bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractBackgroundCommon 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.MethodsA 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.ResultsWe 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).ConclusionsWe 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

Abstract
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

Abstract

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

AbstractSecond-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

Abstract
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

AbstractBackgroundRTS,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.MethodsWe 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.ResultsOur 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 &lt; .05), and (5) nonprotected subjects had higher levels of anti-CSP IgM.ConclusionsOur 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 RegistrationNCT00075049
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

AbstractThe 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 &lt; 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 &lt; 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 &lt; 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 &lt; 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 &lt; 0.01). Ruminal Jsm-urea was unaffected by diet. Duodenal Jsm-urea was greater (P &lt; 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

Abstract
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

AbstractEntrepreneurs 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

Abstract
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

Abstract

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 &lt; .05). Also, serum CEA and salivary obestatin concentrations were significantly higher in BC patients than in the control group (P &lt; .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

ABSTRACT
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

ABSTRACT
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) &lt; 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* &gt; 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.