Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic effect on experimental acute cerebral infarction is enhanced after nanoceria labeling of human umbilical cord mesenchymal stem cells

Background: Therapeutic applications of stem cells, especially mesenchymal stem cells, were once regarded as a promising therapy for mitigating acute cerebral infarction. Unfortunately, all the stem cell clinical trials have been futile. A new stroke therapeutic strategy of combining stem cells with nanotechnology has recently gained significant attention. The objective of this study was to evaluate the application of cerium oxide nanoparticle (nanoceria)-labeled human umbilical cord mesenchymal stem cells (HucMSCs) for stroke therapy. Methods: In our study, cerium oxide nanoparticles were precovered with hyaluronic acid before labeling HucMSCs and the synergistic effects from both HucMSCs and cerium oxide nanoparticles were analyzed in in vivo and in vitro experiments Results: The nanoceria-labeled HucMSCs combined advantages from both sides, including the capacity for inflammatory modulation of HucMSCs and the antioxidant effects of nanoceria. Compared with either HucMSCs or nanoceria individually, nanoceria-labeled HucMSCs exerted significantly enhanced capacities after gaining combined antioxidant and anti-inflammatory effects. Conclusion: Our findings suggest a novel strategy with effective and well-tolerated applications of stem cells for acute cerebral infarction therapy after modification of cells with nanomaterials.
Differences in mitochondrial efficiency explain individual variation in growth performance

The physiological causes of intraspecific differences in fitness components such as growth rate are currently a source of debate. It has been suggested that differences in energy metabolism may drive variation in growth, but it remains unclear whether covariation between growth rates and energy metabolism is: (i) a result of certain individuals acquiring and consequently allocating more resources to growth, and/or is (ii) determined by variation in the efficiency with which those resources are transformed into growth. Studies of individually housed animals under standardized nutritional conditions can help shed light on this debate. Here we quantify individual variation in metabolic efficiency in terms of the amount of adenosine triphosphate (ATP) generated per molecule of oxygen consumed by liver and muscle mitochondria and examine its effects, both on the rate of protein synthesis within these tissues and on the rate of whole-body growth of individually fed juvenile brown trout (Salmo trutta) receiving either a high or low food ration. As expected, fish on the high ration on average gained more in body mass and protein content than those maintained on the low ration. Yet, growth performance varied more than 10-fold among individuals on the same ration, resulting in some fish on low rations growing faster than others on the high ration. This variation in growth for a given ration was related to individual differences in mitochondrial properties: a high whole-body growth performance was associated with high mitochondrial efficiency of ATP production in the liver. Our results show for the first time, to our knowledge, that among-individual variation in the efficiency with which substrates are converted into ATP can help explain marked variation in growth performance, independent of food intake. This study highlights the existence of inter-individual differences in mitochondrial efficiency and its potential importance in explaining intraspecific variation in whole-animal performance.
Evaluation of ambiguous genitalia.

PURPOSE OF REVIEW To provide a framework for the evaluation of ambiguous genitalia. RECENT FINDINGS The most pressing evaluation of ambiguous genitalia is assessment for life-threatening causes such as salt-wasting congenital adrenal hyperplasia (CAH) or syndromes with underlying anomalies such as neurologic or cardiac malformations. A multidisciplinary team, including specialists in Gynecology, Endocrinology, Urology, Genetics, Clinical Psychology/Psychiatry, Radiology, Nursing, Neonatology, and Pediatric Surgery, should be involved. Each patient should be approached in an individualized manner to assign sex of rearing in the most expeditious yet thoughtful means possible.As knowledge on the natural history of sex preference and fertility of individuals with ambiguous genitalia increases, controversy regarding the indication for and timing of genital surgery continues. Considerations include gender identity, future fertility, malignancy risk, infection prevention, and functional anatomy for sexual activity. SUMMARY The evaluation of ambiguous genitalia should involve a multidisciplinary team. A combination of history taking, physical examination, laboratory evaluation, and radiologic assessment can assist with the diagnosis. Care should be taken to emphasize karyotypic sex is not equivalent to gender and to use caution with regards to irreversible medical and surgical therapies which may impact fertility and sexual function and nonconform with future sex identity.
Establishing the Impact of Vascular Damage on Tumor Response to High-Dose Radiation Therapy.

Approximately half of all cancer patients receive radiation therapy, which is conventionally delivered in relatively small doses (1.8 to 2 Gy) per daily fraction over 1-2 months. Stereotactic body radiation therapy (SBRT), in which a high daily radiation dose is delivered in 1 to 5 fractions, has improved local control rates for several cancers. However, despite the wide-spread adoption of SBRT in the clinic, controversy surrounds the mechanism by which SBRT enhances local control. Some studies suggest that high doses of radiation (≥10 Gy) trigger tumor endothelial cell death, resulting in indirect killing of tumor cells through nutrient depletion. On the other hand, mathematical models predict that the high radiation dose per fraction used in SBRT increases direct tumor cell killing suggesting that disruption of the tumor vasculature is not a critical mediator of tumor cure. Here, we review the application of genetically engineered mouse models to radiosensitize tumor cells or endothelial cells in order to dissect the role of these cellular targets in mediating the response of primary tumors to high dose radiotherapy in vivo. These studies demonstrate a role for endothelial cell death in mediating tumor growth delay, but not local control following SBRT.
The channel for hidden data transmission in WSN

This paper describes an idea and realisation of hidden data transmision using Tiny Aggregation Covert Channel (TAGCC)in Wireless Sensor Networks. Our solution uses data aggregation mechanism called Tiny Aggregation (TAG). The protocol is based on idea of hidden messages sending without generate additional data packets and encryption. The paper describes details of proposed algorithm and simulation results obtained during testing of the sensor networks with hidden channel TAGCC.
NIR-II Driven Plasmon-Enhanced Catalysis for Timely Supply of Oxygen to Overcome Hypoxia Induced Radiotherapy Tolerance.

Hypoxia, as a characteristic feature of solid tumor, can significantly adversely affect the outcomes of cancer radiotherapy (RT), photodynamical therapy or chemotherapy. In this study, we have developed a novel strategy to overcome tumor hypoxia induced radiotherapy tolerance. Specifically, a novel two-dimensional Pd@Au bimetallic core-shell nanostructures (TPAN) was employed for the sustainable and robust production of O2 in long-term via the catalysis of endogenous H2O2. Notably, the catalytic activity of TPAN could be enhanced via surface plasmon resonance (SPR) effect triggered by NIR-II laser irradiation, to enhance the O2 production and thereby relieve tumor hypoxia. Thus, TPAN could enhance radiotherapy outcomes by three aspects: (i) NIR-II laser triggered SPR enhanced the catalysis of TPAN to produce O2 for relieving tumor hypoxia; (ii) high-Z element effect arising from Au and Pd to capture X-ray energy within tumor; (iii) TPAN affording X-ray, photoacoustic and NIR-II laser derived photothermal imaging, for precisely guiding cancer therapy, so as to reduce the side effects from irradiation.
Effect of Long-Term Omega 3 Polyunsaturated Fatty Acid Supplementation with or without Multidomain Lifestyle Intervention on Muscle Strength in Older Adults: Secondary Analysis of the Multidomain Alzheimer Preventive Trial (MAPT)

BACKGROUND The benefits of long-term omega 3 polyunsaturated fatty acid (ω3-PUFA) supplementation on muscle strength in older adults remains to be investigated. OBJECTIVES We assessed the effect of ω3-PUFA supplementation and a multidomain (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on muscle strength. We also hypothesized that ω3-PUFA supplementation resulted in additional benefit in participants with a low docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) erythrocyte level at baseline and high adherence to the multidomain intervention sessions. DESIGN We performed secondary analyses of the Multidomain Alzheimer Preventive Trial (MAPT), a 3-year, multicenter, randomized, placebo-controlled trial with four parallel groups. Participants were non-demented, aged 70 years or older. They were recruited in 13 memory clinics in France and Monaco between 30 May 2008 and 24 February 2011. Participants were randomly assigned to either ω3-PUFA alone (two capsules a day providing a total daily dose of 800 mg DHA and 225 mg EPA), ω3-PUFA plus the multidomain intervention (43 group sessions integrating advice for physical activity (PA), and nutrition, cognitive training, and three preventive consultations), the multidomain intervention plus placebo, or placebo alone. Our primary outcome was the change from baseline to 36 months of the muscle strength assessed with the repeated chair stand test and handgrip strength. RESULTS A total of 1680 participants (75.34 years ± 4.42) were randomized. In the modified intention-to-treat population (n = 1679), no significant differences at 3-year follow-up were observed in the repeated chair stand test score between any of the three intervention groups and the placebo group. The between-group differences compared with placebo were -0.05388 (-0.6800 to 0.5723; Standard Error, SE = 0.3192; p = 0.8660) for the ω3-PUFA group, -0.3936 (-1.0217 to 0.2345; SE = 0.3180; p = 0.2192) for the multidomain intervention plus placebo group, and -0.6017 (-1.2255 to 0.02222; SE = 0.2092; p = 0.3202) for the combined intervention group. No significant effect was also found for the handgrip strength. Sensitivity analyses performed among participants with low (DHA+EPA) erythrocyte level at baseline (first quartile vs. others) or highly adherent participants (≥75% of the multidomain intervention sessions) revealed similar results. CONCLUSION Low dose ω3-PUFA supplementation, either alone or in combination with a multidomain lifestyle intervention comprising physical activity counselling, had no significant effects on muscle strength over 3 years in elderly people.
"Keep it simple": Perspectives of patients with low back pain on how to qualify a patient-centred consultation using patient-reported outcomes.

BACKGROUND Patient-reported outcomes are expected to play an important role in patient-centred health care. To capture patients' perspectives, patient involvement in the development of patient-reported outcome (PRO) instruments is essential, but often lacking. This qualitative study explored the perspectives of patients with low back pain, to gain an understanding of how to qualify a patient-centred consultation by using PROs. This was done by exploring patients' perspectives regarding the assessment of functioning and disability as part of the development of a new PRO instrument based on the International Classification of Functioning, Disability and Health Core Set. METHODS Semi-structured focus group interviews with seven patients with low back pain were conducted. Data were analysed by drawing on the Interpretive Description methodology. RESULTS The analysis revealed three core themes: simplicity, individuality and application. Simplicity represented keeping items to a minimum and avoiding overlaps; individuality implied the need for individualized answers; and application signified that PROs should be utilized during the consultation, and that they can provide useful information for clinical decision-making. CONCLUSIONS The study provides essential knowledge about elements of importance to patients with low back pain when aiming for a patient-centred consultation using PROs. Furthermore, it underlines the importance of involving patients in PRO development because their perspectives improved the new PRO instrument.
Case-only analysis of gene-environment interactions using polygenic risk scores

Investigations of gene (G)-environment (E) interactions have led to limited findings to date, possibly due to weak effects of individual genetic variants. Polygenic risk scores (PRS), which capture the genetic susceptibility associated with a set of variants, can be a powerful tool for detecting global patterns of interaction. Motivated by the case-only method for evaluating interactions with a single variant, we propose a case-only method for the analysis of interactions with a PRS in case-control studies. Assuming the PRS and E are independent, we show how a linear regression of the PRS on E in a sample of cases can be used to efficiently estimate the interaction parameter. Furthermore, if an estimate of the mean of the PRS in the underlying population is available, the proposed method can estimate the PRS main effect. Extensions allow for PRS-E dependence due to associations between variants in the PRS and E. Simulation studies indicate the proposed method offers appreciable gains in efficiency over logistic regression and can recover much of the efficiency of a cohort study. As an illustration, we apply the proposed method to investigate interactions between a PRS and epidemiologic factors on breast cancer risk in the UK Biobank study.
Fibroblast growth factor 21 in patients with cardiac cachexia: a possible role of chronic inflammation

Cardiac cachexia is a wasting syndrome characterized by chronic inflammation and high mortality. Fibroblast growth factor 21 (FGF‐21) and monocyte chemoattractant protein 1 (MCP‐1) are associated with cardiovascular disease and systemic inflammation. We investigated FGF‐21 and MCP‐1 in relations to cardiac function, inflammation, and wasting in patients with heart failure with reduced ejection fraction (HFrEF) and cardiac cachexia.
Mental well-being, job satisfaction and self-rated workability in general practitioners and hospitalisations for ambulatory care sensitive conditions among listed patients: a cohort study combining survey data on GPs and register data on patients

Background Physicians’ work conditions and mental well-being may affect healthcare quality and efficacy. Yet the effects on objective measures of healthcare performance remain understudied. This study examined mental well-being, job satisfaction and self-rated workability in general practitioners (GPs) in relation to hospitalisations for ambulatory care sensitive conditions (ACSC-Hs), a register-based quality indicator affected by referral threshold and prevention efforts in primary care. Methods This is an observational study combining data from national registers and a nationwide questionnaire survey among Danish GPs. To ensure precise linkage of each patient with a specific GP, partnership practices were not included. Study cases were 461 376 adult patients listed with 392 GPs. Associations between hospitalisations in the 6-month study period and selected well-being indicators were estimated at the individual patient level and adjusted for GP gender and seniority, list size, and patient factors (comorbidity, sociodemographic characteristics). Results The median number of ACSC-Hs per 1000 listed patients was 10.2 (interquartile interval: 7.0–13.7). All well-being indicators were inversely associated with ACSC-Hs, except for perceived stress (not associated). The adjusted incidence rate ratio was 1.26 (95% CI 1.13 to 1.42) for patients listed with GPs in the least favourable category of self-rated workability, and 1.19 (95% CI 1.05 to 1.35), 1.15 (95% CI 1.04 to 1.27) and 1.14 (95% CI 1.03 to 1.27) for patients listed with GPs in the least favourable categories of burn-out, job satisfaction and general well-being (the most favourable categories used as reference). Hospitalisations for conditions not classified as ambulatory care sensitive were not equally associated. Conclusions ACSC-H frequency increased with decreasing levels of GP mental well-being, job satisfaction and self-rated workability. These findings imply that GPs’ work conditions and mental well-being may have important implications for individual patients and for healthcare expenditures.
Interaction of Genetic Variations in NFE2L2 and SELENOS Modulates the Risk of Hashimoto's Thyroiditis

Background: Several single-nucleotide polymorphisms (SNPs) are known to increase the risk of Hashimoto's thyroiditis (HT); such SNPs reside in thyroid-specific genes or in genes related to autoimmunity, inflammation, and/or cellular defense to stress. The transcription factor Nrf2, encoded by NFE2L2, is a master regulator of the cellular antioxidant response. This study aimed to evaluate the impact of genetic variation in NFE2L2 on the risk of developing HT. Methods: In a case–control candidate gene association study, functional SNPs in the NFE2L2 promoter (rs35652124, rs6706649, and rs6721961) were examined either as independent risk factors or in combination with a previously characterized HT risk allele (rs28665122) in the gene SELENOS, encoding selenoprotein S (SelS). A total of 997 individuals from the north of Portugal (Porto) were enrolled, comprising 481 HT patients and 516 unrelated healthy controls. SELENOS and NFE2L2 SNPs were genotyped using TaqMan® assays and Sanger sequencing, respectively. Odds ratios (ORs) were calculated using logistic regression, with adjustment for sex and age. Expression of SelS was analyzed by immunohistochemistry in thyroid tissue from HT patients and control subjects. Molecular interactions between the Nrf2 and SelS pathways were investigated in thyroid tissues from mice and in rat PCCL3 thyroid follicular cells. Results: When all three NFE2L2 SNPs were considered together, the presence of one or more minor alleles was associated with a near-significant increased risk (OR = 1.43, p = 0.072). Among subjects harboring only major NFE2L2 alleles, there was no increased HT risk associated with heterozygosity or homozygosity for the SELENOS minor allele. Conversely, in subjects heterozygous or homozygous for the SELENOS risk allele, the presence of an NFE2L2 minor allele significantly increased HT risk by 2.8-fold (p = 0.003). Immunohistochemistry showed reduced expression of SelS in thyroid follicular cells of HT patients. In Nrf2 knockout mice, there was reduced expression of SelS in thyroid follicular cells; conversely, in PCCL3 cells, reducing SelS expression caused reduced activity of Nrf2 signaling. Conclusions: The NFE2L2 promoter genotype interacts with the SELENOS promoter genotype to modulate the risk of HT in a Portuguese population. This interaction may be due to a bidirectional positive feedback between the Nrf2 and SelS pathways.
Delivery room interventions to prevent bronchopulmonary dysplasia in preterm infants: a protocol for a systematic review and network meta-analysis

Introduction As gestational age decreases, incidence of bronchopulmonary dysplasia (BPD) and chronic lung disease increases. There are many interventions used in the delivery room to prevent acute lung injury and consequently BPD in these patients. The availability of different treatment options often poses a practical challenge to the practicing neonatologist when it comes to making an evidence-based choice as the multitude of pairwise systematic reviews including Cochrane reviews that are currently available only provide a narrow perspective through head-to-head comparisons. Methods and analysis We will conduct a systematic review of all randomised controlled trials evaluating delivery room interventions within the first golden hour after birth for prevention of BPD. The primary outcome includes BPD. Secondary outcomes include death at 36 weeks of postmenstrual age or before discharge; severe intraventricular haemorrhage (grade 3 or 4 based on the Papile criteria); any air leak syndromes (including pneumothorax or pulmonary interstitial emphysema); retinopathy of prematurity (any stage) and neurodevelopmental impairment at 18–24 months. We will search from their inception to August 2018, the following databases: Medline, EMBASE and Cochrane Central Register of Controlled Trials as well as grey literature resources. Two reviewers will independently screen titles and abstracts, review full texts, extract information and assess the risk of bias and the confidence in the estimate (with Grading of Recommendations Assessment, Development and Evaluation approach). This review will use Bayesian network meta-analysis approach which allows the comparison of the multiple delivery room interventions for prevention of BPD. We will perform a Bayesian network meta-analysis to combine the pooled direct and indirect treatment effect estimates for each outcome, effectiveness and safety of delivery room interventions for prevention of BPD. Ethics and dissemination The proposed protocol is a network meta-analysis, which has been registered on PROSPERO International prospective register of systematic reviews (CRD42018078648). The results will provide an evidence-based guide to choosing the right sequence of early postnatal interventions that will be associated with the least likelihood of inducing lung injury and BPD in preterm infants. Furthermore, we will identify knowledge gaps and will encourage further research for other therapeutic options. Therefore, its results will be disseminated through peer-reviewed publications and conference presentations. Due to the nature of the design, no ethics approval is necessary.
Gradient Response Harvesting for Continuous System Characterization During MR Sequences

MRI gradient systems are required to generate magnetic field gradient waveforms with very high fidelity. This is commonly implemented by gradient system calibration and pre-emphasis. However, a number of mechanisms, particularly thermal changes, cause variation in the gradient response over time, which cannot be addressed by calibration approaches. To overcome this limitation, we present a novel method termed gradient response harvesting, where the gradient response is continuously characterized during the course of a normal MR sequence. Snippets of field measurements are repeatedly acquired during an MR sequence, and from these multiple field measurements and the known nominal MR sequence gradients, the gradient response and gradient/field offsets are calculated. The calculation is implemented in a model-based and a model-free variant. The method is demonstrated for EPI with high gradient duty-cycle, where the continuous gradient characterization is used to obtain k-space trajectory estimates that are employed in the subsequent image reconstruction. During the course of the MR sequence, changes in both the envelope and the phase of the gradient response functions were observed, including shifts of mechanical resonances. The gradient response changes were also reflected in the calculated uninterrupted gradient waveforms and thus in the k-space trajectories. Using the updated encoding information in the image reconstruction removed ghosting artifacts, that otherwise impaired the image quality. We introduced the concept of gradient response harvesting and demonstrated its feasibility. The obtained gradient response functions may be used for quality assurance/preventive maintenance, real-time adaptation of gradient pre-emphasis or to calculate uninterrupted gradient field evolutions.