Miracle-dz/UniFAR-FTUs huggingface dataset:
Reproducing human and cross-species drug toxicities using a Liver-Chip

A rat, dog, and human Liver-Chip designed using microengineered Organs-on-Chips technology recapitulates species-specific drug toxicities. Spotting species-specific toxicity Candidate drug testing using standard preclinical models cannot accurately predict which compounds are likely to cause drug-induced liver injury in humans. To improve selection of promising drug candidates, Jang et al. developed a Liver-Chip consisting of rat, dog, or human hepatocytes, endothelial cells, Kupffer cells, and stellate cells. Using the microfluidic chips, the authors confirmed mechanism of action of several known hepatotoxic drugs and an experimental compound. A second experimental compound that induced fibrosis in a rat Liver-Chip did not alter hepatocyte function in human chips, whereas a third compound demonstrated increased toxicity in a dog Liver-Chip. Results support using multispecies chips to identify species-specific differences in drug metabolism and toxicity. Nonclinical rodent and nonrodent toxicity models used to support clinical trials of candidate drugs may produce discordant results or fail to predict complications in humans, contributing to drug failures in the clinic. Here, we applied microengineered Organs-on-Chips technology to design a rat, dog, and human Liver-Chip containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, with or without Kupffer cells and hepatic stellate cells, cultured under physiological fluid flow. The Liver-Chip detected diverse phenotypes of liver toxicity, including hepatocellular injury, steatosis, cholestasis, and fibrosis, and species-specific toxicities when treated with tool compounds. A multispecies Liver-Chip may provide a useful platform for prediction of liver toxicity and inform human relevance of liver toxicities detected in animal studies to better determine safety and human risk.
RNA-Seq-Based Comparative Transcriptome Analysis Highlights New Features of the Heat-Stress Response in the Extremophilic Bacterium Deinococcus radiodurans

Deinococcus radiodurans is best known for its extraordinary resistance to diverse environmental stress factors, such as ionizing radiation, ultraviolet (UV) irradiation, desiccation, oxidation, and high temperatures. The heat response of this bacterium is considered to be due to a classical, stress-induced regulatory system that is characterized by extensive transcriptional reprogramming. In this study, we investigated the key functional genes involved in heat stress that were expressed and accumulated in cells (R48) following heat treatment at 48 °C for 2 h. Considering that protein degradation is a time-consuming bioprocess, we predicted that to maintain cellular homeostasis, the expression of the key functional proteins would be significantly decreased in cells (RH) that had partly recovered from heat stress relative to their expression in cells (R30) grown under control conditions. Comparative transcriptomics identified 15 genes that were significantly downregulated in RH relative to R30, seven of which had previously been characterized to be heat shock proteins. Among these genes, three hypothetical genes (dr_0127, dr_1083, and dr_1325) are highly likely to be involved in response to heat stress. Survival analysis of mutant strains lacking DR_0127 (a DNA-binding protein), DR_1325 (an endopeptidase-like protein), and DR_1083 (a hypothetical protein) showed a reduction in heat tolerance compared to the wild-type strain. These results suggest that DR_0127, DR_1083, and DR_1325 might play roles in the heat stress response. Overall, the results of this study provide deeper insights into the transcriptional regulation of the heat response in D. radiodurans.
Dysregulated Iron Metabolism-Associated Dietary Pattern Predicts an Altered Body Composition and Metabolic Syndrome

Diet plays an important role in the development of obesity and may contribute to dysregulated iron metabolism (DIM). A cross-sectional survey of 208 adults was conducted in Taipei Medical University Hospital (Taipei, Taiwan). A reduced-rank regression from 31 food groups was used for a dietary pattern analysis. DIM was defined as at least four of the following criteria: serum hepcidin (men >200 ng/mL and women >140 ng/mL), hyperferritinemia (serum ferritin of >300 ng/mL in men and >200 ng/mL in women), central obesity, non-alcoholic fatty liver disease, and two or more abnormal metabolic profiles. Compared to non-DIM patients, DIM patients were associated with an altered body composition and had a 4.52-fold (95% confidence interval (CI): (1.95–10.49); p < 0.001) greater risk of metabolic syndrome (MetS) after adjusting for covariates. A DIM-associated dietary pattern (high intake of deep-fried food, processed meats, chicken, pork, eating out, coffee, and animal fat/skin but low intake of steamed/boiled/raw foods and dairy products) independently predicted central obesity (odds ratio (OR): 1.57; 95% CI: 1.05–2.34; p < 0.05) and MetS (OR: 1.89; 95% CI: 1.07–3.35; p < 0.05). Individuals with the highest DIM pattern scores (tertile 3) had a higher visceral fat mass (%) (β = 0.232; 95% CI: 0.011–0.453; p < 0.05) but lower skeletal muscle mass (%) (β = −1.208; 95% CI: −2.177–−0.239; p < 0.05) compared to those with the lowest DIM pattern scores (tertile 1). In conclusion, a high score for the identified DIM-associated dietary pattern was associated with an unhealthier body composition and a higher risk of MetS.
Prediction of PD-L1 inhibition effects for HIV-infected individuals

The novel therapies with immune checkpoint inhibitors hold great promises for patients with chronic virus infections and cancers. This is based mainly on the partial reversal of the exhausted phenotype of antigen-specific cytotoxic CD8 T cells (CTL). Recently, we have shown that the restoration of HIV-specific T cell function depends on the HIV infection stage of an infected individual. Here we aimed to answer two fundamental questions: (i) Can one estimate growth parameters for the HIV-specific proliferative responsiveness upon PD-L1 blockade ex vivo? (ii) Can one use these parameter estimates to predict clinical benefit for HIV-infected individuals displaying diverse infection phenotypes? To answer these questions, we first analyzed HIV-1 Gag-specific CD8 T cell proliferation by time-resolved CFSE assays and estimated the effect of PD-L1 blockade on division and death rates, and specific precursor frequencies. These values were then incorporated into a model for CTL-mediated HIV control and the effects on CTL frequencies, viral loads and CD4 T cell counts were predicted for different infection phenotypes. The biggest absolute increase in CD4 T cell counts was in the group of slow progressors while the strongest reduction in virus loads was observed in progressor patients. These results suggest a significant clinical benefit only for a subgroup of HIV-infected individuals. However, as PD1 is a marker of lymphocyte activation and expressed on several lymphocyte subsets including also CD4 T cells and B cells, we subsequently examined the multiple effects of anti-PD-L1 blockade beyond those on CD8 T cells. This extended model then predicts that the net effect on HIV load and CD4 T cell number depends on the interplay between positive and negative effects of lymphocyte subset activation. For a physiologically relevant range of affected model parameters, PD-L1 blockade is likely to be overall beneficial for HIV-infected individuals.
Fundamental Significance of Physical Activity for Seniors’ Health

Physical activity is a basic component of geriatric prevention. Lower physical activity of seniors is a cause and effect of many chronic conditions, e.g. type 2 diabetes, obesity, diseases of musculoskeletal system or cancer. This paper analyzes Polish and international literature in terms of significance of physical activity for keeping and improving health of seniors. Numerous studies carried out at large research facilities all over the world proved that taking up physical activity by seniors is one of the key factors for ensuring better health. It is, however, important to precede workout with medical examination. After that, suitable exercises, their frequency, duration and intensity need to be determined. The conclusion of this paper is as follows: regular physical activity improves effectiveness of preventive measures and treatments related to diseases such as cardiovascular disease; it also reduces mortality rate and prolongs the period of physical and mental activity of seniors.
Effect of Using Triclosan-Impregnated Polyglactin Suture to Prevent Infection of Saphenectomy Wounds in CABG: A Prospective, Double-Blind, Randomized Clinical Trial

Objective To evaluate the efficacy of triclosan-coated suture for the reduction of infection in saphenectomy wounds of patients undergoing coronary artery bypass graft (CABG) surgery. Methods A total of 508 patients who underwent saphenectomy in CABG surgery were included in a prospective, randomized, double-blind trial from February/2011 to June/2014. Patients were randomized into the triclosan-coated suture group (n= 251) and the conventional non-antibiotic suture group (n=257). Demographic (gender and age), clinical (body mass index, diabetes, and use of analgesics), and intraoperative (cardiopulmonary bypass and cross-clamp times) variables and those related to the saphenectomy wound (pain, dehiscence, erythema, infection, necrosis, and hyperthermia) were measured and analyzed. Results Of the 508 patients who underwent saphenectomy, 69.9% were males and 40.2% were diabetic. Thirty-three (6.5%) patients presented infection: 13 (5.3%) with triclosan and 20 (7.9%) with conventional suture (P=0.281). Among diabetic patients (n=204), triclosan suture was used in 45.1% with four cases of infection; conventional suture was used in 54.9% of them, with 11 cases of infection. Most patients (94.3%) underwent on-pump CABG. Wound pain was observed in 9.9% of patients with triclosan-coated suture and in 17.9% with conventional suture (P=0.011). Wound hyperthermia was found in 1.6% of patients with triclosan-coated suture and in 5.4% of those with conventional suture (P=0.028). Conclusion Triclosan-coated suture shows lower infection rate in saphenectomy of patients undergoing CABG, although the differences were not statistically significant. Pain and wound hyperthermia were less frequent in patients with triclosan-coated sutures compared with conventional sutures.
Clinical study of 100 cases of hoarseness of voice: a hospital based study

<p class="abstract"><strong>Background:</strong> Hoarseness is defined as roughness of voice resulting from variations of periodicity or intensity of consecutive sound waves. Hoarseness is a symptom not a disease. </p><p class="abstract"><strong>Methods:</strong> The present study was carried out in the Department of ENT and Head and Neck Surgery, SMGS Hospital, Jammu over a period of 2 years from March 2016 to February 2018. During this period the patients who presented with hoarseness of voice were evaluated. </p><p class="abstract"><strong>Results:</strong> Total 100 cases were studied. Average age group was found to be between 15-85 years. The number of female patients were 36 (36%) and male 64 (64%). In the present series the most common lesion was vocal nodule (30%) followed by vocal polyp (23%), squamous cell carcinoma (16%), papilloma (10%), Reinkes oedema (9%), keratosis (7%), vocal cord paralysis (4%) and laryngeal tuberculosis (1%). </p><p class="abstract"><strong>Conclusions:</strong> Hoarseness is a common symptom of laryngeal dysfunction. The micro laryngeal surgery is a minimally invasive procedure used to correct voice disorder or other problems affecting the larynx. </p>
Kindergarten antecedents of the developmental course of active and passive parental monitoring strategies during middle childhood and adolescence

Abstract Decades of research have highlighted the significance of parenting in children's development, yet few studies have focused specifically on the development of parental monitoring strategies in diverse families living in at-risk neighborhoods. The current study investigated the development of active (i.e., parental discussions and curfew rules) and passive (i.e., child communication with parents) parental monitoring strategies across different developmental periods (middle childhood and adolescence; Grades 4–5 and 7–11) as well as individual (child, parent), family, and contextual antecedents (measured in kindergarten) of this parenting behavior. Using an ecological approach, this study evaluated longitudinal data from 753 participants in the Fast Track Project, a multisite study directed at the development and prevention of conduct problems in at-risk children. Latent trajectory modeling results identified little to no mean growth in these monitoring strategies over time, suggesting that families living in at-risk environments may engage in consistent levels of monitoring strategies to ensure children's safety and well-being. Findings also identified several kindergarten antecedents of the growth factors of these parental monitoring strategies including (a) early child conduct problems; (b) parental warmth/involvement, satisfaction, and efficacy; and (c) parent–child relationship quality. These predictive effects largely highlighted the important role of early parenting behaviors on later levels of and growth in parental monitoring strategies. These findings have important implications for potential prevention and intervention targets to promote the development of parental monitoring strategies among families living in more at-risk contexts.
Perinatal Outcome and Long-Term Gastrointestinal Morbidity of Offspring of Women with Celiac Disease

The aim of this study was to evaluate perinatal outcome and long-term offspring gastrointestinal morbidity of women with celiac disease. Perinatal outcomes, as well as long-term gastrointestinal morbidity of offspring of mothers with and without celiac disease were assessed. The study groups were followed until 18 years of age for gastrointestinal-related morbidity. For perinatal outcomes, generalized estimation equation (GEE) models were used. A Kaplan–Meier survival curve was used to compare cumulative incidence of long-term gastrointestinal morbidity, and Cox proportional hazards models were constructed to control for confounders. During the study period, 243,682 deliveries met the inclusion criteria, of which 212 (0.08%) were to mothers with celiac disease. Using GEE models, maternal celiac disease was noted as an independent risk factor for low birth weight and cesarean delivery. Offspring born to mothers with celiac disease had higher rates of gastrointestinal related morbidity (Kaplan–Meier log rank test p < 0.001). Using a Cox proportional hazards model, being born to a mother with celiac disease was found to be an independent risk factor for long-term gastrointestinal morbidity of the offspring. Pregnancy of women with celiac disease is independently associated with adverse perinatal outcome as well as higher risk for long-term gastrointestinal morbidity of offspring.
Tari Pendet News on Metro TV in 2009: Reviving National Sentiment

This paper contains idea that sensationality could also appear in the news of bilateral misunderstanding. In this study, I assume that rather than framing the international public issues into subtantial frames, sensational news of international affairs would merely expose the news into emotionaly-sensitive or provocative frames of involving countries. In addition, I presume that the sensationality of international newscast could find its source in the emotional aspect of cultural identity relations between the relating countries. If the assumptions are confirmed, I would like to emphasize also what kind of sensational frames are being used and the logic order of the frames. I apply qualitative frame analysis approach to prove whether Metro TV newscast frame the news of ‘confrontations’ between Indonesia and Malaysia in the case of Pendet Dance usage in Malaysian advertisements whether in sensational frames or whether not. Employing Pan method, I identify four structural dimensions affecting frame formations: syntax, script, thematic, and rhetoric of the narrative. In the other hand, I use interpretation method to analyzing voice, facial expressions, visual symbols and camera techniques which are parts of televison news text. The research found that sensationalism of Metro TV news about ‘Tari Pendet controversy’ is embodied through national sentiment frame and with several news framing that employed text features leading to sensationalism such as partiality, imbalance proportion, inaccurate information, labelisation that leads to negative connotation, and judgemental non-verbal expressions.
Diversity, distribution and dynamics of large trees across an old-growth lowland tropical rain forest landscape

Large trees, here defined as ≥60 cm trunk diameter, are the most massive organisms in tropical rain forest, and are important in forest structure, dynamics and carbon cycling. The status of large trees in tropical forest is unclear, with both increasing and decreasing trends reported. We sampled across an old-growth tropical rain forest landscape at the La Selva Biological Station in Costa Rica to study the distribution and performance of large trees and their contribution to forest structure and dynamics. We censused all large trees in 238 0.50 ha plots, and also identified and measured all stems ≥10 cm diameter in 18 0.50 ha plots annually for 20 years (1997–2017). We assessed abundance, species diversity, and crown conditions of large trees in relation to soil type and topography, measured the contribution of large trees to stand structure, productivity, and dynamics, and analyzed the decadal population trends of large trees. Large trees accounted for 2.5% of stems and ~25% of mean basal area and Estimated Above-Ground Biomass, and produced ~10% of the estimated wood production. Crown exposure increased with stem diameter but predictability was low. Large tree density was about twice as high on more-fertile flat sites compared to less fertile sites on slopes and plateaus. Density of large trees increased 27% over the study interval, but the increase was restricted to the flat more-fertile sites. Mortality and recruitment differed between large trees and smaller stems, and strongly suggested that large tree density was affected by past climatic disturbances such as large El Niño events. Our results generally do not support the hypothesis of increasing biomass and turnover rates in tropical forest. We suggest that additional landscape-scale studies of large trees are needed to determine the generality of disturbance legacies in tropical forest study sites.
The influence of 12 weeks application of dynamic and static stretching on the range of joint mobility for the group of soccer players

Background & Study Aim: The optimal level of flexibility helps to streamline the movement, thereby becoming one of the important components of sports performance. The aim of this study is the effect of six weeks applications of dynamic and static stretching on active mobility of the hip joint in selected soccer players. Material & Methods: To obtain the data used a stretching program developer focusing on dynamic or static stretching. Two selected male soccer player groups were during the intervention period of six weeks evaluated for changes in the range of joint mobility. Static stretching program we applied to the players (aged 19-30 years) of TJ Krupka three times a week in the final part of the training unit for six weeks. Dynamic stretching program was applied to players (agend 18-29 years) TJ Česká Lípa three times a week twelve minutes in the warm up of the training unit for six weeks. Active mobility of the hip joint – flexion and extension of both legs was evaluated before and after the stretching program. Results: Statistically significant differences in the active range of motion when exposed to static and dynamic stretching with dominant and non-dominant leg. Motion interventions using dynamic stretching has proven significantly more effective for the dominant limb and with the non-dominant lower limb, rather than static stretching method. Conclusions: Static stretching program has proven suitable for use in the final part of the training unit, which is used for general calming of the body and the release of a muscle tension. Dynamic stretching program, by contrast, proved to be suitable for inclusion in the warm-up of the training unit. In terms of increasing the range of motion in the monitored joint-muscular unit, the dynamic stretching during prolonged application proved more effective than using static stretching. Therefore, we recommend such a methodology.
Flexible UHF RFID Tag for Blood Tubes Monitoring

Low-cost and flexible radio frequency identification (RFID) tag for automatic identification, tracking, and monitoring of blood products is in great demand by the healthcare industry. A robust performance to meet security and traceability requirements in the different blood sample collection and analysis centers is also required. In this paper, a novel low-cost and flexible passive RFID tag is presented for blood sample collection tubes. The tag antenna is based on two compact symmetrical capacitive structures and works at the ultra-high frequency (UHF) European band (865 MHz–868 MHz). The tag antenna is designed considering the whole dielectric parameters such as the blood, substrate and tube. In this way, it operates efficiently in the presence of blood, which has high dielectric permittivity and loss. Measurement results of the proposed tag have confirmed simulation results. The measured performance of the tag shows good matching in the desired frequency band, leading to reading ranges up to 2.2 m, which is 4.4 times higher than typical commercial tags. The potential of this tag as a sensor to monitor the amount of blood contained in clinic tubes is also demonstrated. It is expected that the proposed tag can be useful and effective in future RFID systems to introduce security and traceability in different blood sample collection and analysis centers.
Characterization of striatal phenotypes in heterozygous Disc1 mutant mice, a model of haploinsufficiency

Disrupted‐in‐Schizophrenia 1 (DISC1) is a susceptibility gene for several psychiatric illnesses. To study the pathogenesis of these disorders, we generated Disc1 mutant mice by introducing the 129S6/SvEv 25‐bp deletion Disc1 variants into the C57BL/6J strain. In this study, we used heterozygous Disc1 mutant (Het) mice to evaluate the DISC1 haploinsufficiency model of schizophrenia. No changes in locomotor behaviors were observed in Het mice; however, after amphetamine injection, greater locomotor activity was observed in Het mice compared with wild‐type (WT) mice. Moreover, amphetamine‐induced elevations of c‐Fos expression and dopamine level in the striatum were greater in Het mice than in WT controls, suggesting an altered dopaminergic regulation in the striatum of Het mice. Compared with those in WTs, the striatal protein levels of dopamine transporter and D2 dopamine receptor were increased in Het mice, while D1 dopamine receptor level was decreased. DISC1 interacting proteins, GSK3α and GSK3β, were downregulated in Het mice, whereas the levels of PDE4B and CREB were not altered. Morphologically, the complexities of striatal median spiny neurons (MSNs), parvalbumin‐positive interneurons and Iba1‐positive microglia were all decreased in Het mice. The density and head diameter of dendritic spines in the MSNs of Het mice were also reduced. Our results indicate that mice lacking one WT Disc1 allele are more sensitive to psychostimulant amphetamine challenge, which might be attributed to the altered structure and function of the striatal dopaminergic system. Here, we demonstrated striatal phenotypes in heterozygous Disc1 mutant mice, which could be a promising model of DISC1 haploinsufficiency.