Miracle-dz/UniFAR-FTUs huggingface dataset:
The Dative Dispositional Construction in Russian

The article sheds new light on the so-called dative dispositional construction in Russian. We revise the characterization of the classes of verbs able to feed the construction, showing that its input is best defined in terms of the Theta System (Reinhart’s (2002, 2016) approach to thematic relations). To resolve controversies in the literature regarding the licensing conditions of the construction and its possible interpretations, we ran two surveys whose design and findings we report. We then discuss the properties of the construction comparatively, define the operation deriving it, and provide evidence that the operation is lexical. This has consequences regarding the nature of the lexical component.
Smartphone-Based Device for Non-Invasive Heart-Rate Measurement of Chicken Embryos

Heart rate (HR) is an important parameter in the study of the developmental physiology of chicken embryos and a crucial indicator of dead or live embryo grading in artificial incubation processes. A non-invasive HR measurement technique is required for long-term and routine HR assessment with minimal influence on embryo development. Accordingly, in this study, a non-invasive HR measurement technique of chicken embryos using a smartphone is demonstrated. The detection method of the proposed device is based on the photoplethysmography principle in which a smartphone camera is used for video recording, and the chicken embryonic HR is obtained from the recorded video images using a custom Android application. We used a smartphone to measure the embryonic HR of 60 native chicken eggs and found that it can measure the chicken embryonic HR from day 4 to day 20. The proposed smartphone HR device will be beneficial for scientific research and industrial applications. With internet connectivity, users can utilize their smartphone to measure the HR, display, share, and store the results.
Long-term effects of low-dose 17β-estradiol plus dydrogesterone on 24-h ambulatory blood pressure in healthy postmenopausal women: A 1-year, randomized, prospective study

The aim of the present 12-month, randomized, prospective controlled study was to investigate the long-term effects of low-dose oral hormone replacement therapy (HRT) on 24-h blood pressure in healthy, normotensive postmenopausal women. A total of 80 postmenopausal women received either 1 mg micronized 17β-estradiol daily, sequentially combined with 10 mg dydrogesterone for 14 days of each 28-day cycle (n = 44), or no treatment (n = 36). Ambulatory blood pressure was recorded for a 24-h period at baseline and after 12 months. After 12 months, mean 24-h systolic ambulatory blood pressure fell significantly in the HRT group (−5.4 mmHg; p < 0.01). The difference between the values in the HRT and control groups after 12 months was significant (p < 0.01). Mean 24-h heart rate also fell significantly with HRT (−4.9 beats/min; p < 0.05), and the value was significantly lower than in the control group (p < 0.05). Mean daytime systolic blood pressure fell significantly in the HRT group (−6.6 mmHg; p < 0.001), and the value was significantly lower than in the control group (p < 0.05). There were no significant changes in blood pressure in the control group. In conclusion, sequential low-dose oral HRT with 17β-estradiol/dydrogesterone caused a significant decrease in 24-h and daytime systolic ambulatory blood pressure in normotensive postmenopausal women.
MYC gene associated polymorphisms and Wilms tumor risk in Chinese children: a four-center case-control study.

Background Wilms tumor (WT) is a common embryonal malignancy in the kidney, ranking fourth in childhood cancer worldwide. MYC, a critical proto-oncogene, plays an important role in tumorigenesis. Single nucleotide polymorphisms in the MYC gene may lead to the deregulation of MYC proto-oncogene protein and thereby promote the initiation and development of tumors. Methods Here, we assessed the association between MYC gene associated polymorphisms and WT susceptibility by performing a case-control study with 355 cases and 1070 controls. Two MYC gene associated polymorphisms (rs4645943 C > T, rs2070583 A > G) were genotyped by TaqMan technique. Odds ratios (ORs) and 95% confidence intervals (CIs) were used for evaluating the association between these two polymorphisms and WT susceptibility. Results No significant association was detected between the selected polymorphisms and WT risk in the overall analysis as well as stratification analysis. Conclusions These results indicate that neither of two selected MYC gene associated polymorphisms might affect WT susceptibility in the Chinese population. Large well-designed studies with diverse ethnicities are warranted to verify these results.
QUALITY MANAGEMENT IN HOSPITALS: ANALYSIS OF THE PRESCRIBING PRACTICE OF CARDIOVASCULAR MEDICINES

The goal of this study is to analyse the prescribing practice and risk of drug related errors in a Cardiology clinic of University Hospital. Semistructured open-ended interview aiming to reveal the risk of potential errors was performed with physicians, nurses, pharmacists, and hospital managers. Observational analysis of 915 prescriptions, prescribed by the physicians in two cardiology departments was conducted. Prescribing practice was evaluated by the means of its complexity, frequency of prescribing of particular pharmacology groups, and the related costs. Most often gaps detected in prescribing and dispensing of medicinal products were associated with missing or incorrect dosages, and unspecified quantity. Our analysis showed preference to combination therapies. Monotherapy was given only in 24.82% of the acute cases treated and in 24% of the cases treated in the internal ward. Two medicinal products were identified in 24.48% of the prescriptions (intensive care unit) and in 19.24% of the prescriptions from the internal ward. The most prescribed medicinal products were bisoprolol and glyceryl trinitrate in a combination. Approximately 45% of the patients were prescribed up to 3 medicinal products.The increase of therapy complexity leads to increase of probability for drug-drug interactions and nearly 30% of prescriptions were evaluated as potentially risky for interactions. The relative shares of potentially risky combinations vary from 4% to 32% out of all prescriptions reviewed. The likelihood of drug-related problems in WO
The different faces of the macrophage in asthma

Purpose of review Asthma is a chronic inflammatory disease in which changes in macrophage polarization have been shown to contribute to the pathogenesis. The present review discusses the contribution of changes in macrophage function to asthma related to polarization changes and elaborates on possible therapeutic strategies targeting macrophage function and polarization. Recent findings Macrophage function alterations were shown to contribute to asthma pathology in several ways. One is by impaired phagocytosis and efferocytosis. Another is by changing inflammation, by altered (anti)inflammatory cytokine production and induction of the inflammasome. Finally, macrophages can contribute to remodeling in asthma, although little evidence is present in humans yet. Novel therapeutic strategies targeting macrophages include dampening inflammation by changing polarization or by inhibiting the NLRP3 inflammasome, and by targeting efferocytosis. However, many of these studies were performed in animal models leaving their translation to the clinic for future research. Summary The present review emphasizes the contribution of altered macrophage function to asthma, gives insight in possible new therapeutic strategies targeting macrophages, and indicates which knowledge gaps remain open.
Assessment of the Corticospinal Tract Profile in Pure Lower Motor Neuron Disease: A Diffusion Tensor Imaging Study

Aim: The aim of this study was to evaluate the corticospinal tract (CST) diffusion profile in pure lower motor neuron disease (pLMND) patients who at baseline did not show any clinical or electrophysiological involvement of upper motor neurons (UMN), and in amyotrophic lateral sclerosis (ALS) patients. Materials and Methods: Fifteen ALS patients with delayed central motor conduction time (CMCT) and 14 pLMND patients with normal CMCT were enrolled together with 15 healthy controls. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) maps were obtained. The tract profile of CST was reconstructed with the automated fiber quantification tool and its diffusion properties were quantified voxel-by-voxel and then compared pairwise between groups. Moreover, a random forest (RF) classifier was trained to evaluate the ability of CST diffusion metrics in distinguishing pairwise the groups from the controls. Results: ALS patients presented wide microstructural abnormalities in the entire CST as assessed by FA decrease and RD increase while pLMND patients showed focal FA decrease and a larger AD increase in the cerebral peduncle and posterior limb of the internal capsule in comparison with controls. RF revealed that diffusion tensor imaging (DTI) metrics accurately distinguished ALS patients and pLMND patients from controls (96.67 and 95.71% accuracy, respectively). Conclusions: Our study demonstrates that the CST was impaired in both ALS and pLMND patients, thus suggesting that DTI metrics are a reliable tool in detecting subtle changes of UMN in pLMND patients, also in the absence of clinical and CMCT abnormalities.
Selection of reference genes for normalization of cranberry (Vaccinium macrocarpon Ait.) gene expression under different experimental conditions

Real-time fluorescent quantitative PCR (qRT-PCR) is often chosen as an effective experimental method for analyzing gene expression. However, an appropriate reference gene as a standard is needed to obtain accurate gene expression data. To date, no internal reference genes have been reported for research on cranberries. Expanding the selection of internal reference genes for cranberry will enable reliable gene expression analysis, and, at the same time, can also lay a solid foundation for revealing the biological characteristics of cranberry. Here, we selected ten candidate reference gene families and used three statistical software tools—geNorm, NormFinder and BestKeeper—to evaluate their expression stability under the influence of different experimental factors. The results showed that protein phosphatase 2A regulatory subunit (PP2A) or RNA helicase-like 8 (RH 8) was the best choice for an internal reference gene when analyzing different cranberry cultivars. In two sample sets comprising different cranberry organs and three abiotic stress treatments, sand family protein (SAND) was the best choice as a reference gene. In this study, we screened genes that are stably expressed under the influence of various experimental factors by qRT-PCR. Our results will guide future studies involving gene expression analysis of cranberry.
In vitro prebiotic potential of agricultural by-products on intestinal fermentation, gut barrier and inflammatory status of piglets

Abstract The inclusion of fibre-rich ingredients in diets is one possible strategy to enhance intestinal fermentation and positively impact gut ecology, barrier and immunity. Nowadays, inulin-type fructans are used as prebiotics in the feed of piglets to manipulate gut ecology for health purposes. Likewise, some by-products could be considered as sustainable and inexpensive ingredients to reduce gut disorders at weaning. In the present study, chicory root and pulp, citrus pulp, rye bran and soya hulls were tested in a three-step in vitro model of the piglet’s gastro-intestinal tract combining a pepsin-pancreatin hydrolysis (digestion), a dialysis step using cellulose membranes (absorption) and a colonic batch fermentation (fermentation). The fermentation kinetics, SCFA and microbiota profiles in the fermentation broth were assessed as indicators of prebiotic activity and compared with the ones of inulin. The immunomodulatory effects of fermentation supernatant (FS) were investigated in cultured intestinal porcine epithelial cells (IPEC-J2) by high-throughput quantitative PCR. Chicory root displayed a rapid and extensive fermentation and induced the second highest butyrate ratio after inulin. Citrus pulp demonstrated high acetate ratios and induced elevated Clostridium clusters IV and XIVa levels. Chicory root and pulp FS promoted the intestinal barrier integrity with up-regulated tight and adherens junction gene expressions in comparison with inulin FS. Chicory pulp FS exerted anti-inflammatory effects in cultured IPEC-J2. The novel approach combining an in vitro fermentation model with IPEC-J2 cells highlighted that both chicory root and pulp appear to be promising ingredients and should be considered to promote intestinal health at weaning.
The Role of Inflammasome-Dependent and Inflammasome-Independent NLRP3 in the Kidney

Cytoplasmic nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) forms an inflammasome with apoptosis-associated speck-like protein containing a CARD (ASC) and pro-caspase-1, which is followed by the cleavage of pro-caspase-1 to active caspase-1 and ultimately the activation of IL-1β and IL-18 and induction of pyroptosis in immune cells. NLRP3 activation in kidney diseases aggravates inflammation and subsequent fibrosis, and this effect is abrogated by genetic or pharmacologic deletion of NLRP3. Inflammasome-dependent NLRP3 mediates the progression of kidney diseases by escalating the inflammatory response in immune cells and the cross-talk between immune cells and renal nonimmune cells. However, recent studies have suggested that NLRP3 has several inflammasome-independent functions in the kidney. Inflammasome-independent NLRP3 regulates apoptosis in tubular epithelial cells by interacting with mitochondria and mediating mitochondrial reactive oxygen species production and mitophagy. This review will summarize the mechanisms by which NLRP3 functions in the kidney in both inflammasome-dependent and inflammasome-independent ways and the role of NLRP3 and NLRP3 inhibitors in kidney diseases.
Genomic Analyses of PMBL Reveal New Drivers and Mechanisms of Sensitivity to PD-1 Blockade.

Primary mediastinal large B-cell lymphomas (PMBL) are aggressive tumors that typically present as large mediastinal masses in young women. PMBLs share clinical, transcriptional and molecular features with classical Hodgkin lymphoma (cHL), including constitutive activation of NF-kB, JAK/STAT signaling and PD-1-mediated immune evasion. The demonstrated efficacy of PD-1 blockade in relapsed/refractory PMBL led to recent approval by the US Food and Drug Administration (FDA) and underscored the importance of characterizing targetable genetic vulnerabilities in this disease. Here, we report a comprehensive analysis of recurrent genetic alterations - somatic mutations, somatic copy number alterations (SCNAs) and structural variants - in a cohort of 37 newly diagnosed PMBLs. We identified a median of 9 genetic drivers per PMBL, including known and newly identified components of the JAK/STAT and NF-kB signaling pathways and frequent B2M alterations that limit MHC class I expression, as in cHL. PMBL also exhibited frequent, newly identified driver mutations in ZNF217 and an additional epigenetic modifier, EZH2. The majority of these alterations were clonal supporting their role as early drivers. In PMBL, we identified several previously uncharacterized molecular features that may increase sensitivity to PD-1 blockade, including high tumor mutational burden, microsatellite instability (MSI) and APOBEC mutational signatures. The shared genetic features between PMBL and cHL provide a framework for analyzing the mechanism of action of PD-1 blockade in these related lymphoid malignancies.
The burden of pneumococcal disease in children—advances in the fight of this epidemic

Abstract Streptococcus pneumoniae, the most important cause of acute otitis media, pneumonia, septicaemia and meningitis worldwide, comes in 90 different serotypes. Only a few serotypes cause most of the serious disease. Different serotypes are distinguished by differences in the complex sugars that made up the bacteria's capsule that provide protection against the host's specific defenses. The burden of invasive pneumococcal disease in South Africa subjects is estimated to be 100–200 per 100 000. The conjugate pneumococcal vaccine has been shown to be effective in reducing invasive pneumococcal disease due to vaccine serotypes in all countries where it has been introduced. This benefit has extended to unvaccinated subjects. Reduction in penicillin resistant pneumococcus related to vaccine serotypes has been recorded. Replacement disease by non vaccine serotype has eroded the benefit of the vaccine. Industry, donors and governments need to interact to ensure accelerated implementation of this vaccine in developing countries.
Does microvascular invasion in Barcelona Clinic Liver Cancer stage A multinodular hepatocellular carcinoma indicate early-stage behavior?

Background To identify the impact of tumor number on Barcelona Clinic Liver Cancer (BCLC) early-stage hepatocellular carcinoma (HCC) and the impact of microvascular invasion (MVI) on multinodular HCC (MHCC). Methods We retrospectively analyzed 1,548 patients who had early-stage HCC [solitary HCC (SHCC, n=1,481) and MHCC (n=67)], according to the BCLC classification, after curative resection. Recurrence-free survival (RFS) and overall survival (OS) were compared. Propensity score matching (PSM) was used to balance potential confounding factors. Results Both before and after PSM, significant differences were noted between the MHCC group and the SHCC group in RFS but not in OS. For the PSM cohort, the 5-year RFS rates were 7.5% and 41.2% for the MVI-positive MHCC group and the SHCC group, respectively (P<0.001). The 5-year OS rates were 48.9% and 75.2% for the MVI-positive MHCC group and the SHCC group, respectively (P=0.017). The RFS and OS were not significantly different between the MVI-negative MHCC group and the SHCC group. MVI (P=0.029) and multiple nodules (P=0.029) were associated with early recurrence. Conclusions The presence of MVI in BCLC early-stage MHCC was highly suggestive of a poor prognosis and should not be classified as early-stage biological behavior.
Self-Perceived Preparedness of Undergraduate Dental Students In Dental Public Universities In Malaysia: A National Study.

AIMS To evaluate the self-perceived preparedness of final year dental undergraduate students in dental public universities in Malaysia. METHODS Final year dental undergraduate students from six dental public universities in Malaysia were invited to participate in an online study using a validated Dental Undergraduates Preparedness Assessment Scale DU-PAS. RESULTS In total about 245 students responded to the online questionnaire yielding a response rate of 83.05%. The age range of the respondents was 23 to 29 years with a mean age of 24.36 (SD 0.797). The total score obtained by the respondents were ranged from 48 to 100 with a mean score of 79.56 (SD 13.495). Weaknesses were reported in several clinical skills, cognitive and behavioural attributes. CONCLUSIONS The preparedness of undergraduate students at six dental institutions in Malaysia was comparable to students from developed countries. The dental undergraduate preparedness assessment scale is a useful tool and dental institutions may be used for self-assessment as well as to obtain feedback from the supervisors.
A multicenter, open-label, phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors.

Emicizumab, a bispecific humanized monoclonal antibody, bridges activated factor (F) IX and FX to restore the function of missing activated FVIII in hemophilia A. Emicizumab prophylaxis in children with hemophilia A and FVIII inhibitors was investigated in a phase 3 trial (HAVEN 2; NCT02795767). Participants, previously receiving episodic/prophylactic bypassing agents (BPAs), were treated with subcutaneous emicizumab: 1.5 mg/kg weekly (group A), 3 mg/kg every 2 weeks (group B), or 6 mg/kg every 4 weeks (group C). Pharmacokinetics, safety, and efficacy (including an intraindividual comparison of participants from a noninterventional study) were evaluated. Eighty-five participants aged <12 years were enrolled. In group A (n=65), the annualized rate of treated bleeding events (ABR) was 0.3 (95% CI, 0.17-0.50), and 77% had no treated bleeding events. Intraindividual comparison of 15 participants who previously took BPA prophylaxis showed that emicizumab prophylaxis reduced the ABR by 99% (95% CI, 97.4-99.4). In groups B (n=10) and C (n=10), ABRs were 0.2 (95% CI, 0.03-1.72) and 2.2 (95% CI, 0.69-6.81), respectively. The most frequent adverse events were nasopharyngitis and injection-site reactions; no thrombotic events occurred. Two of 88 participants developed antidrug antibodies (ADAs) with neutralizing potential, ie, associated with decreased emicizumab plasma concentrations; 1 experienced loss of efficacy; in the other, ADAs disappeared over time without intervention or breakthrough bleeding. All other participants achieved effective emicizumab plasma concentrations, regardless of the treatment regimen. Emicizumab prophylaxis has been shown to be a highly effective novel medication for children with hemophilia A and inhibitors.
Investigational drugs for the treatment of binge eating disorder (BED): an update

ABSTRACT Introduction: Binge eating disorder (BED) is the most common eating disorder and is frequently associated with psychiatric and medical comorbidities and functional impairment. Although psychological treatments have been the cornerstones of BED treatment, pharmacologic interventions also play an important part of the multimodal management of this condition. Areas covered: This review examines investigational, approved and other pharmacological agents for the treatment of BED. We searched PubMed and clinicaltrials.gov to identify pharmacological interventions for the management of this condition. Expert opinion: BED pharmacological studies have incorporated new drug targets based on our enhanced understanding of the pathophysiology of BED. Neurobiological dysregulation in the reward center and impulse control circuitry and related disturbances in dopamine neurotransmission are among the neurobiological explanations that have been suggested for BED. These mechanisms serve as a pharmacodynamic foundation for the development of new compounds such as lisdexamfetamine (LDX) and dasotraline. Despite these advances, pharmacological trials in BED have numerous challenges that must be overcome. For most compounds studied, larger and more definitive trials is a high priority.