bluuebunny/crossref_metadata_2025 huggingface dataset:
Serine threonine kinase 11/liver kinase B1 mutation in sporadic scirrhous-type gastric cancer cells
Authors: Nishimura Sadaaki , Yashiro Masakazu , Sera Tomohiro , Yamamoto Yurie , Kushitani Yukako , Sugimoto Atsushi , Kushiyama Shuhei , Togano Shingo , Kuroda Kenji , Okuno Tomohisa , Murakami Yoshiki , Ohira Masaichi
Published: March 2020

Scirrhous-type gastric carcinoma (SGC), which is characterized by the rapid proliferation of cancer cells accompanied by extensive fibrosis, shows extremely poor survival. A reason for the poor prognosis of SGC is that the driver gene responsible for SGC has not been identified. To identify the characteristic driver gene of SGC, we examined the genomic landscape of six human SGC cell lines of OCUM-1, OCUM-2M, OCUM-8, OCUM-9, OCUM-12 and OCUM-14, using multiplex gene panel testing by next-generation sequencing. In this study, the non-synonymous mutations of serine threonine kinase 11/liver kinase B1 (STK11/LKB1) gene were detected in OCUM-12, OCUM-2M and OCUM-14 among the six SGC cell lines. Capillary sequencing analysis confirmed the non-sense or missense mutation of STK11/LKB1 in the three cell lines. Western blot analysis showed that LKB1 expression was decreased in OCUM-12 cells and OCUM-14 cells harboring STK11/LKB1 mutation. The mammalian target of rapamycin (mTOR) inhibitor significantly inhibited the proliferation of OCUM-12 and OCUM-14 cells. The correlations between STK11/LKB1 expression and clinicopathologic features of gastric cancer were examined using 708 primary gastric carcinomas by immunochemical study. The low STK11/LKB1 expression group was significantly associated with SGC, high invasion depth and frequent nodal involvement, in compared with the high STK11/LKB1 expression group. Collectively, our study demonstrated that STK11/LKB1 mutation might be responsible for the progression of SGC, and suggested that mTOR signaling by STK11/LKB1 mutation might be one of therapeutic targets for patients with SGC.
Type I Interferon in Children with Viral or Bacterial Infections
Authors: Trouillet-Assant Sophie , Viel Sébastien , Ouziel Antoine , Boisselier Lucille , Rebaud Philippe , Basmaci Romain , Droz Nina , Belot Alexandre , Pons Sylvie , Brengel-Pesce Karen , Gillet Yves , Javouhey Etienne ,   Antoine Study Group, Mommert Marine , Guichard Audrey , Bartolo François , Generenaz Laurence , Pachot Alexandre , Capella Claire , Hees Laure , Mezgueldi Ellia , Toumi Chadia , Bouchiat-Sarabi Coralie , Casalegno Jean-sebastien , Portefaix Aurelie , de Cambronne Romain Deshayes , Perret Magali
Published: March 2020

Background

Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians’ decisions and limit antibiotic overuse.

Methods

Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology.

Results

Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83).

Conclusions

IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse.

Clinical Trials Registration

clinicaltrials.gov (NCT03163628).
Integrating cost–benefit analysis into the NIST Cybersecurity Framework via the Gordon–Loeb Model
Authors: Gordon Lawrence A , Loeb Martin P , Zhou Lei
Published: March 2020

The National Institute for Standards and Technology (NIST) Cybersecurity Framework has rapidly become a widely accepted approach to facilitating cybersecurity risk management within organizations. An insightful aspect of the NIST Cybersecurity Framework is its explicit recognition that the activities associated with managing cybersecurity risk are organization specific. The NIST Framework also recognizes that organizations should evaluate their cybersecurity risk management on a cost–benefit basis. The NIST Framework, however, does not provide guidance on how to carry out such a cost–benefit analysis. This article provides an approach for integrating cost–benefit analysis into the NIST Cybersecurity Framework. The Gordon–Loeb (GL) Model for cybersecurity investments is proposed as a basis for deriving a cost-effective level of spending on cybersecurity activities and for selecting the appropriate NIST Implementation Tier level. The analysis shows that the GL Model provides a logical approach to use when considering the cost–benefit aspects of cybersecurity investments during an organization’s process of selecting the most appropriate NIST Implementation Tier level. In addition, the cost–benefit approach provided in this article helps to identify conditions under which there is an incentive to move to a higher NIST Implementation Tier.
Biodiversity of Lactobacillus helveticus isolates from dairy and cereal fermentations reveals habitat-adapted biotypes
Authors: Schuster Julian A , Vogel Rudi F , Ehrmann Matthias A
Published: March 2020

For the present study, we collected 22 Lactobacillus helveticus strains from different dairy (n = 10) and cereal (n  = 12) fermentations to investigate their biodiversity and to uncover habitat-specific traits. Biodiversity was assessed by comparison of genetic fingerprints, low-molecular-weight subproteomes, metabolic and enzymatic activities, growth characteristics and acidification kinetics in food matrices. A clear distinction between the dairy and cereal strains was observed in almost all examined features suggesting that the different habitats are domiciled by different L. helveticus biotypes that are adapted to the specific environmental conditions. Analysis of the low-molecular-weight subproteome divided the cereal isolates into two clusters, while the dairy isolates formed a separate homogeneous cluster. Differences regarding carbohydrate utilization were observed for lactose, galactose, sucrose and cellobiose as well as for plant-derived glucosides. Enzymatic differences were observed mainly for ß-galactosidase and ß-glucosidase activities. Further, growth temperature was optimal in the range from 33 to 37°C for the cereal strains, whereas the dairy strains showed optimal growth at 40°C. Taken together, adaptation of the various biotypes results in a growth benefit in the particular environment. Acidification and growth tests using either sterile skim milk or a wheat flour extract confirmed these results. Differentiation of these biotypes and their physiological characteristics enables knowledge-based starter culture development for cereal versus dairy products within one species.
A systematic review and comprehensive legislative framework to address chemical assault globally
Authors: Kazerooni Yasaman , Mishra Brijesh , Gibran Nicole , Adu Emmanual , Clarke Damian , Pham Tam , Stewart Barclay T
Published: March 2020

The incidence of chemical assault is increasing globally. In response, a number of countries are proposing legislation. However, current legislative initiatives are uncoordinated and do not address the spectrum of activities to prevent and care for victims of chemical assaults. To fill this gap, we aimed to review legislation, policies and regulations relevant to chemical assault to classify and catalogue current strategies into a legislative framework. Terms related to chemical assault were used to systematically search the academic, lay and legal literatures. Chemical assault was defined as the use of acid or another caustic or corrosive substance or vitriol by one person against another with the intent to injure or disfigure. Reports that described the use of chemical weapons in warfare were excluded. A second search of national legislations of countries with reports of chemical assaults was performed to identify enacted laws and gaps in legislative approaches to chemical assault control. Data regarding relevant laws, policies and regulations were extracted. The findings were used to classify and catalogue current strategies into a legislative framework using content analysis. The search returned 3769 records. Chemical assaults were reported from 104 countries. Using legislation from those countries, a framework consisting of five legislative priorities was developed: (a) apply a public health approach; (b) adopt legal definitions specific to chemical assault; (c) control chemical supply, sales and procurement; (d) facilitate justice; and (e) support survivors. Although many countries have implemented one or more of these legislative priorities, no country has a comprehensive address to chemical assault control. Comparative policy analysis and assessments of the impacts of legislative efforts may further inform strategies to prevent, prosecute and mitigate the impact of chemical assaults. In the meantime, advocacy groups and governments might consider implementation and enforcement of one or more components of this legislative framework to control the growing epidemic of chemical assault.
Representations of the National Health Service (NHS) in UK print media
Authors: Walker Carl , Hanna Paul , Raisborough Jayne
Published: March 2020

Generating negative news coverage of state welfare provision has been identified as a strategy designed to create public support for radical policies aimed to reduce such provision. To date, research of this kind has focused on scandals and crises. However, little is known about the complex relationship between media representations of specific events, and those of media representations in the lead up to these events, what we refer to as periphery representations. Employing a content and frame analysis, this paper analyses the frequency and intensity of peripheral representations of the National Health Service (NHS) in the British print media for 1 week a month before and for 1 week during three key events in recent NHS history: the official consultation period for the Health and Social Care Act; the publication of Five-Year Forward View, and the first Junior Doctor Strike. This article finds that negative NHS representations in articles that are peripheral to particular topical issues of controversy evidence fluctuations, amplifications and intensities across time periods, depending on the particular context. The paper concludes by arguing that repetition of negative themes in news helps to build a sensibility of ‘inadequacy’ of vital services. We hope that this focus on the ways in which amplifications and de-amplifications in negative intensity of peripheral NHS representations across time and content, helps to contribute to debate about the complex interplay between public health services, media representation and policy consent.
Family-based exome sequencing identifies rare coding variants in age-related macular degeneration
Authors: Ratnapriya Rinki , Acar İlhan E , Geerlings Maartje J , Branham Kari , Kwong Alan , Saksens Nicole T M , Pauper Marc , Corominas Jordi , Kwicklis Madeline , Zipprer David , Starostik Margaret R , Othman Mohammad , Yashar Beverly , Abecasis Goncalo R , Chew Emily Y , Ferrington Deborah A , Hoyng Carel B , Swaroop Anand , den Hollander Anneke I
Published: March 2020

Genome-wide association studies (GWAS) have identified 52 independent variants at 34 genetic loci that are associated with age-related macular degeneration (AMD), the most common cause of incurable vision loss in the elderly worldwide. However, causal genes at the majority of these loci remain unknown. In this study, we performed whole exome sequencing of 264 individuals from 63 multiplex families with AMD and analyzed the data for rare protein-altering variants in candidate target genes at AMD-associated loci. Rare coding variants were identified in the CFH, PUS7, RXFP2, PHF12 and TACC2 genes in three or more families. In addition, we detected rare coding variants in the C9, SPEF2 and BCAR1 genes, which were previously suggested as likely causative genes at respective AMD susceptibility loci. Identification of rare variants in the CFH and C9 genes in our study validated previous reports of rare variants in complement pathway genes in AMD. We then extended our exome-wide analysis and identified rare protein-altering variants in 13 genes outside the AMD-GWAS loci in three or more families. Two of these genes, SCN10A and KIR2DL4, are of interest because variants in these genes also showed association with AMD in case-control cohorts, albeit not at the level of genome-wide significance. Our study presents the first large-scale, exome-wide analysis of rare variants in AMD. Further independent replications and molecular investigation of candidate target genes, reported here, would assist in gaining novel insights into mechanisms underlying AMD pathogenesis.
A genome-wide association study finds genetic variants associated with neck or shoulder pain in UK Biobank
Authors: Meng Weihua , Chan Brian W , Harris Cameron , Freidin Maxim B , Hebert Harry L , Adams Mark J , Campbell Archie , Hayward Caroline , Zheng Hua , Zhang Xianwei , Colvin Lesley A , Hales Tim G , Palmer Colin N A , Williams Frances M K , McIntosh Andrew , Smith Blair H
Published: March 2020

Background

Common types of musculoskeletal conditions include pain in the neck and shoulder areas. This study seeks to identify the genetic variants associated with neck or shoulder pain based on a genome-wide association approach using 203 309 subjects from the UK Biobank cohort and look for replication evidence from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and TwinsUK.

Methods

A genome-wide association study was performed adjusting for age, sex, BMI and nine population principal components. Significant and independent genetic variants were then sent to GS:SFHS and TwinsUK for replication.

Results

We identified three genetic loci that were associated with neck or shoulder pain in the UK Biobank samples. The most significant locus was in an intergenic region in chromosome 17, rs12453010, having P = 1.66 × 10−11. The second most significant locus was located in the FOXP2 gene in chromosome 7 with P = 2.38 × 10−10 for rs34291892. The third locus was located in the LINC01572 gene in chromosome 16 with P = 4.50 × 10−8 for rs62053992. In the replication stage, among four significant and independent genetic variants, rs2049604 in the FOXP2 gene and rs62053992 in the LINC01572 gene were weakly replicated in GS:SFHS (P = 0.0240 and P = 0.0202, respectively).

Conclusions

We have identified three loci associated with neck or shoulder pain in the UK Biobank cohort, two of which were weakly supported in a replication cohort. Further evidence is needed to confirm their roles in neck or shoulder pain.
Spatial monitoring of urban growth of Mansoura City, Egypt
Authors: Hegazy Ibrahim Rizk , Helmi Mansour Rifaat
Published: March 2020

Urbanization is a global trend determined primarily by excessive population growth, particularly in the developing countries such as Egypt. The configuration and boundaries of urbanization and their model can be observed at a distance of space and time. In this research, geographic information system and remote sensing were used to analyze urbanization and trends in the past 30 years of Mansoura City, which is one of the largest medium-sized cities in Egypt. Four Landsat images, obtained in 1985, 1995, 2005 and 2015, were adjusted and compared using the ArcGIS software. The classified images were analyzed to determine urbanization trends in Mansoura city during the three periods 1985–1995, 1995–2005 and 2005–2015. The results of the change disclosure showed areas and trends in urbanization. The urban area has grown by approximately five times over 30 years. The results showed that the eastern direction was predominant during the periods (1985–1995) and (1995–2005) with 53 and 53% of the city total growth, respectively. During the period (2005–2015), the northern trend was dominant with 38% of the city total growth. This research promotes future urban planning strategies by evaluating temporal spatial transformation and urbanization trends.
A Randomized Trial of the N-Methyl-d-Aspartate Receptor Glycine Site Antagonist Prodrug 4-Chlorokynurenine in Treatment-Resistant Depression
Authors: Park Lawrence T , Kadriu Bashkim , Gould Todd D , Zanos Panos , Greenstein Deanna , Evans Jennifer W , Yuan Peixiong , Farmer Cristan A , Oppenheimer Mark , George Jomy M , Adeojo Lilian W , Snodgrass H Ralph , Smith Mark A , Henter Ioline D , Machado-Vieira Rodrigo , Mannes Andrew J , Zarate Carlos A
Published: March 2020

Background

Ketamine has rapid-acting antidepressant effects but is associated with psychotomimetic and other adverse effects. A 7-chlorokynurenic acid is a potent and specific glycine site N-methyl-d-aspartate receptor antagonist but crosses the blood-brain barrier inefficiently. Its prodrug, L-4-chlorokynurenine (4-Cl-KYN), exerts acute and sustained antidepressant-like effects in rodents and has no reported psychotomimetic effects in either rodents or healthy volunteers. This study examined whether 4-Cl-KYN has rapid antidepressant effects in individuals with treatment-resistant depression.

Methods

After a 2-week drug-free period, 19 participants with treatment-resistant depression were randomized to receive daily oral doses of 4-Cl-KYN monotherapy (1080 mg/d for 7 days, then 1440 mg/d for 7 days) or placebo for 14 days in a randomized, placebo-controlled, double-blind, crossover manner. The primary outcome measure was the Hamilton Depression Rating Scale score, assessed at several time points over a 2-week period; secondary outcome measures included additional rating scale scores. Pharmacokinetic measures of 7-chlorokynurenic acid and 4-Cl-KYN and pharmacodynamic assessments were obtained longitudinally and included 1H-magnetic resonance spectroscopy brain glutamate levels, resting-state functional magnetic resonance imaging, and plasma and cerebrospinal fluid measures of kynurenine metabolites and neurotrophic factors.

Results

Linear mixed models detected no treatment effects, as assessed by primary and secondary outcome measures. No difference was observed for any of the peripheral or central biological indices or for adverse effects at any time between groups. A 4-Cl-KYN was safe and well-tolerated, with generally minimal associated adverse events.

Conclusions

In this small crossover trial, 4-Cl-KYN monotherapy exerted no antidepressant effects at the doses and treatment duration studied.

ClinicalTrials.gov identifier: NCT02484456.
Current and Novel Approaches to Mitigate Cardiometabolic Adverse Effects of Second-Generation Antipsychotics
Authors: Skonieczna-Żydecka Karolina , Łoniewski Igor , Stachowska Ewa , Marlicz Wojciech , Correll Christoph U
Published: March 2020

Second-generation antipsychotic–related weight gain and metabolic disturbances are a major public health issue given the widespread prescribing of these medications. The lack of clearly known mechanisms of cardiometabolic adverse effects and the relevance of cardiometabolic health for survival make this an important area for research. While nonpharmacologic and some pharmacologic treatments have shown benefits vs control conditions or placebo, the effects are modest and long-term benefits are less clear. Therefore, new approaches to mitigate second-generation antipsychotic–associated cardiometabolic burden are sorely needed.
A Transformation Rule for Natural Multiplicities
Authors: Jeffries Jack , Smirnov Ilya
Published: March 2020

For multiplicities arising from a family of ideals we provide a general approach to transformation rules for a ring extension that is étale in codimension one. Our result can be applied to bound the size of the local étale fundamental group of a singularity in terms of F-signature, recovering a recent result of Carvajal-Rojas, Schwede, and Tucker, and differential signature, providing the 1st characteristic-free effective bound.
Multifunctional Antibodies Are Induced by the RTS,S Malaria Vaccine and Associated With Protection in a Phase 1/2a Trial
Authors: Kurtovic Liriye , Atre Tanmaya , Feng Gaoqian , Wines Bruce D , Chan Jo-Anne , Boyle Michelle J , Drew Damien R , Hogarth P Mark , Fowkes Freya J I , Bergmann-Leitner Elke S , Beeson James G
Published: March 2020

Background

RTS,S is the leading malaria vaccine candidate but only confers partial efficacy against malaria in children. RTS,S is based on the major Plasmodium falciparum sporozoite surface antigen, circumsporozoite protein (CSP). The induction of anti-CSP antibodies is important for protection; however, it is unclear how these protective antibodies function.

Methods

We quantified the induction of functional anti-CSP antibody responses in healthy malaria-naive adults (N = 45) vaccinated with RTS,S/AS01. This included the ability to mediate effector functions via the fragment crystallizable (Fc) region, such as interacting with human complement proteins and Fcγ-receptors (FcγRs) that are expressed on immune cells, which promote various immunological functions.

Results

Our major findings were (1) RTS,S-induced antibodies mediated Fc-dependent effector functions, (2) functional antibodies were generally highest after the second vaccine dose, (3) functional antibodies targeted multiple regions of CSP, (4) participants with higher levels of functional antibodies had a reduced probability of developing parasitemia following homologous challenge (P < .05), and (5) nonprotected subjects had higher levels of anti-CSP IgM.

Conclusions

Our data suggest a role for Fc-dependent antibody effector functions in RTS,S-induced immunity. Enhancing the induction of these functional activities may be a strategy to improve the protective efficacy of RTS,S or other malaria vaccines.

Clinical Trials Registration

NCT00075049
Influence of forage level and corn grain processing on whole-body urea kinetics, and serosal-to-mucosal urea flux and expression of urea transporters and aquaporins in the ovine ruminal, duodenal, and cecal epithelia
Authors: Scott Karen A , Penner Gregory B , Mutsvangwa Timothy
Published: March 2020

The objectives were to determine the effects of forage level and grain processing on whole-body urea kinetics, N balance, serosal-to-mucosal urea flux (Jsm-urea), and messenger ribonucleic acid (mRNA) abundance of urea transporter-B (UT-B; SLC14a1) and aquaporins (AQP) in ovine ruminal, duodenal, and cecal epithelia. Thirty-two wether lambs were blocked by body weight into groups of four and assigned to one of four diets (n = 8) in a 2 × 2 factorial design. Dietary factors were forage level (30% [LF] vs. 70% [HF]) and corn grain processing (whole-shelled [WS] vs. steam-flaked [SF]). Four blocks of lambs (n = 4) were used to determine urea kinetics and N balance using 4-d [15N15N]-urea infusions with concurrent fecal and urine collections. Lambs were killed after 23 d of dietary adaptation. Ruminal, duodenal, and cecal epithelia were collected to determine Jsm-urea and mRNA abundance of UT-B and AQP. Lambs fed LF had greater intakes of dry matter (DMI; 1.20 vs. 0.86 kg/d) and N (NI; 20.1 vs. 15.0 g/d) than those fed HF (P < 0.01). Lambs fed SF had greater DMI (1.20 vs. 0.86 kg/d) and NI (20.6 vs. 14.5 g/d) than those fed WS (P < 0.01). As a percentage of NI, total N excretion was greater in lambs fed HF compared with those fed LF (103% vs. 63.0%; P < 0.01) and was also greater in lambs fed WS compared with those fed SF (93.6% vs. 72.1%; P = 0.02). Retained N (% of NI) was greater in lambs fed LF compared with those fed HF (37.0% vs. −2.55%; P < 0.01). Lambs fed SF had a greater (P = 0.02) retained N (% of NI; 28.0% vs. 6.50%) compared with those fed WS. Endogenous urea production (UER) tended (P = 0.09) to be greater in lambs fed HF compared with those fed LF. As a proportion of UER, lambs fed HF had a greater urinary urea-N loss (0.38 vs. 0.22) and lower urea-N transferred to the gastrointestinal tract (GIT; 0.62 vs. 0.78) or urea-N used for anabolism (as a proportion of urea-N transferred to the GIT; 0.12 vs. 0.26) compared with lambs fed LF (P < 0.01). Ruminal Jsm-urea was unaffected by diet. Duodenal Jsm-urea was greater (P < 0.01) in lambs fed HF compared with LF (77.5 vs. 57.2 nmol/[cm2 × h]). Lambs fed LF had greater (P = 0.03) mRNA expression of AQP3 in ruminal epithelia and tended (P = 0.06) to have greater mRNA expression of AQP3 in duodenal epithelia compared with lambs fed HF. Expression of UT-B mRNA was unaffected by diet. Our results showed that feeding more ruminally available energy improved N utilization, partly through a greater proportion of UER being transferred to the GIT and being used for anabolic purposes.
The Enzymatic Debridement for the Treatment of Burns of Indeterminate Depth
Authors: Bernagozzi Fabio , Orlandi Catuscia , Purpura Valeria , Morselli Paolo Giovanni , Melandri Davide
Published: March 2020

The rapid eschar removal by surgical debridement is currently considered the standard of care for the treatment of burned patients. However, the excision of viable dermal residues can frequently occur when this procedure is applied affecting, in turn, the possible spontaneous re-epithelialization of the lesion area and increasing the amount of autologous skin grafts required for its treatment. To overcome these problems, the use of enzymatic debridement by proteolytic enzymes enriched in Bromelain has aroused great interest in the clinical field as a valid alternative to surgical procedure for the treatment of burns when they appear of indeterminate depth. With the aim to evaluate the effectiveness of this new approach in comparison with a surgical procedure for the treatment of these types of burns we performed a retrospective data analysis taking into account patients hospitalized in our Burn Center from 2014 to 2017. The results obtained show a significant reduction in the time frame to perform debridement when an enzymatic approach is chosen, with the maintenance of viable dermal tissue on the superficial areas of the wounds, their spontaneous re-epithelialization, and a reduction of the bleeding time in the treated patients. A reduced amount of autologous skin grafts is also used when enzymatic treatment is applied. The length of stay of the patients treated with enzymatic debridement did not show significant differences compared to that treated with surgery, with excellent aesthetic results after 1 to 3 years.
The Small Predicts Large Effect in Crowdfunding
Authors: Fan Tingting , Gao Leilei , Steinhart Yael
Published: March 2020

Entrepreneurs are increasingly relying on online crowdfunding—the use of online platforms to raise money from a large number of people—to finance their ventures. This research explores the proposition that the amounts contributed by the majority of funders in the early stages of a crowdfunding campaign may have a counterintuitive influence on follow-up contributions and on the campaign’s fundraising success. Findings from an analysis of real-world large-scale crowdfunding data and five experiments show that potential funders are more (vs. less) likely to contribute to a newly launched project when early contributions consist mainly of relatively small (vs. large) amounts. The results further show that this Small Predicts Large effect is driven by people’s relationship inferences: when contributions made at the early stages of a crowdfunding campaign mainly comprise relatively large amounts, consumers tend to infer that those large contributions were made by the entrepreneur’s friends or relatives. Because of this relationship inference, prospective funders perceive larger contributions as being less diagnostic of others’ true opinions of the project and this perception negatively affects their willingness to contribute. However, if a crowdfunding campaign provides sufficient justification for the early-stage large contributions, this Small Predicts Large effect will be eliminated.
Terrible triad of the elbow with an ipsilateral Essex-Lopresti injury: case report
Authors: Ramzi Zakaria , Juanos Cabans Jordi , Jennart Harold
Published: March 2020

Terrible triad of the elbow and the Essex-Lopresti injury are both rare lesions with a historically poor clinical outcome. We present the case of a unique association of the two injuries with an elbow dislocation, radial and coronoid process fractures and a distal radioulnar joint dislocation due to an interosseous membrane rupture. The case was managed with closed reduction of the elbow dislocation and distal radioulnar joint followed by open reduction and repair of the damaged structures in the elbow and an unloading of the interosseous membrane. A high index of suspicion with a detailed examination of the elbow, forearm and wrist associated to a comprehensive imaging were mandatory for a complete diagnosis and an adequate treatment. Six months after the accident, the patient made a good recovery.
Serum and Saliva Levels of Cancer Antigen 15-3, Carcinoembryonic Antigen, Estradiol, Vaspin, and Obestatin as Biomarkers for the Diagnosis of Breast Cancer in Postmenopausal Women
Authors: Farahani Hyder , Amri Jamal , Alaee Mona , Mohaghegh Fathollah , Rafiee Mohammad
Published: March 2020

Objective

To find suitable biomarkers for diagnosis of Breast cancer in serum and saliva; also, to examine the correlation between salivary and serum concentrations of suitable biomarkers.

Methods

This case-control study included 30 women with breast cancer as a case group and 30 healthy women as a matched control group. Blood and saliva specimens were collected from all participants. We evaluated serum and salivary cancer antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), estradiol, vaspin, and obestatin concentrations. Mann-Whitney U testing and Spearman correlation coefficients were used for statistical analysis.

Results

Serum and salivary concentrations of estradiol were significantly higher in patients with breast cancer (BC) than in healthy women (P < .05). Also, serum CEA and salivary obestatin concentrations were significantly higher in BC patients than in the control group (P < .05). However, there was no significant difference between other parameters in patients with BC and controls. We observed a positive correlation between serum and salivary concentrations of CA15-3, as well as a negative correlation between serum and salivary concentrations of vaspin and obestatin.

Conclusion

The results of this study demonstrated that concentrations of CEA and estradiol in serum, obestatin in serum and saliva, and estradiol in saliva were significantly different between the 2 groups.
Timing stability of three black widow pulsars
Authors: Bak Nielsen Ann-Sofie , Janssen Gemma H , Shaifullah Golam , Verbiest Joris P W , Champion David J , Desvignes Grégory , Guillemot Lucas , Karuppusamy Ramesh , Kramer Michael , Lyne Andrew G , Possenti Andrea , Stappers Ben W , Bassa Cees , Cognard Ismaël , Liu Kuo , Theureau Gilles
Published: March 2020

We study the timing stability of three black widow pulsars (BWPs), both in terms of their long-term spin evolution and their shorter term orbital stability. The erratic timing behaviour and radio eclipses of the first two BWP systems discovered (PSRs B1957+20 and J2051−0827) were assumed to be representative for this class of pulsars. With several new black widow systems added to this population in the last decade, there are now several systems known that do not show these typical orbital variations or radio eclipses. We present timing solutions using 7–8 yr of observations from four of the European Pulsar Timing Array telescopes for PSRs J0023+0923, J2214+3000, and J2234+0944, and confirm that two of these systems do not show any significant orbital variability over our observing time span, both in terms of secular or orbital parameters. The third pulsar PSR J0023+0923 shows orbital variability and we discuss the implications for the timing solution. Our results from the long-term timing of these pulsars provide several new or improved parameters compared to earlier works. We discuss our results regarding the stability of these pulsars, and the stability of the class of BWPs in general, in the context of the binary parameters, and discuss the potential of the Roche lobe filling factor of the companion star being an indicator for stability of these systems.
Weak evolution of the mass–metallicity relation at cosmic dawn in the FirstLight simulations
Authors: Langan Ivanna , Ceverino Daniel , Finlator Kristian
Published: March 2020

Little is known about the mass–metallicity relation (MZR) in galaxies at cosmic dawn. Studying the first appearance of the MZR is one of the keys to understand the formation and evolution of the first galaxies. In order to lay the groundwork for upcoming observational campaigns, we analyse 290 galaxies in haloes spanning Mh = 109–1011 M⊙ selected from the FirstLight cosmological zoom simulations to predict the MZR at z = 5–8. Over this interval, the metallicity of FirstLight galaxies with stellar mass M* = 108 M⊙ declines by ≤0.2 dex. This contrasts with the observed tendency for metallicities to increase at lower redshifts, and reflects weakly evolving or even increasing gas fractions. We assess the use of the R3 strong-line diagnostic as a metallicity indicator, finding that it is informative for 12 + log (O/H) < 8 but saturates to R3 ≈ 3 at higher metallicities owing to a cancellation between enrichment and spectral softening. None the less, campaigns with JWST should be able to detect a clear trend between R3 and stellar mass for M* > 107.5 M⊙. We caution that, at fixed metallicity, galaxies with higher specific star formation show higher R3 owing to their more intense radiation fields, indicating a potential for selection biases.
Timing of young radio pulsars – II. Braking indices and their interpretation
Authors: Parthasarathy A , Johnston S , Shannon R M , Lentati L , Bailes M , Dai S , Kerr M , Manchester R N , Osłowski S , Sobey C , van Straten W , Weltevrede P
Published: March 2020

In Paper I of this series, we detected a significant value of the braking index (n) for 19 young, high-$\dot{E}$ radio pulsars using ∼10 yr of timing observations from the 64-m Parkes radio telescope. Here, we investigate this result in more detail using a Bayesian pulsar timing framework to model timing noise and to perform selection to distinguish between models containing exponential glitch recovery and braking index signatures. We show that consistent values of n are maintained with the addition of substantial archival data, even in the presence of glitches. We provide strong arguments that our measurements are unlikely due to exponential recovery signals from unseen glitches even though glitches play a key role in the evolution of a pulsar’s spin frequency. We conclude that, at least over decadal time-scales, the value of n can be significantly larger than the canonical 3 and discuss the implications for the evolution of pulsars.
A fundamental test for MOND
Authors: Marra Valerio , Rodrigues Davi C , de Almeida Álefe O F
Published: March 2020

The radial acceleration relation (RAR) shows a strong correlation between two accelerations associated with galaxy rotation curves. The relation between these accelerations is given by a non-linear function that depends on an acceleration scale a†. Some have interpreted this as an evidence for a gravity model, such as modified Newtonian dynamics (MOND), which posits a fundamental acceleration scale a0 common to all the galaxies. However, it was later shown, using Bayesian inference, that this seems not to be the case: the a0 credible intervals for individual galaxies were not found to be compatible among themselves. A test like the latter is a fundamental test for MOND as a theory for gravity, since it directly evaluates its basic assumption and this using the data that most favour MOND: galaxy rotation curves. Here we improve upon the previous analyses by introducing a more robust method to assess the compatibility between the credible intervals, in particular without Gaussian approximations. We directly estimate, using a Monte Carlo simulation, that the existence of a fundamental acceleration is incompatible with the data at more than 5σ. We also consider quality cuts in order to show that our results are robust against outliers. In conclusion, the new analysis further supports the claim that the acceleration scale found in the RAR is an emergent quantity.
Origin and evolution of the Galactic inventories of interstellar dust and its composition
Authors: Gupta Anuj , Sahijpal Sandeep
Published: March 2020

Interstellar dust is a significant component of matter in the galaxies. The dust owns its origin and reprocessing in a wide range of astrophysical environments. In order to understand the origin and evolution of the distinct types of interstellar dust grains, we have attempted a comprehensive correlated study of the thermodynamics condensation of dust grains in distinct stellar environments with the Galactic chemical evolution of the Milky Way Galaxy. The Galaxy is evolved in terms of elemental evolution resulting from stellar nucleosynthetic contributions of several generations of stars. Based on the elemental composition of the evolving Galaxy, the relative abundances of the major constituents of interstellar dust are assessed. The major aim is to redistribute the various condensable elements at any epoch during the evolution of the Galaxy into various grain constituents and understand their abundance evolution based on a mass-balance formalism. We also performed thermodynamical equilibrium condensation calculations to understand the stellar origin of various grain constituents that could carry the isotopic signatures of the various stellar nucleosynthetic sources. This is perhaps a novel attempt to estimate the bulk dust mass budget in the evolving Galaxy. The normalized mass of the Galactic dust is predicted to decrease with the increase in distance from the Galactic centre. It increases over time. The supernovae SNe Ia are predicted as the most prominent sources of Fe-dust mass, the supernova SN II+Ib/c produces oxides- and silicate-dust mass, and the AGB stars contribute to carbonaceous dust mass.
Linking compact dwarf starburst galaxies in the RESOLVE survey to downsized blue nuggets
Authors: Palumbo Michael L , Kannappan Sheila J , Frazer Elaine M , Eckert Kathleen D , Norman Dara J , Fraga Luciano , Quint Bruno C , Amram Philippe , Mendes de Oliveira Claudia , Bittner Ashley S , Moffett Amanda J , Stark David V , Norris Mark A , Cleaves Nathaniel T , Carr Derrick S
Published: March 2020

We identify and characterize compact dwarf starburst (CDS) galaxies in the REsolved Spectroscopy Of a Local VolumE (RESOLVE) survey, a volume-limited census of galaxies in the local Universe, to probe whether this population contains any residual ‘blue nuggets,’ a class of intensely star-forming compact galaxies first identified at high redshift z. Our 50 low-z CDS galaxies are defined by dwarf masses (stellar mass M* < 109.5 M⊙), compact bulged-disc or spheroid-dominated morphologies (using a quantitative criterion, $\mu _\Delta \gt 8.6$), and specific star formation rates (SSFRs) above the defining threshold for high-z blue nuggets (log  SSFR [Gyr−1] > −0.5). Across redshifts, blue nuggets exhibit three defining properties: compactness relative to contemporaneous galaxies, abundant cold gas, and formation via compaction in mergers or colliding streams. Those with halo mass below Mhalo ∼ 1011.5 M⊙ may in theory evade permanent quenching and cyclically refuel until the present day. Selected only for compactness and starburst activity, our CDS galaxies generally have Mhalo ≲ 1011.5 M⊙ and gas-to-stellar mass ratio ≳1. Moreover, analysis of archival DECaLS photometry and new 3D spectroscopic observations for CDS galaxies reveals a high rate of photometric and kinematic disturbances suggestive of dwarf mergers. The SSFRs, surface mass densities, and number counts of CDS galaxies are compatible with theoretical and observational expectations for redshift evolution in blue nuggets. We argue that CDS galaxies represent a maximally starbursting subset of traditional compact dwarf classes such as blue compact dwarfs and blue E/S0s. We conclude that CDS galaxies represent a low-z tail of the blue nugget phenomenon formed via a moderated compaction channel that leaves open the possibility of disc regrowth and evolution into normal disc galaxies.
Simulation of a compact object with outflows moving through a gaseous background
Authors: Li Xinyu , Chang Philip , Levin Yuri , Matzner Christopher D , Armitage Philip J
Published: March 2020

A compact object moving relative to surrounding gas accretes material and perturbs the density of gas in its vicinity. In the classical picture of Bondi–Hoyle–Lyttleton accretion, the perturbation takes the form of an overdense wake behind the object, which exerts a dynamical friction drag. We use hydrodynamic simulations to investigate how the accretion rate and strength of dynamical friction are modified by the presence of outflow from the compact object. We show that the destruction of the wake by an outflow reduces dynamical friction, and reverses its sign when the outflow is strong enough, in good quantitative agreement with analytic calculations. For a strong isotropic outflow, the outcome on scales that we have simulated is a negative dynamical friction, i.e. net acceleration. For jet-like outflows driven by reprocessed accretion, both the rate of accretion and the magnitude of dynamical friction drop for more powerful jets. The accretion rate is strongly intermittent when the jet points to the same direction as the motion of the compact object. The dynamical effects of outflows may be important for the evolution of compact objects during the common envelope phase of binary systems, and for accreting compact objects and massive stars encountering active galactic nucleus discs.
The short-chain fatty acids butyrate and propionate protect against inflammation-induced activation of mediators involved in active labor: implications for preterm birth
Authors: Moylan Hope Eveline Carter , Nguyen-Ngo Caitlyn , Lim Ratana , Lappas Martha
Published: March 2020

Spontaneous preterm birth is a global health issue affecting up to 20% of pregnancies and leaves a legacy of neurodevelopmental complications. Inflammation has been implicated in a significant proportion of preterm births, where pro-inflammatory insults trigger production of additional pro-inflammatory and pro-labor mediators. Thus, novel therapeutics that can target inflammation may be a novel avenue for preventing preterm birth and improving adverse fetal outcomes. Short-chain fatty acids (SCFAs), such as butyrate and propionate, are dietary metabolites produced by bacterial fermentation of fiber in the gut. SCFAs are known to possess anti-inflammatory properties and have been found to function through G-coupled-receptors and histone deacetylases. Therefore, this study aimed to investigate the effect of SCFAs on pro-inflammatory and pro-labor mediators in an in vitro model of preterm birth. Primary human cells isolated from myometrium and fetal membranes (decidua, amnion mesenchymal and amnion epithelial cells) were stimulated with the pro-inflammatory cytokines tumor necrosis factor alpha (TNF) or interleukin 1B (IL1B). The SCFAs butyrate and propionate suppressed inflammation-induced expression of pro-inflammatory cytokines and chemokines, adhesion molecules, the uterotonic prostaglandin PGF2alpha and enzymes involved in remodeling of myometrium and degradation of the fetal membranes. Notably, propionate and butyrate also suppressed inflammation-induced prostaglandin signaling and myometrial cell contraction. These effects appear to be mediated through suppression of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation. These results suggest that the SCFAs may be able to prevent myometrial contractions and rupture of membranes. Further in vivo studies are warranted to identify the efficacy of SCFAs as a novel anti-inflammatory therapeutic to prevent inflammation-induced spontaneous preterm birth.
Direct Renin Inhibition in Non-diabetic chronic Kidney disease (DRINK): a prospective randomized trial
Authors: Tang Sydney C W , Chan Kam Wa , Ip Dennis K M , Yap Desmond Y H , Ma Maggie K M , Mok Maggie M Y , Chan Gary C W , Tam Sidney , Lai Kar Neng
Published: March 2020

Background

The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients.

Methods

In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3–4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone. Primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Secondary endpoints included rate of change in urine protein-to-creatinine ratio (UPCR), cardiovascular events and hyperkalemia. Composite renal outcomes of doubling of baseline serum creatinine or a 40% reduction in eGFR or incident end-stage renal disease or death were analyzed as post hoc analysis.

Results

Seventy-six patients were randomized: 37 to aliskiren (mean age 55.1 ± 11.1 years) and 39 to control (mean age 55.0 ± 9.4 years). Their baseline demographics were comparable to eGFR (31.9 ± 9.0 versus 27.7 ± 9.0 mL/min/1.73 m2, P = 0.05) and UPCR (30.7 ± 12.6 versus 47.8 ± 2.8 mg/mmol, P = 0.33) for treatment versus control subjects. After 144 weeks of follow-up, there was no difference in the rate of eGFR change between groups. Six patients in the aliskiren group and seven in the control group reached the renal composite endpoint (16.2% versus 17.9%, P = 0.84). The cardiovascular event rate was 10.8% versus 2.6% (P = 0.217). The hyperkalemia rate was 18.9% versus 5.1% with an adjusted hazard ratio of 7.71 (95% confidence interval 1.14 to 52.3, P = 0.04) for the aliskiren arm.

Conclusion

Aliskiren neither conferred additional renoprotective benefit nor increased adverse events, except for more hyperkalemia in nondiabetic CKD patients.
Coombs-positive Paroxysmal Nocturnal Haemoglobinuria
Authors: Kalam Sabrina , Beale Rupert , Hughes Derralynn , Kulasekararaj Austin , Srirangalingam Umasuthan
Published: March 2020

Autoimmune haemolytic anaemia (AIHA) and paroxysmal nocturnal haemoglobinuria (PNH) are two distinct causes of haemolytic anaemia. They have different mechanisms that underpin their pathogenesis and, therefore, require different treatment strategies. The direct antiglobulin test (DAT) or Coombs test is positive in cases of immune-mediated haemolytic anaemia and, thus, is positive in AIHA but negative in PNH. We report a case of a woman presenting with a haemolytic anaemia who was found to have concomitant evidence of AIHA and PNH. The case highlights the importance of carrying out a comprehensive haemolysis work-up in patients who present with haemolytic anaemia.