Miracle-dz/UniFAR-FTUs huggingface dataset:
T‐cell cross‐reactivity may explain the large variation in how cancer patients respond to checkpoint inhibitors

The therapeutic use of the immune system to specifically attack tumours has been a long‐standing vision among tumour immunologists. Recently, the use of checkpoint inhibitors to turn‐off immunosuppressive signals has proven to be effective in enhancing T‐cell reactivity against patient‐specific neoantigens, resulting from somatic mutations. Several of the identified T‐cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement of pre‐existing microbial cross‐reactive T cells in rapid and durable tumour regression seen in some patients. This notion of T‐cell cross‐reactivity is further supported by the findings that intestinal bacteria can influence checkpoint‐blockade therapy. Moreover, early data indicate the presence of such T cells in long‐term survival breast cancer patients. This review highlights the main challenges for cancer immunotherapy and discusses the potential contribution of T‐cell cross‐reactivity in cancer immunotherapy and whether it can be used as a biomarker to predict the responsiveness to checkpoint inhibitors.
A Longitudinal Twin and Sibling Study of Associations between Insomnia and Depression Symptoms in Young Adults.

STUDY OBJECTIVES To estimate genetic and environmental influences on the associations between insomnia and depression symptoms concurrently and longitudinally. METHODS Behavioral genetic analyses were conducted on data from the British longitudinal G1219 twin/sibling study. One thousand five hundred fiftysix twins and siblings participated at Time 1 (mean age = 20.3 years, SD = 1.76). Eight hundred sixty-two participated at Time 2 (mean age = 25.2 years, SD = 1.73 years). Participants completed the Insomnia Symptoms Questionnaire and the Short Mood and Feelings Questionnaire to assess symptoms of insomnia and depression respectively. RESULTS Genetic effects accounted for 33% to 41% of the variance of the phenotypes. The phenotypic correlations were moderate (r = 0.34 to r = 0.52). The genetic correlations between the variables were high (0.73-1.00). Genetic effects accounted for a substantial proportion of the associations between variables (50% to 90%). Non-shared environmental effects explained the rest of the variance and covariance of the traits. CONCLUSIONS While genetic effects play a modest role in insomnia and depression symptoms separately, they appear to play a more central role in concurrent and longitudinal associations between these phenotypes. This should be acknowledged in theories explaining these common associations.
Different responses to exercise between Andersen–Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia

Aims Andersen-Tawil Syndrome (ATS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are both inherited arrhythmic disorders characterized by bidirectional ventricular tachycardia (VT). The aim of this study was to evaluate the diagnostic value of exercise stress tests for differentiating between ATS and CPVT. Methods and results We included 26 ATS patients with KCNJ2 mutations from 22 families and 25 CPVT patients with RyR2 mutations from 22 families. We compared the clinical and electrocardiographic (ECG) characteristics, responses of ventricular arrhythmias (VAs) to exercise testing, and the morphology of VAs between ATS and CPVT patients. Ventricular arrhythmias were more frequently observed at baseline in ATS patients compared with CPVT patients [the ratio of ventricular premature beats (VPBs)/sinus: 0.83 ± 1.87 vs. 0.06 ± 0.30, P = 0.01]. At peak exercise, VAs were suppressed in ATS patients, whereas they were increased in CPVT patients (0.14 ± 0.40 vs. 1.94 ± 2.71, P < 0.001). Twelve-lead ECG showed that all 25 VPBs and 15 (94%) of 16 bidirectional VTs were right bundle branch block (RBBB) morphology in ATS patients, whereas 19 (86%) of 22 VPBs had left bundle branch block (LBBB), and 12 (71%) of 17 bidirectional VT had LBBB and RBBB morphologies in CPVT patients. Conclusion In patients with ATS, VAs with RBBB morphology were frequently observed at baseline and suppressed at peak exercise. In contrast, exercise provoked VAs with mainly LBBB morphology in patients with CPVT. In adjunct to clinical and baseline ECG assessments, exercise testing might be useful for making the diagnosis of ATS vs. CPVT, both characterized by bidirectional VT.
Pandemic Influenza (H1N1) 2009 Is Associated with Severe Disease in India

Background Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. In absence of reliable information on severity of the disease, the nations are unable to decide on the appropriate response against this disease. Methods Based on the results of laboratory investigations, attendance in outpatient department, hospital admissions and mortality from the cases of influenza like illness from 1 August to 31 October 2009 in Pune urban agglomeration, risk of hospitalization and case fatality ratio were assessed to determine the severity of pandemic H1N1 and seasonal influenza-A infections. Results Prevalence of pandemic H1N1 as well as seasonal-A cases were high in Pune urban agglomeration during the study period. The cases positive for pandemic H1N1 virus had significantly higher risk of hospitalization than those positive for seasonal influenza-A viruses (OR: 1.7). Of 93 influenza related deaths, 57 and 8 deaths from Pune (urban) and 27 and 1 death from Pune (rural) were from pandemic H1N1 positive and seasonal-A positive cases respectively. The case fatality ratio 0.86% for pandemic H1N1 was significantly higher than that of seasonal-A (0.13%) and it was in category 3 of the pandemic severity index of CDC, USA. The data on the cumulative fatality of rural and urban Pune revealed that with time the epidemic is spreading to rural areas. Conclusions The severity of the H1N1 influenza pandemic is less than that reported for ‘Spanish flu 1918’ but higher than other pandemics of the 20th century. Thus, pandemic influenza should be considered as serious health threat and unprecedented global response seems justified.
What Deters Jane from Preventing Identification and Tracking on the Web?

Recent revelations about surveillance by several institutions and de-identification can be expected to have increased public awareness of identification- and tracking-related privacy threats. It is reasonable to expect that the general public has started using corresponding privacy protection mechanisms. Our goal with this research was to determine whether they actually do this. If not, we wanted to explore possible explanations for not uptaken such privacy-protecting countermeasures. We interviewed 20 (mainly lay) people and found that our interviewees did not proactively try to prevent being identified and tracked. We identified seven different types of explanations. Including a number of misconceptions which might explain this puzzling level of apathy. The participants demonstrated confusion between different kinds of sensitive data; and displayed a confusion between the semantics of `privacy' and `security'. The findings also indicate that security being compromised, resulting in losing money for example, is more concrete and more easily brought to mind than privacy-related problems. In terms of the consequences of surveillance, the most commonly cited outcome is the receipt of personalized advertisements, which many consider beneficial. Potentially negative impacts of identification and tracking is often assumed to not occur to them. Our interviews also pointed out a gap between passive and active knowledge about identification and tracking techniques, their impact on privacy and countermeasures against them.
A Web-Based Study of Dog Ownership and Depression Among People Living With HIV

Background People living with human immunodeficiency virus (PLHIV) are approximately twice as likely to be depressed compared with HIV-negative individuals. Depression is consistently associated with low antiretroviral therapy (ART) adherence, an important step within the HIV care continuum related to HIV disease progression and overall health. One factor that may have positive psychosocial benefits and promote ART adherence is dog ownership. Research indicates that dog ownership is associated with lower depression, and initial evidence suggests its positive impact on psychosocial outcomes for PLHIV. Objective The aim of our study was to expand the existing research by examining the relationship between current dog ownership and depression for a sample of PLHIV while controlling for demographic characteristics and other potential confounders. Methods Participants aged 18 years or older and who self-reported an HIV diagnosis were recruited via social media into When Dogs Heal, a cross-sectional Web-based survey to collect data among adult PLHIV. The research visit was conducted via a Web-based survey, and there was no in-person interaction with the participant. Primary outcome measures included demographic questions (age, race, ethnicity, gender, and sexual orientation), pet ownership (type of pet owned and current dog ownership), depression (Center for Epidemiologic Studies Depression Scale, 10 items), and resilience (Resilience Research Centre Adult Resilience Measure, 28 items). Results A total of 252 participants were enrolled into the study in January 2016, with a final analytic sample of 199 participants. Mean age was 49 years, 86.4% (172/199) of participants were male, and 80.4% (160/199) were white. Current dog ownership was prevalent among the sample (68.3%, 136/199). Bivariate analysis indicated that there was no significant relationship between depression and demographic characteristics (age, race, ethnicity, gender, and sexual orientation), with P>. 05. The multivariate logistic regression, including age, race, ethnicity, gender, resilience, and current dog ownership, was significant, with P<. 001. Of the 6 predictor variables, only 2 were statistically significant: dog ownership and resilience. Noncurrent dog owners had 3 times higher odds of depression in comparison with current dog owners: odds ratio 3.01; 95% CI 1.54-6.21. Conclusions Growing evidence suggests that dog ownership reduces the likelihood of depression and, therefore, may confer long-term health benefits on PLHIV. Future studies should explore whether dog-specific interventions are a feasible and efficacious intervention to improve outcomes among PLHIV.
A Comprehensive Phylogenetic Analysis of the Scleractinia (Cnidaria, Anthozoa) Based on Mitochondrial CO1 Sequence Data

Background Classical morphological taxonomy places the approximately 1400 recognized species of Scleractinia (hard corals) into 27 families, but many aspects of coral evolution remain unclear despite the application of molecular phylogenetic methods. In part, this may be a consequence of such studies focusing on the reef-building (shallow water and zooxanthellate) Scleractinia, and largely ignoring the large number of deep-sea species. To better understand broad patterns of coral evolution, we generated molecular data for a broad and representative range of deep sea scleractinians collected off New Caledonia and Australia during the last decade, and conducted the most comprehensive molecular phylogenetic analysis to date of the order Scleractinia. Methodology Partial (595 bp) sequences of the mitochondrial cytochrome oxidase subunit 1 (CO1) gene were determined for 65 deep-sea (azooxanthellate) scleractinians and 11 shallow-water species. These new data were aligned with 158 published sequences, generating a 234 taxon dataset representing 25 of the 27 currently recognized scleractinian families. Principal Findings/Conclusions There was a striking discrepancy between the taxonomic validity of coral families consisting predominantly of deep-sea or shallow-water species. Most families composed predominantly of deep-sea azooxanthellate species were monophyletic in both maximum likelihood and Bayesian analyses but, by contrast (and consistent with previous studies), most families composed predominantly of shallow-water zooxanthellate taxa were polyphyletic, although Acroporidae, Poritidae, Pocilloporidae, and Fungiidae were exceptions to this general pattern. One factor contributing to this inconsistency may be the greater environmental stability of deep-sea environments, effectively removing taxonomic “noise” contributed by phenotypic plasticity. Our phylogenetic analyses imply that the most basal extant scleractinians are azooxanthellate solitary corals from deep-water, their divergence predating that of the robust and complex corals. Deep-sea corals are likely to be critical to understanding anthozoan evolution and the origins of the Scleractinia.
Fluxless Reflow Process Using Solder Balls by Hydrogen Radical

In this study, we examined how to lower the reflow temperature using a method in which oxide film is removed by generating hydrogen radicals in a vacuum. As a result, the joint strength obtained was almost equal to that of Sn-37Pb solder. To confirm the possibility of reflow processes without flux, the reduction effect of hydrogen radicals and SnO2 were considered. We increased the reflow temperature up to 10•Ž higher than the melting point, after removing the oxide film which was previously melted at a temperature lower than the melting point by generating hydrogen radicals without using flux. As a result, the same levels of surface properties and joint strength were obtained, and void creation was suppressed. Therefore, we conclude that introducing hydrogen radicals makes it possible to reflow process lead-free solders such as Sn-3.0Ag-0.5Cu without using flux and without void creation. In addition, this method was applied to bump formation reflow.
Bacterial and Pneumocystis Infections in the Lungs of Gene-Knockout Rabbits with Severe Combined Immunodeficiency

Using the CRISPR/Cas9 gene-editing technology, we recently produced a number of rabbits with mutations in immune function genes, including FOXN1, PRKDC, RAG1, RAG2, and IL2RG. Seven founder knockout rabbits (F0) and three male IL2RG null (−/y) F1 animals demonstrated severe combined immunodeficiency (SCID), characterized by absence or pronounced hypoplasia of the thymus and splenic white pulp, and absence of immature and mature T and B-lymphocytes in peripheral blood. Complete blood count analysis showed severe leukopenia and lymphocytopenia accompanied by severe neutrophilia. Without prophylactic antibiotics, the SCID rabbits universally succumbed to lung infections following weaning. Pathology examination revealed severe heterophilic bronchopneumonia caused by Bordetella bronchiseptica in several animals, but a consistent feature of lung lesions in all animals was a severe interstitial pneumonia caused by Pneumocystis oryctolagi, as confirmed by histological examination and PCR analysis of Pneumocystis genes. The results of this study suggest that these SCID rabbits could serve as a useful model for human SCID to investigate the disease pathogenesis and the development of gene and drug therapies.
Comorbid Mental Disorders in Fetal Alcohol Spectrum Disorders: A Systematic Review

Objective: A systematic review of published literature to estimate prevalence of comorbid mental disorders in fetal alcohol spectrum disorders (FASDs) and compare with general population prevalence estimates. Methods: A PubMed search was used to locate articles reporting on FASD and mental disorders published through June 2015. Next, lists of published studies from all issues of the National Organisation for Foetal Alcohol Syndrome—UK publication Fetal Alcohol Forum—were searched. Weighted average prevalence was estimated for the comorbid mental disorders with sufficient data for analysis. We then compared prevalence of mental disorders in the FASD population with rates in the mental health literature. Results: We identified 26 articles reporting 5984 cases of FASD. Of the 15 comorbid mental disorders, 11 had sufficient data for inclusion in the analysis. Attention-deficit/hyperactivity disorder occurred in 50% of persons with FASD (10 times the expected rate). Intellectual disability occurred at 23 times the expected rate. In 5 of the 12 disorders, rates in the FASD population significantly exceeded expected rates by 10% to 45%. Conclusion: Increased rates of mental disorders in people with FASD are commonly reported. Mental health providers should routinely consider FASD in the diagnosis and management of mental illness and developmental disorders. The quality of the research and precision of comorbidity estimates would be improved by additional studies including people with FASD and non-FASD comparison subjects. Until these studies are available, this review provides the best available estimates of comorbid mental disorders in people with FASD.
Dexmedetomidine pharmacodynamics in healthy volunteers: 2. Haemodynamic profile

Background Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, with little respiratory depression and rousability during sedations. We characterized the haemodynamic properties of dexmedetomidine by developing a pharmacokinetic-pharmacodynamic (PKPD) model with a focus on changes in mean arterial blood pressure (MAP) and heart rate. Methods Dexmedetomidine was delivered i.v. to 18 healthy volunteers in a step-up fashion by target-controlled infusion using the Dyck model. Exploratory PKPD modelling and covariate analysis were conducted in NONMEM. Results Our model adequately describes dexmedetomidine-induced hypotension, hypertension, and bradycardia, with a greater effective concentration for the hypertensive effect. Changes in MAP were best described by a double-sigmoidal E max model with hysteresis. Covariate analysis revealed no significant covariates apart from age on the baseline MAP in the population pharmacokinetic model used to develop this PKPD model. Simulations revealed good general agreement with published descriptive studies of haemodynamics after dexmedetomedine infusion. Conclusions The present integrated PKPD model should allow tighter control over the desired level of sedation, while limiting potential haemodynamic side-effects. Clinical trial registration NCT01879865.
The Impact Damage and Medium Leakage of CFRP Laminates with Different Thickness

The effects of thickness and impact energy on the impact damage and the medium leakage of CFRP laminates were studied in this paper. Impact tests for the CFRP laminates with the size of 600 mm×700 mm with five different thicknesses were subjected to the impact energy levels from 5 J to 65 J. The matrix length was investigated according to different energy levels and different thicknesses. The experimental results reveal that the crack length increases linearly with the increasing impact energy. For the same impact energy, the crack lengths decrease with the increasing specimen thickness. The impact energy initial value of medium leakage increases with the increasing thickness. The impact energy initial value of aviation kerosene leakage is about 6.7416 times of the thicknesses of laminates, which is coordinate with the experience value of 6.75 times.
Load-, Force-, and Power-Velocity Relationships in the Prone Pull-Up Exercise.

PURPOSE To analyze the load-, force-, and power-velocity relationships and determine the load that optimizes power output on the pull-up exercise. METHODS Eighty-two resistance-trained men (age 26.8 ± 5.0 y; pull-up 1-repetition maximum [1-RM; normalized per kg of body mass] 1.5 ± 0.34) performed 2 repetitions with 4 incremental loads (range 70-100%1-RM) in the pull-up exercise while mean propulsive velocity (MPV), force (MPF), and power (MPP) were measured using a linear transducer. Relationships between variables were studied using first- and second-order least-squares regression, and subjects were divided into 3 groups depending on their 1-RM for comparison purposes. RESULTS Almost perfect individual load-velocity (R2 = .975 ± 0.02), force-velocity (R2 = .954 ± 0.04), and power-velocity (R2 = .966 ± 0.04) relationships, which allowed to determine the velocity at each %1-RM, as well as the maximal theoretical force (F0), velocity (V0), and power (Pmax) for each subject were observed. Statistically significant differences between groups were observed for F0 (P < .01) but not for MPV at each %1-RM, V0, and Pmax (P > .05). In addition, high correlations between F0 and 1-RM (r = .811) and V0 and Pmax (r = .865) were observed. Finally, the authors observed that the load that maximized MPP was 71.0% ± 6.6%1-RM. CONCLUSIONS The very high load-velocity, force-velocity, and power-velocity relationships enables estimation of 1-RM by measuring movement velocity, as well as determination of maximal force, velocity, and power capabilities. This information could be of great interest to strength and conditioning coaches who wish to monitor pull-up performance.
Exercise Training for Preventing Dementia, Mild Cognitive Impairment, and Clinically Meaningful Cognitive Decline: A Systematic Review and Meta-analysis

Background To assess the effects of long-term exercise on the onset of dementia, mild cognitive impairment (MCI), and other clinically meaningful cognitive decline in the elderly adults. Methods Systematic review with preplanned meta-analysis. Electronic searches were performed between November 2016 and May 2017. Randomized controlled trials (RCTs) examining the effects of long-term exercise (intervention length 12 months or longer) on the onset of dementia, MCI, or clinically meaningful cognitive decline in older adults without dementia at baseline were eligible. Two authors extracted the data independently. Four binary outcomes were defined: dementia onset, MCI onset, other clinically meaningful cognitive decline, and any of these three outcomes combined. Results Five studies (n = 2,878 participants randomized) were included in this review. Outcomes' incidence for exercisers and controls were, respectively: 3.7% (n = 949) and 6.1% (n = 1,017) for dementia (three studies), 10.2% (n = 686) and 9.1% (n = 682) for MCI (one study), 14.5% (n = 124) and 15.4% (n = 123) for other clinically meaningful cognitive decline (two studies), and 11.4% (n = 1,073) and 12.5% (n = 1,140) for all outcomes combined. Meta-analyses found no significant effects of exercise for reducing the risk of dementia, MCI, other clinically meaningful cognitive decline, or all outcomes combined. Conclusions Evidence from RCTs is limited and does not support that exercise reduces the risk of developing clinically important cognitive outcomes. Further long-term exercise RCTs are needed before solid conclusions can be drawn.
Biogeography and Virulence of Staphylococcus aureus

Background Staphylococcus aureus is commonly carried asymptomatically in the human anterior nares and occasionally enters the bloodstream to cause invasive disease. Much of the global diversity of S. aureus remains uncharacterised, and is not clear how disease propensity varies between strains, and between host populations. Methodology We compared 147 isolates recovered from five kindergartens in Chengdu, China, with 51 isolates contemporaneously recovered from cases of pediatric infection from the main hospital serving this community. The samples were characterised by MLST, the presence/absence of PVL, and antibiotic resistance profiling. Principal Findings Genotype frequencies within individual kindergartens differ, but the sample recovered from cases of disease shows a general enrichment of certain MLST genotypes and PVL positive isolates. Genotypes under-represented in the disease sample tend to correspond to a single sequence cluster, and this cluster is more common in China than in other parts of the world. Conclusions/Significance Virulence propensity likely reflects a synergy between variation in the core genome (MLST) and accessory genome (PVL). By combining evidence form biogeography and virulence we demonstrate the existence of a “native” clade in West China which has lowered virulence, possibility due to acquired host immunity.