Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of analytical accuracy of HER2 status in patients with breast cancer

Human epidermal growth factor receptor 2 (HER2) gene status and overexpression, occurring in ~ 13.6% of primary breast cancers, is essential for identifying patients likely to benefit from biological treatment. In this method of evaluation study, we tested and compared the HER2 gene–protein assay (GPA) with routine HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The GPA was evaluated using 67 formalin‐fixed paraffin‐embedded (FFPE) HER2 equivoval IHC (2+) breast cancer tissue samples. Overall, agreement between GPA silver in situ hybridization (SISH) and FISH was 91.9% (57/62). Regression analysis revealed slightly higher, but non‐significant difference in HER2/chromosome enumeration probe 17 (CEP17) ratio for GPA as compared to FISH (p = 0.074). Intraclass correlation coefficients (ICCs) of 0.94 and Spearman´s rank correlation coefficients of 0.93 (p < 0.0001) for FISH and GPA SISH suggested strong inter‐observer association for methods with one observer counting on average 0.23 significant higher for GPA SISH (p = 0.014). Intra‐observer IHC method reproducibility was 52.6% (κ = 0.3122, p = 0.004) and 79.7% (κ = 0.6428, p = 0.9197), suggesting fair significant and substantial non‐significant difference between tests for reviewers. Inter‐observer reproducibility for IHC methods was 53%. While inter‐observer reproducibility for experienced IHC interpretation suggested significant differences (κ = 0.3636, p = 0.0332), unexperienced interpretation of IHC GPA suggested fair non‐significant difference between reviewers (κ = 0.3101, p = 0.0747). Using FISH as reference, the diagnostic indices for GPA SISH were as follows: sensitivity 100%, specificity 95% and accuracy 92%. Inaccuracy between tests was in 80% of cases due to ISH categorization as equivocal by one of the methods. IHC results highlight that it may be beneficial with a method for simultaneously visualization of HER2 gene and protein status.
To Be Continued? Long-Term Treatment Effects of Antidepressant Drug Classes and Individual Antidepressants on the Risk of Developing Dementia: A German Case-Control Study.

BACKGROUND Given the need for disease-modifying therapies for dementia, drug repurposing appears to be a promising approach, at least as a risk reduction treatment. Preclinical studies suggest that antidepressants-in particular selective serotonin reuptake inhibitors-have beneficial effects on dementia-related biomarkers and functional outcomes, although clinical data are inconclusive. The present case-control study aimed to evaluate the effects of antidepressant drug classes and individual compounds with different treatment durations on the risk of developing dementia. METHODS Analyses are based on data from the German Disease Analyzer database (owned and maintained by IQVIA) and included 62,317 subjects with an incident dementia diagnosis (ICD-10: F01, F03, G30, F06.7) and controls matched by age, sex, and physician between January 2013 and December 2017. Logistic regression analyses adjusting for health insurance status and comorbid diseases associated with dementia or antidepressant use were performed to investigate the association between dementia incidence and treatment with 4 major antidepressant drug classes and 14 of the most frequently prescribed individual substances. RESULTS In 17 of 18 comparisons, long-term treatment (≥ 2 years) with any antidepressant was associated with a lower incidence of dementia than short-term treatment. Tricyclic and herbal antidepressants were associated with a decrease in dementia incidence, especially with long-term treatment. The lowest risks for dementia on an individual substance basis were identified for long-term treatment with escitalopram (odds ratio [OR] = 0.66; 95% CI, 0.50-0.89) and Hypericum perforatum (OR = 0.6; 95% CI, 0.51-0.70). CONCLUSIONS Long-term treatment with tricyclic antidepressants, Hypericum perforatum, or escitalopram may be associated with reduced incidence of dementia. If antidepressant therapy is well tolerated, continuation-even if depressive symptoms have resolved-may be considered even beyond the purpose of relapse prevention. Future combined analyses of multinational registries and long-term clinical trials are needed to substantiate these findings.
Age-related changes in audiovisual simultaneity perception and their relationship with working memory.

OBJECTIVE Perceiving simultaneity of a visual and an auditory signal is critical for humans to integrate these multisensory inputs effectively and respond properly. We examined age-related changes in audiovisual simultaneity perception, and the relationships between this perception and working memory performances with aging. METHODS Audiovisual simultaneity perception of young, middle-aged, and older adults was measured using a simultaneity judgment (SJ) task, in which a flash and a beep were presented at one of 11 stimulus onset asynchronies (SOAs). Participants judged whether these two stimuli were perceived simultaneously. Precision of simultaneity perception, the SOA corresponding to the peak probability of subjective simultaneity (PSS), and response errors at each SOA were estimated using model fitting. The precision and PSS are associated with multisensory perception per se whereas the response error reflects executive ability when performing the SJ task. Visual working memory of the same middle-aged and older adults was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB) beforehand. RESULTS Compared to young adults' performances, middle-aged and older adults showed a decreased precision, a shift of PSS toward the visual-leading SOAs, and increased response errors at the visual-leading SOAs. Among these changes, only the increased response errors correlated with worse spatial recognition memory in middle-aged and older adults. DISCUSSION Age-related decrements in audiovisual simultaneity perception start from middle age and are manifested in both perceptual and executive parameters. Furthermore, higher-order executive ability is plausibly a common cause for age-related degenerations in the audiovisual simultaneity perception and visual working memory.
Membrane progesterone receptors (mPRs/PAQRs) in Schwann cells represent a promising target for the promotion of neuroregeneration

Schwann cells and neuroregeneration: Peripheral nerve injury is a common cause of morbidity, which affects millions of people worldwide. The peripheral nervous system, differently from the central nervous system, has an intrinsic ability to regenerate after injury. However, in most cases the regenerative outcome is not completely satisfactory, in particular for long-gap peripheral nerve injuries in which the microsurgical approach is not possible. In these cases, the current research effort is mostly aimed at the identification of pharmacological and/or cell therapy approaches that, coupled with the use of biomaterial conduits, provide scaffold, mechanical support and guidance to the regeneration process, and can increase regeneration speed and efficiency (Faroni et al., 2015).
Infant drug exposure via breast milk

More than half of women take medications during breastfeeding, predisposing their infants to medication exposure via breast milk. As a result, adverse drug reactions may emerge in the infant, although they are rarely reported. Disposition of maternal drugs in breast milk is described with several key parameters, which include relative infant dose (RID): infant drug intake via milk (weight‐ and time‐adjusted) expressed as a percentage of the similarly adjusted mother's dose. Most drugs show RID values of <10%, indicating that drug concentrations in infant serum do not reach a level known to be therapeutic in adults unless drug clearance is markedly lower than the adult level on a weight basis. RID is a function of milk‐to‐(maternal) plasma drug concentration ratio (MP ratio) and maternal drug clearance. Therefore, MP ratio between drugs must be interpreted not by itself but with maternal drug clearance of each drug. This is why some drugs such as phenobarbital show an MP ratio of <1 but an RID as high as 50–70%, while morphine shows an MP ratio of 2 but an RID in the range of 5%. Using RID, we interpreted case reports of infant adverse outcomes, and we observed cases with relatively low infant serum concentrations of drug, consistent with low RID, as well as those with near‐ or above‐adult therapeutic serum concentrations, with or without increased drug intake (i.e. high RID). It is important to consider both pharmacokinetic and pharmacodynamic factors in interpreting adverse outcomes in infants breastfed by a mother taking medications.
Bullying and Cyberbullying in Adolescents from Disadvantaged Areas: Validation of Questionnaires; Prevalence Rates; and Relationship to Self-Esteem, Empathy and Social Skills

Although bullying and cyberbullying have been widely studied in diverse geographical areas, the number of studies in isolated regions, located in rainforests such as the Peruvian Amazonia, is low. Most research has been conducted in wealthy, Western countries, although disadvantaged areas are usually the most affected by various problems. Thus, the aims of this study were to validate bullying and cyberbullying measurement instruments among adolescents in the Peruvian Amazonia, to determine the prevalence rates of bullying and cyberbullying among this population, and to examine how bullying and cyberbullying relate to self-esteem, empathy, and social skills. The sample included 607 students from the region of Loreto (Peruvian Amazonia) who completed self-report questionnaires. Both questionnaires used in the sample were found to have good psychometric properties. Results showed that bullying and cyberbullying are prevalent among teenagers in the Amazonia. Low self-esteem and high affective empathy predicted bullying victimization. Being a bully was related to high assertiveness. Being a bully-victim was related to low self-esteem and low assertiveness. Cybervictims showed higher cognitive empathy. Cyberbullies showed higher affective empathy in comparison to uninvolved adolescents. Having low self-esteem and higher affective empathy were related to being a cyberbully/victim. This study provides a validated questionnaire that can be used for research and practice in the Amazonia. Based on the current results, tailored anti-bullying and anti-cyberbullying interventions with components focused on self-esteem, empathy, and social skills should be implemented in Peruvian secondary schools.
Silicon suppresses zinc uptake through down-regulating zinc transporter gene in rice.

One of the beneficial effects of silicon (Si) is to improve nutrient imbalance including deficiency and excess of nutrients, however the molecular mechanisms underlying this effect are still poorly understood. In this study, we investigated the interaction between Si and zinc (Zn) in rice by using a mutant (lsi1) defective in Si uptake and its wild type (WT, cv. Oochikara) at different Zn levels. High Zn inhibited the root elongation of both WT and lsi1 mutant, but Si did not alleviate this inhibition in both lines. By contrast, Si supply decreased Zn concentration in both the roots and shoots of the WT, but not in the lsi1 mutant. A short-term (24 h) labeling experiment with stable isotope 67 Zn showed that Si decreased 67 Zn uptake, but did not affect the root-to-shoot translocation and distribution ratio to different organs of 67 Zn in the WT. Furthermore, Si accumulated in the shoots, rather than Si in the external solution, is required for suppressing Zn uptake, but this was not caused by Si-decreased transpiration. A kinetic study showed that Si did not affect Km value of root Zn uptake, but decreased Vmax value in the WT. Analysis of genes related with Zn transport showed that among ZIP family genes, the expression of only OsZIP1 implicated in Zn uptake, was down-regulated by Si in the WT, but not in the lsi1 mutant. These results indicate that Si accumulated in the shoots suppresses the Zn uptake through down-regulating the transporter gene involved in Zn uptake in rice. This article is protected by copyright. All rights reserved.
Relationship between the composition of the intestinal microbiota and the tracheal and intestinal colonization by opportunistic pathogens in intensive care patients

Objective Infections caused by multidrug-resistant Gram-negative bacilli (MDR-GNB) are a major issue in intensive care. The intestinal and oropharyngeal microbiota being the reservoir of MDR-GNB. Our main objective was to assess the link between the composition of the intestinal microbiota and the tracheal and intestinal colonization by MDR-GNB, and also by Enterococcus spp. and yeasts. Methods We performed a 2-month prospective, monocentric cohort study in the medical intensive care unit of our hospital. Patients ventilated >3 days and spontaneously passing feces were included. A fecal sample and an endotracheal aspiration (EA) were collected twice a week. MDR-GNB but also Enterococcus faecium and yeasts (as potential dysbiosis surrogate markers) were detected by culture methods. The composition of the intestinal microbiota was assessed by 16S profiling. Results We collected 62 couples of feces and EA from 31 patients, including 18 feces and 9 EA positive for MDR-GNB. Forty-eight fecal samples were considered for 16S profiling. We did not observe a link between the diversity and the richness of the intestinal microbiota and the MDR-GNB intestinal relative abundance (RA). Conversely, we observed a negative link between the intestinal diversity and richness and the RA of Enterococcus spp. (p<0.001). Conclusion The fecal MDR-GNB RA was not associated to the diversity nor the richness of the intestinal microbiota, but that of Enterococcus spp. was.
Physical Activity, Step Counts, and Grip Strength in the Chinese Children and Families Cohort Study

Objectives: This paper describes the development of a physical activity questionnaire (PAQ) designed for Chinese adolescents and their mothers in urban and rural settings, and reports on results of the PAQ, pedometry, and hand grip dynamometry from the Chinese Children and Families Cohort Study pilot investigation (CFCS). Methods: As part of a pilot investigation to evaluate the feasibility to follow-up and obtain detailed nutrition, dietary, physical activity, and ultraviolet radiation (UVR) data from CFCS participants, data were collected in 2013 for 93 adolescent/mother pairs from a rural (n = 41) and an urban site (n = 52) in two provinces. Respondents were asked to wear a pedometer for seven days (Omron HJ-151), use a Takei Digital Grip Strength Dynamometer on (each hand; three trials; two separate days), and complete a 39 item, eight domain PAQ covering the past year. Self-reported physical activity (PA) was linked to metabolic equivalent of task (MET) scores in kcal/kg/hr and used to calculate METs for different domains of PA and intensity categories. Results: Compliance was high (95%) in this measurement protocol administered by health staff during a series of data collection efforts at home and local clinics or health centers. Step counts were highly variable, averaging between 5000 and 10000 per day with somewhat higher step counts in rural adolescent boys. Maximum grip strength (Kgs) was greater in children (Mean = 36.5, SE = 0.8) than mothers (Mean = 28.8, SE = 0.8) and similar in the urban (Mean = 29.6, SE = 0.6) compared to the rural (Mean = 29.6, SE = 0.5) communities overall. Grip strength, step counts, and measures of time spent in different activities or activity intensities were uncorrelated. Conclusion: Device and question-based measurement of PA and strength were readily accepted in these Chinese urban and rural populations. The PAQ on physical activity in the past year produced some plausible population averages, but individual responses suggested recall challenges. If data about specific activities are required, future studies should explore use of standardized survey questions concerning such fewer specific activities or instruments examining shorter time periods such as one, three, or seven day recalls.
Differences in Sweet Taste Perception and Its Association with the Streptococcus mutans Cariogenic Profile in Preschool Children with Caries

The aim of the study was to verify the hypothesis about differences in sweet taste perception in the group of preschool children with and without caries, and to determine its relationship with cariogenic microbiota and the frequency of sweets consumption in children. The study group included of 63 children aged 2–6 years: 32 with caries and 31 without caries. The study consisted of collecting questionnaire data and assessment of dental status using the decayed, missing, filled in primary teeth index (dmft) and the International Caries Detection and Assessment System (ICDAS II). The evaluation of sweet taste perception was carried out using a specific method that simultaneously assessed the level of taste preferences and the sensitivity threshold for a given taste. The microbiological analysis consisted of the assessment of the quantitative and qualitative compositions of the oral microbiota of the examined children. The sweet taste perception of children with caries was characterized by a lower susceptibility to sucrose (the preferred sucrose solution concentration was >4 g/L) compared to children without caries (in the range ≤ 4 g/L, p = 0.0015, chi-square test). A similar relationship was also observed for frequent snacking between meals (p = 0.0038, chi-square test). The analysis of studied variables showed the existence of a strong positive correlation between the perception of sweet taste and the occurrence and intensity of the cariogenic process (p = 0.007 for dmft; and p = 0.012 for ICDAS II), as well as the frequency of consuming sweets (p ≤ 0.001 for frequent and repeated consumption of sweets during the day, Spearman test) in children with caries. Additionally, children with an elevated sucrose taste threshold were more than 10-times more likely to develop S. mutans presence (OR = 10.21; 95% CI 3.11–33.44). The results of this study suggest the future use of taste preferences in children as a diagnostic tool for the early detection of increased susceptibility to caries through microbial dysbiosis towards specific species of microorganisms.
Tuning the thermal conductivity of nanoparticle suspensions by electric field

Active thermal management is essential for the operation of modern technologies like electronic circuits and spacecraft systems to deal with the complex control and conversion of thermal energy. One basic requirement for the materials is its tunable and reversible thermal properties. Here, we try to provide a systematic investigation of the thermal smart materials composed of low-dimensional solid particles suspended in liquid media, whose structures and properties can be tuned by external field. A two-step theoretical model, which takes into account the effects from particle aggregation and orientational variation, was proposed and obtained reasonable agreement with both literature and our own experimental results. Graphene nanosheets/Mg-Al layered double hydroxides (GNS/LDH) were fabricated and their silicone oil suspension shows reversible thermal conductivity switching under DC electric field due to the formation/break-up of chain-like structures with a maximum switching ratio around 1.35×. This study reveals the underlying mechanism of thermal conductivity enhancement in nanoparticle suspensions, and provides a preliminary example to design and fabricate responsive thermal materials for the next generation technologies.
Scalable Kernel Ordinal Regression via Doubly Stochastic Gradients

Ordinal regression (OR) is one of the most important machine learning tasks. The kernel method is a major technique to achieve nonlinear OR. However, traditional kernel OR solvers are inefficient due to increased complexity introduced by multiple ordinal thresholds as well as the cost of kernel computation. Doubly stochastic gradient (DSG) is a very efficient and scalable kernel learning algorithm that combines random feature approximation with stochastic functional optimization. However, the theory and algorithm of DSG can only support optimization tasks within the unique reproducing kernel Hilbert space (RKHS), which is not suitable for OR problems where the multiple ordinal thresholds usually lead to multiple RKHSs. To address this problem, we construct a kernel whose RKHS can contain the decision function with multiple thresholds. Based on this new kernel, we further propose a novel DSG-like algorithm, DSGOR. In each iteration of DSGOR, we update the decision functional as well as the function bias with appropriately set learning rates for each. Our theoretic analysis shows that DSGOR can achieve $O(1/t)$ convergence rate, which is as good as DSG, even though dealing with a much harder problem. Extensive experimental results demonstrate that our algorithm is much more efficient than traditional kernel OR solvers, especially on large-scale problems.
A MATHEMATICAL MODEL OF THE FUNCTIONAL RELATIONSHIP BETWEEN DENSITY AND SPATIAL DISTRIBUTION OF A POPULATION

SUMMARY (1) A model of the functional relationship between the mean population density and the proportion of unoccupied patches in a patchy environment is proposed. (2) Provided a population is distributed according to the negative binomial distribution, the zero-term of this distribution can be set equal to the model predicted proportion of empty patches. The parameter k of the negative binomial will, for a given mean density u, be a root in this equation. (3) The model is fitted to the data of the two-spotted spider mite (Tetranychus urticae) and its phytoseiid predator Phytoseiulus persimilis, and the density behaviour of 1/k is predicted. The agreement between observed and expected values of 1/k is relatively poor due to the large scatter of the empirical values of 1/k obtained by the method of maximum likelihood. A test for goodness of fit, however, reveals that the model provides better fit to the data than an alternative model of Taylor, Woiwod & Perry (1979) does, although the two models are qualitatively very similar.
The Oocysts of Coccidia from Domestic Cattle in Alabama (U.S.A.)., with Descriptions of Two New Species

There is little information available on the bovine coccidia to supplement oocyst studies in the definition of species. The relative pathogenicity, localization in the tissues, and morphology of the intracellular stages of coccidia from bovines have not been worked out on a comparative basis. To be reliable, such information should be based on experimental work with pure cultures and coccidia-free hosts. Considering the difficulties involved in providing these experimental conditions with bovines, a long time will elapse before speciation in these coccidia can be established with a thoroughness approaching that accomplished for chicken coccidia.
Chromosome Patterns in Mexican Boophilus annulatus and B. micropolus

Chromosome patterns in excised gonads of laboratory-reared Mexican Boophilus annulatus (Say) and B. microplus (Canestrini) were studied. Mitotic and meiotic divisions were observed in spermatocytes of both species, but only mitotic oogonia, with one exception, were detected in both species. 2n=21 and 22 (20 autosomes) was observed in males and females of both species, respectively. Sex determination is by an XX:XO mechanism with the male being heterogametic. At metaphase I, male autosome lengths ranged from 2.9 to 4. 5µ in B. annulatus and from 2.3 to 9. 4µ in B. microplus . Male X chromosome length averged 7. 1µ in B. annulatus and 5. 6µ in B. microplus . Near homomorphic female X chromosome lengths ranged from 6.5 to 7. 0µ in B. annulatus , and autosomes from 1.4 to 2.9µ definitive measurements in B. microplus were difficult, but X chromosomes appeared to be homomorphic and ranged from 1.5X to 4X the length of autosomes.