bluuebunny/crossref_metadata_2025_split huggingface dataset:
United in earnest: first pilot sites for increased surgical capacity for rheumatic heart disease announced by cardiac surgery intersociety alliance
Authors: Enumah Zachary Obinna , Bolman Ralph Morton , Zilla Peter , Boateng Percy , Wilson Barry , Kumar A. Sampath , Chotivatanapong Taweesak , Beyersdorf Friedhelm , Pomar Jose , Sliwa Karen , Eiselé Jean-Luc , Dearani Joseph , Higgins Robert 
Published: April 2021

Abstract OBJECTIVESRheumatic heart disease (RHD) affects &gt;33 000 000 individuals, mostly from low- and middle-income countries. The Cape Town Declaration on Access to Cardiac Surgery in the Developing World was published in August 2018, signalling the commitment of the global cardiac surgery and cardiology communities to improving care for patients with RHD.METHODSAs the Cape Town Declaration formed the basis for which the Cardiac Surgery Intersociety Alliance (CSIA) was formed, the purpose of this article is to describe the history of the CSIA, its formation, ongoing activities and future directions, including the announcement of selected pilot sites.RESULTSThe CSIA is an international alliance consisting of representatives from major cardiothoracic surgical societies and the World Heart Federation. Activities have included meetings at annual conferences, exhibit hall participation for advertisement and recruitment and publication of selection criteria for cardiac surgery centres to apply for CSIA support. Criteria focused on local operating capacity, local championing, governmental and facility support, appropriate identification of a specific gap in care and desire to engage in future research. Eleven applications were received for which 3 finalist sites were selected and site visits conducted. The 2 selected sites were Hospital Central Maputo (Mozambique) and King Faisal Hospital Kigali (Rwanda).CONCLUSIONSSubstantial progress has been made since the passing of the Cape Town Declaration and the formation of the CSIA, but ongoing efforts with collaboration of all committed parties—cardiac surgery, cardiology, industry and government—will be necessary to improve access to life-saving cardiac surgery for patients with RHD.
The usefulness of uroflowmetry and ultrasound bladder scanning as diagnostic tools in primary care for new male patients with lower urinary tract symptoms; a cluster randomized controlled trial
Authors: Lammers Huub A , Teunissen Theodora A M , Akkermans Reinier P , Wolfs Pieter T , Lagro-Janssen Antoinette L M 
Published: April 2021

Abstract

Background
Uroflowmetry and ultrasound scanning of the post-void residual volume are diagnostic instruments in specialist urological care of men referred with lower urinary tract symptoms (LUTS). We hypothesized that implementing uroflowmetry and post-void ultrasound bladder scanning in primary care for men with LUTS will reduce the number of referrals to urologists.

Objective
To assess the effect on referrals to urologists for new male patients over 50 years of age with LUTS when performing uroflowmetry and post-void ultrasound bladder scanning in primary care.

Methods
A cluster randomized controlled trial was conducted among Dutch general practitioners (GPs). The GPs enrolled male patients with the first-time presentation of LUTS, these were randomized to primary-care treatment with or without uroflowmetry and post-void bladder scanning. Primary outcome: percentage of patients referred to urologists within 3 and 12 months. Secondary outcomes: changes in the International Prostate Symptom Score (IPSS) and the IPSS-Quality of Life, patient satisfaction and urologic medication usage after 12 months.

Results
Four GPs were randomly assigned to the intervention group (132 patients) and seven to the control group (212 patients). The percentage of patients referred to urologists did not differ significantly between the intervention group vs the control group: within 3 months 19.7% versus 10.4% (OR 1.9, 95% CI 0.8 to 5.0), and within 12 months 28.8% versus 21.2% (OR 1.5, 95% CI 0.9 to 2.5).

Conclusions
Performing uroflowmetry and ultrasound bladder scanning in primary care as additional diagnostic tools do not reduce the number of referrals to urologists. We do not recommend using these diagnostic tools in general practice in the diagnostic work-up of these patients.
Meiotic mutants that cause a polar decrease in recombination on the X chromosome in Caenorhabditis elegans.
Authors: Broverman S A , Meneely P M 
Published: April 2021

Abstract
Recessive mutations in three autosomal genes, him-1, him-5 and him-8, cause high levels of X chromosome nondisjunction in hermaphrodites of Caenorhabditis elegans, with no comparable effect on autosomal disjunction. Each of the mutants has reduced levels of X chromosome recombination, correlating with the increase in nondisjunction. However, normal or elevated levels of recombination occur at the end of the X chromosome hypothesized to contain the pairing region (the left end), with recombination levels decreasing in regions approaching the right end. Thus, both the number and the distribution of X chromosome exchange events are altered in these mutants. As a result, the genetic map of the X chromosome in the him mutants exhibits a clustering of genes due to reduced recombination, a feature characteristic of the genetic map of the autosomes in non-mutant animals. We hypothesize that these him genes are needed for some processive event that initiates near the left end of the X chromosome.
The generation and genetic analysis of suppressors of lethal mutations in the Caenorhabditis elegans rol-3(V) gene.
Authors: Barbazuk W B , Johnsen R C , Baillie D L 
Published: April 2021

Abstract
The Caenorhabditis elegans rol-3(e754) mutation is a member of a general class of mutations affecting gross morphology, presumably through disruption of the nematode cuticle. Adult worms homozygous for rol-3(e754) exhibit rotation about their long axis associated with a left-hand twisted cuticle, musculature, gut and ventral nerve cord. Our laboratory previously isolated 12 recessive lethal alleles of rol-3. All these lethal alleles cause an arrest in development at either early or mid-larval stages, suggesting that the rol-3 gene product performs an essential developmental function. Furthermore, through the use of the heterochronic mutants lin-14 and lin-29, we have established that the expression of rol-3(e754)'s adult specific visible function is not dependent on the presence of an adult cuticle. In an attempt to understand rol-3's developmental role we sought to identify other genes whose products interact with that of rol-3. Toward this end, we generated eight EMS induced and two gamma irradiation-induced recessive suppressors of the temperature sensitive (ts) mid-larval lethal phenotype of rol-3(s1040ts). These suppressors define two complementation groups srl-1 II and srl-2 III; and, while they suppress the rol-3(s1040) lethality, they do not suppress the adult specific visible rolling phenotype. Furthermore, there is a complex genetic interaction between srl-2 and srl-1 such that srl-2(s2506) fails to complement all srl alleles tested. These results suggest that srl-1 and srl-2 may share a common function and, thus, possibly constitute members of the same gene family. Mutations in both srl-1 and srl-2 produce no obvious hermaphrodite phenotypes in the absence of rol-3(s1040ts); however, males homozygous for either srl-1 or srl-2 display aberrant tail morphology. We present evidence suggesting that the members of srl-2 are not allele specific with respect to their suppression of rol-3 lethality, and that rol-3 may act in some way to influence proper posterior morphogenesis. Finally, based on our genetic analysis of rol-3 and the srl mutations, we present a model whereby the wild-type products of the srl loci act in a concerted manner to negatively regulate the rol-3 gene.
Modifications of the notch function by Abruptex mutations in Drosophila melanogaster.
Authors: de Celis J F , Garcia-Bellido A 
Published: April 2021

Abstract
The function of the Notch gene is required in cell interactions defining alternative cell fates in several developmental processes. The Notch gene encodes a transmembrane protein with 36 epidermal growth factor (EGF)-like repeats in its extracellular domain. This protein functions as a receptor that interacts with other transmembrane proteins, such as Serrate and Delta, which also have EGF repeats in their extracellular domain. The Abruptex mutations of the Notch locus are associated with amino acid substitutions in the EGF repeats 24-29 of the Notch protein. We have studied, in genetic combinations, the modifications of Notch function caused by Abruptex mutations. These mutations lead to phenotypes which are opposite to those caused by Notch deletions. The Abruptex phenotypes are modified by the presence of mutations in other loci, in particular in the genes Serrate and Delta as well as Hairless, and groucho. The results suggest that all Abruptex mutations cause stronger than normal Notch activation by the Delta protein. Some Abruptex alleles also display an insufficiency of N function. Abruptex alleles which produce stronger enhancement of Notch activation also display stronger Notch insufficiency. This insufficiency could be due to reduced ability of Abruptex proteins to interact with Notch ligands and/or to form functional Notch dimers.
Co-segregation of intermale aggression with the pseudoautosomal region of the Y chromosome in mice.
Authors: Roubertoux P L , Carlier M , Degrelle H , Haas-Dupertuis M C , Phillips J , Moutier R 
Published: April 2021

Abstract
The sexual dimorphism of aggression has led to a search for its Y chromosomal correlates. We have previously confirmed that initiation of attack behavior against a conspecific male is Y-dependent in two strains of laboratory mice (NZB and CBA/H). We provide evidence that the non-pseudoautosomal region of the Y is not involved and that only the pseudoautosomal region of the Y is correlated with initiation of attack behavior. The autosomal correlates also contribute to this behavior in an additive or interactive manner with the pseudoautosomal correlates.
A microsatellite linkage map of the porcine genome.
Authors: Rohrer G A , Alexander L J , Keele J W , Smith T P , Beattie C W 
Published: April 2021

Abstract
We report the most extensive genetic linkage map for a livestock species produced to date. We have linked 376 microsatellite (MS) loci with seven restriction fragment length polymorphic loci in a backcross reference population. The 383 markers were placed into 24 linkage groups which span 1997 cM. Seven additional MS did not fall into a linkage group. Linkage groups are assigned to 13 autosomes and the X chromosome (haploid n = 19). This map provides the basis for genetic analysis of quantitative inheritance of phenotypic and physiologic traits in swine.
Evidence for the partial dominance of viability genes contributing to inbreeding depression in Mimulus guttatus.
Authors: Fu Y B , Ritland K 
Published: April 2021

Abstract
The relative importance of different modes of gene expression of viability genes contributing to inbreeding depression was investigated in the wild plant, Mimulus guttatus. Viability genes were identified by self-fertilizing 31 outbred plants, each heterozygous for three to nine unlinked allozyme markers, and analyzing segregation ratios of selfed progeny at maturity for deviations from 1:2:1 ratios. In this study, 24 linkages of viability genes to marker loci were detected. To infer the nature of gene action for these viability genes, a "model-free" graphical method was developed that examines the "space" of segregation ratios allowed by each of seven selection models (i.e., overdominance, complete recessivity, partial recessivity, additivity, partial dominance, complete dominance and underdominance). Using this method, we found that, of 24 linkages detected, 18 were consistent with either partial dominance, complete dominance or underdominance. Six were consistent with either partial recessivity, complete recessivity or overdominance. This finding indicates that, in these chromosomal segments identified by allozyme markers, partial dominance plays the predominant role in inbreeding depression. This is inconsistent with either the dominance or overdominance hypotheses proposed to account for inbreeding depression.
Statistical approaches for analyzing mutational spectra: some recommendations for categorical data.
Authors: Piegorsch W W , Bailer A J 
Published: April 2021

Abstract
In studies examining the patterns or spectra of mutational damage, the primary variables of interest are expressed typically as discrete counts within defined categories of damage. Various statistical methods can be applied to test for heterogeneity among the observed spectra of different classes, treatment groups and/or doses of a mutagen. These are described and compared via computer simulations to determine which are most appropriate for practical use in the evaluation of spectral data. Our results suggest that selected, simple modifications of the usual Pearson X2 statistic for contingency tables provide stable false positive error rates near the usual alpha = 0.05 level and also acceptable sensitivity to detect differences among spectra. Extensions to the problem of identifying individual differences within and among mutant spectra are noted.
M26 recombinational hotspot and physical conversion tract analysis in the ade6 gene of Schizosaccharomyces pombe.
Authors: Grimm C , Bähler J , Kohli J 
Published: April 2021

Abstract
At the ade6 locus of Schizosaccharomyces pombe flanking markers have been introduced as well as five silent restriction site polymorphisms: four in the 5' upstream region and one in the middle of the gene. The mutations ade6-706, ade6-M26 (both at the 5' end) and ade6-51 (middle of the gene) were used as partners for crosses with the 3' mutation ade6-469. From these three types of crosses, wild-type recombinants were selected and analyzed genetically to assess association with crossing-over and physically to determine conversion tract lengths. The introduced restriction site polymorphisms (five vs. only one) neither influenced the pattern of recombinant types nor the distribution of conversion tracts. The hotspot mutation M26 enhances crossing-over and conversion to the same proportion. M26 not only stimulates conversion at the 5' end, but does this also (to a lower extent) at the 3' end of ade6 at a distance of more than 1 kb. The majority of meiotic conversion tracts are continuous and postmeiotic segregation of polymorphic sites is rare. Conversion tracts are slightly shorter with M26 in comparison with its control 706. The mean minimal length of tracts varies from 670 bp (M26) to 890 bp (706) to 1290 bp (51). It is concluded that M26 acts as an initiation site of recombination or enhances initiation of recombination. M26 does not act by termination of conversion. A region of recombination initiation exists at the 5' end of the ade6 gene also in the absence of the ade6-M26 hotspot mutation.
The yeast med1 mutant undergoes both meiotic homolog nondisjunction and precocious separation of sister chromatids.
Authors: Rockmill B , Roeder G S 
Published: April 2021

Abstract
A mutant at the yeast MED1 locus was isolated in a screen for sporulation-proficient, meiotic-lethal mutants. Synaptonemal complex formation in the med1 mutant is apparently normal and med1 strains undergo meiotic crossing over at approximately 50% of the wild-type level. The med1 mutant undergoes homolog nondisjunction at meiosis I, presumably as a consequence of the decrease in crossing over. In addition, the mutant undergoes precocious separation of sister chromatids, resulting in chromosome missegregation at both meiotic divisions. We suggest that the med1 mutation perturbs chromosome structure, leading to a reduction in recombination and a defect in sister chromatid cohesion.
Translational maintenance of frame: mutants of Saccharomyces cerevisiae with altered -1 ribosomal frameshifting efficiencies.
Authors: Dinman J D , Wickner R B 
Published: April 2021

Abstract
A special site on the (+) strand of the L-A dsRNA virus induces about 2% of ribosomes translating the gag open reading frame to execute a -1 frameshift and thus produce the viral gag-pol fusion protein. Using constructs in which a -1 ribosomal frameshift at this site was necessary for expression of lacZ we isolated chromosomal mutants in which the efficiency of frameshifting was increased. These mutants comprise eight genes, named mof (maintenance of frame). The mof1-1, mof2-1, mof4-1, mof5-1 and mof6-1 strains cannot maintain M1 dsRNA at 30 degrees, but, paradoxically, do not lose L-A. The mof2-1, mof5-1 and mof6-1 strains are temperature sensitive for growth at 37 degrees, and all three show striking cell cycle phenotypes. The mof2-1 strains arrest with mother and daughter cells almost equal in size, mof5-1 arrests with multiple buds and mof6-1 arrests as single large unbudded cells. mof2-1 and mof5-1 strains are also Pet-. The mof mutations show differential effects on various frameshifting signals.
Dietary Total Antioxidant Capacity and Late-Life Cognitive Impairment: The Singapore Chinese Health Study
Authors: Sheng Li-Ting , Jiang Yi-Wen , Feng Lei , Pan An , Koh Woon-Puay 
Published: April 2021

Abstract

Background
With the dramatically rapid rate of aging worldwide, the maintenance of cognitive function in old age is a major public health priority. The association between total antioxidant capacity (TAC) of midlife diet and cognitive function in late life is still unclear.

Method
The study included 16 703 participants from a prospective cohort study in Singapore. Dietary intakes and selected supplementary use were assessed with a validated 165-item food frequency questionnaire at baseline (1993–1998). Two dietary TACs were calculated from the intake of antioxidant nutrients: the Comprehensive Dietary Antioxidant Index (CDAI) and the Vitamin C Equivalent Antioxidant Capacity (VCEAC). Cognitive function was assessed 20.2 years later using a Singapore-modified version of the Mini-Mental State Examination when subjects were 61–96 years old. Cognitive impairment was defined using education-specific cutoffs. Multivariable logistic regression models were utilized to estimate the associations between dietary TACs, component nutrients, and cognitive impairment.

Results
A total of 2 392 participants (14.3%) were defined to have cognitive impairment. Both CDAI and VCEAC scores were inversely associated with odds of cognitive impairment in a dose-dependent manner. The odds ratio (95% confidence interval; p-trend) comparing the highest with the lowest quartile was 0.84 (0.73, 0.96; p-trend = .003) for the CDAI and 0.75 (0.66, 0.86; p-trend &lt; .001) for the VCEAC. Higher intakes of vitamin C, vitamin E, carotenoids, and flavonoids were all inversely associated with cognitive impairment.

Conclusions
Higher dietary TAC was associated with lower odds of cognitive impairment in later life in a Chinese population in Singapore.
The Role of Trademarks on Online Retail Platforms: An EU Trademark Law Perspective
Authors: RandakeviČiŪtĖ-Alpman Jurgita 
Published: April 2021

Abstract
This article analyses the possible implications of the application of AI on online retail platforms for the role of EU trademarks and in particular their functions in this digital environment. It comes to the conclusion that the influence of AI on the importance of functions of origin and quality may differ from that on the accessory functions. Also, to a certain extent, this influence may vary depending on the parameters under which AI is set to function. Nevertheless, regardless of the parameters, it seems likely that the importance of the origin and quality functions may be diminished. In contrast, the significance of the accessory trademark functions may depend on the parameters under which AI is set to operate. If the goal of an AI implemented by a platform is to satisfy the needs of a consumer whose main preference is to acquire products with a specific trademark then ideally such an AI should seek to achieve this goal and, as a result, that mark may become a criterion for offering a product or service or acquiring it on behalf of the user. In this case, accessory functions may gain importance on online retail platforms, in turn encouraging trademark owners to invest more in the goodwill and attractiveness of their marks. However, if the parameters of the AI are such that it offers or makes purchases based on criteria that only serve the commercial interests of online retail platforms or their clients, and the trademarks preferred by consumers are not among such criteria, the importance of accessory functions may be weakened.
Towards an Access Paradigm in Innovation Law?
Authors: Leistner Matthias 
Published: April 2021

Abstract
The article generally discusses today’s meaning of an access paradigm in innovation law. Starting from concrete examples of access problems, it examines future research perspectives and the respective role of an access paradigm in innovation law. This concerns inter alia the possibility of common principles for public interest exceptions, in particular exceptions in the interest of free competition, throughout the different IP rights, as well as a closer look at the possibility of IP-external, sector-specific access regulation and the principles which should guide such approaches in research and policy.
Functional rescue in an Angelman syndrome model following treatment with lentivector transduced hematopoietic stem cells
Authors: Adhikari Anna , Copping Nycole A , Beegle Julie , Cameron David L , Deng Peter , O’Geen Henriette , Segal David J , Fink Kyle D , Silverman Jill L , Anderson Joseph S 
Published: April 2021

Abstract
Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by impaired communication skills, ataxia, motor and balance deficits, intellectual disabilities, and seizures. The genetic cause of AS is the neuronal loss of UBE3A expression in the brain. A novel approach, described here, is a stem cell gene therapy which uses lentivector-transduced hematopoietic stem and progenitor cells to deliver functional UBE3A to affected cells. We have demonstrated both the prevention and reversal of AS phenotypes upon transplantation and engraftment of human CD34+ cells transduced with a Ube3a lentivector in a novel immunodeficient Ube3amat−/pat+ IL2rg−/y mouse model of AS. A significant improvement in motor and cognitive behavioral assays as well as normalized delta power measured by electroencephalogram was observed in neonates and adults transplanted with the gene modified cells. Human hematopoietic profiles observed in the lymphoid organs by detection of human immune cells were normal. Expression of UBE3A was detected in the brains of the adult treatment group following immunohistochemical staining illustrating engraftment of the gene-modified cells expressing UBE3A in the brain. As demonstrated with our data, this stem cell gene therapy approach offers a promising treatment strategy for AS, not requiring a critical treatment window.