Miracle-dz/UniFAR-FTUs huggingface dataset:
An fMRI-based neurologic signature of physical pain.

BACKGROUND Persistent pain is measured by means of self-report, the sole reliance on which hampers diagnosis and treatment. Functional magnetic resonance imaging (fMRI) holds promise for identifying objective measures of pain, but brain measures that are sensitive and specific to physical pain have not yet been identified. METHODS In four studies involving a total of 114 participants, we developed an fMRI-based measure that predicts pain intensity at the level of the individual person. In study 1, we used machine-learning analyses to identify a pattern of fMRI activity across brain regions--a neurologic signature--that was associated with heat-induced pain. The pattern included the thalamus, the posterior and anterior insulae, the secondary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray matter, and other regions. In study 2, we tested the sensitivity and specificity of the signature to pain versus warmth in a new sample. In study 3, we assessed specificity relative to social pain, which activates many of the same brain regions as physical pain. In study 4, we assessed the responsiveness of the measure to the analgesic agent remifentanil. RESULTS In study 1, the neurologic signature showed sensitivity and specificity of 94% or more (95% confidence interval [CI], 89 to 98) in discriminating painful heat from nonpainful warmth, pain anticipation, and pain recall. In study 2, the signature discriminated between painful heat and nonpainful warmth with 93% sensitivity and specificity (95% CI, 84 to 100). In study 3, it discriminated between physical pain and social pain with 85% sensitivity (95% CI, 76 to 94) and 73% specificity (95% CI, 61 to 84) and with 95% sensitivity and specificity in a forced-choice test of which of two conditions was more painful. In study 4, the strength of the signature response was substantially reduced when remifentanil was administered. CONCLUSIONS It is possible to use fMRI to assess pain elicited by noxious heat in healthy persons. Future studies are needed to assess whether the signature predicts clinical pain. (Funded by the National Institute on Drug Abuse and others.).
P-values for classification

Let $(X,Y)$ be a random variable consisting of an observed feature vector $X\in \mathcal{X}$ and an unobserved class label $Y\in \{1,2,. ,L\}$ with unknown joint distribution. In addition, let $\mathcal{D}$ be a training data set consisting of $n$ completely observed independent copies of $(X,Y)$. Usual classification procedures provide point predictors (classifiers) $\widehat{Y}(X,\mathcal{D})$ of $Y$ or estimate the conditional distribution of $Y$ given $X$. In order to quantify the certainty of classifying $X$ we propose to construct for each $\theta =1,2,. ,L$ a p-value $\pi_{\theta}(X,\mathcal{D})$ for the null hypothesis that $Y=\theta$, treating $Y$ temporarily as a fixed parameter. In other words, the point predictor $\widehat{Y}(X,\mathcal{D})$ is replaced with a prediction region for $Y$ with a certain confidence. We argue that (i) this approach is advantageous over traditional approaches and (ii) any reasonable classifier can be modified to yield nonparametric p-values. We discuss issues such as optimality, single use and multiple use validity, as well as computational and graphical aspects.
Cervical Anterolisthesis: A Predictor of Poor Neurological Outcomes in Cervical Spondylotic Myelopathy Patients After Cervical Laminoplasty

Study Design. A retrospective cohort study. Objective. To clarify the influence of cervical spondylolisthesis on neurological outcomes in cervical spondylotic myelopathy (CSM) patients after cervical laminoplasty. Summary of Background Data. Studies focusing on the surgical outcomes in CSM patients with cervical spondylolisthesis are limited. Methods. We retrospectively reviewed 125 CSM patients after cervical laminoplasty. Neurological outcomes were evaluated by calculating the Japanese Orthopedic Association (JOA) recovery rate at 2 years after surgery. We defined anterolisthesis as a more than 3-mm anterior vertebral displacement in a flexion radiograph and retrolisthesis as a more than 3-mm posterior vertebral displacement in an extension radiograph. We further assessed potential risk factors for poor neurological outcomes after cervical laminoplasty, including cervical alignment, degree of spinal cord compression, duration of myelopathic symptoms, diabetes mellitus, and preoperative JOA score. Multivariate logistic regression analysis was performed to investigate the risk factors for poor outcomes (JOA recovery rate <50%) after cervical laminoplasty. Results. Our study included 86 men and 39 women with mean age of 64 (range, 30–89) years. Average JOA scores were 9.9 and 13.3 points before and at 2 years after surgery, respectively. Average recovery rate was 47.2% (range, −68% to 100%), with 62 patients having poor outcomes (JOA recovery rate <50%) at 2 years after surgery. Anterolisthesis and retrolisthesis were observed in 13 and 24 patients, respectively. Multivariate logistic regression analysis revealed that the anterolisthesis was a significant risk factor for poor outcomes (JOA recovery rate <50%) after cervical laminoplasty (P = 0.01), whereas retrolisthesis did not affect the neurological outcomes (P = 0.6). Conclusion. Anterolisthesis, but not retrolisthesis, is a significant risk factor for and predictor of poor neurological outcomes after cervical laminoplasty. Cervical laminoplasty should not be considered in CSM patients with anterolisthesis. Level of Evidence: 2
A Collateral Theory of Endogenous Debt Maturity

We build a theory of corporate debt maturity based on two empirically relevant observations: 1) firms tend to issue bonds with different maturities, and 2) firm’s often have multiple creditors. Splitting debt financing into multiple debt maturities (maturity dispersion) serves two purposes. It allows firms to sell a larger proportion of risky debt claims to investors who value them most, and it limits the amount of debt issued on a single (concentrated) maturity profile; both purposes reduce financing costs. We characterize when a dispersed versus concentrated debt maturity profile is optimal based on measurable parameters such as the growth potential of the investment, managerial beliefs, and cash-flow shocks. We show that the interaction between these parameters determines the optimal debt liability structure in subtle ways. Our theory highlights the importance of agent heterogeneity in explaining the issuance of maturity-specific debt claims, and the value of debt financed investments.
Bioassays with Plants in the Monitoring of Water Quality

Currently, the concern with hydric resources has a global reach as regards the availability of this finite natural resource. The scarcity of drinking water is alarming, and many factors contribute with this scenario; the water bodies pollution occurs indiscriminately throughout the world, there is an enormous lack of control and management policies regarding the basic sanitation and proper effluents treatment. Thus, the awareness on the rational use of water, effective monitoring and treatment policies, establishing strict goals for water quality control, are more and more urgent, to ensure the survival of all forms of life.
The importance of BRCA 1 and BRCA 2 genes mutations in breast cancer development

Many factors including genetic, environmental, and acquired are involved in breast cancer development across various societies. Among all of these factors in families with a history of breast cancer throughout several generations, genetics, like predisposing genes to develop this disease, should be considered more. Early detection of mutation carriers in these genes, in turn, can play an important role in its prevention. Because this disease has a high prevalence in half of the global population, female screening of reported mutations in predisposing genes, which have been seen in breast cancer patients, seems necessary. In this review, a number of mutations in two predisposing genes (BRCA1 and BRCA2) that occurred in patients with a family history was investigated. We studied published articles about mutations in genes predisposed to breast cancer between 2000 and 2015. We then summarized and classified reported mutations in these two genes to recommend some exons which have a high potential to mutate. According to previous studies, exons have been reported as most mutated exons presented in this article. Considering the large size and high cost of screening all exons in these two genes in patients with a family history, especially in developing countries, the results of this review article can be beneficial and helpful in the selection of exon to screen for patients with this disease.
Methylenetetrahydrofolate reductase 677C-->T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial.

BACKGROUND Low folate status and elevated plasma homocysteine are associated with increased risk of neural tube defects and cardiovascular disease. Homocysteine responses to folate may be influenced by genetic variants in folate metabolism. OBJECTIVE We determined the effect of folate-enhancing dietary interventions on plasma folate and plasma total homocysteine (tHcy) with respect to the methylenetetrahydrofolate reductase 677C-->T genotype. DESIGN A total of 126 healthy subjects (42 TT, 42 CT, and 42 CC genotypes) completed 3 dietary interventions (4 mo each) in random order: 1) exclusion diet (avoidance of folic acid-fortified foods and ingestion of a placebo daily), 2) folate-rich diet (increased intake of fortified and naturally folate-rich foods to achieve 400 microg folate/d), and 3) supplement (exclusion diet plus a folate supplement of 400 microg/d). RESULTS Plasma folate was higher (P < or = 0.001) and plasma tHcy lower (P < or = 0.001) after the folate-rich and supplement interventions than after the exclusion diet. Plasma folate was significantly greater after supplementation than after the folate-rich diet, but there was no significant difference in tHcy concentration (P = 0.72). TT homozygotes had higher plasma tHcy (14.5 compared with 8.9 micromol/L, P < or = 0.001) and lower plasma folate (14.8 compared with 19.0 nmol/L, P < or = 0.01) than did subjects with the CC genotype after the exclusion diet. CT heterozygotes had intermediate concentrations. The trend toward higher tHcy in TT homozygotes persisted throughout the study but was less marked with increasing folate intake (TT compared with CC after supplementation, P = 0.097). CONCLUSIONS A folate-rich diet including folic acid-fortified foods or low-dose supplements effectively increases folate status. TT homozygotes require higher folate intakes than do individuals with the CT or CC genotype to achieve similar tHcy concentrations but are responsive to folate intervention.
Tocilizumab, tacrolimus and methotrexate for the prevention of acute graft-versus-host disease: low incidence of lower gastrointestinal tract disease

We conducted a phase 2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received tocilizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft-versus-host disease prophylaxis. Thirty-five patients were enrolled between January 2015 and June 2016. The median age of the cohort was 66 (range: 22-76). All patients received busulfan-based conditioning, and were transplanted with human leukocyte antigen-matched related or matched unrelated bone marrow or peripheral stem cell grafts. The cumulative incidences of grades II-IV and III-IV acute graft-versus-host disease were 14% (95% CI 5-30) and 3% (95% CI 0-11) at day 100, and 17% (95% CI 7-31) and 6% (95% CI 1-16) at day 180, respectively. Notably, there were no cases of graft-versus-host disease of the lower gastrointestinal tract within the first 100 days. A comparison to 130 matched controls who only received tacrolimus and methotrexate demonstrated a lower cumulative incidence of grades II-IV acute graft-versus-host disease (17% versus 45%, P=0.003) and a significant increase in grades II-IV acute graft-versus-host disease-free survival at six months (69% versus 42%, P=0.001) with tocilizumab, tacrolimus and methotrexate, which was the primary endpoint of the study. Immune reconstitution was preserved in patients treated with tocilizumab, tacrolimus and methotrexate, as T-cell and B-cell subsets recovered to near normal levels by 6-12 months post-transplantation. We conclude that tocilizumab has promising activity in preventing acute graft-versus-host disease, particularly in the lower gastrointestinal tract, and warrants examination in a randomized setting.
Genetic and tissue level muscle-bone interactions during unloading and reambulation

Little is known about interactions between muscle and bone during the removal and application of mechanical signals. Here, we applied 3wk of hindlimb unloading followed by 3wk of reambulation to a genetically heterogeneous population of 352 adult mice and tested the hypothesis that changes in muscle are associated with changes in bone at the level of the tissue and the genome. During unloading and relative to normally ambulating control mice, most mice lost muscle and cortical bone with large variability across the population. During reambulation, individual mice regained bone and muscle at different rates. Across mice, changes in muscle and trabecular/cortical bone were not correlated to each other during unloading or reambulation. For unloading, we found one significant quantitative trait locus (QTL) for muscle area and five QTLs for cortical bone without overlap between mechano-sensitive muscle and cortical bone QTLs (but some overlap between muscle and trabecular QTLs). The low correlations between morphological changes in muscle and bone, together with the largely distinct genetic regulation of the response indicate that the premise of a muscle-bone unit that co-adjusts its size during (un)loading may need to be reassessed.
Physical activity, protein intake, and appendicular skeletal muscle mass in older men.

BACKGROUND Aging is associated with physical inactivity, low energy intake, and loss of skeletal muscle mass. It is not clear whether regular physical activity and adequate dietary protein intake can attenuate the loss of skeletal muscle mass. OBJECTIVE We hypothesized that the maintenance of physical activity and dietary protein intake would attenuate the age-related decline in total appendicular skeletal muscle mass. DESIGN Total appendicular skeletal muscle mass was determined by dual-energy X-ray absorptiometry in 44 healthy, older white men aged 49-85 y. Physical activity level was determined by using a uniaxial accelerometer over a 9-d period. Dietary protein intake was estimated from a 3-d food record. RESULTS Aging was inversely associated with total appendicular skeletal muscle mass in older men (r = -0.43; slope: -0. 119 +/- 0.039 kg/y; P < 0.01). An effect of age on appendicular skeletal muscle mass persisted after standing height and physical activity were controlled for (r = -0.34; slope: -0.120 +/- 0.052 kg/y; P = 0.03). Furthermore, an effect of age on appendicular skeletal muscle mass persisted after standing height and dietary protein intake per kilogram body mass was controlled for (r = -0.41; slope: -0.127 +/- 0.045 kg/y; P < 0.01). CONCLUSIONS Maintaining regular physical activity and adequate protein intake may not offset the age-related loss of appendicular skeletal muscle mass in older men. Prospective studies are needed to confirm these results and to determine whether anabolic physical activity (eg, strength training) can attenuate the age-related loss of muscle mass in the elderly.
DOG-1 Is the Caenorhabditis elegans BRIP1/FANCJ Homologue and Functions in Interstrand Cross-Link Repair

ABSTRACT Fanconi anemia (FA) is a cancer susceptibility syndrome characterized by defective DNA interstrand cross-link (ICL) repair. Here, we show that DOG-1 is the Caenorhabditis elegans homologue of FANCJ, a helicase mutated in FA-J patients. DOG-1 performs a conserved role in ICL repair, as dog-1 mutants are hypersensitive to ICL-inducing agents, but not to UVC irradiation or X rays. Genetic analysis indicated that dog-1 is epistatic with fcd-2 (C. elegans FANCD2) but is nonepistatic with brc-1 (C. elegans BRCA1), thus establishing the existence of two distinct pathways of ICL repair in worms. Furthermore, DOG-1 is dispensable for FCD-2 and RAD-51 focus formation, suggesting that DOG-1 operates downstream of FCD-2 and RAD-51 in ICL repair. DOG-1 was previously implicated in poly(G)/poly(C) (G/C) tract maintenance during DNA replication. G/C tracts remain stable in the absence of ATL-1, CLK-2 (FA pathway activators), FCD-2, BRC-2, and MLH-1 (associated FA components), implying that DOG-1 is the sole FA component required for G/C tract maintenance in a wild-type background. However, FCD-2 is required to promote deletion-free repair at G/C tracts in dog-1 mutants, consistent with a role for FA factors at the replication fork. The functional conservation between DOG-1 and FANCJ suggests a possible role for FANCJ in G/C tract maintenance in human cells.
Gold nanoparticles promote osteogenic differentiation in human adipose-derived mesenchymal stem cells through the Wnt/β-catenin signaling pathway

Gold nanoparticles (AuNPs) are attractive materials for use in biomedicine due to their physical properties. Increasing evidence suggests that several nanoparticles induce the differentiation of human mesenchymal stem cells into osteoblasts and adipocytes. In this study, we hypothesized that chitosan-conjugated AuNPs promote the osteogenic differentiation of human adipose-derived mesenchymal stem cells. For the evaluation of osteogenic differentiation, alizarin red staining, an alamarBlue® assay, and a quantitative real-time polymerase chain reaction analysis were performed. In order to examine specific signaling pathways, immunofluorescence and a western blotting assay were performed. Our results demonstrate that chitosan-conjugated AuNPs increase the deposition of calcium content and the expression of marker genes related to osteogenic differentiation in human adipose-derived mesenchymal stem cells at nontoxic concentrations. These results indicate that chitosan-conjugated AuNPs promote osteogenesis through the Wnt/β-catenin signaling pathway. Therefore, chitosan-conjugated AuNPs can be used as a reagent for promoting bone formation.
Evaluation of Epididymal Sperm from Post-Mortem Derived Cauda Epididymides of Ram ( Ovis aries )

Cauda epididymides (CEs) collected post-mortem could be an important source of genetic material from male for conservation and use for assisted reproductive technologies. In this study, we characterize the epididymal sperm (ES) collected post-mortem from CEs of ram raised locally. Testicles (n=12) were sliced off from the donor ram post-mortem, placed in a styropore box at ambient temperature and transported to the laboratory within 2 hr. The mean weight of the testicle was 130.2 g with a mean length of 11.2 cm. The epididymis and scrotal sac had a mean weight of 11.5 g and 92.1 g, respectively. The CEs were detached from the testicle and the tail were sliced longitudinally and dropped into a 50-ml conical tube with 15 ml TRIS buffer medium. The ES was collected after 10 min, washed through centrifugation and measured. The mean head area was 380.3 μm and tail length of 183.5 μm. The mean sperm volume was 0.92 ml, pH of 6.6 and a sperm concentration of 2.02x10 cells/ml. Conventionally, the sperm motility rate was between 63-65%, whereas through CASA, the sperm motility reading was 65-69%. The mean progressive motility was 44.5%. The mean viability rate was 80.3% with 63.2% morphologically normal sperm. The results provided basic informations on the sperm head and tail morphometry, motility and viability of epididymal sperm collected post mortem from CEs of ram.
Evidence That the Sympathetic Nervous System Elicits Rapid, Coordinated, and Reciprocal Adjustments of Insulin Secretion and Insulin Sensitivity During Cold Exposure

Dynamic adjustment of insulin secretion to compensate for changes of insulin sensitivity that result from alteration of nutritional or metabolic status is a fundamental aspect of glucose homeostasis. To investigate the role of the brain in this coupling process, we used cold exposure as an experimental paradigm because the sympathetic nervous system (SNS) helps to coordinate the major shifts of tissue glucose utilization needed to ensure that increased thermogenic needs are met. We found that glucose-induced insulin secretion declined by 50% in rats housed at 5°C for 28 h, and yet, glucose tolerance did not change, owing to a doubling of insulin sensitivity. These potent effects on insulin secretion and sensitivity were fully reversed by returning animals to room temperature (22°C) for 4 h or by intravenous infusion of the α-adrenergic receptor antagonist phentolamine for only 30 min. By comparison, insulin clearance was not affected by cold exposure or phentolamine infusion. These findings offer direct evidence of a key role for the brain, acting via the SNS, in the rapid, highly coordinated, and reciprocal changes of insulin secretion and insulin sensitivity that preserve glucose homeostasis in the setting of cold exposure.
Stem Cells and Cloning: Advances and Applications Dovepress Isolation, Characterization, and Gene Expression Analysis of Wharton's Jelly-derived Mesenchymal Stem Cells under Xeno-free Culture Conditions

Mesenchymal stem cells (MSCs) have become an attractive tool for tissue engineering and targets in clinical transplantation due to their regeneration potential and immuno-suppressive capacity. Although MSCs derived from bone marrow are the most widely used, their harvest requires an invasive procedure. The umbilical cord, which is discarded at birth, can provide an inexhaustible source of stem cells for therapy. The Wharton's jelly-derived MSCs (WJ-MSCs), from the umbilical cord, have been shown to have faster proliferation rates and greater expansion capability compared with adult MSCs. The standard isolation and in vitro culture protocol for WJ-MSCs utilizes fetal bovine serum (FBS) or calf serum as a nutrient supplement. However, FBS raises potential safety concerns such as transmission of viral/prion disease and may initiate xenogeneic immune reactions against bovine antigens. Therefore, for therapeutic applications, there is an urgent requirement to establish an alternative nutrient supplement which would favor cell proliferation, retain MSC characteristics, and prove safe in human subjects. In the present study, we isolated and expanded WJ-MSCs in 5% pooled, allogeneic human serum (HS) supplemented with 2 ng/mL of basic fibroblast growth factor. For cell dissociation, porcine trypsin was replaced with TrypLE, a recombinant enzyme, and a protease-free protocol was adapted for isolation of MSCs from WJ. We determined their growth kinetics, in vitro differentiation potential, surface marker expression, and colony-forming unit potential and compared them against standard WJ-MSC cultures expanded in 10% FBS. All these parameters matched quite well between the two MSC populations. To test whether there is any alteration in gene expression on switching from FBS to HS, we analyzed a panel of stem cell and early lineage markers using Taqman ® low density array. No significant deviation in gene expression was observed between the two populations. Thus we established an efficient, complete xeno-free protocol for propagation of human WJ-MSCs.