Miracle-dz/UniFAR-FTUs huggingface dataset:
The structure of the Ctf19c/CCAN from budding yeast

Eukaryotic kinetochores connect spindlemicrotubules to chromosomal centromeres. A group of proteins called the Ctf19 complex (Ctf19c) in yeast and the constitutive centromere associated network (CCAN) in other organisms creates the foundation of a kinetochore. The Ctf19c/CCAN influences the timing of kinetochore assembly, sets its location by associating with a specialized nucleosome containing the histone H3 variant Cse4/CENP-A, and determines the organization of the microtubule attachment apparatus. We present here the structure of a reconstituted 13-subunit Ctf19c determined by cryo-electron microscopy at ~4 Å resolution. The structure accounts for known and inferred contacts with the Cse4 nucleosome and for an observed assembly hierarchy. We describe its implications for establishment of kinetochores and for their regulation by kinases throughout the cell cycle.
A contemporary review of machine learning in otolaryngology–head and neck surgery

One of the key challenges with big data is leveraging the complex network of information to yield useful clinical insights. The confluence of massive amounts of health data and a desire to make inferences and insights on these data has produced a substantial amount of interest in machine‐learning analytic methods. There has been a drastic increase in the otolaryngology literature volume describing novel applications of machine learning within the past 5 years. In this timely contemporary review, we provide an overview of popular machine‐learning techniques, and review recent machine‐learning applications in otolaryngology–head and neck surgery including neurotology, head and neck oncology, laryngology, and rhinology. Investigators have realized significant success in validated models with model sensitivities and specificities approaching 100%. Challenges remain in the implementation of machine‐learning algorithms. This may be in part the unfamiliarity of these techniques to clinician leaders on the front lines of patient care. Spreading awareness and confidence in machine learning will follow with further validation and proof‐of‐value analyses that demonstrate model performance superiority over established methods. We are poised to see a greater influx of machine‐learning applications to clinical problems in otolaryngology–head and neck surgery, and it is prudent for providers to understand the potential benefits and limitations of these technologies. Laryngoscope, 130:45–51, 2020
Survival of the elderly and exposition to polypharmacy in the city of São Paulo, Brazil: SABE Study.

INTRODUCTION The use of polypharmacy may be due to the concomitant presence of chronic conditions, medical care by several doctors simultaneously and self-medication. Combined with the vulnerability of the elderly to the effects of drugs due to pharmacokinetic and pharmacodynamic changes, polypharmacy makes this population more susceptible to adverse outcomes. In Brazil, studies show that polypharmacy is a common problem among elderly people. However, few information is available on the association between polypharmacy and mortality. OBJECTIVE It was assessed the survival of the elderly from São Paulo city exposed to the use of polypharmacy (five or more medications). METHODS That was a population-based cohort, the Health, Well-Being and Aging Study (SABE Study), conducted from 2006 to 2010. The sample was composed of 1,258 individuals aged 60 years or more. The Kaplan-Meier method and Cox proportional risks model were used to examine the association between polypharmacy and mortality. RESULTS The probability of survival after five years of the users of polypharmacy at baseline was 77.2%, while among the non-users was 85.5%. Polypharmacy remained as a risk factor for death even after adjustment in other conditions associated with mortality, such as age, gender, income, chronic diseases and hospitalization. CONCLUSION The results point polypharmacy as an indicator of mortality in elderly people. The use of multiple medications by the elderly should be carefully assessed to avoid or minimize the damage to this population.
Ultrashort infrared 2.5-11  μm pulses: spatiotemporal profiles and absolute nonlinear response of air constituents.

We measure the detailed spatiotemporal profiles of femtosecond laser pulses in the infrared wavelength range of λ=2.5-11 μm and the absolute nonlinear response of major air constituents (N2, O2, and Ar) over this range. The spatiotemporal measurements reveal wavelength-dependent pulse front tilt and temporal stretching in the infrared pulses.
Relationship Between Nut Consumption and Metabolic Syndrome: A Meta-Analysis of Observational Studies

Abstract Objective: Our aim was to examine the relationship between nut consumption and metabolic syndrome (MetS). Methods: The electronic databases of PubMed, Web of Science, and Embase were searched up to November 2018 for observational studies on the relationship between nut consumption and MetS. The pooled relative risk (RR) of MetS for the highest versus lowest category of nut consumption, as well as their corresponding 95% confidence intervals (CIs) were calculated. Results: A total of 11 observational studies (6 cross-sectional and 5 prospective cohort studies), which involved a total of 89,224 participants, were identified for this meta-analysis. The overall multivariable adjusted RR showed that nut consumption was negatively associated with MetS (RR = 0.84; 95% CI, 0.76–0.92; p < 0.001). Of interest, subgroup analysis confirmed that such findings existed in tree nuts (RR = 0.97; 95% CI, 0.94–1.00; p = 0.04), but not in peanuts (RR = 1.01; 95% CI, 0.96–1.06; p = 0.68). Conclusions: The existing evidence suggested that nut consumption was negatively associated with MetS. However, such an inverse relationship only existed in tree nuts, not in peanuts. More well-designed studies with detailed specifications of nut varieties are needed to further elaborate the issues examined in this study.
IMPACT OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVIEW STRATEGY ON DETECTION OF CHOROIDAL NEOVASCULARIZATION.

PURPOSE To compare optical coherence tomography angiography (OCTA) review strategies for optimizing choroidal neovascularization (CNV) detection. METHODS Eyes with CNV in the differential diagnosis were imaged with the Avanti RTVue XR HD (Optovue, Fremont, CA). Three modalities of review for CNV presence were used in each case: a single report generated using automated segmentation within Avanti software; a continuous slab descent video OCTA export; and a manual segmentation approach using cross-sectional OCT with decorrelation signal overlay. Scans were reviewed by two masked expert reviewers; a third reviewer was used for discrepancies. RESULTS The study included 421 eyes, and 350 eyes had reports deemed sufficient quality for interpretation. Choroidal neovascularization was in the differential diagnosis in 107 of 350 patients. Overall CNV was identified in 55% (59/107) eyes. In those eyes with CNV, the automated segmentation identified CNV in 56% (33/59) of cases, continuous slab descent method identified CNV in 53% (31/59) of cases, and the manual segmentation group identified CNV in 92% (54/59) of cases. CONCLUSION Review strategies for detection of CNV on OCTA were highest using the manual segmentation method as compared to both the automated report and continuous slab descent methods. Although the manual segmentation method had a higher rate of detection, the practical aspects of the time required for segmentation make this method challenging in routine clinical practice.
Temporal Thresholds for Infarction and Hypothermic Protection in Long-Evans Rats: Factors Affecting Apparent ‘Reperfusion Injury’ After Transient Focal Ischemia

Background and Purpose— Some previous studies in Long-Evans rats noted larger infarcts after transient middle cerebral artery (MCA) occlusions than after permanent occlusions, interpreted to demonstrate “reperfusion injury. ” Recent experiments failed to reproduce this phenomenon, prompting an investigation of the sources of variability in this animal model. Methods— Male Long-Evans rats were subjected to surgical occlusion of the right MCA and ipsilateral common carotid artery. Variables tested included duration of occlusion and halothane anesthesia exposure and targeting of proximal or distal MCA occlusion sites. The temporal window for hypothermic protection was also investigated. Results— MCA occlusions at the level of the rhinal fissure produced graded increases in infarct volume with ischemia duration, and lesion size did not differ between 3-hour and permanent occlusions independent of anesthesia duration. Occlusions at a more distal site produced infarcts of comparable size after transient 3-hour occlusions and after permanent occlusions accompanied by prolonged anesthesia, but significantly smaller infarcts were seen when permanent occlusions were followed by rapid anesthesia termination. Hypothermia conferred protection only when initiated before reperfusion after transient proximal occlusions. Conclusions— These results indicate that previously described “reperfusion injury” after transient MCA occlusions conversely reflects unexpected injury reduction when rats with permanent occlusions experience early anesthesia termination. More rapid blood pressure recovery under such conditions permits improved collateral perfusion. The absence of a detectable postischemic window for hypothermic protection further argues against a significant component of delayed postreperfusion injury in this model.
“It Doesn’t Freak Us Out the Way It Used to”: An Evaluation of the Domestic Violence Enhanced Home Visitation Program to Inform Practice and Policy Screening for IPV

The Domestic Violence Enhanced Home Visitation (DOVE) intervention used in the Perinatal Nurse Home Visiting Intervention Enhanced With mHealth Technology (RCT: R01HD071771) is a nurse-lead evidenced-based intervention that has been shown to decrease violence overtime. This summative mixed-methods impact evaluation is intended to provide insight to enhance the DOVE IPV protocol for screening and intervention by (a) identifying which core aspects of DOVE facilitated or inhibited its success and what was most critical to optimal IPV (intimate partner violence) screening and intervention practices, (b) informing how DOVE IPV screening and intervention were influenced by the experiences of home visitor (HV), and (c) identifying policy considerations and best practice recommendations for the DOVE protocol. Participants were HVs and managers (N = 13) in rural/urban home visiting programs delivering DOVE across three states. The sample had a mean age of 48.76. Three fourths were baccalaureate-prepared nurses with an average of 10.5 years of home visiting experience. The method used in this study was one-to-one qualitative in-depth interviews with HVs. Data were interpretively analyzed using Nvivo 10 to generate three themes. Participants endorsed screening women for IPV with DOVE being the approach of choice to facilitate IPV screening and intervening with women. HVs found DOVE helped enhance their IPV knowledge, screening, and intervening capabilities while filling an existing void in this type of preparation of HV nurses. Establishing a relationship with the women before initiating screening was an important aspect in delivering DOVE as was the training, support, and increased comfort level in addressing IPV. The evidence offers an understanding of which core aspects of DOVE contributed to its success and what was most critical to optimal IPV screening and intervention practices. Furthermore, this evaluation provided multilevel insights into how best to advance home visiting practices and policies when screening and intervening with perinatal women exposed to IPV.
Outcomes of Patients with Delayed Dialysis Initiation: Results from the AVENIR Study

Background: Some patients who reach end-stage renal disease refuse to start dialysis at the time suggested by their nephrologist and delay it. Whether this delay may affect health-related quality of life (HRQoL), clinical and biological parameters at dialysis onset, and then survival and hospitalization during dialysis is unknown. Methods: We considered all adult patients who began dialysis in Lorraine (France) in 2005–2006 having previously been followed by a nephrologist. Clinical and biological characteristics at dialysis onset were collected from medical records, and nephrologists were interviewed about compliance with the recommended starting date. HRQoL was measured using the French version of the ‘Kidney Disease Quality of Life’ V36 questionnaire. Mortality and total duration of hospitalization during the first year of dialysis were recorded as part of the end-stage renal disease French registry. The effects of delaying dialysis on survival and on duration of hospitalization were determined using log-rank test and polychotomous logistic regression, respectively. Results: Of 541 patients, 88 (16.3%) declined to initiate dialysis at the time recommended by the nephrologist and delayed it. Compared with patients who were compliant with the advice, noncompliers had more comorbidities, poorer clinical and biological profiles at dialysis start, and a higher risk of beginning dialysis in emergency circumstances with greater decline in the ‘burden of kidney disease’ dimension of HRQoL. However, there were no differences in survival or duration of hospitalization during dialysis. Conclusion: Despite a negative effect on clinical and biological parameters at initiation, delaying dialysis did not impact on survival during treatment.
PrimPol is required for the maintenance of efficient nuclear and mitochondrial DNA replication in human cells

Eukaryotic Primase-Polymerase (PrimPol) is an enzyme that maintains efficient DNA duplication by repriming replication restart downstream of replicase stalling lesions and structures. To elucidate the cellular requirements for PrimPol in human cells, we generated PrimPol-deleted cell lines and show that it plays key roles in maintaining active replication in both the nucleus and mitochondrion, even in the absence of exogenous damage. Human cells lacking PrimPol exhibit delayed recovery after UV-C damage and increased mutation rates, micronuclei and sister chromatin exchanges but are not sensitive to genotoxins. PrimPol is also required during mitochondrial replication, with PrimPol-deficient cells having increased mtDNA copy number but displaying a significant decrease in replication rates. Deletion of PrimPol in XPV cells, lacking functional Pol Eta, causes an increase in DNA damage sensitivity and pronounced fork stalling after UV-C treatment. We show that, unlike canonical TLS polymerases, PrimPol is important for allowing active replication to proceed, even in the absence of exogenous damage, thus preventing the accumulation of excessive fork stalling and genetic mutations. Together, these findings highlight the importance of PrimPol for maintaining efficient DNA replication in unperturbed cells and its complementary roles, with Pol Eta, in damage tolerance in human cells.
Spousal Education and Cognitive Functioning in Later Life.

Objectives Numerous studies have documented the relationship between education and cognitive functioning at the individual level. Yet few studies have examined whether a spouse's education spills over to influence the other spouse's cognitive functioning. This study, therefore, investigated the association between spousal education and cognitive functioning, the pathways that may account for this association, and gender differences in this association. Method Growth curve models were analyzed by using longitudinal couple data from the Health and Retirement Study (N=5,846 individuals). Results More years of spousal education is associated with higher level of cognitive functioning at age 65 (γ000=.0532, 95% confidence interval [CI]=.0163.0901) and slower decline in cognitive functioning in later adulthood (γ100 =.0054, 95% CI=.0026.0082). The positive association between spousal education and the level of cognitive functioning at age 65 was fully explained by economic resources. The association of spousal education with the rate of cognitive decline decreased but remained significant after controlling for economic resources and health behaviors (γ100 =.0043, 95% CI =.0014.0072). The association between spousal education and cognitive functioning was similar for men and women. Discussion Findings suggest that more years of spousal education may slow decline in cognitive functioning for men and women in later life.
Evaluating the Impact of Treatment Care Planning on Quality Measures.

PURPOSE: The Center for Medicare & Medicaid Innovation Oncology Care Model (OCM) requires documentation of a 13-point Institute of Medicine care management plan for Medicare patients. In addition, OCM includes evaluation of quality using key performance measures that align with the ASCO Quality Oncology Practice Initiative (QOPI). Both efforts are designed to improve patient-centered care and foster patients' engagement in their care plan. METHODS: A multicenter quality improvement project was conducted to develop a strategy to meet the OCM treatment planning (TP) requirement (Plan), pilot clinician education coupled with use of electronic TP in early-stage breast cancer (Do), evaluate the impact of TP on QOPI measures (Study), and develop recommendations for future implementation (Act). RESULTS: Thirty-three clinical providers and 171 women with breast cancer were included. Improved performance on several QOPI measures was observed for the intervention group compared with the historical control group. CONCLUSION: Meeting the OCM TP requirement through incorporating a technology solution provided an opportunity for quality improvement and preparation for full-scale TP within the OCM. TP delivery was associated with improved performance on select ASCO QOPI measures, which is likely to correspond with improved performance on quality measures within OCM.
XX SRY-Negative True Hermaphrodism in Two Dogs: Clinical, Morphological, Genetic and Cytogenetic Studies

This work aimed at giving a deeper insight into peculiar cases of intersexuality occurring in dogs and known as XX true hermaphrodism due to the existence of both testicular and ovarian tissue in one or both gonads in the presence of an XX chromosome constitution. Clinical, histological and genetic approaches were used in the study of an 8-month-old Cocker Spaniel dog and a 3-year-old mixed-breed Pitbull, both showing a female phenotype, clitoromegaly and male behavior. A normal female karyotype (2n = 78,XX) was noticed, and polymerase chain reaction failed to detect SRY in genomic DNA obtained from peripheral blood lymphocytes of both dogs. The reproductive tract was removed by standard ovariohysterectomy and processed for histology. Thereafter, a normal female phenotype was reconstructed by vaginoplasty. Histological examination revealed bilateral ovotestis in both cases: the gonads showed immature testicular parenchyma containing seminiferous tubules, Sertoli and Leydig cells, but no signs of spermatogenesis, together with differently developed ovarian follicles containing oocytes. In the ovotestes, steroidogenesis was detected by P450c17-immunoreactivity in Leydig cells as well as in theca cells, whereas no MIS-immunoreactivity was shown by the Sertoli cells. Genital tracts of Wolffian and Müllerian origin co-existed in both subjects. Both dogs belong to the very rare cases in which testicular tissue develops in the absence of the key gene, SRY. Up to date very few genetic events have been associated with this abnormal sexual differentiation: SOX9 over-expression and RSPO1 mutation. Nevertheless, neither of them has been found in these dogs.
Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology

Fibrosis is a pivotal player in heart failure development and progression. Measurements of (markers of) fibrosis in tissue and blood may help to diagnose and risk stratify patients with heart failure, and its treatment may be effective in preventing heart failure and its progression. A lack of pathophysiological insights and uniform definitions has hampered the research in fibrosis and heart failure. The Translational Research Committee of the Heart Failure Association discussed several aspects of fibrosis in their workshop. Early insidious perturbations such as subclinical hypertension or inflammation may trigger first fibrotic events, while more dramatic triggers such as myocardial infarction
Force‐generating capacity of the toe flexor muscles and dynamic function of the foot arch in upright standing

The muscle and tendon complex of the foot helps to support the foot arch and generates the muscle force of the foot. The present study investigated the force‐generating capacity of the toe flexor muscles and the dynamic function of the foot arch when standing upright, and the relationships between these indices. The maximum toe flexor force and foot arch height in the sitting and standing positions were studied in the left and right feet of 224 healthy young individuals. To measure the maximum isometric force of the toe flexor muscles, the subjects exerted maximum force on a toe grip dynamometer. Measurements were repeated three times with at least a 1‐min rest period between bouts, and the maximum value among the measurements for each foot was used for further analysis. The absolute value of the toe flexor strength was normalised by body mass. The foot arch height was measured the distance between the tuberosity of the navicular bone and the floor, and normalised by height. The relative foot arch height difference between the sitting and standing positions was evaluated as the foot arch dynamics. The maximum isometric toe flexor strength was 42% higher in the standing position than in the sitting position. There was no relationship between the relative toe flexor strength and the relative foot arch height in either the sitting or standing positions; however, the relative increase in toe flexor strength from sitting to standing (the force amplification factor) was related to the foot arch dynamics, and the flexible foot arch showed a greater increase in the toe flexor strength from sitting to standing compared with the strength in the stiff foot arch. The results of this study suggest that the force‐generating capacity of the toe flexor muscles is augmented by bodyweight bearing in upright standing. Additionally, the force amplification mechanism is mechanically regulated by the dynamic function of the foot arch in conjunction with the stretching of the muscle–tendon complex of the foot.