Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative proteomics reveals that dormancy-related proteins mediate the attenuation in mycobacterium strains

ABSTRACT Although members of the Mycobacterium tuberculosis complex (MTBC) exhibit high similarity, they are characterized by differences with respect to virulence, immune response, and transmissibility. To understand the virulence of these bacteria and identify potential novel therapeutic targets, we systemically investigated the total cell protein contents of virulent H37Rv, attenuated H37Ra, and avirulent M. bovis BCG vaccine strains at the log and stationary phases, based on tandem mass tag (TMT) quantitative proteomics. Data analysis revealed that we obtained deep-coverage protein identification and high quantification. Although 272 genetic variations were reported in H37Ra and H37Rv, they showed very little expression difference in log and stationary phase. Quantitative comparison revealed H37Ra and H37Rv had significantly dysregulation in log phase (227) compared with stationary phase (61). While BCG and H37Rv, and BCG and H37Ra showed notable differences in stationary phase (1171 and 1124) with respect to log phase (381 and 414). In the log phase, similar patterns of protein abundance were observed between H37Ra and BCG, whereas a more similar expression pattern was observed between H37Rv and H37Ra in the stationary phase. Bioinformatic analysis revealed that the upregulated proteins detected for H37Rv and H37Ra in log phase were virulence-related factors. In both log and stationary phases, the dysregulated proteins detected for BCG, which have also been identified as M. tuberculosis response proteins under dormancy conditions. We accordingly describe the proteomic profiles of H37Rv, H37Ra, and BCG, which we believe will potentially provide a better understanding of H37Rv pathogenesis, H37Ra attenuation, and BCG immuno protection.
Correlated Chained Gaussian Processes for Datasets With Multiple Annotators

The labeling process within a supervised learning task is usually carried out by an expert, which provides the ground truth (gold standard) for each sample. However, in many real-world applications, we typically have access to annotations provided by crowds holding different and unknown expertise levels. Learning from crowds (LFC) intends to configure machine learning paradigms in the presence of multilabelers, residing on two key assumptions: the labeler’s performance does not depend on the input space, and independence among the annotators is imposed. Here, we propose the correlated chained Gaussian processes from the multiple annotators (CCGPMA) approach, which models each annotator’s performance as a function of the input space and exploits the correlations among experts. Experimental results associated with classification and regression tasks show that our CCGPMA performs better modeling of the labelers’ behavior, indicating that it consistently outperforms other state-of-the-art LFC approaches.
Toxic Epidermal Necrolysis Caused by Allopurinol: A Serious but Still Underestimated Adverse Reaction

Patient: Female, 75-year-old Final Diagnosis: Toxic epidermal necrolysis Symptoms: Exanthema • rash • shivers • weakness Medication: — Clinical Procedure: Analgesia • ciclosporine • corticosteroids • topical and systemic treatment Specialty: Critical Care Medicine • Dermatology Objective: Rare disease Background: Allopurinol is the first-line therapy for the treatment of symptomatic hyperuricemia (gout). In clinical practice, there is a tendency to overmedicate asymptomatic patients who have elevated serum urate. Because of this practice, serious and life-threatening reactions such as Stevens-Johnson syndrome (SJS) or the more dramatic toxic epidermal necrolysis (TEN), both frequently caused by uricostatics, may occur. To increase awareness of these complications, we present a case with fulminant TEN caused by allopurinol. Case Report: A 75-year-old woman noticed a mildly itching skin rash accompanied by fever, shivering, and weakness approximately 3 weeks after taking newly prescribed allopurinol. The initial clinical examination revealed a generalized maculopapular exanthema. An adverse drug reaction was recognized, and allopurinol was discontinued. Ambulatory supportive therapy using prednisolone and cetirizine was started but failed. The patient developed a progressive exanthema with painful widespread blistering, skin peeling, and mucosal and conjunctival lesions. After recurrent presentations to the Emergency Department, the patient was transferred to our Intensive Care Unit (ICU). The clinical picture confirmed the suspected diagnosis of TEN. Massive fluid replacement, predniso-lone, and cyclosporine were used as anti-inflammatory therapy. Polyhexanide and octenidine were applied for local treatment. All treatment measures were guided daily by a multidisciplinary team. After 7 days in the ICU, the patient was transferred to the Dermatology Department and was discharged from the hospital 42 days later. Conclusions: With the prescription of allopurinol, there should be awareness of potentially life-threatening complications such as SJS or TEN. Patients with SJS or TEN should be immediately transferred to an ICU with dermatological expertise and multidisciplinary therapy.
The Mother–Offspring Conflict: The Association Between Maternal Sleep, Postpartum Depression, and Interbirth Interval Length

To test the hypothesis that infant night waking is an adaptation to increase interbirth intervals (IBIs) (i.e., the time between a mother’s consecutive births) by exhausting the mother, we made an initial attempt at investigating whether maternal sleep disturbance is associated with longer IBIs. We also explored whether postpartum depression symptoms mediated the association between maternal sleep disturbance and IBI length. We used retrospective self-reports from 729 mothers living in Finland. We conducted structural regressions separately for the mother’s two first children at two different age intervals (0–1 and 1–3 years). Infant night waking was associated with maternal sleep disturbance (β = .78–.84) and maternal sleep disturbance was associated with postpartum depression symptoms (β = .69–.81). Postpartum depression symptoms were also associated with longer IBIs for the first child (β = .23–.28). This result supports the notion that postpartum depression in and of itself could be viewed as adaptive for the offspring’s fitness, and not just as an unintentional byproduct of the mother’s sleep disturbance. Contrary to our prediction, maternal sleep disturbance was, however, associated with shorter IBIs for the first child (β = −.22 to −.30) when including postpartum depression symptoms in the model. We discuss the potential role of social support as an explanation for this unexpected result.
Clinical characteristics and postoperative seizure outcome in patients with mild malformation of cortical development and oligodendroglial hyperplasia

We describe for the first time clinical characteristics in a series of 20 pre‐surgically investigated patients with mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) who were operated on in our epilepsy center. We aimed to better diagnose this entity and help surgical planning.
Linking functional and molecular mechanisms of host resilience to malaria infection

It remains challenging to understand why some hosts suffer severe illnesses, while others are unscathed by the same infection. We fitted a mathematical model to longitudinal measurements of parasite and red blood cell density in murine hosts from diverse genetic backgrounds to identify aspects of within-host interactions that explain variation in host resilience and survival during acute malaria infection. Among eight mouse strains that collectively span 90% of the common genetic diversity of laboratory mice, we found that high host mortality was associated with either weak parasite clearance, or a strong, yet imprecise response that inadvertently removes uninfected cells in excess. Subsequent cross-sectional cytokine assays revealed that the two distinct functional mechanisms of poor survival were underpinned by low expression of either pro- or anti-inflammatory cytokines, respectively. By combining mathematical modelling and molecular immunology assays, our study uncovered proximate mechanisms of diverse infection outcomes across multiple host strains and biological scales.
Gray Matter Volume Variability in Young Healthy Adults: Influence of Gender Difference and Brain-Derived Neurotrophic Factor Genotype

Abstract Although brain gray matter (GM) plastically changes during short-term training, it is still unclear whether brain structures are stable for short periods (several months). Therefore, this study aimed to re-test the short-term variability of GM volumes and to clarify the effect of factors (gender and BDNF-genotype) expected to contribute to such variability. The subjects comprised 41 young healthy adults. T1-weighted images were acquired twice with an interval of approximately 4 months using a 3 T-MRI scanner. Voxel-based morphometry (VBM) was used to calculate GM volumes in 47 regions. The intraclass correlation coefficient (ICC) and Test–retest variability (%TRV) were used as indices of variability. As a result, the ICCs in 43 regions were excellent (ICC > 0.90) and those in 3 regions were good (ICC > 0.80), whereas the ICC in the thalamus was moderate (ICC = 0.694). Women had a higher %TRV than men in 5 regions, and %TRV of the Val66Val group was higher than that of the Met carrier group in 2 regions. Moreover, the Female-Val66Val group had a higher %TRV than the Male-Met carrier group in 3 regions. These results indicate that although the short-term variability of GM volumes is small, it is affected by within-subject factors.
Investigation of Emulgen Possibility of Piroxicam and Developing of the Method

The objective of the current research work was to explore the potential of emulgel in enhancing the topical delivery of piroxicam. Emulgel formulations of piroxicam were prepared using three types of gelling agents: Carbopol 934, Xanthan gum and HPMCK15M. Based on solubility studies Tween-80 and Span-80 as emulsifiers and propylene glycol as co-surfactant were selected for preparation of emulgel. The persuade of the type of the gelling agent on the drug release from the prepared emulgel was investigated. The mentha oil is used as permeation enhancer. The formulated emulgel were characterized for their physical appearance, pH determination, viscosity, spreadability, in vitro drug release, ex vivo drug release, skin irritation test, anti inflammatory activity, analgesic activity and stability studies. All the prepared formulations showed acceptable physical properties, homogeneity, consistency, spreadability, viscosity and pH value. In-vitro release study demonstrated diffusion controlled release of piroxicam from formulation up to 8 h. The drug release profile exhibited zero order kinetics.
Fetal akinesia deformation sequence and massive perivillous fibrin deposition resulting in fetal death in six fetuses from one consanguineous couple, including literature review

Massive perivillous fibrin deposition (MPFD) is associated with adverse pregnancy outcomes and is mainly caused by maternal factors with limited involvement of fetal or genetic causes. We present one consanguineous couple with six fetuses developing Fetal Akinesia Deformation Sequence (FADS) and MPFD, with a possible underlying genetic cause. This prompted a literature review on prevalence of FADS and MPFD.
Compositional evaluation of lesion and parent bone in patients with juvenile osteochondritis dissecans of the knee using T2* mapping

Juvenile osteochondritis dissecans (JOCD) lesions contain cartilaginous, fibrous and osseous tissues which are difficult to distinguish with clinical, morphological magnetic resonance imaging (MRI). Quantitative T2* mapping has earlier been used to evaluate microstructure and composition of all aforementioned tissues as well as bone mineral density. However, the ability of T2* mapping to detect changes in tissue composition between different JOCD lesion regions, different disease stages, and between stable and unstable lesions has not been demonstrated. This study analyzed morphological and T2* MRI data from 25 patients (median age, 12.1 years) with 34 JOCD‐affected and 13 healthy knees. Each lesion was assigned a stage reflecting the natural history of JOCD, with stages I and IV representing early and healed lesion, respectively. T2* values were evaluated within the progeny lesion, interface and parent bone of each lesion and in the control bone region. T2* was negatively correlated with JOCD stage in progeny lesion (ρ = −0.871; p < 0.001) and interface regions (ρ = −0.649; p < 0.001). Stage IV progeny showed significantly lower T2* than control bone (p = 0.028). T2* was significantly lower in parent bone than in control bone of patients with stable lesions (p = 0.009), but not in patients with unstable lesions (p = 0.14). Clinical significance: T2* mapping enables differentiation between different stages of JOCD and quantitative measurement of the ossification degree in progeny lesion and interface. The observed T2* decrease in healed and stable lesions may indicate increased bone density as a result of the active repair process. T2* mapping provides quantitative information about JOCD lesion composition.
A new mechanistic insight of DNA base adenine formation from pentamer HCN in the gas phase of interstellar clouds

ABSTRACT The mechanism formation of adenine is determinate in the gas phase, by using density functional theory (DFT) method at the B3LYP hybrid together with 6-311g(d,p) basis set level. Thus, we have investigated the structures and mechanisms pathway as well as the barrier energies involved in this study. The results indicate that adenine formation in the space of primitive Earth is very difficult of energetic point of view of both cases tautomers. In addition, the high activation energies induce a very late reaction, so this conclusion increases suggest that the components necessary for the origin of life may have been formed in stars or by the help of the heat of Earth throughout its geologic formation or in solution phase. Subsequently, the prebiotic syntheses of adenine product by oligomerization process under interstellar conditions is an inefficiently in the gas phase.
Utility of a novel tablet computer software for memory impairment in participants with brain injuries: A randomized control trial

ABSTRACT This study examined the effectiveness of a novel information and communication technology (ICT) tool developed for external memory compensation to improve memory function in participants with brain injuries. In this 3-month randomized control study, participants with memory impairment secondary to brain injury were randomly assigned on a 1:1 basis to either intervention (the ICT tool [ARATA]) or 3-month waitlist control groups. This study’s primary outcome measure was memory-related difficulties in everyday life, assessed using the Everyday Memory Checklist (EMC). Secondary outcomes included tests for memory function and psychosocial status, all of which were administered by blinded assessors. Seventy-eight participants (53 males, 25 females; mean age, 43.5 ± 12.7 [SD] years) were enrolled and 39 participants were allocated to each group (intervention and control). There was no significant difference in EMC scores between the two groups throughout the study (mean 0.26; 95% CI: −2.55–3.07; p=0.853); however, the intervention group scored significantly higher on the Rivermead Behavioural Memory and General Self-Efficacy tests compared to the control group. While the ICT tool did not improve the primary study outcome, evidence suggests that the ICT tool can improve memory functions related to activities of daily living.
Freeze tolerance influenced forest cover and hydrology during the Pennsylvanian

Significance Computer-assisted studies of natural history that consider extinct plant function contribute to the understanding of how Paleozoic glacial cycles controlled the distribution of forest cover and continental surface erosion. Simulated plant water balance supports widespread vegetation during the late Paleozoic ice age (LPIA). However, physiological inference suggests that plant freezing limited the geographic distribution of vegetation. Assuming LPIA plants had limited freeze tolerance, we found that increased surface runoff could have contributed to late Paleozoic climate change. Modeling that combines deep time climate reconstructions and paleobotanical data improves understanding of past Earth systems, which can help project future change. The distribution of forest cover alters Earth surface mass and energy exchange and is controlled by physiology, which determines plant environmental limits. Ancient plant physiology, therefore, likely affected vegetation-climate feedbacks. We combine climate modeling and ecosystem-process modeling to simulate arboreal vegetation in the late Paleozoic ice age. Using GENESIS V3 global climate model simulations, varying pCO2, pO2, and ice extent for the Pennsylvanian, and fossil-derived leaf C:N, maximum stomatal conductance, and specific conductivity for several major Carboniferous plant groups, we simulated global ecosystem processes at a 2° resolution with Paleo-BGC. Based on leaf water constraints, Pangaea could have supported widespread arboreal plant growth and forest cover. However, these models do not account for the impacts of freezing on plants. According to our interpretation, freezing would have affected plants in 59% of unglaciated land during peak glacial periods and 73% during interglacials, when more high-latitude land was unglaciated. Comparing forest cover, minimum temperatures, and paleo-locations of Pennsylvanian-aged plant fossils from the Paleobiology Database supports restriction of forest extent due to freezing. Many genera were limited to unglaciated land where temperatures remained above −4 °C. Freeze-intolerance of Pennsylvanian arboreal vegetation had the potential to alter surface runoff, silicate weathering, CO2 levels, and climate forcing. As a bounding case, we assume total plant mortality at −4 °C and estimate that contracting forest cover increased net global surface runoff by up to 6.1%. Repeated freezing likely influenced freeze- and drought-tolerance evolution in lineages like the coniferophytes, which became increasingly dominant in the Permian and early Mesozoic.
Make the right measurement: Discovery of an allosteric inhibition site for p300-HAT

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) catalyze the dynamic and reversible acetylation of proteins, an epigenetic regulatory mechanism associated with multiple cancers. Indeed, HDAC inhibitors are already approved in the clinic. The HAT paralogs p300 and CREB-binding protein (CBP) have been implicated in human pathological conditions including several hematological malignancies and androgen receptor-positive prostate cancer. Others have reported CoA-competitive inhibitors of p300 and CBP with cell-based activity. Here, we describe 2 compounds, CPI-076 and CPI-090, discovered through p300-HAT high throughput screening screening, which inhibit p300-HAT via binding at an allosteric site. We present the high resolution (1.7 and 2.3 Å) co-crystal structures of these molecules bound to a previously undescribed allosteric site of p300-HAT. Derivatization yielded actionable structure-activity relationships, but the full-length enzymatic assay demonstrated that this allosteric HAT inhibitor series was artifactual, inhibiting only the HAT domain of p300 with no effect on the full-length enzyme.
Using genetic algorithms to uncover individual differences in how humans represent facial emotion

Emotional facial expressions critically impact social interactions and cognition. However, emotion research to date has generally relied on the assumption that people represent categorical emotions in the same way, using standardized stimulus sets and overlooking important individual differences. To resolve this problem, we developed and tested a task using genetic algorithms to derive assumption-free, participant-generated emotional expressions. One hundred and five participants generated a subjective representation of happy, angry, fearful and sad faces. Population-level consistency was observed for happy faces, but fearful and sad faces showed a high degree of variability. High test–retest reliability was observed across all emotions. A separate group of 108 individuals accurately identified happy and angry faces from the first study, while fearful and sad faces were commonly misidentified. These findings are an important first step towards understanding individual differences in emotion representation, with the potential to reconceptualize the way we study atypical emotion processing in future research.
Gut microbiome and telomere length in gull hatchlings

In many animals, recent evidence indicates that the gut microbiome may be acquired during early development, with possible consequences on newborns' health. Thus, it has been hypothesized that a healthy microbiome protects telomeres and genomic integrity against cellular stress. However, the link between the early acquired microbiome and telomere dynamics has not hitherto been investigated. In birds, this link may also be potentially modulated by the transfer of maternal glucocorticoids, since these substances dysregulate microbiome composition during postnatal development. Here, we examined the effect of the interplay between the microbiome and stress hormones on the telomere length of yellow-legged gull hatchlings by using a field experiment in which we manipulated the corticosterone content in eggs. We found that the hatchling telomere length was related to microbiome composition, but this relationship was not affected by the corticosterone treatment. Hatchlings with a microbiome dominated by potential commensal bacteria (i.e. Catellicoccus and Cetobacterium) had larger telomeres, suggesting that an early establishment of the species-specific microbiome during development may have important consequences on offspring health and survival.
A New Species of Photonectes from the Pacific Ocean off Oahu, Hawaii with a Revised Identification Key for the Genus (Teleostei: Stomiidae: Melanostomiinae)

A new species of scaleless black dragonfish, Photonectes klepadloae, new species, is described on the basis of a single specimen collected in the central north Pacific Ocean off the Hawaiian Islands. The new species is readily distinguished from all congeners by the postorbital organ shifted forward to below eye, by the presence of the blue luminous tissue on the body arranged in two widely spaced interrupted lines between IV photophores and a streak-like patch on each side above 10th to 12th PV photophores, and by the structure of the mental barbel lacking a bulb, but having the long unpigmented distal appendage without a terminal swelling, and a pair of enlarged stalked photophore-like structures on the distal extremity of the stem. A revised key of the known species of Photonectes is presented.