bluuebunny/crossref_metadata_2025 huggingface dataset:
A Global Perspective on Firefly Extinction Threats
Authors: Lewis Sara M , Wong Choong Hay , Owens Avalon C S , Fallon Candace , Jepsen Sarina , Thancharoen Anchana , Wu Chiahsiung , De Cock Raphael , Novák Martin , López-Palafox Tania , Khoo Veronica , Reed J Michael
Published: December 2019

Insect declines and their drivers have attracted considerable recent attention. Fireflies and glowworms are iconic insects whose conspicuous bioluminescent courtship displays carry unique cultural significance, giving them economic value as ecotourist attractions. Despite evidence of declines, a comprehensive review of the conservation status and threats facing the approximately 2000 firefly species worldwide is lacking. We conducted a survey of experts from diverse geographic regions to identify the most prominent perceived threats to firefly population and species persistence. Habitat loss, light pollution, and pesticide use were regarded as the most serious threats, although rankings differed substantially across regions. Our survey results accompany a comprehensive review of current evidence concerning the impact of these stressors on firefly populations. We also discuss risk factors likely to increase the vulnerability of certain species to particular threats. Finally, we highlight the need to establish monitoring programs to track long-term population trends for at-risk firefly taxa.
Topography of the pain in classical trigeminal neuralgia: insights into somatotopic organization
Authors: Sindou Marc , Brinzeu Andrei
Published: December 2019

Trigeminal neuralgia is defined by its clinical characteristics of paroxysmal unilateral facial pain in a well-defined territory. Distribution of the pain may be in one or several of the cutaneous and/or mucous territories of the three divisions with V2 pain being the most frequent territory followed by V3 and V1. Factors determining the distribution of pain have not yet been systematically investigated. It is now well recognized that vascular compression factor is a predominant aetiology of classical trigeminal neuralgia. In this study we aimed to find whether there is a relation between the location of the vascular compression and the peripheral distribution of the pain. Patients with classical trigeminal neuralgia in whom microvascular decompression was performed were included. Data recorded pertained to the nature of the conflict, its degree and, most importantly, location around the root: supero-median, supero-lateral or inferior. Equally, clinical data for the distribution of pain were recorded. Most of the patients 318 (89.3%) had the compression coming from above, i.e. 220 (61.7%) had compression from a supero-medial direction and 98 (27.5%) from a supero-lateral direction; inferior compression was present in 38 patients (10.7%). Distribution of the pain was significantly different according to the location of the conflict (P = 0.0005, Fisher Exact test). Odds ratios were computed for each location of compression and painful territory involved. According to the overall distribution of pain, patients with supero-medial compression had an odds ratio of 2.7 [95% confidence interval (CI) 1.66–4.41] of manifesting with V1 pain. Conversely V3 pain was less likely to occur with supero-median compression than the other types of pain (odds ratio 0.53, 95% CI 0.34–0.83). Inferior compression on the other hand was more likely to manifest with V3 pain with an odds ratio of 2.56 (95% CI 1.21–5.45). Overall V2 pain had an odds ratio close to 1 regardless of the type of compression. These findings suggest an association between the location of the neurovascular conflict with its resulting insult and the distribution of pain supporting a somatotopic view of the organization of the trigeminal root and a role of the conflict in the clinical manifestation of trigeminal neuralgia.
Individual-Level Identification of Gene Expression Associated with Volume Differences among Neocortical Areas
Authors: Fu Jilian , Liu Feng , Qin Wen , Xu Qiang , Yu Chunshui ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: December 2019

The human cerebral cortex is the source of many complex behaviors and is a vulnerable target of various neuropsychiatric disorders, but transcriptional profiles linked to cerebral cortical volume (CCV) differences across brain areas remain unknown. Here, we screened CCV-related genes using an across-sample spatial correlation analysis in 6 postmortem brains and then individually validated these correlations in 1091 subjects with different ages and ethnicities. We identified 62 genes whose transcriptional profiles were repeatedly associated with CCV in more than 90% of individuals. CCV-related genes were specifically expressed in neurons and in developmental periods from middle childhood to young adulthood, were enriched in ion channels and developmental processes, and showed significant overlap with genes linked to brain functional activity and mental disorders. The identified genes represent the conserved transcriptional architecture of the human cerebral cortex, suggesting a link between conserved gene transcription and neocortical structural properties.
Immunomodulatory Effect of Urine-derived Stem Cells on Inflammatory Bowel Diseases via Downregulating Th1/Th17 Immune Responses in a PGE2-dependent Manner
Authors: Zhou Chi , Wu Xian-Rui , Liu Hua-Shan , Liu Xuan-Hui , Liu Gui-Hua , Zheng Xiao-Bin , Hu Tuo , Liang Zhen-Xing , He Xiao-Wen , Wu Xiao-Jian , Smith Leona C , Zhang Yuanyuan , Lan Ping
Published: December 2019

Background and Aims

Despite the therapeutic promise of stem cell therapy in the treatment of inflammatory bowel diseases [IBD], most donor cell populations have to be obtained via invasive approaches and often remain insufficiently validated. Urine-derived stem cells [USC] were recently shown to have regenerative properties and can be harvested in a safe, low-cost, and noninvasive way. This study aims to evaluate the immunomodulatory effect of USC and their efficacy in the management of IBD.

Methods

Human USC were isolated and expanded from the urine of healthy male adult volunteers [n = 3, age range 24–30 years]. USC were characterised by cell surface marker expression profile and multipotent differentiation. The in vitro immunomodulatory effect of USC was evaluated by co-culturing with human CD4+ T cells upon stimulation with phytohaemagglutinin [PHA]. The proliferation of CD4+ T was measured by fluorescence-activated cell sorting [FACS]. Cytokine array and quantitative real-time polymerase chain reaction [RT-PCR] were applied to examine cytokine levels. In vivo therapeutic value of USC was assessed using a murine colitis model induced by dextran sulphate sodium [DSS] or 2, 4, 6-trinitrobenzene sulphonic acid [TNBS]. The immunomodulatory effect of USC and bone marrow-derived mesenchymal stem cells [BMSC] was compared when co-cultured with CD4+ T cells. The therapeutic efficacy of USC and BMSC on IBD was compared when administered in an acute DSS model in vivo.

Results

USC were positive for mesenchymal stem cell markers but were negative for haematopoietic stem cell markers. These cells differentiated into osteo-, adipo-, and chondrogenic cell lineages. Similar to BMSC, the proliferation of CD4+ T cells was significantly inhibited when co-cultured with USC, as a consequence of Th1/Th17 immune response inhibition. Systemic administration of USC significantly ameliorated the clinical and histopathological severity of colitis and increased the survival rate in both acute and chronic murine colitis models. Moreover, implantation of USC led to downregulation of the Th1/Th17 immune responses in a PGE2-dependent manner.

Conclusions

This study demonstrated that implantation of USC reduces inflammation in an IBD rodent model via downregulation of Th1/Th17 immune responses, indicating that USC therapy serves as a potential cell-based therapeutic candidate treatment for IBD.
Inequalities in participation in colorectal cancer screening programmes: a systematic review
Authors: Mosquera Isabel , Mendizabal Nere , Martín Unai , Bacigalupe Amaia , Aldasoro Elena , Portillo Isabel ,   from the Desberdinak Group
Published: December 2019

Background

Colorectal cancer (CRC) is a major public health problem due to its incidence and mortality. Screening programmes help decrease its impact on the population through early detection. However, the uneven distribution of social determinants of health can cause inequalities. The aim of this study is to identify the social inequalities in the participation in CRC screening programmes.

Methods

A systematic review of the literature was carried out, searching in both health and social databases for papers published since 2000 in English, Spanish, Portuguese and French. The search strategies combined terms regarding screening, CRC, participation and social inequalities. Included papers were quantitative or qualitative primary studies analyzing gender and socioeconomic inequalities in the participation in CRC screening programmes implemented by public and private health-care providers and addressing 45- to 75-year-old population.

Results

A total of 96 studies, described in 102 articles, were included. Most were quantitative observational studies and analyzed population-based screening programmes. They were carried out mainly in the UK (n=29) and the USA (n=18). Participation in screening programmes varied from 1.1% to 82.8% using several methods. A total of 87 studies assessed participation by sex and one focussed on men, but only two provided an analysis from a gender perspective. Although men are at a higher risk of developing CRC, they generally were less likely to participate in screening programmes. Screening attendance was higher among the least deprived areas.

Conclusions

Gender and socioeconomic inequalities in CRC screening participation should be addressed through the design of tailored interventions with a multidimensional focus.
Parental History of Dementia Is Associated with Increased Small Vessel Cerebrovascular Disease
Authors: Stamm Bessie C , Lao Patrick J , Rizvi Batool , Colon Juliet , Igwe Kay , Chesebro Anthony G , Maas Benjamin , Schupf Nicole , Mayeux Richard , Manly Jennifer J , Brickman Adam M
Published: December 2019

Background

Small vessel cerebrovascular dysfunction that manifests on magnetic resonance imaging (MRI) as white matter hyperintensities (WMH) is linked to increased risk and progression of Alzheimer’s disease (AD), but there is considerable debate about whether it represents a core feature of the disease. Parental history of dementia is a risk factor for AD, suggesting a strong heritable component; the examination of the extent to which parental history of dementia is associated with cerebrovascular disease could provide insight into the aggregation of AD and cerebrovascular disease.

Methods

This study included 481 community-dwelling older adults (mean age = 74.07 ± 5.81; 56% women) with available MRI scans. Participants were classified as having a parental history of dementia or having no parental history based on self-report. Total WMH values were calculated and compared between the two groups with general linear models, adjusting for relevant covariates. We also compared WMH volume between those with a reported sibling history of dementia and those without.

Results

One hundred twelve participants reported having a parental history of dementia and 369 reported no parental history. Those with parental history had greater total WMH volume than those without (F = 4.17, p = .042, partial η 2 = 0.009). Results were strongest for those with maternal versus paternal history (F = 2.43, p = .089, partial η 2 = 0.010 vs <0.001) and among Hispanic (F = 5.57, p = .020, partial η 2 = 0.038) and non-Hispanic White participants (F = 4.17, p = .042, partial η 2 = 0.009). Those with reported sibling history of dementia did not differ from those without.

Conclusions

Older adults with parental, particularly maternal, history of dementia have increased WMH. The results highlight the possibility that cerebrovascular changes are a core feature of AD, as WMH severity and parental history aggregate together.
Improved Human Muscle Biopsy Method To Study Neuromuscular Junction Structure and Functions with Aging
Authors: Aubertin-Leheudre Mylene , Pion Charlotte H , Vallée Joanne , Marchand Sandrine , Morais José A , Bélanger Marc , Robitaille Richard
Published: December 2019

Reduced mobility and physical independence of elders has emerged as a major clinical and public health priority with extended life expectancy. The impact of the neuromuscular function on muscle activity and properties has emerged as a critical factor influencing the progress and outcome of muscle changes with aging. However, very little is known about the neuromuscular junctions (NMJs) in humans, in part due to technical constraints limiting the access to healthy, fresh neuromuscular tissue. Here, we describe a method, called Biopsy using Electrostimulation for Enhanced NMJ Sampling (BeeNMJs) that improves the outcome of muscle biopsies. We used local cutaneous stimulation to identify the area enriched with NMJs for each participant at the right Vastus lateralis (VL). The needle biopsy was then performed in proximity of that point. The BeeNMJs procedure was safe for the participants. We observed NMJs in 53.3% of biopsies in comparison with only 16.7% using the traditional method. Furthermore, we observed an average of 30.13 NMJs per sample compared to only 2.33 for the traditional method. Importantly, high-quality neuromuscular material was obtained whereby pre-, postsynaptic, and glial elements were routinely labeled, simultaneously with myosin heavy chain type I. The BeeNMJs approach will facilitate studies of NMJs, particularly in human disease or aging process.
Prevalence and Loads of Torquetenovirus in the European MARK-AGE Study Population
Authors: Giacconi Robertina , Maggi Fabrizio , Macera Lisa , Spezia Pietro Giorgio , Pistello Mauro , Provinciali Mauro , Piacenza Francesco , Basso Andrea , Bürkle Alexander , Moreno-Villanueva María , Dollé Martijn E T , Jansen Eugène , Grune Tilman , Stuetz Wolfgang , Gonos Efstathios S , Schön Christiane , Bernhardt Jürgen , Grubeck-Loebenstein Beatrix , Sikora Ewa , Dudkowska Magdalena , Janiszewska Dorota , Toussaint Olivier , Debacq-Chainiaux Florence , Franceschi Claudio , Capri Miriam , Hervonen Antti , Hurme Mikko , Slagboom Eline , Breusing Nicolle , Mocchegiani Eugenio , Malavolta Marco
Published: December 2019

Torquetenovirus (TTV) viremia has been associated with increased mortality risk in the elderly population. This work aims to investigate TTV viremia as a potential biomarker of immunosenescence. We compared levels of circulating TTV in 1813 participants of the MARK-AGE project, including human models of delayed (offspring of centenarians [GO]) and premature (Down syndrome [DS]) immunosenescence. The TTV load was positively associated with age, cytomegalovirus (CMV) antibody levels, and the Cu/Zn ratio and negatively associated with platelets, total cholesterol, and total IgM. TTV viremia was highest in DS and lowest in GO, with intermediate levels in the SGO (spouses of GO) and RASIG (Randomly Recruited Age-Stratified Individuals From The General Population) populations. In the RASIG population, TTV DNA loads showed a slight negative association with CD3+T-cells and CD4+T-cells. Finally, males with ≥4log TTV copies/mL had a higher risk of having a CD4/CD8 ratio<1 than those with lower viremia (odds ratio [OR] = 2.85, 95% confidence interval [CI]: 1.06–7.62), as well as reduced CD3+ and CD4+T-cells compared to males with lower replication rates (<4log), even after adjusting for CMV infection. In summary, differences in immune system preservation are reflected in the models of delayed and premature immunosenescence, displaying the best and worst control over TTV replication, respectively. In the general population, TTV loads were negatively associated with CD4+ cell counts, with an increased predisposition for an inverted CD4/CD8 ratio for individuals with TTV loads ≥4log copies/mL, thus promoting an immune risk phenotype.
Everyday Discrimination and Kidney Function Among Older Adults: Evidence From the Health and Retirement Study
Authors: Cobb Ryon J , Thorpe Roland J , Norris Keith C
Published: December 2019

Background

With advancing age, there is an increase in the time of and number of experiences with psychosocial stressors that may lead to the initiation and/or progression of chronic kidney disease (CKD). Our study tests whether one type of experience, everyday discrimination, predicts kidney function among middle and older adults.

Methods

The data were from 10 973 respondents (ages 52–100) in the 2006/2008 Health and Retirement Study, an ongoing biennial nationally representative survey of older adults in the United States. Estimated glomerular filtration rate (eGFR) derives from the Chronic Kidney Disease Epidemiology Collaboration equation. Our indicator of everyday discrimination is drawn from self-reports from respondents. Ordinary Least Squared regression (OLS) models with robust standard errors are applied to test hypotheses regarding the link between everyday discrimination and kidney function.

Results

Everyday discrimination was associated with poorer kidney function among respondents in our study. Respondents with higher everyday discrimination scores had lower eGFR after adjusting for demographic characteristics (B = −1.35, p < .05), and while attenuated, remained significant (B = −0.79, p < .05) after further adjustments for clinical, health behavior, and socioeconomic covariates.

Conclusions

Our study suggests everyday discrimination is independently associated with lower eGFR. These findings highlight the importance of psychosocial factors in predicting insufficiency in kidney function among middle-aged and older adults.
A Praziquantel Treatment Study of Immune and Transcriptome Profiles inSchistosoma haematobium-Infected Gabonese Schoolchildren
Authors: Labuda Lucja A , Adegnika Ayola A , Rosa Bruce A , Martin John , Ateba-Ngoa Ulysse , Amoah Abena Serwaa , Lima Honorine Mbenkep , Meurs Lynn , Mbow Moustapha , Manurung Mikhael D , Zinsou Jeannot F , Smits Hermelijn H , Kremsner Peter G , Mitreva Makedonka , Yazdanbakhsh Maria
Published: December 2019

Background

Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms.

Methods

Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed.

Results

Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were negatively associated with CD4+CD25+FOXP3+ T-cells and accompanied by increased frequency of effector memory T-cells. Innate responses to Toll like receptor (TLR) ligation decreased with treatment and showed positive association with CD4+CD25+FOXP3+ T-cells. At the transcriptome level, schistosome infection was associated with enrichment in cell adhesion, whereas parasite removal was associated with a more quiescent profile. Further analysis indicated that alteration in cellular energy metabolism was associated with S haematobium infection and that the early growth response genes 2 and 3 (EGR 2 and EGR3), transcription factors that negatively regulate T-cell activation, may play a role in adaptive immune hyporesponsiveness.

Conclusions

Using a longitudinal study design, we found contrasting effects of schistosome infection on innate and adaptive immune responses. Whereas the innate immune system appears more activated, the adaptive immunity is in a hyporesponsive state reflected in alterations in CD4+CD25+FOXP3+ T-cells, cellular metabolism, and transcription factors involved in anergy.
Depression screening using mobile phone usage metadata: a machine learning approach
Authors: Razavi Rouzbeh , Gharipour Amin , Gharipour Mojgan
Published: December 2019

Objective

Depression is currently the second most significant contributor to non-fatal disease burdens globally. While it is treatable, depression remains undiagnosed in many cases. As mobile phones have now become an integral part of daily life, this study examines the possibility of screening for depressive symptoms continuously based on patients’ mobile usage patterns.

Materials and Methods

412 research participants reported a range of their mobile usage statistics. Beck Depression Inventory—2nd ed (BDI-II) was used to measure the severity of depression among participants. A wide array of machine learning classification algorithms was trained to detect participants with depression symptoms (ie, BDI-II score ≥ 14). The relative importance of individual variables was additionally quantified.

Results

Participants with depression were found to have fewer saved contacts on their devices, spend more time on their mobile devices to make and receive fewer and shorter calls, and send more text messages than participants without depression. The best model was a random forest classifier, which had an out-of-sample balanced accuracy of 0.768. The balanced accuracy increased to 0.811 when participants’ age and gender were included.

Discussions/Conclusion

The significant predictive power of mobile usage attributes implies that, by collecting mobile usage statistics, mental health mobile applications can continuously screen for depressive symptoms for initial diagnosis or for monitoring the progress of ongoing treatments. Moreover, the input variables used in this study were aggregated mobile usage metadata attributes, which has low privacy sensitivity making it more likely for patients to grant required application permissions.
Surrogacy in China: A Dilemma Between Public Policy and the Best Interests of Children
Authors: Xiao Yongping , Li Jue , Zhu Lei
Published: December 2019

Driven by high demands from society, the surrogacy industry has flourished in recent years in China with an estimate of 10,000 resulting children born every year. The legislature has deliberately chosen to refrain from prescribing rules on how surrogacy should be managed and governed in China. Through adjudicating surrogacy-related disputes, Chinese courts have played a crucial role in establishing the framework under which surrogacy operates. Applying Article 3 of the 2001 Measure expansively in conjunction with some general principles such as public order and morals, the court has laid down a de facto general ban on surrogacy of any form. The assignment of legal parentage has been influenced by this public policy consideration and Chinese courts ruled out the enforceability of parentage transfer agreements between the parties. With the surrogate carrier being designated as the natural mother and intending mother as the social parent, this arrangement creates further uncertainties and confusion over legal parentage and custody, which is not in the best interest of the resulting child.
The power of modal separation logics
Authors: Demri Stéphane , Fervari Raul
Published: December 2019

We introduce a modal separation logic MSL whose models are memory states from separation logic and the logical connectives include modal operators as well as separating conjunction and implication from separation logic. With such a combination of operators, some fragments of MSL can be seen as genuine modal logics whereas some others capture standard separation logics, leading to an original language to speak about memory states. We analyse the decidability status and the computational complexity of several fragments of MSL, obtaining surprising results by design of proof methods that take into account the modal and separation features of MSL. For example, the satisfiability problem for the fragment of MSL with $\Diamond $, the difference modality $\langle \neq \rangle $ and separating conjunction $\ast $ is shown Tower-complete whereas the restriction either to $\Diamond $ and $\ast $ or to $\langle \neq \rangle $ and $\ast $ is only NP-complete. We establish that the full logic MSL admits an undecidable satisfiability problem. Furthermore, we investigate variants of MSL with alternative semantics and we build bridges with interval temporal logics and with logics equipped with sabotage operators.
Making bright giants invisible at the Galactic Centre
Authors: Amaro-Seoane Pau , Chen Xian , Schödel Rainer , Casanellas Jordi
Published: December 2019

Current observations of the Galactic Centre (GC) seem to display a core-like distribution of bright stars from ∼5 arcsec inwards. On the other hand, we observe young, massive stars at the GC, with roughly 20–50 per cent of them in a disc, mostly in the region where the bright giants appear to be lacking. In a previous publication we put the idea forward that the missing stars are deeply connected to the presence of this disc. The progenitor of the stellar disc is very likely to have been a gaseous disc that at some point fragmented and triggered star formation. This caused the appearance of overdensity regions in the disc that had high enough densities to ensure stripping large giants of their atmospheres and thus rendering them very faint. In this paper, we use a stellar evolution code to derive the properties that a red giant would display in a colour–magnitude diagram, as well as a non-linearity factor required for a correct estimate of the mass loss. We find that in a very short time-scale, the red giants leave their standard evolutionary track. The non-linearity factor has values that not only depend on the properties of the clumps, but also on the physical conditions of the giant stars, as we predicted analytically. According to our results, envelope stripping works, moving stars on a short time-scale from the giant branch to the white dwarf stage, thus rendering them invisible to observations.
Impact of Ly α heating on the global 21-cm signal from the Cosmic Dawn
Authors: Ghara Raghunath , Mellema Garrelt
Published: December 2019

The resonance scattering of $\rm {Ly\,{\alpha }}$ photons with neutral hydrogen atoms in the intergalactic medium not only couples the spin temperature to the kinetic temperature but also leads to a heating of the gas. We investigate the impact of this heating on the average brightness temperature of the 21-cm signal from the Cosmic Dawn in the context of the claimed detection by the EDGES low-band experiment. We model the evolution of the global signal taking into account the $\rm {Ly\,{\alpha }}$ coupling and heating and a cooling which can be stronger than the Hubble cooling. Using the claimed detection of a strong absorption signal at z ≈ 17 as a constraint, we find that a strong $\rm {Ly\,{\alpha }}$ background is ruled out. Instead the results favour a weak $\rm {Ly\,{\alpha }}$ background combined with an excess cooling mechanism which is substantially stronger than previously considered. We also show that the cooling mechanism driven by the interaction between millicharged baryons and dark matter particles no longer provides a viable explanation for the EDGES result when $\rm {Ly\,{\alpha }}$ heating is taken into account.
Realistic models for filling and abundance discrepancy factors in photoionized nebulae
Authors: Bergerud Brandon M , Spangler Steven R , Beauchamp Kara M
Published: December 2019

When comparing nebular electron densities derived from collisionally excited lines (CELs) to those estimated using the emission measure, significant discrepancies are common. The standard solution is to view nebulae as aggregates of dense regions of constant density in an otherwise empty void. This porosity is parametrized by a filling factor f < 1. Similarly, abundance and temperature discrepancies between optical recombination lines (ORLs) and CELs are often explained by invoking a dual delta distribution of a dense, cool, metal-rich component immersed in a diffuse, warm, metal-poor plasma. In this paper, we examine the possibility that the observational diagnostics that lead to such discrepancies can be produced by a realistic distribution of density and temperature fluctuations, such as might arise in plasma turbulence. We produce simulated nebulae with density and temperature fluctuations described by various probability distribution functions (pdfs). Standard astronomical diagnostics are applied to these simulated observations to derive estimates of nebular densities, temperatures, and abundances. Our results show that for plausible density pdfs, the simulated observations lead to filling factors in the observed range. None of our simulations satisfactorily reproduce the abundance discrepancy factors (ADFs) in planetary nebulae, although there is possible consistency with H ii regions. Compared to the case of density-only and temperature-only fluctuations, a positive correlation between density and temperature reduces the filling factor and ADF (from optical CELs), whereas a negative correlation increases both, eventually causing the filling factor to exceed unity. This result suggests that real observations can provide constraints on the thermodynamics of small-scale fluctuations.
Infrared photometry of the dwarf nova V2051 Ophiuchi – II. The quiescent accretion disc and its spiral arms
Authors: Baptista Raymundo , Wojcikiewicz Eduardo
Published: December 2019

We report the analysis of time-series of infrared JHKs photometry of the dwarf nova  V2051 Oph in quiescence with eclipse mapping techniques to investigate structures and the spectrum of its accretion disc. The light curves after removal of the ellipsoidal variations caused by the mass-donor star show a double-wave modulation signalling the presence of two asymmetric light sources in the accretion disc. Eclipse maps reveal two spiral arms on top of the disc emission, one at $R_1= 0.28\pm 0.02 \, R_\mathrm{L1}$ and the other at $R_2= 0.42\pm 0.02 \, R_\mathrm{L1}$ (where RL1 is the distance from disc centre to the inner Lagrangian point), which are seen face-on at binary phases consistent with the maxima of the double-wave modulation. The wide open angle inferred for the spiral arms (θs = 21° ± 4°) suggests the quiescent accretion disc of V2051 Oph has high viscosity. The accretion disc is hot and optically thin in its inner regions ($T_\mathrm{gas}\sim 10\!-\!12 \times 10^3\, \mathrm{ K}$ and surface densities $\sim 10^{-3}\text{ to }10^{-2}\, \mathrm{ g}\, \mathrm{ cm}^{-2}$), and becomes cool and opaque in its outer regions.
Stochastic gravitational wave background anisotropies in the mHz band: astrophysical dependencies
Authors: Cusin Giulia , Dvorkin Irina , Pitrou Cyril , Uzan Jean-Philippe
Published: December 2019

We show that the anisotropies of the astrophysical stochastic gravitational wave background in the mHz band have a strong dependence on the modelling of galactic and sub-galactic physics. We explore a wide range of self-consistent astrophysical models for stellar evolution and for the distribution of orbital parameters, all calibrated such that they predict the same number of resolved mergers to fit the number of detections during LIGO/Virgo O1 + O2 observations runs. We show that different physical choices for the process of black hole (BH) collapse and cut-off in the BH mass distribution give fractional differences in the angular power spectrum of anisotropies of up to 50 per cent on all angular scales. We also point out that the astrophysical information which can be extracted from anisotropies is complementary to the isotropic background and individual mergers. These results underline the interest in the anisotropies of the stochastic gravitational wave background as a new and potentially rich field of research, at the cross-road between astrophysics and cosmology.
Genomic Mechanisms of Physiological and Morphological Adaptations of Limestone Langurs to Karst Habitats
Authors: Liu Zhijin , Zhang Liye , Yan Zhongze , Ren Zhijie , Han Fengming , Tan Xinxin , Xiang Zhiyuan , Dong Fang , Yang Zuomin , Liu Guangjian , Wang Ziming , Zhang Jiali , Que Tengcheng , Tang Chaohui , Li Yifeng , Wang Song , Wu Junyi , Li Legong , Huang Chengming , Roos Christian , Li Ming
Published: December 2019

Knowledge of the physiological and morphological evolution and adaptation of nonhuman primates is critical to understand hominin origins, physiological ecology, morphological evolution, and applications in biomedicine. Particularly, limestone langurs represent a direct example of adaptations to the challenges of exploiting a high calcium and harsh environment. Here, we report a de novo genome assembly (Tfra_2.0) of a male François’s langur (Trachypithecus francoisi) with contig N50 of 16.3 Mb and resequencing data of 23 individuals representing five limestone and four forest langur species. Comparative genomics reveals evidence for functional evolution in genes and gene families related to calcium signaling in the limestone langur genome, probably as an adaptation to naturally occurring high calcium levels present in water and plant resources in karst habitats. The genomic and functional analyses suggest that a single point mutation (Lys1905Arg) in the α1c subunit of the L-type voltage-gated calcium channel Cav1.2 (CACNA1C) attenuates the inward calcium current into the cells in vitro. Population genomic analyses and RNA-sequencing indicate that EDNRB is less expressed in white tail hair follicles of the white-headed langur (T. leucocephalus) compared with the black-colored François’s langur and hence might be responsible for species-specific differences in body coloration. Our findings contribute to a new understanding of gene–environment interactions and physiomorphological adaptative mechanisms in ecologically specialized primate taxa.
Sodium-glucose cotransporter 2 inhibitors: extending the indication to non-diabetic kidney disease?
Authors: Dekkers Claire C J , Gansevoort Ron T
Published: December 2019

This year the medical community was pleasantly surprised by the results of the first large outcome trial that primarily examined the renal effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (CANA) in subjects with diabetes and impaired kidney function. The Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) trial showed that CANA, relative to placebo, reduces the risk for end-stage renal disease, doubling of creatinine or renal death by 34% [hazard ratio 0.66 (95% confidence interval 0.53–0.81]. These effects were consistent across baseline estimated glomerular filtration rate (eGFR) and haemoglobin A1c subgroups. In this review we combine the results of the CREDENCE trial with those of several cardiovascular outcome trials with SGLT2 inhibitors and show that, unexpectedly, patients with lower eGFR levels may have greater benefit with respect to cardiovascular outcome than patients with normal kidney function. The cardio- and renoprotective effects of SGLT2 inhibitors seem to be independent of their glucose-lowering effects, as shown in several post hoc analyses. In this review we discuss the alleged mechanisms of action that explain the beneficial effects of this novel class of drugs. Moreover, we discuss whether these findings indicate that this class of drugs may also be beneficial in non-diabetic chronic kidney diseases.
Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study
Authors: Brenner Andrew J , Peters Katherine B , Vredenburgh James , Bokstein Felix , Blumenthal Deborah T , Yust-Katz Shlomit , Peretz Idit , Oberman Bernice , Freedman Laurence S , Ellingson Benjamin M , Cloughesy Timothy F , Sher Naamit , Cohen Yael C , Lowenton-Spier Noa , Rachmilewitz Minei Tamar , Yakov Niva , Mendel Itzhak , Breitbart Eyal , Wen Patrick Y
Published: December 2019

Background

VB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM).

Methods

Patients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS).

Results

VB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease.

Conclusions

Patients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study.
SAUR49 Can Positively Regulate Leaf Senescence by Suppressing SSPP in Arabidopsis
Authors: Wen Zewen , Mei Yuanyuan , Zhou Jie , Cui Yanjiao , Wang Dan , Wang Ning Ning
Published: December 2019

The involvement of SMALL AUXIN-UP RNA (SAUR) proteins in leaf senescence has been more and more acknowledged, but the detailed mechanisms remain unclear. In the present study, we performed yeast two-hybrid assays and identified SAUR49 as an interactor of SENESCENCE SUPPRESSED PROTEIN PHOSPHATASE (SSPP), which is a PP2C protein phosphatase that negatively regulates Arabidopsis leaf senescence by suppressing the leucine-rich repeat receptor-like protein kinase SENESCENCE-ASSOCIATED RECEPTOR-LIKE KINASE (SARK), as reported previously by our group. The interaction between SAUR49 and SSPP was further confirmed in planta. Functional characterization revealed that SAUR49 is a positive regulator of leaf senescence. The accumulation level of SAUR49 protein increased during natural leaf senescence in Arabidopsis. The transcript level of SAUR49 was upregulated during SARK-induced premature leaf senescence but downregulated during SSPP-mediated delayed leaf senescence. Overexpression of SAUR49 significantly accelerated both natural and dark-induced leaf senescence in Arabidopsis. More importantly, SAUR49 overexpression completely reversed SSPP-induced delayed leaf senescence. In addition, overexpression of SAUR49 reversed the decreased plasma membrane H+-ATPase activity mediated by SSPP. Taken together, the results showed that SAUR49 functions in accelerating the leaf senescence process via the activation of SARK-mediated leaf senescence signaling by suppressing SSPP. We further identified four other SSPP-interacting SAURs, SAUR30, SAUR39, SAUR41 and SAUR72, that may act redundantly with SAUR49 in regulating leaf senescence. All these observations indicated that certain members of the SAUR family may serve as an important hub that integrates various hormonal and environmental signals with senescence signals in Arabidopsis.
Brexit is just a symptom: the constitutional weaknesses it reveals have serious consequences for health
Authors: Jarman Holly , Greer Scott L , McKee Martin
Published: December 2019

Brexit has direct and indirect negative health consequences, whether from economic damage or from the political paralysis and distraction from public health that it has created. Brexit is a public health problem in its own right, as other literature has shown—but, we argue, it is also a symptom of deeper problems in the governance of the United Kingdom. In particular, the combination of executive dominance, partisanship and opacity that give rise to the constitutional casualism of the Brexit decisions has already affected public health policy and will continue to do so unless addressed.
Is background methotrexate advantageous in extending TNF inhibitor drug survival in elderly patients with rheumatoid arthritis? An analysis of the British Society for Rheumatology Biologics Register
Authors: Bechman Katie , Oke Anuoluwapo , Yates Mark , Norton Sam , Dennison Elaine , Cope Andrew P , Galloway James B
Published: December 2019

Objective

To evaluate drug survival with monotherapy compared with combination therapy with MTX in RA older adults.

Methods

Patients from the British Society for Rheumatology Biologics Register, a prospective observational cohort, who were biologic naïve and commencing their first TNF inhibitors (TNFi) were included. The cohort was stratified according to age: <75 and ≥75. Cox-proportional hazards models compared the risk of TNFi discontinuation from (i) any-cause, (ii) inefficacy and (iii) adverse events, between patients prescribed TNFi-monotherapy compared with TNFi MTX combination.

Results

The analysis included 15 700 patients. Ninety-five percent were <75 years old. Comorbidity burden and disease activity were higher in the ≥75 cohort. Fifty-two percent of patients discontinued TNFi therapy during the follow-up period. Persistence with therapy was higher in the <75 cohort. Patients receiving TNFi monotherapy were more likely to discontinue compared with patients receiving concomitant MTX [hazard rate 1.12 (1.06–1.18) P <0.001]. This finding only held true in patients <75 [hazard rate (HR) 1.11 (1.05–1.17) vs ≥75 [HR 1.13 (0.90–1.41)]. Examining TNFi discontinuation by cause revealed patients ≥75 receiving TNFi monotherapy were less likely to discontinue TNFi due to inefficacy [HR 0.66 (0.43–0.99) P=0.04] and more likely to discontinue therapy from adverse events [HR 1.41(1.02–1.96) P =0.04]. These results were supported by the multivariate adjustment in complete case and imputed analyses.

Conclusion

TNFi monotherapy is associated with increased treatment failure. In older adults, the disadvantage of TNFi monotherapy on drug survival is no longer seen. Patients ≥75 have fewer discontinuations due to inefficacy than adverse events compared with younger patients. This likely reflects greater disposition to toxicity but perhaps also a decline in immunogenicity associated with immunosenescence.
Determining factors for pertussis vaccination policy: A study in 5 EU countries
Authors: Wong Anabelle , Opinel Annick , Combes Simon Jean-Baptiste , Toubiana Julie , Brisse Sylvain
Published: December 2019

Pertussis vaccination policy varies across Europe, not only in the type of vaccine – whole cell (wP) vs. acellular (aP1/2/3/5) – but also in the schedule and recommendation for parents. This study aims to investigate the determining factors for the type of vaccine, immunization schedule and maternal immunization recommendation. From March to May 2019, experts in national health agencies and major academic or research institutions from Denmark, France, Poland, Sweden and the UK were invited to a semi-structured interview. Thematic analysis was performed on the transcripts using a codebook formulated by 3 coders. Inter-coder agreement was assessed. Fifteen expert interviews were conducted. The identified driving factors for pertussis vaccine policy were classified into three domains: scientific factors, sociological factors, and pragmatic factors. The determining factors for the type of vaccine were prescriber’s preference, concern of adverse events following immunization (AEFI), effectiveness, and consideration of other vaccine components in combined vaccines. The determining factors for infant schedule were immunity response and the potential to improve coverage and timeliness. The determining factors for maternal immunization were infant mortality and public acceptability. To conclude, socio-political and pragmatic factors were, besides scientific factors, important in determining the vaccine type, schedule of childhood immunization and recommendations for parents.
Urate, blood pressure and cardiovascular disease: updated evidence from Mendelian randomization and meta-analysis of clinical trials
Authors: Gill Dipender , Cameron Alan C. , Burgess Stephen , Li Xue , Doherty Daniel J. , Karhunen Ville , Abdul-Rahim Azmil H , Taylor-Rowan Martin , Zuber Verena , Tsao Philip S. , Klarin Derek ,   VA Million Veteran Program, Evangelou Evangelos , Elliott Paul , Damrauer Scott M. , Quinn Terence J , Dehghan Abbas , Theodoratou Evropi , Dawson Jesse , Tzoulaki Ioanna
Published: December 2019

Aims

To investigate the effect of serum urate on blood pressure and cardiovascular disease (CVD) risk by updating evidence from Mendelian randomization (MR) analysis and meta-analysis of randomized controlled trials (RCTs).

Methods and Results

Using recently available data from the Million Veterans Program and UK Biobank, the main MR analyses showed that every 1-standard deviation increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio 1.19, 95% confidence interval 1.10-1.30,P=4×10−5), peripheral artery disease (1.12, 95%CI 1.03 to 1.21,P=9×10−3), and stroke (1.11, 95%CI 1.05 to 1.18,P=2×10−4). In MR mediation analyses, SBP was estimated to mediate approximately one third the effect of urate on CVD risk. Systematic review and meta-analysis of RCTs showed a favorable effect of urate-lowering treatment on SBP (mean difference -2.55mmHg, 95%CI -4.06 to -1.05,P=1×10−3) and major adverse cardiovascular events (MACE) in those with previous CVD (OR 0.40, 95%CI 0.22 to 0.73,P=3×10−3), but no significant effect on MACE in all individuals (OR 0.73, 95%CI 0.48 to 1.09,P=0.12).

Conclusion

MR and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on CVD risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate-lowering may be of cardiovascular benefit.
Mendelian randomization of smoking behavior on cognitive status among older Americans
Authors: Fu Mingzhou , Faul Jessica D. , Jin Yuan , Ware Erin B. , Bakulski Kelly M.
Published: December 2019

Background

Smoking is a likely risk factor for dementia, and smoking behavior has a strong genetic component. In this study, we jointly test the associations between cumulative genetic risk for smoking, smoking behavior, and cognitive status using a Mendelian randomization framework.

Methods

We conducted a cross-sectional study using the 2010 wave of the Health and Retirement Study database. Individuals aged between 50 and 90 were included. Smoking status was self-reported. Polygenic scores (PGSs) were calculated by weighting participant genotype by published smoking genome-wide association estimates. Cognitive status (normal, impaired, dementia) was measured using multiple assessments. A Mendelian randomization framework was used to infer causal relationships between smoking behavior and cognitive status via genetic instruments.

Results

Among European ancestry participants (N = 8,735), current smoking behavior was positively associated with cognitive impairment (OR = 1.62, 95% CI: 1.29, 2.01) relative to normal cognition. Using smoking PGS as an instrumental variable, a causal relationship was observed between current smoking and cognitive impairment (OR = 1.53, 95% CI: 1.07, 2.18). There were no associations between smoking PGS, smoking behaviors and cognitive status in the African ancestry study sample (N = 2,511).

Conclusions

Current smoking is a modifiable risk factor which causes cognitive impairment. Promotion of smoking cessation is important for public health. Further studies on dose and duration of smoking behaviors on cognitive impairment are critically needed, as well as in research other ancestries.