Miracle-dz/UniFAR-FTUs huggingface dataset:
Emotion and decision-making: Induced mood influences IGT scores and deck selection strategies

ABSTRACT The somatic marker hypothesis (SMH) represents a rich neuropsychological framework to study emotion-based decision-making. It originates from early brain lesion studies using the Iowa Gambling Task (IGT), which showed that adaptive decision-making relies on intact ventromedial prefrontal cortex for the integration of so-called “hot” affective signals and rational “cold” perceptual cognitive computations. Subsequent studies over the past 20 years have provided converging evidence for the reliability and validity of the IGT in assessing decision-making in both healthy and clinical samples, although some discrepancies remain. In healthy individuals, it has been shown that differences in emotional states prior to taking the IGT result in different outcomes, thus potentially accounting for some of the variation within this group. However, the precise role of such transient modulations of emotional states remains unclear. In this study we sought to examine the role of specific induced moods under carefully controlled conditions. Accordingly, we randomly assigned 44 healthy college undergraduates to a positive, negative, or neutral affect condition in which they simultaneously viewed images and listened to music that previous studies had shown to induce specific moods. Results indicated that mood induction was successful, and the positive affect group showed a clearly different pattern of IGT performance compared to the other two groups, in that they showed a rapidly established and stable bias favoring the positive expected value (EV) card decks. The negative affect group showed significantly lower bias towards the positive EV decks, although this group was not different from the neutral affect group. Bayesian analyses confirmed these findings. While consistent with SMH, these current findings may be best understood in support of a more general effect of normal mood on cognition as outlined in the broaden-and-build theory of positive emotions.
3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice

3K3A-activated protein C (APC), a cell-signaling analogue of endogenous blood serine protease APC, exerts vasculoprotective, neuroprotective, and anti-inflammatory activities in rodent models of stroke, brain injury, and neurodegenerative disorders. 3K3A-APC is currently in development as a neuroprotectant in patients with ischemic stroke. Here, we report that 3K3A-APC inhibits BACE1 amyloidogenic pathway in a mouse model of Alzheimer’s disease (AD). We show that a 4-mo daily treatment of 3-mo-old 5XFAD mice with murine recombinant 3K3A-APC (100 µg/kg/d i.p.) prevents development of parenchymal and cerebrovascular amyloid-&bgr; (A&bgr;) deposits by 40–50%, which is mediated through NF&kgr;B–dependent transcriptional inhibition of BACE1, resulting in blockade of A&bgr; generation in neurons overexpressing human A&bgr;-precursor protein. Consistent with reduced A&bgr; deposition, 3K3A-APC normalized hippocampus-dependent behavioral deficits and cerebral blood flow responses, improved cerebrovascular integrity, and diminished neuroinflammatory responses. Our data suggest that 3K3A-APC holds potential as an effective anti-A&bgr; prevention therapy for early-stage AD.
Lymphocyte-to-Monocyte Ratio Is an Independent Predictor for Neurological Deterioration and 90-Day Mortality in Spontaneous Intracerebral Hemorrhage

Background Lymphocyte-to-monocyte ratio (LMR) is an independent predictive factor of clinical outcome of acute ischemic stroke and cancer, but the predictive effect of LMR in spontaneous intracerebral hemorrhage (ICH) is unknown. Thus, the aim of this study was to explore the impact of peripheral LMR on the neurological deterioration (ND) during the initial week after spontaneous ICH onset, as well as 90-day mortality. Material/Method The clinical data of 558 consecutive patients with ICH were retrospectively analyzed. LMR is calculated by absolute lymphocyte count divided by absolute monocyte count. Results Of these patients, 166 patients experienced ND during the first week after admission and 72 patients died within 90 days. Multivariate analysis indicated that white blood cells (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), LMR were significantly associated with ND during the initial week after ICH onset and also were associated with 90-day mortality. Moreover, NLR and LMR showed a higher predictive ability in ND during the initial week after ICH onset than 90-day mortality in receiver operating characteristic analysis. The best cut-off points of NLR and LMR in predicting ND and 90-day mortality were 10.24 and 2.21 and 16.81 and 2.19, respectively. Conclusions Our results suggest that LMR on admission is a predictive factor for ND during the initial week after ICH onset, as well as 90-day mortality.
Multidisciplinary Treatment for Provoked Vestibulodynia: Treatment Trajectories, Predictors, and Moderators of Sexual Distress and Pain

Objectives: Multidisciplinary treatment programs for provoked vestibulodynia (PVD) are recommended, yet few have been evaluated. This study examined women’s symptom trajectories over time, as well as baseline demographic, psychosocial and pain characteristics as predictors/ moderators of sexual pain and distress following treatment at a clinic using multidisciplinary concurrent methods. We also examined the impact of baseline variables on the probability of having low sexual distress scores following treatment. Materials and Methods: Women attending a multidisciplinary treatment program for PVD were invited to complete questionnaires before, following, and at 6 and 18 months after program completion. Questionnaires included the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), State-Trait Anxiety Inventory (STAI), Pain Catastrophizing Scale (PCS), Painful Intercourse Self-Efficacy Scale (PISES), and Pain Vigilance and Awareness Questionnaire (PVAQ). Linear mixed-effects models evaluated the FSDS and FSFI pain subscale as criterion variables, and the other baseline variables as predictors and moderators. Results: Significant improvements in sexual distress and pain were observed over time. No significant moderators were identified, but higher baseline levels of FSFI desire and arousal predicted greater improvements in sexual distress. Similarly, higher baseline levels of desire predicted greater improvements in pain. Among women distressed at baseline and with 6 month FSDS scores, 25% (n=35) were no longer sexually distressed at 6 months; higher baseline levels of desire were associated with greater probability of having low sexual distress at 6 months. Discussion: Although global improvements were observed, women with poorer baseline sexual functioning were less likely to improve after multidisciplinary treatment.
Turning the Tide against Antibiotic Resistance by Evaluating Novel, Halogenated Phenazine, Quinoline, and NH125 Compounds against Ureaplasma Species Clinical Isolates and Mycoplasma Type Strains

Escalating levels of antibiotic resistance in mycoplasmas, particularly macrolide resistance in Mycoplasma pneumoniae and M. genitalium, have narrowed our antibiotic arsenal. Further, mycoplasmas lack a cell wall and do not synthesize folic acid, rendering common antibiotics, such as beta-lactams, vancomycin, sulfonamides, and trimethoprim, of no value. ABSTRACT Escalating levels of antibiotic resistance in mycoplasmas, particularly macrolide resistance in Mycoplasma pneumoniae and M. genitalium, have narrowed our antibiotic arsenal. Further, mycoplasmas lack a cell wall and do not synthesize folic acid, rendering common antibiotics, such as beta-lactams, vancomycin, sulfonamides, and trimethoprim, of no value. To address this shortage, we screened nitroxoline, triclosan, and a library of 20 novel, halogenated phenazine, quinoline, and NH125 analogues against Ureaplasma species and M. hominis clinical isolates from urine. We tested a subset of these compounds (n = 9) against four mycoplasma type strains (M. pneumoniae, M. genitalium, M. hominis, and Ureaplasma urealyticum) using a validated broth microdilution or agar dilution method. Among 72 Ureaplasma species clinical isolates, nitroxoline proved most effective (MIC90, 6.25 µM), followed by an N-arylated NH125 analogue (MIC90, 12.5 µM). NH125 and its analogue had significantly higher MICs against U. urealyticum isolates than against U. parvum isolates, whereas nitroxoline did not. Nitroxoline exhibited bactericidal activity against U. parvum isolates but bacteriostatic activity against the majority of U. urealyticum isolates. Among the type strains, the compounds had the greatest activity against M. pneumoniae and M. genitalium, with 8 (80%) and 5 (71.4%) isolates demonstrating MICs of ≤12.5 µM, respectively. Triclosan also exhibited lower MICs against M. pneumoniae and M. genitalium. Overall, we identified a promising range of quinoline, halogenated phenazine, and NH125 compounds that showed effectiveness against M. pneumoniae and M. genitalium and found that nitroxoline, approved for use outside the United States for the treatment of urinary tract infections, and an N-arylated NH125 analogue demonstrated low MICs against Ureaplasma species isolates.
Biofilm diversity, structure and matrix seasonality in a full-scale cooling tower

Abstract Biofilms commonly colonise cooling water systems, causing equipment damage and interference with the operational requirements of the systems. In this study, next-generation sequencing (NGS), catalysed reporter deposition fluorescence in situ hybridisation (CARD-FISH), lectin staining and microscopy were used to evaluate temporal dynamics in the diversity and structure of biofilms collected seasonally over one year from an open full-scale cooling tower. Water samples were analysed to evaluate the contribution of the suspended microorganisms to the biofilm composition and structure. Alphaproteobacteria dominated the biofilm communities along with Beta- and Gammaproteobacteria. The phototrophic components were mainly cyanobacteria, diatoms and green algae. Bacterial biodiversity decreased from winter to autumn, concurrently with an increase in cyanobacterial and microalgal richness. Differences in structure, spatial organisation and glycoconjugates were observed among assemblages during the year. Overall, microbial variation appeared to be mostly affected by irradiance and water temperature rather than the source of the communities. Variations in biofilms over seasons should be evaluated to develop specific control strategies.
Knowledge among important actors in the field of adaptive equipment for young people with disabilities

Abstract Purpose: Access to adaptive equipment is a crucial factor that can determine if a child or youth with disabilities is going to participate in physical activities, sports and play in different local settings. A prerequisite for success is awareness of and specific knowledge concerning the equipment and its use among relevant actors. The aim of this paper is to explore how important groups of actors working with young people with disabilities perceive their level of knowledge concerning adaptive equipment and discuss these actors’ role in children and youths’ opportunities to obtain relevant equipment to participate in activities. Methods: An online, population-based national survey was distributed to: (1) occupational therapists and physiotherapists, (2) teachers, and (3) leaders and coaches in sports clubs in Norway. Results: The findings generally indicate that overall knowledge concerning adaptive equipment among the three groups is limited. However, significant statistical difference is found, indicating that occupational therapists and physiotherapists have higher levels of general knowledge, about the accessibility of equipment, regulations and legislation and that they are more familiar with adaptive equipment than teachers, leaders and coaches. Conclusions: A practical implication of the results is that the actors’ varying knowledge and experiences need to be brought together to form a coherent picture of how the equipment will be used and by whom. This can contribute to an increased understanding concerning adaptive equipment and its importance among different actors, which could help more young people with disabilities to participate. Implications for Rehabilitation Important actors must utilize the knowledge and experience possessed by young people with disabilities concerning adaptive equipment. Improved access to knowledge concerning adaptive equipment among important actors is required. Increased collaboration between different actors relating to adaptive equipment and participation is needed.
Optic Nerve Head Astrocytes Display Axon-Dependent and -Independent Reactivity in Response to Acutely Elevated Intraocular Pressure

Purpose Optic nerve head (ONH) astrocytes provide support for axons, but exhibit structural and functional changes (termed reactivity) in a number of glaucoma models. The purpose of this study was to determine if ONH astrocyte structural reactivity is axon-dependent. Methods Using rats, we combine retrobulbar optic nerve transection (ONT) with acute controlled elevation of intraocular pressure (CEI), to induce total optic nerve axon loss and ONH astrocyte reactivity, respectively. Animals were euthanized immediately or 1 day post CEI, in the presence or absence of ONT. ONH sections were labeled with fluorescent-tagged phalloidin and antibodies against β3 tubulin, phosphorylated cortactin, phosphorylated paxillin, or complement C3. ONH label intensities were quantified after confocal microscopy. Retrobulbar nerves were assessed for axon injury by light microscopy. Results While ONT alone had no effect on ONH astrocyte structural orientation, astrocytes demonstrated significant reorganization of cellular extensions within hours after CEI, even when combined with ONT. However, ONH astrocytes displayed differential intensities of actin (phosphorylated cortactin) and focal adhesion (phosphorylated paxillin) mediators in response to CEI alone, ONT alone, or the combination of CEI and ONT. Lastly, label intensities of complement C3 within the ONH were unchanged in eyes subjected to CEI alone, ONT alone, or the combination of CEI and ONT, relative to controls. Conclusions Early ONH astrocyte structural reactivity to elevated IOP is multifaceted, displaying both axon dependent and independent responses. These findings have important implications for pursuing astrocytes as diagnostic and therapeutic targets in neurodegenerative disorders with fluctuating levels of axon injury.
Not only cancer: the long non-coding RNA MALAT1 affects the repertoire of alternatively spliced transcripts and circular RNAs in multiple sclerosis

Long non-coding RNAs (lncRNAs) are post-transcriptional and epigenetic regulators, whose implication in neurodegenerative and autoimmune diseases remains poorly understood. We analyzed publicly available microarray data sets to identify dysregulated lncRNAs in multiple sclerosis (MS), a neuroinflammatory autoimmune disease. We found a consistent upregulation in MS of the lncRNA MALAT1 (2.7-fold increase; meta-analysis, P = 1.3 × 10-8; 190 cases, 182 controls), known to regulate alternative splicing (AS). We confirmed MALAT1 upregulation in two independent MS cohorts (1.5-fold increase; P < 0.01; 59 cases, 50 controls). We hence performed MALAT1 overexpression/knockdown in cell lines, demonstrating that its modulation impacts on endogenous expression of splicing factors (HNRNPF and HNRNPH1) and on AS of MS-associated genes (IL7R and SP140). Minigene-based splicing assays upon MALAT1 modulation recapitulated IL7R and SP140 isoform unbalances observed in patients. RNA-sequencing of MALAT1-knockdown Jurkat cells further highlighted MALAT1 role in splicing (approximately 1100 significantly-modulated AS events) and revealed its contribution to backsplicing (approximately 50 differentially expressed circular RNAs). Our study proposes a possible novel role for MALAT1 dysregulation and the consequent AS alteration in MS pathogenesis, based on anomalous splicing/backsplicing profiles of MS-relevant genes.
Suppression of chemotherapy-induced cytokine/lipid mediator surge and ovarian cancer by a dual COX-2/sEH inhibitor

Significance Our study demonstrates that ovarian tumor cell debris generated by front-line chemotherapy promotes tumor growth by stimulating the release of proinflammatory cytokines and lipid mediators in the tumor microenvironment. Targeting the debris-mediated surge of protumorigenic factors provides a strategy for enhancing the efficacy of cytotoxic therapies. Here, we show that the dual cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) inhibitor PTUPB prevented the chemotherapy-induced cytokine/lipid surge and suppressed debris-stimulated ovarian tumor growth. Dual COX-2/sEH inhibition may have clinical implications for use in combination with cytotoxic cancer therapies to alleviate debris-mediated inflammation. Our results indicate that PTUPB may act as a “surge protector” against therapy-induced protumorigenic mediators to improve patient survival by preventing tumor recurrence. Although chemotherapy is a conventional cancer treatment, it may induce a protumorigenic microenvironment by triggering the release of proinflammatory mediators. In this study, we demonstrate that ovarian tumor cell debris generated by first-line platinum- and taxane-based chemotherapy accelerates tumor progression by stimulating a macrophage-derived “surge” of proinflammatory cytokines and bioactive lipids. Thus, targeting a single inflammatory mediator or pathway is unlikely to prevent therapy-induced tumor progression. Here, we show that combined pharmacological abrogation of the cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) pathways prevented the debris-induced surge of both cytokines and lipid mediators by macrophages. In animal models, the dual COX-2/sEH inhibitor PTUPB delayed the onset of debris-stimulated ovarian tumor growth and ascites leading to sustained survival over 120 days postinjection. Therefore, dual inhibition of COX-2/sEH may be an approach to suppress debris-stimulated ovarian tumor growth by preventing the therapy-induced surge of cytokines and lipid mediators.
Day 7 blastocyst euploidy supports routine implementation for cycles using preimplantation genetic testing

Objective: To determine if Day 7 blastocysts merit biopsy, vitrification and transfer consideration by contrasting their aneuploidy and implantation rates to Day 5 and 6 blastocysts. Methods: A total of 1,925 blastocysts were biopsied from 402 PGT-A cycles over a 12 to 16 month interval. All embryos were cultured under tri-gas, humidified conditions (37ºC) for up to 7 days (168 hours post-insemination). Biopsied blastocysts were vitrified and trophectoderm samples analyzed using NextGen sequencing. Single euploid embryo transfers were performed (n=254) using either a Day 5 (n=145), Day 6 (n=92) or a Day 7 blastocyst (n=16) post-warming. Euploidy rates and pregnancy outcomes were subsequently assessed and differences determined by day of development and blastocyst quality grade. Results: No differences were observed in implantation, pregnancy loss or ongoing pregnancy rates between Day 5 and Day 6 blastocysts. Development to Day 7 accounted for 6.6% of all blastocysts. Euploidy rates were higher in Day 5 blastocysts (53.5%; p<0.05) compared to Day 6 (40.4%) and Day 7 (35.9%). High implantation potential (56.3% to 79.3%) of vitrified-warmed euploid blastocyst occurred independent to the day of development. However, miscarriage/loss rates increased (22.2% vs. 2%; p<0.05) with Day 7 blastocysts, resulting in lower (p<0.05) live birth rates (43.8% vs. 67.4-77.2%). Conclusion: Culturing blastocysts to Day 7 has proven beneficial by achieving viable euploid embryos that would have otherwise been discarded. An extra Day of embryo growth allows select patients additional opportunities for in vitro development and possible healthy term live births.
Evaluation of a new generation phytase on phytate phosphorus release for egg production and tibia strength in hens fed a corn-soybean meal diet

ABSTRACT To test the effect of several inclusion levels of Citrobacter braakii phytase (CBP), on phytate P release, 420 50‐wk‐old‐Bovans White hens were randomly allocated to 7 treatments with 5 replicates of 12 hens each. The experimental period lasted 12 weeks, first 8 for adaptation and last 4 for data collection. Feed and water were provided ad libitum. Treatments were: (1) a 0.12% basal corn‐soybean meal diet deficient only in non‐phytate P. Treatments 2 and 3 were added with constant increases of 0.11% inorganic P, to get a linear hen response to P addition. Treatments 4 to 7 were the addition of 300; 600; 1,200; and 1,800 phytase units (FYT)/kg to the basal diet. Variables analyzed were hen productive performance (HPP) and tibia resistance to fracture (TRF), and mineral content. Data were analyzed as a Complete Randomized Design (CRD). The results from treatments 1 to 3 were analyzed by a regression model to test for a significant linear response (P < 0.05). Then for every level of CBP added (treatments 4 to 7), the linear regression equation was solved to find out the equivalent value of released P. Based on hen health and welfare, the response variables that yielded realistic P equivalence values for the CBP levels used in the present trial were the tibia data. Following the significant (P < 0.001) linear response, the equations; TRF, kg (Y = 28.16X + 17.42 R2 = 0.84); Tibia Ca, % (Y = 11.6X + 14.2 R2 = 0.80); Tibia P, % (Y = 11.6X + 6.1 R2 = 0.81); and T ash, % (Y = 33.3X + 38.1 R2 = 0.80). Under the experimental conditions of this trial, the HPP variables were not a sensitive parameter to measure P release; whereas, tibia parameters showed the following average P release values per level of CBP inclusion in the corn‐ soybean meal diet; 300 FYT/kg = 0.099%, 600 FYT/kg = 0.141%, 1,200 FYT/kg = 0.182%, and 1,800 FYT/kg = 0.198%.
Discovering heritable modes of MEG spectral power

Brain structure and many brain functions are known to be genetically controlled, but direct links between neuroimaging measures and their underlying cellular‐level determinants remain largely undiscovered. Here, we adopt a novel computational method for examining potential similarities in high‐dimensional brain imaging data between siblings. We examine oscillatory brain activity measured with magnetoencephalography (MEG) in 201 healthy siblings and apply Bayesian reduced‐rank regression to extract a low‐dimensional representation of familial features in the participants' spectral power structure. Our results show that the structure of the overall spectral power at 1–90 Hz is a highly conspicuous feature that not only relates siblings to each other but also has very high consistency within participants' own data, irrespective of the exact experimental state of the participant. The analysis is extended by seeking genetic associations for low‐dimensional descriptions of the oscillatory brain activity. The observed variability in the MEG spectral power structure was associated with SDK1 (sidekick cell adhesion molecule 1) and suggestively with several other genes that function, for example, in brain development. The current results highlight the potential of sophisticated computational methods in combining molecular and neuroimaging levels for exploring brain functions, even for high‐dimensional data limited to a few hundred participants.