Miracle-dz/UniFAR-FTUs huggingface dataset:
Modified ischaemic nerve block of the forearm: use for the induction of cortical plasticity in distal hand muscles

Ischaemic nerve block (INB) of the forearm rapidly reduces somatosensory input to a part of the body, which leads to the functional reorganization of the temporarily deafferented primary motor cortex (M1). We applied a novel modified INB (mINB) to the forearm, maintaining mean blood pressure, to assess cortical plasticity in the primary somatosensory cortex (S1) and the M1 regions associated with small hand muscles. S1 excitability was measured by median nerve somatosensory‐evoked potentials (SEPs), while M1 excitability was evaluated by motor‐evoked potentials (MEPS), using transcranial magnetic stimulation. The finding that S1 excitability increased and M1 excitability decreased after the mINB was removed reflects the differential short‐term cortical plasticity of the S1 and M1 regions. These opposite effects observed for the S1 and M1 regions following the mINB may indicate a possible intra‐hemispheric interaction between the S1 and M1 regions.
Increased Apoptosis Coincides with Onset of Involution in Infantile Hemangioma

Objective: Hemangioma is an endothelial cell tumor that grows rapidly during infancy and regresses slowly during childhood. However, little is known about the natural history of this common tumor. To gain insight into the cellular mechanisms that underlie the switch from uncontrolled growth to involution of endothelium, we investigated the extent of cellular apoptosis versus proliferation in hemangioma specimens that spanned the natural life cycle of the tumor.
Obscurins: Unassuming giants enter the spotlight

Discovered about a decade ago, obscurin (∼720 kDa) is a member of a family of giant proteins expressed in striated muscle that are essential for normal muscle function. Much of what we understand about obscurin stems from its functions in cardiac and skeletal muscle. However, recent evidence has indicated that variants of obscurin (“obscurins”) are expressed in diverse cell types, where they contribute to distinct cellular processes. Dysfunction or abrogation of obscurins has also been implicated in the development of several pathological conditions, including cardiac hypertrophy and cancer. Herein, we present an overview of obscurins with an emphasis on novel findings that demonstrate their heretofore‐unsuspected importance in cell signaling and disease progression. © 2013 IUBMB Life, 65(6):479–486, 2013.
Effect of Geometrical Structure, Drying, and Synthetic Method on Aminated Chitosan-Coated Magnetic Nanoparticles Utility for HSA Effective Immobilization †

Human serum albumin (HSA) is one of the most frequently immobilized proteins on the surface of carriers, including magnetic nanoparticles. This is because the drug–HSA interaction study is one of the basic pharmacokinetic parameters determined for drugs. In spite of many works describing the immobilization of HSA and the binding of active substances, research describing the influence of the used support on the effectiveness of immobilization is missing. There are also no reports about the effect of the support drying method on the effectiveness of protein immobilization. This paper examines the effect of both the method of functionalizing the polymer coating covering magnetic nanoparticles (MNPs), and the drying methods for the immobilization of HSA. Albumin was immobilized on three types of aminated chitosan-coated nanoparticles with a different content of amino groups long distanced from the surface Fe3O4-CS-Et(NH2)1–3. The obtained results showed that both the synthesis method and the method of drying nanoparticles have a large impact on the effectiveness of immobilization. Due to the fact that the results obtained for Fe3O4-CS-Et(NH2)2 significantly differ from those obtained for the others, the influence of the geometry of the shell structure on the ability to bind HSA was also explained by molecular dynamics.
Excitability and irritability in preschoolers predicts later psychopathology: The importance of positive and negative emotion dysregulation

Abstract Emotion dysregulation is a risk factor for the development of a variety of psychopathologic outcomes. In children, irritability, or dysregulated negative affect, has been the primary focus, as it predicts later negative outcomes even in very young children. However, dysregulation of positive emotion is increasingly recognized as a contributor to psychopathology. Here we used an exploratory factor analysis and defined four factors of emotion dysregulation: irritability, excitability, sadness, and anhedonia, in the preschool-age psychiatric assessment collected in a sample of 302 children ages 3–5 years enriched for early onset depression. The irritability and excitability factor scores defined in preschoolers predicted later diagnosis of mood and externalizing disorders when controlling for other factor scores, social adversity, maternal history of mood disorders, and externalizing diagnoses at baseline. The preschool excitability factor score predicted emotion lability in late childhood and early adolescence when controlling for other factor scores, social adversity, and maternal history. Both excitability and irritability factor scores in preschoolers predicted global functioning into the teen years and early adolescence, respectively. These findings underscore the importance of positive, as well as negative, affect dysregulation as early as the preschool years in predicting later psychopathology, which deserves both further study and clinical consideration.
Detection of lung transplant rejection in a rat model using hyperpolarized [1‐13C] pyruvate‐based metabolic imaging

The current standard for noninvasive imaging of acute rejection consists of X‐ray/CT, which derive their contrast from changes in ventilation, inflammation and edema, as well as remodeling during rejection. We propose the use of hyperpolarized [1‐13C] pyruvate MRI—which provides real‐time metabolic assessment of tissue—as an early biomarker for tissue rejection.
Machine learning reveals systematic accumulation of electric current in lead-up to solar flares

Significance Reliable flare forecasting is essential for improving preparedness for severe space weather consequences. Flares also serve as probes of solar magnetic processes and the emergence of flux at the solar surface. Training machine-learning (ML) algorithms using magnetic-field observations for improving flare forecasting has been extensively studied in prior literature. Instead, here we use ML to understand the underlying mechanisms governing flares. We train ML algorithms to classify flaring and nonflaring active regions (ARs) with high fidelity and report statistical trends for AR evolution days before and after M- and X-class flares. These trends are interpreted in terms of existing models of subsurface magnetic field and flux emergence. Our results also provide hypotheses for achieving reliable flare forecasting. Solar flares—bursts of high-energy radiation responsible for severe space weather effects—are a consequence of the occasional destabilization of magnetic fields rooted in active regions (ARs). The complexity of AR evolution is a barrier to a comprehensive understanding of flaring processes and accurate prediction. Although machine learning (ML) has been used to improve flare predictions, the potential for revealing precursors and associated physics has been underexploited. Here, we train ML algorithms to classify between vector–magnetic-field observations from flaring ARs, producing at least one M-/X-class flare, and nonflaring ARs. Analysis of magnetic-field observations accurately classified by the machine presents statistical evidence for (i) ARs persisting in flare-productive states—characterized by AR area—for days, before and after M- and X-class flare events; (ii) systematic preflare buildup of free energy in the form of electric currents, suggesting that the associated subsurface magnetic field is twisted; and (iii) intensification of Maxwell stresses in the corona above newly emerging ARs, days before first flares. These results provide insights into flare physics and improving flare forecasting.
Dichloroacetate Affects Mitochondrial Function and Stemness-Associated Properties in Pancreatic Cancer Cell Lines

Targeting metabolism represents a possible successful approach to treat cancer. Dichloroacetate (DCA) is a drug known to divert metabolism from anaerobic glycolysis to mitochondrial oxidative phosphorylation by stimulation of PDH. In this study, we investigated the response of two pancreatic cancer cell lines to DCA, in two-dimensional and three-dimension cell cultures, as well as in a mouse model. PANC-1 and BXPC-3 treated with DCA showed a marked decrease in cell proliferation and migration which did not correlate with enhanced apoptosis indicating a cytostatic rather than a cytotoxic effect. Despite PDH activation, DCA treatment resulted in reduced mitochondrial oxygen consumption without affecting glycolysis. Moreover, DCA caused enhancement of ROS production, mtDNA, and of the mitophagy-marker LC3B-II in both cell lines but reduced mitochondrial fusion markers only in BXPC-3. Notably, DCA downregulated the expression of the cancer stem cells markers CD24/CD44/EPCAM only in PANC-1 but inhibited spheroid formation/viability in both cell lines. In a xenograft pancreatic cancer mouse-model DCA treatment resulted in retarding cancer progression. Collectively, our results clearly indicate that the efficacy of DCA in inhibiting cancer growth mechanistically depends on the cell phenotype and on multiple off-target pathways. In this context, the novelty that DCA might affect the cancer stem cell compartment is therapeutically relevant.
The immune repressor BIR1 contributes to antiviral defense and undergoes transcriptional and post-transcriptional regulation during viral infections.

BIR1 is a receptor-like kinase that functions as a negative regulator of basal immunity and cell death in Arabidopsis. Using Arabidopsis thaliana and Tobacco rattle virus (TRV), we investigate the antiviral role of BIR1, the molecular mechanisms of BIR1 gene expression regulation during viral infections, and the effects of BIR1 overexpression on plant immunity and development. We found that SA acts as a signal molecule for BIR1 activation during infection. Inactivating mutations of BIR1 cause strong antiviral resistance that is not due to constitutive cell death or SA defense priming in the bir1-1 mutant. RNA-directed DNA methylation (RdDM) and post-transcriptional silencing are both required to negatively regulate BIR1 expression upon viral induction. BIR1 overexpression causes severe developmental defects, cell death and premature death that correlate with the constitutive activation of plant immune responses. Our findings suggest that BIR1 acts as a negative regulator of antiviral defense in plants, and indicate that RNA silencing contributes, alone or in conjunction with other regulatory mechanisms, to define a threshold expression for proper BIR1 function beyond which an autoimmune response may occur. This work provides novel mechanistic insights into the regulation of BIR1 homeostasis that may be common for other plant immune components. This article is protected by copyright. All rights reserved.
Young age and tobacco use are predictors of lower medication adherence in inflammatory bowel disease

Background Medication adherence is crucial in the management of patients with inflammatory bowel disease (IBD) because medication nonadherence in these patients is associated with an increased risk of flare-up, relapse, recurrence, loss of response to anti-tumour necrosis factor agents, morbidity and mortality, and poor quality of life. Data on risk factors are very controversial in the literature. Aim To assess the prevalence of medication nonadherence and to identify predictors of low medication adherence in Spanish patients with IBD. Patients and methods We carried out a cross-sectional study that included consecutive outpatients with IBD attending in our adult tertiary clinic in a 3-month period. Morisky 8-Item Medication Adherence Scale questionnaire as well as a survey of sociodemographic data were used. Results A total of 181 patients were evaluated. Almost half of the patients (46.4%) had high medication adherence, 30.9% had medium adherence, and 22.7% had low adherence. In relation to predictive factors of medication adherence, multivariate analysis showed that age was associated with high adherence [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.01–1.06; P=0.002]. However, being a smoker and presence of Crohn’s disease were associated with low adherence (OR: 3.47; 95% CI: 1.36–8.90; P<0.01 and OR: 2.54; 95% CI: 1.12–5.79; P<0.05, respectively). Conclusion Only half of patients were high medication adherers. Young age, active smoking, and Crohn’s disease seems to be predictors of low medication adherence. On the basis of these data, efforts for reinforce medication adherence should be especially directed to young patients and smokers.
Is antipsychotic medication stigmatizing for people with mental illness?

Antipsychotic medications are clearly identified as important in the treatment of individuals with schizophrenia and with bipolar disorder. However, negative societal reaction related to having a serious mental illness and the socially undesirable side effects associated with antipsychotic medication treatment may combine to worsen stigma associated with treatment for mental illness. Specific stigmatizing effects of antipsychotic therapy may be difficult to evaluate independently from factors such as symptoms, insight into illness and side effects. Attitudes towards antipsychotic medication may be positive in individuals who recognize therapeutic drug effects, however other individuals may view medications negatively due to a sense of stigma. Stigma among individuals with bipolar disorder in relation to treatment with antipsychotic medication has not been well addressed in the literature. An additional concern among individuals with bipolar disorder who receive antipsychotic medications may be the notion that antipsychotics are ‘schizophrenia drugs’, and thus an inappropriate treatment for their condition. Antipsychotic medications can be stigmatizing for patients with serious mental illness, however the roots of stigma are extensive, and efforts to minimize stigma can only be successful when addressed by the individual with illness, their families and loved ones, treatment providers and society at large.
Emotional dysregulation, internalizing symptoms, and self-injurious and suicidal behavior: Structural equation modeling analysis

ABSTRACT This study used structural equation modeling to examine the relationships between emotion dysregulation, internalizing symptoms, nonsuicidal self-injury (NSSI), and suicide. One hundred forty-eight undergraduates completed a brief structured interview and self-report measures of emotion dysregulation, internalizing symptoms, and NSSI and suicidal behaviors. Results indicated a significant indirect effect of emotion dysregulation on NSSI via internalizing symptoms and on suicide attempts via NSSI. Findings provide a more nuanced understanding of the indirect association between emotion dysregulation and NSSI and suicidal behaviors. Implications for the potential utility of targeting internalizing symptoms as well as emotion dysregulation in interventions addressing NSSI and suicidal behaviors are discussed.
Three New Isoflavonoid Glycosides from the Mangrove-Derived Actinomycete Micromonospora aurantiaca 110B

The mangrove ecosystem is a rich resource for the discovery of actinomycetes with potential applications in pharmaceutical science. Besides the genus Streptomyces, Micromonospora is also a source of new bioactive agents. We screened Micromonospora from the rhizosphere soil of mangrove plants in Fujian province, China, and 51 strains were obtained. Among them, the extracts of 12 isolates inhibited the growth of human lung carcinoma A549 cells. Strain 110B exhibited better cytotoxic activity, and its bioactive constituents were investigated. Consequently, three new isoflavonoid glycosides, daidzein-4′-(2-deoxy-α-l-fucopyranoside) (1), daidzein-7-(2-deoxy-α-l-fucopyranoside) (2), and daidzein-4′,7-di-(2-deoxy-α-l-fucopyranoside) (3) were isolated from the fermentation broth of strain 110B. The structures of the new compounds were determined by spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). The result of medium-changing experiments implicated that these new compounds were microbial biotransformation products of strain M. aurantiaca 110B. The three compounds displayed moderate cytotoxic activity to the human lung carcinoma cell line A549, hepatocellular liver carcinoma cell line HepG2, and the human colon tumor cell line HCT116, whereas none of them showed antifungal or antibacterial activities.
Neural Speech Tracking in the Theta and in the Delta Frequency Band Differentially Encode Clarity and Comprehension of Speech in Noise

Humans excel at understanding speech even in adverse conditions such as background noise. Speech processing may be aided by cortical activity in the delta and theta frequency bands, which have been found to track the speech envelope. However, the rhythm of non-speech sounds is tracked by cortical activity as well. It therefore remains unclear which aspects of neural speech tracking represent the processing of acoustic features, related to the clarity of speech, and which aspects reflect higher-level linguistic processing related to speech comprehension. Here we disambiguate the roles of cortical tracking for speech clarity and comprehension through recording EEG responses to native and foreign language in different levels of background noise, for which clarity and comprehension vary independently. We then use a both a decoding and an encoding approach to relate clarity and comprehension to the neural responses. We find that cortical tracking in the theta frequency band is mainly correlated to clarity, whereas the delta band contributes most to speech comprehension. Moreover, we uncover an early neural component in the delta band that informs on comprehension and that may reflect a predictive mechanism for language processing. Our results disentangle the functional contributions of cortical speech tracking in the delta and theta bands to speech processing. They also show that both speech clarity and comprehension can be accurately decoded from relatively short segments of EEG recordings, which may have applications in future mind-controlled auditory prosthesis. SIGNIFICANCE STATEMENT Speech is a highly complex signal whose processing requires analysis from lower-level acoustic features to higher-level linguistic information. Recent work has shown that neural activity in the delta and theta frequency bands track the rhythm of speech, but the role of this tracking for speech processing remains unclear. Here we disentangle the roles of cortical entrainment in different frequency bands and at different temporal lags for speech clarity, reflecting the acoustics of the signal, and speech comprehension, related to linguistic processing. We show that cortical speech tracking in the theta frequency band encodes mostly speech clarity, and thus acoustic aspects of the signal, whereas speech tracking in the delta band encodes the higher-level speech comprehension.
Mechanisms of radiation in a bat group from the genus Pipistrellus inferred by phylogeography, demography and population genetics

Here, we present a study of the Pipistrellus pipistrellus species complex, a highly diversified bat group with a radiation centre in the Mediterranean biodiversity hotspot. The study sample comprised 583 animals from 118 localities representatively covering the bats’ range in the western Palearctic. We used fast‐evolving markers (the mitochondrial D‐loop sequence and 11 nuclear microsatellites) to describe the phylogeography, demography and population structure of this model taxon and address details of its diversification. The overall pattern within this group includes a mosaic of phylogenetically basal, often morphologically distant, relatively small and mostly allopatric demes in the Mediterranean Basin, as well as two sympatric sibling species in the large continental part of the range. The southern populations exhibit constant size, whereas northern populations show a demographic trend of growth associated with range expansion during the Pleistocene climate oscillations. There is evidence of isolation by distance and female philopatry in P. pipistrellus sensu stricto. Although the northern populations are reproductively isolated, we detected introgression events among several Mediterranean lineages. This pattern implies incomplete establishment of reproductive isolating mechanisms in these populations as well as the existence of a past reinforcement stage in the continental siblings. The occurrence of reticulations in the radiation centre among morphologically and ecologically derived relict demes suggests that adaptive unequal gene exchange within hybridizing populations could play a role in speciation and adaptive radiation within this group.
Lipopeptides induce cell-mediated anti-HIV immune responses in seronegative volunteers

ObjectiveTest the efficacy of a mixture of six NEF (N1, N2, N3), GAG (G1, G2) and ENV (E) lipopeptides in the induction of B- and T-cell anti-HIV responses. DesignA randomized phase I open-label dose-finding trial. Twenty-eight healthy seronegative volunteers received the lipopeptides, with or without the adjuvant QS21. MethodsAnti-HIV-peptide antibodies were detected by enzyme-linked immunosorbent assay and Western blotting. Induction of cellulary responses was assessed by proliferative test and 51Cr-release assay. ResultsLocal and systemic adverse reactions were always mild or moderate. After three injections an antibody response was detected in 25 out of 28 volunteers (89%). T cells from 19 (79%) of the 24 volunteers proliferated in response to at least one peptide. The majority of the volunteers had induced a multispecific proliferative response; that is, cells from volunteers proliferated to two (five of 19), three (five of 19), four (three of 19) or five peptides (one of 19). Cytotoxic responses by anti-HIV CD8+ lymphocytes could be tested in 24 volunteers, 13 (54%) of whom had clear and reproducible responses, with strong activity in the remaining 12 (> 20% of specific lysis), and polyepitopic responses were detected in at least seven of the 13 responders. Cytotoxic responses were found against the whole NEF protein (clade B LAI) in three of four tested volunteers and cross-reactions with the proteins of clade B (MN) and clade A (Bangui) HIV-1 strains, and also HIV-2 ROD, were detected in one of two tested volunteers. ConclusionsLipopeptides are promising immunogens for an AIDS vaccine.
The outcome of bone graft surgery for nonunion of fractures of the scaphoid

Data on 806 patients undergoing bone graft surgery for a scaphoid fracture nonunion were retrospectively collected at 19 centres in the United Kingdom. Each centre contributed at least 30 cases. Sufficient data were available in 462 cases to study factors that influenced the outcome of surgery. Overall union occurred in at least 69%, and nonunion in at least 22%, with 9% of cases having ‘uncertain union status’. Union appeared to be adversely influenced by smoking and the time between acute scaphoid fracture and nonunion surgery, with adjusted odds ratios of 1.8 and 2.4, respectively, but neither achieved the pre-determined significance level of 0.003. The type of bone graft (vascular vs non-vascular; iliac crest vs distal radius) did not appear to influence outcome. Further large multicentre prospective studies with clear definitions of ‘union’ and other factors are needed to clarify whether modification of surgical technique can influence union. Level of evidence: IV