Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential requirements for the EF-hand domains of human centrin 2 in primary ciliogenesis and nucleotide excision repair

ABSTRACT Centrin 2 is a small conserved calcium-binding protein that localizes to the centriolar distal lumen in human cells. It is required for efficient primary ciliogenesis and nucleotide excision repair (NER). Centrin 2 forms part of the xeroderma pigmentosum group C protein complex. To explore how centrin 2 contributes to these distinct processes, we mutated the four calcium-binding EF-hand domains of human centrin 2. Centrin 2 in which all four EF-hands had been mutated to ablate calcium binding (4DA mutant) was capable of supporting in vitro NER and was as effective as the wild-type protein in rescuing the UV sensitivity of centrin 2-null cells. However, we found that mutation of any of the EF-hand domains impaired primary ciliogenesis in human TERT-RPE1 cells to the same extent as deletion of centrin 2. Phenotypic analysis of the 4DA mutant revealed defects in centrosome localization, centriole satellite assembly, ciliary assembly and function and in interactions with POC5 and SFI1. These observations indicate that centrin 2 requires calcium-binding capacity for its primary ciliogenesis functions, but not for NER, and suggest that these functions require centrin 2 to be capable of forming complexes with partner proteins. This article has an associated First Person interview with the first author of the paper. Highlighted Article: Mutagenesis analysis of human centrin 2 reveals a separation of functions whereby centrin 2 that is defective in calcium binding can support nucleotide excision repair but not primary ciliogenesis.
Antibiotic Prescribing by Informal Healthcare Providers for Common Illnesses: A Repeated Cross-Sectional Study in Rural India

Informal healthcare providers (IHCPs) are predominant healthcare providers in rural India, who prescribe without formal training. Antibiotic prescription by IHCPs could provide crucial information for controlling antibiotic resistance. The aim of this study is to determine the practices and seasonal changes in antibiotic prescribing for common illnesses by IHCPs. A repeated cross-sectional study was conducted over 18 months, covering different seasons in the rural demographic surveillance site, at Ujjain, India. Prescriptions given to outpatients by 12 IHCPs were collected. In total, 15,322 prescriptions for 323 different complaint combinations were analyzed, of which 11,336 (74%) included antibiotics. The results showed that 14,620 (95%) of antibiotics prescribed were broad spectrum and the most commonly prescribed were fluoroquinolones (4771,31%), followed by penicillin with an extended spectrum (4119,27%) and third-generation cephalosporin (3069,20%). Antibiotics were prescribed more frequently in oral and dental problems (1126,88%), fever (3569,87%), and upper respiratory tract infections (3273, 81%); more during the monsoon season (2350,76%); and more frequently to children (3340,81%) than to adults (7996,71%). The study concludes that antibiotics were the more commonly prescribed drugs compared to other medications for common illnesses, most of which are broad-spectrum antibiotics, a situation that warrants further investigations followed by immediate and coordinated efforts to reduce unnecessary antibiotic prescriptions by IHCPs.
Combined effects of ocean acidification and temperature on larval and juvenile growth, development and swimming performance of European sea bass (Dicentrarchus labrax)

Ocean acidification and ocean warming (OAW) are simultaneously occurring and could pose ecological challenges to marine life, particularly early life stages of fish that, although they are internal calcifiers, may have poorly developed acid-base regulation. This study assessed the effect of projected OAW on key fitness traits (growth, development and swimming ability) in European sea bass (Dicentrarchus labrax) larvae and juveniles. Starting at 2 days post-hatch (dph), larvae were exposed to one of three levels of PCO2 (650, 1150, 1700 μatm; pH 8.0, 7.8, 7.6) at either a cold (15°C) or warm (20°C) temperature. Growth rate, development stage and critical swimming speed (Ucrit) were repeatedly measured as sea bass grew from 0.6 to ~10.0 (cold) or ~14.0 (warm) cm body length. Exposure to different levels of PCO2 had no significant effect on growth, development or Ucrit of larvae and juveniles. At the warmer temperature, larvae displayed faster growth and deeper bodies. Notochord flexion occurred at 0.8 and 1.2 cm and metamorphosis was completed at an age of ~45 and ~60 days post-hatch for sea bass in the warm and cold treatments, respectively. Swimming performance increased rapidly with larval development but better swimmers were observed in the cold treatment, reflecting a potential trade-off between fast grow and swimming ability. A comparison of the results of this and other studies on marine fish indicates that the effects of OAW on the growth, development and swimming ability of early life stages are species-specific and that generalizing the impacts of climate-driven warming or ocean acidification is not warranted.
Health Monitoring of Metallic Structures with Electromechanical Impedance and Piezoelectric Sensors

In order to monitor the health condition of structures in a more sensitive and accurate way, a novel and universal methodology called direct coupling mechanical impedance (DCMI) for characteristic signatures extraction is presented in this paper. This methodology is used to obtain DCMI signatures from measured raw signatures (RSs) with the surface-bonded piezoelectric sensors (PZT), which is developed from a pertinent electromechanical impedance (EMI) theoretical model for surface-bonded circular PZT. The proposed DCMI methodology has the advantages of simple calculation and magnifying the signatures when compared with the existing methods. Combining the extracted DCMI signatures with the root mean square deviation (RMSD) index is able to quantify the correlation between the health condition and the signatures variation more effectively. To verify the effectiveness of proposed DCMI methodology, experiments are conducted on aluminum plates and a part of fuselage in detail. The experimental results sufficiently demonstrate that the presented universal DCMI methodology possesses better sensitivity than the raw signatures when utilized for evaluating the health condition of metallic structures, including those made of metal-matrix nanomaterials.
Closing the Gap in Surveillance and Audit of Invasive Mold Diseases for Antifungal Stewardship Using Machine Learning

Clinical audit of invasive mold disease (IMD) in hematology patients is inefficient due to the difficulties of case finding. This results in antifungal stewardship (AFS) programs preferentially reporting drug cost and consumption rather than measures that actually reflect quality of care. We used machine learning-based natural language processing (NLP) to non-selectively screen chest tomography (CT) reports for pulmonary IMD, verified by clinical review against international definitions and benchmarked against key AFS measures. NLP screened 3014 reports from 1 September 2008 to 31 December 2017, generating 784 positives that after review, identified 205 IMD episodes (44% probable-proven) in 185 patients from 50,303 admissions. Breakthrough-probable/proven-IMD on antifungal prophylaxis accounted for 60% of episodes with serum monitoring of voriconazole or posaconazole in the 2 weeks prior performed in only 53% and 69% of episodes, respectively. Fiberoptic bronchoscopy within 2 days of CT scan occurred in only 54% of episodes. The average turnaround of send-away bronchoalveolar galactomannan of 12 days (range 7–22) was associated with high empiric liposomal amphotericin consumption. A random audit of 10% negative reports revealed two clinically significant misses (0.9%, 2/223). This is the first successful use of applied machine learning for institutional IMD surveillance across an entire hematology population describing process and outcome measures relevant to AFS. Compared to current methods of clinical audit, semi-automated surveillance using NLP is more efficient and inclusive by avoiding restrictions based on any underlying hematologic condition, and has the added advantage of being potentially scalable.
An Assessment of Physical Activity Data Collected via a Smartphone App and a Smart Band in Breast Cancer Survivors: Observational Study

Background Although distress screening is crucial for cancer survivors, it is not easy for clinicians to recognize distress. Physical activity (PA) data collected by mobile devices such as smart bands and smartphone apps have the potential to be used to screen distress in breast cancer survivors. Objective The aim of this study was to assess data collection rates of smartphone apps and smart bands in terms of PA data, investigate the correlation between PA data from mobile devices and distress-related questionnaires from smartphone apps, and demonstrate factors associated with data collection with smart bands and smartphone apps in breast cancer survivors. Methods In this prospective observational study, patients who underwent surgery for breast cancer at Asan Medical Center, Seoul, Republic of Korea, between June 2017 and March 2018 were enrolled and asked to use both a smartphone app and smart band for 6 months. The overall compliance rates of the daily PA data collection via the smartphone walking apps and wearable smart bands were analyzed in a within-subject manner. The longitudinal daily collection rates were calculated to examine the dropout pattern. We also performed multivariate linear regression analysis to examine factors associated with compliance with daily collection. Finally, we tested the correlation between the count of daily average steps and distress level using Pearson correlation analysis. Results A total of 160 female patients who underwent breast cancer surgeries were enrolled. The overall compliance rates for using a smartphone app and smart bands were 88.0% (24,224/27,513) and 52.5% (14,431/27,513), respectively. The longitudinal compliance rate for smartphone apps was 77.8% at day 180, while the longitudinal compliance rate for smart bands rapidly decreased over time, reaching 17.5% at day 180. Subjects who were young, with other comorbidities, or receiving antihormonal therapy or targeted therapy showed significantly higher compliance rates to the smartphone app. However, no factor was associated with the compliance rate to the smart band. In terms of the correlation between the count of daily steps and distress level, step counts collected via smart band showed a significant correlation with distress level. Conclusions Smartphone apps or smart bands are feasible tools to collect data on the physical activity of breast cancer survivors. PA data from mobile devices are correlated with participants’ distress data, which suggests the potential role of mobile devices in the management of distress in breast cancer survivors. Trial Registration ClinicalTrials.gov NCT03072966; https://clinicaltrials.gov/ct2/show/NCT03072966
Biomaterial-Based Approaches for Regeneration of Periodontal Ligament and Cementum Using 3D Platforms

Currently, various tissue engineering strategies have been developed for multiple tissue regeneration and integrative structure formations as well as single tissue formation in musculoskeletal complexes. In particular, the regeneration of periodontal tissues or tooth-supportive structures is still challenging to spatiotemporally compartmentalize PCL (poly-ε-caprolactone)-cementum constructs with micron-scaled interfaces, integrative tissue (or cementum) formations with optimal dimensions along the tooth-root surfaces, and specific orientations of engineered periodontal ligaments (PDLs). Here, we discuss current advanced approaches to spatiotemporally control PDL orientations with specific angulations and to regenerate cementum layers on the tooth-root surfaces with Sharpey’s fiber anchorages for state-of-the-art periodontal tissue engineering.
Efficacy of 3D Culture Priming is Maintained in Human Mesenchymal Stem Cells after Extensive Expansion of the Cells

The use of non-optimal preparations of mesenchymal stem cells (MSCs), such as extensively expanded cells, might be necessary to obtain the large numbers of cells needed for many clinical applications. We previously demonstrated that minimally expanded (early passage) MSCs can be pre-activated as spheroids to produce potentially therapeutic factors in 3D cultures. Here, we used extensively expanded (late passage) MSCs and studied their 3D-culture activation potential. MSCs were culture-expanded as 2D monolayers, and cells from various passages were activated by 3D culture in hanging drops with either fetal bovine serum (FBS)-containing media or a more clinically-applicable animal product-free (xeno-free) media. Gene expression analyses demonstrated that MSC spheroids prepared from passage 3, 5, and 7 cells were similar to each other but different from 2D MSCs. Furthermore, the expression of notable anti-inflammatory/immune-modulatory factors cyclooxygenase-2 (PTGS2), TNF alpha induced protein 6 (TNFAIP6), and stanniocalcin 1 (STC-1) were up-regulated in all spheroid preparations. This was confirmed by the detection of secreted prostaglandin E2 (PGE-2), tumor necrosis factor-stimulated gene 6 (TSG-6, and STC-1. This study demonstrated that extensively expanded MSCs can be activated in 3D culture through spheroid formation in both FBS-containing and xeno-free media. This work highlights the possibility of activating otherwise less useable MSC preparations through 3D culture generating large numbers of potentially therapeutic MSCs.
The Importance of DS-14 and HADS Questionnaires in Quantifying Psychological Stress in Type 2 Diabetes Mellitus

Background and Objectives: The comorbid association between type 2 diabetes mellitus (T2DM) and a psychological profile characterized by depression and/or anxiety has been reported to increase the risk of coronary heart disease (CAD), the most striking macrovascular complication of diabetes. The purpose of the present study was to quantify anxiety, depression and the presence of type D personality, and to correlate the scores obtained with cardiovascular risk factors and disease severity in diabetic patients. Materials and methods: The retrospective study included 169 clinically stable diabetic patients divided into two groups: group 1 without macrovascular complications (n = 107) and group 2 with CAD, stroke and/or peripheral vascular disease (n = 62). A biochemical analysis and an assessment of psychic stress by applying the Hospital Anxiety and Depression Scale (HADS)and the Type D scale (DS-14) to determine anxiety, depression and D personality scores were done in all patients. Statistical analysis was made using SPSSv17 and Microsoft Excel, non-parametric Kruskal–Wallis and Mann–Whitney tests. Results: Following application of the HAD questionnaire for the entire group (n = 169), anxiety was present in 105 patients (62.2%), and depression in 96 patients (56.8%). Group 2 showed significantly higher anxiety scores compared to group 1 (p = 0.014), while depression scores were not significantly different. Per entire group, analysis of DS-14 scores revealed social inhibition (SI) present in 56 patients (33%) and negative affectivity (NA) in 105 patients (62%). TheDS-14 SI score was significantly higher in group 2 compared to group 1 (p = 0.036). Type D personality, resulting from scores above 10 in both DS-14 parameter categories, was present in 51 patients of the study group (30%). There was a direct and significant correlation (r = 0.133, p = 0.025) between the Hospital Anxiety and Depression Scale-Anxiety (HAD-A) score and the LDL-c values. Conclusions: The results of this study demonstrated that more than a half of patients with diabetes had anxiety and/or depression and one third had Type D personality, sustaining that monitoring of emotional state and depression should be included in the therapeutic plan of these patients. New treatment strategies are needed to improve the well-being of diabetic patients with psychological comorbidities.
"Chemotherapy-periodized" Exercise to Accommodate for Cyclical Variation in Fatigue.

PURPOSE The purpose of this study was to provide a rationale for 'chemotherapy-periodized' exercise by characterizing cyclical variations in fatigue and exercise response across a chemotherapy cycle and comparing exercise adherence during chemotherapy between a prescription that is periodized according to chemotherapy cycle length and a standard linearly progressed prescription. METHODS Women with breast cancer who were prescribed taxane-based chemotherapy were randomly assigned to a supervised aerobic and resistance exercise program following a chemotherapy-periodized exercise prescription (n=12) or to usual care during chemotherapy (n=15). Fatigue and steady state exercise responses were assessed in both groups prior to the first taxane treatment and across the third treatment (i.e., 0-3 days prior and 3-5 days after the third treatment, and 0-3 days prior to the fourth treatment) to assess cyclical variations. Adherence to the chemotherapy-periodized exercise prescription was compared to adherence to a standard linear prescription from a prior study in a similar population (n=51). RESULTS Fatigue increased from baseline (marginal mean±standard error: 3.2±0.4) to prior to the third treatment (4.1±0.4, p=0.025), then peaked at 3-5 days after the third treatment (5.1±0.4, p=0.001), before recovering prior to the next treatment (4.3±0.5, p=0.021). The peak in fatigue at 3-5 days post-third treatment corresponded to a decrease in steady state exercise oxygen consumption (VO2) (p=0.013). Compared to a standard linear exercise prescription during chemotherapy, a chemotherapy-periodized exercise prescription resulted in higher attendance during the week after chemotherapy (57±30% vs 77±28%, p=0.04) and overall attendance (63+25% vs 78±23%, p=0.05). CONCLUSION Fatigue and exercise VO2 vary across a chemotherapy cycle. A chemotherapy-periodized exercise prescription that accommodates cyclical variations in fatigue may increase adherence to supervised exercise.
A Correlational Analysis of the Relationships among Intolerance of Uncertainty, Anxiety Sensitivity, Subjective Sleep Quality, and Insomnia Symptoms

In this study, we used structural equation modeling to investigate the interplay among Intolerance of Uncertainty (IU), Anxiety Sensitivity (AS), and sleep problems. Three hundred undergraduate students completed the Intolerance of Uncertainty Scale, the Intolerance of Uncertainty Inventory, the Anxiety Sensitivity Index, the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. 68% and 40% of the students reported poor sleep quality or sub-threshold insomnia problems, respectively. Depression and anxiety levels were above the cut-off for about one-fourth of the participants. Structural equation modeling revealed that IU was strongly associated with AS, in turn influencing both insomnia severity and sleep quality via depression and anxiety. Significant indirect effects revealed that an anxious pathway was more strongly associated with insomnia severity, while a depression pathway was more relevant for worsening the quality of sleep. We discussed the results in the frameworks of cognitive models of insomnia. Viewing AS and IU as antecedents of sleep problems and assigning to AS a pivotal role, our study suggested indications for clinical interventions on a population at risk for sleep disorders.
An Experimental Study on Hydrodynamic Retention of Low and High Molecular Weight Sulfonated Polyacrylamide Polymer

Polymers are often added with water as a viscosifier to improve oil recovery from hydrocarbon reservoirs. Polymer might be lost wholly or partially from the injected polymer solution by adsorption on the grain surfaces, mechanical entrapment in pores, and hydrodynamic retention in stagnant zones. Therefore, having a clear picture of polymer losses (and retention) is very important for designing a technically and economically successful polymer flood project. The polymer adsorption and mechanical entrapment are discussed more in depth in the literature, though the effect of hydrodynamic retention can be just as significant. This research investigates the effect of the hydrodynamic retention for low and high molecular weight (AN 113 VLM and AN 113 VHM) sulfonated polyacrylamide polymer. Two high permeability Bentheimer core plugs from outcrops were used to perform polymer corefloods. Polymer retention was first determined by injecting 1 cm3/min, followed by polymer core floods at 3, 5, and 8 cm3/min to determine the hydrodynamic retention (incremental retention). A higher molecular weight polymer (AN 113 VHM) showed higher polymer retention. In contrast, hydrodynamic retention for lower molecular weight (AN 113 VLM) was significantly higher than that of the higher molecular weight polymer. Other important observations were the reversibility of the hydrodynamic retention, no permanent permeability reduction, the shear thinning behavior in a rheometer, and shear thickening behavior in core floods.
The influence of antiresorptive bone medication on the effect of high-intensity resistance and impact training on osteoporotic fracture risk in postmenopausal women with low bone mass: protocol for the MEDEX-OP randomised controlled trial

Introduction Antiresorptive medications increase bone density and decrease vertebral fracture, while high-intensity resistance and impact training (HiRIT) increases balance, bone and muscle strength decreasing risk for falls and fractures. Medications are typically prescribed by doctors and exercise by exercise specialists, frequently in isolation. Objective Our primary aim is to determine the effect of an 8-month HiRIT programme with or without osteoporosis medications on bone mineral density (BMD) of the spine and hip in postmenopausal women with low bone mass. Methods and analysis One hundred and sixty postmenopausal women with low bone mass will be recruited from the community to participate in an 8-month randomised controlled trial. Participants will be on stable doses of antiresorptive bone medication for at least 12 months (n=80) or have not taken bone medications for at least 12 months (n=80). Participants will be block randomised, stratified by medication intake, to twice-weekly 40-min supervised sessions of HiRIT or a low-intensity exercise programme (control). Primary outcomes include change in lumbar spine and total hip areal bone mineral density. Secondary outcomes include whole body, femoral neck and forearm BMD, proximal femur bone geometry and volumetric density, vertebral morphology, body composition, anthropometry, physical function, posture, rate of falls, osteoarthritis symptoms, pelvic floor health, quality of life, physical activity enjoyment, resting blood pressure, safety and compliance. All outcomes will be assessed at baseline and 8 months and intention-to-treat and per-protocol analyses will be conducted. Repeated measure analysis of covariance will be used to determine intervention effects on outcome measures, controlling for initial values, compliance and other variables found to differ between groups at baseline. Ethics and dissemination The study has been approved by Griffith University Human Research Ethics Committee (Ref: 2017/739). Results will be reported in peer-reviewed journals and at conferences. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12617001511325).