julilili42/papers huggingface dataset:
Discovery of a planetary-mass companion within the gap of the transition disk around PDS 70★★★
2020-01-03

Context. Young circumstellar disks are the birthplaces of planets. Their study is of prime interest to understand the physical and chemical conditions under which planet formation takes place. Only very few detections of planet candidates within these disks exist, and most of them are currently suspected to be disk features. Aims. In this context, the transition disk around the young star PDS 70 is of particular interest, due to its large gap identified in previous observations, indicative of ongoing planet formation. We aim to search for the presence of an embedded young planet and search for disk structures that may be the result of disk–planet interactions and other evolutionary processes. Methods. We analyse new and archival near-infrared images of the transition disk PDS 70 obtained with the VLT/SPHERE, VLT/NaCo, and Gemini/NICI instruments in polarimetric differential imaging and angular differential imaging modes. Results. We detect a point source within the gap of the disk at about 195 mas (~22 au) projected separation. The detection is confirmed at five different epochs, in three filter bands and using different instruments. The astrometry results in an object of bound nature, with high significance. The comparison of the measured magnitudes and colours to evolutionary tracks suggests that the detection is a companion of planetary mass. The luminosity of the detected object is consistent with that of an L-type dwarf, but its IR colours are redder, possibly indicating the presence of warm surrounding material. Further, we confirm the detection of a large gap of ~54 au in size within the disk in our scattered light images, and detect a signal from an inner disk component. We find that its spatial extent is very likely smaller than ~17 au in radius, and its position angle is consistent with that of the outer disk. The images of the outer disk show evidence of a complex azimuthal brightness distribution which is different at different wavelengths and may in part be explained by Rayleigh scattering from very small grains. Conclusions. The detection of a young protoplanet within the gap of the transition disk around PDS 70 opens the door to a so far observationally unexplored parameter space of planetary formation and evolution. Future observations of this system at different wavelengths and continuing astrometry will allow us to test theoretical predictions regarding planet–disk interactions, planetary atmospheres, and evolutionary models.
Does obesity impact the outcome of severely burned patients?
2020-01-03

Abstract Although obesity appears to be an important predictor of mortality and morbidity, little data about the impact of body mass index (BMI) on the outcome of severely burned patients are available. Patients admitted to the General Hospital Vienna between 1994 and 2014, who underwent surgery because of burn injuries, were enrolled in this study. BMI was used to divide patients into five groups: BMI 18.5 to 24.9, 25 to 29.9, 30 to 34.9, 35 to 39.9, and &gt; 40. The groups were compared in terms of difference of mortality and morbidity. Of 460 patients, 34.3% (n = 158) died. Mortality rates were the lowest in patients with obesity class III and the highest in patients with BMI 35 to 39.9 (BMI 18.5‐24.9: 30.5%, BMI 25‐29.9: 31.5%, BMI 30‐34.9: 41.3%, BMI 35‐39.9: 55.5%, BMI &gt; 40: 30%; P = .031). BMI was not found to be an independent risk factor when corrected with age, percent total body surface area burned, full‐thickness burns, and inhalation injury. No significant differences in length of stay, inhalation trauma, pneumonia, wound infection, sepsis, and invasive ventilation were observed. BMI as an independent risk factor for severely burned patients could not be confirmed via multivariate analysis.
PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
2020-01-03

<title>Abstract</title> Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.
Glucagon-like peptide 1 (GLP-1).
2020-01-03

BACKGROUND:The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity. SCOPE OF REVIEW:In this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases. MAJOR CONCLUSIONS:Since its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders.
Sleep enhances numbers and function of monocytes and improves bacterial infection outcome in mice
2020-01-05

Sleep strongly impacts both humoral and cellular immunity; however, its acute effects on the innate immune defense against pathogens are unclear. Here, we elucidated in mice whether sleep affects the numbers and functions of innate immune cells and their defense against systemic bacterial infection. Sleep significantly increased numbers of classical monocytes in blood and spleen of mice that were allowed to sleep for six hours at the beginning of the normal resting phase compared to mice kept awake for the same time. The sleep-induced effect on classical monocytes was neither caused by alterations in corticosterone nor myelopoiesis, bone marrow egress or death of monocytes and did only partially involve Gαi-protein coupled receptors like chemokine receptor 2 (CCR2), but not the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) or lymphocyte function-associated antigen 1 (LFA-1). Notably, sleep suppressed the expression of the clock gene Arntl in splenic monocytes and the sleep-induced increase in circulating classical monocytes was abrogated in Arntl-deficient animals, indicating that sleep is a prerequisite for clock-gene driven rhythmic trafficking of classical monocytes. Sleep also enhanced the production of reactive oxygen species by monocytes and neutrophils. Moreover, sleep profoundly reduced bacterial load in blood and spleen of mice that were allowed to sleep before systemic bacterial infection and consequently increased survival upon infection. These data provide the first evidence that sleep enhances numbers and function of innate immune cells and therewith strengthens early defense against bacterial pathogens.
Effectiveness and safety of insulin glargine 300 U/mL in insulin‐naïve patients with type 2 diabetes after failure of oral therapy in a real‐world setting
2020-01-05

Abstract Aim To evaluate the effectiveness and safety of initiating basal insulin‐supported oral therapy (BOT) with insulin glargine 300 U/mL (Gla‐300) in patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs (OADs). Materials and Methods This non‐interventional, multi‐centre, prospective 52‐week study, conducted in Germany and Switzerland, documented patients with type 2 diabetes with an HbA1c of between 7.5% and 10.0%, currently treated with OADs, after the physician had decided to start a BOT regimen with Gla‐300. The primary endpoint was the rate of achievement of the individualized predefined HbA1c target. Results Of 1748 patients included, 1153 comprised the full analysis set, of whom 721 completed documentation of 12 months of Gla‐300 treatment. Twelve months after starting Gla‐300, 49.9% achieved their individualized HbA1c target, and 61.1% achieved either their HbA1c target or a fasting plasma glucose (FPG) of ≤110 mg/dL. Mean HbA1c decreased by −1.22% ± 1.05% to 7.28% ± 0.92% and mean FPG by −51.5 (±48.63) mg/dl to 132.9 ± 33.0 mg/dL. Median duration of HbA1c target achievement was 341 days and probability to remain on target after 6 months was 81%. Hypoglycaemia incidence and rates remained low after 12 months of Gla‐300 treatment; no severe or severe nocturnal hypoglycaemia was observed. Body weight remained unchanged. Conclusions Starting a BOT regimen with Gla‐300 allowed about 60% of 721 German and Swiss patients with inadequately controlled type 2 diabetes to achieve glycaemic control within 12 months in daily clinical practice. Glycaemic control was achieved without weight gain or increased risk of nocturnal or severe hypoglycaemia.
From functional to mechanistic: coordination between turgor loss point and traits related to drought tolerance in herbaceous plants
2020-01-05

We addressed the recent plea for a use of traits with a direct mechanistic link to drought tolerance to be considered in trait-based and global change ecology. On 122 herbaceous species covering a broad range of water availability conditions in temperate grasslands, we demonstrated the feasibility of the use of turgor loss point (πtlp), a key leaf drought tolerance trait that becomes operational for large-scale studies via the novel osmometry method. We investigated the coordination of this mechanistic trait with other commonly used proxies of drought tolerance. πtlpwas not or very weakly coordinated with the first two leading dimension of the global spectrum of form and function, plant height and specific leaf area. πtlp was tightly coordinated with intrinsic water use efficiency and leaf dry matter content. We suggest that stratification by plant functional types and/or accounting for species phylogeny might help to identify trait relationships that may be transferable among different systems.
Interpreting neural decoding models using grouped model reliance
2020-01-06

Machine learning algorithms are becoming increasingly popular for decoding psychological constructs based on neural data. However, as a step towards bridging the gap between theory-driven cognitive neuroscience and data-driven decoding approaches, there is a need for methods that allow to interpret trained decoding models. The present study demonstrates grouped model reliance as a model-agnostic permutation-based approach to this problem. Grouped model reliance indicates the extent to which a trained model relies on conceptually related groups of variables, such as frequency bands or regions of interest in electroencephalographic (EEG) data. As a case study to demonstrate the method, random forest and support vector machine models were trained on within-participant single-trial EEG data from a Sternberg working memory task. Participants were asked to memorize a sequence of digits (0-9), varying randomly in length between one, four and seven digits, where EEG recordings for working memory load estimation were taken from a 3-second retention interval. The present results confirm previous findings insofar as both random forest and support vector machine models relied on alpha-band activity in most subjects. However, as revealed by further analyses, patterns in frequency and topography varied considerably between individuals, pointing to more pronounced inter-individual differences than previously reported.
Aplasia cutis congenita of the scalp: Histopathologic features and clinicopathologic correlation in a case series
2020-01-06

Abstract Background Aplasia cutis congenita (ACC) is a rare and heterogeneous disorder characterized by congenital absence of skin. The scalp is the most commonly affected site and lesions may overlie deeper ectodermal abnormalities. The exact etiology is still unknown, and histopathologic features are poorly defined. Methods A series of 10 cases from nine patients was analyzed to characterize the clinicopathologic spectrum and age‐related changes of ACC of the scalp. Hematoxylin and eosin, S100, Elastica van Gieson, and Weigert elastic stains were performed, and clinical information was retrieved from archived medical files. Results Patient ages ranged from 1 day to 39 years (median 57 months). All cases resembled deep‐reaching scars with almost complete loss of all adnexal structures. Isolated residual hair follicles were present in 8/10 and sweat glands and ducts in 2/10 cases. The subcutis was thinned or absent. Elastic fibers were always more fragmented than in normal tissue, and the thickness and density increased over time. There was no gain of adnexal structures with increasing age. Conclusions ACC represents a congenital scarring alopecia with permanent loss of skin appendages. Histopathologic changes resemble a deep‐reaching scar with fragmented elastic fibers and differentiate ACC from all other forms of non‐traumatic congenital alopecias.
Mid-term results after proximal humeral fractures following angular stable plate fixation in elderly patients—which scores can be evaluated by a telephone-based assessment?
2020-01-06

Abstract Background The aim was to evaluate postsurgical outcome in elderly patients (&gt; 70 years) after open reduction and internal fixation (ORIF) of proximal humeral fractures and compare the test-retest agreement of scores which are frequently used to assess the outcome of upper extremity disorders. Methods Ninety patients (78.1 ± 5.2 years) with a minimum follow-up of 2 years (3.7 ± 0.9 years) following angular stable plate fixation of a proximal humeral fracture (2-part: 34, 3-part: 41, 4-part: 12) were enrolled. Two telephone-based interviews assessed Disabilities of the Arm, Shoulder and Hand Score (DASH), Oxford Shoulder Score (OSS), and Constant Score adjusted for interview assessment (CS) by two independent interviewers. Correlations, Bland-Altman analyses, Cross tabulation, and weighted Kappa measure of agreement ( k ) were calculated to assess differences and the test-retest agreement between the categories of each score. Results In the first and second interview, we could state fair outcomes: CS 91 (range 40–100) and 65.5 (23–86), DASH 12.5 (0–64.2) and 18.3 (0–66.7), and OSS 58 (33–60) and 55 (25–60) points. The test-retest correlations were r = 0.67, r = 0.77, and r = 0.71 for CS, DASH, and OSS. Bland-Altman analyses showed absolute mean individual score differences of − 22.3, 4.9, and − 3.0 for CS, DASH, and OSS. Limits of agreement represented possible differences of 21.6%, 15.5%, and 9.0% of CS, DASH, and OSS. The category agreements were medium to high: CS 55.9% ( k = 0.08), DASH 87.2% ( k = 0.62), and OSS 99.3% ( k = 0.74). Conclusion Patients showed good subjective outcomes. The test-retest agreement of the interview-adjusted CS was low, but telephone-based assessment of OSS and DASH present as an alternative to collect outcomes in elderly patients. Trial registration ( 250/2011BO2 ).
Yeast can express and assemble bacterial secretins in the mitochondrial outer membrane
2020-01-06

Secretins form large multimeric pores in the outer membrane (OM) of Gram-negative bacteria. These pores are part of type II and III secretion systems (T2SS and T3SS, respectively) and are crucial for pathogenicity. Recent structural studies indicate that secretins form a structure rich in β-strands. However, little is known about the mechanism by which secretins assemble into the OM. Based on the conservation of the biogenesis of β-barrel proteins in bacteria and mitochondria, we used yeast cells as a model system to study the assembly process of secretins. To that end, we analyzed the biogenesis of PulD (T2SS), SsaC (T3SS) and InvG (T3SS) in wild type cells or in cells mutated for known mitochondrial import and assembly factors. Our results suggest that secretins can be expressed in yeast cells, where they are enriched in the mitochondrial fraction. Interestingly, deletion of mitochondrial import receptors like Tom20 and Tom70 reduces the mitochondrial association of PulD but does not affect that of InvG. SsaC shows another dependency pattern and its membrane assembly is enhanced by the absence of Tom70 and compromised in cells lacking Tom20 or the topogenesis of outer membrane β-barrel proteins (TOB) complex component, Mas37. Collectively, these findings suggest that various secretins can follow different pathways to assemble into the bacterial OM.
Bouncing Back: Queer Resilience in Twentieth and Twenty-First Century English Literature and Culture
2020-01-06

LGBTQ people have strategies of resilience at their disposal to help them deal with the challenge that heteronormativity as a power structure poses to their affective lives. This book makes the concept of resilience available to queer literary and cultural studies, analysing these strategies in terms of narration, performance, bodies, and space. Resilience turns out to be a highly interactive mode of being in the world, which can set free creative energy as well as draw inspiration and energy from artistic work. Authors and artists discussed include Katherine Mansfield, Christopher Isherwood, Sylvia Townsend Warner, Jeanette Winterson, Michael Cunningham, and Ian McKellen.
Whole genome characterization of autochthonous Bos taurus brachyceros and introduced Bos indicus indicus cattle breeds in Cameroon regarding their adaptive phenotypic traits and pathogen resistance
2020-01-06

Abstract Background West African indigenous taurine cattle display unique adaptive traits shaped by husbandry management, regional climate and exposure to endemic pathogens. They are less productive with respect to milk and meat production which has been associated with a number of factors, amongst others small size, traditional beliefs and husbandry practices. This resulted in the severe dwindling of their populations size rendering them vulnerable to extinction. The Namchi (Doayo) taurine cattle breed has documented resistance traits against trypanosome infection and exposure to tick infestation. Nonetheless, the historically later introduced Zebu cattle are the main cattle breeds in Africa today, even though they suffer more from locally prevailing pathogens. By using a reference-based whole genome sequencing approach, we sequenced for the first time the genomes of five cattle breeds from Cameroon: the Namchi (Doayo), an endangered trypanotolerant taurine breed, the Kapsiki, an indigenous trypanosusceptible taurine breed, and three Zebu ( Bos indicus indicus ) breeds: Ngaoundere Gudali, White Fulani and Red Fulani. Results Approximately 167 Giga bases of raw sequencing data were generated and mapped to the cattle reference genome UMD3.1. The coverage was 22 to 30-fold. The single nucleotide polymorphisms (SNPs) were compared with reference genomes of European Bos taurus Holstein and of Asian Bos indicus Brahman and the African trypanotolerant N’Dama breeds.Of a total of 50 million SNPs identified, 3.43 million were breed-specific ranging from 0.37 to 0.47 million SNPs in the domestic Cameroonian breeds and approximately 0.58 million constituted of small insertions and deletions. We identified breed specific-non-synonymous variants as genetic traits that could explain certain cattle-breed specific phenotypes such as increased tolerance against trypanosome parasites in the Namchi (Doayo) breed, heat tolerance in the Kapsiki breed, and growth, metabolism and meat quality in the Gudali breeds. Phylogenetic comparison grouped Namchi (Doayo) to the African Zebu clade indicating a hybrid status of the selected animal with a Zebu breed, albeit it showed the Namchi breed’s phenotype. Conclusions The findings provide the first comprehensive set of full genome variant data of the most important Cameroonian cattle breeds. The genomic data shall constitute a foundation for breed amelioration whilst exploiting the heritable traits and support conservation efforts for the endangered local cattle breeds.
Availability, prices and affordability of selected antibiotics and medicines against non-communicable diseases in western Cameroon and northeast DR Congo
2020-01-07

Access to safe, effective and affordable medicines of good quality is included into the Sustainable Development Goals of the United Nations. Furthermore, WHO has developed a Global Action Plan with the aim to raise access to essential medicines against non-communicable diseases (NCDs) to 80%, and to improve their affordability. In order to contribute to the monitoring of progress towards these goals, the present study investigated the availability and affordability of seven antibiotics and six medicines against non-communicable diseases in the northeast of the Democratic Republic of Congo and the west of the Republic of Cameroon. Data on availability and prices of these medicines were collected in 60 different sites (34 in the DR Congo, 26 in Cameroon), including government health facilities, church health facilities, private pharmacies and informal vendors, as part of a study on medicine quality. The data were analyzed using a standardized procedure developed by WHO and Health Action International (HAI). Average availability of the investigated antibiotics ranged from 62% to 98% in the different types of facilities in both countries, including the informal vendors. Average availability for medicines against NCDs in the different types of facilities showed a higher variation in both countries, ranging from 11% up to 87%. The average availability of medicines against NCDs in government health facilities was only 33% in Cameroon, and as low as 11% in the DR Congo. In contrast, availability of medicines against NCDs in church health facilities in Cameroon was 70%, not far from the 80% availability goal set by WHO. Medicine prices were clearly higher in Cameroon than in the DR Congo, with median price ratios to an international reference price of 5.69 and 2.17, respectively (p < 0.001). In relation to the daily minimum wages in both countries, treatment courses with five of the seven investigated antibiotics could be considered as affordable, while in each country only one out of the five investigated medicines against NCDs could be considered as affordable. Especially generic medicines provided by government and church health facilities showed reasonable affordability in most cases, while originator medicines offered by private pharmacies were clearly unaffordable to a major part of the population. Despite some encouraging findings on the availability of antibiotics in both countries, the availability and affordability of medicines against NCDs urgently requires further improvements.