Miracle-dz/UniFAR-FTUs huggingface dataset:
Conjunctival Injection Reduction in Patients with Atopic Keratoconjunctivitis Due to Synergic Effect of Bovine Enteric-Coated Lactoferrin in 0.1% Tacrolimus Ophthalmic Suspension

Lactoferrin (LF), a multifunctional glycoprotein found in mammalian milk, is reported to have immunoregulatory effects. The present study aimed to evaluate whether enteric-coated LF (eLF) could improve symptoms in patients with atopic keratoconjunctivitis (AKC). This randomized double-blind placebo-controlled single-center trial comprised Japanese patients (n = 20; aged 22–60 years) with AKC. Patients treated with 0.1% tacrolimus ophthalmic suspension (TALYMUS®) were administered eLF (400 mg/d of bovine LF) or placebo tablets for 12 weeks. Conjunctival injection was examined, papillae formation in the palpebral conjunctiva was evaluated, and corneal fluorescein score, itchy sensation in end-point itching scale, and serum allergic parameters were assessed. Conjunctival injection was significantly reduced in the LF group than in the placebo group (p = 0.0017, Mann–Whitney U-test). Papillae formation in the palpebral conjunctiva showed a statistical decrease in the LF group than in the placebo group (p = 0.010, unpaired T-test). LF combined with TALYMUS® could be a promising treatment strategy to mitigate AKC.
Comment on “Homozygous familial hypercholesterolemia with severe involvement of the aortic valve: A sibling‐controlled case study on the efficacy of lipoprotein apheresis”

Dear Editor, We read with interest the report of Galiano et al entitled “Homozygous familial hypercholesterolemia with severe involvement of the aortic valve-A sibling-controlled case study on the efficacy of lipoprotein apheresis” where is highlighted that in Homozygous familial hypercholesterolemia (HoFH) the lipid-lowering therapy, including Lipoprotein Apheresis (LA), should be initiated as early as possible following the diagnosis, because the HoFH prognosis is substantially treatment-dependent. Furthermore, a recent paper comparing HoFH different management approaches, highlights the importance in these patients of LA therapy for a correct treatment aiming to reduce cardiovascular events. However, the combination of LA with drug therapy, even though delays the development of atherosclerosis, it does not completely arrest its progression. For decades, LA had stood as sole, safe and lifesaving treatment. The new cholesterol-lowering drugs, recently introduced, even though very effective, do not have the right observation time to rule out their long-time safety. Therefore, it is not possible to anticipate the long-term consequences of Lomitapide, even if the Lomitapide Observational Worldwide Evaluation Registry (LOWER ClincalTrial.gov identifier NCT0213570) can give us some answers. This drug is available in Italy and it is refunded by the National Health System (€ 34.50986 for 28 days of therapy). Also, PCSK9 inhibitors are not effective in null receptor HoFH and the effects on Lp(a) levels are quite unpredictable. The importance of personalized LA management has been recently discussed in an explicative case report: a HoFH patient, treated out of the general recommendations (LA interval of 14 days and filtered plasma extended to 2.5-3 volume) for 21 years, showed atherosclerotic regression and no cardiovascular event. In our point of view, there is still place to design studies for better personalize LA treatment in terms of intervals and treated plasma volume, in order to improve patient's quality of life and to reduce healthcare costs.
Relation of outcomes to ABC (Atrial Fibrillation Better Care) pathway adherent care in European patients with atrial fibrillation: an analysis from the ESC-EHRA EORP Atrial Fibrillation General Long-Term (AFGen LT) Registry.

AIMS There has been an increasing focus on integrated, multidisciplinary, and holistic care in the treatment of atrial fibrillation (AF). The 'Atrial Fibrillation Better Care' (ABC) pathway has been proposed to streamline integrated care in AF. We evaluated the impact on outcomes of an ABC adherent management in a contemporary real-life European-wide AF cohort. METHODS AND RESULTS Patients enrolled in the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry with baseline data to evaluate ABC criteria and available follow-up data were considered for this analysis. Among the original 11 096 AF patients enrolled, 6646 (59.9%) were included in this analysis, of which 1996 (30.0%) managed as ABC adherent. Patients adherent to ABC care had lower CHA2DS2-VASc and HAS-BLED scores (mean ± SD, 2.68 ± 1.57 vs. 3.07 ± 1.90 and 1.26 ± 0.93 vs. 1.58 ± 1.12, respectively; P < 0.001). At 1-year follow-up, patients managed adherent to ABC pathway compared to non-adherent ones had a lower rate of any thromboembolic event (TE)/acute coronary syndrome (ACS)/cardiovascular (CV) death (3.8% vs. 7.6%), CV death (1.9% vs. 4.8%), and all-cause death (3.0% vs. 6.4%) (all P < 0.0001). On Cox multivariable regression analysis, ABC adherent care showed an association with a lower risk of any TE/ACS/CV death [hazard ratio (HR): 0.59, 95% confidence interval (CI): 0.44-0.79], CV death (HR: 0.52, 95% CI: 0.35-0.78), and all-cause death (HR: 0.57, 95% CI: 0.43-0.78). CONCLUSION In a large contemporary cohort of European AF patients, a clinical management adherent to ABC pathway for integrated care is associated with a significant lower risk for cardiovascular events, CV death, and all-cause death.
Genetic variability of the sws1 cone opsin gene among New World monkeys

Vision is a major sense for Primates and the ability to perceive colors has great importance for the species ecology and behavior. Visual processing begins with the activation of the visual opsins in the retina, and the spectral absorption peaks are highly variable among species. In most Primates, LWS/MWS opsins are responsible for sensitivity to long/middle wavelengths within the visible light spectrum, and SWS1 opsins provide sensitivity to short wavelengths, in the violet region of the spectrum. In this study, we aimed to investigate the genetic variation on the sws1 opsin gene of New World monkeys (NWM) and search for amino acid substitutions that might be associated with the different color vision phenotypes described for a few species. We sequenced the exon 1 of the sws1 opsin gene of seven species from the families Callitrichidae, Cebidae, and Atelidae, and searched for variation at the spectral tuning sites 46, 49, 52, 86, 90, 93, 114, 116, and 118. Among the known spectral tuning sites, only residue 114 was variable. To investigate whether other residues have a functional role in the SWS1 absorption peak, we performed computational modeling of wild‐type SWS1 and mutants A50I and A50V, found naturally among the species investigated. Although in silico analysis did not show any visible effect caused by these substitutions, it is possible that interactions of residue 50 with other sites might have some effect in the spectral shifts in the order of ~14 nm, found among the NWM. We also performed phylogenetic reconstruction of the sws1 gene, which partially recovered the species phylogeny. Further studies will be important to uncover the mutations responsible for the phenotypic variability of the SWS1 of NWM, and how spectral tuning may be associated with specific ecological features such as preferred food items and habitat use.
Factors Affecting Nitrogen Fixation by White Clover (Trifolium repens) on Colliery Spoil

(1) The nitrogen fixation of white clover established on colliery spoil was measured by the acetylene reduction technique at weekly intervals between May and November. (2) Spoil chemical characteristics, moisture and temperature, sunshine hours, air temperature and rainfall were also monitored over the same period. (3) Residual spoil phosphate levels from two rates of phosphate fertilizer applied 5 years previously affected fixation. High residual phosphate gave significantly higher nitrogen fixation than low. These differences resulted in higher spoil nitrogen on high phosphate plots. (4) Sunshine hours, spoil temperature and moisture levels most affected nitrogen fixation over the sampling period. Between June and September fixation was most highly correlated with rainfall between 12 and 27 days prior to sampling. When moisture supplies were adequate, temperature and sunshine hours assumed greater importance. (5) The estimated annual nitrogen inputs by fixation were 146-167 kg N ha-1 on high phosphate plots and 90-103 kg N ha-1 on low phosphate plots. No nitrogen fixation was detected on plots not containing white clover. (6) Cutting apparently decreased nitrogen fixation rates. (7) Ways of maximizing nitrogen fixation on colliery spoil are discussed in the light of these findings.
Ephemeroptera ): An Effective Indicator of Water Bodies Conditions in Jordan

In this article, the quality of Ephemeroptera) as biological indicators species from the study area that covers streams determined and dist inguished from each other including gr simile , Caenis antoninae , Caenis sp associated with Caenidae larvae in running as an indicator of clean to moderately freshwater but it is so rare that their values indicator in Jordan is pollutants while Caenis antoninae is a good indicator for stand Cloeon gr simile could tolerate salty water and can be considered as a good indicator of Only one species Nigrobaetis vuatazi was found to tolerate In Jordan, species of Baetidae family show more fauna are absent in eutrophic and thermal water bodies. indicators for water quality monitoring.
Shedding ‘light’ on cigarette pack design: colour differences in product perceptions, use and exposure following the US descriptor ban

Introduction Many countries removed misleading descriptors (eg, ‘light,’ ‘mild’) from cigarette packaging because they falsely conveyed messages of reduced risk. It is unclear if relabelled products currently promote misperceptions or differences in product use and toxicant exposure. We compared product perceptions, use and exposure between a US sample of Marlboro Gold (formerly ‘light’) and Red smokers. Methods 240 non-treatment-seeking adult daily Marlboro smokers (70% male, 71% White, mean cigarettes/day=16.4 (SD=8.3)) completed two laboratory sessions over a 5-day period. During sessions, participants smoked two cigarettes through a topography device to capture their puffing behaviour, provided precigarette and postcigarette carbon monoxide (CO) assessments, and completed risk perception and subjective rating questionnaires. Self-reported cigarettes per day were verified via daily filter collection; urine collected at the end of the period was assayed for nicotine metabolites. Results Gold (n=49) smokers were more likely than Red (n=191) to incorrectly believe their cigarettes had less nicotine and tar than regular cigarettes (ps<0.001), and rated them as weaker, less harsh, and mild tasting (ps<0.05). Differences between Red and Gold smokers in cigarettes per day and puffing behaviours trended towards significance (ps<0.1). Notably, there were no group differences on CO boost or total nicotine equivalents (ps>0.1). Conclusions Misperceptions about nicotine and tar exist years after rebranding Marlboro Lights as Marlboro Gold. Biological results support that Gold smokers do not have lower toxicant exposure. The US should consider comprehensive packaging or product design regulations to properly inform smokers of product risks. Trial registeration number NCT02301351.
Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity

Phosphatidic acid (PA) is a glycerophospholipid intermediate in the triglyceride synthesis pathway that has incredibly important structural functions as a component of cell membranes and dynamic effects on intracellular and intercellular signaling pathways. Although there are many pathways to synthesize and degrade PA, a family of PA phosphohydrolases (lipin family proteins) that generate diacylglycerol constitute the primary pathway for PA incorporation into triglycerides. Previously, it was believed that the pool of PA used to synthesize triglyceride was distinct, compartmentalized, and did not widely intersect with signaling pathways. However, we now know that modulating the activity of lipin 1 has profound effects on signaling in a variety of cell types. Indeed, in most tissues except adipose tissue, lipin-mediated PA phosphohydrolase activity is far from limiting for normal rates of triglyceride synthesis, but rather impacts critical signaling cascades that control cellular homeostasis. In this review, we will discuss how lipin-mediated control of PA concentrations regulates metabolism and signaling in mammalian organisms.
An optimal cortical bone trajectory technique to prevent early surgical complications.

BACKGROUND Cortical bone trajectory (CBT) technique has a theoretical benefit for patients with osteoporosis, and leads to reduce screw loosening. However, there are no reports of complications and outcomes of CBT. METHODS Consecutive patients (n = 34) with degenerative lumbar spines who underwent PLIF between December 2013 and December 2015 and were followed up for at least six months were analyzed in this study. Bone mineral density, fusion rate, cage subsidence, C-arm, screw loosening, screw violation, trajectory angle of the screw, Hounsfield unit and extent of facetectomy were examined. Outcome assessments were obtained in all patients preoperatively and postoperatively. RESULTS There were 34 patients and 73 screw levels. After the surgery with cortical screw fixation and PLIF, patients had good clinical outcomes. However, ten of the 34 patients had problems with cortical screw fixation such as screw loosening or cage migration. In the patients with screw loosening, two underwent revision surgery due to cage migration, and one had an infection. Incorrect trajectory angles of the screw were significantly related with screw loosening. Low BMD and HU at screw fixation level were associated with screw loosening. Cage subsidence was statistically related with clinical outcomes. CONCLUSION The cortical screw offers improved clinical outcomes since it requires minimal muscle dissection. However, we have experienced some early complications using this technique. To reduce complications such as screw loosening, an exact insertion angle of the screw and osteoporotic bone quality should be considered carefully.
Nuclear translocation ability of Lipin differentially affects gene expression and survival in fed and fasting Drosophila

Lipins are eukaryotic proteins with functions in lipid synthesis and the homeostatic control of energy balance. They execute these functions by acting as phosphatidate phosphatase enzymes in the cytoplasm and by changing gene expression after translocation into the cell nucleus, in particular under fasting conditions. Here, we asked whether nuclear translocation and the enzymatic activity of Drosophila Lipin serve essential functions and how gene expression changes, under both fed and fasting conditions, when nuclear translocation is impaired. To address these questions, we created a Lipin null mutant, a mutant expressing Lipin lacking a nuclear localization signal (LipinΔNLS), and a mutant expressing enzymatically dead Lipin. Our data support the conclusion that the enzymatic but not nuclear gene regulatory activity of Lipin is essential for survival. Notably, adult LipinΔNLS flies were not only viable but also exhibited improved life expectancy. In contrast, they were highly susceptible to starvation. Both the improved life expectancy in the fed state and the decreased survival in the fasting state correlated with changes in metabolic gene expression. Moreover, increased life expectancy of fed flies was associated with a decreased metabolic rate. Interestingly, in addition to metabolic genes, genes involved in feeding behavior and the immune response were misregulated in LipinΔNLS flies. Altogether, our data suggest that the nuclear activity of Lipin influences the genomic response to nutrient availability with effects on life expectancy and starvation resistance. Thus, nutritional or therapeutic approaches that aim at lowering nuclear translocation of lipins in humans may be worth exploring.
A retrospective cohort study exploring diltiazem as a pharmaco‐enhancer for tacrolimus, in a post–heart transplant setting

A significant proportion of heart transplant–associated expenditure are attributable to immunosuppressants. Post‐transplant hypertension adds to the pill burden and subsequent costs. In this study, we describe the effect of diltiazem—the antihypertensive and pharmaco‐enhancer—on reducing the required oral dose of tacrolimus.
Bacterial Chromosome Engineering for Applications in Metabolic Engineering

As genetic engineering technologies continue to advance and metabolic engineering projects become more ambitious, the need for chromosome engineering tools is increased. In this thesis, I have described the development of a ΦC31 phage integrase based cassette exchange system. This system is called integrase mediated cassette exchange (IMCE). IMCE allows for the integration of a ΦC31 attB flanked DNA cassette, carried on a mobilizable donor vector, into a chromosomal landing pad locus. The landing pad locus, consisting of ΦC31 attP sites flanking marker genes, was integrated into the chromosome of three members of the Rhizobiales, by homologous recombination to create landing pad strains (LP-strains). The integration of the donor cassette is catalyzed by ΦC31 integrase, expressed from a mobilizable vector. To accomplish IMCE, a tetraparental conjugative mating is carried out, including the attB donor vector strain, the ΦC31 integrase expression plasmid strain, the LP-strain, and the mobilizer strain. A variation on IMCE , reverse IMCE, was also accomplished with the addition of a recombination directionality factor gene to the integrase expression plasmid, and the use of attL and attR sites. Reverse IMCE was used to create a new LP-strain containing the counter-selectable marker gene sacB. A strategy to assemble overlapping DNA cassettes post-IMCE using genetic crosses was developed. An application of this system was to assemble synthetic operons for the metabolic engineering of Sinorhizobium meliloti to produce medium chain length (mcl) polyhydroxyalkanoates (PHA). Two homologues each of phaC (PHA synthase gene) and phaG (3-hydroxydecanoyl-[acyl-carrier-protein]:CoA transacylase gene) were chosen. The genes were successfully combined in all four possible configurations on the chromosome of S. meliloti. It was observed that the phaC construct did not integrate into the expected location, and therefore its expression was not guaranteed, but promising preliminary results showing the detection of mcl-PHA were obtained.
The essentiality of α‐2‐macroglobulin in human salivary innate immunity against new H1N1 swine origin influenza A virus

A novel strain of influenza A H1N1 emerged in the spring of 2009 and has spread rapidly throughout the world. Although vaccines have recently been developed that are expected to be protective, their availability was delayed until well into the influenza season. Although anti-influenza drugs such as neuraminidase inhibitors can be effective, resistance to these drugs has already been reported. Although human saliva was known to inhibit viral infection and may thus prevent viral transmission, the components responsible for this activity on influenza virus, in particular, influenza A swine origin influenza A virus (S-OIV), have not yet been defined. By using a proteomic approach in conjunction with beads that bind a-2,6-sialylated glycoprotein, we determined that an a-2macroglobulin (A2M) and an A2M-like protein are essential components in salivary innate immunity against hemagglutination mediated by a clinical isolate of S-OIV (San Diego/ 01/09 S-OIV). A model of an A2M-based ‘‘double-edged sword’’ on competition of a-2,6-sialylated glycoprotein receptors and inactivation of host proteases is proposed. We emphasize that endogenous A2M in human innate immunity functions as a natural inhibitor against S-OIV. Scheme of A2M functions as a ‘‘double-edged sword’’ on the blocking and inactivating influenza virus infection.
Variation in the amphi-Atlantic plant Vahlodea atropurpurea (Poaceae)

Vahlodea atropurpurea ssp. atropurpurea is a analysis of leaf traits supported the isozyme analyses in perennial grass with an amphi-Atlantic distribution. The lack of variation. The lack of intra- and interpopulational degree of variation in this taxon was studied by biochemi- heterogeneity is discussed. cal genetic methods and by morphometric analyses in pop- ulations from both sides of the Atlantic Ocean. Genetic screening at seventeen loci revealed monomorphism and Key words. Vahlodea atropurpurea, isozyme analysis, genetic identity among populations. The morphometric genetic monomorphism, morphometry, phytogeography.
Identification of 14‐3‐3β in human gastric cancer cells and its potency as a diagnostic and prognostic biomarker

Gastric cancer is the second most common cause of cancer deaths worldwide and due to its poor prognosis, it is important that specific biomarkers are identified to enable its early detection. Through 2-D gel electrophoresis and MALDI-TOF-TOF-based proteomics approaches, we found that 14-3-3b, which was one of the proteins that were differentially expressed by 5-fluorouracil-treated gastric cancer SC-M1 cells, was upregulated in gastric cancer cells. 14-3-3b levels in tissues and serum were further validated in gastric cancer patients and controls. The results showed that 14-3-3b levels were elevated in tumor tissues (n 5 40) in comparison to normal tissues (n 5 40; po0.01), and serum 14-3-3b levels in cancer patients (n 5 145) were also significantly higher than those in controls (n 5 63; po0.0001). Elevated serum 14-3-3b levels highly correlated with the number of lymph node metastases, tumor size and a reduced survival rate. Moreover, overexpression of 14-3-3b enhanced the growth, invasiveness and migratory activities of tumor cells. Twenty-eight proteins involved in antiapoptosis and tumor progression were also found to be differentially expressed in 14-3-3b-overexpressing gastric cancer cells. Overall, these results highlight the significance of 14-3-3b in gastric cancer cell progression and suggest that it has the potential to be used as a diagnostic and prognostic biomarker in gastric cancer.
Editorial

What makes a mountain a mountain? As readers of MRD, we all have implicit knowledge of what a mountain is and assume that this is general knowledge and therefore uncontestable: ‘‘a mountain is a mountain,’’ most of us will reply. However, immediately after having answered the question in this manner, we are likely to realize that the answer is just a little too obvious to be true. What matters to our hearts and minds will not necessarily be a category that will be accepted by all in the same way. A mountain can be ‘‘prominent;’’ it can be ‘‘rugged’’, have ‘‘slopes and elevation gradients’’; it can also be a ‘‘remote and harsh environment;’’ or a ‘‘biodiversity hotspot;’’ or a ‘‘sacred place;’’ or many other things. Each of these characteristics will influence our relation to and action in and for mountains—whether we are researchers, development actors, policymakers, or just simply inhabitants living in a place we call a mountain, which is under the influence of numerous external factors. This is why we cannot escape discussing definitions of mountains, declaring what the conceptual premises of these definitions are, and agreeing—at least temporarily—on why and for what we need these definitions.