Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychological resilience associates with pain experience in women treated for breast cancer

Abstract Background and aims Psychological resilience refers to successful adaptation or a positive outcome in the context of significant life adversity, such as chronic pain. On the other hand, anxiety closely associates with pain. The aim of this study was to explore how anxiety and psychological resilience together associate with persistent and experimental pain. Methods In a cross-sectional design, we studied 160 patients who had previously been treated for breast cancer and who now reported at least moderate pain (NRS ≥ 4) in any area of the body. Psychological resilience was measured on the Resilience Scale-14, anxiety on the Hospital Anxiety and Depression Scale, and intensity and interference of persistent pain by means of the Brief Pain Inventory. The cold pressor test was conducted to assess sensitivity to experimental cold pain. Results The results showed that resilience associated with pain interference in persistent pain, and that anxiety moderated this effect. Higher psychological resilience was associated with lower pain interference and this association was stronger in patients with low anxiety than among patients with high anxiety. These effects were visible with regard to persistent pain but not in experimental cold pain. Conclusions These results indicate that chronic pain and experimental pain as well as pain severity and pain interference are psychologically different phenomena. Psychological resilience protects against pain interference but effectively only in patients with low anxiety. It is necessary also to consider protective factors in addition to vulnerability factors in cases of persistent pain. Implications Resilience has been considered a potential target for intervention in chronic pain. However, high levels of anxiety might diminish the protective effect of psychological resilience in clinical settings. Therefore, it is important to treat anxiety in addition to resilience enhancing interventions. Patients with low psychological distress might be more suitable for resilience enhancing interventions than patients with high anxiety.
Effects of parenteral glutamine in critically ill surgical patients: a systematic review and meta-analysis.

INTRODUCTION glutamine (GLN), the most abundant non-essential amino acid in the plasma, tends to be rapidly depleted in cells in situations of metabolic stress. Some studies have demonstrated the benefits of GLN supplementation on mortality, infection, and length of hospital stay. The objective of this review was to analyze whether parenteral supplementation with GLN has any relevant effect in critically ill surgical patients. METHODS based on a systematic database search, randomized clinical trials (RCTs) published since 1985 were included if they had evaluated the effect of parenteral GLN supplementation in critical surgical patients. The statistical analysis was performed using the RevMan 5.3 software. RESULTS seven RCTs were eligible for the meta-analysis. Parenteral glutamine supplementation was associated with a non-significant 24 % reduction in mortality (RR = 0.76; 95 % CI: 0.50-1.15). Infections were significantly reduced (RR = 0.60; 95 % CI: 0.45-0.80), and length of hospital stay was 4.09 days shorter (95 % CI: -6.71 to -1.46). CONCLUSION parenteral GLN usage in critical surgical patients seems to decrease infection and length of hospital stay, but we could not demonstrate a significant reduction in mortality.
In vivo cutaneous antinuclear antibody positivity in palisaded neutrophilic and granulomatous dermatitis

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is commonly associated with underlying systemic inflammatory and neoplastic diseases, infections, and drug reactions. In vivo cutaneous antinuclear antibodies (ANA) have been described in skin biopsies from patients with known autoimmune disorders, but not previously reported in the setting of PNGD. We present two patients with systemic lupus erythematosus (SLE) and histopathologically confirmed PNGD. Direct immunofluorescence (DIF) studies revealed in vivo cutaneous ANA positivity in both patients. DIF findings in the skin mirrored serum autoantibody results. ANA positivity in skin specimens is reported as highly predictive of systemic connective tissue diseases (SCTD), although specific testing is not currently recommended as part of the laboratory work‐up or diagnostic criteria for these disorders. In this case report, positive ANA results in skin biopsies of PNGD reflect the serological findings and clinical evidence of SLE in both patients. In vivo cutaneous ANA positivity is an interesting and supportive finding in PNGD in the setting of SCTD.
Isradipine enhancement of virtual reality cue exposure for smoking cessation: Rationale and study protocol for a double-blind randomized controlled trial.

Cigarette smoking remains a leading cause of preventable death in the United States, contributing to over 480,000 deaths each year. Although significant strides have been made in the development of effective smoking cessation treatments, most established interventions are associated with high relapse rates. One avenue for increasing the effectiveness of smoking cessation interventions is to design focused, efficient, and rigorous experiments testing engagement of well-defined mechanistic targets. Toward this aim, the current protocol will apply a pharmacologic augmentation strategy informed by basic research in animal models of addiction. Our goal is to evaluate the enhancing effect of isradipine, an FDA-approved calcium channel blocker, on the extinction of craving-a key mechanism of drug relapse after periods of abstinence. To activate craving robustly in human participants, we will use multimodal smoking cues including novel 360° video environments developed for this project and delivered through consumer virtual reality headsets. Adult smokers will take either isradipine or placebo and complete the cue exposure protocol in a double-blind randomized control trial. In order to test the hypothesis that isradipine will enhance retention of craving extinction, participants will repeat cue exposure 24 h later without the administration of isradipine or placebo. The study will be implemented in a primary care setting where adult smokers receive healthcare, and smoking behavior will be tracked throughout the trial with ecological momentary assessment.
Altered functional connectivity of the insula in a rat model of recurrent headache

Migraine is a pain disorder accompanied by various symptoms. The insula, a “cortical hub,” is involved in many functions. Few studies have focused on the insula in migraine. We explored the resting-state functional connectivity between the insula and other brain areas in rats subjected to repeated meningeal nociception which was commonly used as animal model of migraine. Inflammatory soup was infused through supradural catheters in conscious rats. The rats were subdivided based on the frequency of the inflammatory soup infusions. Magnetic resonance imaging data were acquired on rats 21 days after inflammatory soup infusion and functional connectivity seeded on the insula was analyzed. In the low-frequency inflammatory soup group, magnetic resonance imaging was performed again 1 h after the glyceryl trinitrate injection following baseline scanning. The cerebellum showed increased functional connectivity with the insula in the inflammatory soup groups. The insula showed increased functional connectivity with the medulla and thalamus in the ictal period in the low-frequency inflammatory soup rats. In the high-frequency inflammatory soup group, several areas showed increased functional connectivity with the insula, including the pons, midbrain, thalamus, temporal association cortex, and retrosplenial, visual, and sensory cortices. Our findings support the hypothesis that the headache phase of migraine depends on the activation and sensitization of the trigeminovascular system, and that the chronification of migraine may be related to higher brain centers and limbic cortices. The insula may be a new target for treatment of migraine.
Methods for clarifying criteria for study continuation at interim analysis

In monitoring clinical trials, the question of futility, or whether the data thus far suggest that the results at the final analysis are unlikely to be statistically successful, is regularly of interest over the course of a study. However, the opposite viewpoint of whether the study is sufficiently demonstrating proof of concept (POC) and should continue is a valuable consideration and ultimately should be addressed with high POC power so that a promising study is not prematurely terminated. Conditional power is often used to assess futility, and this article interconnects the ideas of assessing POC for the purpose of study continuation with conditional power, while highlighting the importance of the POC type I error and the POC type II error for study continuation or not at the interim analysis. Methods for analyzing subgroups motivate the interim analyses to maintain high POC power via an adjusted interim POC significance level criterion for study continuation or testing against an inferiority margin. Furthermore, two versions of conditional power based on the assumed effect size or the observed interim effect size are considered. Graphical displays illustrate the relationship of the POC type II error for premature study termination to the POC type I error for study continuation and the associated conditional power criteria.
Subliminal affective priming changes the ‘feeling’ towards neutral objects in infancy

ABSTRACT In everyday life, our preferences are governed by influences that we are frequently not aware of. Studies investigating visual subliminal priming have shown that emotions are particularly able to modulate the affective judgments both at a behavioural and neural level. In this study, we investigated whether emotional unconscious learning is a core feature of human development, by testing infants as young as 3 months of age on a subliminal affective priming task, in which infants were primed with subliminal happy and angry faces (Experiment 1) or subliminal neutral and scrambled faces (Experiment 2), followed by two neutral objects. We found that arousal to the neutral objects – as indexed through skin conductance – changed when they were primed with faces displaying emotional valence, and particularly anger, but not when the face had a neutral expression. This change in physiological state only partially corresponded to a change in explicit behaviour – as indexed through looking times – suggesting that emotional unconscious learning likely influences explicit behaviour at later stages of development, when subcortical-to-cortical connections have strengthened.
Is Methotrexate as Efficacious as Etanercept in Psoriatic Arthritis Patients? Comment on the Article by Mease et al

We read with great interest the recent publication on the comparison of the efficacy of etanercept (ETN) or etanercept plus methotrexate (MTX) versus MTX monotherapy in patients with psoriatic arthritis (SEAM-PsA trial) by Mease et al (1). The authors reported significantly greater response rates in both biologic arms versus MTX for the primary endpoint, the ACR20 response, and several secondary endpoints. Interestingly, in the discussion the authors expressed their surprise about the high efficacy level conveyed by MTX alone.
Prevalence of somatic-mental multimorbidity and its prospective association with disability among older adults in China

We aimed to identify prevalent somatic-mental multimorbidity (SMM) and examine its prospective association with disability among a nationally representative sample. A total of 6728 participants aged 60 years and older in the China Health and Retirement Longitudinal Study were included. A total of 14 somatic or mental conditions were assessed in 2013. SMM was defined as any combination of two or more conditions in which at least one condition was somatic and at least one condition was mental. Disability risk was measured using the combined Activities of Daily Living (ADL)-Instrumental Activities of Daily Living (IADL) index (range 0–11; higher index indicates higher disability) in 2013 and 2015. Overall, the prevalence of SMM was 35.7% (95% confidence interval (CI): 34.1%-37.3%) in 2013. After adjustment for sociodemographic characteristics, lifestyles and baseline ADL-IADL index, over a maximum follow-up period of 2 years, SMM was associated with a 2.61 (95% CI: 2.12-3.22)-fold increase in ADL-IADL disability risk compared with that of healthy participants. In conclusion, SMM was prevalent in older Chinese adults, and it was associated with a higher risk of prospective disability.
Inhibitory checkpoints in human natural killer cells: IUPHAR Review 28

Immune checkpoint inhibitors have revolutionized cancer therapy leading to exceptional success. However, there is still the need to improve their efficacy in non‐responder patients. Natural killer (NK) cells represent the first line of defence against tumours, due to their ability to release immunomodulatory cytokines and kill target cells that have undergone malignant transformation. Harnessing NK cell response will open new possibilities to improve control of tumour growth. In this respect inhibitory checkpoints expressed on these innate lymphocytes represents a promising target for next‐generation immunotherapy. In this review, we will summarize recent evidences on the expression of NK cells receptors in cancer, with a focus on the inhibitory checkpoint programmed cell death protein 1 (PD‐1). We will also highlight the strength and limitations of the blockade of PD‐1 inhibitory pathway and suggest new combination strategies that may help to unleash more efficiently NK cell anti‐tumour response.
Health-related masculine values, depression and suicide risk in men: associations among men with a history of childhood maltreatment

Abstract Background Identification of masculine values associated with men’s depression and suicide risk may generate new intervention targets for those with known static risk factors (e.g., exposure to childhood maltreatment). Aims To validate the factor structure of a measure of health-related masculine values and examine correlates relative to childhood maltreatment exposure. Method Self-report data was collected from 530 Canadian men, mean age 47.91 years (SD = 14.51). Results Confirmatory factor analysis validated an abbreviated eight-item, two-factor model of the Intensions Masculine Values Scale (IMVS-8; CFI = .984, TLI = .977, RMSEA = .054, SRMR = .032). Cluster groups of low (n = 57), moderate (n = 206) and high (n = 267) adherence to these health-related masculine values were identified, equivalent on exposure to childhood maltreatment and previous mental health treatment. A multivariate group × maltreatment interaction was observed (p = .017) whereby males in the low cluster with a maltreatment history endorsed higher mood-related symptomology. This same pattern was observed in a univariate group × maltreatment interaction for suicide risk (p = .006). Conclusions Health-related masculine values were associated with lower depression and suicide risk in men who have a history of childhood maltreatment. Future intervention studies should investigate whether development of health-related masculine values can reduce depression and suicide risk among men with a history of childhood maltreatment.
HDAC6-dependent ciliophagy is involved in ciliary loss and cholangiocarcinoma growth in human cells and murine models.

Reduced ciliary expression is reported in several tumors, including cholangiocarcinoma (CCA). We previously showed primary cilia have tumor suppressor characteristics and HDAC6 is involved in ciliary loss. However, mechanisms of ciliary disassembly are unknown. Herein, we tested the hypothesis that HDAC6-dependent autophagy of primary cilia, i.e. ciliophagy, is the main mechanism driving ciliary disassembly in CCA. Utilizing the cancer genome atlas database, human CCA cells, and a rat orthotopic CCA model, we assessed basal and HDAC6-regulated autophagy levels. The effects of RNA-silencing or pharmacological manipulations of ciliophagy on ciliary expression were assessed. Interactions of ciliary proteins with autophagy machinery was assessed by immunoprecipitations. Cell proliferation was assessed by MTS and IncuCyte. A CCA rat model was used to assess the effects of pharmacological inhibition of ciliophagy in vivo. Autophagy is increased in human CCA as well as in a rat orthotopic CCA model and human CCA cell lines. Autophagic flux was decreased via inhibition of HDAC6, while increased by its overexpression. Inhibition of autophagy and HDAC6 restores cilia and decreases cell proliferation. LC3 interacts with HDAC6 and ciliary proteins, and the autophagy cargo receptor involved in targeting ciliary components to the autophagy machinery is primarily NBR1. Treatment with chloroquine, ACY1215 or its combination decreased tumor growth in vivo. Mice that overexpress the autophagy transcription factor TFEB show a decrease of ciliary number. These results suggest ciliary disassembly is mediated by HDAC6-regulated autophagy, i.e. ciliophagy. Inhibition of ciliophagy may decrease cholangiocarcinoma growth and warrant further investigations as a potential therapeutic approach.
Comprehensive assessment of deceased donor kidneys with clinical characteristics, pre-implant biopsy histopathology and hypothermic mechanical perfusion parameters is highly predictive of delayed graft function

Abstract Background Due to the current high demand for transplant tissue, an increasing proportion of kidney donors are considered extended criteria donors, which results in a higher incidence of delayed graft function (DGF) in organ recipients. Therefore, it is important to fully investigate the risk factors of DGF, and establish a prediction system to assess donor kidney quality before transplantation. Methods A total of 333 donation after cardiac death kidney transplant recipients were included in this retrospective study. Both univariate and multivariate analyses were used to analyze the risk factors of DGF occurrence. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of variables on DGF posttransplant. Results The donor clinical scores, kidney histopathologic Remuzzi scores and hypothermic mechanical perfusion (HMP) parameters (flow and resistance index) were all correlated. 46 recipients developed DGF postoperatively, with an incidence of 13.8% (46/333). Multivariate logistic regression analysis of the kidney transplants revealed that the independent risk factors of DGF occurrence post-transplantation included donor score (OR = 1.12, 95% CI 1.06–1.19, p < 0.001), Remuzzi score (OR = 1.21, 95% CI 1.02–1.43, p = 0.029) and acute tubular injury (ATI) score (OR = 4.72, 95% CI 2.32–9.60, p < 0.001). Prediction of DGF with ROC curve showed that the area under the curve was increased to 0.89 when all variables (donor score, Remuzzi score, ATI score and HMP resistance index) were considered together. Conclusions Combination of donor clinical information, kidney pre-implant histopathology and HMP parameters provide a more accurate prediction of DGF occurrence post-transplantation than any of the measures alone.
Quantification of the sensitivity of early detection surveillance

Abstract Early detection surveillance is used for various purposes, including the early detection of non‐communicable diseases (e.g. cancer screening), of unusual increases of disease frequency (e.g. influenza or pertussis outbreaks), and the first occurrence of a disease in a previously free population. This latter purpose is particularly important due to the high consequences and cost of delayed detection of a disease moving to a new population. Quantifying the sensitivity of early detection surveillance allows important aspects of the performance of different systems, approaches and authorities to be evaluated, compared and improved. While quantitative evaluation of the sensitivity of other branches of surveillance has been available for many years, development has lagged in the area of early detection, arguably one of the most important purposes of surveillance. This paper, using mostly animal health examples, develops a simple approach to quantifying the sensitivity of early detection surveillance, in terms of population coverage, temporal coverage and detection sensitivity. This approach is extended to quantify the benefits of risk‐based approaches to early detection surveillance. Population‐based clinical surveillance (based on either farmers and their veterinarians, or patients and their local health services) provides the best combination of sensitivity, practicality and cost‐effectiveness. These systems can be significantly enhanced by removing disincentives to reporting, for instance by implementing effective strategies to improve farmer awareness and engagement with health services and addressing the challenges of well‐intentioned disease notification policies that inadvertently impose barriers to reporting.
Alternative therapy in prevention of experimental and clinical inflammatory bowel disease. Impact of regular physical activity, intestinal alkaline phosphatase and herbal products.

Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are multifactorial, chronic, disabling, and progressive diseases characterised by cyclical nature, alternating between active and quiescent states. While the aetiology of IBD is not fully understood, this complex of diseases involve a combination of factors including the genetic predisposition and changes in microbiome as well as environmental risk factors such as highfat and low-fibre diets, reduced physical activity, air pollution and exposure to various toxins and drugs such as antibiotics. The prevalence of both IBD and obesity is increasing in parallel, undoubtedly proving the existing interactions between these risk factors common to both disorders to unravel poorly recognized cell signaling and molecular alterations leading to human IBD. Therefore there is still a significant and unmet need for supportive and adjunctive therapy for IBD patients directed against the negative consequences of visceral obesity and bacterial dysbiosis. Among the alternative therapies, a moderate-intensity exercise can benefit the health and well-being of IBD patients and improve both, the healing of human IBD and experimental animal colitis. Intestinal alkaline phosphatase (IAP) plays essential role in maintenance of intestinal homeostasis intestinal and the mechanism of mucosal defence. The administration of exogenous IAP could be recommended as a therapeutic strategy for the cure of diseases resulting from the intestinal barrier dysfunction such as IBD. Curcumin, a natural anti-inflammatory agent, which is capable of stimulating the synthesis of endogenous IAP, represents another alternative approach in the treatment of IBD. This review was designed to discuss potential "non-pharmacological" alternative and supplementary therapeutic approaches taking into account epidemiological and pathophysiological links between obesity and IBD, including changes in the functional parameters of intestinal mucosa and alterations in the intestinal microbiome.