Miracle-dz/UniFAR-FTUs huggingface dataset:
Childhood sexual and physical abuse: age at exposure modulates impact on functional outcome in early psychosis patients

Background Evidence suggests a relationship between exposure to trauma during childhood and functional impairments in psychotic patients. However, the impact of age at the time of exposure has been understudied in early psychosis (EP) patients. Method Two hundred and twenty-five patients aged 18–35 years were assessed at baseline and after 2, 6, 18, 24, 30 and 36 months of treatment. Patients exposed to sexual and/or physical abuse (SPA) were classified according to age at the time of first exposure (Early SPA: before age 11 years; Late SPA: between ages 12 and 15 years) and then compared to patients who were not exposed to such trauma (Non-SPA). The functional level in the premorbid phase was measured with the Premorbid Adjustment Scale (PAS) and with the Global Assessment of Functioning (GAF) scale and the Social and Occupational Functioning Assessment Scale (SOFAS) during follow-up. Results There were 24.8% of patients with a documented history of SPA. Late SPA patients were more likely to be female (p = 0.010). Comparison with non-SPA patients revealed that: (1) both Early and Late SPA groups showed poorer premorbid social functioning during early adolescence, and (2) while patients with Early SPA had poorer functional level at follow-up with lower GAF (p = 0.025) and lower SOFAS (p = 0.048) scores, Late SPA patients did not. Conclusion Our results suggest a link between exposure to SPA and the later impairment of social functioning before the onset of the disease. EP patients exposed to SPA before age 12 may present long-lasting functional impairment, while patients exposed at a later age may improve in this regard and have a better functional outcome.
The role of thioredoxin reductase 1 in melanoma metabolism and metastasis

Although significant progress has been made in targeted and immunologic therapeutics for melanoma, many tumors fail to respond, and most eventually progress when treated with the most efficacious targeted combination therapies thus far identified. Therefore, alternative approaches that exploit distinct melanoma phenotypes are necessary to develop new approaches for therapeutic intervention. Tissue microarrays containing human nevi and melanomas were used to evaluate levels of the antioxidant protein thioredoxin reductase 1 (TR1), which was found to increase as a function of disease progression. Melanoma cell lines revealed metabolic differences that correlated with TR1 levels. We used this new insight to design a model treatment strategy that creates a synthetic lethal interaction wherein targeting TR1 sensitizes melanoma to inhibition of glycolytic metabolism, resulting in a decrease in metastases in vivo. This approach holds the promise of a new clinical therapeutic strategy, distinct from oncoprotein inhibition.
Effect of vegf gene therapy and hyaluronic acid film sheath on peripheral nerve regeneration

Functional nerve regeneration after reconstructive nerve surgery remains unsatisfying. In this study, vascular endothelial growth factor (VEGF) gene therapy combined with a hyaluronic acid (HA)‐enriched microenvironment in nerve regeneration was investigated. Sciatic nerve was transected, and end‐to‐end neurorrhaphy was performed on 32 male Sprague‐Dawley rats, which were randomly divided into four groups (n = 8 per group): nerve coaptation without treatment (group I); nerve coaptation covered with HA film sheath (group II); nerve coaptation with intramuscular VEGF gene in plasmid injection (group III); and nerve coaptation combined with HA film sheath and intramuscular VEGF gene in plasmid injection (group IV). Contralateral sciatic nerves were used as control. VEGF expression was verified from gluteal muscle biopsies surrounding the sciatic nerve by reverse transcriptase‐PCR. Electrophysiological, histopathological, and electron microscopic evaluations were performed after 4 weeks. Mean peak amplitude of groups I–IV and nonoperated sciatic nerve were 4.5 ± 0.6 mV, 6.4 ± 0.4 mV, 6.7 ± 0.5 mV, 8.5 ± 0.4 mV, and 9.8 ± 0.5 mV, respectively. Mean myelinated axonal counts of groups I–IV and nonoperated sciatic nerve were 105 ± 24, 165 ± 19, 181 ± 22, 271 ± 23, and 344 ± 17, respectively. Treatment with HA film sheath coverage combined with intramuscular VEGF gene in plasmid injection yielded statistically significant higher peak amplitudes and myelinated axonal counts (P < 0.001). In addition, significantly less scar formation with HA administration (groups II and IV; P < 0.001) was found. Thus, it was found that VEGF might crucially regulate nerve regeneration processes and that HA can reduce the scar formation. This study showed that the combination of HA film sheath and VEGF gene may synergistically promote peripheral nerve regeneration. © 2013 Wiley Periodicals, Inc. Microsurgery 34:209–216, 2014.
Behavioral and neurodevelopmental precursors to binge-type eating disorders: support for the role of negative valence systems

Background. Pediatric loss-of-control (LOC) eating is a robust behavioral precursor to binge-type eating disorders. Elucidating precursors to LOC eating and binge-type eating disorders may refine developmental risk models of eating disorders and inform interventions. Method. We review evidence within constructs of the Negative Valence Systems (NVS) domain, as specified by the Research Domain Criteria framework. Based on published studies, we propose an integrated NVS model of binge-type eating-disorder risk. Results. Data implicate altered corticolimbic functioning, neuroendocrine dysregulation, and self-reported negative affect as possible risk factors. However, neuroimaging and physiological data in children and adolescents are sparse, and most prospective studies are limited to self-report measures. Conclusions. We discuss a broad NVS framework for conceptualizing early risk for binge-type eating disorders. Future neural and behavioral research on the developmental trajectory of LOC and binge-type eating disorders is required.
Soft tissue reconstruction with omental free flap in complex upper extremity injuries: Report of 13 cases

Although there is a wide list of free flaps options for soft tissue reconstruction of complex upper extremity injuries, the omental flap has some useful anatomical and biochemical advantages. We report 13 patients who underwent hand or upper extremity reconstruction with omental free flaps. Nine patients had extensive tissue damage, resulting with digital cyanosis and hypothermia, and some of them with areas of cutaneous necrosis, or avulsed tissues with tendons and bones exposed or infected. The remaining four patients had minor extensive tissue damage without circulatory problems. Patient's average age was 34.6 years. Twelve flaps were harvested through laparotomy and one laparoscopically. All flaps were covered with a skin graft. None of the flaps were lost. The average follow‐up time was 20 months. There was one major and two minor donor site complications. One patient had minor loss of the skin graft in the recipient site, and two required minor additional surgeries to improve the appearance or function of the hand or upper extremity. There were no late abdominal complications in any patient. The morphological appearance and functional results were favorable in 11 of them, and permitted their reincorporation into society without the need for additional complex surgeries. Only two patients had a poor outcome. Our experience confirms that the omental flap may be a good option for reconstruction of some complex hand and upper extremity injuries. © 2014 Wiley Periodicals, Inc. Microsurgery 34:425–433, 2014.
Investigation of metamemory functioning in the at-risk mental state for psychosis

Background Metamemory describes the monitoring and knowledge about one's memory capabilities. Patients with schizophrenia have been found to be less able in differentiating between correct and false answers (smaller confidence gap) when asked to provide retrospective confidence ratings in previous studies. Furthermore, higher proportions of very-high-confident but false responses have been found in this patient group (high knowledge corruption). Whether and how these biases contribute to the early pathogenesis of psychosis is yet unclear. This study thus aimed at investigating metamemory function in the early course of psychosis. Method Patients in an at-risk mental state for psychosis (ARMS, n = 34), patients with a first episode of psychosis (FEP, n = 21) and healthy controls (HCs, n = 38) were compared on a verbal recognition task combined with retrospective confidence-level ratings. Results FEP patients showed the smallest confidence gap, followed by ARMS patients, followed by HCs. All groups differed significantly from each other. Regarding knowledge corruption, FEP patients differed significantly from HCs, whereas a statistical trend was revealed in comparison of ARMS and FEP groups. Correlations were revealed between metamemory, measures of positive symptoms and working memory performance. Conclusions These data underline the presence of a metamemory bias in ARMS patients which is even more pronounced in FEP patients. The bias might represent an early cognitive marker of the beginning psychotic state. Longitudinal studies are needed to unravel whether metacognitive deficits predict the transition to psychosis and to evaluate therapeutic interventions.
Neural reward processing in individuals remitted from major depression

Background. Dysfunctional behavioural and neural processing of reward has been found in currently depressed individuals. However, little is known about altered reward processing in remitted depressed individuals. Method. A total of 23 medication-free individuals with remitted major depressive disorder (rMDD) and 23 matched healthy controls (HCs) performed a reward task during functional magnetic resonance imaging. We also investigated reward dependence, novelty seeking and harm avoidance using the Tridimensional Personality Questionnaire and their association with neural responses of reward processing. Results. Compared to HCs, individuals with rMDD exhibited enhanced responses to reward-predicting cues in the hippocampus, amygdala and superior frontal gyrus. When reward was delivered, rMDD subjects did not significantly differ from HCs. In both groups neural activity during reward anticipation was negatively correlated with harm avoidance. Conclusions. Our results show that rMDD is characterized by hyperactivation in fronto-limbic regions during reward anticipation. Alterations in neural activation during reward processing might reflect an increased effort in remitted depressed individuals to allocate neural activity for executive and evaluative processes during anticipatory reward processing.
The amnion muscle combined graft (AMCG) conduits: A new alternative in the repair of wide substance loss of peripheral nerves

The use of autologous sural nerve grafts is still the current gold standard for the repair of peripheral nerve injuries with wide substance losses, but with a poor rate of functional recovery after repair of mixed and motor nerves, a limited donor nerve supply, and morbidity of donor site. At present, tubulization through the muscle vein combined graft, is a viable alternative to the nerve autografts and certainly is a matter of tissue engineering still open to continuous development, although this technique is currently limited to a critical gap of 3 cm with less favorable results for motor function recovery. In this report, we present a completely new tubulization method, the amnion muscle combined graft (AMCG) technique, that consists in the combination of the human amniotic membrane hollow conduit with autologous skeletal muscle fragments for repairing the substance loss of peripheral nerves and recover both sensory and motor functions. In a series of five patients with loss of substance of the median nerve ranging 3–5 cm at the wrist, excellent results graded as S4 in two cases, S3+ in two cases, and S3 in one case; M4 in four cases and M3 in one case were achieved. No iatrogenic damage due to withdrawal of a healthy nerve from donor site was observed. This technique allows to repair extensive loss of substance up to 5 cm with a good sensory and motor recovery. The AMCG thus may be considered a reasonable alternative to traditional nerve autograft in selected clinical conditions. © 2014 Wiley Periodicals, Inc. Microsurgery 34:616–622, 2014.
Transcription factors as critical players in melanoma invasiveness, drug resistance, and opportunities for therapeutic drug development

Resistance to targeted therapy in cancer is often coupled with the acquisition of a pro‐invasive phenotype by tumors cells and a highly permissive tumor microenvironment promoting drug resistance. Transcription factors are frequently shown as major points of convergence of multiple dysregulated receptors and signaling pathways in cancer. Several transcription factors are now incriminated as drivers of both drug resistance and invasiveness. We focused this review on critical transcription factors playing a causal role in both the resistance to BRAF V600E‐targeted therapy and the pro‐invasive behavior of melanoma cells. Simultaneous rewiring of pro‐oncogenic signaling pathways, phenotype switching or phenotypic plasticity supporting pro‐invasive/pro‐metastatic behavior, actin remodeling, and bidirectional interactions between tumor microenvironment and melanoma cells represent major challenges for overcoming resistance to BRAF V600E inhibitors (BRAFi) and will be discussed. Although it represents an underdeveloped area of translational investigation, inhibition of transcription factors may open new avenues to combat resistance to BRAFi.
Neural correlates of improved executive function following erythropoietin treatment in mood disorders

Background Cognitive dysfunction in depression and bipolar disorder (BD) is insufficiently targeted by available treatments. Erythropoietin (EPO) increases neuroplasticity and may improve cognition in mood disorders, but the neuronal mechanisms of these effects are unknown. This functional magnetic resonance imaging (fMRI) study investigated the effects of EPO on neural circuitry activity during working memory (WM) performance. Method Patients with treatment-resistant major depression, who were moderately depressed, or with BD in partial remission, were randomized to eight weekly infusions of EPO (40 000 IU) (N = 30) or saline (N = 26) in a double-blind, parallel-group design. Patients underwent fMRI, mood ratings and blood tests at baseline and week 14. During fMRI patients performed an n-back WM task. Results EPO improved WM accuracy compared with saline (p = 0.045). Whole-brain analyses revealed that EPO increased WM load-related activity in the right superior frontal gyrus (SFG) compared with saline (p = 0.01). There was also enhanced WM load-related deactivation of the left hippocampus in EPO-treated compared to saline-treated patients (p = 0.03). Across the entire sample, baseline to follow-up changes in WM performance correlated positively with changes in WM-related SFG activity and negatively with hippocampal response (r = 0.28–0.30, p < 0.05). The effects of EPO were not associated with changes in mood or red blood cells (p ⩾0.08). Conclusions The present findings associate changes in WM-load related activity in the right SFG and left hippocampus with improved executive function in EPO-treated patients. Clinical trial registration: clinicaltrials.gov: NCT00916552.
Relationship between dietary intake in children with diabetes mellitus type I, their management at diagnosis, social factors, anthropometry and glycaemic control

Background: In diabetes mellitus, dietary intake is important for metabolic control and contributes to the risk of developing microvascular and macrovascular complications. Little is known about factors influencing dietary intake. Objectives: To ascertain the long-term influence of two initial programmes of treatment of diabetes mellitus type I in children and adolescents on dietary intake and to compare with dietary recommendations. To examine for correlations with social factors, anthropometry and glycaemic control. Design: Children, 3-15 years of age, were chosen at random to be treated either in a paediatric ward (the control group) or, partly, in an apartment where their families were provided with extra psychological support and practical education (the study group). A prospective dietary assessment of 34 children with diabetes mellitus was performed, using 4 day food diaries at 6, 12 and 24 months after diagnosis. Results: Both management groups complied we ll with the dietary recommendations, showed stable nutritional habits during the first 2 years after diagnosis and had favourable intake concerning fat and carbohydrates compared with healthy children. The study group demonstrated less day-to-day variation in their consumption of polyunsaturated fat. Few dietary correlations to social factors were shown. There were no significant correlations between dietary intake and age or gender. High long-term HbA1c (8.3%, 5 years) was significantly associated with a higher intake of total fat, and more pronounced day-to-day variation in energy, carbohydrates and polyunsaturated fat. Conclusions: Both treatment programmes appear well suited for establishing and maintaining recommended dietary intake. The home-like environment of the training apartment made it possible to illustrate the dietary customs of the child and family, and permitted an individual nutritional education with behaviour modification. The importance of the quantity an d quality of fat consumed must be emphasized strongly. Keywords: children; diet; glycaemic control; insulin-dependent diabetes mellitus (type I); management regimen; social factors
Impact of childhood and adulthood psychological health on labour force participation and exit in later life

Background Adulthood psychological health predicts labour force activity but few studies have examined childhood psychological health. We hypothesized that childhood psychological ill-health would be associated with labour force exit at 55 years. Method Data were from the 55-year follow-up of the National Child Development Study (n = 9137). Labour force participation and exit (unemployment, retirement, permanent sickness, homemaking/other) were self-reported at 55 years. Internalizing and externalizing problems in childhood (7, 11 and 16 years) and malaise in adulthood (23, 33, 42, 50 years) were assessed. Education, social class, periods of unemployment, partnership separations, number of children, and homemaking activity were measured throughout adulthood. Results Childhood internalizing and externalizing problems were associated with unemployment, permanent sickness and homemaking/other at 55 years, after adjustment for adulthood psychological health and education: one or two reports of internalizing was associated with increased risk for unemployment [relative risk (RR) 1.59, 95% confidence interval (CI) 1.12–2.25; RR 2.37, 95% CI 1.48–3.79] and permanent sickness (RR 1.32, 95% CI 1.00–1.74; RR, 1.48, 95% CI 1.00–2.17); three reports of externalizing was associated with increased risk for unemployment (RR 2.26, 95% CI 1.01–5.04), permanent sickness (RR 2.63, 95% CI 1.46–4.73) and homemaking/other (RR 1.95, 95% CI 1.00–3.78). Conclusions Psychological ill-health across the lifecourse, including during childhood, reduces the likelihood of working in older age. Support for those with mental health problems at different life stages and for those with limited connections to the labour market, including homemakers, is an essential dimension of attempts to extend working lives.
Using self-report surveys at the beginning of service to develop multi-outcome risk models for new soldiers in the U.S. Army

Background The U.S. Army uses universal preventives interventions for several negative outcomes (e.g. suicide, violence, sexual assault) with especially high risks in the early years of service. More intensive interventions exist, but would be cost-effective only if targeted at high-risk soldiers. We report results of efforts to develop models for such targeting from self-report surveys administered at the beginning of Army service. Methods 21 832 new soldiers completed a self-administered questionnaire (SAQ) in 2011–2012 and consented to link administrative data to SAQ responses. Penalized regression models were developed for 12 administratively-recorded outcomes occurring by December 2013: suicide attempt, mental hospitalization, positive drug test, traumatic brain injury (TBI), other severe injury, several types of violence perpetration and victimization, demotion, and attrition. Results The best-performing models were for TBI (AUC = 0.80), major physical violence perpetration (AUC = 0.78), sexual assault perpetration (AUC = 0.78), and suicide attempt (AUC = 0.74). Although predicted risk scores were significantly correlated across outcomes, prediction was not improved by including risk scores for other outcomes in models. Of particular note: 40.5% of suicide attempts occurred among the 10% of new soldiers with highest predicted risk, 57.2% of male sexual assault perpetrations among the 15% with highest predicted risk, and 35.5% of female sexual assault victimizations among the 10% with highest predicted risk. Conclusions Data collected at the beginning of service in self-report surveys could be used to develop risk models that define small proportions of new soldiers accounting for high proportions of negative outcomes over the first few years of service.
Probabilistic Modeling of Conformational Space for 3D Machine Learning Approaches

We present a new probabilistic encoding of the conformational space of a molecule that allows for the integration into common similarity calculations. The method uses distance profiles of flexible atom‐pairs and computes generative models that describe the distance distribution in the conformational space. The generative models permit the use of probabilistic kernel functions and, therefore, our approach can be used to extend existing 3D molecular kernel functions, as applied in support vector machines, to build QSAR models. The resulting kernels are valid 4D kernel functions and reduce the dependency of the model quality on suitable conformations of the molecules. We showed in several experiments the robust performance of the 4D kernel function, which was extended by our approach, in comparison to the original 3D‐based kernel function. The new method compares the conformational space of two molecules within one kernel evaluation. Hence, the number of kernel evaluations is significantly reduced in comparison to common kernel‐based conformational space averaging techniques. Additionally, the performance gain of the extended model correlates with the flexibility of the data set and enables an a priori estimation of the model improvement.
Letter to the Editor: Is poor sleep, and loneliness linked by increased use of technology?

Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.