bluuebunny/crossref_metadata_2025 huggingface dataset:
Transgenerational effects of polychlorinated biphenyls: 2. Hypothalamic gene expression in rats
Authors: Gore Andrea C , Thompson Lindsay M , Bell Mandee , Mennigen Jan A
Published: April 2021

Polychlorinated biphenyls (PCBs) are endocrine-disrupting chemicals (EDCs) with well-established effects on reproduction and behavior in developmentally-exposed (F1) individuals. Because of evidence for transgenerational effects of EDCs on the neuroendocrine control of reproductive physiology, we tested the hypothesis that prenatal PCB exposure leads to unique hypothalamic gene-expression profiles in three generations. Pregnant Sprague–Dawley rats were treated on gestational days 16 and 18 with the PCB mixture Aroclor 1221 (A1221), vehicle (3% DMSO in sesame oil), or estradiol benzoate (EB, 50 μg/kg), the latter a positive control for estrogenic effects of A1221. Maternal- and paternal-lineage F2 and F3 generations were bred using untreated partners. The anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC), involved in the hypothalamic control of reproduction, were dissected from F1 to F3 females and males, RNA extracted, and gene expression measured in a qPCR array. We detected unique gene-expression profiles in each generation, which were sex- and lineage-specific. In the AVPV, treatment significantly changed 10, 25, and 11 transcripts in F1, F2, and F3 generations, whereas 10, 1, and 12 transcripts were changed in these generations in the ARC. In the F1 AVPV and ARC, most affected transcripts were decreased by A1221. In the F2 AVPV, most effects of A1221 were observed in females of the maternal lineage, whereas only Pomc expression changed in the F2 ARC (by EB). The F3 AVPV and ARC were mainly affected by EB. It is notable that results in one generation do not predict results in another, and that lineage was a major determinant in results. Thus, transient prenatal exposure of F1 rats to A1221 or EB can alter hypothalamic gene expression across three generations in a sex- and lineage-dependent manner, leading to the conclusion that the legacy of PCBs continues for generations.
Kisspeptin-54 injection induces a physiological luteinizing hormone surge and ovulation in mice
Authors: Owen Corie M , Zhou Xiang , Bernard Daniel J , Jaffe Laurinda A
Published: April 2021

Intraperitoneal injection of kisspeptin-54 induces a surge-like release of luteinizing hormone that stimulates ovulation in mice.
Real-World Experience of Bamlanivimab for Coronavirus Disease 2019 (COVID-19): A Case-Control Study
Authors: Kumar Rebecca N , Wu En-Ling , Stosor Valentina , Moore William J , Achenbach Chad , Ison Michael G , Angarone Michael P
Published: April 2021

Background

Coronavirus disease 2019 (COVID-19) has strained healthcare systems with patient hospitalizations and deaths. Anti-spike monoclonal antibodies, including bamlanivimab, have demonstrated reduction in hospitalization rates in clinical trials, yet real-world evidence is lacking.

Methods

We conducted a retrospective case-control study across a single healthcare system of nonhospitalized patients, age 18 years or older, with documented positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, risk factors for severe COVID-19, and referrals for bamlanivimab via emergency use authorization. Cases were defined as patients who received bamlanivimab; contemporary controls had a referral order placed but did not receive bamlanivimab. The primary outcome was 30-day hospitalization rate from initial positive SARS-CoV-2 polymerase chain reaction (PCR). Descriptive statistics, including χ 2 and Mann-Whitney U test, were performed. Multivariable logistic regression was used for adjusted analysis to evaluate independent associations with 30-day hospitalization.

Results

Between 30 November 2020 and 19 January 2021, 218 patients received bamlanivimab (cases), and 185 were referred but did not receive drug (controls). Thirty-day hospitalization rate was significantly lower among patients who received bamlanivimab (7.3% vs 20.0%, risk ratio [RR] 0.37, 95% confidence interval [CI]: .21–.64, P < .001), and the number needed to treat was 8. On logistic regression, odds of hospitalization were increased in patients not receiving bamlanivimab and with a higher number of pre-specified comorbidities (odds ratio [OR] 4.19 ,95% CI: 1.31–2.16, P < .001; OR 1.68, 95% CI: 2.12–8.30, P < .001, respectively).

Conclusions

Ambulatory patients with COVID-19 who received bamlanivimab had a lower 30-day hospitalization than control patients in real-world experience. We identified receipt of bamlanivimab and fewer comorbidities as protective factors against hospitalization.

Bamlanivimab’s role in preventing hospitalization associated with coronavirus disease 2019 (COVID-19) remains unclear. In a real-world, retrospective study of 403 high-risk, ambulatory patients with COVID-19, receipt of bamlanivimab compared to no monoclonal antibody therapy was associated with lower 30-day hospitalization.
Influence of lighting environment on social preferences in sticklebacks from two different photic habitats. II. Shoaling and mate preferences of lab-bred fishes
Authors: Hiermes Meike , Marder Michael B , Reher Stephanie , Rick Ingolf P , Vitt Simon , Bakker Theo C M
Published: April 2021

Different environmental conditions may lead to diverse morphological, behavioral, and physiological adaptations of different populations of the same species. Lighting conditions, for example, vary vastly especially between aquatic habitats, and have been shown to elicit adaptations. The availability of short-wave ultraviolet (UV) light is especially fluctuating, as UV wavelengths are attenuated strongly depending on water properties. The island of North Uist, Scotland, comprises 2 differential habitat types, tea-stained and clear-water lakes, varying considerably in UV transmission. In previous studies, wild-caught 3-spined stickleback Gasterosteus aculeatus populations (3 populations of each habitat type) were tested with respect to their shoaling and mate preferences for fish viewed under UV-present and UV-absent conditions. The results revealed a habitat-dependent preference of UV cues during shoal choice (tea-stained populations: preference for UV-absent condition in tea-stained water; clear-water populations: no preference in clear-water) but an overall preference for UV-present conditions during mate choice. To assess genetic influences on these behavioral patterns, similar experiments were conducted with lab-bred F1-generations of the same stickleback populations that were raised in a common environment (i.e. standardized clear-water conditions). Offspring of sticklebacks from tea-stained lakes tended to prefer shoals viewed under UV-absent conditions (only in tea-stained water), while sticklebacks from clear-water lakes showed a significant preference for the shoal viewed under UV-present conditions in clear-water but not in tea-stained water. Mate-preference experiments demonstrated that females from the tea-stained lakes significantly preferred and females from the clear-water lakes preferred by trend the male viewed under UV-present conditions in the clear-water treatment. The results for both shoaling- and mate-preference tests were largely similar for wild-caught and lab-bred sticklebacks, thus hinting at a genetic basis for the preference patterns.
Matrix Metalloproteinase MMP-12 Promotes Macrophage Transmigration Across Intestinal Epithelial Tight Junctions and Increases Severity of Experimental Colitis
Authors: Nighot Meghali , Ganapathy Ashwinkumar Subramenium , Saha Kushal , Suchanec Eric , Castillo Eliseo F , Gregory Alyssa , Shapiro Steven , Ma Thomas , Nighot Prashant
Published: April 2021

Background and Aims

Matrix metalloproteinases [MMPs] play an important role in extracellular matrix regulation during cell growth and wound healing. Increased expression of MMP-12 [human macrophage elastase] has been reported in inflammatory bowel disease [IBD] which is characterised by the loss of epithelial tight junction [TJ] barrier function and an excessive inflammatory response. The aim of this study was to investigate the role of MMP-12 in intestinal TJ barrier function and inflammation.

Methods

Wild type [WT] and MMP-12-/- mice were subjected to experimental acute or chronic dextran sodium sulphate [DSS] colitis. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon and ex vivo by Ussing chamber studies.

Results

DSS administration increased colonic permeability through modulation of TJ proteins and also increased MMP-12 expression in the colonic mucosa of WT mice. The acute as well as chronic DSS-induced increase in colonic TJ permeability and the severity of DSS colitis was found to be markedly attenuated in MMP-12-/- mice. The resistance of MMP-12-/- mice to DSS colitis was characterised by reduced macrophage infiltration and transmigration, and reduced basement membrane laminin degradation. Further in vitro and in vivo studies show that macrophage transmigration across the epithelial layer is MMP-12 dependent and the epithelial TJ barrier is compromised during macrophage transmigration.

Conclusions: Together, these data demonstrate that MMP-12 mediated degradation of basement membrane laminin, macrophage transmigration, and associated loss of intestinal TJ barrier are key pathogenic factors for intestinal inflammation.
Landscape Effects on Native Bees (Hymenoptera: Anthophila) Captured in Pheromone Traps for Noctuid Crop Pests (Lepidoptera: Noctuidae)
Authors: Parys Katherine A , Elkins Blake H , Little Nathan S , Allen K Clint , Crow Whitney , Cook Don , Wright Karen W , Zhu Yu Cheng , Griswold Terry
Published: April 2021

Noctuid pests, including tobacco budworm (Chloridea virescens (Fab.)) and bollworm (Helicoverpa zea (Boddie)), are significant pests of southern row crops including cotton (Gossypium hirsutum L.), corn (Zea mays L.), and soybean (Glycine max (L.) Moench.). This pest complex is seasonally monitored through Hartstack traps that are baited with synthetic lepidopteran pheromones across the southern United States. We examined bycatch from the noctuid traps deployed across the Mississippi Delta in 2015, 2016, and 2017 for the presence of bees. The most abundant species collected were honey bees (Apis mellifera L.), bumble bees (Bombus spp.), and long-horned bees (Melissodes spp.); these three genera accounted for 82.4% of specimens collected. We also evaluated the proportion of local- and landscape-level habitats on the abundance and richness of the bees caught as bycatch. The proportion of natural and semi-natural habitat affected the abundance and richness of bees collected at the landscape level, but not at more local scales. Additional research is needed to better understand these interactions between bycatch and landscape factors to minimize non-target collections.
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

OBJECTIVES

Rheumatic heart disease (RHD) affects >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.

METHODS

As 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.

RESULTS

The 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).

CONCLUSIONS

Substantial 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

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

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

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

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

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

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

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

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

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

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

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

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 < .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

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

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

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.
Does robotic-assisted thymectomy have advantages over video-assisted thymectomy in short-term outcomes? A systematic view and meta-analysis
Authors: Wu Wen-Jie , Zhang Fu-Yu , Xiao Qin , Li Xiao-Kun
Published: April 2021

OBJECTIVES

A thymic epithelial tumour is the most common primary tumour in the anterior mediastinum of adults. A few retrospective studies compared the short-term outcomes between robotic-assisted thymectomy (RAT) and video-assisted thymectomy (VAT). So, it is necessary to conduct a meta-analysis to further compare these 2 surgical techniques.

METHODS

EMBASE, Medline and Web of Science were used. Thesaurus terms and medical subject headings were used in Medline and EMBASE, respectively. The Newcastle-Ottawa scale was used for grading because the included studies were all case-control studies.

RESULTS

Nine studies were included in the meta-analysis with a total of 723 patients, including 315 patients in the RAT group and 408 patients in the VAT group. The meta-analysis [odds ratio (OR) 0.24, 95% confidence interval (CI) 0.06–0.94; P = 0.041], indicating that RAT yielded a significantly lower rate of conversion compared with VAT. Duration of drainage with RAT was significantly less than that with VAT (weighted mean difference = −1.10; 95% CI −1.98 to −0.22; P = 0.014). The pooled analysis (weighted mean difference = −103.6; 95% CI −199.21 to −7.98; P = 0.034) suggested that patients in the RAT group had less drainage than those in the VAT group. The recurrence rates in both groups were comparable (OR 0.19, 95% CI 0.03–1.20; P = 0.078).

CONCLUSIONS

RAT has advantages over VAT in terms of short-term outcomes such as shorter duration of drainage, less total drainage and a lower rate of conversion. The recurrence rate was comparable between the 2 techniques. Therefore, RAT could be considered as an alternative treatment for diseases of the thymus.
Paediatric subaortic stenosis: long-term outcome and risk factors for reoperation
Authors: De Wolf Rik , François Katrien , Bové Thierry , Coomans Ilse , De Groote Katya , De Wilde Hans , Panzer Joseph , Vandekerckhove Kristof , De Wolf Daniël
Published: April 2021

OBJECTIVES

Surgical repair of subaortic stenosis (SAS) is associated with a substantial reoperation risk. We aimed to identify risk factors for reintervention in relation to discrete and tunnel-type SAS morphology.

METHODS

Single-centre retrospective study of paediatric SAS diagnosed between 1992 and 2017. Multivariable Cox regression analysis was performed to identify reintervention risk factors.

RESULTS

Eighty-five children [median age 2.5 (0.7–6.5) years at diagnosis] with a median follow-up of 10.1 (5.5–16.4) years were included. Surgery was executed in 83% (n = 71). Freedom from reoperation was 88 ± 5% at 5 years and 82 ± 6% at 10 years for discrete SAS, compared to, respectively, 33 ± 16% and 17 ± 14% for tunnel-type SAS (log-rank P < 0.001). Independent risk factors for reintervention were a postoperative gradient >20 mmHg [hazard ratio (HR) 6.56, 95% confidence interval (CI) 1.41–24.1; P = 0.005], tunnel-type SAS (HR 7.46, 95% CI 2.48–22.49; P < 0.001), aortic annulus z-score <−2 (HR 11.07, 95% CI 3.03–40.47; P < 0.001) and age at intervention <2 years (HR 3.24, 95% CI 1.09–9.86; P = 0.035). Addition of septal myectomy at initial intervention was not associated with lesser reintervention. Fourteen children with a lower left ventricular outflow tract (LVOT) gradient (P < 0.001) and older age at diagnosis (P = 0.024) were followed expectatively.

CONCLUSIONS

Children with SAS remain at risk for reintervention, despite initially effective LVOT relief. Regardless of SAS morphology, age <2 years at first intervention, a postoperative gradient >20 mmHg and presence of a hypoplastic aortic annulus are independent risk factors for reintervention. More extensive LVOT surgery might be considered at an earlier stage in these children. SAS presenting in older children with a low LVOT gradient at diagnosis shows little progression, justifying an expectative approach.
Connected cars, SEP and FRAND—CJEU referral with a focus on multi-tier supply chains
Authors: Stief Marco , Röder-Hitschke Heike
Published: April 2021

Düsseldorf Regional Court, referral to the Court of Justice of the European Union, case 4c O 17/19, 26 November 2020

A recent referral of the Düsseldorf Regional Court to the Court of Justice of the European Union raises important questions on the interpretation of fair, reasonable and non-discriminatory licensing obligations in the context of supply chains.
Environmental Correlates of Lyme Disease Emergence in Southwest Virginia, 2005–2014
Authors: Lantos Paul M , Tsao Jean , Janko Mark , Arab Ali , von Fricken Michael E , Auwaerter Paul G , Nigrovic Lise E , Fowler Vance , Ruffin Felicia , Gaines David , Broyhill James , Swenson Jennifer
Published: April 2021

Lyme disease is the most common tick-borne disease in North America. Though human infection is mostly transmitted in a limited geography, the range has expanded in recent years. One notable area of recent expansion is in the mountainous region of southwestern Virginia. The ecological factors that facilitate or constrain the range of human Lyme disease in this region remain uncertain. To evaluate this further, we obtained ecological data, including remotely sensed data on forest structure and vegetation, weather data, and elevation. These data were aggregated within the census block groups of a 9,153 km2 area around the cities of Blacksburg and Roanoke, VA, an area with heterogeneous Lyme disease transmission. In this geographic area, 755 individuals were reported to have Lyme disease in the 10 yr from 2006 to 2015, and these cases were aggregated by block group. A zero-inflated negative binomial model was used to evaluate which environmental variables influenced the abundance of Lyme disease cases. Higher elevation and higher vegetation density had the greatest effect size on the abundance of Lyme disease. Measures of forest edge, forest integrity, temperature, and humidity were not associated with Lyme disease cases. Future southward expansion of Lyme disease into the southeastern states may be most likely in ecologically similar mountainous areas.
Fucoxanthin alters the apelin-13/APJ pathway in certain organs of γ-irradiated mice
Authors: El Bakary Nermeen M , Thabet Noura Magdy , El Fatih Neama M , Abdel-Rafei Mohamed Khairy , El Tawill Ghada , Azab Khaled Shaaban
Published: April 2021

Apelin-13 and APJ are implicated in different key physiological processes. This work aims at exploring the radioprotective effect of fucoxanthin (FX) on γ-radiation (RAD)-induced changes in the apelin-13/APJ pathway, which causes damage in the liver, kidney, lung and spleen of mice. Mice were administered FX (10 mg kg–1 day–1, i.p) and exposed to γ-radiation (2.5 Gy week–1) for four consecutive weeks. The treatment of irradiated mice by FX resulted in a significant amendment in protein expression of the apelin-13/APJ/NF-κB signalling pathway concurrently with reduced hypoxia (hypoxia-inducible factor-1α), suppressed oxidative stress marker (malondialdehyde), enhanced antioxidant defence mechanisms (reduced glutathione and glutathione peroxidase), a modulated inflammatory response [interleukin-6 (IL-6), monocyte chemoattractant protein-1, IL-10 and α-7-nicotinic acetylcholine receptor) and ameliorated angiogenic regulators [matrix metalloproteinase (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1), as well as the tissue damage indicator (lactate dehydrogenase) in organ tissues. In addition, there were significant improvement in serum inflammatory markers tumour necrosis factor-α, IL-10, IL-1β and C-reactive protein compared with irradiated mice. The histopathological investigation of the FX + RAD organ tissues support the biochemical findings where the improvements in the tissues’ architecture were obvious when compared with those of RAD. FX was thus shown to have a noticeable radioprotective action mediated through its regulatory effect on the apelin-13/APJ/NF-κB signalling pathway attributed to its antioxidant and anti-inflammatory activity that was reflected in different physiological processes. It could be recommended to use FX in cases of radiation exposure to protect normal tissues.
Modelling the Rongorongo tablets: A new transcription of the Échancrée tablet and the foundation for decipherment attempts
Authors: Lastilla Lorenzo , Ravanelli Roberta , Valério Miguel , Ferrara Silvia
Published: April 2021

The Rongorongo is a system of writing, still undeciphered, from Easter Island in the Pacific. It consists of a corpus of twenty-six inscriptions, scattered around the world. This article presents the state-of-the art in the study of one of these inscriptions, Text D or the ‘Échancrée’ tablet housed in a museum in Rome, Italy. Through an integrated methodology based on photogrammetry and high-precision structured light scanning, a 3D model of the inscriptions is made available through a public 3D Viewer for the first time. The technique made use of the benefits of both methods of image acquisition: a very accurate, precise, high resolution, and metric reconstruction of the tablet geometry gained through the scanning process, and a high-quality texture achieved through photogrammetry. In addition, we present a new analysis of the text, through a close palaeographic examination of its signs, and corrections of previous hand drawings and transcriptions. The ultimate aim is to reach unbiased ‘readings’ of the signs through an integrated synergy of traditional palaeographic analysis and an advanced 3D model. These, applied to all the inscriptions, constitute the necessary stepping-stones for any decipherment attempt.
Employment After Vocational Rehabilitation Predicts Decreased Health Care Utilization in Veterans With Mental Health Diagnoses
Authors: Abraham Kristen M , Chang Ming-Un Myron , Van Tony , Resnick Sandra G , Zivin Kara
Published: April 2021

Introduction

Although the benefits of employment for veterans with mental health conditions are well-known, the effect of veterans’ employment on a health system has not been evaluated. The purpose of this study was to evaluate the effect of veterans’ employment (versus unemployment) on subsequent health care utilization in the Veterans Health Administration (VHA).

Materials and Methods

This study used a sample of 29,022 veterans with mental health and substance use disorders who were discharged from VHA’s employment services programs between fiscal years 2006 and 2010. Veterans’ employment status (employed/unemployed) upon discharge from VHA employment programs was ascertained from program discharge forms and linked with VHA administrative health care utilization data for the subsequent 1- and 5-year periods.

Results

Multivariable ordinary least-squares and logistic regression models adjusted for site clustering and covariates indicated that employment (versus unemployment) predicted less health care utilization 1 year and 5 years post-discharge from employment services, including fewer outpatient mental health visits, homelessness services visits, employment services visits, primary care visits, and lower odds of mental health hospitalizations, mental health or vocational rehabilitation residential stays, and medical hospitalizations. Employment did not predict emergency department visits.

Conclusions

VHA’s investment in employment services for veterans with mental health and substance use disorders could reduce health care utilization system wide.
A lack of constraints on the cold opaque H i mass: H i spectra in M31 and M33 prefer multicomponent models over a single cold opaque component
Authors: Koch Eric W , Rosolowsky Erik W , Leroy Adam K , Chastenet Jérémy , Chiang (江宜達) I-Da , Dalcanton Julianne , Kepley Amanda A , Sandstrom Karin M , Schruba Andreas , Stanimirović Snežana , Utomo Dyas , Williams Thomas G
Published: April 2021

Previous work has argued that atomic gas mass estimates of galaxies from 21-cm H i emission are systematically low due to a cold opaque atomic gas component. If true, this opaque component necessitates a $\sim 35{{\ \rm per\ cent}}$ correction factor relative to the mass from assuming optically thin H i emission. These mass corrections are based on fitting H i spectra with a single opaque component model that produces a distinct ‘top-hat’ shaped line profile. Here, we investigate this issue using deep, high spectral resolution H i VLA observations of M31 and M33 to test if these top-hat profiles are instead superpositions of multiple H i components along the line of sight. We fit both models and find that ${\gt}80{{\ \rm per\ cent}}$ of the spectra strongly prefer a multicomponent Gaussian model while ${\lt}2{{\ \rm per\ cent}}$ prefer the single opacity-corrected component model. This strong preference for multiple components argues against previous findings of lines of sight dominated by only cold H i. Our findings are enabled by the improved spectral resolution (0.42 ${\rm km\, s^{-1}}$), whereas coarser spectral resolution blends multiple components together. We also show that the inferred opaque atomic ISM mass strongly depends on the goodness-of-fit definition and is highly uncertain when the inferred spin temperature has a large uncertainty. Finally, we find that the relation of the H i surface density with the dust surface density and extinction has significantly more scatter when the inferred H i opacity correction is applied. These variations are difficult to explain without additionally requiring large variations in the dust properties. Based on these findings, we suggest that the opaque H i mass is best constrained by H i absorption studies.
The central region of a void: an analytical solution
Authors: Baushev A N
Published: April 2021

We offer an exact analytical equation for the void central region. We show that the central density is solely determined by the amplitude of the initial perturbation. Our results suggest that N-body simulations somewhat overestimate the emptiness of voids: the majority of them should have the central underdensity $\delta _\mathrm{ c} \gt -73{{\ \rm per\ cent}}$ , and there should be almost no voids with $\delta _\mathrm{ c} \lt -88{{\ \rm per\ cent}}$. The central region of a void is a part of an open Friedmann’s ‘universe’, and its evolution differs drastically from the Universe evolution: there is a long stage when the curvature term dominates that prevents the formation of galaxy clusters and massive galaxies inside voids. The density profile in the void centre should be very flat. We discuss some void models obtained by N-body simulations and offer some ways to improve them. We also show that the dark energy makes the voids less underdense.