Miracle-dz/UniFAR-FTUs huggingface dataset:
Oleate-induced PTX3 promotes head and neck squamous cell carcinoma metastasis through the up-regulation of vimentin

The association between metabolic diseases and the risk of developing cancer is emerging. However, the impact of long pentraxin-3 (PTX3) on dyslipidemia-associated tumor metastasis remains unknown. In this study, we found that oleate induced PTX3 expression and secretion through the activation of Akt/NF-κB pathway in head and neck squamous cell carcinomas (HNSCCs). The activation of NF-κB was essential for the oleate-induced stabilization of PTX3 mRNA. In addition, both the depletion of PTX3 and the inhibition of NF-κB significantly inhibited oleate-induced tumor cell migration and invasion. The enhancement of binding between tumor and endothelial cells was observed in oleate-treated cells but not in the depletion and neutralization of PTX3 with siPTX3 and anti-PTX3 antibodies, respectively. The levels of oleate-induced epithelial-mesenchymal transition (EMT) markers, such as vimentin and MMP-3, were significantly reduced in PTX3-depleted cells. Knocking down vimentin also repressed oleate-induced HNSCC invasion. Furthermore, the depletion of PTX3 blocked the oleate-primed metastatic seeding of tumor cells in the lungs. These results demonstrate that oleate enhances HNSCC metastasis through the PTX3/vimentin signaling axes. The inhibition of PTX3 could be a potential strategy for the treatment of dyslipidemia-mediated HNSCC metastasis.
Weight cycling and the subsequent onset of type 2 diabetes mellitus: 10-year cohort studies in urban and rural Japan

Objective To investigate how weight cycling (gaining and losing weight) affects the risk of diabetes. Design Cohort studies. Setting Primary healthcare in urban and rural Japan. Participants 20 708 urban and 9670 rural residents. Primary outcome measures ORs for diabetes in those with weight loss, weight loss-gain, stable weight, weight gain-loss and weight gain over 10 years. Weight gain and loss were defined as a change of more than ±4% from baseline weight. Results In the urban region, the ORs relative to the stable group for the loss-gain and gain-loss groups were 0.63 (95% CI 0.45 to 0.89) and 0.51 (95% CI 0.32 to 0.82) for men and 0.72 (95% CI 0.39 to 1.34) and 1.05 (95% CI 0.57 to 1.95) for women. In the rural region, they were 1.58 (95% CI 0.78 to 3.17) and 0.44 (95% CI 0.15 to 1.29) in men and 0.41 (95% CI 0.12 to 1.44) and 0.77 (95% CI 0.28 to 2.14) in women. The ORs for an increase in weight between 5 and 10 kg from the age of 20 years were 1.54 (95% CI 1.03 to 2.30) in men and 0.96 (95% CI 0.55 to 1.65) in women. Conclusions In Japan, weight cycling was associated with a significant reduction in the risk of diabetes for men from urban regions. The associations were unclear for women from urban regions and both men and women from rural regions. These results differ from those in Western studies, probably because of differences in diet, insulin secretion and sensitivity and weight-consciousness.
Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males

OBJECTIVEWe aimed to determine the prevalence of 25(OH)D (D2 and D3 independently) inadequacy in healthy young/middle-aged men and to investigate its relationship with BMD, bone markers, demographic and lifestyle parameters such as age, BMI, smoking, alcohol consumption and dietary calcium intake.DESIGNWe determined 25(OH)D levels using LC-MS/MS, a robust method for measurement of both 25(OH)D3 and 25(OH)D2, iPTH, osteocalcin, beta C terminal cross-linked telopeptides of type I collagen (b-CTXs), procollagen type 1 amino-terminal propeptide (PINP), BMD at L2-L4 and proximal femur, smoking habits, daily dietary calcium intake and alcohol consumption in 181 randomly selected healthy men aged 20–50y.RESULTSThe prevalence of vitamin D deficiency (25(OH)D <20ng/ml) was 50.3%. Only 8.8% of the participants had vitamin D sufficiency (25(OH)D ≥30ng/ml). We found a strong correlation between 25(OH)D and smoking in the totality of participants (p<0.001). 25(OH)D level was lower by approximately 4.3 ng/dl (p<0.001) in a smoker compared to a non-smoker among the totality of participants, while this value increased to 9.2ng/ml in the 40–50y subgroup (p=0.003). A multinomial logistic regression model demonstrated that a young smoker (20–29y) had 58% increased likelihood of having vitamin D deficiency compared to a non-smoker of the same age group (p=0.041). CONCLUSIONSA high prevalence of vitamin D deficiency was identified in a young and middle-aged male population. Smoking is a significant determinant of serum 25(OH)D, while it increases significantly the likelihood of having vitamin D deficiency. In our hands, vitamin D levels are not a determinant of bone turnover and BMD in this population.
Detection of oncogenic mutations in resected bronchial margins by next-generation sequencing indicates early relapse in stage IA lung adenocarcinoma patients

Stage I non-small cell lung cancer (NSCLC) patients experience a relatively high rate of recurrence, ranging from about 30-35%. We hypothesized that this elevated risk of recurrence is due to the presence of tumor cells at bronchial margins which was undetected by conventional light microscopy. Patients with clinical stage IA (T1N0M0) NSCLC were enrolled in this study, which included 8 early-relapse(ER) and 6 no-relapse(NR) patients. Primary tumor, bronchial margin, and normal lung tissues were collected and sent to a central site for targeted next-generation sequencing analysis. All of the patients were lung adenocarcinoma. Gene mutations were identified in all tumor tissue samples (100%). Oncogenic mutations were identified in 87.5%(7/8) bronchial margins of early relapse patients, whereas only 16.7%(1/6) no-relapse (NR) patient of marginal tissue had identified gene mutation. Additionally, concordance between primary tumor and bronchial margins was relatively high, with 4 of 8 (50%) ER patients having at least one identical mutation. Moreover, according to the gene mutation status in marginal tissue, 87.5% (7/8) of patients with at least one gene mutation in the bronchial margins had local recurrence or metastasis, whereas only 16.7% (1/6) of patients without any mutation detected had signs of relapse, the recurrence rate was significantly higher than that of the negative mutation margin group ((p (log-rank) = 0.023). The existence of oncogenic mutations in bronchial margins may represent occult residual tumor and elevated risk of recurrence in early stage NSCLC patients. Thus, assessing molecular status in bronchial margins may help identify patients who might benefit from extensive surgery or adjuvant treatment.
Oral glucose tolerance test performance in olanzapine‐treated schizophrenia‐spectrum patients is predicted by BMI and triglycerides but not olanzapine dose or duration

Olanzapine, an atypical antipsychotic, is associated with glucoregulatory abnormalities, but the nature of this link is not fully elucidated. This is the first olanzapine oral glucose tolerance test (oGTT) study to consider treatment dose and duration, and to compare complementary indices respectively assessing insulin sensitivity (Matsuda index) and resistance (homeostasis model assessment).
Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis.

BACKGROUND The clinical benefit of memantine for Alzheimer's disease (AD) remains inconclusive. OBJECTIVE We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD. METHODS We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses. RESULTS Thirty studies (n = 7,567; memantine versus placebo: N = 11, n = 3,298; memantine + cholinesterase inhibitors (M+ChEIs) versus ChEIs: N = 17, n = 4,175) were identified. Memantine showed a significant improvement in CF [standardized mean difference (SMD) = -0.24, 95% confidence intervals (95% CIs) = -0.34, -0.15, p < 0.00001, I2 = 35% ] and BD (SMD = -0.16, 95% CIs = -0.29, -0.04, p = 0.01, I2 = 52%) compared with placebo. In the sensitivity analysis including only patients with moderate-severe AD, memantine was superior to the placebo in reducing BD without considerable heterogeneity (SMD = -0.20, 95% CIs = -0.34, -0.07, p = 0.003, I2 = 36%). Compared with ChEIs, M+ChEIs showed a greater reduction in BD (SMD = -0.20, 95% CIs = -0.36, -0.03, p = 0.02, I2 = 77%) and a trend of CF improvement (SMD = -0.11, 95% CIs = -0.22, 0.01, p = 0.06, I2 = 56%). However, in the sensitivity analysis of double-blind, placebo-controlled studies only, M+ChEIs showed a significant reduction in BD compared with ChEIs without considerable heterogeneity (SMD = -0.11, 95% CIs = -0.21, -0.01, p = 0.04, I2 = 40%). When performing the sensitivity analysis of donepezil studies only, M+ChEIs was superior to ChEIs in improving CF without considerable heterogeneity (SMD = -0.18, 95% CIs = -0.31, -0.05, p = 0.006, I2 = 49%). No differences were detected in all-cause discontinuation between the groups. CONCLUSIONS The meta-analyses suggest the credible efficacy and safety of memantine in treating AD when used alone or in combination with ChEIs.
Rare case of Cushing’s disease due to double ACTH-producing adenomas, one located in the pituitary gland and one into the stalk

We describe a patient affected by Cushing’s disease due to the presence of double pituitary adenomas, one located within the anterior pituitary and the other in the infundibulum associated with a remnant of Rakthe’s pouch. Cure was achieved only after the infundibulum lesion was surgically removed. CASE REPORT: A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. Hormonal studies indicated Cushing’s disease and MRI showed an enlarged pituitary gland with a marked and homogeneous enhancement after injection of gadolinium and an enlarged infundibulum with a maximum diameter of 8 mm. As a venous sampling of the inferior petrosal sinus after 10 µg iv desmopressin stimulation revealed a central to peripheral ACTH ratio consistent with a pituitary ACTH-secreting tumor, transphenoidal explorative surgery was performed and a 4-mm pituitary adenoma immunopositive for ACTH was disclosed and removed. Since postoperative hormonal evaluation showed persistent hypercortisolism, confirmed by dynamic tests, the patient again underwent surgery by transcranial access and the infundibulum mass was removed. Histology and immunochemistry were consistent with an ACTH-secreting adenoma. A few months after the second operation, cushingoid features were significantly reverted and symptoms improved. CONCLUSION Although Cushing’s patients bearing multiple adenomas have already been documented, the presence of two adenomas both immunohistochemically positive for ACTH is a very rare cause of Cushing’s disease and this is the first report of a case of double ACTH-producing adenomas, one located in the pituitary gland and one attached to the stalk.
Usual blood pressure, atrial fibrillation and vascular risk: evidence from 4.3 million adults

Abstract Background: Although elevated blood pressure is associated with an increased risk of atrial fibrillation (AF), it is unclear if this association varies by individual characteristics. Furthermore, the associations between AF and a range of different vascular events are yet to be reliably quantified. Methods: Using linked electronic health records, we examined the time to first diagnosis of AF and time to first diagnosis of nine vascular events in a cohort of 4.3 million adults, aged 30 to 90 years, in the UK. Results: A 20-mmHg higher usual systolic blood pressure was associated with a higher risk of AF [hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.19, 1.22]. The strength of the association declined with increasing age, from an HR of 1.91 (CI 1.75, 2.09) at age 30-40 to an HR of 1.01 (CI 0.97, 1.04) at age 80-90 years. AF without antithrombotic use at baseline was associated with a greater risk of any vascular event than AF with antithrombotic usage (P interaction < 0.0001). AF without baseline antithrombotic usage was associated with an increased risk of ischaemic heart disease (HR 2.52, CI 2.23, 2.84), heart failure (HR 3.80, CI 3.50, 4.12), ischaemic stroke (HR 2.72, CI 2.19, 3.38), unspecified stroke (HR 2.59, CI 2.25, 2.99), haemorrhagic stroke, chronic kidney disease, peripheral arterial disease and vascular dementia, but not aortic aneurysm. Conclusions: The association between elevated blood pressure and AF attenuates with increasing age. AF without antithrombotic usage is associated with an increased risk of eight vascular events.
Assessment of Tobacco Habits, Attitudes, and Education Among Medical Students in the United States and Italy: A Cross-sectional Survey

Objectives Medical students represent a primary target for tobacco cessation training. This study assessed the prevalence of medical students’ tobacco use, attitudes, clinical skills, and tobacco-related curricula in two countries, the US and Italy, with known baseline disparities in hopes of identifying potential corrective interventions. Methods From September to December 2013, medical students enrolled at the University of Bologna and at Brown University were recruited via email to answer survey questions assessing the prevalence of medical students’ tobacco use, attitudes and clinical skills related to patients’ smoking, and elements of medical school curricula related to tobacco use. Results Of the 449 medical students enrolled at Brown and the 1426 enrolled at Bologna, 174 Brown students (38.7%) and 527 Bologna students (36.9%) participated in this study. Italian students were more likely to smoke (29.5% vs. 6.1%; p<0.001) and less likely to receive smoking cessation training (9.4% vs. 80.3%; p<0.001) than their American counterparts, even though the majority of students in both countries desired smoking cessation training (98.6% at Brown, 85.4% at Bologna; p<0.001). Additionally, negative beliefs regarding tobacco usage, the absence of formal training in smoking cessation counseling, and a negative interest in receiving specific training on smoking cessation were associated with a higher risk of not investigating a patient’s smoking status during a routine history and not offering tobacco cessation treatment to patients. Conclusions Medical curricula on tobacco-related health hazards and on smoking cessation should be mandatory in order to reduce smoking among medical students, physicians, and patients, thereby improving tobacco-related global health.
Inferring influence and leadership in moving animal groups

Collective decision-making is a daily occurrence in the lives of many group-living animals, and can have critical consequences for the fitness of individuals. Understanding how decisions are reached, including who has influence and the mechanisms by which information and preferences are integrated, has posed a fundamental challenge. Here, we provide a methodological framework for studying influence and leadership in groups. We propose that individuals have influence if their actions result in some behavioural change among their group-mates, and are leaders if they consistently influence others. We highlight three components of influence (influence instances, total influence and consistency of influence), which can be assessed at two levels (individual-to-individual and individual-to-group). We then review different methods, ranging from individual positioning within groups to information-theoretic approaches, by which influence has been operationally defined in empirical studies, as well as how such observations can be aggregated to give insight into the underlying decision-making process. We focus on the domain of collective movement, with a particular emphasis on methods that have recently been, or are being, developed to take advantage of simultaneous tracking data. We aim to provide a resource bringing together methodological tools currently available for studying leadership in moving animal groups, as well as to discuss the limitations of current methodologies and suggest productive avenues for future research. This article is part of the theme issue ‘Collective movement ecology’.
REGENERATION: Regeneration of fat cells from myofibroblasts during wound healing

&NA; Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro. Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans.
Father's environment before conception and asthma risk in his children: a multi-generation analysis of the Respiratory Health In Northern Europe study.

Background Whereas it is generally accepted that maternal environment plays a key role in child health, emerging evidence suggests that paternal environment before conception also impacts child health. We aimed to investigate the association between children's asthma risk and parental smoking and welding exposures prior to conception. Methods In a longitudinal, multi-country study, parents of 24 168 offspring aged 2-51 years provided information on their life-course smoking habits, occupational exposure to welding and metal fumes, and offspring's asthma before/after age 10 years and hay fever. Logistic regressions investigated the relevant associations controlled for age, study centre, parental characteristics (age, asthma, education) and clustering by family. Results Non-allergic early-onset asthma (asthma without hay fever, present in 5.8%) was more common in the offspring with fathers who smoked before conception {odds ratio [OR] = 1.68 [95% confidence interval (CI) = 1.18-2.41]}, whereas mothers' smoking before conception did not predict offspring asthma. The risk was highest if father started smoking before age 15 years [3.24 (1.67-6.27)], even if he stopped more than 5 years before conception [2.68 (1.17-6.13)]. Fathers' pre-conception welding was independently associated with non-allergic asthma in his offspring [1.80 (1.29-2.50)]. There was no effect if the father started welding or smoking after birth. The associations were consistent across countries. Conclusions Environmental exposures in young men appear to influence the respiratory health of their offspring born many years later. Influences during susceptible stages of spermatocyte development might be important and needs further investigation in humans. We hypothesize that protecting young men from harmful exposures may lead to improved respiratory health in future generations.
Real vs. Fake Emotion Challenge: Learning to Rank Authenticity from Facial Activity Descriptors

Distinguishing real from fake expressions is an emergent research topic. We propose a new method to rank authenticity of multiple videos from facial activity descriptors, which won the ChaLearn real vs. fake emotion challenge. Two studies with 22 human observers show that our method outperforms humans by a large margin. Further, it shows that our proposed ranking method is superior to direct classification. However, when humans are asked to compare two videos from the same subject and emotion before deciding which is fake or real there is no significant increase in performance compared to classifying each video individually. This suggests that our computer vision model is able to exploit facial attributes that are invisible for humans. The code is available at https://github.com/fsaxen/NIT-ICCV17Challenge.
Seroprevalence of hepatitis B virus infection in Cameroon: a systematic review and meta-analysis

Objective Better knowledge of hepatitis B virus (HBV) infection prevalence at the national level can help to implement pertinent strategies to address HBV related burden. The aim was to estimate the seroprevalence of HBV infection in Cameroon. Design Systematic review and meta-analysis. Participants People residing in Cameroon. Data sources Electronic databases including PubMed/MEDLINE, African Journals Online (AJOL), ScienceDirect, WHO-Afro Library, WHO-IRIS, African Index Medicus, National Institute of Statistics and National AIDS Control Committee, Cameroon; regardless of language and from 1 January 2000 to 30 September 2016. This was completed with a manual search of references of relevant papers. Risk of bias in methodology of studies was measured using the Newcastle-Ottawa Scale. Results Out of 511 retrieved papers, 44 studies with a total of 105 603 individuals were finally included. The overall pooled seroprevalence was 11.2% (95% CI 9.7% to 12.8%) with high heterogeneity between studies (I 2=97.9%). Egger’s test showed no publication bias (p=0.167). A sensitivity analysis excluding individuals at high risk of HBV infection and after adjustment using trim and fill method showed a pooled seroprevalence of 10.6% (95% CI 8.6% to 12.6%) among 100 501 individuals (general population, blood donors and pregnant women). Sources of heterogeneity included geographical regions across country and setting (rural 13.3% vs urban 9.0%), and implementation of HBV universal immunisation (born after 9.2% vs born before 0.7%). Sex, site, timing of data collection, HBV screening tools and methodological quality of studies were not sources of heterogeneity. Limitation Only a third of the studies had low risk of bias in their methodology. Conclusion The seroprevalence of HBV infection in Cameroon is high. Effective strategies to interrupt the transmission of HBV are urgently required. Specific attention is needed for rural settings, certain regions and people born before the implementation of the HBV universal immunisation programme in Cameroon in 2005. Registration PROSPERO, CRD42016042654.
The Role of Kinase Modulators in Cellular Senescence for Use in Cancer Treatment

Recently, more than 30 small molecules and eight monoclonal antibodies that modulate kinase signaling have been approved for the treatment of several pathological conditions, including cancer, idiopathic pulmonary fibrosis, and rheumatoid arthritis. Among them, kinase modulators have been a primary focus for use in cancer treatment. Cellular senescence is believed to protect cells from tumorigenesis by irreversibly halting cell cycle progression and avoiding the growth of damaged cells and tissues. Senescence can also contribute to tumor suppression and be utilized as a mechanism by anti-cancer agents. Although the role of kinase modulators in cancer treatment and their effects on senescence in tumor development have been extensively studied, the relationship between kinase modulators for cancer treatment and senescence has not been fully discussed. In this review, we discuss the pro- and anti-tumorigenesis functions of senescence and summarize the key roles of kinase modulators in the regulation of senescence against tumors.