Miracle-dz/UniFAR-FTUs huggingface dataset:
Progression of cardiac disease in patients with lamin A/C mutations

Abstract Aims We aimed to study the progression of cardiac dysfunction in patients with lamin A/C mutations and explore markers of adverse cardiac outcome. Methods and results We followed consecutive lamin A/C genotype-positive patients divided into tertiles according to age. Patients underwent repeated clinical examinations, electrocardiograms (ECGs), and echocardiograms. We followed left ventricular (LV) and right ventricular (RV) size and function, and the severity atrioventricular-valve regurgitations. Outcome was death, LVAD implant, or cardiac transplantation. We included 101 patients [age 44 (29–54) years, 39% probands, 50% female]. We analysed 576 echocardiograms and 258 ECGs during a follow-up of 4.9 (interquartile range 2.5–8.2) years. The PR-interval increased at young age from 204 ± 73 to 212 ± 69 ms (P < 0.001), LV ejection fraction (LVEF) declined from middle age from 50 ± 12% to 47 ± 13% (P < 0.001), while LV volumes remained unchanged. RV function and tricuspid regurgitation worsened from middle age with accelerating rates. Progression of RV dysfunction [odds ratio (OR) 1.3, 95% confidence interval (CI) (1.03–1.65), P = 0.03] and tricuspid regurgitation [OR 4.9, 95% CI (1.64–14.9), P = 0.004] were associated with outcome when adjusted for age, sex, comorbidities, LVEF, and New York Heart Association functional class. Conclusion In patients with lamin A/C genotype, electrical disease started at young age. From middle age, LV function deteriorated progressively, while LV size remained unchanged. Worsening of RV function and tricuspid regurgitation accelerated in older age and were associated with outcome. Our systematic map on cardiac deterioration may help optimal monitoring and prognostication in lamin A/C disease.
Randomized Trial Testing an Online Responsible Vendor Training in Recreational Marijuana Stores in the United States.

OBJECTIVE An online training in responsible marijuana vendor (RMV) practices was evaluated for effects on compliance with ID checking regulations. METHOD A random sample of state-licensed recreational marijuana stores (n = 175) in Colorado and Washington State was selected in 2016-2017 and was enrolled in a randomized pretest-posttest controlled design. After baseline assessment, 75 stores were randomly assigned to a usual and customary training control group, stratified by state and region. The remaining stores (n = 100) were invited to use the RMV training. Stores were posttested at 3 and 9 months postrandomization. The primary outcome was refusal of sale measured with pseudo-underage patrons who attempted to enter stores and purchase cannabis without a state-approved ID. RESULTS There was no difference by treatment group in refusal of pseudo-underage patron buyers (baseline: 92.5% intervention vs. 94.7% control; 3-month posttest 94.8% vs. 97.5%; 9-month posttest 97.5% vs. 97.1%, p = .286 [one tailed, adjusted for covariates]). The use of training increased refusals at store entry (trained: 65.9% baseline 82.5%, 3 months 79.9%, 9 months; not trained: 82.6%, 83.1%, 84.5%, p = .020 [two tailed, adjusted for covariates]). This difference was especially evident in Washington State (trained: 40.3%, 65.1%, 60.4%; not trained: 57.9%, 68.5%, 72.3%) but not in Colorado (trained: 95.2%, 101.0%, 101.4; not trained: 95.7%, 98.6%, 99.2%, p = .033 [two tailed, adjusted for covariates]). CONCLUSIONS When used by store personnel, online RMV training increased refusal of buyers who appeared young and did not provide a state-approved ID. However, it did not improve refusal rates overall. Stores that had lower refusals at baseline and used the training may have benefited from it.
Can I Commercialise? Norms Regulating Commercialisation Behaviours in Open Source Hardware Communities

“[. ] the unwritten rules of Open Hardware and rule #1 is you don’t copy, you innovate. [. ] One thing I’ve learned about the OSHW1 community, after years of following it with intense interest: the unwritten rules can sink an OSHW business! ” Quotes like these have aroused our interest in the way open source communities, where household innovators share their innovations freely, regulate the behaviours of those, both from within and from outside the community, who exploit the entrepreneurial opportunities created by free access to these innovations. What these quotes suggest is that commercialisation behaviours are regulated by unwritten rules.This is striking because open source communities have licences that spell out explicit rules for how these innovations and inputs can be used. The motivation of this paper is thus to study whether open source communities have norms for regulating commercialisation behaviours and if they do what these norms are. To explore these questions, we decided to investigate a particular Open Source Hardware (OSH) community—the RepRap community. Created in 2005, following the launch of an OSH project aiming to democratise 3D printing technology by enabling the production of cheap and easy to build 3D printers,2 this community has existed long enough to enable norms to emerge, evolve and operate. It is also a community of a significantly large size, and a ‘successful’ one, since it has led to the development of several major players in the 3D printing market, as has been an inspiration to virtually all desktop 3D printers. A further interest in the choice of an Open Source Hardware community as opposed to an Open Source Software one, is – beside the fact that the former still stands rather understudied in the literature in comparison to the latter – that unlike Open Source Software, for which commercialisation is purely optional because of the low/negligible diffusion
Emergence of a Salmonella enterica serovar Typhimurium ST34 isolate, CFSA629, carrying a novel mcr-1.19 variant cultured from egg in China.

OBJECTIVES This study aimed to characterize the genomic features of a Salmonella enterica serovar Typhimurium ST34 isolate, CFSA629, which carried a novel mcr-1 variant, designated as mcr-1.19, mapped to an ESBL-encoding IncHI2 plasmid. METHODS Antimicrobial susceptibility assays as well as WGS were carried out on isolate CFSA629. The complete closed genome was obtained and then explored to obtain genomic features. Plasmid sequence comparison was performed for pCFSA629 with similar plasmids and the mcr-1 genetic environment was analysed. RESULTS S. Typhimurium ST34 CFSA629 expressed an MDR phenotype to six classes of compound and consisted of a single circular chromosome and one plasmid. It possessed 11 resistance genes including 2 ESBL genes that mapped to the chromosome and the plasmid; an IS26-flanked composite-like transposon was identified. A novel mcr-1 variant (mcr-1.19) was identified, which had a unique SNP (G1534A) that gave rise to a novel MCR-1 protein containing a Val512Ile amino acid substitution. Plasmid pCFSA629 possessed a conjugative plasmid transfer gene cluster as well as an antimicrobial resistance-encoding gene cluster-containing region that contained two IS26 composite-like transposonal modules, but was devoid of any plasmid-mediated quinolone resistance genes. The background of mcr-1.19 consisted of an ISApl1-mcr-1-PAP2-ter module. CONCLUSIONS We report on an MDR S. Typhimurium ST34 CFSA629 isolate cultured from egg in China, harbouring an mcr-1.19 variant mapped to an IncHI2 plasmid. This highlights the importance of surveillance to mitigate dissemination of mcr-encoding genes among foodborne Salmonella. Improved surveillance is important for tackling the dissemination of mcr genes among foodborne Salmonella around the world.
Affect-Based Problem Drinking Risk: The Reciprocal Relationship between Affective Lability and Problem Drinking.

AIMS Negative affect has been implicated in risk for the development of problematic drinking behavior. Furthermore, there is evidence for reciprocal relationships between negative affect and problem drinking, such that engagement in problem drinking also predicts increases in negative affect. However, affective models of risk often fail to consider affective lability-the experience of rapidly changing mood. Although affective lability appears to increase risk for problem drinking, it is unknown if this relationship persists above and beyond other affect-related constructs (e.g. depression, anxiety) and if it is reciprocal in nature. Accordingly, we used a longitudinal survey design to examine (a) if affective lability predicts problem drinking above and beyond depression and anxiety and (b) if affective lability and problem drinking demonstrate a reciprocal relationship. METHODS First-year college students (n = 358) participated in a three wave longitudinal study. We constructed a structural equation model (SEM) of a random intercept cross-lagged panel model to test our hypotheses. RESULTS Consistent with our hypotheses, affective lability predicted increases in problem drinking while anxiety and depression did not. Problem drinking and affective lability demonstrated a reciprocal relationship in which increases in one predicted increases in the other at subsequent time points. This relationship was present beyond the predictive effects of anxiety or depression. CONCLUSIONS Affective lability appears to be an important affect-based predictor of problem drinking, and there may be a reciprocal, risk-enhancing relationship between affective lability and problem drinking.Components of negative affect, such as depression or anxiety, have been shown to predict risk for problem drinking, and vice versa. A less considered construct, affective lability, predicted problem drinking while anxiety and depression did not add any predictive power. Problem drinking and affective lability also appeared to demonstrate a reciprocal relationship.
Presence of Native and Non-native Ants Linked to Lower Emergence Success of Loggerhead Sea Turtle Nests: Implications for Management

Abstract Ants have been suggested as one of many population pressures sea turtles face potentially affecting nesting-beach survival of eggs and hatchlings. However, little is known about the extent to which ants act as incidental or primary mortality factors. Most research has focused on New World fire ants (genus Solenopsis), with confirmed records of other ant species interactions with sea turtle nests in situ being rare. Our study documented the ant species associated with loggerhead sea turtle Caretta caretta (Linnaeus) (Testudines: Cheloniidae) nests in Georgia and determined if ant presence was linked to lower hatching or emergence success. Samples (n = 116) collected from sea turtle nests on eight islands contained 14 ant species including Solenopsis invicta Buren (Hymenoptera: Formicidae), the red imported fire ant, which was the most common ant species encountered. Ant presence was not correlated with lower hatching success, but when other known disturbances were removed, correlated with significantly lower nest emergence success (P < 0.0001). Logistic modeling suggests that proximity of sea turtle nests to the primary dune significantly increases risk of ant predation on hatchling sea turtles. Population managers can reduce this risk by maintaining a 1-m buffer shoreward between dune vegetation and relocated sea turtle nests. Our results suggest that ants may exert a density-dependent pressure on nesting sea turtle populations and call for additional investigations to determine if managing native and invasive ants augments other efforts to improve hatchling survival.
Indel mutations of sheep PLAG1 gene and their associations with growth traits

Abstract Pleiomorphic adenoma gene 1 (PLAG1) is mainly expressed in embryonic development, and it is reported to take an effect on the growth performance of mice, cattle, pigs, and sheep. To explore how conservative the PLAG1 is in different sheep breeds, the effects of the two indel variants on the growth traits of the Chinese Luxi blackhead (LXBH) sheep were firstly detected. The P2-del 30 bp and P4-del 45 bp indel loci of the sheep PLAG1 gene were significantly related to 15 growth traits (P < 0.05). Genotype ID and genotype II were dominant for the P2-del 30 bp and P4-del 45 bp loci, respectively. The above findings indicated that the two indel mutations in the ovine PLAG1 gene were suggested to become the molecular markers for the selection of economic traits in sheep.
In Vivo–to–In Vitro Extrapolation of Transporter-Mediated Renal Clearance: Relative Expression Factor Versus Relative Activity Factor Approach

About 30% of approved drugs are cleared predominantly by renal clearance (CLr). Of these, many are secreted by transporters. For these drugs, in vitro–to–in vivo extrapolation of transporter-mediated renal secretory clearance (CLsec,plasma) is important to prospectively predict their renal clearance and to assess the impact of drug-drug interactions and pharmacogenetics on their pharmacokinetics. Here we compared the ability of the relative expression factor (REF) and the relative activity factor (RAF) approaches to quantitatively predict the in vivo CLsec,plasma of 26 organic anion transporter (OAT) substrates assuming that OAT-mediated uptake is the rate-determining step in the CLsec,plasma of the drugs. The REF approach requires protein quantification of each transporter in the tissue (e.g., kidney) and transporter-expressing cells, whereas the RAF approach requires the use of a transporter-selective probe substrate (both in vitro and in vivo) for each transporter of interest. For the REF approach, 50% and 69% of the CLsec,plasma predictions were within 2- and 3-fold of the observed values, respectively; the corresponding values for the RAF approach were 65% and 81%. We found no significant difference between the two approaches in their predictive capability (as measured by accuracy and bias) of the CLsec,plasma or CLr of OAT drugs. We recommend that the REF and RAF approaches can be used interchangeably to predict OAT-mediated CLsec,plasma. Further research is warranted to evaluate the ability of the REF or RAF approach to predict CLsec,plasma of drugs when uptake is not the rate-determining step. Significance Statement This is the first direct comparison of the relative expression factor (REF) and relative activity factor (RAF) approaches to predict transporter-mediated renal clearance (CLr). The RAF, but not REF, approach requires transporter-selective probes and that the basolateral uptake is the rate-determining step in the CLr of drugs. Given that there is no difference in predictive capability of the REF and RAF approach for organic anion transporter–mediated CLr, the REF approach should be explored further to assess its ability to predict CLr when basolateral uptake is not the sole rate-determining step.
Modulating the Molecular Geometry and Solution Self-Assembly of Amphiphilic Polypeptoid Block Copolymers by Side Chain Branching Pattern

Solution self-assembly of coil-crystalline diblock copolypeptoids has attracted increasing attention due to its capability to form hierarchical nanostructures with tailorable morphologies and functionalities. While the N-substituent (or side chain) structures are known to affect the crystallization of polypeptoids, their roles in dictating the hierarchical solution self-assembly of diblock copolypeptoids are not fully understood. Herein, we designed and synthesized two types of diblock copolypeptoids, i.e., poly(N-methylglycine)-b-poly(N-octylglycine) (PNMG-b-PNOG) and poly(N-methylglycine)-b-poly(N-2-ethyl-1-hexylglycine) (PNMG-b-PNEHG), to investigate the influence of N-substituent structure on the crystalline packing and hierarchical self-assembly of diblock copolypeptoids in methanol. With a linear aliphatic N-substituent, the PNOG blocks pack into a highly ordered crystalline structure with a board-like molecular geometry, resulting in the self-assembly of PNMG-b-PNOG molecules into a hierarchical microflower morphology composed of radially arranged nanoribbon subunits. By contrast, the PNEHG blocks bearing bulky branched aliphatic N-substituents are rod-like and prefer to stack into a columnar hexagonal liquid crystalline mesophase, which drives PNMG-b-PNEHG molecules to self-assemble into symmetrical hexagonal nanosheets in solution. A combination of time-dependent small/wide-angle X-ray scattering and microscopic imaging analysis further revealed the self-assembly mechanisms for the formation of these microflowers and hexagonal nanosheets. These results highlight the significant impact of the N-substituent architecture (i.e., linear versus branched) on the supramolecular self-assembly of diblock copolypeptoids in solution, which can serve as an effective strategy to tune the geometry and hierarchical structure of polypeptoid-based nanomaterials.
Nutrition education on obesity and diabetes to medical students.

It is important for medical students to understand the relationship between nutrition, obesity, and diabetes to educate their patients in the future. However, medical training does not always include nutritional education. An experiential learning project was incorporated into the medical school curriculum as an effort to implement nutrition in the physiology course. First-year medical students (n = 140) received lectures on the regulation of blood glucose levels and their relationship to carbohydrates with different glycemic indexes (GI), obesity, and diabetes. Lectures were followed by a laboratory exercise where students calculated their body mass index (BMI), percentage body fat, and percentage muscle using a Bioelectrical Impedance Commercial Scale. While 63% of students had normal BMI, 31% were overweight or obese and 5% were underweight. A subgroup of 54 students tested different types of breakfasts with varying GI and provided blood samples at 0, 30, 60, 90, and 120 min. Their glucose responses were plotted based on the breakfast GI. Pre- and posttests were conducted to assess the teaching intervention where the Wilcoxon signed ranks test indicated that posttest ranks were significantly higher than pretest ranks (Z = -6.6, P < 0.001), suggesting the intervention was beneficial to students.
Effects of vaccination against brucellosis and clostridia on the intake, performance, feeding behavior, blood parameters, and immune responses of dairy heifers calves.

The aim of this study was to identify possible effects of different vaccination strategies (concomitantly or not) against brucellosis and clostridia on intake, performance, feeding behavior, blood parameters, and immune responses of dairy heifers calves. Fifty heifers calves were enrolled [38 Gyr (Zebu, Bos taurus indicus) and 12 5/8 Holstein x Gyr]. At 120 days of age, animals were randomly distributed among three groups: B (n = 18), vaccinated against brucellosis; C (n = 14), vaccinated against clostridia and CB (n = 18), vaccinated concomitantly for both. Rectal (RT) and thermographic temperatures were evaluated on days -1, 0, 1, 2, 3, 5, 7,10, 14, and 28 relatives to the vaccination day. Feed and water intake, body weight (BW) and feeding behavior were monitored daily by an electronic feeding system. Blood was sampled on days 0, 3, 7, 14, and 28, relative to the vaccination day for determination of glucose (GLC) and beta-hydroxybutyrate (BHBA) concentrations. Blood sampled on day 0 (pre-vaccination) and on day 28 and 42 were used to evaluate the immune response against Brucella abortus and clostridia. There was an increase in rectal temperature between the first and the third day post-vaccination in the three groups. The thermography revealed an increase of local temperature for seven days on groups B and CB. Group C had increased local temperature for a longer period, lasting for up to 14 d. Dry mater intake was reduced for groups B and CB, but no alteration was observed for group C. No alterations regarding initial BW, final BW, average daily weight gain (ADG) and feed efficiency were observed. No differences were observed for the three vaccination groups for blood parameters throughout the evaluation period. The concomitant vaccination against brucellosis and clostridia led to lower neutralizing antibody titers against epsilon toxin of C. perfringens and botulinum toxin type C of C. botulinum (C > CB > B). When cellular proliferation assay and serological tests to B. abortus were evaluated, no differences were observed between groups B and CB. The present results indicate that the concomitant vaccination against brucellosis and clostridia has no relevant impact on the intake, performance, and feeding behavior of dairy calves. However, the concomitant vaccination of vaccines against these two pathogens impacts animal immunity against clostridial infections.
Pharmacological activation of SERCA ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice

Abstract Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscular weakness because of the loss of dystrophin. Extracellular Ca2+ flows into the cytoplasm through membrane tears in dystrophin-deficient myofibers, which leads to muscle contracture and necrosis. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) takes up cytosolic Ca2+ into the sarcoplasmic reticulum, but its activity is decreased in dystrophic muscle. Here, we show that an allosteric SERCA activator, CDN1163, ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice. The administration of CDN1163 prevented exercise-induced muscular damage and restored mitochondrial function. In addition, treatment with CDN1163 for 7 weeks enhanced muscular strength and reduced muscular degeneration and fibrosis in mdx mice. Our findings provide preclinical proof-of-concept evidence that pharmacological activation of SERCA could be a promising therapeutic strategy for DMD. Moreover, CDN1163 improved muscular strength surprisingly in wild-type mice, which may pave the new way for the treatment of muscular dysfunction.
Heterometallic Clusters with Multiple Rare Earth Metal-Transition Metal Bonding.

Although a series of complexes with rare earth (RE) metal-metal bonds have been reported, complexes which have multiple RE-Rh bonds are unknown. Here we present the identification of the first example of a molecule containing multiple RE-Rh bonds. The complex with multiple Ce-Rh bonds was synthesized by the reduction of a d-f heterometallic molecular cluster Ce{N[(CH2CH2NPiPr2)RhCl(COD)]3} with excess potassium-graphite. The oxidation state of Ce in 3a appears to be a mixture of Ce(III) and Ce(IV), which was confirmed by X-ray photoelectron spectroscopy, magnetism, and theoretical investigations (DFT and CASSCF). For comparison, the analogous species with multiple La(III)-Rh and Nd(III)-Rh bonds were also constructed. This study provides a possible route for the construction of complexes with multiple RE metal-metal bonds and an investigation of their potential properties and applications.