aged 65 or older because of death from causes other than breast cancer. Thirty-three deaths (0.5% of all patients) were attributed to treatment, and older women had higher treatment-related mortality. Older women and younger women derived similar reductions in breast cancer mortality and recurrence from regimens containing more chemotherapy. CONCLUSION Age alone should not be a contraindication to the use of optimal chemotherapy regimens in older women who are in good general health.
BALB/c alleles at modifier loci increase the severity of the maternal effect of the "DDK syndrome".

The Om locus was first described in the DDK inbred mouse strain: DDK mice carry a mutation at Om resulting in a parental effect lethality of F(1) embryos. When DDK females are mated with males of other (non-DDK) inbred strains, e.g., BALB/c, they exhibit a low fertility, whereas the reciprocal cross, non-DDK females x DDK males, is fertile (as is the DDK intrastrain cross). The low fertility is due to the death of (DDK x non-DDK)F(1) embryos at the late-morula to blastocyst stage, which is referred to as the "DDK syndrome. " The death of these F(1) embryos is caused by an incompatibility between a DDK maternal factor and the non-DDK paternal pronucleus. Previous genetic studies showed that F(1) mice have an intermediate phenotype compared to parental strains: crosses between F(1) females and non-DDK males are semisterile, as are crosses between DDK females and F(1) males. In the present studies, we have examined the properties of mice heterozygous for BALB/c and DDK Om alleles on an essentially BALB/c genetic background. Surprisingly, we found that the females are quasi-sterile when mated with BALB/c males and, thus, present a phenotype similar to DDK females. These results indicate that BALB/c alleles at modifier loci increase the severity of the DDK syndrome.
Cadmium and Proliferation in Human Uterine Leiomyoma Cells: Evidence of a Role for EGFR/MAPK Pathways but Not Classical Estrogen Receptor Pathways

Background: It has been proposed that cadmium (Cd) is an environmental “metalloestrogen” and that its action is mediated via the estrogen receptor (ER). Cd mimics the effects of estrogen in the rat uterus, and blood Cd concentrations positively correlate with ER levels in uteri of women with fibroids. Objectives: In the present study we explored whether Cd could stimulate proliferation of estrogen-responsive human uterine leiomyoma (ht-UtLM) cells and uterine smooth muscle cells (ht-UtSMCs) through classical interactions with ERα and ERβ, or by nongenomic mechanisms. Methods: We used estrogen response element (ERE) reporters, phosphorylated receptor tyrosine kinase arrays, Western blot analysis, estrogen binding, and cell proliferation assays to evaluate the effects of Cd on ht-UtLM cells and ht-UtSMCs. Results: Cd stimulated growth of both cell types at lower concentrations and inhibited growth at higher concentrations (≥ 50 μM). Cd did not significantly bind to ERα or ERβ, nor did it show transactivation in both cell types transiently transfected with ERE reporter genes. However, in both cells types, Cd (0.1 μM and 10 μM) activated p44/42 MAPK (ERK1/2), and a MAPK inhibitor (PD98059) abrogated Cd-induced cell proliferation. Cd in ht-UtLM cells, but not in ht-UtSMCs, activated the growth factor receptors EGFR, HGFR, and VEGF-R1 upstream of MAPK. Additional studies in ht-UtLM cells showed that AG1478, an EGFR inhibitor, abolished Cd-induced phosphorylation of EGFR and MAPK. Conclusions: Our results show that low concentrations of Cd stimulated cell proliferation in estrogen-responsive uterine cells by nongenomic activation of MAPK, but not through classical ER-mediated pathways. Citation: Gao X, Yu L, Moore AB, Kissling GE, Waalkes MP, Dixon D. 2015. Cadmium and proliferation in human uterine leiomyoma cells: evidence of a role for EGFR/MAPK pathways but not classical estrogen receptor pathways. Environ Health Perspect 123:331–336; http://dx.doi. org/10.1289/ehp.1408234
Multiple Subclass Pattern Recognition: A Maximin Correlation Approach

This paper addresses a correlation based nearest neighbor pattern recognition problem where each class is given as a collection of subclass templates. The recognition is performed in two stages. In the first stage the class is determined. Templates for this stage are created using the subclass templates. Assignment into subclasses occurs in the second stage. This two stage approach may be used to accelerate template matching. In particular, the second stage may be omitted when only the class needs to be determined. The authors present a method for optimal aggregation of subclass templates into class templates. For each class, the new template is optimal in that it maximizes the worst case (i.e. minimum) correlation with its subclass templates. An algorithm which solves this maximin optimization problem is presented and its correctness is proved. In addition, test results are provided, indicating that the algorithm's execution time is polynomial in the number of subclass templates. The authors show tight bounds on the maximin correlation. The bounds are functions only of the number of original subclass templates and the minimum element in their correlation matrix. The algorithm is demonstrated on a multifont optical character recognition problem. >
Process backup in producer-consumer systems

System state restoration after detection of an error is discussed for producer-consumer systems, with emphasis on the control of the domino effect. Recovery primitives MARK, RESTORE, and PURGE are proposed that, in conjunction with the use of SEND-RECEIVE interprocess communication primitives, allow bounds to be placed on the amount of unnecessary restoration that can occur as a result of system state restoration.
Biotransformation of the Mycotoxin Deoxynivalenol in Fusarium Resistant and Susceptible Near Isogenic Wheat Lines

In this study, a total of nine different biotransformation products of the Fusarium mycotoxin deoxynivalenol (DON) formed in wheat during detoxification of the toxin are characterized by liquid chromatography—high resolution mass spectrometry (LC-HRMS). The detected metabolites suggest that DON is conjugated to endogenous metabolites via two major metabolism routes, namely 1) glucosylation (DON-3-glucoside, DON-di-hexoside, 15-acetyl-DON-3-glucoside, DON-malonylglucoside) and 2) glutathione conjugation (DON-S-glutathione, “DON-2H”-S-glutathione, DON-S-cysteinyl-glycine and DON-S-cysteine). Furthermore, conjugation of DON to a putative sugar alcohol (hexitol) was found. A molar mass balance for the cultivar ‘Remus’ treated with 1 mg DON revealed that under the test conditions approximately 15% of the added DON were transformed into DON-3-glucoside and another 19% were transformed to the remaining eight biotransformation products or irreversibly bound to the plant matrix. Additionally, metabolite abundance was monitored as a function of time for each DON derivative and was established for six DON treated wheat lines (1 mg/ear) differing in resistance quantitative trait loci (QTL) Fhb1 and/or Qfhs.ifa-5A. All cultivars carrying QTL Fhb1 showed similar metabolism kinetics: Formation of DON-Glc was faster, while DON-GSH production was less efficient compared to cultivars which lacked the resistance QTL Fhb1. Moreover, all wheat lines harboring Fhb1 showed significantly elevated D3G/DON abundance ratios.
Establishment of a Stringent Large Animal Model of Insulin-Dependent Diabetes for Islet Autotransplantation: Combination of Pancreatectomy and Streptozotocin

Objective A stringent porcine islet autograft diabetes model was developed to enable the assessment of autoislet safety and efficacy in either portal vein or an extrahepatic site. Methods A 95% pancreatectomy was performed preserving the pancreaticoduodenal arcade; however, glycemic control was still maintained at 3.3 ± 0.3 days (mean ± SEM), shown by euglycemic fasting blood glucose levels of 4.9 ± 0.8 mmol/L (mean ± SEM, n = 3). To reduce surgical complications and eliminate remaining islets, pigs were dosed intravenously after a modified 90% pancreatectomy, with 150-mg/kg streptozotocin, producing a diabetic state (18.9 ± 1.8 mmol/L [mean ± SEM], n = 8; P < 0.001) within 2.0 ± 0.9 days (mean ± SEM). Results Animals presented with sustained hyperglycemia, failing a glucose challenge test 12 weeks after diabetic induction, and showed no stimulated C-peptide secretion compared to nondiabetic controls (baseline: 0.479 ± 0.080 ng/mL [mean ± SEM] vs after procedure: 0.219 ± 0.055 ng/mL [mean ± SEM], P = 0.02). Diabetic animals were maintained on daily insulin. Despite an initial decline in body weight acutely after pancreatectomy and streptozotocin administration, the mean body weight increased after induction over the approximately 88-day study, indicating that the animals were in good health. Conclusion This stringent porcine model of diabetic induction should be used to assess autograft transplantation safety and efficacy.
Fixed budget pooling strategies based on fusion methods

The empirical nature of Information Retrieval (IR) mandates strong experimental practices. The Cranfield/TREC evaluation paradigm represents a keystone of such experimental practices. Within this paradigm, the generation of relevance judgments has been the subject of intense scientific investigation. This is because, on one hand, consistent, precise and numerous judgements are key to reduce evaluation uncertainty and test collection bias; on the other hand, however, relevance judgements are costly to collect. The selection of which documents to judge for relevance (known as pooling) has therefore great impact in IR evaluation. In this paper, we contribute a set of 8 novel pooling strategies based on retrieval fusion methods. We show that the choice of the pooling strategy has significant effects on the cost needed to obtain an unbiased test collection; we also identify the best performing pooling strategy according to three evaluation measure.
Using morphology towards better large-vocabulary speech recognition systems

To guarantee unrestricted natural language processing, state-of-the-art speech recognition systems require huge dictionaries that increase search space and result in performance degradations. This is especially true for languages where there do exist a large number of inflections and compound words such as German, Spanish, etc. One way to keep up decent recognition results with increasing vocabulary is the use of other base units than simply words. Different decomposition methods originally based on morphological decomposition for the German language are compared. Not only do they counteract the immense vocabulary growth with an increasing amount of training data, also the rate of out-of-vocabulary words, which worsens recognition performance significantly in German, is decreased. A smaller dictionary also leads to 30 K speed improvement during the recognition process. Moreover even if the amount of available training data is quite huge it is often not enough to guarantee robust language model estimations, whereas morphem-based models are capable to do so.
Robust Speaker Identification in Noisy and Reverberant Conditions

Robustness of speaker recognition systems is crucial for real-world applications, which typically contain both additive noise and room reverberation. However, the combined effects of additive noise and convolutive reverberation have been rarely studied in speaker identification (SID). This paper addresses this issue in two phases. We first remove background noise through binary masking using a deep neural network classifier. Then we perform robust SID with speaker models trained in selected reverberant conditions, on the basis of bounded marginalization and direct masking. Evaluation results show that the proposed system substantially improves SID performance over related systems in a wide range of reverberation time and signal-to-noise ratios.
Genome, diversity, and origins: the Y chromosome as a storyteller.

Analysis of human genome variation may focus on one of two possible goals: understanding the genome region under study or solving historical and evolutionary questions specific to the population(s) analyzed. Understanding of variation of a given genome region has a genetic interest because it is a consequence of the dynamics of the genome and thus the evolutionary forces (mutation, selection in its varieties, drift, recombination, … ) may be understood. It is thus a way to understand the mechanisms that produce variation in the genome. On the other hand, when genetic variation is being analyzed, random individuals from specific populations offer the possibility to trace back their origin beyond the limitation of the genome region sampled. The goal then may be the evolutionary reconstitution of specific populations or, for a global sampling, the origin of our species. The underlying idea is very simple: if we are able to trace back the coalescence of genomic regions from an ample worldwide sample, we can infer the phylogeny of humans. The rationale can be sketched as follows:
Individual Quality Explains Variation in Reproductive Success Better than Territory Quality in a Long-Lived Territorial Raptor

Evolution by natural selection depends on the relationship between individual traits and fitness. Variation in individual fitness can result from habitat (territory) quality and individual variation. Individual quality and specialization can have a deep impact on fitness, yet in most studies on territorial species the quality of territory and individuals are confused. We aimed to determine if variation in breeding success is better explained by territories, individual quality or a combination of both. We analysed the number of fledglings and the breeding quality index (the difference between the number of fledglings of an individual/breeding pair and the average number of fledglings of the monitored territories in the same year) as part of a long term (16 years) peregrine falcon (Falco peregrinus) monitoring program with identification of individuals. Using individual and territory identities as correlates of quality, we built Generalised Linear Models with Mixed effects, in which random factors depicted different hypotheses for sources of variation (territory/individual quality) in the reproductive success of unique breeding pairs, males and females, and assessed their performance. Most evidence supported the hypothesis that variation in breeding success is explained by individual identity, particularly male identity, rather than territory. There is also some evidence for inter year variations in the breeding success of females and a territory effect in the case of males. We argue that, in territorial species, individual quality is a major source of variation in breeding success, often masked by territory. Future ecological and conservation studies on habitat use should consider and include the effect of individuals, in order to avoid misleading results.
Diagnosis of hepatitis C

Currently, the second‐ and third‐generation enzyme immunoassays (EIA‐2 and EIA‐3) for hepatitis C virus antibody (anti‐HCV) are the most practical screening tests for the diagnosis of HCV infection. The need for and the choice of supplementary or confirmatory tests depend on the clinical setting and the likelihood of a true‐positive EIA result. Detection of HCV RNA in serum by polymerase chain reaction (PCR) assay is the gold standard for the diagnosis of HCV infection. However, the lack of uniformity in current PCR assays has tarnished this standard. Confirmatory tests for the diagnosis of HCV infection are in general unnecessary in anti‐HCV‐positive patients who present with chronic liver disease. When indicated, the most appropriate test in this setting is a qualitative PCR assay for HCV RNA. Confirmatory tests should always be performed in anti‐HCV‐positive blood donors and individuals with normal aminotransferase levels. The most appropriate approach is to retest for anti‐HCV using recombinant immunoblot assay (RIBA) and then test for HCV RNA using PCR assay in those who are RIBA positive or indeterminate. Liver histology is the gold standard in assessing severity of liver disease. Quantitative tests for serum HCV RNA levels do not help to determine the severity of liver disease. At the moment, HCV genotyping should be considered a research tool and not a part of the diagnostic work‐up in clinical practice. The goals of treatment for chronic hepatitis C are sustained biochemical and virological response. Viral clearance should be determined by qualitative PCR assay. Quantifying serum HCV RNA level can help in predicting response to interferon treatment, but further studies using more standardized assays are needed to determine if these values can be used to select patients for treatment.