Miracle-dz/UniFAR-FTUs huggingface dataset:
Etching-enabled extreme miniaturization of graded-index fiber-based optical coherence tomography probes

Abstract. We introduced and validated a method to miniaturize graded-index (GRIN) fiber-based optical coherence tomography (OCT) probes down to 70 μm in diameter. The probes consist in an assembly of single-mode (SM), coreless (CL), and graded-index (GRIN) fibers. We opted for a probe design enabling controlled size reduction by hydrogen fluoride etching. The fabrication approach prevents nonuniform etching for both the GRIN and SM fiber components, while it requires no probe polishing postetching. We found that the miniaturized probes present insignificant loss of sensitivity (∼1 dB) compared to their thicker (125 μm) counterparts. We also showed that their focusing capabilities remain tunable and highly predictable. The fabrication process is simple and can be carried out by using inexpensive telecom equipment. Both the fabrication process and the developed probes can benefit the prototyping of minimally invasive endoscopic tools.
The expression of miR‐125b in Nrf2‐silenced A549 cells exposed to hyperoxia and its relationship with apoptosis

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects the quality of life of infants. At present, premature exposure to hyperoxia for extended periods of time is believed to affect the development of lung tissue and vascularity, resulting in BPD. The oxidative stress caused by hyperoxia exposure is an important risk factor for BPD in premature infants. Nuclear factor E2‐related factor 2 (Nrf2) is an important regulator of antioxidant mechanisms. As a microRNA, microRNA‐125b (miR‐125b) plays an important role in cell proliferation, differentiation and apoptosis. Although the Nrf2/ARE pathway has been extensively studied, little is known about the regulatory role of microRNAs in Nrf2 expression. In this study, the expression levels of Nrf2 and miR‐125b in the lung tissues of premature Sprague Dawley (SD) rats and A549 cells exposed to hyperoxia were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR), and the apoptosis of A549 cells was detected by flow cytometry. The results showed that Nrf2 and miRNA‐125b in the lung tissues of premature rats increased significantly upon exposure to hyperoxia and played a protective role. Nrf2 was suppressed by small interfering RNA (siRNA) in A549 cells, miR‐125b was similarly inhibited, and apoptosis was significantly increased. These results suggest that miR‐125b helps protect against BPD as a downstream target of Nrf2.
Human Embryonic Stem Cell-Derived Cardiovascular Progenitors Repair Infarcted Hearts Through Modulation of Macrophages via Activation of Signal Transducer and Activator of Transcription 6.

AIMS Human embryonic stem cell derived-cardiovascular progenitor cells (hESC-CVPCs) are a promising cell source for cardiac repair, while the underlying mechanisms need to be elucidated. We recently observed cardioprotective effects of human pluripotent stem cell (hPSC)-CVPCs in infarcted nonhuman primates, but their effects on inflammation during early phase of myocardial infarction (MI) and the contribution of such effect to the cardioprotection are unclear. RESULTS Injection of hESC-CVPCs into acutely infarcted myocardium significantly ameliorated the functional worsening and scar formation, concomitantly with reduced inflammatory reactions and cardiomyocyte apoptosis as well as increased vascularization. Moreover, hESC-CVPCs modulated cardiac macrophages toward a reparative phenotype in the infarcted hearts, and such modulation was further confirmed in vitro using human cardiovascular progenitor cell (hCVPC)-conditioned medium (hCVPC-CdM) and highly contained interleukin (IL)-4/IL-13. Furthermore, signal transducer and activator of transcription 6 (STAT6) was activated in hCVPC-CdM- and IL-4/IL-13-treated macrophages in vitro and in hESC-CVPC-implanted MI hearts, resulting in the polarization of macrophages toward a reparative phenotype in the post-MI hearts. However, hESC-CVPC-mediated modulation on macrophages and cardioprotection were abolished in STAT6-deficient MI mice. INNOVATION This is the first report about the immunoregulatory role played by hESC-CVPCs in the macrophage polarization in the infarcted hearts, its importance for the infarct repair, and the underlying signaling pathway. The findings provide new insight into the mechanism of microenvironmental regulation of stem cell-based therapy during acute MI. CONCLUSIONS Implantion of hESC-CVPCs during the early phase of MI promotes infarct repair via the modulation of macrophage polarization through secreted cytokine-mediated STAT6 activation. The findings suggest a therapeutic potential by modulating macrophage polarization during acute phase of MI.
Toward a Wearable System for Predicting Freezing of Gait in People Affected by Parkinson's Disease

Some wearable solutions exploiting on-body acceleration sensors have been proposed to recognize Freezing of Gait (FoG) in people affected by Parkinson Disease (PD). Once a FoG event is detected, these systems generate a sequence of rhythmic stimuli to allow the patient restarting the gait. While these solutions are effective in detecting FoG events, they are unable to predict FoG to prevent its occurrence. This paper fills in the gap by presenting a machine learning-based approach that classifies accelerometer data from PD patients, recognizing a pre-FOG phase to further anticipate FoG occurrence in advance. Gait was monitored by three tri-axial accelerometer sensors worn on the back, hip and ankle. Gait features were then extracted from the accelerometer's raw data through data windowing and non-linear dimensionality reduction. A k-nearest neighbor algorithm (k-NN) was used to classify gait in three classes of events: pre-FoG, no-FoG and FoG. The accuracy of the proposed solution was compared to state-of-the-art approaches. Our study showed that: (i) we achieved performances overcoming the state-of-the-art approaches in terms of FoG detection, (ii) we were able, for the very first time in the literature, to predict FoG by identifying the pre-FoG events with an average sensitivity and specificity of, respectively, 94.1% and 97.1%, and (iii) our algorithm can be executed on resource-constrained devices. Future applications include the implementation on a mobile device, and the administration of rhythmic stimuli by a wearable device to help the patient overcome the FoG.
Effect of redox imbalance on protein modifications in lymphocytes of psoriatic patients.

Lymphocytes are one of the most important cells involved in the pathophysiology of psoriasis, therefore the aim of this study was to assess the redox imbalance and protein modifications in the lymphocytes of patients with psoriasis vulgaris (PsV) or psoriatic arthritis (PsA). The results show a stronger shift in redox status to pro-oxidative conditions (observed as an increased reactive oxygen species level, a decrease in catalase activity and lower levels of glutathione peroxidase and vitamin E compared to healthy controls) in the lymphocytes of PsA than PsV patients. It is also favored by the enhanced level of activators of the Nrf2 transcription factor in lymphocytes of PsV compared with decreased of these proteins level in PsA. Moreover, the differential modifications of proteins by lipid peroxidation products 4-ONE (mainly binding proteins) and MDA (mainly catalytic proteins with redox activity), promoted a pro-apoptotic pathway in lymphocytes of PsV, which was manifested by enhanced expression of pro-apoptotic caspases, particularly caspase 3. Taken together, differences in Nrf2 pathway activation may be responsible for the differential level of redox imbalance in lymphocytes of patients with PsV and PsA. This finding may enable identification of a targeted therapy to modify the metabolic pathways disturbed in psoriasis.
Brain activity during reciprocal social interaction investigated using conversational robots as control condition

We present a novel functional magnetic resonance imaging paradigm for second-person neuroscience. The paradigm compares a human social interaction (human–human interaction, HHI) to an interaction with a conversational robot (human–robot interaction, HRI). The social interaction consists of 1 min blocks of live bidirectional discussion between the scanned participant and the human or robot agent. A final sample of 21 participants is included in the corpus comprising physiological (blood oxygen level-dependent, respiration and peripheral blood flow) and behavioural (recorded speech from all interlocutors, eye tracking from the scanned participant, face recording of the human and robot agents) data. Here, we present the first analysis of this corpus, contrasting neural activity between HHI and HRI. We hypothesized that independently of differences in behaviour between interactions with the human and robot agent, neural markers of mentalizing (temporoparietal junction (TPJ) and medial prefrontal cortex) and social motivation (hypothalamus and amygdala) would only be active in HHI. Results confirmed significantly increased response associated with HHI in the TPJ, hypothalamus and amygdala, but not in the medial prefrontal cortex. Future analysis of this corpus will include fine-grained characterization of verbal and non-verbal behaviours recorded during the interaction to investigate their neural correlates. This article is part of the theme issue ‘From social brains to social robots: applying neurocognitive insights to human–robot interaction'.
A 10-Year Longitudinal Observational Study Of Cataplexy In A Cohort Of Narcolepsy Type 1 Patients

Purpose Narcolepsy type 1 (NT1) is thought to have a chronic persistent course. This study aimed to assess the natural course of cataplexy in patients with NT1 at 2, 6, and 10 years after stabilizing symptoms. Other secondary objectives included assessing sleep quality, body mass index (BMI), and comorbidities at recruitment and 10 years later. Patients and methods Cataplexy symptoms, the Epworth sleepiness scale (ESS), sleep quality (assessed using the Pittsburgh sleep quality index [PSQI]), BMI, and comorbid conditions were prospectively monitored in 38 patients with NT1. The study sample comprised 38 patients with narcolepsy (males=27). The mean ages at disease onset and recruitment were 17.7 ± 5.6 years and 24.3 ± 8.6 years, respectively. Results In 42% of the cohort, the anti-cataplectic medications were stopped at the end of the study without disturbing symptoms of cataplexy. Additionally, there was an apparent significant reduction in the frequency of cataplexy over time. The mean ESS score decreased by more than 4 points from 19.4 ± 2.9 to 15 ± 4.3 (p<0.001) while on the same pharmacotherapy. The number of patients with a PSQI score of <5 (indicating good sleep quality) increased from 6 (15.8%) to 15 (39.5%) (p=0.004). The BMI increased from 30 ± 5.1 to 33.3 ± 6 kg/m2 (p=0.001). No changes were documented in comorbidities. Conclusion The findings suggest that the course of NT1 is not stable. Over a 10-year period, cataplexy symptoms improved or disappeared in a large proportion of patients, and there was an improvement in daytime sleepiness and nighttime sleep quality. More prospective studies that repeatedly monitor CSF-HCRT are needed to confirm the current findings.
Spatiotemporal establishment of dense bacterial colonies growing on hard agar

The physical interactions of growing bacterial cells with each other and with their surroundings significantly affect the structure and dynamics of biofilms. Here a 3D agent-based model is formulated to describe the establishment of simple bacterial colonies expanding by the physical force of their growth. With a single set of parameters, the model captures key dynamical features of colony growth by non-motile, non EPS-producing E. coli cells on hard agar. The model, supported by experiment on colony growth in different types and concentrations of nutrients, suggests that radial colony expansion is not limited by nutrients as commonly believed, but by mechanical forces. Nutrient penetration instead governs vertical colony growth, through thin layers of vertically oriented cells lifting up their ancestors from the bottom. Overall, the model provides a versatile platform to investigate the influences of metabolic and environmental factors on the growth and morphology of bacterial colonies.
Examining Mobile Technologies to Support Older Adults With Dementia Through the Lens of Personhood and Human Needs: Scoping Review

Background With the world’s rapidly growing older adult population, there is an increase in the number of people living with dementia. This growth leads to a strain on their caregivers and our health care system and to an increased attention on mitigating strain by using mobile technology to sustain the independence of people with dementia. However, less attention is given to whether these technologies meet the stated and unstated needs of people with dementia. Objective The aim of this study was to provide an overview of the current research on mobile technologies for people with dementia, considering the current research through the lens of personhood and human needs, and to identify any gaps that represent research opportunities. Methods We performed a systematic search in Medical Literature Analysis and Retrieval System Online (MEDLINE), Web of Science, PsycINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Excerpta Medica dataBASE (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL) in October 2018. We screened 5560 articles and identified 24 that met our inclusion and exclusion criteria. We then performed thematic analysis to organize the articles by the types of support mobile technologies provide and mapped those types of support to human needs to identify the gaps in support. Results Articles described research on mobile technologies that support people with dementia to (1) perform daily activities, (2) maintain social interaction, (3) aid memory, (4) engage in leisure activities, (5) track location, and (6) monitor health. At least one type of support mapped to each human need, with most supporting lower-level needs such as physiological and safety needs. Little attention seems to be paid to personhood. Conclusions Mobile technologies that support daily activities, relationships, memory, leisure activities, health, and safety can partially compensate for decreased function owing to dementia, but the human needs of people with dementia are often not adequately considered. Most technologies support basic physiological and safety needs, whereas many pay little attention to higher-level needs such as self-esteem and agency. Important research opportunities include using person-centered methods to develop technology to meet higher-level needs and to preserve personhood by incorporating human and psychological needs of people with dementia along with ethical considerations.
Cost-Effectiveness Analysis of Sunitinib versus Interferon-Alfa for First-Line Treatment of Advanced and/or Metastatic Renal Cell Carcinoma in Singapore

Abstract Objectives This study was conducted to evaluate the cost-effectiveness of sunitinib versus interferon-alfa for the treatment of advanced and/or metastatic renal cell carcinoma (RCC) in Singapore. Methods A partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from a healthcare payer perspective over a 10-year time horizon. Survival curves from the pivotal trial of sunitinib versus interferon-alfa were extrapolated beyond the trial period to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from local public healthcare institutions. The sunitinib dose in the model reflected local prescribing practices whereby a combination of 50 mg (28 percent) and 37.5 mg (72 percent) strengths are used. Results The base-case analysis comparing sunitinib versus interferon-alfa resulted in an incremental cost effectiveness ratio (ICER) of SGD191,061 (USD139,757) per quality-adjusted life-year gained. Sensitivity analysis demonstrated that the ICER was most sensitive to variations in the utility value assumed for the progression-free health state and the price of sunitinib. Conclusions In the absence of any price reduction, sunitinib had an exceedingly high ICER and was not considered a cost-effective use of healthcare resources in Singapore's context for the first-line treatment of advanced RCC. The findings from our evaluation will be useful to inform local healthcare decision making and resource allocations for tyrosine kinase inhibitors when appraised alongside comparative clinical effectiveness data and payer affordability considerations.
A unique internal ribosome entry site representing a dynamic equilibrium state of RNA tertiary structure in the 5′-UTR of Wheat yellow mosaic virus RNA1

Abstract Internal ribosome entry sites (IRESes) were first reported in RNA viruses and subsequently identified in cellular mRNAs. In this study, IRES activity of the 5′-UTR in Wheat yellow mosaic virus (WYMV) RNA1 was identified, and the 3′-UTR synergistically enhanced this IRES activity via long-distance RNA–RNA interaction between C80U81and A7574G7575. Within the 5′-UTR, the hairpin 1(H1), flexible hairpin 2 (H2) and linker region (LR1) between H1 and H2 played an essential role in cap-independent translation, which is associated with the structural stability of H1, length of discontinuous stems and nucleotide specificity of the H2 upper loop and the long-distance RNA–RNA interaction sites in LR1. The H2 upper loop is a target region of the eIF4E. Cytosines (C55, C66, C105 and C108) in H1 and H2 and guanines (G73, G79 and G85) in LR1 form discontinuous and alternative base pairing to maintain the dynamic equilibrium state, which is used to elaborately regulate translation at a suitable level. The WYMV RNA1 5′-UTR contains a novel IRES, which is different from reported IRESes because of the dynamic equilibrium state. It is also suggested that robustness not at the maximum level of translation is the selection target during evolution of WYMV RNA1.
Prognostic Values Of Preoperative Serum CEA And CA125 Levels And Nomograms For Young Breast Cancer Patients

Background Young breast cancer patients have poor prognosis compared to older patients in both overall survival (OS) and loco-regional failure-free survival. Carcinoembryonic antigen (CEA) and Cancer antigen 125 (CA125) have been widely used, but their prognostic value in young breast cancer patients remains unknown. The objectives of this study were to evaluate the prognostic value of preoperative CEA and CA125 serum levels and to build nomograms for better prognostic prediction of young Chinese breast cancer patients using both tumor markers. Methods We included 576 young breast cancer patients (≤40 years at diagnosis) and collected their preoperative information. The best cut-off values of the CEA and CA125 were identified with receiver operating characteristic (ROC) curves. Univariate and multivariate analyses were used to identify the relative risks of factors for the overall survival (OS), and disease-free survival (DFS), and nomograms were constructed based on these identified factors. Results The best cut-off values for CEA and CA125 in young breast cancer patients was 3.38 ng/mL and 19.38 U/mL, respectively. Kaplan-Meier analysis showed that young patients with low levels of CEA and/or CA125, had longer OS and DFS. Multivariate analysis suggested that both CEA and CA125 levels were independent predictive elements for OS. Nomograms were built and showed a better predictive ability for OS (AUC = 0.856) and DFS (AUC = 0.702) in young breast cancer patients. Conclusion Preoperative serum CEA and CA125 levels could be the independent prognostic factors for OS, and the nomograms including these two variables provide more personal forecasts information to help physicians optimize treatment for young breast cancer patients better.
Action mechanisms of probiotics on Candida spp. and candidiasis prevention: an update

Due to the high incidence of fungal infections caused by Candida species and their increasing resistance to antimicrobial treatments, alternative therapies such as probiotics have been studied. It has been show that several species of the genus Lactobacillus have anti‐Candida activity, probably by direct inhibition, through competition for adhesion sites or production of secondary metabolites, and by indirect inhibition, through stimulation of the immune system of their host. However, the mechanisms of inhibition of these probiotics on Candida species have not yet been fully elucidated since this effect is related to more than one inhibition pathway. In the literature, several in vitro and in vivo studies have been developed seeking to elucidate the probiotics mechanisms of action. These studies have been focused on C. albicans inhibition assays, including analysis of antimicrobial activity, adherence capacity, biofilms formation, filamentation and interference on virulence genes, as well as assays of experimental candidiasis in invertebrate and vertebrate models. In this context, the purpose of this review was to gather different studies focused on the action mechanism of probiotic strains on Candida sp. and to discuss their impact on the candidiasis prevention.
A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Examining the Hormonal and Vitality Effects of Ashwagandha (Withania somnifera) in Aging, Overweight Males

Ashwagandha (Withania somnifera) is a herb commonly used in Ayurvedic medicine to promote youthful vigor, enhance muscle strength and endurance, and improve overall health. In this 16-week, randomized, double-blind, placebo-controlled, crossover study, its effects on fatigue, vigor, and steroid hormones in aging men were investigated. Overweight men aged 40–70 years, with mild fatigue, were given a placebo or an ashwagandha extract (Shoden beads, delivering 21 mg of withanolide glycosides a day) for 8 weeks. Outcome measures included the Profile of Mood States, Short Form (POMS-SF), Aging Males’ Symptoms (AMS) questionnaire, and salivary levels of DHEA-S, testosterone, cortisol, and estradiol. Fifty-seven participants were enrolled, with 50 people completing the first 8-week period of the trial and 43 completing all 16 weeks. Improvements in fatigue, vigor, and sexual and psychological well-being were reported over time, with no statistically significant between-group differences. Ashwagandha intake was associated with an 18% greater increase in DHEA-S (p = .005) and 14.7% greater increase in testosterone (p = .010) compared to the placebo. There were no significant between-group differences in cortisol and estradiol. In conclusion, the intake of a standardized ashwagandha extract (Shoden beads) for 8 weeks was associated with increased levels of DHEA-S and testosterone, although no significant between-group differences were found in cortisol, estradiol, fatigue, vigor, or sexual well-being. Further studies with larger sample sizes are required to substantiate the current findings.
Precise radiative lifetimes in bulk crystals from first principles: the case of wurtzite gallium nitride

Gallium nitride (GaN) is a key semiconductor for solid-state lighting, but its radiative processes are not fully understood. Here we show a first-principles approach to accurately compute the radiative lifetimes in bulk uniaxial crystals, focusing on wurtzite GaN. Our computed radiative lifetimes are in very good agreement with experiment up to 100 K. We show that taking into account excitons (through the Bethe–Salpeter equation) and spin–orbit coupling is essential for computing accurate radiative lifetimes. A model for exciton dissociation into free carriers allows us to compute the radiative lifetimes up to room temperature. Our work enables precise radiative lifetime calculations in III-nitrides and other anisotropic solid-state emitters.