Miracle-dz/UniFAR-FTUs huggingface dataset:
Ex Vivo Transepithelial Collagen Cross-linking in Porcine and Human Corneas Using Human Decorin Core Protein.

PURPOSE To investigate changes in corneal biomechanics after cross-linking with human decorin core protein (decoron), which is a small, naturally occurring proteoglycan that bridges collagen fibrils, organizing and stabilizing lamellar collagen architecture. METHODS Five human donor pairs (10 eyes) and 5 porcine pairs (10 eyes) had one random eye treated transepithelially with decoron, with the untreated fellow eye serving as control. Pretreatment (45 to 60 seconds) and penetration enhancer (45 to 60 seconds) preceded instillation of decoron (45 to 60 seconds). Total treatment time was less than 4 minutes per eye. Human donor eyes were evaluated using the CorVis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) at 15, 20, 30, 40, and 50 mm Hg of intraocular pressure. Elastic modulus was calculated for human corneas, using parameters derived from Scheimpflug images. Analysis of variance was performed. Porcine corneas underwent uniaxial tensile testing with a Rheometrics Systems Analyzer (RSA III; TA Instruments, New Castle, DE). Secant modulus was calculated and paired t tests were performed between treated and control groups. RESULTS One human eye pair was excluded based on initial corneal thickness greater than 850 µm. Analysis of variance of the included four pairs demonstrated a significant treatment effect (P < .05) in deformation amplitude, first applanation velocity, initial curvature, and pachymetry, with all lower in the treatment group, consistent with stiffening and cross-linking. Elastic modulus demonstrated a significant treatment effect with a higher elastic modulus in the treatment group. In porcine eye pairs, the secant modulus was significantly higher in the treated than the untreated corneas at 4%, 5%, and 6% strain (P < .05). CONCLUSIONS Treatment with decorin core protein produced stiffer biomechanical behavior and higher elastic modulus in both human and porcine corneas in this preliminary ex vivo study. Further studies are needed to evaluate clinical safety, efficacy, and long-term stability. [J Refract Surg. 2016;32(6):410-417. ].
Psychedelics as Medicines: An Emerging New Paradigm

Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5‐HT2A receptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms, with potential advantages over existing antiinflammatory agents. We propose that psychedelics exert therapeutic effects for psychiatric disorders by acutely destabilizing local brain network hubs and global network connectivity via amplification of neuronal avalanches, providing the occasion for brain network “resetting” after the acute effects have resolved. Antiinflammatory effects may hold promise for efficacy in treatment of inflammation‐related nonpsychiatric as well as potentially for psychiatric disorders. Serotonergic psychedelics operate through unique mechanisms that show promising effects for a variety of intractable, debilitating, and lethal disorders, and should be rigorously researched.
Involvement of Substance P in Peripheral Neuropathy Induced by Paclitaxel but Not Oxaliplatin

The painful peripheral neuropathy occurring frequently during chemotherapy with paclitaxel or oxaliplatin is one of their dose-limiting factors. We reported previously that substance P is involved in the pathogenesis of pulmonary hypersensitivity reaction to paclitaxel in rats, and an antiallergic agent pemirolast reverses this reaction via the blockade of release of substance P. In the present study, we investigated the involvement of substance P in paclitaxel-induced peripheral neuropathy compared with that by oxaliplatin. In von Frey and acetone tests in rats repeated administration of paclitaxel (6 mg/kg i.p., once a week for 4 weeks) or oxaliplatin (4 mg/kg i.p., twice a week for 4 weeks) induced both mechanical allodynia and cold hyperalgesia. Paclitaxel-induced peripheral neuropathy was reversed primarily by the acute administration of pemirolast (0.1 and 1 mg/kg p.o.). Moreover, coadministration of the receptor antagonists neurokinin 1 [N-acetyl-l-tryptophan 3,5-bis(trifluoromethyl)benzylester (L-732,138), 100 μg/body i.t. ] and neurokinin 2 [5-fluoro-3-[2-[4-methoxy-4-[[(R)-phenylsulphinyl]methyl]-1-piperidinyl]ethyl]-1H-indole (GR159897), 100 μg/body i.t. ] strongly reversed paclitaxel-induced neuropathy. On the other hand, oxaliplatin-induced peripheral neuropathy was not reversed by pemirolast. In the in vitro study using cultured adult rat dorsal root ganglion neurons paclitaxel (1000 ng/ml) significantly increased the release of substance P, and pemirolast (100 and 1000 nM) significantly inhibited this increase of substance P release. Oxaliplatin, by contrast, did not increase the release of substance P. These results suggest that substance P is involved in paclitaxel-induced neuropathy, and the mechanism of its action is clearly different from that of oxaliplatin.
Increasing HIV subtype diversity and its clinical implications in a sentinel North American population.

BACKGROUND HIV-1 is a highly diverse virus; subtypes may exhibit differences in rates of transmission, disease progression, neurotoxicity, antiretroviral treatment failure profiles and accuracy of viral load measurements. To date, the HIV epidemic in Canada and the rest of the developed world has been largely due to subtype B; however, shifts in subtype epidemiology could have significant implications. OBJECTIVE To determine whether there has been an increase in HIV subtype diversity in southern Alberta, Canada. METHODS All 2358 patients receiving any HIV care between December 31, 2001 and December 31, 2010 were included in a retrospective analysis of subtype prevalence and incidence. In an indexed analysis, subtype trends from 1994 to 2010 were also evaluated. RESULTS Between 2001 and 2010, the prevalence of non-B HIV subtypes in patients with a known subtype increased from 7% to 24%. In 2010, the most prevalent non-B subtypes were C (65%), A (11%), CRF02_AG (9.7%), CRF01_AE (4.9%), D (3.9%), G (2.9%) and CRF06_cpx (1.5%). In the indexed analysis, there was an overall proportional increase in non-B subtypes of 2.3% per year. The year-over-year increase in the prevalence of patients infected with a nonsubtype B virus increased from 13% from 1995 to 2002 to 27% from 2003 to 2010 (P=0.01). Incident non-B subtype cases increased from 9.6% to 32.4% over these time periods. CONCLUSIONS This recent and dramatic shift in HIV strain diversity in Canada is unprecedented and may have important public health, research and clinical consequences.
Risk of trauma exposure among persons with mental illness in jails and prisons: what do we really know?

Purpose of review Traumatic victimization, particularly sexual abuse, is a serious problem in correctional facilities and those suffering from mental illnesses are especially vulnerable. This review examines our current knowledge regarding trauma victimization among persons with mental illness serving time in jails/prisons, considers methodological challenges, and provides recommendations for future research. Recent findings Traumatic victimization, particularly sexual abuse, has consistently been identified as a high-frequency problem within jails and prisons. Lifetime, 6-month, and 12-month prevalence rates of physical and sexual violence among incarcerated people are quite high relative to nonincarcerated populations, and women report much higher rates of most traumatic events than men. Moreover, data show that inmates with mental illnesses are up to eight times more likely to be victims of sexual abuse than nonmentally ill inmates. Summary Additional research is needed to improve our understanding of this issue and inform change efforts. Future research should include: epidemiological studies to improve our knowledge of risk factors and correlates of victimization; prospective studies to determine causality between trauma victimization and mental illness or other adverse outcome; and intervention studies to examine strategies for reducing violence and traumatic victimization inside correctional facilities, effective treatments for posttraumatic psychopathology, and improved re-entry outcomes.
Effects of social determinants on food choice and skipping meals among Turkish adolescents.

PURPOSE To present data that contributes to understanding factors that influence food choice and skipping meals in adolescents. METHODS A cross sectional study is carried in selected high schools in Bornova. Study sample compromises of 527 students chosen randomly by class from a population of 2410 first year in high school students. Self-administered questionnaires containing sociodemographic determinants, self reported weight and height, food choices and meal patterns were used. FINDINGS A psychosocial factor that affects almost all of the students is the "taste and sensory perception of food". The second noticable factor is the "health and nutritious value of food". The time conserved and the convenience in the preparation of food is one of the lifestyle factors that affect more than half of the students. The cost of the food was also found to have an effect. Among the third group of factors categorized as "media", the leading factor is advertisement, effective in one third of the students. Among boys and girls, there was no statistical difference in the type of meal skipped. Living in Izmir for more than 10 years compared to less than ten years, being in a nuclear family to extended family, and belonging to the "owner" social class to "wage laborer" class also do not statistically differ with regard to skipping meals. However, the mother's and father's education level and having a working mother are associated with skipping meals. CONCLUSIONS These results provide important evidence to support opportunities to positively influence the adoption of healthful eating.
New Force Field on Modeling Intrinsically Disordered Proteins

Intrinsically disordered proteins or intrinsically disordered protein regions comprise a large portion of eukaryotic proteomes (between 35% and 51%). These intrinsically disordered proteins were found to link with cancer and various other diseases. However, widely used additive force field parameter sets are insufficient in quantifying the structural properties of intrinsically disordered proteins. Therefore, we explored to a systematic correction of a base additive force field parameter set (chosen as Amber ff99SBildn) to correct the biases that was first demonstrated in simulations with the base parameter set. Specifically, the φ/ψ distributions of disorder‐promoting residues were systematically corrected with the CMAP method. Our simulations show that the CMAP corrected Amber parameter set, termed ff99IDPs, improves the φ/ψ distributions of the disorder‐promoting residues with respect to the benchmark data of intrinsically disordered protein structures, with root mean‐squared percentage deviation less than 0.15% between the simulation and the benchmark. Our further validation shows that the chemical shifts from the ff99IDPs simulations are in quantitative agreement with those from reported NMR measurements for two tested IDPs, MeV NTAIL, and p53. The predicted residue dipolar couplings also show high correlation with experimental data. Interestingly, our simulations show that ff99IDPs can still be used to model the ordered state when the intrinsically disordered proteins are in complex, in contrast to ff99SBildn that can be applied well only to the ordered complex structures. These findings confirm that the newly proposed Amber ff99IDPs parameter set provides a reasonable tool in further studies of intrinsically disordered protein structures. In addition, our study also shows the importance of considering intrinsically disordered protein structures in general‐purposed force field developments for both additive and non‐additive models.
Response of Inorganic Fine Particulate Matter to Emission Changes of Sulfur Dioxide and Ammonia: The Eastern United States as a Case Study

Abstract A three-dimensional chemical transport model (PMCAMx) was used to investigate changes in fine particle (PM2.5) concentrations in response to changes in sulfur dioxide (SO2) and ammonia (NH3) emissions during July 2001 and January 2002 in the eastern United States. A uniform 50% reduction in SO2 emissions was predicted to produce an average decrease of PM2.5 concentrations by 26% during July but only 6% during January. A 50% reduction of NH3 emissions leads to an average 4 and 9% decrease in PM2.5 in July and January, respectively. During the summer, the highest concentration of sulfate is in South Indiana (12.8 μg m-3), and the 50% reduction of SO2 emissions results in a 5.7 μg m-3(44%) sulfate decrease over this area. During winter, the SO2 emissions reduction results in a 1.5 μg m-3 (29%) decrease of the peak sulfate levels (5.2 μg m-3) over Southeast Georgia. The maximum nitrate and ammonium concentrations are predicted to be over the Midwest (1.9 μg m-3 in Ohio and 5.3 μg m-3 in South Indiana, respectively) in the summer whereas in the winter these concentrations are higher over the Northeast (3 μg m-3 of nitrate in Connecticut and 2.7 μg m-3 of ammonium in New York). The 50% NH3 emissions reduction is more effective for controlling nitrate, compared with SO2 reductions, producing a 1.1 μg m-3 nitrate decrease over Ohio in July and a 1.2 μg m-3 decrease over Connecticut in January. Ammonium decreases significantly when either SO2 or NH3 emissions are decreased. However, the SO2 control strategy has better results in July when ammonium decreases, up to 2 μg m-3 (37%), are predicted in South Indiana. The NH3 control strategy has better results in January (ammonium decreases up to 0.4 μg m-3 in New York). The spatial and temporal characteristics of the effectiveness of these emission control strategies during the summer and winter seasons are discussed.
Differential recruitment of tetratricorpeptide repeat domain immunophilins to the mineralocorticoid receptor influences both heat-shock protein 90-dependent retrotransport and hormone-dependent transcriptional activity.

The mineralocorticoid receptor (MR) forms oligomers with the heat-shock protein 90 (Hsp90) -based heterocomplex, which contains tetratricopeptide repeat (TPR) domain immunophilins (IMMs). Here we investigated the unknown biological role of IMMs in the MR.Hsp90 complex. Upon hormone binding, FKBP52 was greatly recruited to MR.Hsp90 complexes along with dynein motors, whereas FKBP51 was dissociated. Importantly, the Hsp90 inhibitor geldanamycin impaired the retrograde transport of MR, suggesting that the Hsp90.IMM. dynein molecular machinery is required for MR movement. To elucidate the mechanism of action of MR, the synthetic ligand 11,19-oxidoprogesterone was used as a tool. This steroid showed equivalent agonistic potency to natural agonists and was able to potentiate their mineralocorticoid action. Importantly, aldosterone binding recruited greater amounts of FKBP52 and dynein than 11,19-oxidoprogesterone binding to MR. Interestingly, 11,19-oxidoprogesterone binding also favored the selective recruitment of the IMM-like Ser/Thr phosphatase PP5. Each hormone/MR complex yielded different proteolytic peptide patterns, suggesting that MR acquires different conformations upon steroid binding. Also, hormone/MR complexes showed different nuclear translocation rates and subnuclear redistribution. All these observations may be related to the selective swapping of associated factors. We conclude that (a) the Hsp90.FKBP52. dyenin complex may be responsible for the retrotransport of MR; (b) a differential recruitment of TPR proteins such as FKBP51, FKBP52, and PP5 takes place during the early steps of hormone-dependent activation of the receptor; (c) importantly, this swapping of TPR proteins depends on the nature of the ligand; and (d) inasmuch as FKBP51 also showed an inhibitory effect on MR-dependent transcription, it should be dissociated from the MR.Hsp90 complex to positively regulate the mineralocorticoid effect.
Dual Airgap Stator- and Rotor-Permanent Magnet Machines With Spoke-Type Configurations Using Phase-Group Concentrated Coil Windings

This paper presents an advanced design procedure for stator-based and rotor-based permanent magnet (PM) machines to improve the electromagnetic performance by incorporating the spoke-type magnet configurations, phase-group concentrated coil windings, and an unaligned arrangement of two rotors/stators. The dual-rotor switched flux PM machine (SFPMM), designated as the stator-PM machine, and the dual-stator spoke-type interior PM machine (S-IPMM), termed the rotor-PM machine, are designed by the proposed design procedure to obtain high torque density and low pulsating torques for direct-drive applications. A quantitative comparison is performed between the proposed SFPMM and S-IPMM, and a conventional SFPMM with concentrated windings is adopted as the referenced model to evaluate the contribution of the proposed design procedure. The machine performance including back electromotive force, cogging torque, and electromagnetic torque is first analyzed by a finite element method under the same operating conditions. Finally, a prototype of the dual-stator S-IPMM is manufactured, and some key simulation results are verified by the experimental tests.
The pharmacology of neuroplasticity induced by non‐invasive brain stimulation: building models for the clinical use of CNS active drugs

Abstract The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto‐temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non‐invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS‐induced plasticity can explore and potentially predict the therapeutic efficacy of CNS‐acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment.
The Reverse Remodeling Effect of Mesenchymal Stem Cells is Independent from the Site of Epimyocardial Cell Transplantation

Objective The transplantation of mesenchymal stem cells (MSCs) represents a promising approach for treating the ischemic and the nonischemic diseased heart. The positive effects of transplanting these cells could be shown, but the exact mechanisms remain unknown. We evaluated whether the injection site affects the improvement in left ventricular (LV) ejection fraction (EF) and angiogenesis in doxorubicin (Dox)–induced failing hearts. Methods Heart failure was induced in New Zealand white rabbits by doxorubicin treatment, followed by right ventricular MSC transplantation (RV-MSC, n = 6), LV MSC transplantation (LV-MSC, n = 6), sham treatment (sham group, n = 6), or no therapy (Dox group, n = 5). Healthy rabbits were used as control group (n = 8). Cells were isolated after bone marrow aspiration and transplanted locally into the ventricular myocardium. After 4 weeks, cardiac function and capillary density (CD31 staining) were measured. Results The transplantation of MSCs increased the EF significantly (LV-MSC, 39.0% ± 1.4%, and RV-MSC, 39.2% ± 2.6%, vs sham group, 29.8% ± 3.7%; P < 0.001), without significance between the MSC groups (P = 0.858). Neither the evidence of a transdifferentiation nor any signs of cell engraftment of transplanted cells could be found. The capillary density (capillaries/high-power field) increased in both MSC groups compared with the sham group (LV-MSC by 8.3% ± 3.4%; and RV-MSC, 8.1% ± 2.2%; P < 0.05), without significance between the two MSC groups (P = 0.927). Conclusions Injection of autologous MSCs in doxorubicin-induced cardiomyopathic rabbit hearts improves EF and enhances angiogenesis. Despite local application, we observed global effects on heart function and capillary density without significant difference between right and LV injection. The paracrine mechanism might be one possible explanation for these findings.
Gender Differences in Polysomnographic Sleep in Young Healthy Sleepers

Middle‐aged and elderly populations exhibit gender differences in polysomnographic (PSG) sleep; however, whether young men and women also show such differences remains unclear. Thirty‐one young healthy sleepers (16 men and 15 women, aged 18 to 30 yr, mean±SD, 20.5±2.4 yr) completed 3 consecutive overnight sessions in a sleep laboratory, after maintaining a stable sleep‐wake cycle for 1 wk before study entry. Standard PSG sleep and self‐rated sleepiness data were collected each night. Across nights, women showed better sleep quality than men: they fell asleep faster (shorter sleep onset latency) and had better sleep efficiency, with more time asleep and less time awake (all differences showed large effect sizes, d=0.98 to 1.12). By contrast, men were sleepier than women across nights. Both men and women demonstrated poorer overall sleep quality on the first night compared with the subsequent 2 nights of study. We conclude young adult healthy sleepers show robust gender differences in PSG sleep, like older populations, with better sleep quality in women than in men. These results highlight the importance of gender in sleep and circadian rhythm research studies employing young subjects and have broader implications for women's health issues relating to these topics.