Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of systolic blood pressure on the safety and tolerability of initiating and up‐titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study

The TITRATION trial investigated two strategies to initiate and up‐titrate sacubitril/valsartan (LCZ696) to the same target dose, over a condensed (3‐week) or conservative (6‐week) period, in patients with heart failure with reduced ejection fraction (HFrEF) and systolic blood pressure (SBP) of ≥100 mmHg. This post hoc analysis examined the relationship between baseline SBP at screening and achievement of the target dose of sacubitril/valsartan of 97 mg/103 mg (also termed ‘LCZ696 200 mg’) twice per day during the study.
The adoption of care robots in home care—A survey on the attitudes of Finnish home care personnel

AIMS AND OBJECTIVES This article examines the attitudes of Finnish home care registered nurses, licensed vocational nurses and other health and social care personnel towards the introduction and use of care robots in home care. BACKGROUND The significance of care robotics has been highlighted in recent years. However, personnel-related social psychological barriers to the introduction of care robots have been given very little study. DESIGN Cross-sectional study conducted by questionnaire. The theoretical framework of the study is based on Ajzen's theory of planned behaviour and the research discussion about attitudes towards robots. METHODS The research data were collected in five municipalities in different parts of Finland in 2016, and the questionnaire was answered by a total of 200 home care workers. The research data were analysed using exploratory factor analysis, Pearson product-moment correlation, one-way analysis of variance and linear regression analysis. RESULTS The results are consistent with Ajzen's theory and previous studies on the acceptance of information systems in health care. Personnel behavioural intentions related to the introduction of robot applications in home care are influenced by their personal appreciation of the usefulness of robots, the expectations of their colleagues and supervisors, as well as by their own perceptions of their capacity to learn to use care robots. In particular, personnel emphasised the value of care robots in providing reminders and guidance, as well as promoting the safety of the older people. CONCLUSIONS The study shows that an intimate human-robot relationship can pose a challenge from the perspective of the acceptance of care robots. RELEVANCE TO CLINICAL PRACTICE From the perspective of the introduction of care robots in home care, personnel training and the construction of a positive working atmosphere play a key role. In addition, the introduction of robots requires further consideration of a number of ethical issues.
Conflict Structures in Family Networks of Older Adults and Their Relationship With Health-Related Quality of Life

This study explores the interrelationships between health-related quality of life and conflict structures in family networks of older adults. Data were derived from a sample of 2,858 elders (aged 65 years and older) from the Vivre/Leben/Vivere study, a large survey addressing family life and health conditions of older people in Switzerland. Conflict density in family networks and the betweenness centrality of respondents in family conflict are significantly associated with health-related quality of life measures. Furthermore, the results demonstrate that conflict–health associations are mediated by the level of perceived individual stress where psychological health is concerned. Family conflict structures depend to a large extent on family composition and age. This study stresses the importance of older adults actively shaping the composition of their family contexts in ways that promote both conflict and stress avoidance.
Small separators, upper bounds for $l^\infty$-widths, and systolic geometry

We investigate the dependence on the dimension in the inequalities that relate the volume of a closed submanifold $M^n\subset \mathbb{R}^N$ with its $l^\infty$-width $W^{l^\infty}_{n-1}(M^n)$ defined as the infimum over all continuous maps $\phi:M^n\longrightarrow K^{n-1}\subset\mathbb{R}^N$ of $sup_{x\in M^n}\Vert \phi(x)-x\Vert_{l^\infty}$. We prove that $W^{l^\infty}_{n-1}(M^n)\leq const\ \sqrt{n}\ vol(M^n)^{\frac{1}{n}}$, and if the codimension $N-n$ is equal to $1$, then $W^{l^\infty}_{n-1}(M^n)\leq 3\ vol(M^n)^{\frac{1}{n}}$. As a corollary, we prove that if $M^n\subset \mathbb{R}^N$ is essential, then there exists a non-contractible closed curve on $M^n$ contained in a cube in $\mathbb{R}^N$ with side length $const\ \sqrt{n}\ vol^{\frac{1}{n}}(M^n)$ with sides parallel to the coordinate axes. If the codimension is $1$, then the side length of the cube is $12\cdot vol^{\frac{1}{n}}(M^n)$.
Further analysis of barley MORC1 using a highly efficient RNA‐guided Cas9 gene‐editing system

Summary Microrchidia (MORC) proteins comprise a family of proteins that have been identified in prokaryotes and eukaryotes. They are defined by two hallmark domains: a GHKL‐type ATPase and an S5‐fold. In plants, MORC proteins were first discovered in a genetic screen for Arabidopsis thaliana mutants compromised for resistance to a viral pathogen. Subsequent studies expanded their role in plant immunity and revealed their involvement in gene silencing and genome stabilization. Little is known about the role of MORC proteins of cereals, especially because knockout (KO) mutants were not available and assessment of loss of function relied only on RNAi strategies, which were arguable, given that MORC proteins in itself are influencing gene silencing. Here, we used a Streptococcus pyogenes Cas9 (SpCas9)‐mediated KO strategy to functionally study HvMORC1, one of the current seven MORC members of barley. Using a novel barley RNA Pol III‐dependent U3 small nuclear RNA (snRNA) promoter to drive expression of the synthetic single guide RNA (sgRNA), we achieved a very high mutation frequency in HvMORC1. High frequencies of mutations were detectable by target sequencing in the callus, the T0 generation (77%) and T1 generation (70%–100%), which constitutes an important improvement of the gene‐editing technology in cereals. Corroborating and extending earlier findings, SpCas9‐edited hvmorc1‐ KO barley, in clear contrast to Arabidopsis atmorc1 mutants, had a distinct phenotype of increased disease resistance to fungal pathogens, while morc1 mutants of either plant showed de‐repressed expression of transposable elements (TEs), substantiating that plant MORC proteins contribute to genome stabilization in monocotyledonous and dicotyledonous plants.
Motion video-based quantitative analysis of the ‘lifting-thrusting’ method: a comparison between teachers and students of acupuncture

Objective To compare objective measures of needle manipulation between students and teachers of acupuncture using motion video analysis technology, to help support instructional acupuncture education. Methods A total of 30 teachers and 60 students participated in this study. Acupuncture needles were inserted at LI11 and motion videos were recorded for three subtypes of ‘lifting-thrusting’ manipulation: (1) ‘mild reinforcing-attenuating’; (2) ‘reinforcing’; and (3) ‘attenuating’. The videos were analysed using Simi Motion 3D software to acquire the movement parameters of four trace marks: ‘thumb tip’; ‘forefinger tip’; ‘forefinger middle joint’; and ‘forefinger base joint’. Differences between the two groups were compared using t-tests, X2 tests and/or rank-sum tests. Results Changes in the near-end interphalangeal joint were positively associated with a range of movement along the X axis. Motion parameters for the thumb tip, the proximal interphalangeal (PIP) joint of the forefinger and the X axis shaft swing near the end of the forefinger in the teacher group were higher than those in the student group. The teacher group featured smaller trough dispersion and smaller crest dispersion during ‘reinforcing’ and ‘attenuating’ manipulations, respectively. Conclusions The ‘lifting-thrusting’ manipulation could be simplified as a fixed-axis rotation using metacarpophalangeal joints in the thumb and forefinger as the shaft centre. Teachers opened at a larger angular variation for the PIP during the lifting and thrusting processes with better spatial control. Temporal control was similar between groups and therefore appears easier to grasp. Repetitive training might be helpful for improving athletic and spatial stability during needle manipulation.
Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure

Significance Recoding viral genomes by numerous synonymous substitutions provided live attenuated vaccine candidates predicted to have a low risk of reversion. However, their stability under selective pressure was largely unknown. We evaluated the phenotypic reversion of representative genome-scale deoptimized human respiratory syncytial virus (RSV) vaccine candidates in the context of strong selective pressure. We found that a virus bearing a deoptimized L-polymerase ORF evolved to escape temperature sensitivity restriction by mutations in L and multiple other proteins. Additional analysis revealed that single mutations in the M2-1 ORF were able to substantially escape the restriction imposed by the deoptimized polymerase. Based on this information, we generated a stable deoptimized RSV vaccine candidate with improved attenuation and immunogenicity suitable for additional development. Recoding viral genomes by numerous synonymous but suboptimal substitutions provides live attenuated vaccine candidates. These vaccine candidates should have a low risk of deattenuation because of the many changes involved. However, their genetic stability under selective pressure is largely unknown. We evaluated phenotypic reversion of deoptimized human respiratory syncytial virus (RSV) vaccine candidates in the context of strong selective pressure. Codon pair deoptimized (CPD) versions of RSV were attenuated and temperature-sensitive. During serial passage at progressively increasing temperature, a CPD RSV containing 2,692 synonymous mutations in 9 of 11 ORFs did not lose temperature sensitivity, remained genetically stable, and was restricted at temperatures of 34 °C/35 °C and above. However, a CPD RSV containing 1,378 synonymous mutations solely in the polymerase L ORF quickly lost substantial attenuation. Comprehensive sequence analysis of virus populations identified many different potentially deattenuating mutations in the L ORF as well as, surprisingly, many appearing in other ORFs. Phenotypic analysis revealed that either of two competing mutations in the virus transcription antitermination factor M2-1, outside of the CPD area, substantially reversed defective transcription of the CPD L gene and substantially restored virus fitness in vitro and in case of one of these two mutations, also in vivo. Paradoxically, the introduction into Min L of one mutation each in the M2-1, N, P, and L proteins resulted in a virus with increased attenuation in vivo but increased immunogenicity. Thus, in addition to providing insights on the adaptability of genome-scale deoptimized RNA viruses, stability studies can yield improved synthetic RNA virus vaccine candidates.
Gene expression differs in codominant prairie grasses under drought

Grasslands of the central United States are expected to experience severe droughts and other climate extremes in the future, yet we know little about how these grasses will respond in terms of gene expression. We compared gene expression in Andropogon gerardii and Sorghastrum nutans, two closely related codominant C4 grasses responsible for the majority of ecosystem function, using RNA‐seq. We compared Trinity assemblies within each species to determine annotated functions of transcripts responding to drought. Subsequently, we compared homologous annotated gene‐groups across the two species using cross‐species meta‐level analysis and functional clustering based on key terms. The majority of variation was found between species, as opposed to between drought and watered treatments. However, there is evidence for differential responses; Andropogon allocated gene expression differently compared to Sorghastrum, suggesting Andropogon focuses on stress alleviation (such as oxygen radical scavenging) rather than prevention. In contrast, Sorghastrum may employ a drought avoidance strategy by modulating osmotic response, especially with hormonal regulation. We found Sorghastrum tended to be more sensitive within 10 key gene‐groups related to stress, abscisic acid and trichomes, suggesting gene expression may mechanistically parallel sensitivity at the physiological level. Our findings corroborate phenotypic and physiological differences in the field and may help explain the phenotypic mechanisms of these two species in the tallgrass prairie community under future drought scenarios.
Prepositional Phrase Attachment in Shallow Parsing

In this paper we extend a shallow parser [6] with prepositional phrase attachment. Although the PP attachment task is a well-studied task in a discriminative learning context, it is mostly addressed in the context of artificial situations like the quadruple classification task [18] in which only two possible attachment sites, each time a noun or a verb, are possible. In this paper we provide a method to evaluate the task in a more natural situation, making it possible to compare the approach to full statistical parsing approaches. First, we show how to extract anchor-pp pairs from parse trees in the GENIA and WSJ treebanks. Next, we discuss the extension of the shallow parser with a PP-attacher. We compare the PP attachment module with a statistical full parsing approach [4] and analyze the results. More specifically, we investigate the domain adaptation properties of both approaches (in this case domain shifts between journalistic and medical language).
Bioelectric impact of pathological angiogenesis on vascular function

Significance Angiogenesis is essential for the health of all vertebrates, but the outgrowth of new blood vessels also plays a role in disease by facilitating tumorigenesis, boosting inflammation, and causing blindness. Despite intensive investigation, pathological angiogenesis remains a formidable clinical challenge. Here we adopted an experimental strategy focusing on the bioelectric impact of neovascularization. Surprisingly, although the transmembrane voltage of vascular cells is known to regulate blood flow, no previous electrophysiological analysis of pathological angiogenesis has been reported. Using animal models and human specimens of retinal neovascularization, we discovered that neovascular complexes generate an extremely high voltage, whose transmission into the retinovascular network exerts a function-altering impact. Uncovering bioelectric mechanisms in the pathogenesis of neovascularization is likely to reveal new therapeutic targets. Pathological angiogenesis, as seen in many inflammatory, immune, malignant, and ischemic disorders, remains an immense health burden despite new molecular therapies. It is likely that further therapeutic progress requires a better understanding of neovascular pathophysiology. Surprisingly, even though transmembrane voltage is well known to regulate vascular function, no previous bioelectric analysis of pathological angiogenesis has been reported. Using the perforated-patch technique to measure vascular voltages in human retinal neovascular specimens and rodent models of retinal neovascularization, we discovered that pathological neovessels generate extraordinarily high voltage. Electrophysiological experiments demonstrated that voltage from aberrantly located preretinal neovascular complexes is transmitted into the intraretinal vascular network. With extensive neovascularization, this voltage input is substantial and boosts the membrane potential of intraretinal blood vessels to a suprahyperpolarized level. Coincident with this suprahyperpolarization, the vasomotor response to hypoxia is fundamentally altered. Instead of the compensatory dilation observed in the normal retina, arterioles constrict in response to an oxygen deficiency. This anomalous vasoconstriction, which would potentiate hypoxia, raises the possibility that the bioelectric impact of neovascularization on vascular function is a previously unappreciated pathophysiological mechanism to sustain hypoxia-driven angiogenesis.
Agent-based Abstractions for Verifying Alternating-time Temporal Logic with Imperfect Information

We introduce a 3-valued abstraction technique for alternating-time temporal logic (ATL) in contexts of imperfect information. We introduce under- and over-approximations of an agent's strategic abilities in terms of must- and may-strategies and provide a 3-valued semantics for ATL based on agents in interpreted systems (IS). We define a relation of simulation between the agents and prove that it preserves defined truth values of ATL formulas. Finally, we introduce a notion of abstraction on IS and show that it simulates the concrete interpreted system. Under this setting we present a procedure that enables the direct construction of a finite abstraction from an infinite-state system.
Quality of both parents’ cognitive guidance and quantity of early childhood education: Influences on pre‐mathematical development

BACKGROUND Only a handful of longitudinal studies have explored the effects of both parents in early parenthood on children's cognitive development, and no study has controlled for simultaneous early childhood education and care (ECEC) experiences. AIMS To examine the similarity of each parent's cognitive guidance and contribution to children's pre-mathematical outcomes across parent gender while controlling for amount of ECEC. SAMPLE A longitudinal study on 66 Finnish two-parent families and their children. METHODS Both parents' autonomy support and scaffolding behaviour were observed during play interactions with the child at 2;0. Children's numerical and spatial skills were tested at 3;0 and 4;0. Parental reports on amount of ECEC in months were collected at 2;0, 3;0, and 4;0. RESULTS The two parenting constructs were conceptually similar across parent gender as demonstrated by fairly strong measurement equivalence. While mothers on average showed more scaffolding and equal amounts of autonomy support compared to fathers during play interaction, they displayed less variability in the former and more variability in the latter behaviour. The contribution of mothers' and fathers' cognitive guidance was more similar for children's numerical than spatial development. Both parents' education positively predicted autonomy support but not amount of ECEC exposure, which was positively related to numerical development. As expected, parents' education did not predict ECEC exposure, and child gender was not related to child outcomes. CONCLUSIONS The findings are discussed in relation to measurement invariance and gender-neutral parenting in the context of early childhood.
Exel's crossed product and relative Cuntz–Pimsner algebras

We consider Exel's new construction of a crossed product of a $C^*$-algebra $A$ by an endomorphism $\alpha$. We prove that this crossed product is universal for an appropriate family of covariant representations, and we show that it can be realised as a relative Cuntz–Pimsner algbera. We describe a necessary and sufficient condition for the canonical map from $A$ into the crossed product to be injective, and present several examples to demonstrate the scope of this result. We also prove a gauge-invariant uniqueness theorem for the crossed product.
Rat small intestinal morphology and tissue regulatory peptides: effects of high dietary fat

Sprague–Dawley rats (3 weeks old) were fed on isoenergetic diets in which 40 % of the total energy was provided as fat either in the form of butter (high saturated fat), olive oil (high monounsaturated fat) or maize oil (high polyunsaturated fat), with one group on low-fat (10% of total energy) standard diet as a control. Animals were killed after 8.4 (se 0.8) weeks by cardiac puncture. Similar pieces of jejunum and ileum were prepared for morphometric studies. Extracts of tissue from the proximal and distal segments of the whole small intestine from four animals per group were assayed using established techniques for enteroglucagon, motilin, neurotensin, somatostatin, substance P and vasoactive intestinal peptide (VIP). We found that maize oil and olive oil increased villus height: crypt depth ratio in both jejunum and ileum. Maize oil increased tissue concentrations of somatostatin (P < 0.05) and substance P (P < 0.005) in the proximal segment. Both maize oil and olive oil increased tissue concentrations of neurotensin and substance P (P < 0.005) in the distal segments. These observations may explain the improvement of intestinal absorption of fluid following supplementation with polyunsaturated fat
ATG5 Promotes Death Signaling in Response to the Cyclic Depsipeptides Coibamide A and Apratoxin A

Our understanding of autophagy and lysosomal function has been greatly enhanced by the discovery of natural product structures that can serve as chemical probes to reveal new patterns of signal transduction in cells. Coibamide A is a cytotoxic marine natural product that induces mTOR-independent autophagy as an adaptive stress response that precedes cell death. Autophagy-related (ATG) protein 5 (ATG5) is required for coibamide-induced autophagy but not required for coibamide-induced apoptosis. Using wild-type and autophagy-deficient mouse embryonic fibroblasts (MEFs) we demonstrate that coibamide-induced toxicity is delayed in ATG5−/− cells relative to ATG5+/+ cells. Time-dependent changes in annexin V staining, membrane integrity, metabolic capacity and caspase activation indicated that MEFs with a functional autophagy pathway are more sensitive to coibamide A. This pattern could be distinguished from autophagy modulators that induce acute ER stress (thapsigargin, tunicamycin), ATP depletion (oligomycin A) or mTORC1 inhibition (rapamycin), but was shared with the Sec61 inhibitor apratoxin A. Coibamide- or apratoxin-induced cell stress was further distinguished from the action of thapsigargin by a pattern of early LC3-II accumulation in the absence of CHOP or BiP expression. Time-dependent changes in ATG5-ATG12, PARP1 and caspase-3 expression patterns were consistent with the conversion of ATG5 to a pro-death signal in response to both compounds.
The Timed 180° Turn Test for Assessing People with Hemiplegia from Chronic Stroke

Background Turning is ubiquitous in activities of daily living. For people with hemiplegia, persistent impairments in strength, balance, and coordination will affect their ability to turn safely. Consequently, turning retraining should be addressed in rehabilitation programs. To measure turning for these individuals, a reliable clinical tool is required. Objective To investigate (i) the intrarater, interrater, and test-retest reliability of the timed 180° turn test; (ii) the correlation of the timed 180° turn test with other measures of stroke-specific impairments; and (iii) the cut-off time that best discriminates individuals with hemiplegia from chronic stroke and healthy older adults. Methods 33 individuals with hemiplegia due to chronic stroke and 32 healthy elderly individuals participated in this cross-sectional study. The timed 180° turn test was administered along with other measures of stroke-specific impairment. Results The timed 180° turn test demonstrated excellent intrarater, interrater, and test-retest reliability in individuals with hemiplegia from chronic stroke. The timed 180° turn test (times) significantly correlated with the Fugl-Meyer Assessment of the Lower Extremities (FMA-LE), affected ankle plantar flexion strength, the 5-Times-Sit-To-Stand test, the Berg Balance Scale (BBS), and the Timed Up and Go (TUG) test. Conclusion The timed 180° turn test is a reliable clinical tool to assess the turning ability of subjects with hemiplegia from chronic stroke.