Miracle-dz/UniFAR-FTUs huggingface dataset:
Otitis Media and Nasopharyngeal Colonization in ccl3−/− Mice

ABSTRACT We previously found CC chemokine ligand 3 (CCL3) to be a potent effector of inflammation during otitis media (OM): exogenous CCL3 rescues the OM phenotype of tumor necrosis factor-deficient mice and the function of macrophages deficient in several innate immune molecules. To further delineate the role of CCL3 in OM, we evaluated middle ear (ME) responses of ccl3−/−mice to nontypeable Haemophilus influenzae (NTHi). CCL chemokine gene expression was evaluated in wild-type (WT) mice during the complete course of acute OM. OM was induced in ccl3−/− and WT mice, and infection and inflammation were monitored for 21 days. Phagocytosis and killing of NTHi by macrophages were evaluated by an in vitro assay. The nasopharyngeal bacterial load was assessed in naive animals of both strains. Many CCL genes showed increased expression levels during acute OM, with CCL3 being the most upregulated, at levels 600-fold higher than the baseline. ccl3−/− deletion compromised ME bacterial clearance and prolonged mucosal hyperplasia. ME recruitment of leukocytes was delayed but persisted far longer than in WT mice. These events were linked to a decrease in the macrophage capacity for NTHi phagocytosis and increased nasopharyngeal bacterial loads in ccl3−/− mice. The generalized impairment in inflammatory cell recruitment was associated with compensatory changes in the expression profiles of CCL2, CCL7, and CCL12. CCL3 plays a significant role in the clearance of infection and resolution of inflammation and contributes to mucosal host defense of the nasopharyngeal niche, a reservoir for ME and upper respiratory infections. Therapies based on CCL3 could prove useful in treating or preventing persistent disease.
Hepatocellular carcinoma in 2 young adolescents with chronic hepatitis C.

Hepatitis C virus (HCV) infection is a global health problem affecting 170 million individuals worldwide. In the United States, there are approximately 7 million adults and 100,000 children chronically infected with HCV (1,2). The importance of HCV infection stems from its proclivity to cause insidious liver damage over many years, including chronic hepatitis, cirrhosis, and liver cancer. In adults, HCV infection is a leading cause for liver cancer worldwide (3). The financial burden of this viral infection is staggering, with projected medical costs of $10.7 billion in adults from 2010 to 2019 and approximately $426 million during the next 10 years in children (4,5). The epidemiology, clinical outcome, and risk factors associated with progression of HCV-related liver disease are fairly well characterized in adults. Although the natural history of childhood HCV infection is poorly defined, it appears to be an indolent disease in most children (6–13); however, progressive liver disease, including chronic hepatitis and cirrhosis necessitating liver transplantation, can occur in children (14,15). Unlike in adults, liver cancer, particularly hepatocellular carcinoma (HCC), is rare in children (16), but it was described in 2 young adults infected with HCV during childhood (17). Herein we extend these observations and present 2 children with chronic hepatitis C who developed HCC as adolescents. To our knowledge, they are the
Phylogenetic lineages in Vanguerieae (Rubiaceae) associated with Burkholderia bacteria in sub-Saharan Africa.

PREMISE OF THE STUDY It is well known that mutualistic bacteria can provide substantial benefits to their host plants. However, 'how,' 'why,' and the possible applications of such an interaction are only second to the questions 'who is involved? ', and 'where does it occur? '. In the coffee family (Rubiaceae), certain species closely interact with endophytic leaf bacteria that are freely distributed among the mesophyll cells. This type of interaction was recently discovered in South Africa. Our aim is to document the bacterial diversity associated with Rubiaceae ('who') and to establish the geographic range of the interaction ('where'). METHODS Representatives of the Vanguerieae tribe in Rubiaceae were investigated for the presence of endophytes with special emphasis on the distributional range of the plant-bacteria association by collecting specimens from different African regions. KEY RESULTS The interaction is found in five genera and is restricted to three major host lineages. The endophytic bacteria belong to the genus Burkholderia and are part of the plant-associated beneficial and environmental group. Some endophytes are similar to B. caledonica, B. graminis, B. phenoliruptrix or B. phytofirmans, while others are classified in OTUs that show no similarity with any previously described Burkholderia species of bacteria. CONCLUSIONS The association is not obligate from the bacterial point of view and is considered a loose and recent interaction, which is demonstrated by the fact that there is no evidence for coevolution. The geographical distribution of the association is restricted by the distributional range of the host plants covering the whole of sub-Saharan Africa.
Tumor-Stroma Crosstalk in Bone Tissue: The Osteoclastogenic Potential of a Breast Cancer Cell Line in a Co-Culture System and the Role of EGFR Inhibition

Although bone metastases represent a major challenge in the natural history of breast cancer (BC), the complex interactions involved have hindered the development of robust in vitro models. The aim of this work is the development of a preclinical model of cancer and bone stromal cells to mimic the bone microenvironment. We studied the effects on osteoclastogenesis of BC cells and Mesenchymal stem cells (MSC) cultured alone or in combination. We also analyzed: (a) whether the blockade of the Epithelial Growth Factor Receptor (EGFR) pathway modified their influence on monocytes towards differentiation, and (b) the efficacy of bone-targeted therapy on osteoclasts. We evaluated the osteoclastogenesis modulation of human peripheral blood monocytes (PBMC) indirectly induced by the conditioned medium (CM) of the human BC cell line SCP2, cultured singly or with MSC. Osteoclastogenesis was evaluated by TRAP analysis. The effect of the EGFR blockade was assessed by treating the cells with gefitinib, and analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western Blot (WB). We observed that SCP2 co-cultured with MSC increased the differentiation of PBMC. This effect was underpinned upon pre-treatment of the co-culture with gefitinib. Co-culture of SCP2 with MSC increased the expression of both the bone-related marker Receptor Activator of Nuclear Factor κB (RANK) and EGFR in BC cells. These upregulations were not affected by the EGFR blockade. The effects of the CM obtained by the cells treated with gefitinib in combination with the treatment of the preosteoclasts with the bone-targeted agents and everolimus enhanced the inhibition of the osteoclastogenesis. Finally, we developed a fully human co-culture system of BC cells and bone progenitor cells. We observed that the interaction of MSC with cancer cells induced in the latter molecular changes and a higher power of inducing osteoclastogenesis. We found that blocking EGFR signaling could be an efficacious strategy for breaking the interactions between cancer and bone cells in order to inhibit bone metastasis.
Effect of exercise intensity on Nrf2 signalling in young men

Abstract Introduction: The transcription factor Nrf2 is the master regulator of antioxidant defence. Recent data indicate a single bout of moderate-intensity stationary cycling at a constant workload upregulates Nrf2 signalling in young, but not older men; however, the role of exercise intensity on Nrf2 activation has not been tested. We hypothesised that a high-intensity interval session would elicit a greater Nrf2 response than moderate aerobic exercise. Methods: Nrf2 signalling in response to two 30-min cycling protocols (high-intensity interval and constant workload) was compared in young men (25 ± 1y, n = 16). Participants completed exercise trials in random order with blood collected pre-, immediately post-, and 30-mins post exercise. Five participants completed a control trial without any physical activity. Nrf2 signalling was determined by measuring protein expression of Nrf2 in whole cell and nuclear fractions. Plasma 8-isoprostanes as well as peripheral mononuclear cell glutathione reductase (GR) and superoxide dismutase activity were measured as markers of oxidative stress. Results: The exercise trials elicited significant increases in nuclear Nrf2 (p < .01), but increases in whole cell Nrf2 did not reach statistical significance. GR activity and plasma 8-isoprostanes increased significantly in response to exercise (p < .05), and GR response was higher in the high-intensity trial (p < .05). Conclusion: Our findings indicate that acute aerobic exercise elicits activation of nuclear Nrf2, regardless of exercise intensity, but that higher-intensity exercise results in greater activity of GR. Future experiments should explore the effect of exercise mode and duration on Nrf2 signalling, and the role of intensity in compromised populations.
Catalytic Hydrodefluorination of C-F Bonds by an Air-Stable PIII Lewis Acid.

Catalytic hydrodefluorination (HDF) of unactivated fluoroalkanes or CF3 -substituted aryl species is performed using the PIII Lewis acids, [(bipy)PPh]2+ (12+ ) and [(terpy)PPh]2+ (22+ ) under mild conditions (25 or 50 °C). Mechanistic studies indicate that activation of C-F bond by the PIII center is key. Particularly noteworthy is that the catalyst 2[B(C6 F5 )4 ]2 is air-stable and readily accessible from bench-stable, commercially available reagents in one-step and can be used without isolation.
Common Visual Preference for Curved Contours in Humans and Great Apes

Among the visual preferences that guide many everyday activities and decisions, from consumer choices to social judgment, preference for curved over sharp-angled contours is commonly thought to have played an adaptive role throughout human evolution, favoring the avoidance of potentially harmful objects. However, because nonhuman primates also exhibit preferences for certain visual qualities, it is conceivable that humans’ preference for curved contours is grounded on perceptual and cognitive mechanisms shared with extant nonhuman primate species. Here we aimed to determine whether nonhuman great apes and humans share a visual preference for curved over sharp-angled contours using a 2-alternative forced choice experimental paradigm under comparable conditions. Our results revealed that the human group and the great ape group indeed share a common preference for curved over sharp-angled contours, but that they differ in the manner and magnitude with which this preference is expressed behaviorally. These results suggest that humans’ visual preference for curved objects evolved from earlier primate species’ visual preferences, and that during this process it became stronger, but also more susceptible to the influence of higher cognitive processes and preference for other visual features.
Physical activity and hippocampal volume in middle-aged patients with type 1 diabetes

Objective: To examine the cross-sectional association between physical activity (PA) and hippocampal volume in middle-aged adults with childhood-onset type 1 diabetes (T1D), and whether hyperglycemia and insulin sensitivity contribute to this relationship. Methods: We analyzed neuroimaging and self-reported PA data from 79 adults with T1D from the Pittsburgh Epidemiology of Diabetes Complications Study (mean age 50 years, mean duration 41 years) and 122 similarly aged adults without T1D (mean age 48 years). Linear regression models, controlling for intracranial volume, sex, education, and age, tested associations between PA and gray matter volumes of hippocampi and total brain in the 2 groups. For the T1D group, models further controlled for hyperglycemia and glucose disposal rate, a measure of insulin sensitivity. Results: PA was significantly lower in the T1D than in the non-T1D group (median [interquartile range] 952 kcal [420–2,044] vs 1,614 kcal [588–3,091], respectively). Higher PA was significantly associated with larger hippocampi for T1D, but not for non-T1D (standardized β [p values] from regression models adjusted for intracranial volume, sex, age, and education: 0.270 [p < 0.001] and 0.098 [p = 0.12], respectively). Neither hyperglycemia nor glucose disposal rate substantially modified this association. Relationships between PA and total brain gray matter volume were similar. Conclusions: A cross-sectional association between higher PA and larger hippocampi is already detectable by middle age for these patients with T1D, and it appears robust to chronic hyperglycemia and insulin sensitivity. Proof-of-concept studies should investigate whether increasing PA preserves hippocampal volume and the mechanisms underlying the effects of PA on hippocampal volume.
Behavioural and neural sequelae of stressor exposure are not modulated by controllability in females

The degree of behavioural control that an organism has over a stressor is a potent modulator of the stressor's impact; controllable stressors produce none of the neurochemical and behavioural sequelae that occur if the stressor is uncontrollable. Research demonstrating the importance of control and the neural mechanisms responsible has been conducted almost entirely with male rats. It is unknown if behavioural control is stress blunting in females, and whether or not a similar resilience circuitry is engaged. Female rats were exposed to controllable, yoked uncontrollable or no tailshock. In separate experiments, behavioural (juvenile social exploration, fear and shuttle box escape) and neurochemical (activation of dorsal raphe serotonin and dorsal raphe‐projecting prelimbic neurons) outcomes, which are sensitive to the dimension of control in males, were assessed. Despite successful acquisition of the controlling response, behavioural control did not mitigate dorsal raphe serotonergic activation and behavioural outcomes induced by tailshock, as it does in males. Moreover, behavioural control failed to selectively engage prelimbic cells that project to the dorsal raphe as in males. Pharmacological activation of the prelimbic cortex restored the stress‐buffering effects of control. Collectively, the data demonstrate stressor controllability phenomena are absent in females and that the protective prelimbic circuitry is present but not engaged. Reduced benefit from coping responses may represent a novel approach for understanding differential sex prevalence in stress‐related psychiatric disorders.
Dissecting seed dormancy and germination in Aquilegia barbaricina, through thermal kinetics of embryo growth.

Threshold-based thermal time models provide insight into the physiological switch from the dormant to the non-dormant germinating seed. This approach was used to quantify the different growth responses of the embryo of seeds purported to have morphophysiological dormancy (MPD) through the complex phases of dormancy release and germination. Aquilegia barbaricina seeds were incubated at constant temperatures (10-25 °C) and 25/10 °C, without pre-treatment, after warm+cold stratification (W+C) and GA3 treatment. Embryo growth was assessed and the time of testa and endosperm rupture scored. Base temperatures (Tb ) and thermal times for 50% (θ50 ) of embryo growth and seed germination were calculated. W+C enabled slow embryo growth. W+C and GA3 promoted rapid embryo growth and subsequent radicle emergence. The embryo internal growth base temperature (Tbe ) was ca. 5 °C for W+C and GA3 -treated seeds. GA3 treatment also resulted in similar Tb estimates for radicle emergence. The thermal times for embryo growth (θe50 ) and germination (θg50 ) were four- to six-fold longer in the presence of GA3 compared to W+C. A. barbaricina is characterised by a multi-step seed germination. The slow embryo growth during W+C reflects continuation of the maternal programme of development, whilst the thermal kinetics of both embryo and radicle growth after the removal of physiological dormancy are distinctly different. The effects of W+C on the multiphasic germination response in MPD seeds are only partially mimicked by 250 mg·l-1 GA3 . The thermal time approach could be a valid tool to model thermal kinetics of embryo growth and radicle protrusion.
Ventral Pallidum Encodes Contextual Information and Controls Aversive Behaviors

Abstract Successful avoidance of aversive outcomes is crucial for the survival of animals. Although accumulating evidence indicates that an indirect pathway in the basal ganglia is involved in aversive behavior, the ventral pallidum (VP), which is an important component of this pathway, has so far been implicated primarily in appetitive behavior. In this study, we used single‐cell recordings and bicuculline (GABAA antagonist) injections to elucidate the role of VP both in the encoding of aversive context and in active avoidance. We found 2 populations of neurons that were preferentially activated by appetitive and aversive conditioned stimuli (CSs). In addition, VP showed appetitive and aversive outcome anticipatory activities. These activity patterns indicate that VP is involved in encoding and maintaining CS‐induced aversive contextual information. Furthermore, the disturbance of VP activity by bicuculline injection increased the number of error trials in aversive trials. In particular, the subjects released the response bar prematurely, showed no response at all, or failed to avoid the aversive outcome. Overall, these results suggest that VP plays a central role in controlling CS‐induced negative motivation to produce avoidance behavior.
“I couldn't even talk to the patient”: Barriers to communicating with cancer patients as perceived by nursing students

Communication is closely related to safe practice and patient outcomes. Given that most clinicians fall into routines when communicating with patients, it is important to address communication issues early. This study explores Taiwanese nursing students' experiences of communication with patients with cancer and their families. Senior nursing students who had cared for cancer patients were recruited to participate in focus group interviews. These semi-structured interviews were recorded and transcribed for content analysis. Among the 45 participants, about 36% of them never received any communication training. Up to 76% of the participants stated that their communication with cancer patients was difficult and caused them emotional stress. Subsequent data analysis revealed four themes: disengagement, reluctance, regression and transition. Students' negative communication experiences were related to the patients' terminally ill situation; the students' lack of training, low self-efficacy and power status, poor emotional regulation, and cultural considerations. The findings of this study provide a deeper understanding of nursing students' communication experiences in oncology settings within the cultural context. Early and appropriate communication training is necessary to help students regulate their emotions and establish effective communication skills. Further studies are needed to examine the relationship among students' emotional labour, communication skills and outcomes.
CNN oriented fast HEVC intra CU mode decision

The real-time requirements of hardwired HEVC encoder demand that, at the grain of coding tree unit (CTU), the maximum computation should be reduced by a fast CU mode decision algorithm. In addition, to realize the parallel rate-distortion optimization (RDO) of different CU modes, the current CU mode decision should not use the auxiliary information from other CU modes. Considering the above constraints, we applied convolutional neural network (CNN) to analyze the textures of source picture blocks, and then reduce the maximum number of CU modes, which will undergo the exhaustive RDO. In the CNN architecture design, we introduced the quantization parameter by considering the effect of quantization to the coding costs. We further optimized the CNN training strategy to improve the prediction accuracy. Experimental results demonstrated that, the proposed algorithm can save 63% Intra encoding time at the cost of the averaged 2.66% BDBR increase.
Modulation of the photoluminescence in carbon dots through surface modification: from mechanism to white light-emitting diodes

Carbon dots (CDs) have emerged as a new type of fluorescent material because of their unique optical advantages, such as high photoluminescence quantum yields (QYs), excellent photo-stability, excitation-dependent emissions, and low toxicity. However, the photoluminescence mechanism for CDs remains unclear, which limits their further practical application. Here, CDs were synthesized via a solvothermal route from citric acid and urea. Through the oxidation and reduction treatment of pristine CDs, the origin of the photoluminescence and the involved mechanism were revealed. We found that the blue/green/red emissions originated from three diverse emitting states, i.e. the intrinsic state, and C=O- and C=N-related surface states, respectively. Based on the as-prepared CDs, a pH sensor depending on the radiometric luminescence detection was developed. Furthermore, we constructed CD/PVP (PVP, polyvinylpyrrolidone) composite films, which exhibited white light emission with photoluminescence QYs of 15.3%. The white light emission with different correlated color temperatures (CCTs), from 4807 K to 3319 K, was obtained by simply changing the amount of PVP solution. Benefiting from the white light-emitting solid-state films, single-component white light-emitting diodes were fabricated with an average color rendering index value (Ra) of 80.0, luminous efficiency of 10.2 lm W−1, and good working stability, thus indicating a promising potential for practical lighting applications.