Miracle-dz/UniFAR-FTUs huggingface dataset:
The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

Trypanosoma cruzi interacts with the different arms of the innate and adaptive host's immune response in a very complex and flowery manner. The history of host-parasite co-evolution has provided this protozoan with means of resisting, escaping or subverting the mechanisms of immunity and establishing a chronic infection. Despite many decades of research on the subject, the infection remains incurable, and the factors that steer chronic Chagas disease from an asymptomatic state to clinical onset are still unclear. As the relationship between T. cruzi and the host immune system is intricate, so is the amount and diversity of scientific knowledge on the matter. Many of the mechanisms of immunity are fairly well understood, but unveiling the factors that lead each of these to success or failure, within the coordinated response as a whole, requires further research. The intention behind this Review is to compile the available information on the different aspects of the immune response, with an emphasis on those phenomena that have been studied and confirmed in the human host. For ease of comprehension, it has been subdivided in sections that cover the main humoral and cell-mediated components involved therein. However, we also intend to underline that these elements are not independent, but function intimately and concertedly. Here, we summarize years of investigation carried out to unravel the puzzling interplay between the host and the parasite.
Achieving IT‐based synergies through regulation‐oriented and consensus‐oriented IT governance capabilities

This study aims at exploring the IT governance capabilities that enable organizations to achieve IT‐based synergies. Following existing work on the contextualization of theories and drawing on the resource‐based view of the firm (RBV), we develop an RBV of IT‐based synergies in two steps. First, we adopt existing context‐specific constructs and relationships from prior work on IT governance capabilities, IT relatedness, and synergies to develop a preliminary contextualization of the RBV. Second, to further refine our theoretical framework, we conduct an exploratory field study that includes interviews with 26 CIOs and other IT executives from 21 multibusiness firms. Our findings suggest that IT governance capabilities lead to IT‐based synergies through IT relatedness and business process relatedness. We found regulation‐oriented IT governance capabilities (IT roles and IT processes) to increase IT relatedness, while consensus‐oriented IT governance capabilities (IT groups and relational capabilities) had a positive effect on business process relatedness. Our results suggest that, in isolation, IT and business process relatedness lead to IT cost synergies, while collectively enabling IT‐induced business synergies. Our study is among the first to treat IT relatedness as an endogenous construct and to explicitly integrate business process relatedness into the IT governance domain. Our context‐specific decomposition of IT governance capabilities helps to better explain their links to IT and business process relatedness. These findings contribute to a better understanding of the tension between IT‐based synergies and business‐IT alignment. Decision‐makers are guided in developing IT governance capabilities to achieve IT‐based synergies.
Arginine-deprivation–induced oxidative damage sterilizes Mycobacterium tuberculosis

Significance Tuberculosis results in over 1.7 million deaths annually; this problem is worsened by the emergence of drug-resistant strains. New drugs and a better understanding of the mechanisms of existing interventions are needed to prevent the development of drug resistance. Reactive oxygen species (ROS)-mediated lethality by bactericidal drugs was observed in Mycobacterium tuberculosis (Mtb). Our studies demonstrate that arginine deprivation sterilizes for Mtb in vitro and in the host. Using several complementary approaches, we show that arginine deprivation leads to the depletion of thiols, accumulation of ROS, DNA damage, and rapid Mtb death. We propose enzymes in the de novo arginine biosynthesis pathway represent promising drug target candidates to be inhibited to treat Mtb and its drug-resistant strains. Reactive oxygen species (ROS)-mediated oxidative stress and DNA damage have recently been recognized as contributing to the efficacy of most bactericidal antibiotics, irrespective of their primary macromolecular targets. Inhibitors of targets involved in both combating oxidative stress as well as being required for in vivo survival may exhibit powerful synergistic action. This study demonstrates that the de novo arginine biosynthetic pathway in Mycobacterium tuberculosis (Mtb) is up-regulated in the early response to the oxidative stress-elevating agent isoniazid or vitamin C. Arginine deprivation rapidly sterilizes the Mtb de novo arginine biosynthesis pathway mutants ΔargB and ΔargF without the emergence of suppressor mutants in vitro as well as in vivo. Transcriptomic and flow cytometry studies of arginine-deprived Mtb have indicated accumulation of ROS and extensive DNA damage. Metabolomics studies following arginine deprivation have revealed that these cells experienced depletion of antioxidant thiols and accumulation of the upstream metabolite substrate of ArgB or ArgF enzymes. ΔargB and ΔargF were unable to scavenge host arginine and were quickly cleared from both immunocompetent and immunocompromised mice. In summary, our investigation revealed in vivo essentiality of the de novo arginine biosynthesis pathway for Mtb and a promising drug target space for combating tuberculosis.
Ego-depletion increases selfish decision making, but may also increase self-conflict and regret about those decisions

ABSTRACT The effect of ego-depletion on self-control conflict identification is the subject of ongoing debate with only limited and indirect empirical assessment. The present research used behavioral and self-report measures to test if ego-depletion affects self-control conflict identification across two studies: in an economic social dilemma game and a probe reaction task. In the social dilemma game, ego-depleted participants acted more selfishly, but also reported feeling more conflicted about their decisions and were more likely to go back and change choices they had made earlier in the game. These results replicated and extended earlier findings on ego-depletion and prosocial behavior. Study Two tested the effect of ego-depletion on self-control conflict identification using a probe recognition task designed to measure goal conflict accessibility, but found no significant effects of ego-depletion.
The rise of the rosette agent in Europe: An epidemiological enigma

International biodiversity assessments often overlook the role of emerging infectious pathogens in the decline of freshwater fish populations despite the many examples of emerging diseases in other more visible taxa on a global scale. Whilst the introduction of the rosette agent Sphaerothecum destruens in Europe remained an epidemiological enigma, recent findings have shown that this parasite arrived in Europe with the introduction of the healthy carrier Pseudorasbora parva from China nearly 60 years ago and its emergence went unnoticed for over 45 years despite its severe impact on European fish biodiversity. Recent reports on the host and pathogen phylogeny point towards an ancient host-pathogen co-evolution with direct implications on disease risk. Here, we postulate that the observed rapid population decline of native fish species following their infection with virulent strains of S. destruens has underpinned the rapid establishment of P. parva populations during the invasion process. We reviewed the existing evidence supporting the claim of an S. destruens' emergence worldwide and also suggest that the origin of the US strains is to be found among contaminated Asian Oncorhynchus tshawytscha living in sympatry with native Asian P. parva population. Finally, several important preventative steps are suggested as a way to manage the impact of S. destruens on local fish communities.
Induction of p53 Phosphorylation at Serine 20 by Resveratrol Is Required to Activate p53 Target Genes, Restoring Apoptosis in MCF-7 Cells Resistant to Cisplatin

Resistance to cisplatin (CDDP) is a major cause of cancer treatment failure, including human breast cancer. The tumor suppressor protein p53 is a key factor in the induction of cell cycle arrest, DNA repair, and apoptosis in response to cellular stimuli. This protein is phosphorylated in serine 15 and serine 20 during DNA damage repair or in serine 46 to induce apoptosis. Resveratrol (Resv) is a natural compound representing a promising chemosensitizer for cancer treatment that has been shown to sensitize tumor cells through upregulation and phosphorylation of p53 and inhibition of RAD51. We developed a CDDP-resistant MCF-7 cell line variant (MCF-7R) to investigate the effect of Resv in vitro in combination with CDDP over the role of p53 in overcoming CDDP resistance in MCF-7R cells. We have shown that Resv induces sensitivity to CDDP in MCF-7 and MCF-7R cells and that the downregulation of p53 protein expression and inhibition of p53 protein activity enhances resistance to CDDP in both cell lines. On the other hand, we found that Resv induces serine 20 (S20) phosphorylation in chemoresistant cells to activate p53 target genes such as PUMA and BAX, restoring apoptosis. It also changed the ratio between BCL-2 and BAX, where BCL-2 protein expression was decreased and at the same time BAX protein was increased. Interestingly, Resv attenuates CDDP-induced p53 phosphorylation in serine 15 (S15) and serine 46 (S46) probably through dephosphorylation and deactivation of ATM. It also activates different kinases, such as CK1, CHK2, and AMPK to induce phosphorylation of p53 in S20, suggesting a novel mechanism of p53 activation and chemosensitization to CDDP.
Burden of disease associated with a COPD eosinophilic phenotype

Purpose Based on blood and sputum samples, up to 40% of patients with COPD have eosinophilic inflammation; however, there is little epidemiology data characterizing the health care burden within this sub-population. Given that COPD-attributable medical costs in the USA are predicted to approach $50 billion by 2020, we analyzed the effect of blood eosinophil counts and exacerbations on health care resource utilization and costs. Patients and methods This cross-sectional study used electronic medical records and insurance claims data from the Reliant Medical Group (January 2011–December 2015). Eligible patients were ≥40 years of age, continuously enrolled during the year of interest (2012, 2013, 2014, or 2015), had ≥1 COPD-related code in the preceding year, and documented maintenance therapy use. Patients with ≥1 blood eosinophil count recorded were stratified into 2 cohorts: <150 cells/µL and ≥150 cells/µL. Endpoints included demographics, clinical characteristics, health care resource utilization, and costs. The impact of blood eosinophil count and exacerbation patterns on health care resource utilization and costs was assessed with multivariate analyses. Results On average, 2,832 eligible patients were enrolled annually, of whom ~28% had ≥1 eosinophil count recorded during the year. The ≥150 cells/µL cohort had numerically higher all-cause and COPD-related health care resource utilization and cost each year compared with the <150 cells/µL cohort, but varied by service and year. Among patients with exacerbations, the ≥150 cells/µL cohort exhibited significantly higher COPD-related costs compared with the <150 cells/µL cohort. Conclusion Blood eosinophil counts may be a useful biomarker for burden of disease in a subgroup of patients with COPD.
Adenosquamous carcinoma of the lung

Adenosquamous carcinoma of the lung (ASC), a relatively rare subtype of non-small-cell lung cancer, is defined as a malignancy containing components of lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SCC). Although ASC has biological characteristics of ADC and SCC, it is not by any means a simple hybrid of two components above. It is extremely difficult to diagnose preoperatively; pathology of surgically resected gross specimen is the most effective means for adequate diagnosis of ASC. Platinum-based postoperative adjuvant chemotherapy for at least four cycles can significantly improve the survival in stage III patients with ASC. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib and gefitinib can be the effective therapeutic strategies for advanced EGFR-mutant ASC. The studies of crizotinib in the treatment of patients with ASC are very limited. Immune checkpoint blockade therapy may be a potential treatment choice for ASC patients.
Which neoadjuvant chemotherapy regimen should be recommended for patients with advanced nasopharyngeal carcinoma?

Background: The clinical application has widespread disagreement on the different regimens of neoadjuvant chemotherapy (NCT) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). We conducted a network meta-analysis (NMA) to evaluate the efficacy of the different NCT regimens in the treatment of NPC. Methods: A systematic literature search was performed using PubMed, Embase, and Cochran Library. Totally, 31 randomized controlled trials (RCTs) (n = 4062) met study selection criteria and were incorporated in this NMA study. Results: Our study showed that certain NCT regimens improved the prognosis of patients, and found out the relative best solution for each endpoint, such as paclitaxel, carboplatin, and gemcitabine for 1-year overall survival (OS) rate, cisplatin, calcium folinate, and 5-fluorouracil for 2-year OS rate, vinorelbine and cisplatin (NP) for 3-year OS rate, cyclophosphamide, cisplatin, and 5-fluorouracil for 5-year OS rate, NP for complete remission rate, cisplatin and gemcitabine for overall remission rate of the primary tumor. In addition, for certain grade 3 and above toxicity, the results of the NMA reflected certain NCT regimens can reduce toxicity of chemoradiotherapy (CRT) to a minimum, such as NP for anemia, mucositis, and thrombocytopenia, paclitaxel, epirubicin, and cisplatin for neutropenia and skin toxicity. Conclusion: Our NMA showed that certain cisplatin-based NCT regimens improved the prognosis of patients with NPC and reduced the toxicity of CRT. However, in view of survival rate and response rate, the best NCT regimen is not entirely consistent. Therefore, which NCT regimen will benefit most patients will need further explored.
The Defense Response of Nicotiana benthamiana to Peanut Stunt Virus Infection in the Presence of Symptom Exacerbating Satellite RNA

Peanut stunt virus (PSV) is a widespread pathogen infecting legumes. The PSV strains are classified into four subgroups and some are defined by the association of satellite RNAs (satRNAs). In the case of PSV, the presence of satRNAs alters the symptoms of disease in infected plants. In this study, we elucidated the plant response to PSV-G strain, which occurs in natural conditions without satRNA. However, it was found that it might easily acquire satRNA, which exacerbated pathogenesis in Nicotiana benthamiana. To explain the mechanisms underlying PSV infection and symptoms exacerbation caused by satRNA, we carried out transcriptome profiling of N. benthamiana challenged by PSV-G and satRNA using species-specific microarrays. Co-infection of plants with PSV-G + satRNA increased the number of identified differentially expressed genes (DEGs) compared with the number identified in PSV-G-infected plants. In both treatments, the majority of up-regulated DEGs were engaged in translation, ribosome biogenesis, RNA metabolism, and response to stimuli, while the down-regulated DEGs were required for photosynthesis. The presence of satRNA in PSV-G-infected plants caused different trends in expression of DEGs associated with phosphorylation, ATP binding, and plasma membrane.
Adaptive fault-tolerant control for a class of uncertain switched nonlinear systems with multiple state time delays

ABSTRACT This paper studies the adaptive fault-tolerant control problem for a class of uncertain switched nonlinear time-delayed systems with mismatching parameter uncertainties, nonlinear functions, external disturbances and actuator failures. By using the estimations of the unknown upper bounds of uncertain parameters, the novel adaptive laws based on state-dependent switching strategy are constructed, and then the effects of multiple state time delays and actuator failures can be eliminated. Moreover, by using the robust technique and multiple Lyapunov functions method, the designed controller can guarantee the asymptotic stability and the desired performances of the switched closed-loop systems in the presence of parameter uncertainties and time-delayed perturbation simultaneously. Finally, simulation results are provided to show the efficiency of the proposed robust adaptive control scheme.
Effect of dietary supplementation of cinnamon oil and sodium butyrate on carcass characteristics and meat quality of broiler chicken

Aim: An in vivo experiment was conducted to investigate the effect of supplementation of cinnamon oil (CO) and sodium butyrate on carcass characteristics and meat quality of broiler chicken compared with the antibiotic supplementation. Materials and Methods: A biological experiment was carried out with 216-day-old Vencobb-400 broiler chicks randomly distributed to six experimental treatments with six replicates, each replicate containing six chicks with equal numbers of male and female chicks. The experimental diets were prepared with isocaloric and isonitrogenous basis. The experimental groups, namely control (T1), control with antibiotic (T2), control with CO at 250 mg/kg and coated sodium butyrate (CSB) either at 0.09 (T3) or 0.18% (T4), and control with CO at 500 mg/kg and CSB either at 0.09 (T5) or 0.18% (T6). The trial was carried out in deep litter pen for 35 days. The carcass characteristics such as ready to cooked yield, eviscerated weight, heart, liver, gizzard, giblet, and abdominal fat percent in slaughtered birds and meat quality properties such as pH, water-holding capacity (WHC), tyrosine, shear force, cooking loss, thiobarbituric acid, sensory characteristics, and muscle cholesterol in breast muscle samples were evaluated. Results: The carcass characteristics such as ready-to-cook yield, eviscerated weight, and weight of heart, liver, gizzard, giblet, and abdominal fat as a percent of live body weight were not influenced by supplementation of CO and CSB at the levels attempted or by antibiotic supplementation in broilers. The pH, cooking loss, shear force and WHC of meat, appearance, flavor, texture, mouth coating, juiciness and overall acceptability of meat were not influenced by the supplementation of different levels of CO and CSB or by antibiotic supplementation but decreased meat cholesterol level in broilers. Conclusion: The results indicated that the supplementation of CO and CSB in broiler diet did not alter the carcass characteristics and meat quality parameters except meat cholesterol content in broilers.
Early and late do-not-resuscitate (DNR) decisions in patients with terminal COPD: a retrospective study in the last year of life

Purpose The unpredictable trajectory of COPD can present challenges for patients when faced with a decision regarding a do-not-resuscitate (DNR) directive. The current retrospective analysis was conducted to investigate factors associated with an early DNR decision (prior to last hospital admission) and differences in care patterns between patients who made DNR directives early vs late. Patients and methods Electronic health records (EHR) were reviewed from 271 patients with terminal COPD who died in a teaching hospital in Taiwan. Clinical parameters, patterns of DNR decisions, and medical utilization were obtained. Those patients who had a DNR directive earlier than their last (terminal) admission were defined as “Early DNR” (EDNR). Results A total of 234 (86.3%) patients died with a DNR directive, however only 30% were EDNR. EDNR was associated with increased age (OR=1.07; 95% CI: 1.02–1.12), increased ER visits (OR=1.22; 95% CI: 1.10–1.37), rapid decline in lung function (OR=3.42; 95% CI: 1.12–10.48), resting heart rate ≥100 (OR=3.02; 95% CI: 1.07–8.51), and right-sided heart failure (OR=2.38; 95% CI: 1.10–5.19). The median time period from a DNR directive to death was 68.5 days in EDNR patients and 5 days in “Late DNR” (LDNR) patients, respectively (P<0.001). EDNR patients died less frequently in the intensive care unit (P<0.001), received less frequent mechanical ventilation (MV; P<0.001), more frequent non-invasive MV (P=0.006), and had a shorter length of hospital stay (P=0.001). Conclusions Most patients with terminal COPD had DNR directives, however only 30% of DNR decisions were made prior to their last (terminal) hospital admission. Further research using these predictive factors obtained from EHR systems is warranted in order to better understand the relationship between the timing associated with DNR directive decision making in patients with terminal COPD.
Acute effects of meditation training on the waking and sleeping brain: Is it all about homeostasis?

Our recent finding of a meditation‐related increase in low‐frequency NREM sleep EEG oscillatory activities peaking in the theta‐alpha range (4–12 Hz) was not predicted. From a consolidated body of research on sleep homeostasis, we would expect a change peaking in slow wave activity (1–4 Hz) following an intense meditation session. Here we compared these changes in sleep with the post‐meditation changes in waking rest scalp power to further characterize their functional significance. High‐density EEG recordings were acquired from 27 long‐term meditators (LTM) on three separate days at baseline and following two 8‐hr sessions of either mindfulness or compassion‐and‐loving‐kindness meditation. Thirty‐one meditation‐naïve participants (MNP) were recorded at the same time points. As a common effect of meditation practice, we found increases in low and fast waking EEG oscillations for LTM only, peaking at eight and 15 Hz respectively, over prefrontal, and left centro‐parietal electrodes. Paralleling our previous findings in sleep, there was no significant difference between meditation styles in LTM as well as no difference between matched sessions in MNP. Meditation‐related changes in wakefulness and NREM sleep were correlated across space and frequency. A significant correlation was found in the EEG low frequencies (<12 Hz). Since the peak of coupling was observed in the theta‐alpha oscillatory range, sleep homeostatic response to meditation practice is not sufficient to explain our findings. Another likely phenomenon into play is a reverberation of meditation‐related processes during subsequent sleep. Future studies should ascertain the interplay between these processes in promoting the beneficial effects of meditation practice.