Miracle-dz/UniFAR-FTUs huggingface dataset:
Design and development of a commercially potential in situ nanoemulgel for the treatment of postmenopausal osteoporosis.

Aim: To investigate the potential of a thermosensitive intranasal formulation of raloxifene hydrochloride (RH) for systemic delivery with the possibility of enhanced bioavailability and anti-osteoporotic efficacy. Methods: In this work, a commercially scalable nanoemulsion in thermosensitive gel aligned with better clinical acceptability has been developed and evaluated. Results: A significant 7.4-fold improvement in bioavailability of RH was recorded when compared with marketed tablets. Likewise, in vivo pharmacodynamics studies suggested 162% enhanced bone density and significantly improved biochemical markers compared with per-oral marketed tablet. Conclusion: The formulation, being safe and patient compliant, successfully tuned anti-osteoporotic effects with improved therapeutic performance. Further, the work provided an exceptional lead to carry out the study in clinical settings.
RESIDUES OF MANCOZEB, MANEB AND ETHYLENETHIOUREA IN FUNGICIDE-TREATED FIELD AND GREENHOUSE TOMATOES

Residues of the ethylenbisdithiocarbamate (EBDC) fungicides maneb and mancozeb on tomato fruits ranged between 0.03 and 0.80 ppm (mean 0.31 ppm) when field crops were sprayed five or eight times at intervals of 3–4 days. Ethylenethiourea (ETU) was detected only in one sample, at 0.03 ppm. In canned juice made from whole fruit, EBDC levels ranged from non-detectable to 0.62 ppm (mean 0.31 ppm) and ETU levels from non-detectable to 0.07 ppm (mean 0.02 ppm). These levels were generally higher than in canned peeled fruit where the range of EBDC was from non-detectable to 0.27 ppm (mean 0.09 ppm) and of ETU from non-detectable to 0.05 ppm (mean 0.01 ppm). On greenhouse tomatoes, two or four sprays with mancozeb resulted in residues of up to 2.81 ppm EBDC (mean 0.714 ppm) and 0.08 ppm ETU (mean 0.0097 ppm) on the fruit. All levels of EBDC were below the Canadian tolerance level of 4 ppm but ETU is unacceptable in food in Canada.
Effect of leaf herbivory by spider mite Tetranychus urticae on flower characteristics of different cucurbits

Cucumber, melon, watermelon, courgette, pumpkin and bitter gourd are some economically very important (cultivated) fruits that belong to the Cucurbitaceae family, which is troubled by the spider mite Tetranychus urticae. This herbivore causes chlorotic lesions in the leaves, which can have a tremendous effect on the plant’s performance, for example by changes in flower morphology and metabolism. Most cucurbits depend on pollination for fruit and seed production. In this study the variation among different cucurbit species with respect to flower characteristics that may be influenced by herbivory on leaves by spider mites is explored. With LC-MS and GC-MS the production of endogenous metabolites and volatiles are investigated, respectively. For the non-bitter cucumber and the bitter Chinese cucumber the RNA of flowers and leaves will be isolated to test which terpene synthase family (TPS) genes (TPS1, TPS9 and TPS19) are expressed in control and infested samples, and therefore may be responsible for the volatile emission identified with GC-MS. This study demonstrates a large range of qualitative and quantitative variation in volatile emission induced by leaf herbivory of spider mites (Tetranychus urticae) in leaves of different cucurbit. But there was no significant effect on flower volatile emission. The TPS genes investigated in this study were presumably not (always) the ones that were responsible for the emission of certain volatiles. Some flowers were most probably not able to produce plant-defence related volatiles, because of the tremendous drop in JA-Ile/JA ratio in flowers when plants were infested with spider mites.
Sex-specific cardiac remodeling in early and advanced stages of hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiac disease with a prevalence of 1:500 to 1:200. While most patients show obstructive HCM and a relatively stable clinical phenotype (stage II), a small group of patients progresses to end-stage HCM (stage IV) within a relatively brief period. Previous research has shown sex-differences in stage II HCM with more diastolic dysfunction in female than in male patients. Moreover, female patients more often show progression to heart failure. Here we investigated if differences in functional and structural properties of the heart may underlie sex-differences in disease progression from stage II to stage IV HCM. Cardiac tissue from stage II and IV patients was obtained during myectomy (n = 54) and heart transplantation (n = 10), respectively. Isometric force was measured in membrane-permeabilized cardiomyocytes to define active and passive myofilament force development. Titin isoform composition was assessed using gel electrophoresis, and the amount of fibrosis and capillary density were determined with histology. In accordance with disease stage-dependent adverse cardiac remodeling end-stage patients showed a thinner interventricular septal wall and larger left ventricular and atrial diameters compared to stage II patients. Cardiomyocyte contractile properties and fibrosis were comparable between stage II and IV, while capillary density was significantly lower in stage IV compared to stage II. Women showed more adverse cellular remodeling compared to men at stage II, evident from more compliant titin, more fibrosis and lower capillary density. However, the disease stage-dependent reduction in capillary density was largest in men. In conclusion, the more severe cellular remodeling in female compared to male stage II patients suggests a more advanced disease stage at the time of myectomy in women. Changes in cardiomyocyte contractile properties do not explain the progression of stage II to stage IV, while reduced capillary density may underlie disease progression to end-stage heart failure.
FGFR Inhibition Enhances Sensitivity to Radiation in Non–Small Cell Lung Cancer

FGFRs are commonly altered in non–small cell lung cancer (NSCLC). FGFRs activate multiple pathways including RAS/RAF/MAPK, PI3K/AKT, and STAT, which may play a role in the cellular response to radiation. We investigated the effects of combining the selective FGFR 1-3 tyrosine kinase inhibitor AZD4547 with radiation in cell line and xenograft models of NSCLC. NSCLC cell lines were assessed with proliferation, clonogenic survival, apoptosis, autophagy, cell cycle, and DNA damage signaling and repair assays. In vivo xenografts and IHC were used to confirm in vitro results. NSCLC cell lines demonstrated varying degrees of FGFR protein and mRNA expression. In vitro clonogenic survival assays showed radiosensitization with AZD4547 in two NSCLC cell lines. In these two cell lines, an increase in apoptosis and autophagy was observed with combined radiation and AZD4547. The addition of AZD4547 to radiation did not significantly affect γH2AX foci formation. Enhanced xenograft tumor growth delay was observed with the combination of radiation and AZD4547 compared with radiation or drug alone. IHC results revealed inhibition of pMAPK and pS6 and demonstrated an increase in apoptosis in the radiation plus AZD4547 group. This study demonstrates that FGFR inhibition by AZD4547 enhances the response of radiation in FGFR-expressing NSCLC in vitro and in vivo model systems. These results support further investigation of combining FGFR inhibition with radiation as a clinical therapeutic strategy.
Body Size in White Whales, Delphinapterus leucas

Measurements of length, girth, and weight show that male white whales grow larger than females. The smallest white whales come from western Hudson Bay, the White Sea, and Bristol Bay, Alaska. Animals of intermediate size inhabit all other arctic Canadian localities sampled and also the St. Lawrence River and the Kara and Barents seas. The largest white whales inhabit West Greenland waters, the Okhotsk Sea, and the coast of Sakhalin. Extreme differences in body weight of adult males are about threefold. Nonoverlapping differences in size indicate isolation of some adjacent populations of white whales; equal or overlapping sizes suggest, but cannot prove, mixing of other populations. Size can be positively correlated with marine productivity, being lowest in the arctic and in estuaries and highest in subarctic seas. Since white whales most often grow largest at the southern ends of their range, their restriction to the arctic is attributed either to competition with certain of the Delphinidae or to predatio.
Severe COVID‐19 infection and thrombotic microangiopathy: success does not come easily

Recent evidence suggests that signs and symptoms of severe COVID-19 infection resemble more the pathophysiology and phenotype of complement-mediated thrombotic micoangiopathies (TMA), rather than sepsis-induced coagulopathy or disseminated intravascular coagulation (DIC) (Campbell and Kahwash 2020, Zhang, et al 2020). Since effective treatment is available for complement-mediated TMA (Gavriilaki 2020), we aim to systematically describe relevant features (clinical phenotype, pathophysiology and management) in patients with severe COVID-19 infection.
The reliability and transparency bases of trust in human-swarm interaction: principles and implications

Abstract Automation reliability and transparency are key factors for trust calibration and as such can have distinct effects on human reliance behaviour and mission performance. One question that remains unexplored is: what are the implications of reliability and transparency on trust calibration for human-swarm interaction? We investigate this research question in the context of human-swarm interaction, as swarm systems are becoming more popular for their robustness and versatility. Thirty-two participants performed swarm-based tasks under different reliability and transparency conditions. The results indicate that trust, whether it is reliability- or transparency-based, indicates high reliance rates and shorter response times. Reliability-based trust is negatively correlated with correct rejection rates while transparency-based trust is positively correlated with these rates. We conclude that reliability and transparency have distinct effects on trust calibration. Practitioner Summary: Reliability and transparency have distinct effects on trust calibration. Findings from our human experiments suggest that transparency is a necessary design requirement if and when humans need to be involved in the decision-loop of human-swarm systems, especially when swarm reliability is high. Abbreviations: HRI: human-robot interaction; IOS: inter-organisational systems; LMM: liner mixed models; MANOVA: multivariate analysis of variance; UxV: heterogeneous unmanned vehicles; UAV: unmanned aerial vehicle
Treatment and re-treatment results of HCV patients in the DAA era

Background Re-treatment in patients with a chronic hepatitis C virus (HCV) infection and a previous failure to direct-acting antiviral (DAA) treatment remains a challenge. Therefore, we investigated the success rate of treatment and re-treatment regimens used at our center from October 2011 to March 2018. Methods A retrospective analysis of DAA-based HCV therapies of 1096 patients was conducted. Factors associated with a virological relapse were identified by univariable and multivariable logistic regression, treatment success of the re-treatment regimens was evaluated by an analysis of sustained virological response (SVR) rates in patients with a documented follow-up 12 weeks after the end of treatment. Results Of 1096 patients treated with DAA-based regimens, 91 patients (8%) were lost to follow-up, 892 of the remaining 1005 patients (89%) achieved an SVR12. Most patients (65/113, 58%) who experienced a virological relapse received an interferon-based DAA regimen. SVR rates were comparable in special cohorts like liver transplant recipients (53/61, 87%) and people with a human immunodeficiency virus (HIV) coinfection (41/45, 91%). On multivariable analysis, interferon-based DAA therapy was associated with treatment failure (odds ratio 0.111, 95%-confidence interval 0.054–0.218) among others. One hundred seventeen patients with multiple DAA treatment courses were identified, of which 97 patients (83%) experienced a single relapse, but further relapses after two (18/117, 15%) or even three (2/117, 2%) treatment courses were also observed. Eighty-two of 96 (85%) re-treatment attempts with all-oral DAA regimens were successful after an initial treatment failure. Conclusion Overall, DAA re-treatments were highly effective in this real-world cohort and only a minority of patients failed more than two treatment courses. Switching to–or addition of–a new drug class seem to be valid options for the re-treatment of patients especially after failure of an interferon-based regimen.
Change in Growth and Diet Quality Among Preschool Children in Tokyo, Japan

Dietary intake of adequate quality and quantity in early life is essential for healthy growth and development. This study aimed to examine the association between one-year change in growth and diet quality in preschool children in Adachi City, Tokyo, Japan. A total of 110 participants (49% boys, four to five years old at baseline) were included in this analysis. Body mass index for age z-score (BAZ) and height for age z-score (HAZ) were calculated in accordance with WHO reference. Dietary intakes were assessed using the brief-type self-administered diet history questionnaire for children (BDHQ3y), and daily quality score was calculated based on the Japanese Food Guide Spinning Top (JFGST score). Regression analyses found no significant association between one-year change in growth and diet quality (compared to a low JFGST score, BAZ: β = 0.16, 95% CI: −0.29 to 0.60 for a middle JFGST score, β = −0.14, 95% CI: −0.61 to 0.33 for a high JFGST score, HAZ: β = −0.15, 95% CI: −0.50 to 0.21 for a middle JFGST score, β = −0.06, 95% CI: −0.43 to 0.30 for a high JFGST score). Further studies are needed to develop an appropriate diet quality index for healthy growth in Japanese preschool children.
Activation of c-Jun by human cytomegalovirus UL42 through JNK activation

c-Jun is a major component of the AP-1 transactivator complex. In this report, we demonstrated that AP-1 was activated by the expression of UL42, a human cytomegalovirus-encoded membrane protein that has two PPXY (PY) motifs and a C-terminal transmembrane domain (TMD). Although UL42 interacts with Itch, an ubiquitin E3 ligase, through the PY motifs, UL42 phosphorylated c-Jun and c-Jun N-terminal kinase (JNK) in the absence of any interaction with Itch. Experiments using mutated versions of UL42 suggest the importance of the carboxyl half (a.a. 52–124) of UL42 for the activation of the JNK signaling, while C-terminal TMD alone is not sufficient. Thus, we hypothesize that UL42 plays a role in the activation of JNK signaling in HCMV-infected cells. (118 words).
Association Between Marital Status and Racial Disparities in Esophageal Cancer Care.

PURPOSE This study was designed to examine the impact of marital status on racial disparities in esophageal cancer care. PATIENTS AND METHODS We performed a secondary analysis of data collected from the state cancer registry maintained by the Michigan Department of Health and Human Services. We identified patients with an esophageal cancer diagnosis between January 1, 2000, and December 31, 2013. χ2 test and logistics regression were used to analyze 6,809 patients who met our eligibility criteria. Statistical significance was defined as P ≤ . 05. RESULTS Approximately 88.4% of our patients were White and 11.6% were Black. A significantly higher number of White patients were married when compared with Blacks (62.9% v 31.8%, respectively; P < .0001). There was no significant difference in cancer staging between the 2 groups (P = .0671). Married Blacks had similar rates of esophagectomy, chemotherapy, and radiation as married Whites. Both single groups had lower rates of esophagectomy and chemotherapy than married Whites, but single Blacks were the least likely to undergo esophagectomy. Single patients were more likely to refuse treatment. CONCLUSION Marital status differs significantly in Black and White patients with esophageal cancer and may help explain racial disparities in cancer care. Further research is needed to explore reasons for care underutilization in single patients and whether these differences translate into clinical outcomes.
Effects of Creating Two Forest Structures and Using Prescribed Fire on Coarse Woody Debris in Northeastern California, USA

Little is known about the dynamics of coarse woody debris (CWD) in forests that were originally characterized by frequent, low-moderate intensity fires. We investigated effects of prescribed burning at the Blacks Mountain Experimental Forest in northeastern California following creation of two stand structure conditions: 1) high structural diversity (HiD) that included retaining large, old-growth trees while thinning smaller trees in the understory through whole-tree harvesting, and 2) low structural diversity (LoD) simulating a more traditional approach that removed overstory trees by individual tree selection while thinning the vigorous younger trees and removing the suppressed understory by whole-tree harvesting. Each of the two structures was replicated six times in a randomized block design for a total of 12 approximately 100 ha factorial plots. Each factorial plot was split and prescribed fire applied to one half of each plot. We classified CWD as either: sound or decayed. Coarse woody debris was abundant on all plots regardless of stand structure. Statistically significant differences (α = 0.05) were found in the mass of the CWD between the burned and unburned splits across all experimental units combined for both sound and decayed material. However, when analyzed separately, the difference in the burned and unburned splits was statistically significant for LoD condition but not for HiD condition, likely due to greater heterogeneity of burn in the HiD condition. Coarse woody debris mass declined even in unburned units following treatments (p ≤ 0.1).
Habitat associations of carabid beetles in fields and forests on the Åland Islands, SW Finland

Carabid beetles (Coleoptera, Carabidae) were collected by using pitfall traps in 68 sites on the Aland Islands, SW Finland The sites were divided into four environmental types 1) cultivated fields and grazed pastures. 2) recently abandoned fields, 3) abandoned, overgrown cultivations, and 4) forests A total of 4901 carabids belonging to 77 species were caught Twenty of the most abundant species were classified into four distributional types according to their occurrence among the various environmental types 1) generalists (five species), 2) field species (five species), 3) species of open habitat (seven species), and 4) forest species (three species) Associations with environmental types were strictest among field species and forest species However, most of the species were found in low numbers outside each preferred environmental type The number of species and species diversity was highest in fields and pastures and lowest in forests, which agrees with previously detected patterns on the mainland Finland Pairwise similarity of the carabid assemblages among the environmental types was highest between the two types of abandoned cultivations The spatial distribution of two carabid species, Pterostichus melanarius and P niger, were examined in detail to ascertain whether any interspecific interaction could help explain their different island-mainland distribution observed in previous studies
Comprehensive characterization of bovine milk lipids: Phospholipids, sphingolipids, glycolipids and ceramides.

A comprehensive survey on phospholipids (PLs), sphingolipids, glycolipids and ceramides (Cer) of bovine milk was conducted by LC-MS/MS. A total of 514 species belonging to 15 classes were identified by automated search tool (LipidSearch) and manual analysis of MS2 spectra. Over 60 species were detected for the classes of phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS) and sphingomyelin (SM), between 20-45 species for phosphatidylethanolamine (PE), phosphatidic acid (PA) and lactosylceramide (LacCer), and between 7-20 species for phosphatidylglycerol (PG), lyso-phosphatidylcholine (LPC), lyso-phosphatidylethanolamine (LPE), glucosylceramide (GluCer), PC-plasmalogen (PC-P), PE-plasmalogen (PE-P), ganglioside and Cer. The structural assignment for PL classes is straight-forward based on class-specific product ions/neutral losses and fatty acid (FA)-related product ions. By contrast, structural determination of lipid classes containing a backbone of sphingoid bases (SM, GluCer, LacCer, ganglioside and Cer) is much more challenging and combining MS2/MS3 information acquired in both positive and negative mode is sometimes needed. The quantification of all the 15 classes of lipids was performed at the species level. A large variation in abundance was observed across the lipid classes; PC, PE and SM are the most abundant polar lipid classes with concentrations reaching 120, 150 and 90 µmoles/L, respectively, whereas PA, PG and PC-P are present at very low levels (< 1.5 µmoles/L) and the remaining classes at an intermediate level (2-45 µmoles/L). This is the first comprehensive characterization of minor lipid classes from bovine milk and the information provided can be used as a reference for studying milk lipids.
Morphological and scanning electron microscopic study of the lingual papillae in the Javan Pipistrelle (Pipistrellus javanicus)

There are vast numbers of bats, in terms of both individuals and species, in Indonesia, although the precise species count is currently unknown. These bats demonstrate great variation in feeding patterns, with some being insectivorous, frugivorous, nectar‐eating or carnivorous. One of the insectivorous bats found on Java Island, Indonesia, is the Javan pipistrelle (Pipistrellus javanicus). This paper presents a detailed morphological description of the tongue and lingual papillae of P. javanicus, using scanning electron microscopy (SEM) and light microscopy (LM). Macroscopically, the elongated tongue of P. javanicus can be divided into three sections: the apex, corpus and radix. On the dorsal part of the tongue (corpus), there is a prominence called the mediodorsal lobe, the lobe begin from the end of apex. On the radix, in the medial part, we describe the presence of a sulcus medianus. The SEM and LM observations show that the apex of the tongue bears three types of papillae: crown filiform, pronged filiform and fungiform. The corpus bears conical and fungiform papillae, whereas the radix bears vallate, large filiform, small filiform and fungiform papillae. Taken together, these results contribute to research on the tongue anatomy and feeding habits of the bat.