Miracle-dz/UniFAR-FTUs huggingface dataset:
D3.2 - Towards a Gigahertz Microfluidic Impedance Cytometer

We present a microfluidic impedance cytometer enabling dielectric characterization of single cells at frequencies up to 500 MHz, which represents a more than ten-fold frequency increase compared to other devices. The dielectric properties at lower frequencies reveal information about cell size and membrane capacitance. The increased frequency range of the presented cytometer potentially allows for characterization of subcellular components such as vacuoles or the cell nuclei. We demonstrate the capabilities of the cytometer by discriminating polystyrene beads from Chinese hamster ovary (CHO) cells, based on the difference in dielectric properties at frequencies up to 500 MHz. The low frequency data show similar responses of cells and beads, which indicate that they are of comparable size. The high frequency results show a smaller response of the cells, due to the higher conductivity of cytoplasm and nucleus in comparison to the non-conducting beads.
Prolonged sleep duration as a marker of early neurodegeneration predicting incident dementia

Objective: To evaluate the association between sleep duration and the risk of incident dementia and brain aging. Methods: Self-reported total hours of sleep were examined in the Framingham Heart Study (n = 2,457, mean age 72 ± 6 years, 57% women) as a 3-level variable: <6 hours (short), 6–9 hours (reference), and >9 hours (long), and was related to the risk of incident dementia over 10 years, and cross-sectionally to total cerebral brain volume (TCBV) and cognitive performance. Results: We observed 234 cases of all-cause dementia over 10 years of follow-up. In multivariable analyses, prolonged sleep duration was associated with an increased risk of incident dementia (hazard ratio [HR] 2.01; 95% confidence interval [CI] 1.24–3.26). These findings were driven by persons with baseline mild cognitive impairment (HR 2.83; 95% CI 1.06–7.55) and persons without a high school degree (HR 6.05; 95% CI 3.00–12.18). Transitioning to sleeping >9 hours over a mean period of 13 years before baseline was associated with an increased risk of all-cause dementia (HR 2.43; 95% CI 1.44–4.11) and clinical Alzheimer disease (HR 2.20; 95% CI 1.17–4.13). Relative to sleeping 6–9 hours, long sleep duration was also associated cross-sectionally with smaller TCBV (β ± SE, −1.08 ± 0.41 mean units of TCBV difference) and poorer executive function (β ± SE, −0.41 ± 0.13 SD units of Trail Making Test B minus A score difference). Conclusions: Prolonged sleep duration may be a marker of early neurodegeneration and hence a useful clinical tool to identify those at a higher risk of progressing to clinical dementia within 10 years.
Testing Local Host Adaptation and Phenotypic Plasticity in a Herbivore When Alternative Related Host Plants Occur Sympatrically

Host race formation in phytophagous insects can be an early stage of adaptive speciation. However, the evolution of phenotypic plasticity in host use is another possible outcome. Using a reciprocal transplant experiment we tested the hypothesis of local adaptation in the aphid Brevicoryne brassicae. Aphid genotypes derived from two sympatric host plants, Brassica oleracea and B. campestris, were assessed in order to measure the extent of phenotypic plasticity in morphological and life history traits in relation to the host plants. We obtained an index of phenotypic plasticity for each genotype. Morphological variation of aphids was summarized by principal components analysis. Significant effects of recipient host on morphological variation and life history traits (establishment, age at first reproduction, number of nymphs, and intrinsic growth rate) were detected. We did not detected genotype × host plant interaction; in general the genotypes developed better on B. campestris, independent of the host plant species from which they were collected. Therefore, there was no evidence to suggest local adaptation. Regarding plasticity, significant differences among genotypes in the index of plasticity were detected. Furthermore, significant selection on PC1 (general aphid body size) on B. campestris, and on PC1 and PC2 (body length relative to body size) on B. oleracea was detected. The elevation of the reaction norm of PC1 and the slope of the reaction norm for PC2 (i.e., plasticity) were under directional selection. Thus, host plant species constitute distinct selective environments for B. brassicae. Aphid genotypes expressed different phenotypes in response to the host plant with low or nil fitness costs. Phenotypic plasticity and gene flow limits natural selection for host specialization promoting the maintenance of genetic variation in host exploitation.
Drug Resistance Missense Mutations in Cancer Are Subject to Evolutionary Constraints

Several tumour types are sensitive to deactivation of just one or very few genes that are constantly active in the cancer cells, a phenomenon that is termed ‘oncogene addiction’. Drugs that target the products of those oncogenes can yield a temporary relief, and even complete remission. Unfortunately, many patients receiving oncogene-targeted therapies relapse on treatment. This often happens due to somatic mutations in the oncogene (‘resistance mutations’). ‘Compound mutations’, which in the context of cancer drug resistance are defined as two or more mutations of the drug target in the same clone may lead to enhanced resistance against the most selective inhibitors. Here, it is shown that the vast majority of the resistance mutations occurring in cancer patients treated with tyrosin kinase inhibitors aimed at three different proteins follow an evolutionary pathway. Using bioinformatic analysis tools, it is found that the drug-resistance mutations in the tyrosine kinase domains of Abl1, ALK and exons 20 and 21 of EGFR favour transformations to residues that can be identified in similar positions in evolutionary related proteins. The results demonstrate that evolutionary pressure shapes the mutational landscape in the case of drug-resistance somatic mutations. The constraints on the mutational landscape suggest that it may be possible to counter single drug-resistance point mutations. The observation of relatively many resistance mutations in Abl1, but not in the other genes, is explained by the fact that mutations in Abl1 tend to be biochemically conservative, whereas mutations in EGFR and ALK tend to be radical. Analysis of Abl1 compound mutations suggests that such mutations are more prevalent than hitherto reported and may be more difficult to counter. This supports the notion that such mutations may provide an escape route for targeted cancer drug resistance.
Clinical Implications of Accuracy Measurements of Continuous Glucose Sensors

The accuracy of a continuous glucose monitor (CGM) now supports its use by persons with diabetes and clinicians caring for them. This article reviews measures of CGM accuracy, factors contributing to accuracy, comparative accuracy assessment, clinical implications of CGM sensor accuracy, and recent clinical trials that have demonstrated the utility of CGMs.
SynchroWatch

SynchroWatch is a one-handed interaction technique for smartwatches that uses rhythmic correlation between a user's thumb movement and on-screen blinking controls. Our technique uses magnetic sensing to track the synchronous extension and reposition of the thumb, augmented with a passive magnetic ring. The system measures the relative changes in the magnetic field induced by the required thumb movement and uses a time-shifted correlation approach with a reference waveform for detection of synchrony. We evaluated the technique during three distraction tasks with varying degrees of hand and finger movement: active walking, browsing on a computer, and relaxing while watching online videos. Our initial offline results suggest that intentional synchronous gestures can be distinguished from other movement. A second evaluation using a live implementation of the system running on a smartwatch suggests that this technique is viable for gestures used to respond to notifications or issue commands. Finally, we present three demonstration applications that highlight the technique running in real-time on the smartwatch.
Evidence for interannual variation in genetic structure of Dungeness crab (Cancer magister) along the California Current System

Using a combination of population‐ and individual‐based analytical approaches, we provide a comprehensive examination of genetic connectivity of Dungeness crab (Cancer magister) along ~1,200 km of the California Current System (CCS). We sampled individuals at 33 sites in 2012 to establish a baseline of genetic diversity and hierarchal population genetic structure and then assessed interannual variability in our estimates by sampling again in 2014. Genetic diversity showed little variation among sites or across years. In 2012, we observed weak genetic differentiation among sites (FST range = −0.005–0.014) following a pattern of isolation by distance (IBD) and significantly high relatedness among individuals within nine sampling sites. In 2014, pairwise FST estimates were lower (FST range = −0.014–0.007), there was no spatial autocorrelation, and fewer sites had significant evidence of relatedness. Based on these findings, we propose that interannual variation in the physical oceanographic conditions of the CCS influences larval recruitment and thus gene flow, contributing to interannual variation in population genetic structure. Estimates of effective population size (Ne) were large in both 2012 and 2014. Together, our results suggest that Dungeness crab in the CCS may constitute a single evolutionary population, although geographically limited dispersal results in an ephemeral signal of IBD. Furthermore, our findings demonstrate that populations of marine organisms may be susceptible to temporal changes in population genetic structure over short time periods; thus, interannual variability in population genetic measures should be considered.
Subtype Distribution of Blastocystis Isolates in Sebha, Libya

Background Blastocystis is a genetically diverse and a common intestinal parasite of humans with a controversial pathogenic potential. This study was carried out to identify the Blastocystis subtypes and their association with demographic and socioeconomic factors among outpatients living in Sebha city, Libya. Methods/Findings Blastocystis in stool samples were cultured followed by isolation, PCR amplification of a partial SSU rDNA gene, cloning, and sequencing. The DNA sequences of isolated clones showed 98.3% to 100% identity with the reference Blastocystis isolates from the Genbank. Multiple sequence alignment showed polymorphism from one to seven base substitution and/or insertion/deletion in several groups of non-identical nucleotides clones. Phylogenetic analysis revealed three assemblage subtypes (ST) with ST1 as the most prevalent (51.1%) followed by ST2 (24.4%), ST3 (17.8%) and mixed infections of two concurrent subtypes (6.7%). Blastocystis ST1 infection was significantly associated with female (P = 0.009) and low educational level (P = 0.034). ST2 was also significantly associated with low educational level (P= 0.008) and ST3 with diarrhoea (P = 0.008). Conclusion Phylogenetic analysis of Libyan Blastocystis isolates identified three different subtypes; with ST1 being the predominant subtype and its infection was significantly associated with female gender and low educational level. More extensive studies are needed in order to relate each Blastocystis subtype with clinical symptoms and potential transmission sources in this community.
Clinical Use of Continuous Glucose Monitoring in Adults with Type 2 Diabetes

BACKGROUND Hemoglobin A1c is an excellent population health measure for the risk of vascular complications in diabetes, while continuous glucose monitoring (CGM) is a tool to help personalize a diabetes treatment plan. The value of CGM in individuals with type 1 diabetes (T1D) has been well demonstrated when compared with utilizing self-monitoring of blood glucose (SMBG) to guide treatment decisions. CGM is a tool for patients and clinicians to visualize the important role that diet, exercise, stress management, and the appropriate selection of diabetes medications can have in managing type 2 diabetes (T2D). Several diabetes organizations have recently reviewed the literature on the appropriate use of CGM in diabetes management and concluded CGM may be a useful educational and management tool particularly for patients on insulin therapy. The indications for using CGM either as a clinic-based loaner distribution model for intermittent use (professional CGM) or a CGM system owned by the patient and used at home with real-time glucose reading (personal CGM) are only beginning to be addressed in T2D. Most summaries of CGM studies conclude that having a standardized glucose pattern report, such as the ambulatory glucose profile (AGP) report, should help facilitate effective shared decision-making sessions. The future of CGM indications for the use of CGM is evolving rapidly. In some instances, CGM is now approved for making medication adjustments without SMBG confirmation and it appears that some forms of CGM will be approved for use in the Medicare population in the United States in the near future. Many individuals with T1D and T2D and their care teams will come to depend on CGM as a key tool for diabetes management.
Impact of El Niño Southern Oscillation on infectious disease hospitalization risk in the United States

Although the global climate is changing at an unprecedented rate, links between weather and infectious disease have received little attention in high income countries. The “El Niño Southern Oscillation” (ENSO) occurs irregularly and is associated with changing temperature and precipitation patterns. We studied the impact of ENSO on infectious diseases in four census regions in the United States. We evaluated infectious diseases requiring hospitalization using the US National Hospital Discharge Survey (1970–2010) and five disease groupings that may undergo epidemiological shifts with changing climate: (i) vector-borne diseases, (ii) pneumonia and influenza, (iii) enteric disease, (iv) zoonotic bacterial disease, and (v) fungal disease. ENSO exposure was based on the Multivariate ENSO Index. Distributed lag models, with adjustment for seasonal oscillation and long-term trends, were used to evaluate the impact of ENSO on disease incidence over lags of up to 12 mo. ENSO was associated more with vector-borne disease [relative risk (RR) 2.96, 95% confidence interval (CI) 1.03–8.48] and less with enteric disease (0.73, 95% CI 0.62–0.87) in the Western region; the increase in vector-borne disease was attributable to increased risk of rickettsioses and tick-borne infectious diseases. By contrast, ENSO was associated with more enteric disease in non-Western regions (RR 1.12, 95% CI 1.02–1.15). The periodic nature of ENSO may make it a useful natural experiment for evaluation of the impact of climatic shifts on infectious disease risk. The impact of ENSO suggests that warmer temperatures and extreme variation in precipitation events influence risks of vector-borne and enteric disease in the United States.
Actigraphy features for predicting mobility disability in older adults

Actigraphy has attracted much attention for assessing physical activity in the past decade. Many algorithms have been developed to automate the analysis process, but none has targeted a general model to discover related features for detecting or predicting mobility function, or more specifically, mobility impairment and major mobility disability (MMD). Men (N = 357) and women (N = 778) aged 70–89 years wore a tri-axial accelerometer (Actigraph GT3X) on the right hip during free-living conditions for 8.4 ± 3.0 d. One-second epoch data were summarized into 67 features. Several machine learning techniques were used to select features from the free-living condition to predict mobility impairment, defined as 400 m walking speed <0.80 m s−1. Selected features were also included in a model to predict the first occurrence of MMD—defined as the loss in the ability to walk 400 m. Each method yielded a similar estimate of 400 m walking speed with a root mean square error of ~0.07 m s−1 and an R-squared values ranging from 0.37–0.41. Sensitivity and specificity of identifying slow walkers was approximately 70% and 80% for all methods, respectively. The top five features, which were related to movement pace and amount (activity counts and steps), length in activity engagement (bout length), accumulation patterns of activity, and movement variability significantly improved the prediction of MMD beyond that found with common covariates (age, diseases, anthropometry, etc). This study identified a subset of actigraphy features collected in free-living conditions that are moderately accurate in identifying persons with clinically-assessed mobility impaired and significantly improve the prediction of MMD. These findings suggest that the combination of features as opposed to a specific feature is important to consider when choosing features and/or combinations of features for prediction of mobility phenotypes in older adults.
Bone Inner Structure Suggests Increasing Aquatic Adaptations in Desmostylia (Mammalia, Afrotheria)

Background The paleoecology of desmostylians has been discussed controversially with a general consensus that desmostylians were aquatic or semi-aquatic to some extent. Bone microanatomy can be used as a powerful tool to infer habitat preference of extinct animals. However, bone microanatomical studies of desmostylians are extremely scarce. Methodology/Principal Findings We analyzed the histology and microanatomy of several desmostylians using thin-sections and CT scans of ribs, humeri, femora and vertebrae. Comparisons with extant mammals allowed us to better understand the mode of life and evolutionary history of these taxa. Desmostylian ribs and long bones generally lack a medullary cavity. This trait has been interpreted as an aquatic adaptation among amniotes. Behemotops and Paleoparadoxia show osteosclerosis (i.e. increase in bone compactness), and Ashoroa pachyosteosclerosis (i.e. combined increase in bone volume and compactness). Conversely, Desmostylus differs from these desmostylians in displaying an osteoporotic-like pattern. Conclusions/Significance In living taxa, bone mass increase provides hydrostatic buoyancy and body trim control suitable for poorly efficient swimmers, while wholly spongy bones are associated with hydrodynamic buoyancy control in active swimmers. Our study suggests that all desmostylians had achieved an essentially, if not exclusively, aquatic lifestyle. Behemotops, Paleoparadoxia and Ashoroa are interpreted as shallow water swimmers, either hovering slowly at a preferred depth, or walking on the bottom, and Desmostylus as a more active swimmer with a peculiar habitat and feeding strategy within Desmostylia. Therefore, desmostylians are, with cetaceans, the second mammal group showing a shift from bone mass increase to a spongy inner organization of bones in their evolutionary history.
Experiment study on the flocculation settlement characteristic of unclassified tailings

Laboratory experiments were carried out by uniform design to investigate the effects of flocculant unit consumption,flocculant solution concentration and feed-slurry concentration on settling velocity and settling concentration in solid-liquid separation.According to the regression analysis of experimental data,the influence degrees of the three factors on settling velocity in descending order are feed-slurry concentration,flocculant unit consumption and flocculant solution concentration.Settling velocity shows a positive correlation with flocculant solution concentration and flocculant unit consumption,but a negative correlation with feed-slurry concentration.The influence degrees of the three factors on settling concentration in descending order are feed-slurry concentration,flocculant unit consumption and flocculant solution concentration.Settling concentration exhibits a positive correlation with flocculant solution concentration and feed-slurry concentration,but is independent of flocculant unit consumption.Nonlinear programme is used to find the optimal ratio,and the deviation of the predicted values and the measured ones from verification experiments is less than 8%. The recommended operating parameters for deep cone thickeners are the flocculant unit consumption of 5g·t-1,the flocculant solution concentration of 0.05% and feed-slurry concentration of 5.233%.
Shot-peening and low-cycle fatigue of titanium alloys : instrumented indentation and X-ray diffraction

There are two problems when investigating the effects of shot-peening on fatigue process. The first one is characterizing residual stresses (RS) and strain hardening (WH) on the sample surface. The second one is the evolution of RS and WH during fatigue. In order to solve the first problem, this thesis proposes a “simultaneous function method” to measure RS and WH with nanoindentation. Accumulated plastic strain (PP) is used to represent WH. Then, by establishing functions of normalized indentation responses through a series of finite element method (FEM) simulations, normalized indentation responses obtained from nanoindentation experiments can be used to extract RS and PP values, assuming that the constitutive behavior is known. Although the simultaneous function method shows fairly high accuracy from a pure numerical view point, experiments performed on T40 commercial pure titanium are not completely satisfying. However, if the residual stress profile is known, the method can be used to derive the work hardening profile.In order to study the second problem, a series of strain-controlled fatigue tests are performed on Ti-18 alloy. Fatigue specimens of 4 material states, including raw, shot-peened, prestrained and prestrained + shot-peened, were tested under 3 different strain amplitudes over 100 cycles. X-ray diffraction tests on the sample surfaces showed that the RS relaxation and the cyclic softening increase together with the strain amplitude. IIT tests showed that shot-peening may induce a softening of the surface of Ti-18 alloy samples
Depression and poor outcome after an acute coronary event: Clarification of risk periods and mechanisms

Objective: Lifetime depression and depression around the time of an acute coronary syndrome event have been associated with poor cardiac outcomes. Our study sought to examine the persistence of this association, especially given modern cardiac medicine’s successes. Methods: For 332 patients admitted for an acute coronary syndrome, a baseline interview assessed major depression status, and psychological measures were administered. At 1 and 12 months post–acute coronary syndrome event, telephone interviews collected rates of hospital readmission and/or death and major depression status, while biomarker information was examined using medical records. Results: The 12-month mortality rate was 2.3% and cardiac readmission rate 21.0%. Depression subsequent to an acute coronary syndrome event resulted in a threefold and 2.5-fold increase in 1-month and 12-month odds of cardiac readmission or death, respectively. No relationship with past depressive episodes was found. Poor sleep was associated with higher trait anxiety and neuroticism scores and with more severe depression. Conclusion: Lifetime depression may increase the risk of depression around the time of an acute coronary syndrome but not influence cardiac outcomes. We suggest that poor sleep quality may be causal or indicate high anxiety/neuroticism, which increases risk to depression and contributes to poor cardiac outcomes rather than depression being the primary causal factor.