Miracle-dz/UniFAR-FTUs huggingface dataset:
Sumatriptan in clinical practice: effectiveness in migraine and the problem of psychiatric comorbidity

Migraine is a multifactorial and disabling syndrome often in comorbidity with psychiatric illnesses. Triptans are the first-line treatment in acute attacks and the most effective drugs in various types of migraine. Sumatriptan was the first medication of this group. Thanks to multiple types of formulations that greatly increase patient's compliance, sumatriptan is so far the most commonly used drug for moderate-to-severe acute migraine attacks. Although generally safe and well tolerated, sumatriptan has to be carefully administered in patients suffering from various types of medical conditions (such as cardiovascular and cerebrovascular disease and some psychiatric illnesses) and/or treated with various medications (such as monoamine oxidase inhibitors and selective serotonin reuptake inhibitors). The administration of sumatriptan in some psychiatric condition in which serotonin plays an important role (i.e., major depressive disorder and obsessive-compulsive disorder) has been underestimated so far. In fact, at present, literature studies are few, with non-conclusive and often contrasting findings. Thus, sumatriptan should continue to be used with caution in patients diagnosed with psychiatric illness and/or treated with drugs where serotonin is crucially involved in, until further data demonstrating complete safety become available.
Oxidized phosphatidylserine–CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells

The phagocytosis of apoptotic cells within an organism is a critical terminal physiological process in programmed cell death. Evidence suggests that apoptotic cell engulfment and removal by macrophages is facilitated by phosphatidylserine (PS) displayed at the exofacial surface of the plasma membrane; however, neither the macrophage receptors responsible for PS recognition, nor characterization of the PS molecular species potentially involved, have been clearly defined. We show that the class B scavenger receptor CD36 plays an essential role in macrophage clearance of apoptotic cells in vivo. Further, macrophage recognition of apoptotic cells via CD36 is shown to occur via interactions with membrane-associated oxidized PS (oxPS) and, to a lesser extent, oxidized phosphatidylcholine, but not nonoxidized PS molecular species. Mass spectrometry analyses of oxPS species identify structures of candidate ligands for CD36 in apoptotic membranes that may facilitate macrophage recognition. Collectively, these results identify oxPS–CD36 interactions on macrophages as potential participants in a broad range of physiologic processes where macrophage-mediated engulfment of apoptotic cells is involved.
Cross-Protective Peptide Vaccine against Influenza A Viruses Developed in HLA-A*2402 Human Immunity Model

Background The virus-specific cytotoxic T lymphocyte (CTL) induction is an important target for the development of a broadly protective human influenza vaccine, since most CTL epitopes are found on internal viral proteins and relatively conserved. In this study, the possibility of developing a strain/subtype-independent human influenza vaccine was explored by taking a bioinformatics approach to establish an immunogenic HLA-A24 restricted CTL epitope screening system in HLA-transgenic mice. Methodology/Principal Findings HLA-A24 restricted CTL epitope peptides derived from internal proteins of the H5N1 highly pathogenic avian influenza A virus were predicted by CTL epitope peptide prediction programs. Of 35 predicted peptides, six peptides exhibited remarkable cytotoxic activity in vivo. More than half of the mice which were subcutaneously vaccinated with the three most immunogenic and highly conserved epitopes among three different influenza A virus subtypes (H1N1, H3N2 and H5N1) survived lethal influenza virus challenge during both effector and memory CTL phases. Furthermore, mice that were intranasally vaccinated with these peptides remained free of clinical signs after lethal virus challenge during the effector phase. Conclusions/Significance This CTL epitope peptide selection system can be used as an effective tool for the development of a cross-protective human influenza vaccine. Furthermore this vaccine strategy can be applicable to the development of all intracellular pathogens vaccines to induce epitope-specific CTL that effectively eliminate infected cells.
Company matters: The presence of other genotypes alters traits and intraspecific selection in an Arctic diatom under climate change

Arctic phytoplankton and their response to future conditions shape one of the most rapidly changing ecosystems on the planet. We tested how much the phenotypic responses of strains from the same Arctic diatom population diverge and whether the physiology and intraspecific composition of multistrain populations differs from expectations based on single strain traits. To this end, we conducted incubation experiments with the diatom Thalassiosira hyalina under present‐day and future temperature and pCO2 treatments. Six fresh isolates from the same Svalbard population were incubated as mono‐ and multistrain cultures. For the first time, we were able to closely follow intraspecific selection within an artificial population using microsatellites and allele‐specific quantitative PCR. Our results showed not only that there is substantial variation in how strains of the same species cope with the tested environments but also that changes in genotype composition, production rates, and cellular quotas in the multistrain cultures are not predictable from monoculture performance. Nevertheless, the physiological responses as well as strain composition of the artificial populations were highly reproducible within each environment. Interestingly, we only detected significant strain sorting in those populations exposed to the future treatment. This study illustrates that the genetic composition of populations can change on very short timescales through selection from the intraspecific standing stock, indicating the potential for rapid population level adaptation to climate change. We further show that individuals adjust their phenotype not only in response to their physicochemical but also to their biological surroundings. Such intraspecific interactions need to be understood in order to realistically predict ecosystem responses to global change.
Retinal layer thickness in preclinical Alzheimer's disease

There is urgent need for non‐invasive diagnostic biomarkers in the preclinical phase of Alzheimer's Disease (AD). Several studies suggest that retinal thickness is reduced in AD. Here, we aim to test the diagnostic value of retinal thickness in preclinical AD, as defined by cognitively normal individuals with amyloid pathology on PET.
Ionic Conductance Changes in Voltage Clamped Crayfish Axons at Low pH

Giant axons from the crayfish have been voltage clamped with an axial wire system. General characterististics of observed ionic currents under normal conditions are similar to those measured in other giant axons and in nodes of Ranvier. As the pH of the external bath is lowered below 7, a marked, reversible slowing of potassium currents is seen with little effect on sodium currents. The steady-state potassium conductance-voltage curve is shifted along the voltage axis in a manner consistent with the development of a hyperpolarizing surface charge. Results suggest that this potential shift accounts for part, though not all, of the observed increase in τn. From the behavior of the kinetics of the delayed current with external pH these alterations in potassium conductance are attributed to the titration of a histidine imidazole residue of a membrane protein. Chemical modification of histidine by carbethoxylation at pH 6 slows and strongly depresses potassium currents. The results suggest that in addition to the introduction of electrostatic forces, possibly resulting from a hyperpolarizing surface charge, protonation of a histidine group at low pH also alters the nonelectrostatic chemical interactions determining the ease with which potassium gates open and close. The evidence indicates that the modified histidine residue is closely associated with the membrane components involved in the control of potassium conductance.
A Friend in Need? Exploring the Influence of Disease and Disability Onset on the Number of Close Friends among Older Adults.

OBJECTIVES This research examines whether onset of life-threatening disease (i.e., cancer, lung disease, heart disease, or stroke) or Activities of Daily Living (ADL) disability influences the reported number of close friends. METHODS Using data from the Health and Retirement Study (HRS) (2006-2012), this research capitalizes on panel data to assess changes in number of close friends over a four-year period. Lagged dependent variable (LDV) and change score (CS) approaches were employed. RESULTS Both the LDV and CS models provide evidence that onset of life-threatening disease was associated with reporting more friends four years later. In particular, onset of cancer was associated with reporting more close friends. DISCUSSION This research provides evidence of the network activation hypothesis following onset of life-threatening disease among older adults.
A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection

Herpes simplex virus 2 (HSV2) causes genital herpes in >400 million persons worldwide. We conducted a randomized, double-blinded, placebo-controlled trial of a replication-defective HSV2 vaccine, HSV529. Twenty adults were enrolled in each of 3 serogroups of individuals: those negative for both HSV1 and HSV2 (HSV1−/HSV2−), those positive or negative for HSV1 and positive for HSV2 (HSV1±/HSV2+), and those positive for HSV1 and negative for HSV2 (HSV1+/HSV2−). Sixty participants received vaccine or placebo at 0, 1, and 6 months. The primary end point was the frequency of solicited local and systemic reactions to vaccination. Eighty-nine percent of vaccinees experienced mild-to-moderate solicited injection site reactions, compared with 47% of placebo recipients (95% confidence interval [CI], 12.9%–67.6%; P = .006). Sixty-four percent of vaccinees experienced systemic reactions, compared with 53% of placebo recipients (95% CI, −17.9% to 40.2%; P = .44). Seventy-eight percent of HSV1−/HSV2− vaccine recipients had a ≥4-fold increase in neutralizing antibody titer after 3 doses of vaccine, whereas none of the participants in the other serogroups had such responses. HSV2-specific CD4+ T-cell responses were detected in 36%, 46%, and 27% of HSV1−/HSV2−, HSV1±/HSV2+, and HSV1+/HSV2− participants, respectively, 1 month after the third dose of vaccine, and CD8+ T-cell responses were detected in 14%, 8%, and 18% of participants, respectively. HSV529 vaccine was safe and elicited neutralizing antibody and modest CD4+ T-cell responses in HSV-seronegative vaccinees. NCT01915212.
Disparity of sensitivities in detection of radiation-naïve and postirradiation recurrent nasopharyngeal carcinoma of the undifferentiated type by quantitative analysis of circulating Epstein-Barr virus DNA1,2.

PURPOSE The purpose of this research was to compare the sensitivities of plasma EBV DNA in detection of postirradiation locally recurrent nasopharyngeal carcinoma (NPC), postirradiation distant metastatic NPC, and radiation-naïve NPC. EXPERIMENTAL DESIGN Twenty-four patients with postirradiation local recurrence of NPC were assessed for plasma EBV DNA levels by a real-time quantitative PCR system. The results were compared with those of a cohort of 140 patients with newly diagnosed NPC and with those of 25 patients with distant metastatic relapse. EBV-encoded RNA positivity was also assessed in locally recurrent tumors and newly diagnosed tumors with undetectable plasma EBV DNA levels. RESULTS Postirradiation locally recurrent tumors were associated with a significantly lower rate of detectable plasma EBV DNA compared with radiation-naïve tumors of comparable stage [stage I-II tumors: 5 of 12 (42%) versus 47 of 51 (92%), P = 0.0002; stage III-IV tumors: 10 of 12 (83%) versus 88 of 89 (99%), P = 0.01; Fisher's exact test], and compared with distant metastatic recurrences [15 of 24 (63%) versus 24 of 25 (96%), P < 0.02; Fisher's exact test]. The median EBV DNA level in patients with detectable EBV DNA was also significantly lower in locally recurrent tumors than in radiation-naïve tumors. All of the tissue samples of tumors associated with undetectable EBV DNA levels, where available, were EBV-encoded RNA positive. CONCLUSIONS The sensitivity of EBV DNA in the detection of tumors regrowing from an irradiated site is much lower than that from a radiation-naïve site. Although plasma EBV DNA is very effective in detecting distant metastatic relapse of NPC, it cannot be relied on as the sole surveillance tool for detection of local relapse.
TIDAL DWARF GALAXIES AROUND A POST-MERGER GALAXY, NGC 4922

One possible channel for the formation of dwarf galaxies involves birth in the tidal tails of interacting galaxies. We report the detection of a bright UV tidal tail and several young tidal dwarf galaxy (TDG) candidates in the post-merger galaxy NGC 4922 in the Coma cluster. Based on a two-component population model (combining young and old stellar populations), we find that the light of tidal tail predominantly comes from young stars (a few Myr old). The Galaxy Evolution Explorer ultraviolet data played a critical role in the parameter (age and mass) estimation. Our stellar mass estimates of the TDG candidates are ∼106−7 M☉, typical for dwarf galaxies.
Flaxseed and dried tomato waste used together in laying hens diet

ABSTRACT The aim of this study was to investigate the effects of simultaneous supplementation of laying hens with dietary sources of n-3 polyunsaturated fatty acids (PUFA) and carotenoids on egg quality, fatty acids and carotenoid profile of the egg yolk and on feed and yolk lipid peroxidation. A 6-week experiment was carried out with 53-week old laying hens (96 Tetra SL) assigned to a control and three treatment groups supplemented with 5% flaxseeds and different levels of dried tomato waste (DTW, 2.5%, 5.0% and 10.0%). Hens from the groups supplemented with 5% and 7.5% DTW had a significantly lower average daily feed intake and laying percentage as compared to the control. Increased doses of dietary DTW enhanced yolk Roche colour score in direct correlation with the enrichment of egg yolk in carotenoids but decreased their transfer efficiency from feed to egg. After 4 weeks, egg yolk from hens fed with 5% flaxseeds and 7.5% DTW had increased lutein and zeaxanthin levels (by 29% and 24%, respectively) and the colour score was 3.5 fold higher compared to the control group. As a result of the dietary supplementation with flaxseed, the n-3 fatty acid content was 3.1–3.7-fold higher in egg yolk compared with the control and the n-6/n-3 ratio decreased from 18.3 (control) to 4.1–5.4 in supplemented diets. Dietary supplementation with 5% DTW effectively prevented lipid oxidation of eggs enriched with n-3 PUFA, but the increase in DTW content depressed the absorption and deposition of n-3 PUFA in egg yolk.
Pregnancy and Litter Size, But Not Lamb Sex, Affect Feed Intake and Wool Production by Merino-Type Ewes

Simple Summary We examined whether feed intake and wool production are affected by pregnancy, litter size, or lamb sex on Merino genotype ewes. We observed that feed intake was influenced during pregnancy and lactation by litter size; whereas, wool production was influenced by litter size, but not by the sex of the lambs during pregnancy. Abstract Two experiments (Australia and Mexico) tested whether feed intake (FI) and wool production (WP) are affected by pregnancy (PRG), litter size (LZ), or lamb sex (LS) in Merino-type ewes. In Experiment-1, ewes were either not pregnant (NPR; n = 6), or carrying 1 (PR1; n = 7) or 3 (PR3; n = 11) fetuses, were studied in individual pens. NPR ewes had lower (p < 0.02) FI throughout PRG and lactation (LAC), except around lambing (p < 0.001). Following lambing, FI increased in PRG ewes (p < 0.001) to double the values in NPR ewes. PRG reduced WP (p < 0.001); in PR3, WP was lower than for both PR1 and NPR (p < 0.001). WP decreased during LAC and was lower in ewes rearing lambs than in NPR ewes (p < 0.001). Experiment-2 used 48 pregnant ewes (28 bearing singles and 20 bearing twins). Dam and lamb live weights (LW) and body condition (BC) were recorded from birth to weaning at 60 d, and dam fleece weight (DFW) was measured at weaning (12 months growth). WP was higher in ewes bearing and rearing single lambs than in ewes bearing twins (p < 0.001). DFW was positively (p < 0.01) related to LZ, dam LW, and BC, but not to changes in dam LW during LAC, or to lamb weight at birth or weaning, or LW gain, or LS. In conclusion, FI was affected during PRG and by LZ during LAC, whereas WP was influenced by LZ, but not LS, only during pregnancy.
Association of Chromosome Territories with the Nuclear Matrix

To study the possible role of the nuclear matrix in chromosome territory organization, normal human fibroblast cells are treated in situ via classic isolation procedures for nuclear matrix in the absence of nuclease (e.g., DNase I) digestion, followed by chromosome painting. We report for the first time that chromosome territories are maintained intact on the nuclear matrix. In contrast, complete extraction of the internal nuclear matrix components with RNase treatment followed by 2 M NaCl results in the disruption of higher order chromosome territory architecture. Correlative with territorial disruption is the formation of a faint DNA halo surrounding the nuclear lamina and a dispersive effect on the characteristically discrete DNA replication sites in the nuclear interior. Identical results were obtained using eight different human chromosome paints. Based on these findings, we developed a fractionation strategy to release the bulk of nuclear matrix proteins under conditions where the chromosome territories are maintained intact. A second treatment results in disruption of the chromosome territories in conjunction with the release of a small subset of acidic proteins. These proteins are distinct from the major nuclear matrix proteins and may be involved in mediating chromosome territory organization.
Macroscopic evaluation of the placenta of the alpaca (Vicugna pacos).

Macroscopic evaluation of the placenta is an essential post-partum examination in the alpaca and can be of special interest in case of abortion, premature birth or stillbirth. Since there are not many reference values regarding macroscopic properties of normal alpaca placentas, a small descriptive study was conducted. Only placentae from normally foaling alpaca mares, giving birth to healthy crias, after a full-term and uneventful gestation (±350 days; range 335-360 days) were taken into account (N = 11). Crias weighed (±SD) 7.7 ± 2.25 kg (range 5.5-10 kg), while the mean weight of the full-term placentas was 0.8 ± 0.19 kg, that is 10% of the bodyweight of the crias. The weight of the allantoamnion and chorion was 0.2 ± 0.07 kg and 0.5 ± 0.13 kg, respectively. The umbilical cord length was 8.8 ± 2.84 cm, and the length of the pregnant and non-pregnant uterine horns was 69.4 ± 12.77 cm and 54.5 ± 6.81 cm, respectively. The length of the corpus was 14.6 ± 4.68 cm, and the distance from the umbilicus to the corpus was 18.5 ± 6.13 cm. The tissue volume of the allantoamnion was 0.14 ± 0.079 L, and the chorionic volume was 0.37 ± 0.078 L. The surface area of the allantoamnion and the chorion was 87.6 ± 15.56 dm2 and 72.3 ± 9.28 dm2 , respectively. All placentas had small calcifications either around the umbilical cord alone or around the umbilicus and blood vessels of the pregnant uterine horn. These measurements could be used to macroscopically evaluate alpaca placentas, although more research is needed to extend our knowledge of macroscopic evaluation of normal and abnormal placentas.
Global patterns of intraspecific leaf trait responses to elevation

Elevational gradients are often used to quantify how traits of plant species respond to abiotic and biotic environmental variations. Yet, such analyses are frequently restricted spatially and applied along single slopes or mountain ranges. Since we know little on the response of intraspecific leaf traits to elevation across the globe, we here perform a global meta‐analysis of leaf traits in 109 plant species located in 4 continents and reported in 71 studies published between 1983 and 2018. We quantified the intraspecific change in seven morpho‐ecophysiological leaf traits along global elevational gradients: specific leaf area (SLA), leaf mass per area (LMA), leaf area (LA), nitrogen concentration per unit of area (Narea), nitrogen concentration per unit mass (Nmass), phosphorous concentration per unit mass (Pmass) and carbon isotope composition (δ13C). We found LMA, Narea, Nmass and δ13C to significantly increase and SLA to decrease with increasing elevation. Conversely, LA and Pmass showed no significant pattern with elevation worldwide. We found significantly larger increase in Narea, Nmass, Pmass and δ13C with elevation in warmer regions. Larger responses to increasing elevation were apparent for SLA of herbaceous compared to woody species, but not for the other traits. Finally, we also detected evidences of covariation across morphological and physiological traits within the same elevational gradient. In sum, we demonstrate that there are common cross‐species patterns of intraspecific leaf trait variation across elevational gradients worldwide. Irrespective of whether such variation is genetically determined via local adaptation or attributed to phenotypic plasticity, the leaf trait patterns quantified here suggest that plant species are adapted to live on a range of temperature conditions. Since the distribution of mountain biota is predominantly shifting upslope in response to changes in environmental conditions, our results are important to further our understanding of how plants species of mountain ecosystems adapt to global environmental change.