Miracle-dz/UniFAR-FTUs huggingface dataset:
Lactoferrin in Human Milk of Prolonged Lactation

Among the immunologically important bioactive factors present in human milk, lactoferrin (Lf) has emerged as a key player with wide-ranging features that directly and indirectly protect the neonate against infection caused by a variety of pathogens. The concentration of Lf in human milk is lactation-stage related; colostrum contains more than 5 g/L, which then significantly decreases to 2–3 g/L in mature milk. The milk of mothers who are breastfeeding for more than one year is of a standard value, containing macronutrients in a composition similar to that of human milk at later stages. The aim of this study was to evaluate lactoferrin concentration in prolonged lactation from the first to the 48th month postpartum. Lactating women (n = 120) up to 48 months postpartum were recruited to the study. The mean value of lactoferrin concentration was the lowest in the group of 1–12 months of lactation (3.39 ± 1.43 g/L), significantly increasing in the 13–18 months group (5.55 ± 4.00 g/L; p < 0.006), and remaining at a comparable level in the groups of 19–24 month and over 24 months (5.02 ± 2.97 and 4.90 ± 3.18 g/L, respectively). The concentration of lactoferrin in mother’s milk also showed a positive correlation with protein concentration over lactation from the first to the 48th month (r = 0.3374; p = 0.0002). Our results demonstrate the high immunology potential of human milk during prolonged lactation and that Lf concentration is close to the Lf concentration in colostrum. Evidence of stable or rising immunoprotein levels during prolonged lactation provides an argument for foregoing weaning; however, breastfeeding must be combined with solid foods meet the new requirements of a rapidly growing six-month or older baby.
Swimming on Peritoneal Dialysis: Recommendations from Australian PD Units

Background: There is no evidence to support the need for protection of the peritoneal dialysis (PD) catheter and exit site for people on PD who want to swim. Swimming with a PD catheter is perceived to potentially put that person at increased risk of infection. Objectives of this study were to determine the proportion of Australian PD units supporting swimming for people on PD, recommendations made to protect the PD catheter, and exit site and any subsequent infective complications. Method: Phone surveys were conducted with PD nurses from a cross section of 39 Australian PD units. Results: Almost all units reported that patients on PD do swim despite only 77% of units advocating swimming. Swimming in sea water (85%) or a private swimming pool (90%) is mostly recommended. Covering the exit site and PD catheter is recommended with a waterproof film dressing or colostomy bag. Performing routine exit-site care after swimming is recommended (100%). There were 7 reported exit-site infections and 2 episodes of peritonitis perceived to be associated with swimming with a PD catheter. Conclusion: Most PD units in Australia report that patients on PD swim. Swimming is recommended in either sea water or private swimming pools. The PD catheter and exit site should be covered with either a clear waterproof dressing or colostomy bag. Routine exit-site care should be performed after swimming. Infections were rarely reported in those who swim. Until further research is available, best practice recommendations are warranted for the safety of those on PD who want to swim.
Myosin motor domains carrying mutations implicated in early or late onset hypertrophic cardiomyopathy have similar properties

Hypertrophic cardiomyopathy (HCM) is a common genetic disorder characterized by left ventricular hypertrophy and cardiac hyper-contractility. Mutations in the β-cardiac myosin heavy chain gene (β-MyHC) are a major cause of HCM, but the specific mechanistic changes to myosin function that lead to this disease remain incompletely understood. Predicting the severity of any β-MyHC mutation is hindered by a lack of detailed examinations at the molecular level. Moreover, because HCM can take ≥20 years to develop, the severity of the mutations must be somewhat subtle. We hypothesized that mutations that result in early onset disease would have more severe changes in function than do later onset mutations. Here, we performed steady-state and transient kinetic analyses of myosins carrying one of seven missense mutations in the motor domain. Of these seven, four were previously identified in early onset cardiomyopathy screens. We used the parameters derived from these analyses to model the ATP-driven cross-bridge cycle. Contrary to our hypothesis, the results indicated no clear differences between early and late onset HCM mutations. Despite the lack of distinction between early and late onset HCM, the predicted occupancy of the force-holding actin·myosin·ADP complex at [Actin] = 3 Kapp along with the closely related duty ratio (the fraction of myosin in strongly attached force-holding states), and the measured ATPases all changed in parallel (in both sign and degree of change) compared with wildtype (WT) values. Six of the seven HCM mutations were clearly distinct from a set of previously characterized DCM mutations.
Evaluation of Infection Prevention and Control Readiness at Frontline Health Care Facilities in High-Risk Districts Bordering Ebola Virus Disease–Affected Areas in the Democratic Republic of the Congo — Uganda, 2018

Infection prevention and control (IPC) in health care facilities is essential to protecting patients, visitors, and health care personnel from the spread of infectious diseases, including Ebola virus disease (Ebola). Patients with suspected Ebola are typically referred to specialized Ebola treatment units (ETUs), which have strict isolation and IPC protocols, for testing and treatment (1,2). However, in settings where contact tracing is inadequate, Ebola patients might first seek care at general health care facilities, which often have insufficient IPC capacity (3-6). Before 2014-2016, most Ebola outbreaks occurred in rural or nonurban communities, and the role of health care facilities as amplification points, while recognized, was limited (7,8). In contrast to these earlier outbreaks, the 2014-2016 West Africa Ebola outbreak occurred in densely populated urban areas where access to health care facilities was better, but contact tracing was generally inadequate (8). Patients with unrecognized Ebola who sought care at health care facilities with inadequate IPC initiated multiple chains of transmission, which amplified the epidemic to an extent not seen in previous Ebola outbreaks (3-5,7). Implementation of robust IPC practices in general health care facilities was critical to ending health care-associated transmission (8). In August 2018, when an Ebola outbreak was recognized in the Democratic Republic of the Congo (DRC), neighboring countries began preparing for possible introduction of Ebola, with a focus on IPC. Baseline IPC assessments conducted in frontline health care facilities in high-risk districts in Uganda found IPC gaps in screening, isolation, and notification. Based on findings, additional funds were provided for IPC, a training curriculum was developed, and other corrective actions were taken. Ebola preparedness efforts should include activities to ensure that frontline health care facilities have the IPC capacity to rapidly identify suspected Ebola cases and refer such patients for treatment to protect patients, staff members, and visitors.
Cognitive impairment and transcriptomic profile in hippocampus of young mice after multiple neonatal exposures to sevoflurane

Children with repeated inhalational anesthesia may develop cognitive disorders. This study aimed to investigate the transcriptome-wide response of hippocampus in young mice that had been exposed to multiple sevoflurane in the neonatal period. Mice received 3% sevoflurane for 2 h on postnatal day (PND) 6, 8, and 10, followed by arterial blood gas test on PND 10, behavioral experiments on PND 31–36, and RNA sequencing (RNA-seq) of hippocampus on PND 37. Functional annotation and protein-protein interaction analyses of differentially expressed genes (DEGs) and quantitative reverse transcription polymerase chain reaction (qPCR) were performed. Neonatal sevoflurane exposures induced cognitive and social behavior disorders in young mice. RNA-seq identified a total of 314 DEGs. Several enriched biological processes (ion channels, brain development, learning, and memory) and signaling pathways (oxytocin signaling pathway and glutamatergic, cholinergic, and GABAergic synapses) were highlighted. As hub-proteins, Pten was involved in nervous system development, synapse assembly, learning, memory, and behaviors, Nos3 and Pik3cd in oxytocin signaling pathway, and Cdk16 in exocytosis and phosphorylation. Some top DEGs were validated by qPCR. This study revealed a transcriptome-wide profile in mice hippocampus after multiple neonatal exposures to sevoflurane, promoting better understanding of underlying mechanisms and investigation of preventive strategies.
Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques

Uterus transplantation (UTx) is an option for women with uterine factor infertility to have a child, but is still in the experimental stage. Therefore, allogeneic animal models of UTx are required for resolution of clinical issues. In this study, long-term outcomes were evaluated in four recipients (cases 1–4) after allogeneic UTx in cynomolgus macaques. Immunosuppression with antithymocyte globulin induction and a triple maintenance regimen was used. Postoperative ultrasonography and biopsy of the transplanted uterus and immunoserological examinations were performed. All four recipients survived for >3 months after surgery, but continuous menstruation did not resume, although temporary menstruation occurred (cases 1 and 2). All animals were euthanized due to irreversible rejection and no uterine blood flow (cases 1, 2 and 4) and post-transplant lymphoproliferative disorder (case 3). Donor-specific antibodies against MHC class I and II were detected in cases 1, 2 and 4, but not in case 3. Peripheral lymphocyte counts tended to elevate for CD3+, CD20+ and NK cells in conjunction with uterine rejection, and all animals had elevated stimulation indexes of mixed lymphocyte reaction after surgery. Establishment of allogeneic UTx in cynomolgus macaque requires further exploration of immunosuppression, but the clinicopathological features of uterine rejection are useful for development of human UTx.
Subjective Age in the Oldest Old: What is the Association with Disability and Sensory Impairment?

Abstract Background and Purpose Disability and sensory impairment are particularly pronounced among the oldest old population (80 years and older). Considering these specificities, we analyzed the association of such parameters with subjective age, a strong predictor of health-related outcomes. We assumed that greater disability and sensory impairment (hearing and visual) would be linked with an older subjective age. Research Design Prospective population-based study. Study Sample Data were gathered from the 27th year follow-up of the PAQUID cohort, visit where the question on subjective age was collected. Our sample included 75 participants older than 93 years, with a mean age of 96 years. Data Collection and Analysis Disability was assessed with Activities of Daily Living and sensory impairments by asking participants if they have visual or hearing difficulties. A multiple linear regression model was performed with subjective age as the dependent variable. Independent variables were functional disability and visual and hearing impairments. Results On average, the participants felt 12 years younger than their actual age. Multiple regression analyses controlled for age, gender, education, depression, and dementia indicated that self-reported hearing loss (p = 0.03) was associated with an older subjective age, whereas no significant associations were observed for disability (p = 0.42) and self-reported visual loss (p = 0.18). Conclusions Hearing impairment, in contrast to visual impairment and disability, is associated with feeling older. These results are discussed in light of health consequences and age stigma carried by hearing impairment.
CircRNA Cdr1as functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Recent years, circular RNA (circRNA) have been shown to exert vital functions in the pathological progressions of many diseases. A growing number of evidences have identified the representative function of exosomal circRNAs in the physiological state of donor cells, which further induces cellular responses after captured by recipient cells. However, the contributions of circRNAs to HCC remain largely unknown. In vitro and in vivo regulatory roles of circRNA Cdr1as in proliferative and migratory abilities of HCC were evaluated by CCK8, EdU, Transwell and tumourigenicity assays, respectively. Results showed circRNA Cdr1as was highly expressed in HCC cell lines and tissues. Overexpression of circRNA Cdr1as greatly accelerated HCC cells to proliferate and migrate. Mechanistically, we found that Cdr1as could promote the expression of AFP, a well-known biomarker for HCC, by sponging miR-1270. Further studies showed exosomes extracted from HCC cells overexpressing circRNA Cdr1as accelerated the proliferative and migratory abilities of surrounding normal cells. In all, circRNA Cdr1as serves as a ceRNA to promote the progression of HCC. Meanwhile, it is directly transferred from HCC cells to surrounding normal cells via exosomes to further mediate the biological functions of surrounding cells.
Differential associations between impaired autobiographical memory recall and future thinking in people with and without schizophrenia.

OBJECTIVES The ability to think about future events serves a range of important functions. People with schizophrenia show impairments in future thinking. However, whether these impairments are specific to positive or negative events and to what extent they are associated with impairments in verbal fluency and autobiographical memory remains poorly understood. METHODS People with schizophrenia (n = 93) and people without psychiatric diagnoses (n = 111) were asked to generate future events and retrieve past autobiographical events and they also completed a test of verbal fluency. Participants also completed questionnaire measures of the positive and negative dimensions of schizophrenia and depression symptoms. RESULTS People with schizophrenia generated significantly fewer positive and negative future events than controls. In a linear regression, the interaction between diagnosis and autobiographical memory retrieval explained a significant amount of variance in the number of future events that participants generated even when accounting for symptoms and verbal fluency. Past and future thinking abilities were correlated in controls but not in people with schizophrenia. CONCLUSIONS People with schizophrenia may not rely on autobiographical content to imagine the future and may rely instead on semantic processes. Interventions that improve past and future thinking amongst people with schizophrenia are warranted. PRACTITIONER POINTS Compared to control participants, people with schizophrenia have marked difficulty generating possible, positive and negative, future events. Unlike controls, for people with schizophrenia there is no relation between their ability to remember past events and their ability to think about the future. People with schizophrenia may have difficulty using their memories for their past to imagine and simulate possible future events.
Weather‐informed Light–tissue Model–Based Dose Planning for Indoor Daylight Photodynamic Therapy

Daylight activation for photodynamic therapy (PDT) of skin lesions is now widely adopted in many countries as a less painful and equally effective treatment mechanism, as compared to red or blue light activation. However, seasonal daylight availability and transient weather conditions complicate light dose estimations. A method is presented for dose planning without placing a large burden on clinical staff, by limiting spectral measurements to a one‐time site assessment, and then using automatically acquired weather reports to track transient conditions. The site assessment tools are used to identify appropriate treatment locations for the annual and daily variations in sunlight exposure for clinical center planning. The spectral information collected from the site assessment can then be integrated with real‐time daily electronic weather data. It was shown that a directly measured light exposure has strong correlation (R2: 0.87) with both satellite cloud coverage data and UV index, suggesting that the automated weather indexes can be surrogates for daylight PDT optical dose. These updated inputs can be used in a dose‐planning treatment model to estimate photodynamic dose at depth in tissue. A simple standardized method for estimating light dose during daylight‐PDT could help improve intersite reproducibility while minimizing treatment times.
Hyperthermia versus busulfan: Finding the effective method in animal model of azoospermia induction

Animal models of azoospermia are very applicable when evaluating new treatment methods for research purposes. The present study aimed to compare azoospermia induction in mice using busulfan or hyperthermia. To do this, about 36 adult male mice (28–30 g) were included into three experimental groups randomly (n = 12): control, busulfan (injected by a single dose of 40 mg/kg busulfan intraperitoneally) and hyperthermia (exposure to a temperature of 43°C every other day for 5 weeks). Animals were preserved for 35 and 70 days following interventions and then were sacrificed for further evaluations. After 35 days, busulfan and hyperthermia groups revealed a significant decrease in the sperm count and weight of testis compared to the control group (p < .0001). In addition, after 70 days, sperm count and weight of testis in group busulfan showed a significant increase compared to group hyperthermia (p < .01). No significant difference was observed regarding the mortality of mice between busulfan and hyperthermia groups. In group busulfan, degenerative changes in the germinal epithelium were detected in some tubules, although in group hyperthermia, degenerative changes and complete depletion of all tubules were observed. Continuous hyperthermia is a more effective method in the induction of as animal model of azoospermia compared to the busulfan.
Correlation between B7-H4 and Survival of Non-Small-Cell Lung Cancer Patients Treated with Nivolumab

Reliable predictors of benefit from immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are still limited. We aimed to evaluate the association between the expression of selected molecules involved in immune response and clinical outcomes in NSCLC patients receiving nivolumab. In our study, the outcomes of 46 NSCLC patients treated with nivolumab in second or subsequent lines (Nivolumab Cohort) were compared with the expression of PD-L1, PD-L2, PD-1, B7-H3, and B7-H4 assessed by immunohistochemistry (IHC). Samples from 17 patients (37.0%) in the Nivolumab Cohort were positive for B7-H4 expression. At univariate analyses, only B7-H4 expression was associated with significantly decreased progression-free survival (PFS; 1.7 vs. 2.0 months; p = 0.026) and with a disadvantage in terms of overall survival (OS) close to statistical significance (4.4 vs. 9.8 months; p = 0.064). At multivariate analyses, B7-H4 expression was significantly associated with decreased PFS (hazard ratio (HR) = 2.28; p = 0.021) and OS (HR = 2.38; p = 0.022). Subsequently, B7-H4 expression was compared with clinical outcomes of 27 NSCLC patients receiving platinum-based chemotherapy (Chemotherapy Cohort), but no significant association was observed. Our results suggest a negative predictive role of B7-H4 in a population of NSCLC treated with immune checkpoint inhibitors, which deserves further research.
Spatial and Temporal Genetic Diversity of the Peach Potato Aphid Myzus persicae (Sulzer) in Tunisia

The peach potato aphid, Myzus persicae (Sulzer), is a worldwide pest of many crops, and the most important aphid pest of peach and potato crops in Tunisia, mainly due to virus transmission, for which insecticides are frequently applied. We studied the genetic structure of M. persicae populations in Tunisia, in order to further our understanding of the biotic and abiotic factors shaping populations and to predict their evolutionary responses to the present management practices. We monitored peach orchards and seed potato crops in different seasons and regions from 2011–2013 and in 2016 (19 populations), assessing the genetic diversity of M. persicae at six microsatellite loci. Temporal and spatial changes in the frequency and distribution of 397 genotypes in 548 sampled aphids were studied. Only 37 genotypes were found more than once (clonal amplification), as most genotypes were found only once (91.60% in peach; 88.73% in potato crops). A similarly high genetic diversity was observed in aphids sampled from peach (G/N = 0.76; Ho = 0.617) and potato (G/N = 0.70; Ho = 0.641). Only a weak genetic differentiation among populations was found, mainly between geographic locations. Clustering analysis revealed genotypes to be grouped mainly according to host plant. The availability of the primary host, high proportion of unique genotypes, high genetic diversity and lack of structuring suggest that the aphid reproduces mainly through cyclical parthenogenesis in Tunisia. On the other hand, we provide a farm-scale study that shows how easily M. persicae can colonize different areas and hosts, which may have important implications in relation to plant virus vectoring.
Impact of age, sex, ethnicity, socio‐economic deprivation and novel pharmaceuticals on the overall survival of patients with multiple myeloma in New Zealand

The impact of age, ethnicity and socio‐economic deprivation in the era of novel anti‐myeloma agents is unclear. Using linked national data from New Zealand, we evaluated the incidence, prevalence and overall survival (OS) of individuals who were diagnosed with myeloma between 2004 and 2016. The crude incidence rate increased from 5·42 to 8·47/100 000 and the age‐standardised rate increased from 4·01 to 5·28/100 000. The estimated prevalence in December 2016 was 37·8/100 000. Median OS increased from 34·8 (95% CI 31·4, 39·3) months in 2004–2007 to 50·7 (48·5, 57·3) months in 2012–2016. Following the public funding of bortezomib in 2011, the median OS for individuals >70 years increased from 19·4 (16·3, 23·1) to 28·6 (24·5, 32·8) months. For those ≤70 years of age who did not have autologous stem cell transplantation (ASCT), median OS increased from 49·1 (37·1, 57·5) to 62·7 (51·7, 79·2) months; but for those who had ASCT, there was no difference in median OS. Socio‐economic deprivation was an independent adverse prognostic factor. Māori/Pasifika and those in the most deprived quintile experienced no improvement in survival after bortezomib was funded. Our study confirms the increasing incidence and improving survival of myeloma patients, and the negative impact of Māori/Pasifika ethnicity and socio‐economic deprivation on survival.