Miracle-dz/UniFAR-FTUs huggingface dataset:
Ixazomib for the treatment of multiple myeloma

ABSTRACT Introduction: Proteasome inhibitors (PIs) are among the backbones of multiple myeloma (MM) treatment; however, their long-term use can be limited by parenteral administration and treatment-related toxicities. Ixazomib, the first oral PI to enter the clinic, is approved around the world, in combination with lenalidomide and dexamethasone, for the treatment of patients with MM who have received at least one prior therapy. Areas covered: This review summarizes the clinical data leading to approval of ixazomib; its pharmacology, efficacy, and safety. Building on the data in relapsed/refractory MM (RRMM), it also reviews the available clinical trial data for ixazomib across the MM treatment algorithm in newly diagnosed MM, RRMM, and as maintenance therapy, and looks ahead to ongoing clinical trials and the expanding role of ixazomib in these indications. Expert opinion: Ixazomib is an efficacious and well-tolerated addition to the treatment armamentarium for RRMM, with benefit as a long-term, continuous therapy for all patients, including ‘poor prognosis’ patients, such as those with advanced stage disease, high-risk cytogenetic abnormalities, and elderly and frail patients. Data from ongoing clinical studies are expected to expand the role of ixazomib across the MM treatment algorithm and in a broader range of combination regimens.
Not all forms of dietary phosphorus are equal: an evaluation of postprandial phosphorus concentrations in the plasma of the cat

Abstract Phosphorus is present in diets as naturally occurring P from raw materials or added as an inorganic salt. However, little is known about postprandial kinetics of P absorption in cats. Here, we describe several studies quantifying postprandial kinetics following the ingestion of diets of varying composition. Briefly, cats were fed a meal consisting of 50 % of their metabolic energy requirement in a randomised crossover design. A pre-meal baseline blood sample was taken via cephalic catheter and repeated measurements taken regularly up to 6 h post-meal to assess the whole blood ionised Ca, plasma P and parathyroid hormone concentrations. A diet containing 4·8 g total P/4184 kJ (1000 kcal), 3·5 g P from sodium dihydrogen phosphate (NaH2PO4)/4184 kJ (1000 kcal) and Ca:P 0·6 caused a marked increase in plasma P from baseline to a peak of 1·976 (95% CI 1·724, 2·266) mmol/l (P <0·001), whereas a diet containing 3·38 g total P/4184 kJ (1000 kcal), no added inorganic P and Ca:P 1·55 resulted in a postprandial decrease in plasma P (P = 0·008). Subsequent data indicate that added inorganic P salts in the diet above 0·5 g P/4184 kJ (1000 kcal) cause an increase in plasma P in cats, while diets below this do not. The data presented here demonstrate that sources of added inorganic P salts cause a temporary postprandial increase in plasma P in a dose-dependent manner, prolonged in diets with Ca:P <1·0. Dietary P derived from natural food ingredients (e.g. meat or vegetable matter) does not appear to have any effect on postprandial plasma P.
Comparison of Vector Space Representations of Documents for the Task of Matching Contents of Educational Course Programmes

This article presents the study of the topical problem of semantic analysis and comparison of educational courses. This is required in order to update educational programmes in the reality of continuous growth of the amount of available educational content on the Internet, recurring changes in the requirements of standards and the labor market demands. At the moment there are no effective tools for intellectual analysis and processing of educational content. We review various approaches to the semantic analysis of the educational courses programmes via their vector representations. We present the first to our knowledge experimental quality evaluation of vector space models for text representations of educational course programme documents. More specifically we compare the quality of various popular algorithms: TF-IDF, LSA, LDA, averaged word2vec, paragraph2vec. The evaluation is carried out using various algorithms of clustering and classification on our experimental corpus of educational course programme, used by Russian universities.
Concentration of the Frobenius Norm of Generalized Matrix Inverses

In many applications it is useful to replace the Moore-Penrose pseudoinverse (MPP) by a different generalized inverse with more favorable properties. We may want, for example, to have many zero entries, but without giving up too much of the stability of the MPP. One way to quantify stability is by how much the Frobenius norm of a generalized inverse exceeds that of the MPP. In this paper we derive finite-size concentration bounds for the Frobenius norm of $\ell^p$-minimal general inverses of iid Gaussian matrices, with $1 \leq p \leq 2$. For $p = 1$ we prove exponential concentration of the Frobenius norm of the sparse pseudoinverse; for $p = 2$, we get a similar concentration bound for the MPP. Our proof is based on the convex Gaussian min-max theorem, but unlike previous applications which give asymptotic results, we derive finite-size bounds.
The inferior occipital gyrus is a major cortical source of the face‐evoked N170: Evidence from simultaneous scalp and intracerebral human recordings

The sudden onset of a face image leads to a prominent face‐selective response in human scalp electroencephalographic (EEG) recordings, peaking 170 ms after stimulus onset at occipito–temporal (OT) scalp sites: the N170 (or M170 in magnetoencephalography). According to a widely held view, the main cortical source of the N170 lies in the fusiform gyrus (FG), whereas the posteriorly located inferior occipital gyrus (IOG) would rather generate earlier face‐selective responses. Here, we report neural responses to upright and inverted faces recorded in a unique patient using multicontact intracerebral electrodes implanted in the right IOG and in the OT sulcus above the right lateral FG (LFG). Simultaneous EEG recordings on the scalp identified the N170 over the right OT scalp region. The latency and amplitude of this scalp N170 were correlated at the single‐trial level with the N170 recorded in the lateral IOG, close to the scalp lateral occipital surface. In addition, a positive component maximal around the latency of the N170 (a P170) was prominent above the internal LFG, whereas this region typically generates an N170 (or “N200”) over its external/ventral surface. This suggests that electrophysiological responses in the LFG manifest as an equivalent dipole oriented mostly along the vertical axis with likely minimal projection to the lateral OT scalp region. Altogether, these observations provide evidence that the IOG is a major cortical generator of the face‐selective scalp N170, qualifying the potential contribution of the FG and questioning a strict serial spatiotemporal organization of the human cortical face network.
Modality Attention for End-to-end Audio-visual Speech Recognition

Audio-visual speech recognition (AVSR) system is thought to be one of the most promising solutions for robust speech recognition, especially in noisy environment. In this paper, we propose a novel multimodal attention based method for audio-visual speech recognition which could automatically learn the fused representation from both modalities based on their importance. Our method is realized using state-of-the-art sequence-to-sequence (Seq2seq) architectures. Experimental results show that relative improvements from 2% up to 36% over the auditory modality alone are obtained depending on the different signal-to-noise-ratio (SNR). Compared to the traditional feature concatenation methods, our proposed approach can achieve better recognition performance under both clean and noisy conditions. We believe modality attention based end-to-end method can be easily generalized to other multimodal tasks with correlated information.
Association of Opioid Prescribing With Opioid Consumption After Surgery in Michigan

Importance There is growing evidence that opioids are overprescribed following surgery. Improving prescribing requires understanding factors associated with opioid consumption. Objective To describe opioid prescribing and consumption for a variety of surgical procedures and determine factors associated with opioid consumption after surgery. Design, Setting, and Participants A retrospective, population-based analysis of the quantity of opioids prescribed and patient-reported opioid consumption across 33 health systems in Michigan, using a sample of adults 18 years and older undergoing surgery. Patients were included if they were prescribed an opioid after surgery. Surgical procedures took place between January 1, 2017, and September 30, 2017, and were included if they were performed in at least 25 patients. Exposures Opioid prescription size in the initial postoperative prescription. Main Outcomes and Measures Patient-reported opioid consumption in oral morphine equivalents. Linear regression analysis was used to calculate risk-adjusted opioid consumption with robust standard errors. Results In this study, 2392 patients (mean age, 55 years; 1353 women [57%]) underwent 1 of 12 surgical procedures. Overall, the quantity of opioid prescribed was significantly higher than patient-reported opioid consumption (median, 30 pills; IQR, 27-45 pills of hydrocodone/acetaminophen, 5/325 mg, vs 9 pills; IQR, 1-25 pills; P < .001). The quantity of opioid prescribed had the strongest association with patient-reported opioid consumption, with patients using 0.53 more pills (95% CI, 0.40-0.65; P < .001) for every additional pill prescribed. Patient-reported pain in the week after surgery was also significantly associated with consumption but not as strongly as prescription size. Compared with patients reporting no pain, patients used a mean (SD) 9 (1) more pills if they reported moderate pain and 16 (2) more pills if they reported severe pain (P < .001). Other significant risk factors included history of tobacco use, American Society of Anesthesiologists class, age, procedure type, and inpatient surgery status. After adjusting for these risk factors, patients in the lowest quintile of opioid prescribing had significantly lower mean (SD) opioid consumption compared with those in the highest quintile (5 [2] pills vs 37 [3] pills; P < .001). Conclusions and Relevance The quantity of opioid prescribed is associated with higher patient-reported opioid consumption. Using patient-reported opioid consumption to develop better prescribing practices is an important step in combating the opioid epidemic.
The Guatemalan Construction Industry: Approach of Knowledge Regarding Work Risks Prevention

In the present work, the results are presented for the characterization of work risk prevention in the Guatemalan construction industry. This characterization has been carried out using a simple random sampling technique, employing a questionnaire that was structured into 3 groups of variables: 1. General company data; 2. Prevention and management activities regarding health and safety in the company and on the worksite; and 3. Health and safety in the contractor companies. Following the sampling phase, the data were introduced in a database format, and a preliminary analysis was performed on the studied variables, followed by a descriptive analysis and a multiple correspondence analysis. The main findings of the study emphasize that companies in the Guatemalan construction sector are characterized as dedicating most of their activity (52.0%) indistinctly between civil engineering work, building construction and other specialized construction, mainly working as contractors (47.5%). These are “medium-sized” companies, employing an average of 81.1 on-site workers, having an average of 6.8 on-site work crews, and grossing an average turnover of 1.29 million euros annually. Likewise, it found that the larger construction companies adopt better prevention and management measures for worksite health and safety the larger companies are correlated with a high awareness of experiencing worksite accidents, while medium-sized companies have medium-level awareness. Companies with fewer workers manage workplace risk prevention worse, with low accident risk awareness. This correlation between these indicative variables of company size and workplace risk management and prevention is clearly reflected in the four company “clusters” that have been identified as having homogenous characteristics using the multiple correspondence analysis technique. Companies in the Guatemalan construction sector should make a greater effort to improve manager and worker training regarding workplace risk prevention to increase the effectiveness of company prevention management.
TRPV4 Inhibition Improved Myelination and Reduced Glia Reactivity and Inflammation in a Cuprizone-Induced Mouse Model of Demyelination

The inhibition of demyelination and the promotion of remyelination are both considerable challenges in the therapeutic process for many central nervous system (CNS) diseases. Increasing evidence has demonstrated that neuroglial activation and neuroinflammation are responsible for myelin sheath damage during demyelinating disorders. It has been revealed that the nonselective cation channel transient receptor potential vanilloid 4 (TRPV4) profoundly affects a variety of physiological processes, including inflammation. However, its roles and mechanisms in demyelination have remained unclear. Here, for the first time, we found that there was a significant increase in TRPV4 in the corpus callosum in a demyelinated mouse model induced by cuprizone (CPZ). RN-1734, a TRPV4-antagonist, clearly alleviated demyelination and inhibited glial activation and the production of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) without altering the number of olig2-positive cells. In vitro, RN-1734 treatment clearly inhibited the influx of calcium and decreased the levels of IL-1β and TNF-α in lipopolysaccharide (LPS)-activated microglial cells by suppressing NF-κB P65 phosphorylation. Apoptosis of oligodendrocyte induced by LPS-activated microglia was also alleviated by RN-1734. The results suggest that activation of TRPV4 in microglia is involved in oligodendrocyte apoptosis through the activation of the NF-κB signaling pathway, thus revealing a new mechanism of CNS demyelination.
The Effect of Different Habitat Types and Ontogenetic Stages on the Diet Shift of a Critically Endangered Fish Species, Coreius guichenoti (Sauvage and Dabry de Thiersant, 1874)

This study examined the effect of habitat types and ontogenetic stages on the diet shift of Coreius guichenoti (Sauvage and Dabry de Thiersant, 1874), a critically endangered fish species. Based on the stable isotope analysis method, the following was explored: the variations in δ13C and δ15N values, isotopic niche width and four basal food sources (Mollusks, Macrocrustaceans, Aquatic insect larvae and particulate organic matters (POMs)) among three essential habitat types (the spawning ground, natural riverine feeding and nursery area, and Three Gorges Reservoir area) and between two ontogenetic stages (immature and fully mature stages). A diet shift associated with habitat type changes was observed, but there were no obvious differences in diet composition between the two ontogenetic stages. Dietary plasticity and a preference for specific foods were the important determinants of feeding behavior through the life history of this species. POM was important for the survival of this species in the resource-limited spawning ground, but this species fed more heavily on higher-order consumers in resource-abundant areas. This study highlights the importance of maintaining free connectivity among different habitats (particularly spawning grounds) to ensure the long-term sustainability of potamodromous fish species as well as the full investigation of all types of critical habitats for understanding the trophic ecology of a single fish species.
The Interplay Between Immune Response and Bacterial Infection in COPD: Focus Upon Non-typeable Haemophilus influenzae

Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease and one of the leading causes of morbidity and mortality worldwide. It is characterized by persistent respiratory symptoms and airflow limitation due to abnormalities in the lower airway following consistent exposure to noxious particles or gases. Acute exacerbations of COPD (AECOPD) are characterized by increased cough, purulent sputum production, and dyspnea. The AECOPD is mostly associated with infection caused by common cold viruses or bacteria, or co-infections. Chronic and persistent infection by non-typeable Haemophilus influenzae (NTHi), a Gram-negative coccobacillus, contributes to almost half of the infective exacerbations caused by bacteria. This is supported by reports that NTHi is commonly isolated in the sputum from COPD patients during exacerbations. Persistent colonization of NTHi in the lower airway requires a plethora of phenotypic adaptation and virulent mechanisms that are developed over time to cope with changing environmental pressures in the airway such as host immuno-inflammatory response. Chronic inhalation of noxious irritants in COPD causes a changed balance in the lung microbiome, abnormal inflammatory response, and an impaired airway immune system. These conditions significantly provide an opportunistic platform for NTHi colonization and infection resulting in a “vicious circle. ” Episodes of large inflammation as the consequences of multiple interactions between airway immune cells and NTHi, accumulatively contribute to COPD exacerbations and may result in worsening of the clinical status. In this review, we discuss in detail the interplay and crosstalk between airway immune residents and NTHi, and their effect in AECOPD for better understanding of NTHi pathogenesis in COPD patients.
Probabilistic programming with densities in SlicStan: efficient, flexible, and deterministic

Stan is a probabilistic programming language that has been increasingly used for real-world scalable projects. However, to make practical inference possible, the language sacrifices some of its usability by adopting a block syntax, which lacks compositionality and flexible user-defined functions. Moreover, the semantics of the language has been mainly given in terms of intuition about implementation, and has not been formalised. This paper provides a formal treatment of the Stan language, and introduces the probabilistic programming language SlicStan --- a compositional, self-optimising version of Stan. Our main contributions are (1) the formalisation of a core subset of Stan through an operational density-based semantics; (2) the design and semantics of the Stan-like language SlicStan, which facilities better code reuse and abstraction through its compositional syntax, more flexible functions, and information-flow type system; and (3) a formal, semantic-preserving procedure for translating SlicStan to Stan.
The Necessity of Ambiguity in Self–Other Processing: A Psychosocial Perspective With Implications for Mental Health

While distinguishing between the actions and physical boundaries of self and other (non-self) is usually straightforward there are contexts in which such differentiation is challenging. For example, self–other ambiguity may occur when actions of others are similar or complementary to those of the self. Even in the absence of such situational challenges, individuals experiencing hallucinations have difficulties with this distinction, often experiencing thoughts or actions of self as belonging to other agents. This paper explores the role of ambiguity in self–other differentiation, drawing from developmental, psychodynamic, and neurocognitive perspectives. A key proposal is that engagement in contexts that make distinctions between self and other challenging yet necessary allow reality-testing skills related to agency to develop. Attunement in typical caregiver–infant interactions is framed as a safe but inherently ambiguous environment that provides optimal condition for the infant to develop a coherent self–other sense. Vulnerability to psychosis may be related to limited access to such an environment in early development. However, the perceptual, cognitive, and social skills that contribution to attribution are likely to be malleable following infancy and improve though opportunities for boundary play in similarly ambiguous settings. Using music-making to illustrate, we postulate that engagement in intricate joint-actions that blurs agentic boundaries can contribute to the continued development of an adaptive sense of self and other essential to healthy social functioning. Increased insight into the self–other ambiguity may enhance our understanding of mechanisms underlying “self-disorders” such as schizophrenia and eventually extend the range of social and arts-based therapeutic possibilities.
Haplotype Loci Under Selection in Canadian Durum Wheat Germplasm Over 60 Years of Breeding: Association With Grain Yield, Quality Traits, Protein Loss, and Plant Height

Durum wheat was introduced in the southern prairies of western Canada in the late nineteenth century. Breeding efforts have mainly focused on improving quality traits to meet the pasta industry demands. For this study, 192 durum wheat lines were genotyped using the Illumina 90K Infinium iSelect assay, and resulted in a total of 14,324 polymorphic SNPs. Genetic diversity changed over time, declining during the first 20 years of breeding in Canada, then increased in the late 1980s and early 1990s. We scanned the genome for signatures of selection, using the total variance Fst-based outlier detection method (Lositan), the hierarchical island model (Arlequin) and the Bayesian genome scan method (BayeScan). A total of 407 outliers were identified and clustered into 84 LD-based haplotype loci, spanning all 14 chromosomes of the durum wheat genome. The association analysis detected 54 haplotype loci, of which 39% contained markers with a complete reversal of allelic state. This tendency to fixation of favorable alleles corroborates the success of the Canadian durum wheat breeding programs over time. Twenty-one haplotype loci were associated with multiple traits. In particular, hap_4B_1 explained 20.6, 17.9 and 16.6% of the phenotypic variance of pigment loss, pasta b∗ and dough extensibility, respectively. The locus hap_2B_9 explained 15.9 and 17.8% of the variation of protein content and protein loss, respectively. All these pleiotropic haplotype loci offer breeders the unique opportunity for further improving multiple traits, facilitating marker-assisted selection in durum wheat, and could help in identifying genes as functional annotations of the wheat genome become available.