Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of SEC61G as a Novel Prognostic Marker for Predicting Survival and Response to Therapies in Patients with Glioblastoma

Background The survival and therapeutic outcome vary greatly among glioblastoma (GBM) patients. Treatment resistance, including resistance to temozolomide (TMZ) and radiotherapy, is a great obstacle for these therapies. In this study, we aimed to evaluate the predictive value of SEC61G on survival and therapeutic response in GBM patients. Material/Methods Survival analyses were performed to assess the correlation between SEC61G expression and survival of GBM patients from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets. Univariate and multivariate Cox proportional hazard regression analysis was introduced to determine prognostic factors with independent impact power. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were conducted to illustrate possible biological functions of SEC61G. Results High expression of SEC61G was significantly correlated with poor prognosis in all GBM patients. High expression of SEC61G was also associated with poor outcome in those who received TMZ treatment or radiotherapy in TCGA GBM cohort. Univariate and multivariate Cox proportional hazards regression demonstrated that SEC61G was an independent prognostic factor affecting the prognosis and therapeutic outcome. The combination of age, SEC61G expression, and MGMT promoter methylation in survival analysis could provide better outcome assessment. Finally, a strong correlation between SEC61G expression and Notch pathway was observed in GSEA and GSVA, which suggested a possible mechanism that SEC61G affected survival and TMZ resistance. Conclusions SEC61G expression may be a potential prognostic marker of poor survival, and a predictor of poor outcome to TMZ treatment and radiotherapy in GBM patients.
New evidence on the link between genes, psychological traits, and political engagement

Abstract. We investigate the link between genes, psychological traits, and political engagement using a new data set containing information on a large sample of young German twins. The TwinLife Study enables us to examine the predominant model of personality, the Big Five framework, as well as traits that fall outside the Big Five, such as cognitive ability, providing a more comprehensive understanding of the underpinnings of political engagement. Our results support previous work showing genetic overlap between some psychological traits and political engagement. More specifically, we find that cognitive ability and openness to experience are correlated with political engagement and that common genes can explain most of the relationship between these psychological traits and political engagement. Relationships between genes, psychological traits, and political engagement exist even at a fairly young age, which is an important finding given that previous work has relied heavily on older samples to study the link between genes, psychological traits, and political engagement.
Myocardial injury after non-cardiac surgery: diagnosis and management.

Myocardial injury after non-cardiac surgery (MINS) is due to myocardial ischaemia (i.e. supply-demand mismatch or thrombus) and is associated with an increased risk of mortality and major vascular complications at 30 days and up to 2 years after non-cardiac surgery. The diagnostic criteria for MINS includes an elevated post-operative troponin measurement judged as resulting from myocardial ischaemia (i.e. no evidence of a non-ischaemic aetiology), during or within 30 days after non-cardiac surgery, and without the requirement of an ischaemic feature (e.g. ischaemic symptom, ischaemic electrocardiography finding). For patients with MINS who are not at high risk of bleeding, physicians should consider initiating dabigatran 110 mg twice daily and low-dose aspirin. Physicians should also consider initiating statin therapy in patients with MINS. Most MINS patients should only be referred to cardiac catheterization if they demonstrate recurrent instability (e.g. cardiac ischaemia, heart failure). Patients ≥65 years of age or with known atherosclerotic disease should have troponin measurements on days 1, 2, and 3 after surgery while the patient is in hospital to avoid missing >90% of MINS and the opportunity to initiate secondary prophylactic measures and follow-up.
Theory of hot electrons: general discussion.

Javier Aizpurua, Francesca Baletto, Jeremy Baumberg, Phillip Christopher, Bart de Nijs, Preeti Deshpande, Yuri Diaz Fernandez, Laura Fabris, Simon Freakley, Sylwester Gawinkowski, Alexander Govorov, Naomi Halas, Romain Hernandez, Bartlomiej Jankiewicz, Jacob Khurgin, Mikael Kuisma, Priyank Vijaya Kumar, Johannes Lischner, Jie Liu, Andrea Marini, Reinhard J. Maurer, Niclas Sven Mueller, Matteo Parente, Jeong Y. Park, Stephanie Reich, Yonatan Sivan, Giulia Tagliabue, Laura Torrente-Murciano, Madasamy Thangamuthu, Xiaofei Xiao and Anatoly Zayats
Effect of adding midazolam to bupivacaine during rectus sheath block: a randomised controlled trial

Various adjuvants have been tried to improve quality and increase duration of local anaesthetics during various nerve blocks. We aimed to evaluate the effect of adding midazolam to bupivacaine on rectus sheath (RS) block in patients undergoing umbilical or epigastric hernia repair.
DC Bead embolic drug-eluting bead: clinical application in the locoregional treatment of tumours

Introduction: DC Bead is an embolic drug-eluting bead designed to be loaded with chemotherapeutic agents (such as doxorubicin and irinotecan), delivered intra-arterially into tumor blood vessels to block nutrient flow and then to deliver the drug locally in a sustained fashion. This product is finding increasing use in the treatment of patients with both primary and secondary liver cancers. Areas covered: This review positions DC Bead in the field of targeted embolic drug delivery and with respect to other competitive technologies in the treatment of liver cancer. An overview of the studies that demonstrate the product's performance, safety and efficacy is presented. The clinical application of the doxorubicin loaded DC Bead is firstly reviewed, in the context of treatment of patients with various stages of hepatocellular carcinoma. Its combination with other therapies is also discussed, together with consideration of the treatment of other liver tumors. Secondly, the use of irinotecan loaded DC Bead, primarily for the treatment of colorectal cancer metastases to the liver, but also some additional rare metastases, is summarized. Expert Opinion: An opinion is proffered as to how this technology and its application is evolving, illustrating a move towards synergistic combination therapies and into other cancer indications.
Limited agreement between two noninvasive measurements of blood volume during fluid removal: ultrasound of inferior vena cava and finger-clip spectrophotometry of hemoglobin concentration

Objective: Plots of blood volume measurements over time (profiles) may identify euvolemia during fluid removal for acute heart failure. We assessed agreement between two noninvasive measurements of blood volume profiles during mechanical fluid removal, which exemplifies the interstitial fluid shifts that occur during diuretic-induced fluid removal. Approach: During hemodialysis we compared change in maximum diameter of the inferior vena cava by ultrasound () to change in relative blood volume derived from capillary hemoglobin concentration from finger-clip spectrophotometry (RBVSpHb). We grouped profiles of these measurements into three distinct shapes using an unbiased, data-driven modeling technique. Methods: Fifty patients who were not in acute heart failure underwent a mean of five paired measurements while an average of 1.3 liters of fluid was removed over 2 h during single hemodialysis sessions. changed −1.0 mm (95% CI −1.9 to −0.2 mm) and the RBVSpHb changed −1.1% (95% CI −2.7 to +0.5%), but these changes were not correlated (r −0.04, 95% CI −0.32 to +0.24). Nor was there agreement between categorization of profiles of change in the two measurements (kappa −0.1, 95% CI −0.3 to +0.1). Significance: and RBVSpHb estimates of blood volume do not agree during mechanical fluid removal, likely because regional changes in blood flow and pressure modify IVC dimensions as well as changes total blood volume.
Syphilis treatment response among HIV-discordant couples in Zambia and Rwanda.

BACKGROUND Syphilis continues to be a common sexually transmitted infection, despite the availability of inexpensive and effective treatment. Infection in human immunodeficiency virus (HIV)-discordant couples is important because syphilis increases the risk of HIV acquisition. Current US treatment guidelines recommend 1 dose of benzathine penicillin for early syphilis, irrespective of HIV status, but data from coinfected patients are limited. METHODS Retrospective analysis of 1321 individuals in 2 African HIV-discordant couple cohorts was performed. Cox proportional hazards analysis and multivariable modeling were used to assess predictors of serologic response to treatment at 180 days and 400 days. Modeling was performed for all episodes of positive rapid plasma reagin (RPR) test results and on a subset with higher RPR titers (≥1:4). RESULTS A total of 1810 episodes of syphilis among 1321 individuals were treated with penicillin between 2002 and 2008. Although a positive RPR was more common in the HIV-infected partners, HIV infection did not impact the likelihood of serologic response to therapy (odds ratio [OR], 1.001; P = .995). By 400 days, 67% had responded to therapy, 27% were serofast, and 6.5% had documented reinfection. Prevalent infections were more likely to remain serofast than incident infections (33% vs 20% at 400 days). CONCLUSIONS In 2 HIV-serodiscordant couple cohorts in Africa, incident syphilis had a very good likelihood of response to penicillin therapy, irrespective of HIV infection. This supports current Centers for Disease Control and Prevention treatment guidelines. A high proportion of prevalent RPR-positive infections remain serofast despite treatment.
Predicting short- and long-term cognitive training success in healthy older adults: who benefits?

ABSTRACT Identifying factors predicting effects of cognitive trainings (CT) is important for developing trainings for individuals with specific profiles. The objective of the present study was to evaluate predictors of CT success in several cognitive domains directly after and 1 year after a 7-week group CT in healthy older adults. Sociodemographic variables, baseline cognitive performance, physical activity parameters, apolipoprotein E-4 (apoE-4), levels of insulin-like growth factor 1 (IGF-1), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) were analysed as possible predictors of CT success. Outcomes were assessed directly after training and 1 year after CT. Results indicate that lower initial baseline performance was a significant predictor for CT success in most of the investigated domains. All tested predictors (except age and BDNF) predicted CT success in different domains. Our data indicate that healthy older adults with lower cognitive baseline scores show stronger benefits of a CT group intervention.
Using Computer Games to Support Mental Health Interventions: Naturalistic Deployment Study

Background Recent research has highlighted naturalistic uptake as a key barrier to maximizing the impact of mental health technologies. Although there is increasing evidence regarding the efficacy of digital interventions for mental health, as demonstrated through randomized controlled trials, there is also evidence that technologies do not succeed as expected when deployed in real-world settings. Objective This paper describes the naturalistic deployment of Pesky gNATs, a computer game designed to support cognitive behavioral therapy (CBT) for children experiencing anxiety or low mood. The objective of this deployment study was to identify how therapists use Pesky gNATs in real-world settings and to discover positive and negative factors. On the basis of this, we aimed to derive generalizable recommendations for the development of mental health technologies that can have greater impact in real-world settings. Methods Pesky gNATs has been made available through a not-for-profit organization. After 18 months of use, we collected usage and user experience data from therapists who used the game. Data were collected through an online survey and semistructured interviews addressing the expectations and experiences of both therapists and young people. Thematic analysis was used to identify key themes in the interview and survey data. Results A total of 21 therapists, who used Pesky gNATs with 95 young people, completed the online survey. Furthermore, 5 therapists participated in the follow-up interview. Confirming previous assessments, data suggest that the game can be helpful in delivering therapy and that young people generally liked the approach. Therapists shared diverse opinions regarding the young people for whom they deemed the game appropriate. The following 3 themes were identified: (1) stages of use, (2) impact on the delivery of therapy, and (3) customization. We discuss therapists’ reflections on the game with regard to their work practices and consider the question of customization, including the delicate balance of adaptable interaction versus the need for fidelity to a therapeutic model. Conclusions This study provides further evidence that therapeutic games can support the delivery of CBT for young people in real-world settings. It also shows that deployment studies can provide a valuable means of understanding how technologies integrate with the overall mental health ecosystem and become a part of therapists' toolbox. Variability in use should be expected in real-world settings. Effective training, support for therapist autonomy, careful consideration of different approaches to customization, the reporting of deployment data, and support for communities of practice can play an important role in supporting variable, but effective, use.
Imipramine Protects against Bone Loss by Inhibition of Osteoblast-Derived Microvesicles

The maintenance of bone homeostasis is largely dependent upon cellular communication between osteoclasts and osteoblasts. Microvesicles (MVs) represent a novel mechanism for osteoblasts and osteoclasts communication, as has been demonstrated in our previous study. Sphingomyelinases catalyze the hydrolysis of sphingomyelin, which leads to increased membrane fluidity and facilitates MV generation. This effect can be inhibited by imipramine, an inhibitor of acid sphingomyelinase (ASM), which is also known as a member of tricyclic antidepressants (TCAs). A recent study has reported that in vitro treatment of imipramine blocked MVs release from glial cells. However, whether imipramine has this effect on osteoblast-derived MVs and whether it is involved in MV generation in vivo is unclear. Here, our investigations found that imipramine slightly reduced the expression of osteoblast differentiation of related genes, but did not impact parathyroid hormone (PTH) regulation for these genes and also did not affect receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast formation; however, imipramine treatment blocked MVs released from osteoblasts and inhibited MV-induced osteoclast formation. In vivo, mice administrated with imipramine were protected from ovariectomy-induced bone loss as evaluated by various bone structural parameters and serum levels of biochemical markers. Our results suggest that inhibiting the production of MVs containing RANKL in vivo is very important for preventing bone loss.
Inclusion of Vitamin A Intake Data Provides Improved Compartmental Model-Derived Estimates of Vitamin A Total Body Stores and Disposal Rate in Older Adults

ABSTRACT Background Sampling times and study duration impact estimates of kinetic parameters and variables including total body stores (TBS) and disposal rate (DR) when compartmental analysis is used to analyze vitamin A kinetic data. Objective We hypothesized that inclusion of dietary intake (DI) of vitamin A as an additional input would improve confidence in predictions of TBS and DR when modeling results appear to indicate that studies are not long enough to accurately define the terminal slope of the plasma retinol isotope response curve. Methods We reanalyzed previously published data on vitamin A kinetics monitored over 52 d in 7 US and 6 Chinese adults (means: 56 y, BMI 26.6 kg/m2, 38% males), adding an estimate for vitamin A intake [2.8 µmol/d (mean RDA)] as an input during application of the Simulation, Analysis and Modeling software. Results Use of a model with 1 extravascular compartment (1 EV), as in the original analysis, resulted in predictions of vitamin A intake that were higher than physiologically reasonable; inclusion of intake data in a model with 2 extravascular compartments (2 EV DI) resulted in more realistic estimates of intake and DR. Specifically, predictions of DR by the 2 EV DI (versus 1 EV) model were 2.10 compared with 12.2 µmol/d (US) and 2.21 compared with 5.13 µmol/d (Chinese). Predictions of both TBS [2056 compared with 783 µmol (US) and 594 compared with 219 µmol (Chinese)] and days of vitamin A stores [981 compared with 64 d (US) and 269 compared with 43 d (Chinese)] were higher using the new approach. Conclusions Inclusion of vitamin A intake as additional data input when modeling vitamin A kinetics can compensate for less-than-optimal study duration, providing more realistic predictions of vitamin A TBS and DR. This approach advances the application of compartmental analysis to the study of vitamin A and, potentially, other nutrients.
Single nucleotide polymorphisms of vitamin D binding protein, vitamin D receptor and retinoid X receptor alpha genes and response to hepatitis B vaccination in renal replacement therapy patients

Aim: Vitamin D (VD) was recently associated with response to hepatitis B vaccination in chronic kidney disease. We investigated whether polymorphisms in VD binding protein (GC), VD receptor (VDR) and retinoid X receptor α (RXRA) genes were associated with response to hepatitis B vaccination in renal replacement therapy (RRT) patients. Method: The study was carried out on 692 responders and 223 non-responders. Results: After adjustment for gender, age at the RRT onset, RRT vintage, chronic glomerulonephritis as a cause of renal failure and mean serum parathyroid hormone level, VDR rs1544410 polymorphism was the only one significantly associated with response to hepatitis B vaccination: homozygotes AA (adjusted OR 1.50, 95% CI: 1.17–1.94, p = 0.002) had higher risk to be non-responders than GG homozygotes. Discussion: The VDR rs1544410 AA genotype may play a negative role (but not as an independent factor) in determining response to hepatitis B vaccination in RRT patients.
Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor.

Allosteric kinase inhibitors offer a potentially complementary therapeutic strategy to ATP-competitive kinase inhibitors due to their distinct sites of target binding. In this study, we identify and study a mutant-selective EGFR allosteric inhibitor, JBJ-04-125-02, which as a single agent can inhibit cell proliferation and EGFRL858R/T790M/C797S signaling in vitro and in vivo However, increased EGFR dimer formation limits treatment efficacy and leads to drug resistance. Remarkably, osimertinib, an ATP-competitive covalent EGFR inhibitor, uniquely and significantly enhances the binding of JBJ-04-125-02 for mutant EGFR. The combination of osimertinib and JBJ-04-125-02 results in an increase in apoptosis, a more effective inhibition of cellular growth, and an increased efficacy in vitro and in vivo compared with either single agent alone. Collectively, our findings suggest that the combination of a covalent mutant-selective ATP-competitive inhibitor and an allosteric EGFR inhibitor may be an effective therapeutic approach for patients with EGFR-mutant lung cancer.SIGNIFICANCE: The clinical efficacy of EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutant lung cancer is limited by acquired drug resistance, thus highlighting the need for alternative strategies to inhibit EGFR. Here, we identify a mutant EGFR allosteric inhibitor that is effective as a single agent and in combination with the EGFR TKI osimertinib.
Move on Bikes Program: A Community-Based Physical Activity Strategy in Mexico City

Open streets programs are free and multisectoral programs in which streets are temporally closed allowing access to walkers, runners, rollerbladers, and cyclists. The Move on Bikes program (by its name in Spanish Muévete en Bici) (MEB) consists of 55 km of interconnected streets in middle-high income areas of Mexico City. There is scarce evidence on the evaluation of this program in Mexico. The purposes of this study were to estimate the participation, physical activity levels among the MEB participants, and the association of the frequency of participation with sociodemographic, physical, and program characteristics. Methods: From October 2017 to July 2018, six hundred seventy-nine MEB participants were surveyed using a questionnaire that contains sociodemographic, physical, and program characteristics. A wide-angle video camera was used to estimate the average speed of each activity per event per participant. Based on the information collected by the program authorities and survey interviews, we estimated the number of participants per event. Results: On a typical MEB program day, 21,812 people participated. MEB program users accumulated an average of 221 min of moderate-to-vigorous physical activity (MVPA) per typical Sunday and 88.4% accumulated at least 150 min of MVPA. In total, 29.6% of users attended the program every Sunday. Those who were more likely to attend the program frequently included: men, those aged 41 to 64 years old, users classified as very and sufficiently active, those that used active transportation to travel to the program, and participants that came alone. Conclusions: This study provides evidence that the MEB program adds an extra 71 min/week of MVPA to more than 20,000 users.
Physical Activity, Cognition, and Brain Outcomes: A Review of the 2018 Physical Activity Guidelines

Purpose Physical activity (PA) is known to improve cognitive and brain function, but debate continues regarding the consistency and magnitude of its effects, populations and cognitive domains most affected, and parameters necessary to achieve the greatest improvements (e.g., dose). Methods In this umbrella review conducted in part for the 2018 Health and Human Services Physical Activity Guidelines for Americans Advisory Committee, we examined whether PA interventions enhance cognitive and brain outcomes across the life span, as well as in populations experiencing cognitive dysfunction (e.g., schizophrenia). Systematic reviews, meta-analyses, and pooled analyses were used. We further examined whether engaging in greater amounts of PA is associated with a reduced risk of developing cognitive impairment and dementia in late adulthood. Results Moderate evidence from randomized controlled trials indicates an association between moderate- to vigorous-intensity PA and improvements in cognition, including performance on academic achievement and neuropsychological tests, such as those measuring processing speed, memory, and executive function. Strong evidence demonstrates that acute bouts of moderate- to vigorous-intensity PA have transient benefits for cognition during the postrecovery period after exercise. Strong evidence demonstrates that greater amounts of PA are associated with a reduced risk of developing cognitive impairment, including Alzheimer’s disease. The strength of the findings varies across the life span and in individuals with medical conditions influencing cognition. Conclusions There is moderate-to-strong support that PA benefits cognitive functioning during early and late periods of the life span and in certain populations characterized by cognitive deficits.