Miracle-dz/UniFAR-FTUs huggingface dataset:
TGFα Promotes Chemoresistance of Malignant Pleural Mesothelioma

Background: There is no standard chemotherapy for refractory or relapsing malignant pleural mesothelioma (MPM). Our previous reports nevertheless indicated that a combination of an anthracycline (doxorubicin) and a lysine deacetylase inhibitor (valproic acid, VPA) synergize to induce the apoptosis of MPM cells and reduce tumor growth in mouse models. A Phase I/II clinical trial indicated that this regimen is a promising therapeutic option for a proportion of MPM patients. Methods: The transcriptomes of mesothelioma cells were compared after Illumina HiSeq 4000 sequencing. The expression of differentially expressed genes was inhibited by RNA interference. Apoptosis was determined by cell cycle analysis and Annexin V/7-AAD labeling. Protein expression was assessed by immunoblotting. Preclinical efficacy was evaluated in BALB/c and NOD-SCID mice. Results: To understand the mechanisms involved in chemoresistance, the transcriptomes of two MPM cell lines displaying different responses to VPA-doxorubicin were compared. Among the differentially expressed genes, transforming growth factor alpha (TGFα) was associated with resistance to this regimen. The silencing of TGFα by RNA interference correlated with a significant increase in apoptosis, whereas the overexpression of TGFα desensitized MPM cells to the apoptosis induced by VPA and doxorubicin. The multi-targeted inhibition of histone deacetylase (HDAC), HER2 and TGFα receptor (epidermal growth factor receptor/EGFR) improved treatment efficacy in vitro and reduced tumor growth in two MPM mouse models. Finally, TGFα expression but not EGFR correlated with patient survival. Conclusions: Our data show that TGFα but not its receptor EGFR is a key factor in resistance to MPM chemotherapy. This observation may contribute to casting light on the promising but still controversial role of EGFR signaling in MPM therapy.
Amount of Dentifrice and Fluoride Concentration Influence Salivary Fluoride Concentrations and Fluoride Intake by Toddlers

The present study evaluated fluoride (F) concentrations in saliva of toddlers after brushing with dentifrices containing different F concentrations, applied in different quantities, and estimated F intake from toothbrushing. The study comprised a double-blind, crossover protocol, in which toddlers (n = 18, 2–3 years old) were randomly assigned into six groups, according to possible combinations of dentifrices (0/550/1,100 ppm F, as NaF) and amounts (rice grain, pea size, and transverse technique). Volunteers used a F-free dentifrice during 1 week. On the 7th day, saliva samples were collected before (baseline), and at 5/15/30/60 min after toothbrushing. All dentifrice expectorated after brushing was collected. F concentrations (saliva and expectorate) were determined with an ion-specific electrode. Data were submitted to ANOVA or Kruskal-Wallis test, followed by Fisher’s LSD or Student-Newman-Keuls’ tests (p <0.05). Brushing with 550 ppm F dentifrice (pea size or transversal technique) increased the area under the curve (AUC) at similar levels compared to 1,100 ppm F (rice grain). The highest AUC and salivary F at 5 min after brushing were achieved by 1,100 ppm F (pea size), followed by 550 ppm F (transversal technique). Regarding F intake, the highest values were observed for 550 ppm F (transversal technique), followed by 1,100 ppm F (pea size). It is possible to conclude that the amount of dentifrice and F concentration in the product significantly affected both salivary F concentrations and F intake during toothbrushing.
Social and behavioural determinants of areca nut consumption in adolescents.

OBJECTIVE This study aimed to investigate the prevalence of areca nut consumption and to identify social and behavioural determinants among a Taiwanese adolescent population. SUBJECTS AND METHODS A random sample of 5,343 high school students aged between 15 to 18 years in Kaohsiung, Taiwan, participated in the study. Participants underwent a clinical dental examination and completed a self-administered questionnaire. Data analyses were performed using multivariate logistic regression to establish a relationship between areca nut consumption as well as social and behavioural characteristics. RESULTS The prevalence of areca nut consumption was 3.0%. The chewing habit was more prevalent among older adolescents (p<0.001, OR=1.50, 95% CI: 1.26, 1.78), males (p<0.001, OR=17.91, 95% CI: 8.57, 37.40), pupils living with non-birth parent(s) (p=0.003, OR=2.13, 95% CI: 1.29, 3.50), children of family heads with primary (p=0.001, OR=2.90, 95% CI: 1.50, 5.59) or secondary level of education (p<0.001, OR=2.78, 95% CI: 1.74, 4.46), frequent risk takers (p<0.001, OR=1.35, 95% CI: 1.27, 1.43) and students of low physical fitness (p<0.001, OR=3.65, 95% CI: 1.81, 7.35). CONCLUSIONS Areca nut consumption has become an ongoing pertinent issue in adolescent health. Future investigations into neurocognitive influences of risk taking behaviour on areca nut consumption and social dependence of the habit are indicated.
Association of Dietary Patterns and Type-2 Diabetes Mellitus in Metabolically Homogeneous Subgroups in the KORA FF4 Study

There is evidence that a change in lifestyle, especially physical activity and diet, can reduce the risk of developing type-2 diabetes mellitus (T2DM). However, the response to dietary changes varies among individuals due to differences in metabolic characteristics. Therefore, we investigated the association between dietary patterns and T2DM while taking into account these differences. For 1287 participants of the population-based KORA FF4 study (Cooperative Health Research in the Region of Augsburg), we identified three metabolically-homogenous subgroups (metabotypes) using 16 clinical markers. Based on usual dietary intake data, two diet quality scores, the Mediterranean Diet Score (MDS) and the Alternate Healthy Eating Index (AHEI), were calculated. We explored the associations between T2DM and diet quality scores. Multi-variable adjusted models, including metabotype subgroup, were fitted. In addition, analyses stratified by metabotype were carried out. We found significant interaction effects between metabotype and both diet quality scores (p < 0.05). In the analysis stratified by metabotype, significant negative associations between T2DM and both diet quality scores were detected only in the metabolically-unfavorable homogenous subgroup (Odds Ratio (OR) = 0.62, 95% confidence interval (CI) = 0.39–0.90 for AHEI and OR = 0.60, 95% CI = 0.40–0.96 for MDS). Prospective studies taking metabotype into account are needed to confirm our results, which allow for the tailoring of dietary recommendations in the prevention of T2DM.
“Outsourcing” Diatoms in Fabrication of Metal-Doped 3D Biosilica

Diatoms have an ability that is unique among the unicellular photoautotrophic organisms to synthesize an intricately ornamented siliceous (biosilica) exoskeleton with an ordered, hierarchical, three-dimensional structure on a micro- to nanoscale. The unique morphological, structural, mechanical, transport, photonic, and optoelectronic properties of diatomaceous biosilica make it a desirable material for modern technologies. This review presents a summary and discussion of published research on the metabolic insertion of chemical elements with specific functional activity into diatomaceous biosilica. Included in the review is research on innovation in methods of synthesis of a new generation of functional siliceous materials, where the synthesis process is “outsourced” to intelligent microorganisms, referred to here as microtechnologists, by providing them with appropriate conditions and reagents.
A systematic quantitative analysis of the published literature on the efficacy of essential oils as sanitizers in fresh leafy vegetables

Abstract This study carried out a systematic quantitative analysis of published literature on the efficacy of essential oils (EOs) as sanitizers in fresh leafy vegetables (FLVs). Efficacy of EO was measured by determining if their application could cause a reduction of microbial population in FLV, as well as by identifying experimental factors that might affect the achieved reduction levels. Data on efficacy of EO to reduce the microbial population and experimental conditions were collected from selected studies and compiled for a distribution and relational analysis. Reduction of an artificial inoculum and/or natural microbiota of FLV caused by 14 different EO were measured in 404 (73.8%) and 143 (26.2%) experiments, respectively. Results of quantitative analysis showed that EO are consistently effective to reduce microbial population in FLV either when the target microorganisms are forming an artificial inoculum or the natural microbiota, being overall similarly effective to or more effective than substances used ordinarily as sanitizers. EO were more effective to reduce the population of microorganisms forming an artificial inoculum than the natural microbiota. EO concentration and inoculum size had no significant effect on achieved reductions. Duration of sanitization treatment with EO had significant effect on achieved reductions and highest reductions were found when the sanitization time was >3 min. Although with the inherent variability in experimental designs found in available literature, the results of this quantitative analysis provide strong evidence that EO are promising candidates for use in strategies to sanitize FLV.
Course of scar quality of donor sites following split skin graft harvesting: Comparison between patients and observers

There exists little to no data on the development of donor‐site scars that remain after split skin graft harvesting. The objectives of this study were to (a) examine changes in characteristics of donor‐site scar quality over time and (b) assess the agreement between patient‐reported and observer‐reported donor‐site scar quality in a burn population. A prospective cohort study was conducted including patients who underwent split skin grafting for their burn injury. Patients and observers completed the Patient and Observer Scar Assessment Scale (POSAS) for the first harvested donor site at 3 and 12 months post‐surgery. This study included 80 patients with a median age of 34 years. At 3 months post‐surgery, the patients scored the POSAS items itch and color as most deviant from normal skin, both improved between 3 and 12 months (3.1 vs 1.5 and 5.0 vs 3.5, respectively [P < .001]). Other scar characteristics did not show significant change over time. The patients' overall opinion score improved from 3.9 to 3.2 (P < .001). Observers rated the items vascularization and pigmentation most severe, only vascularization improved significantly between both time points. Their overall opinion score decreased from 2.7 to 2.3 (P < .001). The inter‐observer agreement between patients and observers was considered poor (ICC < 0.4) at both time points. Results of current study indicate that observers underestimate the impact of donor‐site scars. This has to be kept in mind while guiding therapy and expectations.
Alteration of gene expression profile in mouse embryonic stem cells and neural differentiation deficits by ethephon

Ethephon, a member of the organophosphorus compounds, is one of the most widely used plant growth regulators for artificial ripening. Although million pounds of this chemical is being used annually, the knowledge regarding its molecular toxicity is yet not sufficient. The purpose of this study was to evaluate the potential developmental toxicity of ethephon using embryonic stem cell model. The mouse embryonic stem cells (mESCs) were exposed to various concentrations of ethephon and the viability, cell cycle alteration and changes in the gene expression profile were evaluated using high-throughput RNA sequencing. Further, the effect of ethephon on neural differentiation potential was examined. The results showed that ethephon at noncytotoxic doses induced cell cycle arrest in mESCs. Gene ontology enrichment analysis showed that terms related to cell fate and organismal development, including neuron fate commitment, embryo development and cardiac cell differentiation, were markedly enriched in ethephon-treated cells. Neural induction of mESCs in the presence of ethephon was inhibited and the expression of neural genes was decreased in differentiated cells. Results obtained from this work clearly demonstrate that ethephon affects the gene expression profile of undifferentiated mESCs and prevents neural differentiation. Therefore, more caution against the frequent application of ethephon is advised.
How non-drug interventions affect the quality of life of patients suffering from progressive cognitive decline and their main caregiver

Background: In the absence of cure for age-related neurodegenerative diseases, non-drug interventions (NDIs) represent useful options. Quality of life (QOL) is a multidimensional concept progressively affected by cognitive decline. How single or multiple NDIs impact QOL is unknown. Results: We found no significant effect of multiple over single NDI on QOL. Socio-demographic variables influenced patients’ (age, gender, caregivers’ occupational status, management of patients’ financial affairs) and caregivers’ (gender, occupational status, patients’ severity of cognitive decline) QOL. When dyads interrupted interventions after 6 months, their QOL was lower and caregivers’ anxiety, depression and physical symptoms were higher at the end of the study. Conclusions: While the type and number of interventions do not appear to be critical, the continuity of adapted interventions in the long-term might be important for maintaining QOL of patients and caregivers. Methods: This is a multicenter (7 Swiss Memory Clinics), quasi-experimental, one-year follow-up study including 148 subjects (mild cognitive impairment or mild dementia patients and their caregivers). Primary outcome was the effect of multiple vs single NDIs on QOL. Secondary outcome included NDIs effect on patients’ cognitive impairment and functional autonomy, caregivers’ burden, severity of patients’ neuropsychiatric symptoms and dyads’ anxiety and depression.
A first glimpse at the influence of body mass in the morphological integration of the limb long bones: an investigation in modern rhinoceroses

The appendicular skeleton of tetrapods is a particularly integrated structure due to the shared developmental origin or similar functional constraints exerted on its elements. Among these constraints, body mass is considered strongly to influence its integration but its effect on shape covariation has rarely been addressed in mammals, especially in heavy taxa. Here, we propose to explore the covariation patterns of the long bones in heavy animals and their link to body mass. We investigate the five modern rhinoceros species, which display an important range of bodyweight. We used a 3D geometric morphometric approach to describe the shape covariation of the six bones composing the stylopodium and zeugopodium both among and within species. Our results indicate that the appendicular skeleton of modern rhinos is a strongly integrated structure. At the interspecific level, the shape covariation is roughly similar between all pairs of bones and mainly concerns the muscular insertions related to powerful flexion and extension movements. The forelimb integration appears higher and more related to body mass than that of the hind limb, suggesting a specialization for weight support. The integration of the stylopodium elements does not seem to relate to body mass in our sample, which suggests a greater effect of shared developmental factors. Conversely, the covariation of the zeugopodium bones seems more associated with body mass, particularly for the radius‐ulna pair. The fibula appears poorly integrated with other bones, especially within non‐Rhinoceros species, which may represent a case of parcellation due to a functional dissociation between the hind limb bones. The exploration of the integration patterns at the intraspecific level also highlights a more prominent effect of age over individual body mass on shape covariation within C. simum. This study lends support to previous hypotheses indicating a link between high body mass and high integration level.
Evolution of indicators and service capacity at the beginning of the COVID-19 epidemic in Northeast Brazil, 2020.

OBJECTIVE to describe the evolution of indicators and capacity for health care in the initial phase of the COVID-19 epidemic in the Northeast region of Brazil. METHODS this was a descriptive study based on COVID-19 case epidemiological bulletins released by the Ministry of Health up until April 1st, 2020. The incidence rate, lethality and number of cumulative daily cases were calculated. RESULTS 1,005 confirmed cases of COVID-19 were identified, most of them in Ceará and Bahia states. The incidence rate was 1.8/100,000 inhabitants and lethality was 2.7%. Ceará was the state with the highest number of cases, with 29.6 new cases per day on average. Average intensive care bed availability in the Northeast region (1.04/10,000 inhab.) was below the national average (2.8/10,000 inhab.). CONCLUSION the indicators suggest that COVID-19 impact is heterogeneous and signal the challenges for health systems in the Northeast Region.
How honey bees of successive age classes are distributed over a one storey, ten frames hive

Summary In honey bee studies focusing on physiology, disease diagnosis or bio indication, bees are sampled from the colony. This raises the question of where in the colony samples must be taken from for specific study objectives. In this study we recorded where bees of known age are found in the hive. We recorded in a single brood box with ten frames in August that the mean proportion of bees of one (41%), two (23%), three (17%), four (11%) and five (8%) week old bees did not differ between frames. Additionally we found that there was a significant mortality of young bees in the first week after emergence. This may be partly due to the study set up but is also a natural phenomenon.
THE EX-VIVO PERFUSED HUMAN LUNG IS RESISTANT TO INJURY BY HIGH-DOSE S. PNEUMONIAE BACTEREMIA.

Few patients with bacteremia from a non-pulmonary source develop ARDS. However, the mechanisms that protect the lung from injury in bacteremia have not been identified. We simulated bacteremia by adding S. pneumoniae to the perfusate of the ex vivo perfused human lung model. In contrast to a pneumonia model in which bacteria were instilled into the distal air spaces of one lobe, injection of high doses of S. pneumoniae into the perfusate was not associated with alveolar epithelial injury as demonstrated by low protein permeability of the alveolar epithelium, intact alveolar fluid clearance, and the absence of alveolar edema. Unexpectedly, the ex vivo human lung rapidly cleared large quantities of S. pneumoniae even though the perfusate had very few intravascular phagocytes and lacked immunoglobulins or complement. The bacteria were cleared in part by the small number of neutrophils in the perfusate, alveolar macrophages in the airspaces, and probably by interstitial pathways. Together, these findings identify one mechanism by which the lung and the alveolar epithelium are protected from injury in bacteremia.
Circulating Exosomal Gastric Cancer–Associated Long Noncoding RNA1 as a Biomarker for Early Detection and Monitoring Progression of Gastric Cancer

Key Points Questions What role does circulating exosomal long noncoding RNA-GC1 (lncRNA-GC1) play in gastric cancer (GC), and does lncRNA-GC1 exhibit sufficient diagnostic performance for detecting early-stage GC and for monitoring disease progression? Findings In this multiphase study involving 826 participants, including patients with GC, patients with gastric precancerous lesions, and healthy donor individuals, circulating exosomal lncRNA-GC1 served as a noninvasive biomarker for detecting early-stage GC and for monitoring disease progression. Meaning For patients with gastric cancer, detection of circulating exosomal lncRNA-GC1 may improve the early diagnostic rate and monitor disease progression.
Genotype and phenotype associations with drought tolerance in barley tested in North Africa

A review is presented of genetic strategies deployed in a 3-yr project on drought tolerance in barley. Data were collected on genetic, physiological and agronomic traits in non-irrigated and irrigated field trials in Egypt, Morocco and Tunisia. A wide range of barley germplasm (developed from African and European cultivars, adapted landraces and wild barleys) was tested, and positive traits were found in each gene pool. The contrasting environments of the three North African countries had major effects on plant/genotype performance. Genetic effects were also detected, as were genotype x environment interactions. A range of strategies were deployed to investigate the physiology and genetics of quantitative traits associated with field performance. Quantitative trait locus (QTL) analysis was performed using backcross lines, recombinant inbred lines and doubled haploid mapping populations. A detailed genetic map was generated in the Tadmor x (ER/Apm) recombinant inbred lines, an important mapping population specifically developed by ICARDA (Centre for Agricultural Research in Dry Areas) and CIMMYT (International Maize and Wheat Improvement Center) to study drought. Quantitative trait loci (QTLs) for grain yield and other important morphological and physiological traits were also identified in a population of doubled haploids derived from F 2 BC 1 plants from a cross between a cultivar and a wild barley accession. Significantly, the wild parental line was found to contribute a number of positive alleles for yield. Effects of major developmental genes could explain many of the responses observed. QTLs were found to cluster around major genes controlling flowering time (sghl), plant stature (sdw1 and ari-e.GP) and ear type (vrs1), and it is highly likely that the associations represent pleiotropic effects. Some QTLs were associated with candidate genes such as dehydrins and rubisco activase. One of the most significant results was the identification and generation of material that out performed the best local standards in the three participating North African countries; the selected lines have now entered local breeding programmes. The strategies adopted provided information on physiological traits, genotypes and genetic markers that could be used for marker-assisted selection. Target QTLs and their associated genetic markers may be deployed in marker assisted selection programmes to match crop phenology to the field environment.