Miracle-dz/UniFAR-FTUs huggingface dataset:
Pulmonary adverse events of small molecule JAK inhibitors in autoimmune disease: systematic review and meta-analysis.

OBJECTIVES Small molecule tyrosine kinase inhibitors [smTKI, comprising mostly of Janus kinase (JAK) and to a lesser extent, spleen tyrosine kinase (SyK) inhibitors] modulate the cytokine receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies. As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical. METHODS We performed a systematic review and meta-analysis of all published trial data on the pulmonary and serious adverse effects of smTKIs in autoimmune disease. EMBASE, MEDLINE, CENTRAL and Pneumotox databases were searched up to April 2019 for randomized controlled trials, observational studies and post marketing surveillance, comparing any smTKI with placebo or another therapy, or as monotherapy at different doses. Primary outcomes comprised of any respiratory complications including upper and lower respiratory tract infections (URTI, LRTI), influenza, pneumonia, opportunistic respiratory infections, drug-induced interstitial lung disease, pulmonary embolism and lung neoplasm. RESULTS We identified 4667 citations for screening, and selected 319 studies for full text review. Seventy-nine studies were analysed, including 47 randomized controlled trials, 25 observational studies and seven post-marketing surveillance studies, comprising 159 652 participants. There were significantly increased risks of URTI [risk difference (RD) 0.03; 95% CI: 0.01, 0.05; P = 0.00; 36 studies, 14 724 participants], LRTI (RD 0.01; 95% CI: 0.00, 0.02; P = 0.02; 24 studies, 12 302 participants), influenza (RD 0.01; 95% CI: 0.00, 0.01; P = 0.04; 22 studies, 10 684 participants), and pneumonia (RD 0.00; 95% CI: 0.00, 0.01; P = 0.02; 33 studies, 15 511 participants). No increased risk was found for other respiratory complications, including pulmonary embolism. CONCLUSION SmTKI increases the risk of non-opportunistic respiratory infections compared with placebo. The risk of any serious pulmonary adverse events is low.
Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis

Abstract Objective To estimate and compare progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) and healthy controls. Design Systematic review and meta-analysis. Data sources Medline and Embase between January 2000 and December 2019, studies published in English and conducted on humans. Eligibility criteria for selecting studies Observational studies investigating progression to T2DM. Inclusion criteria were postpartum follow-up for at least 12 months, incident physician based diagnosis of diabetes, T2DM reported as a separate outcome rather than combined with impaired fasting glucose or impaired glucose tolerance, and studies with both a group of patients with GDM and a control group. Results This meta-analysis of 20 studies assessed a total of 1 332 373 individuals (67 956 women with GDM and 1 264 417 controls). Data were pooled by random effects meta-analysis models, and heterogeneity was assessed by use of the I2 statistic. The pooled relative risk for the incidence of T2DM between participants with GDM and controls was estimated. Reasons for heterogeneity between studies were investigated by prespecified subgroup and meta-regression analyses. Publication bias was assessed by funnel plots and, overall, studies were deemed to have a low risk of bias (P=0.58 and P=0.90). The overall relative risk for T2DM was almost 10 times higher in women with previous GDM than in healthy controls (9.51, 95% confidence interval 7.14 to 12.67, P<0.001). In populations of women with previous GDM, the cumulative incidence of T2DM was 16.46% (95% confidence interval 16.16% to 16.77%) in women of mixed ethnicity, 15.58% (13.30% to 17.86%) in a predominantly non-white population, and 9.91% (9.39% to 10.42%) in a white population. These differences were not statistically significant between subgroups (white v mixed populations, P=0.26; white v non-white populations, P=0.54). Meta-regression analyses showed that the study effect size was not significantly associated with mean study age, body mass index, publication year, and length of follow-up. Conclusions Women with a history of GDM appear to have a nearly 10-fold higher risk of developing T2DM than those with a normoglycaemic pregnancy. The magnitude of this risk highlights the importance of intervening to prevent the onset of T2DM, particularly in the early years after pregnancy. Systematic review registration PROSPERO CRD42019123079.
Role of sphingolipid metabolism in neurodegeneration

Sphingolipids are a class of lipids highly enriched in the central nervous system (CNS), which shows great diversity and complexity, and has been implicated in CNS development and function. Alterations in sphingolipid metabolism have been described in multiple diseases, including those affecting the central nervous system (CNS). In this review, we discuss the role of sphingolipid metabolism in neurodegeneration, evaluating its direct roles in neuron development and health, and also in the induction of neurotoxic activities in CNS‐resident astrocytes and microglia in the context of neurologic diseases such as multiple sclerosis and Alzheimer's disease. Finally, we focus on the metabolism of gangliosides and sphingosine‐1‐phosphate, its contribution to the pathogenesis of neurologic diseases, and its potential as a candidate target for the therapeutic modulation of neurodegeneration.
Metabolomics: A Tool to Understand the Impact of Genetic Mutations in Amyotrophic Lateral Sclerosis

Metabolomics studies performed in patients with amyotrophic lateral sclerosis (ALS) reveal a set of distinct metabolites that can shed light on the pathological alterations taking place in each individual. Metabolites levels are influenced by disease status, and genetics play an important role both in familial and sporadic ALS cases. Metabolomics analysis helps to unravel the differential impact of the most common ALS-linked genetic mutations (as C9ORF72, SOD1, TARDBP, and FUS) in specific signaling pathways. Further, studies performed in genetic models of ALS reinforce the role of TDP-43 pathology in the vast majority of ALS cases. Studies performed in differentiated cells from ALS-iPSC (induced Pluripotent Stem Cells) reveal alterations in the cell metabolism that are also found in ALS models and ultimately in ALS patients. The development of metabolomics approaches in iPSC derived from ALS patients allow addressing and ultimately understanding the pathological mechanisms taking place in any patient. Lately, the creation of a “patient in a dish” will help to identify patients that may benefit from specific treatments and allow the implementation of personalized medicine.
Detection of clinical bovine mastitis caused by Mycoplasma bovis in Brazil

Abstract The work reported in this research communication investigated the occurrence of Mycoplasma bovis (M. bovis) in milk samples from cows with clinical mastitis on dairy farms from seven Brazilian states. We hypothesized that M. bovis was present in bovine clinical mastitis milk in Brazil. A total of 561 milk samples were cultured on Hayflick agar and incubated in a microaerophilic atmosphere at 5% CO2. Polymerase chain reaction (PCR) was performed for the detection of Mycoplasma spp. and Mycoplasma bovis in milk samples. Mycoplasma spp. were isolated in 2% of the milk samples, and Mycoplasma bovis was verified in 3% of the milk samples by PCR. The results showed that Mycoplasma bovis is involved in clinical mastitis in Brazilian dairy herds. We emphasize the need for further studies to investigate the infection by this agent in clinical mastitis cases, particularly in Brazil, due to the lack of knowledge about its prevalence.
LSU Digital Commons LSU Digital Commons

Metacommunity theory is an extension of metapopulation theory with the goal of understanding how ecological communities vary through space and time. One oﬀ -shoot of metacommunity theory deals with understanding how community structure varies along biotic or environmental gradients. Th e Elements of Metacommunity Structure framework is a three-tiered analysis of metacommunity structure that enables the user to identify metacommunity properties that arise in site-by-species incidence matrices. Th ese properties can then be related to underlying variables that inﬂ uence species distributions. Th e EMS framework is now implemented in metacom, an open source R package that allows for the analysis and plotting of metacommunities.
Effect of Feeding Adaptation of Italian Simmental Cows before Summer Grazing on Animal Behavior and Milk Characteristics

Simple Summary The traditional transhumant system of rearing dairy cows in mountain areas expects animals to remain indoors in the valley during the cold season, whereas during the summer they are moved to pastures at progressively higher altitudes. The animals transferred from the valley farm to the alpine pasture must adapt to various management changes. This study aimed to evaluate whether a gradual inclusion of fresh grass in the diet of dairy cows in the valley farm can improve the performance and milk characteristics during summer grazing. Three groups of six animals each were considered: one group was kept in the stable, one was transferred from the valley to the summer farm without adaptation, and the other was progressively adapted to grazing with a feeding adaptation period. Compared to animals kept indoors, grazing animals had similar performance and milk characteristics, higher rumination time and, with respect to volatile compounds in milk, higher concentrations of alcohols, aldehydes, hydrocarbons, and ketones but lower concentrations of organic acids, phenolic compounds, and dimethyl sulfone, regardless of the feeding adaptation. In conclusion, the gradual inclusion of fresh grass in the diet in the valley farm did not improve the performance and milk characteristics during summer grazing. Abstract According to the alpine transhumance system, dairy cows are moved from indoor feeding with conserved forage to fresh herbage feeding on pasture. The aim of this study was to assess, as a feeding adaptation technique, the effect of a gradual inclusion of fresh herbage in the diet of Italian Simmental dairy cows before their transfer to alpine pasture on performance, behavior, and milk characteristics. Eighteen cows were assigned to three groups: animals transferred to alpine pasture with a 10-d feeding adaptation period consisting in gradual access to a pasture close to the valley farm (GT), animals transferred to alpine pasture without a feeding adaptation period (AT), and animals kept in the valley farm (IND). During the first two weeks of summer grazing, GT and AT showed higher rumination time and different concentrations of ketones, hydrocarbons, organic acids, toluene, alcohols, phenols, and dimethyl sulfone in milk as compared to IND, whereas no differences were found in milk yield, composition, or coagulation properties. No differences between GT and AT were evident for the studied variables. The feeding adaptation technique used in this study did not influence the performance and milk characteristics of Italian Simmental dairy cows grazing on alpine pasture.
Implications of phenotypic plasticity for numerical taxonomy of Ornithogalum montanum (Liliaceae)

Implications of phenotypic plasticity in a subspecific numerical taxonomic study of Ornithogalum montanum Cyr. (Liliaceae) are discussed. Clones belonging to six natural populations were grown in a glasshouse, and their morphological response to three water dosages was analyzed by means of principal component analysis. PC-1 ranks the three groups of replicated populations, suggesting a high degree of phenotypic plasticity; on the other hand, PC-3 is almost environmentally independent. Proximities in the phenetic space are shown to be at least partially environmentally dependent, suggesting a reaction norm for the character correlation matrix. The results do not corroborate a previous recognition of six subspecies of O. montanum. Key words: phenotypic plasticity, numerical taxonomy, Ornithogalum, reaction norm, principal component analysis.
PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids

Abstract During infection of a host, Pseudomonas aeruginosa orchestrates global gene expression to adapt to the host environment and counter the immune attacks. P. aeruginosa harbours hundreds of regulatory genes that play essential roles in controlling gene expression. However, their contributions to the bacterial pathogenesis remain largely unknown. In this study, we analysed the transcriptomic profile of P. aeruginosa cells isolated from lungs of infected mice and examined the roles of upregulated regulatory genes in bacterial virulence. Mutation of a novel regulatory gene pvrA (PA2957) attenuated the bacterial virulence in an acute pneumonia model. Chromatin immunoprecipitation (ChIP)-Seq and genetic analyses revealed that PvrA directly regulates genes involved in phosphatidylcholine utilization and fatty acid catabolism. Mutation of the pvrA resulted in defective bacterial growth when phosphatidylcholine or palmitic acid was used as the sole carbon source. We further demonstrated that palmitoyl coenzyme A is a ligand for the PvrA, enhancing the binding affinity of PvrA to its target promoters. An arginine residue at position 136 was found to be essential for PvrA to bind palmitoyl coenzyme A. Overall, our results revealed a novel regulatory pathway that controls genes involved in phosphatidylcholine and fatty acid utilization and contributes to the bacterial virulence.
Open-Air Plasma-Deposited Multilayer Thin Film Moisture Barriers.

Emerging moisture sensitive devices require robust encapsulation strategies to inhibit water ingress and prevent premature failure. A scalable, open-air plasma process has been developed to deposit alternating layers of conformal organosilicate and dense SiO2 thin film barriers to prevent moisture ingress. The in-situ low temperature process is suitable for direct deposition on thermally sensitive devices and is compatible with flexible polymeric substrates. Using optical calcium testing, low water vapor transmission rates on the order of 10-3 g/m2/day at an accelerated aging condition of 38°C and 90% relative humidity (RH) are achieved. Using moisture sensitive perovskite devices as a representative moisture-susceptible device, devices retain over 80% of their initial performance for over 660 hours in a 50°C 50%RH accelerated aging environment. The ability of the multilayer barrier to enable device resistance to humid environments is crucial towards realizing longer operating lifetimes.
Chrysophanol protects PC12 cells against oxygen glucose deprivation-evoked injury by up-regulating miR-216a

ABSTRACT Background Cerebral stroke refers to an acute onset of neurological deficit syndrome. In this research, we attempted to probe into the underlying mechanisms by which chrysophanol (CP) performed its regulatory roles in cerebral stroke. Methods OGD inducement was conducted in PC12 cells to construct a cerebral stroke model. Subsequently, CCK-8 assay, western blot, flow cytometry were utilized to determine cell viability, proliferation, and apoptosis, respectively. qRT-PCR was employed for detecting miR-216a expression level. Afterward, cell transfection was performed to alter miR-216a expression. Further, experiments were conducted to determine the expression of crucial factors participated in PI3 K/AKT and JAK2/STAT3 pathways for exploring the underlying mechanisms. Results OGD inducement suppressed cell viability, while promoted cell apoptosis. Besides, it enhanced the expression of proliferation-associated p53, p21, and apoptosis-associated Bax, and Cleaved-caspase-3, while suppressed the expression of Bcl-2. Furthermore, CHR exposure ameliorated the effects that OGD-evoked, and elevated the expression of miR-216a, as well as the expression of crucial factors participated in PI3 K/AKT and JAK2/STAT3 pathways. However, miR-216a silencing markedly reversed the effects triggered by CHR exposure. Conclusion CHR exposure relieved OGD-evoked PC12 cell damage by elevating miR-216a expression and thereby activating of PI3 K/AKT and JAK2/STAT3 pathways.
Population Dynamics Of Magellania Fragilis, a Brachiopod Dominating a Mixed-Bottom Macrobenthic Assemblage on the Antarctic Shelf

A dense assemblage of the brachiopod Magellania fragilis was sampled by trawl and underwater photography during the expedition ANT IX/3 (1991) of RV ‘Polarstern’ on the shelf of the Lazarev Sea, Antarctica. Mean abundance and biomass estimates for M. fragilis were 26.15 individuals m2 and 1.13 g AFDM m2, respectively. Growth bands visible on the shell were interpreted as annual growth marks caused by the strong seasonality of food input to the benthos and were treated as size-at-age data. The von Bertalanffy growth function Lt (mm) = 51.67 (1 - e0020 (t +1.326))3.828 described these data best. The annual somatic P/B ratio was very low, 0.046 y1, and annual production amounted to 0.052 g AFDM m2 y1 at this particular site. These results indicate that M. fragilis is a comparatively slow-growing species with very low annual productivity.
Characterizing the US Population by Patterns of Mobile Health Use for Health and Behavioral Tracking: Analysis of the National Cancer Institute's Health Information National Trends Survey Data

Background Multiple types of mobile health (mHealth) technologies are available, such as smartphone health apps, fitness trackers, and digital medical devices. However, despite their availability, some individuals do not own, do not realize they own, or own but do not use these technologies. Others may use mHealth devices, but their use varies in tracking health, behaviors, and goals. Examining patterns of mHealth use at the population level can advance our understanding of technology use for health and behavioral tracking. Moreover, investigating sociodemographic and health-related correlates of these patterns can provide direction to researchers about how to target mHealth interventions for diverse audiences. Objective The aim of this study was to identify patterns of mHealth use for health and behavioral tracking in the US adult population and to characterize the population according to those patterns. Methods We combined data from the 2017 and 2018 National Cancer Institute Health Information National Trends Survey (N=6789) to characterize respondents according to 5 mutually exclusive reported patterns of mHealth use for health and behavioral tracking: (1) mHealth nonowners and nonusers report not owning or using devices to track health, behaviors, or goals; (2) supertrackers track health or behaviors and goals using a smartphone or tablet plus other devices (eg, Fitbit); (3) app trackers use only a smartphone or tablet; (4) device trackers use only nonsmartphone or nontablet devices and do not track goals; and (5) nontrackers report having smartphone or tablet health apps but do not track health, behaviors, or goals. Results Being in the mHealth nonowners and nonusers category (vs all mHealth owners and users) is associated with males, older age, lower income, and not being a health information seeker. Among mHealth owners and users, characteristics of device trackers and supertrackers were most distinctive. Compared with supertrackers, device trackers have higher odds of being male (odds ratio [OR] 2.22, 95% CI 1.55-3.19), older age (vs 18-34 years; 50-64 years: OR 2.83, 95% CI 1.52-5.30; 65+ years: OR 6.28, 95% CI 3.35-11.79), have an annual household income of US $20,000 to US $49,999 (vs US $75,000+: OR 2.31, 95% CI 1.36-3.91), and have a chronic condition (OR 1.69, 95% CI 1.14-2.49). Device trackers also have higher odds of not being health information seekers than supertrackers (OR 2.98, 95% CI 1.66-5.33). Conclusions Findings revealed distinctive sociodemographic and health-related characteristics of the population by pattern of mHealth use, with notable contrasts between those who do and do not use devices to track goals. Several characteristics of individuals who track health or behaviors but not goals (device trackers) are similar to those of mHealth nonowners and nonusers. Our results suggest patterns of mHealth use may inform how to target mHealth interventions to enhance reach and facilitate healthy behaviors.
15-Lipoxygenase-1 biosynthesis of 7S,14S-diHDHA implicates 15-lipoxygenase-2 in biosynthesis of resolvin D5[S]

The two oxylipins 7S,14S-dihydroxydocosahexaenoic acid (diHDHA) and 7S,17S-diHDHA [resolvin D5 (RvD5)] have been found in macrophages and infectious inflammatory exudates and are believed to function as specialized pro-resolving mediators (SPMs). Their biosynthesis is thought to proceed through sequential oxidations of DHA by lipoxygenase (LOX) enzymes, specifically, by human 5-LOX (h5-LOX) first to 7(S)-hydroxy-4Z,8E,10Z,13Z,16Z,19Z-DHA (7S-HDHA), followed by human platelet 12-LOX (h12-LOX) to form 7(S),14(S)-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-DHA (7S,14S-diHDHA) or human reticulocyte 15-LOX-1 (h15-LOX-1) to form RvD5. In this work, we determined that oxidation of 7(S)-hydroperoxy-4Z,8E,10Z,13Z,16Z,19Z-DHA to 7S,14S-diHDHA is performed with similar kinetics by either h12-LOX or h15-LOX-1. The oxidation at C14 of DHA by h12-LOX was expected, but the noncanonical reaction of h15-LOX-1 to make over 80% 7S,14S-diHDHA was larger than expected. Results of computer modeling suggested that the alcohol on C7 of 7S-HDHA hydrogen bonds with the backbone carbonyl of Ile399, forcing the hydrogen abstraction from C12 to oxygenate on C14 but not C17. This result raised questions regarding the synthesis of RvD5. Strikingly, we found that h15-LOX-2 oxygenates 7S-HDHA almost exclusively at C17, forming RvD5 with faster kinetics than does h15-LOX-1. The presence of h15-LOX-2 in neutrophils and macrophages suggests that it may have a greater role in biosynthesizing SPMs than previously thought. We also determined that the reactions of h5-LOX with 14(S)-hydroperoxy-4Z,7Z,10Z,12E,16Z,19Z-DHA and 17(S)-hydroperoxy-4Z,7Z,10Z,13Z,15E,19Z-DHA are kinetically slow compared with DHA, suggesting that these reactions may be minor biosynthetic routes in vivo. Additionally, we show that 7S,14S-diHDHA and RvD5 have anti-aggregation properties with platelets at low micromolar potencies, which could directly regulate clot resolution.
Biodegradation of phenolic compounds present in palm oil mill effluent as single and mixed substrates by Trametes hirsuta AK04

Abstract The ability of white-rot fungus, Trametes hirsuta AK04, to utilize phenolics as single and mixed substrates was determined in mineral medium and palm oil mill effluent (POME). The strain AK04 was able to rapidly metabolize all ten phenolics as single and mixed substrates at all test concentrations. With single substrates, between 78 and 98% removal was achieved within seven days. The biomass yield increased with increasing concentration from 100 to 500 mg L−1 but slightly decreased when the concentration was increased up to 1,000 mg L−1. When fitted to a Haldane model, the groups of benzoic and cinnamic acid derivatives gave significantly higher maximum specific growth rates than other phenolics. Phenol exhibited the lowest affinity and highest inhibitory effects on fungal metabolism. In mixed substrates, the total concentration ranges of phenolics mixtures between 1,000 and 6,000 mg L−1 did not affect the fungal growth rate and the strain AK04 showed a high degree of resistance to their toxic effects. The addition of glucose and yeast extract enhanced the degradation rates of individual phenolics in the substrate mixtures, demonstrating the advantage of this strain for treating complex media, such as industrial wastewater.