bluuebunny/crossref_metadata_2025_split huggingface dataset:
A parsimonious personalized dose-finding model via dimension reduction
Authors: Zhou Wenzhuo , Zhu Ruoqing , Zeng Donglin 
Published: October 2020

SummaryLearning an individualized dose rule in personalized medicine is a challenging statistical problem. Existing methods often suffer from the curse of dimensionality, especially when the decision function is estimated nonparametrically. To tackle this problem, we propose a dimension reduction framework that effectively reduces the estimation to an optimization on a lower-dimensional subspace of the covariates. We exploit the fact that the individualized dose rule can be defined in a subspace spanned by a few linear combinations of the covariates to obtain a more parsimonious model. Owing to direct maximization of the value function, the proposed framework does not require the inverse probability of the propensity score under observational studies. This distinguishes our approach from the outcome-weighted learning framework, which also solves decision rules directly. Within the same framework, we further propose a pseudo-direct learning approach that focuses more on estimating the dimensionality-reduced subspace of the treatment outcome. Parameters in both approaches can be estimated efficiently using an orthogonality-constrained optimization algorithm on the Stiefel manifold. Under mild regularity assumptions, results on the asymptotic normality of the proposed estimators are established. We also derive the consistency and convergence rate of the value function under the estimated optimal dose rule. We evaluate the performance of the proposed approaches through extensive simulation studies and analysis of a pharmacogenetic dataset.
Dietary carbohydrates restriction inhibits the development of cardiac hypertrophy and heart failure
Authors: Nakamura Michinari , Odanovic Natalija , Nakada Yasuki , Dohi Satomi , Zhai Peiyong , Ivessa Andreas , Yang Zhi , Abdellatif Maha , Sadoshima Junichi 
Published: October 2020

Abstract

Aims
A diet with modified components, such as a ketogenic low-carbohydrate (LC) diet, potentially extends longevity and healthspan. However, how an LC diet impacts on cardiac pathology during haemodynamic stress remains elusive. This study evaluated the effects of an LC diet high in either fat (Fat-LC) or protein (Pro-LC) in a mouse model of chronic hypertensive cardiac remodelling.

Methods and results
Wild-type mice were subjected to transverse aortic constriction, followed by feeding with the Fat-LC, the Pro-LC, or a high-carbohydrate control diet. After 4 weeks, echocardiographic, haemodynamic, histological, and biochemical analyses were performed. LC diet consumption after pressure overload inhibited the development of pathological hypertrophy and systolic dysfunction compared to the control diet. An anti-hypertrophic serine/threonine kinase, GSK-3β, was re-activated by both LC diets; however, the Fat-LC, but not the Pro-LC, diet exerted cardioprotection in GSK-3β cardiac-specific knockout mice. β-hydroxybutyrate, a major ketone body in mammals, was increased in the hearts of mice fed the Fat-LC, but not the Pro-LC, diet. In cardiomyocytes, ketone body supplementation inhibited phenylephrine-induced hypertrophy, in part by suppressing mTOR signalling.

Conclusion
Strict carbohydrate restriction suppresses pathological cardiac growth and heart failure after pressure overload through distinct anti-hypertrophic mechanisms elicited by supplemented macronutrients.
Haploinsufficiency ofTmem43in cardiac myocytes activates the DNA damage response pathway leading to a late-onset senescence-associated pro-fibrotic cardiomyopathy
Authors: Rouhi Leila , Cheedipudi Sirisha M , Chen Suet Nee , Fan Siyang , Lombardi Raffaella , Chen Xiaofan , Coarfa Cristian , Robertson Matthew J , Gurha Priyatansh , Marian Ali J 
Published: October 2020

AbstractAimsArrhythmogenic cardiomyopathy (ACM) encompasses a genetically heterogeneous group of myocardial diseases whose manifestations are sudden cardiac death, cardiac arrhythmias, heart failure, and in a subset fibro-adipogenic infiltration of the myocardium. Mutations in the TMEM43 gene, encoding transmembrane protein 43 (TMEM43) are known to cause ACM. The purpose of the study was to gain insights into the molecular pathogenesis of ACM caused by TMEM43 haploinsufficiency.Methods and resultsThe Tmem43 gene was specifically deleted in cardiac myocytes by crossing the Myh6-Cre and floxed Tmem43 mice. Myh6-Cre:Tmem43W/F mice showed an age-dependent phenotype characterized by an increased mortality, cardiac dilatation and dysfunction, myocardial fibrosis, adipogenesis, and apoptosis. Sequencing of cardiac myocyte transcripts prior to and after the onset of cardiac phenotype predicted early activation of the TP53 pathway. Increased TP53 activity was associated with increased levels of markers of DNA damage response (DDR), and a subset of senescence-associated secretary phenotype (SASP). Activation of DDR, TP53, SASP, and their selected downstream effectors, including phospho-SMAD2 and phospho-SMAD3 were validated by alternative methods, including immunoblotting. Expression of SASP was associated with epithelial–mesenchymal transition and age-dependent expression of myocardial fibrosis and apoptosis in the Myh6-Cre:Tmem43W/F mice.ConclusionTMEM43 haploinsufficiency is associated with activation of the DDR and the TP53 pathways, which lead to increased expression of SASP and an age-dependent expression of a pro-fibrotic cardiomyopathy. Given that TMEM43 is a nuclear envelope protein and our previous data showing deficiency of another nuclear envelope protein, namely lamin A/C, activates the DDR/TP53 pathway, we surmise that DNA damage is a shared mechanism in the pathogenesis of cardiomyopathies caused by mutations involving nuclear envelope proteins.
A different type of acute myocarditis: a case report of acute autoimmune myocarditis mediated by anti-PD-1 T lymphocyte receptor (pembrolizumab)
Authors: Salido Iniesta Mario , López López Laura , Carreras Costa Francesc , Sionis Alessandro 
Published: October 2020

Abstract

Background
Pembrolizumab is an immune check-point inhibitor (ICI), which acts by blocking the T lymphocyte PD-1 inhibitor receptor. It has been increasingly used in advanced or non-responsive tumours with promising results. However, acute myocarditis is an infrequent but potentially life-threatening autoimmune adverse effect related to ICIs.

Case summary
This case deals with a 69-year-old gentleman on second-line therapy with pembrolizumab for advanced non-small cell lung cancer. Three weeks after first dose, the patient was diagnosed with an autoimmune hepatitis, treated with decreasing corticoid dosage, followed by acute heart failure. On admission, his electrocardiogram (ECG) showed diffuse repolarization changes and a transthoracic echocardiography revealed severe left ventricle impairment (left ventricular ejection fraction 32%). High-sensitivity cardiac troponin was elevated and a coronary angiogram was performed showing non-significant obstructive disease. An autoimmune myocarditis was suspected, and high-dose intravenous corticoid, intravenous vasodilators, and loop diuretics were started with favourable response. Cardiac magnetic resonance (CMR) imaging, performed 2 weeks after clinical onset, revealed extracellular oedema in the anteroseptal-apical left ventricle segments. A new transthoracic echocardiography, performed after 3 months, showed preserved left ventricle ejection fraction. Finally, the patient was readmitted due to an autoimmune myasthenia-like syndrome.

Discussion
Acute autoimmune myocarditis related to ICIs is a challenging diagnosis and its incidence has been underestimated in early studies. Endomyocardial biopsy (EMB) is the gold standard test for its diagnosis. Nevertheless, a definite myocarditis diagnosis is possible without EMB when characteristic clinical syndrome, elevated myonecrosis markers, and electrocardiographic, echocardiographic, and CMR changes are present together.
Mitochondrial Genome Evolution of Placozoans: Gene Rearrangements and Repeat Expansions
Authors: Miyazawa Hideyuki , Osigus Hans-Jürgen , Rolfes Sarah , Kamm Kai , Schierwater Bernd , Nakano Hiroaki 
Published: October 2020

Abstract
Placozoans, nonbilaterian animals with the simplest known metazoan bauplan, are currently classified into 20 haplotypes belonging to three genera, Polyplacotoma, Trichoplax, and Hoilungia. The latter two comprise two and five clades, respectively. In Trichoplax and Hoilungia, previous studies on six haplotypes belonging to four different clades have shown that their mtDNAs are circular chromosomes of 32–43 kb in size, which encode 12 protein-coding genes, 24 tRNAs, and two rRNAs. These mitochondrial genomes (mitogenomes) also show unique features rarely seen in other metazoans, including open reading frames (ORFs) of unknown function, and group I and II introns. Here, we report seven new mitogenomes, covering the five previously described haplotypes H2, H17, H19, H9, and H11, as well as two new haplotypes, H23 (clade III) and H24 (clade VII). The overall gene content is shared between all placozoan mitochondrial genomes, but genome sizes, gene orders, and several exon–intron boundaries vary among clades. Phylogenomic analyses strongly support a tree topology different from previous 16S rRNA analyses, with clade VI as the sister group to all other Hoilungia clades. We found small inverted repeats in all 13 mitochondrial genomes of the Trichoplax and Hoilungia genera and evaluated their distribution patterns among haplotypes. Because Polyplacotoma mediterranea (H0), the sister to the remaining haplotypes, has a small mitochondrial genome with few small inverted repeats and ORFs, we hypothesized that the proliferation of inverted repeats and ORFs substantially contributed to the observed increase in the size and GC content of the Trichoplax and Hoilungia mitochondrial genomes.
When I Learn the News is False: How Fact-Checking Information Stems the Spread of Fake News Via Third-Person Perception
Authors: Chung Myojung , Kim Nuri 
Published: October 2020

AbstractWhile fact-checking has received much attention as a potential tool to combat fake news, whether and how fact-checking information lessens intentions to share fake news on social media remains underexplored. Two experiments uncovered a theoretical mechanism underlying the effect of fact-checking on sharing intentions, and identified an important contextual cue (i.e., social media metrics) that interacts with fact-checking effects. Exposure to fake news with fact-checking information (vs. fake news without fact-checking information) yielded more negative evaluations of the news and a greater belief that others are more influenced by the news than oneself (third-person perception [TPP]). Increased TPP, in turn, led to weaker intentions to share fake news on social media. Fact-checking information also nullified the effect of social media metrics on sharing intentions; without fact-checking information, higher (vs. lower) social media metrics induced greater intentions to share the news. However, when fact-checking debunked the news, such an effect disappeared.
Can lifestyle interventions improve Canadian men’s mental health? Outcomes from the HAT TRICK programme
Authors: Sharp Paul , Stolp Sean , Bottorff Joan L , Oliffe John L , Hunt Kate , Caperchione Cristina M 
Published: October 2020

Summary
Engaging men in mental health promotion can be difficult because of reticence about help-seeking, especially for gender neutral programmes. Developments in men’s health research has pointed to the success of gender-sensitized programmes to increase men’s engagement in healthy lifestyle interventions targeting physical activity and healthy eating; however, less is known about the impact of these interventions on men’s mental health. This study explored changes to men’s depression risk and health-related quality of life at post-intervention (12 weeks) and 9-month follow-up, after participating in HAT TRICK, a gender-sensitized lifestyle intervention for overweight men. Participants completed validated self-report measures of mental health at baseline, post-intervention (12 weeks) and 9-month follow-up. Men’s scores on the Male Depression Risk Scale (MDRS) and the SF-12 questionnaire, including physical health (PH12) and mental health (MH12) composite scores, were analyzed using mixed linear models to assess linear trends. At baseline, men (N = 62) had a mean age of 50.98 (SD = 10.09) years and BMI of 35.87 (SD = 5.51) kg/m2. Results show that both the MDRS and the MH12 showed improvements in participants’ mental health, with significant linear trends (p = 0.003; p = 0.003) qualified with significant quadratic trends over time (p = 0.02; p = 0.03). There were no significant changes in the PH12 over time. Gender-sensitized programmes for overweight men, such as HAT TRICK, are a promising approach to positively influence components of men’s mental health, with the potential for sustained improvements over the long term.
Characteristics and long-term outcomes of aortico-left ventricular tunnel
Authors: Sun Jing , Qi Hongxia , Lin Hongyuan , Kang Wenying , Li Shoujun , Guo Hongwei , Qian Xiangyang 
Published: October 2020

Abstract

OBJECTIVES
Aortico-left ventricular tunnel (ALVT) is an extremely rare, abnormal paravalvular communication between the aorta and the left ventricle. Few studies have identified the characteristics and long-term prognosis associated with ALVT.

METHODS
The data of 31 patients with ALVT from July 2002 to December 2019 were reviewed. Echocardiography was performed in all patients during the follow-up period.

RESULTS
The median age of the patients was 11.5 years. Bicuspid aortic valve and dilatation of the ascending aorta were found in 13 patients, respectively. The aortic orifice in 20 patients showed a close relation to the right sinus and the right–left commissure. Of the 31 patients, 26 were operated on. Mechanical valve replacement was performed in 4 patients and aortic valve repair, in 6 patients. Ascending aortoplasty was performed in 5 patients and aortic replacement was done in 2 patients. One patient died of ventricular fibrillation before the operation. Follow-up of the remaining 30 patients ranged from 1 to 210 months (median 64 months). There were 4 deaths during the follow-up period: 1 had mechanical valve replacement and 3 did not undergo surgical repair. In the 26 patients without aortic valve replacement, 6 had severe regurgitation and 2 had moderate regurgitation. In the 28 patients without replacement of the ascending aorta, 11 had continued dilatation of the ascending aorta, including those who had aortoplasty.

CONCLUSIONS
The aortic orifice of ALVT showed an association with the right sinus and the right–left commissure. For patients who did not have surgery, the long-term survival rate remained terrible. Surgical closure should be done as soon as possible after ALVT is diagnosed. The main long-term complications after surgical repair included aortic regurgitation and ascending aortic dilatation.
Carcass and efficiency metrics of beef cattle differ by whether the calf was born in a dairy or a beef herd
Authors: Twomey Alan J , Ring Siobhán C , McHugh Noirin , Berry Donagh P 
Published: October 2020

Abstract
Beef originates from the progeny of either dairy or beef dams. The objective of the present study was to identify contributing factors to the differences in the carcass merit of progeny from both dam types. This goal was achieved using slaughter records from 16,414 bucket-reared dairy animals (DXD), 5,407 bucket-reared dairy-beef animals (BXD), 42,102 suckle-reared animals from a beef × dairy F1 cross dam (BXF1), and 93,737 suckle-reared animals from a beef × beef cow (BXB). Linear mixed models were used to quantify the least squares means for carcass characteristics in the various progeny genotypes. Nuisance fixed effects adjusted for in the models were: animal heterosis and recombination loss, dam parity, age at slaughter, and contemporary group; age at slaughter was replaced as an independent variable with both carcass weight and carcass fat score where the dependent variable was age at slaughter. In a follow-up analysis, models were re-analyzed where the genetic merit of the sire was adjusted for; a further analysis set the genetic merit of the dam for the dependent variable to be identical for both the dairy and beef dams. The final analysis adjusted to a common sire and dam genetic merit facilitating the estimation of just differences in early-life rearing strategies. Irrespective of the genetic merit of the sire and dam, animals originating from beef herds had heavier and more conformed carcasses. BXB animals had a 67 kg heavier carcass, with a conformation score (scale 1 [poor] to 15 [excellent]) of 5 units greater compared with DXD animals. When the genetic merit of all dams was set to be equal, BXB animals were heavier and better conformed than BXD animals. When the genetic merit for both the sire and dam were set to be equal, carcasses of the BXB animals were 15 kg heavier, with a 0.69 unit superior conformation score compared with the DXD animals; this difference is due to early life experiences. In conclusion, the majority of the inferiority in carcass metrics of calves from dairy herds compared with beef herds is due to differences in the genetic merit of the parents. Nevertheless, even after adjusting the parents to the same genetic merit, progeny from dairy herds were still inferior to their contemporaries born in beef herds, due most likely to the persistence of early life experiences.
Validation of a beef cattle maternal breeding objective based on a cross-sectional analysis of a large national cattle database
Authors: Twomey Alan J , Cromie Andrew R , McHugh Noirin , Berry Donagh P 
Published: October 2020

AbstractDespite the importance of validating any technology prior to recommendation for use, few studies exist in the scientific literature which have demonstrated the superior performance of high-ranking animals in a given total merit index; this is especially true for maternal cattle selection indexes. The objective of the present study was to demonstrate the impact of the Irish total merit maternal-based index and provide the benefits of using the Irish total merit maternal-based beef index as part of a breeding policy. The validation exercise was undertaken using 269,407 records (which included the cow’s own records and her progeny records) from 92,300 females differing in a total merit index for maternal value; a comparison was also made with the Irish terminal index. Association analyses were undertaken within the framework of linear and threshold mixed models; the traits analyzed were fertility (e.g., calving interval), slaughter (e.g., harvest weight), live weight (e.g., weaning weight), and producer-recorded traits (e.g., docility). All traits were analyzed with the maternal index and terminal index fitted as covariate(s) separately. Depending on the independent variable analyzed, the other fixed effects included: parity of cow, heterosis and recombination loss of cow and/or progeny, gender of progeny, and the estimated breeding value of the sire; contemporary group was included as a random effect. The results demonstrate the effectiveness of using total merit indexes to improve performance in a whole range of different traits, despite the often antagonistic genetic correlations among traits that underpin the index. Cows excelling on the maternal index had less calving difficulty, superior fertility performance, lighter carcasses, and live weight, as well as being more easily managed. Additionally, progeny of higher maternal index cows were lighter at birth and more docile albeit with a small impact on slaughter traits. In contrast, higher terminal index cows had more calving difficulty, compromised fertility and had heavier carcasses themselves as well as their progeny. While the differences in phenotypic performance between groups on maternal index was, in most instances, relatively small, the benefits are: (1) expected to be greater when more genetically extreme groups of animals are evaluated and (2) expected to accumulate over time given the cumulative and permanent properties of breeding schemes.
Response of lactating dairy cows fed different supplemental zinc sources with and without evaporative cooling to intramammary lipopolysaccharide infusion: metabolite and mineral profiles in blood and milk
Authors: Marins Thiago N , Monteiro Ana P A , Weng Xisha , Guo Jinru , Orellana Rivas Ruth M , Bernard John K , Tomlinson Dana J , DeFrain Jeff M , Tao Sha 
Published: October 2020

Abstract
The objective of this study was to determine the effect of evaporative cooling and dietary supplemental Zn source on blood metabolites, insulin and mineral concentrations, and milk mineral concentrations following intramammary lipopolysaccharide (LPS) infusion. Seventy-two multiparous Holstein cows were assigned to one of four treatments with a 2 × 2 factorial arrangement. Treatments included two environments: with or without evaporative cooling using fans and misters over the freestall and feedbunk, and two dietary sources of supplemental Zn: 75 mg/kg of dry matter (DM) supplied by Zn hydroxychloride (inorganic Zn; IOZ) or Zn hydroxychloride (35 mg of Zn/kg of DM) + Zn–Met complex (ZMC; 40 mg of Zn/kg of DM). A subset of cows (n = 16; 263 ± 63 d in milk) was infused with 10 μg of LPS or a saline control in the left or right rear quarters on day 34 of the environmental treatment. Individual milk samples collected from LPS-infused quarters at −4, 0, 6, 12, 24, 48, 72, 96, and 144 h relative to infusion were analyzed for minerals. Blood samples were collected at the same time with an additional sample collected at 3 h post-infusion to analyze glucose, nonesterified fatty acids (NEFA), insulin, and minerals. Cooling by time interactions (P ≤ 0.07) were observed for plasma glucose, NEFA, and serum insulin. Compared with cooled cows, non-cooled cows had lower concentrations of plasma glucose except at 3 h following intramammary LPS infusion, greater serum insulin at 3 and 12 h, and lower plasma NEFA at 24 and 48 h after infusion. Relative to cooled cows, non-cooled cows tended (P = 0.07) to have lower serum K concentration and had lower (P &lt; 0.01) serum Zn 6 h following infusion (cooling by time interaction: P &lt; 0.01). Relative to ZMC cows, IOZ cows had greater (P ≤ 0.09) concentrations of plasma Se, skim milk Na and Se, and skim milk Na to K ratio. Regardless of treatment, intramammary LPS infusion reduced (P &lt; 0.01) serum or plasma concentrations of Ca, Mg, Zn, Fe, and Se, but increased (P &lt; 0.01) their concentration in skim milk. In conclusion, deprivation of cooling resulted in more rapid and prolonged insulin release and influenced the systemic and mammary mineral metabolism during mammary inflammation induced by LPS of lactating dairy cows. Dietary supplementation of Zn–Met complex reduced blood and milk Se concentrations compared with cows fed Zn from an inorganic source.