Miracle-dz/UniFAR-FTUs huggingface dataset:
Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia

Background Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls. Method Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer). Results In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls. Conclusions This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.
Clarifying the causal relationship in women between childhood sexual abuse and lifetime major depression

Background Childhood sexual abuse (CSA) is strongly associated with risk for major depression (MD) but the degree to which this association is causal remains uncertain. Method We applied structural equation modeling using the Mplus program to 1493 longitudinally assessed female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Results Our model included (i) retrospective self- and co-twin reports on CSA, (ii) major potentially confounding covariates, (iii) assessment of lifetime history of MD at two separate interviews, and (iv) mood-congruent recall (implemented by allowing current depressive symptoms to predict reporting of CSA). In a model with only measurement error, CSA explained 9.6% of MD. Including four key covariates reduced the variance explained to 5.3%, with the largest effects found for parental loss and low parental warmth. Adding the effect of mood-congruent recall to a final well-fitting model reduced the percentage of variance explained in lifetime MD (LTMD) by CSA to 4.4%. In this model, current depressive symptoms significantly predicted recall of CSA. Conclusions In a model correcting for measurement error, confounding and the impact of mood-congruent recall, CSA remains substantially associated with the risk for LTMD in women. These findings strongly suggest, but do not prove, that this association is causal, and are consistent with previous results in this sample using a co-twin control design, but also indicate that more than half of the uncorrected CSA–MD association is probably not causal. Traumatic life experiences contribute substantially to the risk for LTMD.
Continuous Exposure to Simulated Hypergravity-Induced Changes in Proliferation, Morphology, and Gene Expression of Human Tendon Cells.

Gravity influences physical and biological processes, especially during development and homeostasis of several tissues in the human body. Studies under altered gravity have been receiving great attention toward a better understanding of microgravity-, hypogravity (<1 g)-, or hypergravity (>1 g)-induced alterations. In this work, the influence of simulated hypergravity over human tendon-derived cells (hTDCs) was studied at 5, 10, 15, and 20 g for 4 or 16 h, using a large diameter centrifuge. Main results showed that 16 h of simulated hypergravity limited cell proliferation. Cell area was higher in hTDCs cultured at 5, 10, and 15 g for 16 h, in comparison to 1 g control. Actin filaments were more pronounced in hTDCs cultured at 5 and 10 g for 16 h. Focal adhesion kinase (FAK) was mainly expressed in focal adhesion sites upon hypergravity stimulation, in comparison to perinuclear localization in control cells after 16 h; and FAK number/cell increased with increasing g-levels. A tendency toward an upregulation of tenogenic markers was observed; scleraxis (SCX), tenascin C (TNC), collagen type III (COL3A1), and decorin (DCN) were significantly upregulated in hTDCs cultured at 15 g and COL3A1 and DCN were significantly upregulated in hTDCs cultured at 20 g. Overall, simulated hypergravity affected the behavior of hTDCs, with more pronounced effects in the long-term period (16 h) of stimulation.
Late-Night Snacking Decreases Nocturnal Secretion of Growth Hormone

The effect of snacking before going to sleep on the nocturnal secretion of GH was investigated in 7 children with non-GH deficiency short stature. Each child was tested on two nights: on one night, the child ate a snack before going to bed, but on the other night, the child did not. Serum GH concentrations were measured every 20 min during the first 3 h of sleep. GH concentrations in urine collected the following morning were also examined. Mean and maximum serum GH values, and urinary GH concentrations were lower in all of the children when they had eaten a snack before going to bed.
Rice phytoglobins regulate responses under low mineral nutrients and abiotic stresses in Arabidopsis thaliana.

Just like animals, plants also contain haemoglobins (known as phytoglobins in plants). Plant phytoglobins (Pgbs) have been categorized into 6 different classes, namely, Phytogb0 (Pgb0), Phytogb1 (Pgb1), Phytogb2 (Pgb2), SymPhytogb (sPgb), Leghaemoglobin (Lb), and Phytogb3 (Pgb3). Among the 6 Phytogbs, sPgb and Lb have been functionally characterized, whereas understanding of the roles of other Pgbs is still evolving. In our present study, we have explored the function of 2 rice Pgbs (OsPgb1.1 and OsPgb1.2). OsPgb1.1, OsPgb1.2, OsPgb1.3, and OsPgb1.4 displayed increased level of transcript upon salt, drought, cold, and ABA treatment. The overexpression (OX) lines of OsPgb1.2 in Arabidopsis showed a tolerant phenotype in terms of better root growth in low potassium (K+ ) conditions. The expression of the known K+ gene markers such as LOX2, HAK5, and CAX3 was much higher in the OsPgb1.2 OX as compared to wild type. Furthermore, the OsPgb1.2 OX lines showed a decrease in reactive oxygen species (ROS) production and conversely an increase in the K+ content, both in root and shoot, as compared to wild type in K+ limiting condition. Our results indicated the potential involvement of OsPgb1.2 in signalling networks triggered by the nutrient deficiency stresses.
Comparison of non-directive counselling and cognitive behaviour therapy for patients presenting in general practice with an ICD-10 depressive episode: a randomized control trial

Background Most evidence in the UK on the effectiveness of brief therapy for depression concerns cognitive behaviour therapy (CBT). In a trial published in 2000, we showed that non-directive counselling and CBT were equally effective in general practice for patients with depression and mixed anxiety and depression. Our results were criticized for including patients not meeting diagnostic criteria for a depressive disorder. In this reanalysis we aimed to compare the effectiveness of the two therapies for patients with an ICD-10 depressive episode. Method Patients with an ICD-10 depressive episode or mixed anxiety and depression were randomized to counselling, CBT or usual general practitioner (GP) care. Counsellors provided nondirective, interpersonal counselling following a manual that we developed based on the work of Carl Rogers. Cognitive behaviour therapists provided CBT also guided by a manual. Modelling was carried out using generalized estimating equations with the multiply imputed datasets. Outcomes were mean scores on the Beck Depression Inventory, Brief Symptom Inventory, and Social Adjustment Scale at 4 and 12 months. Results A total of 134 participants were randomized to CBT, 126 to counselling and 67 to usual GP care. We undertook (1) an interaction analysis using all 316 patients who were assigned a diagnosis and (2) a head-to-head comparison using only those 130 (41%) participants who had an ICD-10 depressive episode at baseline. CBT and counselling were both superior to GP care at 4 months but not at 12 months. There was no difference in the effectiveness of the two psychological therapies. Conclusions We recommend that national clinical guidelines take our findings into consideration in recommending effective alternatives to CBT.
Alterations in brain structure in adults with anorexia nervosa and the impact of illness duration

Background Brain structure alterations have been reported in anorexia nervosa, but findings have been inconsistent. This may be due to inadequate sample size, sample heterogeneity or differences in methodology. Method High resolution magnetic resonance images were acquired of 33 adult participants with anorexia nervosa and 33 healthy participants, the largest study sample to date, in order to assess whole-brain volume, ventricular cerebrospinal fluid, white matter and grey matter volume. Voxel-based morphometry was conducted to assess regional grey matter volume. Levels of depression, anxiety, obsessionality and eating disorder-related symptoms were measured and used to explore correlations with brain structure. Results Participants with anorexia nervosa had smaller brain volumes as well as a global decrease in grey matter volume with ventricular enlargement. Voxel-based morphometry revealed a decrease in grey matter volume spanning across the cerebellum, temporal, frontal and occipital lobes. A correlation was found between grey matter volume loss and duration of illness in the cerebellum and mesencephalon. No correlations were found with clinical measures. Conclusions Findings are in accordance with several previous studies on brain structure and match functional studies that have assessed the symptomatology of anorexia nervosa, such as body image distortion and cognitive bias to food. The correlation with duration of illness supports the implication of cerebellar atrophy in the maintenance of low weight and disrupted eating behaviour and illustrates its role in the chronic phase of anorexia nervosa. The lack of other correlations suggests that these findings are not related to the presence of co-morbid disorders.
Plasticity of photosynthetic heat tolerance in plants adapted to thermally contrasting biomes.

In many biomes, plants are subject to heatwaves, potentially causing irreversible damage to the photosynthetic apparatus. Field surveys have documented global, temperature-dependent patterns in photosynthetic heat tolerance (PHT ); however, it remains unclear if these patterns reflect acclimation in PHT or inherent differences among species adapted to contrasting habitats. To address these unknowns, we quantified seasonal variations in Tcrit (high temperature where minimal chlorophyll-a fluorescence rises rapidly, reflecting disruption to photosystem II) in 62 species native to 6 sites from 5 thermally contrasting biomes across Australia. Tcrit and leaf fatty acid (FA) composition (important for membrane stability) were quantified in three temperature-controlled glasshouses in 20 of those species. Tcrit was greatest at hot field sites and acclimated seasonally (summer > winter, increasing on average 0.34 °C per °C increase in growth temperature). The glasshouse study showed that Tcrit was inherently higher in species from warmer habitats (increasing 0.16 °C per °C increase in origin annual mean maximum temperature) and acclimated to increasing growth temperature (0.24 °C °C-1 ). Variations in Tcrit were positively correlated with the relative abundance of saturated FAs, with FAs accounting for 40% of Tcrit variation. These results highlight the importance of both plastic adjustments and inherent differences determining contemporary continent-wide patterns in PHT .
Pharmacoeconomics of ciprofloxacin plus metronidazole vs. piperacillin-tazobactam for complicated intra-abdominal infections.

BACKGROUND A series of 459 hospitalized adults with complicated intra-abdominal infections participated in a randomized, double-blind, multicenter clinical trial. The present study was conducted to add a pharmacoeconomic analysis to the results. METHODS A cost-effectiveness analysis from the perspective of the hospital provider was carried out. Decision analysis was used to illustrate outcomes and to provide a basis on which to conduct a sensitivity analysis. Cost-effectiveness ratios, representing the cost per expected successfully treated patient, were calculated to determine the most cost-effective alternative. RESULTS Among 244 economically evaluable patients, enrolled from 34 centers in the U.S. and Canada, 131 patients received ciprofloxacin-metronidazole (75% clinical success rate), and 113 received piperacillin-tazobactam (65% clinical success rate; p = 0.06). Switch to oral antibiotics was possible for 81 patients who received ciprofloxacin-metronidazole (85% clinical success rate) and 67 piperacillin-tazobactam patients (70% clinical success rate; p = 0.027). The mean hospital cost was US$10,662 +/- 7,793 for patients in the ciprofloxacin-metronidazole group and $10,009 +/- 7,023 for patients in the piperacillin-tazobactam group (p = 0.492). Significantly lower costs were documented for patients who could be switched to oral antibiotics than for those continued on intravenous antibiotic orders ($8,684 +/- 4,120 vs. $12,945 +/- 10,204, respectively; p < 0.001). Patients with appendicitis had lower mean hospital costs than those with other infections ($7,169 +/- 3,705 vs. $12,097 +/- 8,342, respectively; p < 0.001). The cost-effectiveness ratios were $14,216:1 for patients in the ciprofloxacin-metronidazole group and $15,398:1 for patients in the piperacillin-tazobactam group. CONCLUSIONS The mean hospital costs associated with ciprofloxacin-metronidazole were similar to those of piperacillin-tazobactam for the treatment of adults with complicated intra-abdominal infections. Lower costs were documented for patients able to be switched to oral antibiotics and for patients with appendicitis.
A phase-specific psychological therapy for people with problematic cannabis use following a first episode of psychosis: a randomized controlled trial

Background Cannabis use is high amongst young people who have recently had their first episode of psychosis, and is associated with worse outcomes. To date, interventions to reduce cannabis consumption have been largely ineffective, and it has been suggested that longer treatment periods are required. Method In a pragmatic single-blind randomized controlled trial 110 participants were randomly allocated to one of three conditions: a brief motivational interviewing and cognitive behavioural therapy (MI-CBT) intervention (up to 12 sessions over 4.5 months) with standard care from an early intervention service; a long MI-CBT intervention (up to 24 sessions over 9 months) with standard care; or standard care alone. The primary outcome was change in cannabis use as measured by Timeline Followback. Results Neither the extended nor the brief interventions conferred benefit over standard care in terms of reductions in frequency or amount of cannabis use. Also the interventions did not result in improvements in the assessed clinical outcomes, including symptoms, functioning, hospital admissions or relapse. Conclusions Integrated MI and CBT for people with cannabis use and recent-onset psychosis does not reduce cannabis use or improve clinical outcomes. These findings are consistent with those in the published literature, and additionally demonstrate that offering a more extended intervention does not confer any advantage. Many participants were not at an action stage for change and for those not ready to reduce or quit cannabis, targeting associated problems rather than the cannabis use per se may be the best current strategy for mental health services to adopt.
Effects of human immunodeficiency virus status on trauma outcomes: a review of the national trauma database.

BACKGROUND The prevalence of human immunodeficiency virus (HIV) is disproportionately elevated in trauma patients. Although HIV traditionally has been associated with poorer outcomes among the critically ill, recent evidence suggests that the outcomes of surgical patients have improved with the greater use of antiretroviral regimens. The purpose of this study was to utilize the National Trauma Data Bank (NTDB) to examine the impact of HIV on surgical outcomes in a large group of trauma patients. METHODS We identified all patients for whom HIV status at time of admission was recorded. Results were stratified by age and Injury Severity Score. Our primary outcome was death. Secondary outcomes were length of hospital stay (LOS), length of intensive care unit (ICU) stay, duration of mechanical ventilation, and complications. Data were analyzed using Student t-tests or chi-square analysis, as appropriate. RESULTS The overall mortality rates were not significantly different in the HIV-positive and HIV-negative groups. Mortality rates remained similar in the two groups even when stratifying by ISS and age, with the exception of those patients who were 65 years or older. The HIV-positive patients had significantly longer LOS (7.6 vs. 5.6 days), shorter duration of mechanical ventilation (6.3 vs. 8.3 days), and no difference in length of ICU stay. The HIV-positive patients were significantly more likely to develop pneumonia, bacteremia, or wound infection. CONCLUSIONS These findings are consistent with those of recent smaller studies that demonstrated no significant difference in the mortality rate for patients with HIV. Although mortality rates are similar, HIV-positive patients are more likely to develop certain infectious complications and to require a longer LOS. Infection with HIV remains a major public health issue in the U.S. and internationally, and further research is necessary to explore the relation between HIV status and trauma outcomes, particularly with regard to the possible effects of antiretroviral treatment and individual immune status.
Role of Rho/ROCK signaling in the interaction of melanoma cells with the blood–brain barrier

We have investigated the role of the Rho/ROCK signaling pathway in the interaction of metastatic melanoma cells with the brain endothelium. ROCK inhibition induced a shift of melanoma cells to the mesenchymal phenotype, increased the number of melanoma cells attached to the brain endothelium, and strengthened the adhesion force between melanoma and endothelial cells. Inhibition of ROCK raised the number of melanoma cells migrating through the brain endothelial monolayer and promoted the formation of parenchymal brain metastases in vivo. We have shown that inhibition of the Rho/ROCK pathway in melanoma, but not in brain endothelial cells, is responsible for this phenomenon. Our results indicate that the mesenchymal type of tumor cell movement is primordial in the transmigration of melanoma cells through the blood–brain barrier.
Impaired subjective well-being in schizophrenia is associated with reduced anterior cingulate activity during reward processing

Background Patients with schizophrenia have substantially reduced subjective well-being (SW) compared to healthy individuals. It has been suggested that diminished SW may be related to deficits in the neural processing of reward but this has not been shown directly. We hypothesized that, in schizophrenia, lower SW would be associated with attenuated reward-related activation in the reward network. Method Twenty patients with schizophrenia with a range of SW underwent a functional magnetic resonance imaging (fMRI) reward task. The brain activity underlying reward anticipation and outcome in schizophrenia was examined and compared to that of 12 healthy participants using a full factorial analysis. Region of interest (ROI) analyses of areas within the reward network and whole-brain analyses were conducted to reveal neural correlates of SW. Results Reward-related neural activity in schizophrenia was not significantly different from that of healthy participants; however, the patients with schizophrenia showed significantly diminished SW. Both ROI and whole-brain analyses confirmed that SW scores in the patients correlated significantly with activity, specifically in the dorsal anterior cingulate cortex (dACC), during both reward anticipation and reward outcome. This association was not seen in the healthy participants. Conclusions In patients with schizophrenia, reduced activation of the dACC during multiple aspects of reward processing is associated with lower SW. As the dACC has been widely linked to coupling of reward and action, and the link to SW is apparent over anticipation and outcome, these findings suggest that SW deficits in schizophrenia may be attributable to reduced integration of environmental rewarding cues, motivated behaviour and reward outcome.
Inverse regulation of melanoma growth and migration by Orai1/STIM2‐dependent calcium entry

Spontaneous melanoma phenotype switching is controlled by unknown environmental factors and may determine melanoma outcome and responsiveness to anticancer therapy. We show that Orai1 and STIM2 are highly expressed and control store‐operated Ca2+ entry in human melanoma. Lower extracellular Ca2+ or silencing of Orai1/STIM2 caused a decrease in intracellular Ca2+, which correlated with enhanced proliferation and increased expression of microphthalmia‐associated transcription factor, a marker for proliferative melanoma phenotype. In contrast, the invasive and migratory potential of melanoma cells was reduced upon silencing of Orai1 and/or STIM2. Accordingly, markers for a non‐proliferative, tumor‐maintaining phenotype such as JARID1B and Brn2 decreased. Immunohistochemical staining of primary melanomas and lymph node metastases revealed a heterogeneous distribution of Orai1 and STIM2 with elevated expression in the invasive rim of the tumor. In summary, our results support a dynamic model in which Orai1 and STIM2 inversely control melanoma growth and invasion. Pharmacological tuning of Orai1 and particularly STIM2 might thus prevent metastatic spread and render melanomas more susceptible to conventional therapy.