Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between Brain and Plasma Glutamine Levels in Healthy Young Subjects Investigated by MRS and LC/MS

Both glutamine (Gln) and glutamate (Glu) are known to exist in plasma and brain. However, despite the assumed relationship between brain and plasma, no studies have clarified the association between them. Proton magnetic resonance spectroscopy (MRS) was sequentially performed twice, with a 60-min interval, on 10 males and 10 females using a 3T scanner. Blood samples for liquid chromatography–mass spectrometry (LC/MS) to measure Gln and Glu concentrations in plasma were collected during the time interval between the two MRS sessions. MRS voxels of interest were localized at the posterior cingulate cortex (PCC) and cerebellum (Cbll) and measured by the SPECIAL sequence. Spearman’s correlation coefficient was used to examine the association between brain and plasma metabolites. The Gln concentrations in PCC (mean of two measurements) were positively correlated with Gln concentrations in plasma (p < 0.01, r = 0.72). However, the Glu concentrations in the two regions were not correlated with those in plasma. Consideration of the different dynamics of Gln and Glu between plasma and brain is crucial when addressing the pathomechanism and therapeutic strategies for brain disorders such as Alzheimer’s disease and hepatic encephalopathy.
Autonomy-Supportive Teaching and Basic Psychological Need Satisfaction among School Students: The Role of Mindfulness

Grounded in self-determination theory, the purpose of this study was to investigate the relationships between autonomy-supportive teaching, mindfulness, and basic psychological need satisfaction/frustration. Secondary school students (n = 390, Mage = 15) responded to a survey form measuring psychological constructs pertaining to the research purpose. A series of multiple regression analysis showed that autonomy-supportive teaching and mindfulness positively predicted need satisfaction and negatively predicted need frustration. In addition, the associations between autonomy-supportive teaching and need satisfaction/frustration were moderated by mindfulness. Students higher in mindfulness were more likely to feel need satisfaction and less likely to experience need frustration, even in a low autonomy-supportive teaching environment. These results speak to the relevance of creating autonomy-supportive teaching environments and highlight mindfulness as a potential pathway to basic psychological need satisfaction in educational settings.
The Combined Effect of FGFR Inhibition and PD-1 Blockade Promotes Tumor-Intrinsic Induction of Antitumor Immunity

Treatments that use a pan-FGFR (fibroblast growth factor receptor) inhibitor plus anti–PD-1 can boost antitumor responses in tumors harboring genetic mutations in driver oncogenes. The agents remodel the tumor microenvironment and enhance the expansion of T-cell clones. The success of targeted or immune therapies is often hampered by the emergence of resistance and/or clinical benefit in only a subset of patients. We hypothesized that combining targeted therapy with immune modulation would show enhanced antitumor responses. Here, we explored the combination potential of erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor under clinical development, with PD-1 blockade in an autochthonous FGFR2K660N/p53mut lung cancer mouse model. Erdafitinib monotherapy treatment resulted in substantial tumor control but no significant survival benefit. Although anti–PD-1 alone was ineffective, the erdafitinib and anti–PD-1 combination induced significant tumor regression and improved survival. For both erdafitinib monotherapy and combination treatments, tumor control was accompanied by tumor-intrinsic, FGFR pathway inhibition, increased T-cell infiltration, decreased regulatory T cells, and downregulation of PD-L1 expression on tumor cells. These effects were not observed in a KRASG12C-mutant genetically engineered mouse model, which is insensitive to FGFR inhibition, indicating that the immune changes mediated by erdafitinib may be initiated as a consequence of tumor cell killing. A decreased fraction of tumor-associated macrophages also occurred but only in combination-treated tumors. Treatment with erdafitinib decreased T-cell receptor (TCR) clonality, reflecting a broadening of the TCR repertoire induced by tumor cell death, whereas combination with anti–PD-1 led to increased TCR clonality, suggesting a more focused antitumor T-cell response. Our results showed that the combination of erdafitinib and anti–PD-1 drives expansion of T-cell clones and immunologic changes in the tumor microenvironment to support enhanced antitumor immunity and survival.
Dynamic MOPSO-Based Optimal Control for Wastewater Treatment Process

To achieve excellent treatment performance of complex and time-varying characteristics, the operation of wastewater treatment process (WWTP) has been considered as a dynamic multiobjective control problem. In this paper, an optimal controller, based on a dynamic multiobjective particle swarm optimization (DMOPSO) algorithm, is developed to deal with the dynamic multiple conflicting criteria [i.e., effluent quality (EQ), operation cost, and operation stability]. The novelties and advantages of this proposed DMOPSO-based optimal controller (DMOPSO-OC) include the following two aspects. First, an integrated optimization framework, where the multiple objectives not only conflict with each other but also change over time, is able to catch more characteristics of WWTP than the existing works. Second, a DMOPSO algorithm, with an adaptive global best selection mechanism, is designed to solve the multiobjective optimization problem (MOP) for the proposed optimal controller, thus leading to a significant improvement of optimal synthesis for performance. Finally, the proposed DMOPSO-OC is tested in the benchmark simulation model No. 1 (BSM1) and implemented in a real WWTP to evaluate its effectiveness. The experimental results demonstrate that this proposed DMOPSO-OC can achieve a significant improvement in optimal control performance and obey the requirement of multiple conflicting criteria.
The Impact of Medical Students’ Individual Teaching Format Choice on the Learning Outcome Related to Clinical Reasoning

Background Repeated formative assessments using key feature questions have been shown to enhance clinical reasoning. Key feature questions augmented by videos presenting clinical vignettes may be more effective than text-based questions, especially in a setting where medical students are free to choose the format they would like to work with. This study investigated learning outcomes related to clinical reasoning in students using video- or text-based key feature questions according to their individual preferences. Objective The aim of this study was to test the hypothesis that repeated exposure to video-based key feature questions enhances clinical reasoning to a greater extent than repeated exposure to text-based key feature questions if students are allowed to choose between those different formats on their own. Methods In this monocentric, prospective, nonrandomized trial, fourth-year medical students attended 12 computer-based case seminars during which they worked on case histories containing key feature questions. Cases were available in a text- and a video-based format. Students chose their preferred presentation format at the beginning of each case seminar. Student performance in key feature questions was assessed in formative entry, exit, and retention exams and was analyzed with regard to preceding exposure to video- or text-based case histories. Results Of 102 eligible students, 75 provided written consent and complete data at all study exams (response rate=73.5%). A majority of students (n=52) predominantly chose the text-based format. Compared with these, students preferring the video-based format achieved a nonsignificantly higher score in the exit exam (mean 76.2% [SD 12.6] vs 70.0% [SD 19.0]; P=.15) and a significantly higher score in the retention exam (mean 75.3% [SD 16.6] vs 63.4% [SD 20.3]; P=.02). The effect was independent of the video- or text-based presentation format, which was set as default in the respective exams. Conclusions Despite students’ overall preference for text-based case histories, the learning outcome with regard to clinical reasoning was higher in students with higher exposure to video-based items. Time-on-task is one conceivable explanation for these effects as working with video-based items was more time-consuming. The baseline performance levels of students do not account for the results as the preceding summative exam results were comparable across the 2 groups. Given that a substantial number of students chose a presentation format that was less effective, students might need to be briefed about the beneficial effects of using video-based case histories to be able to make informed choices about their study methods.
A Recombinant Attenuated Yersinia pseudotuberculosis Vaccine Delivering a Y. pestis YopENt138-LcrV Fusion Elicits Broad Protection against Plague and Yersiniosis in Mice

In this study, a novel recombinant attenuated Yersinia pseudotuberculosis PB1+ strain (χ10069) engineered with ΔyopK ΔyopJ Δasd triple mutations was used to deliver a Y. pestis fusion protein, YopE amino acid 1 to 138-LcrV (YopENt138-LcrV), to Swiss Webster mice as a protective antigen against infections by yersiniae. ABSTRACT In this study, a novel recombinant attenuated Yersinia pseudotuberculosis PB1+ strain (χ10069) engineered with ΔyopK ΔyopJ Δasd triple mutations was used to deliver a Y. pestis fusion protein, YopE amino acid 1 to 138-LcrV (YopENt138-LcrV), to Swiss Webster mice as a protective antigen against infections by yersiniae. χ10069 bacteria harboring the pYA5199 plasmid constitutively synthesized the YopENt138-LcrV fusion protein and secreted it via the type 3 secretion system (T3SS) at 37°C under calcium-deprived conditions. The attenuated strain χ10069(pYA5199) was manifested by the establishment of controlled infection in different tissues without developing conspicuous signs of disease in histopathological analysis of microtome sections. A single-dose oral immunization of χ10069(pYA5199) induced strong serum antibody titers (log10 mean value, 4.2), secretory IgA in bronchoalveolar lavage (BAL) fluid from immunized mice, and Yersinia-specific CD4+ and CD8+ T cells producing high levels of tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin 2 (IL-2), as well as IL-17, in both lungs and spleens of immunized mice, conferring comprehensive Th1- and Th2-mediated immune responses and protection against bubonic and pneumonic plague challenges, with 80% and 90% survival, respectively. Mice immunized with χ10069(pYA5199) also exhibited complete protection against lethal oral infections by Yersinia enterocolitica WA and Y. pseudotuberculosis PB1+. These findings indicated that χ10069(pYA5199) as an oral vaccine induces protective immunity to prevent bubonic and pneumonic plague, as well as yersiniosis, in mice and would be a promising oral vaccine candidate for protection against plague and yersiniosis for human and veterinary applications.
Antonymy in Modern Standard Arabic

Lexical relations have been thoroughly investigated cross-linguistically (Lyons, 1977; Cruse, 1986; Murphy, 2003). Antonymy is particularly interesting because antonymous pairs share both syntagmatic as well as paradigmatic relations. Studies (such as Raybeck and Herrmann, 1996) agree on the universality of this lexical relation; however, different perspectives towards opposition have been noted among different cultures (Murphy et al., 2009; Jones et al., 2012; Hsu, 2015). The present corpus-driven study investigates antonym use in Modern Standard Arabic text using an on-line corpus (arTenTen12) and a newspaper corpus (arabiCorpus). This thesis shows that antonym functions in Arabic are to a certain degree similar to those found in other languages. A new classification of these functions is presented and compared to previously identified functions in English text (Jones, 2002; Davies, 2013). The main difference between this classification and previous ones is in the category Ancillary Antonymy. In this category, canonical antonyms trigger contrast in non-contrastive pairings. The ancillary use of antonyms is presented as an effect projected on other words regardless of the hosting construction. As a consequence of removing this category, other functions of antonym use were identified. The present study also shows that a Sign-Based Construction Grammar (SBCG) account of antonyms can capture their syntagmatic and paradigmatic properties. Antonyms lend themselves well as pairings of meaning and form and therefore can be treated as constructions (Jones et al., 2012). Therefore, a treatment of antonyms using SBCG is presented in this study. Based on this treatment, I present a SBCG account of Arabic coordination as a contrastive construction in which antonyms frequently occur. The coordination construction is then compared to one use of coordination that presents antonym pairs as units referring to one concept.
When Older Adults Outperform Young Adults: Effects of Prior-Task Success in Arithmetic

Background: Older adults improve their cognitive performance on a target task after succeeding in a prior task. We tested whether effects of prior-task success occur via changing older adults’ ability to select the better strategy and/or to execute strategies efficiently. Methods: Young and older participants (n = 162) accomplished a computational estimation task (i.e., providing the best estimates to arithmetic problems) after accomplishing a dot comparison task. Results: Both groups increased their performance on computational estimation following success on dot comparison. Older adults improved most and outperformed young adults following prior-task success. Prior-task success led older adults to select the better strategy more often and to repeat (or not) the same strategy more often when it was appropriate. Better strategy use mediated effects of prior-task success. Individual differences in baseline performance moderated individuals’ sensitivity to effects of prior-task success. Conclusion: Our findings further our understanding of mechanisms underlying effects of prior-task success and provide new perspectives on how social environment modulates age-related differences in cognitive performance.
Sample size computation in phase II designs combining the A’Hern design and the Sargent and Goldberg design

ABSTRACT This work focuses on the modification of two classical phase II trials designs, the A’Hern design, a single-arm single-stage design, and the Sargent and Goldberg design introduced in the context of flexible screening designs. In the first part of the paper, we have proposed a drift-adjusted A’Hern design, a hybrid design combining the A’Hern design and the Sargent and Goldberg design. Indeed, classical single-arm phase II designs such as the A’Hern design are still widely used in oncology. Conducting randomized comparative phase II trials may be challenging in many settings due to the increased sample size and this despite larger type 1 errors. Randomized non-comparative phase II designs first introduced by Herson and Carter include a simultaneous randomized standard-treatment reference arm to detect any drift in the reference arm assumption, but the trial is analyzed against historical controls as if it were a single-arm study. However, not incorporating at all an internal control arm in the trial design has been criticized in the literature. Our new design takes into account the observed response rate in a non-comparative reference arm to reduce the trial’s risk of a false-positive conclusion. In the second part, we have proposed an alternative strategy to determining the sample size of the screened selection design. The latter, introduced in recent years by Yap et al. and Wu et al., extended the Sargent and Goldberg design to include a comparison to a historical control. However, their sample size computations may have potential weaknesses, which motivated us to revisit the existing approaches. A detailed simulation study has been carried out to evaluate the operating characteristics of the drift-adjusted A’Hern design and the different sample size strategies of the screened selection designs.
Transport via Macropinocytic Vesicles Is Crucial for Productive Infection with Bombyx Mori Nucleopolyhedrovirus

Bombyx mori nucleopolyhedrovirus (BmNPV) is a serious viral pathogen in the sericulture industry and enters host cells via macropinocytic endocytosis; however, the current understanding of the BmNPV entry mechanism remains limited. To confirm whether direct membrane fusion (DMF) results in productive BmNPV infection, DMF infectivity induced by low pH during BmNPV infection was investigated, and the infectious viral particle was traced using an eGFP-labeled virion. We found that BmNPV infection efficiently induced fluid uptake, which allowed BmNPV to bypass the cell membrane barrier via macropinocytosis. However, DMF induced by a low pH abolished the infection. While low pH is an essential condition for membrane fusion triggering, it is not sufficient for productive BmNPV infection, and DMF results in failure to transport the nucleocapsid into the nucleus. These results indicate that transport via macropinocytic vesicles facilitates BmNPV entry into the nucleus and contribute to our understanding of the BmNPV entry mechanism.
IoTDS: A One-Class Classification Approach to Detect Botnets in Internet of Things Devices

Internet of Things (IoT) devices have become increasingly widespread. Despite their potential of improving multiple application domains, these devices have poor security, which can be explored by attackers to build large-scale botnets. In this work, we propose a host-based approach to detect botnets in IoT devices, named IoTDS (Internet of Things Detection System). It relies on one-class classifiers, which model only the legitimate device behaviour for further detection of deviations, avoiding the manual labelling process. The proposed solution is underpinned by a novel agent-manager architecture based on HTTPS, which prevents the IoT device from being overloaded by the training activities. To analyse the device’s behaviour, the approach extracts features from the device’s CPU utilisation and temperature, memory consumption, and number of running tasks, meaning that it does not make use of network traffic data. To test our approach, we used an experimental IoT setup containing a device compromised by bot malware. Multiple scenarios were made, including three different IoT device profiles and seven botnets. Four one-class algorithms (Elliptic Envelope, Isolation Forest, Local Outlier Factor, and One-class Support Vector Machine) were evaluated. The results show the proposed system has a good predictive performance for different botnets, achieving a mean F1-score of 94% for the best performing algorithm, the Local Outlier Factor. The system also presented a low impact on the device’s energy consumption, and CPU and memory utilisation.
Neural machine translation of clinical texts between long distance languages

OBJECTIVE To analyze techniques for machine translation of electronic health records (EHRs) between long distance languages, using Basque and Spanish as a reference. We studied distinct configurations of neural machine translation systems and used different methods to overcome the lack of a bilingual corpus of clinical texts or health records in Basque and Spanish. MATERIALS AND METHODS We trained recurrent neural networks on an out-of-domain corpus with different hyperparameter values. Subsequently, we used the optimal configuration to evaluate machine translation of EHR templates between Basque and Spanish, using manual translations of the Basque templates into Spanish as a standard. We successively added to the training corpus clinical resources, including a Spanish-Basque dictionary derived from resources built for the machine translation of the Spanish edition of SNOMED CT into Basque, artificial sentences in Spanish and Basque derived from frequently occurring relationships in SNOMED CT, and Spanish monolingual EHRs. Apart from calculating bilingual evaluation understudy (BLEU) values, we tested the performance in the clinical domain by human evaluation. RESULTS We achieved slight improvements from our reference system by tuning some hyperparameters using an out-of-domain bilingual corpus, obtaining 10.67 BLEU points for Basque-to-Spanish clinical domain translation. The inclusion of clinical terminology in Spanish and Basque and the application of the back-translation technique on monolingual EHRs significantly improved the performance, obtaining 21.59 BLEU points. This was confirmed by the human evaluation performed by 2 clinicians, ranking our machine translations close to the human translations. DISCUSSION We showed that, even after optimizing the hyperparameters out-of-domain, the inclusion of available resources from the clinical domain and applied methods were beneficial for the described objective, managing to obtain adequate translations of EHR templates. CONCLUSION We have developed a system which is able to properly translate health record templates from Basque to Spanish without making use of any bilingual corpus of clinical texts or health records.
The TetR Family Transcription Factor MAB_2299c Regulates the Expression of Two Distinct MmpS-MmpL Efflux Pumps Involved in Cross-Resistance to Clofazimine and Bedaquiline in Mycobacterium abscessus

Mycobacterium abscessus is a human pathogen responsible for severe respiratory infections, particularly in patients with underlying lung disorders. Notorious for being highly resistant to most antimicrobials, new therapeutic approaches are needed to successfully treat M. abscessus-infected patients. Clofazimine (CFZ) and bedaquiline (BDQ) are two antibiotics used for the treatment of multidrug-resistant tuberculosis and are considered alternatives for the treatment of M. abscessus pulmonary disease. ABSTRACT Mycobacterium abscessus is a human pathogen responsible for severe respiratory infections, particularly in patients with underlying lung disorders. Notorious for being highly resistant to most antimicrobials, new therapeutic approaches are needed to successfully treat M. abscessus-infected patients. Clofazimine (CFZ) and bedaquiline (BDQ) are two antibiotics used for the treatment of multidrug-resistant tuberculosis and are considered alternatives for the treatment of M. abscessus pulmonary disease. To get insights into their mechanisms of resistance in M. abscessus, we previously characterized the TetR transcriptional regulator MAB_2299c, which controls expression of the MAB_2300-MAB_2301 genes, encoding an MmpS-MmpL efflux pump. Here, in silico studies identified a second mmpS-mmpL (MAB_1135c-MAB_1134c) target of MAB_2299c. A palindromic DNA sequence upstream of MAB_1135c, sharing strong homology with the one located upstream of MAB_2300, was found to form a complex with the MAB_2299c regulator in electrophoretic mobility shift assays. Deletion of MAB_1135c-1134c in a wild-type strain led to increased susceptibility to both CFZ and BDQ. In addition, deletion of these genes in a CFZ/BDQ-susceptible mutant lacking MAB_2299c as well as MAB_2300-MAB_2301 further exacerbated the sensitivity of this strain to both drugs in vitro and inside macrophages. Overall, these results indicate that MAB_1135c-1134c encodes a new MmpS-MmpL efflux pump system involved in the intrinsic resistance to CFZ and BDQ. They also support the view that MAB_2299c controls the expression of two separate MmpS-MmpL efflux pumps, substantiating the importance of MAB_2299c as a marker of resistance to be considered when assessing drug susceptibility in clinical isolates.