Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemotherapy, en bloc resection, and prosthetic bone replacement in the treatment of osteogenic sarcoma

In an attempt to shrink primary osteogenic sarcoma and allow complete surgical removal of the primary tumor, without amputating the involved limb, intensive preoperative chemotherapy with high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and adriamycin (ADR) was initiated in 20 patients with biopsy‐proven primary osteogenic sarcoma of the distal femur (15 patients) and proximal tibia (five patients). Following intensive chemotherapy, en bloc resection of the primary tumor with prosthetic replacement of the involved bone was planned. After surgery, adjuvant chemotherapy, consisting of HDMTX with CFR, ADR, and high dose cyclophosphamide was given sequentially for 1 year. Of 20 patients with primary osteogenic sarcoma (two with evidence of pulmonary metastases), 18 had primary tumors that could be clinically measured. Of these 18, 17 demonstrated a decrease in the size of primary tumor prior to surgery, while on chemotherapy. To date, 12 of these patients with osteogenic sarcoma of the distal femur have had total femur and knee joint replacement, and three patients with osteogenic sarcoma of the proximal tibia have had total knee replacement. In all 15 patients, surgical margins were grossly and microscopically free of tumor. There has been no evidence of soft tissue recurrence in any of the 15 patients who have undergone surgery for from 2 to 15 months postoperatively. These preliminary results indicate that with the use of aggressive chemotherapy, it is possible to demonstrate objective tumor regression in primary osteogenic sarcoma, allowing the surgeon to perform en bloc resection of tumor and prosthetic replacement of the involved bone. Although the limb is preserved, it is important to stress that extensive surgery yielding tumor‐free margins is performed. The ultimate evaluation of this approach to the treatment of primary osteogenic sarcoma awaits longer observation, to determine limb function and the continued disease‐free status, once adjuvant chemotherapy is discontinued.
Molecular footprint of Medawar’s mutation accumulation process in mammalian aging

Medawar's mutation accumulation hypothesis explains aging by the declining force of natural selection with age: Slightly deleterious germline mutations expressed in old age can drift to fixation and thereby lead to aging‐related phenotypes. Although widely cited, empirical evidence for this hypothesis has remained limited. Here, we test one of its predictions that genes relatively highly expressed in old adults should be under weaker purifying selection than genes relatively highly expressed in young adults. Combining 66 transcriptome datasets (including 16 tissues from five mammalian species) with sequence conservation estimates across mammals, here we report that the overall conservation level of expressed genes is lower at old age compared to young adulthood. This age‐related decrease in transcriptome conservation (ADICT) is systematically observed in diverse mammalian tissues, including the brain, liver, lung, and artery, but not in others, most notably in the muscle and heart. Where observed, ADICT is driven partly by poorly conserved genes being up‐regulated during aging. In general, the more often a gene is found up‐regulated with age among tissues and species, the lower its evolutionary conservation. Poorly conserved and up‐regulated genes have overlapping functional properties that include responses to age‐associated tissue damage, such as apoptosis and inflammation. Meanwhile, these genes do not appear to be under positive selection. Hence, genes contributing to old age phenotypes are found to harbor an excess of slightly deleterious alleles, at least in certain tissues. This supports the notion that genetic drift shapes aging in multicellular organisms, consistent with Medawar's mutation accumulation hypothesis.
Alpha-amylase inhibitory activity and sterol composition of the marine algae, Sargassum glaucescens

Background: Sargassum species (phaeophyceae) are economically important brown algae in southern parts of Iran. Sargassum is mainly harvested as a row material in alginate production industries and is a source of plant foods or plant bio-stimulants even a component of animal foods. Objective: In this study, Sargassum glaucescens, collected from the seashore of Chabahar, was employed for phytochemical and biological evaluations. Materials and Methods: For that purpose, the dried algae was extracted by methanol and subjected to different chromatographic separation methods. Results: Six sterols, fucosterol (1), 24(S)-hydroxy-24-vinylcholesterol (2), 24(R)-hydroxy-24-vinylcholesterol (3), stigmasterol (4), β-sitosterol (5) and cholesterol (6) were identified by spectroscopic methods including 1 H-NMR, 13 C-NMR and mass spectroscopy. In vitro alpha-amylase inhibitory test was performed on the methanolic extract and the results revealed a potent inhibition (IC 50 = 8.9 ± 2.4 mg/mL) of the enzyme compared to acarbose as a positive control. Conclusion: Various biological activities and distribution of sterols in Sargassum genus have been critically reviewed here. The results concluded that these algae are a good candidate for further anti-diabetic investigations in animals and human.
Selection via Penalized Credible Regions

When estimating the effect of an exposure or treatment on an outcome it is important to select the proper subset of confounding variables to include in the model. Including too many covariates increases mean square error on the effect of interest while not including confounding variables biases the exposure effect estimate. We propose a decision-theoretic approach to confounder selection and effect estimation. We first estimate the full standard Bayesian regression model and then post-process the posterior distribution with a loss function that penalizes models omitting important confounders. Our method can be fit easily with existing software and in many situations without the use of Markov chain Monte Carlo methods, resulting in computation on the order of the least squares solution. We prove that the proposed estimator has attractive asymptotic properties. In a simulation study we show that our method outperforms existing methods. We demonstrate our method by estimating the effect of fine particulate matter (PM2.5) exposure on birth weight in Mecklenburg County, North Carolina.
Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B

Abstract The improved safety profile and antifungal efficacy of liposomal amphotericin B (LAmB) compared to conventional amphotericin B deoxycholate (DAmB) is due to several factors including, its chemical composition, rigorous manufacturing standards, and ability to target and transit through the fungal cell wall. Numerous preclinical studies have shown that LAmB administered intravenously distributes to tissues frequently infected by fungi at levels above the minimum inhibitory concentration (MIC) for many fungi. These concentrations can be maintained from one day to a few weeks, depending upon the tissue. Tissue accumulation is dose-dependent with drug clearance occurring most rapidly from the brain and slowest from the liver and spleen. LAmB localizes in lung epithelial lining fluid, within liver and splenic macrophages and in kidney distal tubules. LAmB has been used successfully in therapeutic and prophylactic animal models to treat many different fungal pathogens, significantly increasing survival and reducing tissue fungal burden.
Comparative genomics of Bifidobacterium species isolated from marmosets and humans

The genus Bifidobacterium is purported to have beneficial consequences for human health and is a major component of many gastrointestinal probiotics. Although species of Bifidobacterium are generally at low relative frequency in the adult human gastrointestinal tract, they can constitute high proportions of the gastrointestinal communities of adult marmosets. To identify genes that might be important for the maintenance of Bifidobacterium in adult marmosets, ten strains of Bifidobacterium were isolated from the feces of seven adult marmosets, and their genomes were sequenced. There were six B. reuteri strains, two B. callitrichos strains, one B. myosotis sp. nov. and one B. tissieri sp. nov. among our isolates. Phylogenetic analysis showed that three of the four species we isolated were most closely related to B. bifidum, B. breve and B. longum, which are species found in high abundance in human infants. There were 1357 genes that were shared by at least one strain of B. reuteri, B. callitrichos, B. breve, and B. longum, and 987 genes that were found in all strains of the four species. There were 106 genes found in B. reuteri and B. callitrichos but not in human bifidobacteria, and several of these genes were involved in nutrient uptake. These pathways for nutrient uptake appeared to be specific to Bifidobacterium from New World monkeys. Additionally, the distribution of Bifidobacterium in fecal samples from captive adult marmosets constituted as much as 80% of the gut microbiome, although this was variable between individuals and colonies. We suggest that nutrient transporters may be important for the maintenance of Bifidobacterium during adulthood in marmosets.
Diffusion Tensor Imaging in Athletes Sustaining Repetitive Head Impacts: A Systematic Review of Prospective Studies.

Competitive sport participation, in contact and collision sports, exposes athletes to repetitive head impacts. While these impacts do not always result in overt symptomology or a diagnosed 'concussion,' evidence indicates that cumulative repetitive impacts affect brain pathophysiology. The purpose of this study was to perform a systematic review of prospective, longitudinal trials evaluating repetitive head impact exposure on white matter microstructure in collision and contact sport athletes to inform clinical care and treatment strategies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to determine studies that met pre-determined inclusion and exclusion criteria. 2498 abstracts were initially identified, and 20 studies were critically evaluated herein. The majority of studies demonstrated significant longitudinal changes in anisotropy and/or diffusivity metrics that were associated with the quantity and/or the magnitude of head impact exposure, highlighting the utility of diffusion tensor imaging (DTI) for measuring changes in white matter microstructure. Our review also comments on study methodology and describes how age, sex, sport, and time between sport cessation and DTI measures contribute to divergent findings within the literature. Suggestions for future research are also provided to overcome previous study limitations and maximize our understanding of the role of repetitive head impact exposure on white matter integrity and long-term neurological sequela.
More is not necessarily better: Examining the nature of the temporal reference memory component in timing

Three experiments compared the timing performance of humans on a modified temporal generalization task with 1, 3, or 5 presentations of the standard duration. In all three experiments subjects received presentations of a standard duration at the beginning of a trial block and then had to judge whether each of a number of comparison stimuli was or was not the standard. The duration of the standard changed between blocks. The three experiments varied the experimental design (between or within subjects), task difficulty (how closely the comparison stimuli were spaced around the standards), and presence or absence of feedback on performance accuracy. Number of presentations of the standard never affected the proportion of identifications of the standard when it was presented, nor other features of the temporal generalization gradients observed. The implications for the operation of reference memories within the scalar timing system were explored via models that made different assumptions about how the individual presentations of the standard were stored and used.
The Perception of Disability Among Mothers Living With a Child With Cerebral Palsy in Saudi Arabia

The purpose of this study was to explore the perceptions of disability among Saudi mothers and to understand the implication of the meaning for the mothers of children with disability. A critical ethnographic approach was employed using focus groups and follow-up interviews with the mothers. Three primary themes were identified that specifically influenced and affected the mothers’ experiences: (a) culture and religion, (b) motherhood and disability, and (c) community stigma and discrimination. The study reveals much-needed knowledge and sheds light on a topic, the details of which are rarely available in research literature from the Middle East. The findings further endorse the need for clinicians to listen to the mothers to consider their beliefs and the impact of these beliefs on their experiences. This, in turn, may provide a valuable conceptual lens for health care practitioners to use the family-centered model when working with cerebral palsy children.
Evidence for altered excitatory and inhibitory tone in the post-mortem substantia nigra in schizophrenia

Abstract Objectives: The substantia nigra (SN) receives glutamatergic and GABAergic inputs that regulate dopaminergic neuronal activity. Imaging studies have shown hyperactivity of the SN in schizophrenia (SZ) patients. We examined neurochemically defined inputs to the SN, synaptic density, and neuromelanin content that might contribute to or reflect this hyperexcitability. Methods: Glutamatergic axon terminals were identified by the immunohistochemical localisation of vGLUT1 and vGLUT2; GABA inputs were identified by the immunohistochemical localisation of GAD67. Neuromelanin granules are visible in unstained sections and thus were assessed in unstained sections. Optical densitometry was measured to assess the density of vGLUT1, vGLUT2 or GAD67 immunolabelled axon terminals and neuromelanin granules. Electron microscopy was used to quantify synaptic and mitochondrial density. Results: Compared to controls, SZ subjects had nonsignificant trends toward a decrease in vGLUT1, and an increase in both vGLUT2 and GAD67. vGLUT1 was negatively correlated with GAD67 in normal controls (NCs) and positively correlated in SZ subjects. A correlation of coefficient analysis showed a significant difference between the negative correlation in NCs and the positive correlation in SZ subjects. Frequency histograms showed the distribution of neuromelanin density was different in SZ subjects compared to NCs. Synaptic density data showed a decrease in inhibitory synapses in SZ subjects. Mitochondrial density was normal in SZ subjects. Conclusions: Synaptic density alterations and the lack of a positive correlation between GAD67 and vGLUT1 could contribute to hyperactivity in the SN.
Impaired fat oxidation during exercise in multiple acyl‐CoA dehydrogenase deficiency

We investigated the in vivo skeletal muscle metabolism in patients with multiple acyl‐CoA dehydrogenase deficiency (MADD) during exercise, and the effect of a glucose infusion. Two adults with MADD on riboflavin and l‐carnitine treatment and 10 healthy controls performed an incremental exercise test measuring maximal oxidative capacity (VO2max) and a submaximal exercise test (≤1 hour) on a cycle ergometer. During submaximal exercise, we studied fat and carbohydrate oxidation, using stable isotope tracer methodology and indirect calorimetry. On another day, the patients repeated the submaximal exercise receiving a 10% glucose infusion. The patients had a lower VO2max than controls and stopped the submaximal exercise test at 51 and 58 minutes due to muscle pain and exhaustion. The exercise‐induced increase in total fatty acid oxidation was blunted in the patients (7.1 and 1.1 vs 12 ± 4 μmol × kg−1 × min−1 in the healthy controls), but total carbohydrate oxidation was higher (67 and 63 vs 25 ± 11 μmol × kg−1 × min−1 in controls). With glucose infusion, muscle pain decreased and average heart rate during exercise dropped in both patients from 124 to 119 bpm and 138 to 119 bpm. We demonstrate that exercise intolerance in MADD‐patients relates to an inability to increase fat oxidation appropriately during exercise, which is compensated partially by an increase in carbohydrate metabolism.
LncRNA MIR503HG inhibits cell migration and invasion via miR‐103/OLFM4 axis in triple negative breast cancer

Long non‐coding RNA MIR503 host gene (MIR503HG) is located on chromosome Xq26.3, and has been found to be deregulated in many types of human malignancy and function as tumour suppressor or promoter based on cancer types. The role of MIR503HG in breast cancer was still unknown. In our study, we found MIR503HG expression was significantly decreased in triple‐negative breast cancer tissues and cell lines. Furthermore, we observed low MIR503HG expression was correlated with late clinical stage, lymph node metastasis and distant metastasis. In the survival analysis, we observed that triple‐negative breast cancer patients with low MIR503HG expression had a statistically significant worse prognosis compared with those with high MIR503HG expression, and low MIR503HG expression was a poor independent prognostic factor for overall survival in triple‐negative breast cancer patients. The study in vitro suggested MIR503HG inhibits cell migration and invasion via miR‐103/OLFM4 axis in triple negative breast cancer. In conclusion, MIR503HG functions as a tumour suppressive long non‐coding RNA in triple negative breast cancer.
Aberrant Phenotype and Function of Dendritic Cells in Adult B Lineage Acute Lymphoblastic Leukemia

ABSTRACT Dendritic cells (DCs) play a major role in regulating immune responses, but the aberrant phenotype and function of defective DCs in adult acute lymphoblastic leukemia (ALL) remain unclear. Here, B lineage ALL (B-ALL) patients were divided into groups according to different standards. By course of disease: newly diagnosed (ND), complete remission (CR), consolidation (CONS). By stratification: high risk (HR), standard risk (SR). By minimal residual disease (MRD): MRD positive(MRD+), MRD negative (MRD−). The proportion of plasmacytoid DC(pDC) and myeloid DC(mDC) were compared within these standards. The costimulatory molecule levels of pDC, mDC in ND and CR were measured and the function of peripheral blood monocyte-derived DC(MoDC)s were examined. We found proportions of pDC and mDC in ND were both lower compared to control group and gradually increased after CR. In HR and MRD+, the proportions were also lower compared to SR and MRD− at CR stage, respectively; but there were no difference between these comparisons when newly diagnosed. In ND, both CD80, CD86 levels in pDC, mDC were higher while the levels in activated MoDCs were lower when compared to control and CR group, respectively. The dextran uptake of MoDCs, T cell proliferation promoting ability, IL-12, BAFF, INF-α levels in supernatant and their mRNA relative expression in activated MoDCs in ND were also lower than those in control and CR group. So, DCs in B-ALL display suppressed status in phenotype and function，which would be gradually restored after effective chemotherapy. pDC and mDC could respond to patient condition, DCs proportion may be useful for monitoring disease progression.
Goal Orientation Test: An Objective Behavioral Test

The aim of the present research is to assess goal orientation (mastery and performance) by developing an objective behavioral test. We elaborated the Mastery Performance-Goal Orientation Test, a task that allows assessment of goal orientation along a single dimension. We studied its reliability and validity by conducting two studies. In Study 1 (N = 293 adults), the distribution of scores along the goal orientation variable showed wide variability and high internal consistency. The mastery-oriented participants demonstrated higher levels of category learning, whereas the performance-oriented participants responded in a less discriminative way but achieved higher scores. In Study 2 (N = 41 undergraduate students), the mastery-oriented participants achieved higher scores on a learning task than the performance-oriented subjects. The results also showed that the test had the potential to predict subsequent learning. We conclude that it might be a useful instrument to assess goal orientation.
The timing and duration of a sensitive period in human flavor learning: a randomized trial.

BACKGROUND By using the response to protein hydrolysate formula (PHF) as a model system, we discovered the existence of a sensitive period, before 4 mo, when exposure determines the hedonic tone to flavors. OBJECTIVE We aimed to characterize the timing and duration of this sensitive period. DESIGN Healthy infants, whose parents had chosen formula feeding, were randomly assigned into 1 of 6 groups at age 0.5 mo: 2 control groups, one fed cow milk-based formula (CMF) and the other fed PHF for 7 mo; 2 groups fed PHF for either 1 or 3 mo beginning at 1.5 mo and CMF otherwise; and 2 groups fed PHF for 1 mo beginning at either 2.5 or 3.5 mo and CMF otherwise. Brief access taste tests were conducted monthly, and complete "meals" of both formulas occurred at the end of the study. RESULTS Three months of PHF exposure led to acceptance similar to that at 1 mo of exposure. Although these infants were more accepting than were infants with no exposure, they were less accepting than were infants with 7 mo of exposure, which suggests a dosing effect. The time when flavor experiences began was also significant. Among infants exposed to PHF for 1 mo, those who were first fed PHF at 3.5 mo rejected PHF relative to CMF more than did infants exposed at younger ages. CONCLUSION The general principles observed are likely of broader significance, indicating a fundamental feature of mammalian development and reflecting the importance of familiarizing infants with flavors that their mothers consume and transmit to breast milk. This trial was registered at clinicaltrials.gov as NCT00994747.
Large Variety of Medical Specialties Involved in Management of Pediatric Minor Traumatic Head Injury in the Netherlands

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits noncommercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). Brief Report