bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C therapy with grazoprevir/elbasvir and glecaprevir/pibrentasvir in patients with advanced chronic kidney disease: data from the German Hepatitis C-Registry (DHC-R)
Authors: Stein Kerstin , Stoehr Albrecht , Klinker Hartwig , Teuber Gerlinde , Naumann Uwe , John Christine , Heyne Renate , Serfert Yvonne , Niederau Claus , Zeuzem Stefan , Berg Thomas , Wiegand Johannes ,   German Hepatitis C-Registry
Published: September 2020

Objectives
Grazoprevir/elbasvir and glecaprevir/pibrentasvir (G/P) are the two preferred treatment options for patients with chronic hepatitis C virus (HCV) infection and a glomerular filtration rate (GFR) <30 mL/min. Both therapies have been separately analyzed in different real-life cohorts; however, a direct comparison has not been performed so far. We, therefore, analyzed safety and effectiveness of both regimens in a concerted real-life population.

Methods
The Germany Hepatitis C-Registry is a prospective national real-world registry. The analysis is based on 2773 patients with documented GFR at baseline treated with grazoprevir/elbasvir (N = 1041), grazoprevir/elbasvir + ribavirin (N = 53) and glecaprevir/pibrentasvir (N = 1679).

Results
A total of 93 patients with GFR <30 mL/min were treated with grazoprevir/elbasvir (N = 56), grazoprevir/elbasvir + ribavirin (N = 4), and glecaprevir/pibrentasvir (N = 33). They suffered significantly more frequent from diabetes mellitus, hypertension, and coronary heart disease than individuals with GFR >30 mL/min and showed the following baseline characteristics: 20.4, 55.9, 3.2, 12.9, and 5.3% were infected with HCV-genotypes 1a, 1b, 2, 3, and 4; 12.9% suffered from liver cirrhosis; 80.1% were treatment-naïve. Baseline characteristics except distribution of HCV-genotype 1b (n = 43/52 treated with grazoprevir/elbasvir) and sustained virologic response rates (SVR12) did not differ significantly between glecaprevir/pibrentasvir (SVR12: 100%) and grazoprevir/elbasvir (SVR12: 97.9%).
Fatigue, headache, abdominal discomfort, and arthralgia were the most frequently reported adverse events without a statistical difference between grazoprevir/elbasvir and glecaprevir/pibrentasvir.

Conclusion
In patients with chronic hepatitis C and a baseline GFR ≤30 mL/min grazoprevir/elbasvir and glecaprevir/pibrentasvir show an equally favorable safety profile and antiviral efficacy and can both be recommended for real-life use.
Long-Term Patient Experience with Tetracycline Injections for Festoons
Authors: Chon Brian H. , Hwang Catherine J. , Perry Julian D. 
Published: September 2020

Background:
The purpose of this study was to evaluate the long-term patient experience with tetracycline injections for treatment of festoons.

Methods:
Charts of all patients undergoing tetracycline injection for treatment of lower eyelid festoons at the Cole Eye Institute, Cleveland Clinic, between 2008 and 2018 were identified using billing records. Patients were invited to participate in a questionnaire based on the FACE-Q checklist, a previously validated questionnaire for studying cosmetic procedure outcomes. Data from the questionnaire were summarized with size, mean, and frequency.

Results:
One hundred two patients who received tetracycline injection during the study period were identified and 61 responses were obtained. The average follow-up time after injection was 3.6 years. Of 61 respondents, 36 (59 percent) noted improvement in their festoons after treatment, and 27 of 33 (82 percent) noted that improvement occurred within 2 months of treatment. Overall, 40 of 60 respondents (67 percent) would consider repeating tetracycline treatment. The most common adverse effects included discomfort (18 percent), swelling (15 percent), and bruising (13 percent). There was no statistically significant difference in questionnaire responses between men and women, except that men were more likely to consider repeated injection (92 percent versus 58 percent; p = 0.005).

Conclusion:
Tetracycline injection appears to improve festoons in a majority of patients, with an acceptable side-effect profile, although more data are needed to determine the optimal dose and frequency and to identify possible rare and/or significant side effects.
Granulomatous Mastitis
Authors: Shin Kyungmin , Ruiz-Flores Lorell , Schopp Jennifer , Whitman Gary J. 
Published: September 2020

Abstract
Granulomatous mastitis is a rare benign inflammatory disease of the breast, predominantly affecting women of childbearing age. Because of its low prevalence, the literature is limited, and its treatment algorithm is unclear. However, it is important to understand this disease for timely diagnosis and treatment. Our overview with imaging examples of biopsy-proven cases aims to improve our knowledge and to determine when it would be appropriate to include it in the differential diagnosis.
Should Sleeve Gastrectomy Be Considered Only as a First Step in Super Obese Patients? 5-Year Results From a Single Center
Authors: Vitiello Antonio , Berardi Giovanna , Velotti Nunzio , De Palma Giovanni D. , Musella Mario 
Published: September 2020

Purpose:
Sleeve gastrectomy (SG) has been originally conceived as a first step procedure for super obese (SO) patients, but it is currently considered a stand-alone intervention. Medium-term to long-term studies have shown weight regain and risk of de novo gastroesophageal reflux (GERD). The aim of this study was to evaluate outcomes of SG in SO subjects.

Materials and Methods:
A retrospective analysis of a prospectively maintained database was carried out to find all SO patients who had undergone SG with a minimum follow-up of 5 years. Inclusion criteria were preoperative endoscopy negative for esophagitis and/or hiatal hernia, and no GERD or acid reduction medication before SG. Reflux symptoms were evaluated using a validated questionnaire and endoscopy. Remission rates from comorbidities and percentage of excess body mass index (BMI) loss were recorded.

Results:
A total of 66 (45 male/21 female) patients were included in our study. Mean preoperative BMI and age were 57.4±5.8 kg/m2 and 32.7±11.2 years, respectively. After 5 years, mean percentage of excess BMI loss was 56.42±27.8, and remission rates from hypertension, diabetes, and dyslipidemia were 33.3%, 5.3%, and 20%, respectively. After 5 years, new-onset GERD occurred in 66.7% of patients and 33.3% were taking acid reduction medication. Endoscopy revealed 12 (18.2%) cases of esophagitis ≥grade A.

Conclusions:
After 5 years, weight loss in SO patients is satisfactory, but the vast majority of patients is still in class II obesity, and resolution of comorbidities is disappointing. High rates of de novo GERD and esophagitis may occur.
Demography, life-history trade-offs, and the gastrointestinal virome of wild chimpanzees
Authors: Negrey Jacob D. , Thompson Melissa Emery , Langergraber Kevin E. , Machanda Zarin P. , Mitani John C. , Muller Martin N. , Otali Emily , Owens Leah A. , Wrangham Richard W. , Goldberg Tony L. 
Published: September 2020

In humans, senescence increases susceptibility to viral infection. However, comparative data on viral infection in free-living non-human primates—even in our closest living relatives, chimpanzees and bonobos (Pan troglodytesandP. paniscus)—are relatively scarce, thereby constraining an evolutionary understanding of age-related patterns of viral infection. We investigated a population of wild eastern chimpanzees (P. t. schweinfurthii), using metagenomics to characterize viromes (full viral communities) in the faeces of 42 sexually mature chimpanzees (22 males, 20 females) from the Kanyawara and Ngogo communities of Kibale National Park, Uganda. We identified 12 viruses from at least four viral families possessing genomes of both single-stranded RNA and single-stranded DNA. Faecal viromes of both sexes varied with chimpanzee age, but viral richness increased with age only in males. This effect was largely due to three viruses, salivirus, porprismacovirus and chimpanzee stool-associated RNA virus (chisavirus), which occurred most frequently in samples from older males. This finding is consistent with the hypothesis that selection on males for early-life reproduction compromises investment in somatic maintenance, which has delayed consequences for health later in life, in this case reflected in viral infection and/or shedding. Faecal viromes are therefore useful for studying processes related to the divergent reproductive strategies of males and females, ageing, and sex differences in longevity.This article is part of the theme issue ‘Evolution of the primate ageing process'.
Age-related decline in executive function as a hallmark of cognitive ageing in primates: an overview of cognitive and neurobiological studies
Authors: Lacreuse Agnès , Raz Naftali , Schmidtke Daniel , Hopkins William D. , Herndon James G. 
Published: September 2020

Executive function (EF) is a complex construct that reflects multiple higher-order cognitive processes such as planning, updating, inhibiting and set-shifting. Decline in these functions is a hallmark of cognitive ageing in humans, and age differences and changes in EF correlate with age-related differences and changes in association cortices, particularly the prefrontal areas. Here, we review evidence for age-related decline in EF and associated neurobiological changes in prosimians, New World and Old World monkeys, apes and humans. While EF declines with age in all primate species studied, the relationship of this decline with age-related alterations in the prefrontal cortex remains unclear, owing to the scarcity of neurobiological studies focusing on the ageing brain in most primate species. In addition, the influence of sex, vascular and metabolic risk, and hormonal status has rarely been considered. We outline several methodological limitations and challenges with the goal of producing a comprehensive integration of cognitive and neurobiological data across species and elucidating how ageing shapes neurocognitive trajectories in primates with different life histories, lifespans and brain architectures. Such comparative investigations are critical for fostering translational research and understanding healthy and pathological ageing in our own species.This article is part of the theme issue ‘Evolution of the primate ageing process’.
A neural and behavioral tradeoff underlies exploratory decisions in normative anxiety
Authors: Aberg Kristoffer C. , Toren Ido , Paz Rony 
Published: September 2020

AbstractExploration reduces uncertainty about the environment and improves the quality of future decisions, but at the cost of provisional uncertain and suboptimal outcomes. Although anxiety promotes intolerance to uncertainty, it remains unclear whether and by which mechanisms anxiety modulates exploratory decision-making. We use a dynamic three-armed-bandit task and find that higher trait-anxiety increases exploration, which in turn harms overall performance. We identify two distinct behavioral sources: first, decisions made by anxious individuals were guided towards reduction of uncertainty; and second, decisions were less guided by immediate value gains. Imaging (fMRI) revealed that anxiety correlated negatively with the representation of expected-value in the dorsal-anterior-cingulate-cortex, and in contrast, positively with the representation of uncertainty in the anterior-insula. Moreover, the findings were similar in both loss and gain domains, and demonstrated that affective trait modulates exploration and results in an inverse-U-shaped relationship between anxiety and overall performance. We conclude that a shift in balance towards representation of uncertainty in the insula prevails over reduced value representation in the dACC, and entails maladaptive decision-making in individuals with higher normal-range anxiety.
Systematic Identification of Protein Phosphorylation-Mediated Interactions
Authors: Floyd Brendan M. , Drew Kevin , Marcotte Edward M. 
Published: September 2020

ABSTRACTProtein phosphorylation is a key regulatory mechanism involved in nearly every eukaryotic cellular process. Increasingly sensitive mass spectrometry approaches have identified hundreds of thousands of phosphorylation sites but the functions of a vast majority of these sites remain unknown, with fewer than 5% of sites currently assigned a function. To increase our understanding of functional protein phosphorylation we developed an approach for identifying the phosphorylation-dependence of protein assemblies in a systematic manner. A combination of non-specific protein phosphatase treatment, size-exclusion chromatography, and mass spectrometry allowed us to identify changes in protein interactions after the removal of phosphate modifications. With this approach we were able to identify 316 proteins involved in phosphorylation-sensitive interactions. We recovered known phosphorylation-dependent interactors such as the FACT complex and spliceosome, as well as identified novel interactions such as the tripeptidyl peptidase TPP2 and the supraspliceosome component ZRANB2. More generally, we find phosphorylation-dependent interactors to be strongly enriched for RNA-binding proteins, providing new insight into the role of phosphorylation in RNA binding. By searching directly for phosphorylated amino acid residues in mass spectrometry data, we identified the likely regulatory phosphosites on ZRANB2 and FACT complex subunit SSRP1. This study provides both a method and resource for obtaining a better understanding of the role of phosphorylation in native macromolecular assemblies.
Multimodal mechanosensing enables treefrog embryos to escape egg-predators
Authors: Jung Julie , Serrano-Rojas Shirley J. , Warkentin Karen M. 
Published: September 2020

ABSTRACTMechanosensory-cued hatching (MCH) is widespread, diverse, and improves survival in many animals. From flatworms and insects to frogs and turtles, embryos use mechanosensory cues and signals to inform hatching timing, yet mechanisms mediating mechanosensingin ovoare largely unknown. The arboreal embryos of red-eyed treefrogs,Agalychnis callidryas,hatch prematurely to escape predation, cued by physical disturbance in snake attacks. When otoconial organs in the developing vestibular system become functional, this response strengthens, but its earlier occurrence indicates another sensor must contribute. Post-hatching, tadpoles use lateral line neuromasts to detect water motion. We ablated neuromast function with gentamicin to assess their role inA. callidryas’ hatching response to disturbance. Prior to vestibular function, this nearly eliminated the hatching response to a complex simulated attack cue, egg-jiggling, revealing that neuromasts mediate early MCH. Vestibular function onset increased hatching, independent of neuromast function, indicating young embryos use multiple mechanosensory systems. MCH increased developmentally. All older embryos hatched in response to egg-jiggling, but neuromast function reduced response latency. In contrast, neuromast ablation had no effect on timing or level of hatching in motion-only vibration playbacks. It appears only a subset of egg-disturbance cues stimulate neuromasts; thus embryos in attacked clutches may receive uni- or multimodal stimuli.A. callidryasembryos have more neuromasts than described for any other species at hatching, suggesting precocious sensory development may facilitate MCH. Our findings provide insight into the behavioral roles of two mechanosensory systemsin ovoand open possibilities for exploring sensory perception across taxa in early life stages.SUMMARYRed-eyed treefrog embryos use both their lateral line and vestibular systems to sense the disturbance cues in egg-predator attacks that inform escape-hatching decisions.
A functional variant of the SIDT2 gene involved in cholesterol transport is associated with HDL-C levels and premature coronary artery disease
Authors: León-Mimila Paola , Villamil-Ramírez Hugo , Macias-Kauffer Luis R. , Jacobo-Albavera Leonor , López-Contreras Blanca E. , Posadas-Sánchez Rosalinda , Posadas-Romero Carlos , Romero-Hidalgo Sandra , Morán-Ramos Sofía , Domínguez-Pérez Mayra , Olivares-Arevalo Marisol , Lopez-Montoya Priscilla , Nieto-Guerra Roberto , Acuña-Alonzo Víctor , Macín-Pérez Gastón , Barquera-Lozano Rodrigo , del Río-Navarro Blanca E. , González-González Israel , Campos-Pérez Francisco , Gómez-Pérez Francisco , Valdés Victor J. , Sampieri Alicia , Reyes-García Juan G. , Carrasco-Portugal Miriam del C. , Flores-Murrieta Francisco J. , Aguilar-Salinas Carlos A. , Vargas-Alarcón Gilberto , Shih Diana , Meikle Peter J. , Calkin Anna C. , Drew Brian G. , Vaca Luis , Lusis Aldons J. , Huertas-Vazquez Adriana , Villarreal-Molina Teresa , Canizales-Quinteros Samuel 
Published: September 2020

ABSTRACTLow HDL-C is the most frequent dyslipidemia in Mexicans, but few studies have examined the underlying genetic basis. Moreover, few lipid-associated variants have been tested for coronary artery disease (CAD) in Hispanic populations. Here, we performed a GWAS for HDL-C levels in 2,183 Mexican individuals, identifying 7 loci, including three with genome-wide significance and containing the candidate genes CETP, ABCA1 and SIDT2. The SIDT2 missense Val636Ile variant was associated with HDL-C levels for the first time, and this association was replicated in 3 independent cohorts (P=5.5×10−21 in the conjoint analysis). The SIDT2/Val636Ile variant is more frequent in Native American and derived populations than in other ethnic groups. This variant was also associated with increased ApoA1 and glycerophospholipid serum levels, decreased LDL-C and ApoB levels and a lower risk of premature CAD. Because SIDT2 was previously identified as a protein involved in sterol transport, we tested whether the SIDT2/Ile636 protein affected this function using an in vitro site-directed mutagenesis approach. The SIDT2/Ile636 protein showed increased uptake of the cholesterol analog dehydroergosterol, suggesting this variant is functional. Finally, liver transcriptome data from humans and the Hybrid Mouse Diversity Panel (HMDP) are consistent with the involvement of SIDT2 in lipid and lipoprotein metabolism. In conclusion, this is the first study assessing genetic variants contributing to HDL-C levels and coronary artery disease in the Mexican population. Our findings provide new insight into the genetic architecture of HDL-C and highlight SIDT2 as a new player in cholesterol and lipoprotein metabolism in humans.
A germ cell‐specific ageing pattern in otherwise healthy men
Authors: Laurentino Sandra , Cremers Jann‐Frederik , Horsthemke Bernhard , Tüttelmann Frank , Czeloth Karen , Zitzmann Michael , Pohl Eva , Rahmann Sven , Schröder Christopher , Berres Sven , Redmann Klaus , Krallmann Claudia , Schlatt Stefan , Kliesch Sabine , Gromoll Jörg 
Published: September 2020

AbstractLife‐long sperm production leads to the assumption that male fecundity remains unchanged throughout life. However, recently it was shown that paternal age has profound consequences for male fertility and offspring health. Paternal age effects are caused by an accumulation of germ cell mutations over time, causing severe congenital diseases. Apart from these well‐described cases, molecular patterns of ageing in germ cells and their impact on DNA integrity have not been studied in detail. In this study, we aimed to assess the effects of ‘pure’ ageing on male reproductive health and germ cell quality. We assembled a cohort of 198 healthy men (18–84 years) for which end points such as semen and hormone profiles, sexual health and well‐being, and sperm DNA parameters were evaluated. Sperm production and hormonal profiles were maintained at physiological levels over a period of six decades. In contrast, we identified a germ cell‐specific ageing pattern characterized by a steady increase of telomere length in sperm and a sharp increase in sperm DNA instability, particularly after the sixth decade. Importantly, we found sperm DNA methylation changes in 236 regions, mostly nearby genes associated with neuronal development. By in silico analysis, we found that 10 of these regions are located in loci which can potentially escape the first wave of genome‐wide demethylation after fertilization. In conclusion, human male germ cells present a unique germline‐specific ageing process, which likely results in diminished fecundity in elderly men and poorer health prognosis for their offspring.
Are all forms of ownership prone to tunneling? A meta‐analysis
Authors: Solarino Angelo M. , Boyd Brian K. 
Published: September 2020

AbstractResearch Question/IssueThis study seeks to extend agency theory in the context of tunneling by exploring how different owner types seek private benefits of control. Specifically, we examine how information asymmetries and board representation create different pressures for tunneling for state‐owned, business group‐owned, and family‐owned firms. We tested our hypotheses with a meta‐analytic structural equation model.Research Findings/InsightsOur findings show that the relationship between ownership and tunneling differs across owner types in terms of both directionality and magnitude. Our study offers a substantial theoretical contribution to the principal–principal problem literature by theorizing and testing variations of the problem among owners. Our study also advances our understanding of the role of ownership in firms.Theoretical/Academic ImplicationsOur findings have important theory‐building implications for the principal–principal literature. Controlling shareholders have been linked to performance outcomes or to tunneling in general, yet little is known about their comparative propensity to engage in tunneling. Our results, however, highlight that the propensity to engage in tunneling varies substantially among controlling shareholders. Furthermore, in the robustness checks, we disconfirm some of the assumptions of the principal–principal literature. This study demonstrates the need to theorize about specific types of ownership and reassess the core arguments of principal–principal theory.Practitioner/Policy ImplicationsThis study offers insights for policymakers interested in mitigating the risk of minority shareholders being expropriated by the controlling shareholder. As the key driver of tunneling appears to be access to private information and knowledge of the firm, we offer recommendations on what policymakers can do to minimize the asymmetry of information.