Miracle-dz/UniFAR-FTUs huggingface dataset:
ANG1005, a Brain-Penetrating Peptide–Drug Conjugate, Shows Activity in Patients with Breast Cancer with Leptomeningeal Carcinomatosis and Recurrent Brain Metastases

Purpose: ANG1005, a novel taxane derivative, consists of three paclitaxel molecules covalently linked to Angiopep-2, designed to cross the blood–brain and blood–cerebrospinal barriers and to penetrate malignant cells via LRP1 transport system. Preclinical and clinical evidence of efficacy with ANG1005 has been previously shown. Patients and Methods: A multicenter, open-label phase II study in adult patients with measurable recurrent brain metastases from breast cancer (BCBM), with or without leptomeningeal carcinomatosis was conducted (n = 72 BCBM; n = 28 leptomeningeal carcinomatosis subset). ANG1005 was administered intravenously at 600 mg/m2 every 3 weeks. Tumor assessment was based on central nervous system (CNS) RECIST 1.1 for intracranial, and RECIST 1.1 for extracranial response. The primary endpoint was determination of intracranial objective response rate (iORR). Results: Median age was 47.5 years. Safety profile was similar to that of paclitaxel with myelosuppression as the predominating toxicity. Average number of prior CNS-directed therapies was 2.8 and 94% of the patients had prior taxane treatment. Patient benefit (stable disease or better) was seen in 77% (intracranial) and 86% (extracranial) of the evaluable patients, with iORR of 15% (investigator) or 8% (independent radiology facility [IRF] review). In the leptomeningeal carcinomatosis subset, 79% of the patients had intracranial disease control and estimated median overall survival of 8.0 months (95% CI, 5.4–9.4). Conclusions: Even though the study preset rule for iORR per IRF was not met in this heavily pretreated population, a notable CNS and systemic treatment effect was seen in all patients including symptom improvement and prolonged overall survival compared to historical control for the subset of patients with leptomeningeal carcinomatosis (n = 28).
Designing Ethical Social Robots—A Longitudinal Field Study With Older Adults

Emotional deception and emotional attachment are regarded as ethical concerns in human-robot interaction. Considering these concerns is essential, particularly as little is known about longitudinal effects of interactions with social robots. We ran a longitudinal user study with older adults in two retirement villages, where people interacted with a robot in a didactic setting for eight sessions over a period of 4 weeks. The robot would show either non-emotive or emotive behavior during these interactions in order to investigate emotional deception. Questionnaires were given to investigate participants' acceptance of the robot, perception of the social interactions with the robot and attachment to the robot. Results show that the robot's behavior did not seem to influence participants' acceptance of the robot, perception of the interaction or attachment to the robot. Time did not appear to influence participants' level of attachment to the robot, which ranged from low to medium. The perceived ease of using the robot significantly increased over time. These findings indicate that a robot showing emotions—and perhaps resulting in users being deceived—in a didactic setting may not by default negatively influence participants' acceptance and perception of the robot, and that older adults may not become distressed if the robot would break or be taken away from them, as attachment to the robot in this didactic setting was not high. However, more research is required as there may be other factors influencing these ethical concerns, and support through other measurements than questionnaires is required to be able to draw conclusions regarding these concerns.
Translocation of Drought-Responsive Proteins from the Chloroplasts

Some chloroplast proteins are known to serve as messengers to transmit retrograde signals from chloroplasts to the nuclei in response to environmental stresses. However, whether particular chloroplast proteins respond to drought stress and serve as messengers for retrograde signal transduction are unclear. Here, we used isobaric tags for relative and absolute quantitation (iTRAQ) to monitor the proteomic changes in tobacco (Nicotiana benthamiana) treated with drought stress/re-watering. We identified 3936 and 1087 differentially accumulated total leaf and chloroplast proteins, respectively, which were grouped into 16 categories. Among these, one particular category of proteins, that includes carbonic anhydrase 1 (CA1), exhibited a great decline in chloroplasts, but a remarkable increase in leaves under drought stress. The subcellular localizations of CA1 proteins from moss (Physcomitrella patens), Arabidopsis thaliana and rice (Oryza sativa) in P. patens protoplasts consistently showed that CA1 proteins gradually diminished within chloroplasts but increasingly accumulated in the cytosol under osmotic stress treatment, suggesting that they could be translocated from chloroplasts to the cytosol and act as a signal messenger from the chloroplast. Our results thus highlight the potential importance of chloroplast proteins in retrograde signaling pathways and provide a set of candidate proteins for further research.
Subtype switching in breast cancer brain metastases: a multicenter analysis

Abstract Background Breast cancer (BC) brain metastases (BM) can have discordant hormonal or human epidermal growth factor receptor 2 (HER2) expression compared with corresponding primary tumors. This study aimed to describe incidence, predictors, and survival outcomes of discordant receptors and associated subtype switching in BM. Methods BCBM patients seen at 4 tertiary institutions who had undergone BM resection or biopsy were included. Surgical pathology reports were retrospectively assessed to determine discordance between the primary tumor and the BCBM. In discordant cases, expression in extracranial metastases was also assessed. Results In BM from 219 patients, prevalence of any discordance was 36.3%; receptor-specific discordance was 16.7% for estrogen, 25.2% for progesterone, and 10.4% for HER2. Because estrogen and progesterone were considered together for hormonal status, 50 (22.8%) patients switched subtype as a result; 20 of these switches were HER2 based. Baseline subtype predicted switching, which occurred in up to 37.5% of primary HR+ patients. Moreover, 14.8% of initially HER2-negative patients gained HER2 in the BM. Most (63.6%) discordant patients with extracranial metastases also had discordance between BM and extracranial subtype. Loss of receptor expression was generally associated with worse survival, which appeared to be driven by estrogen loss (hazard ratio = 1.80, P = 0.03). Patients gaining HER2 status (n = 8) showed a nonsignificant tendency toward improved survival (hazard ratio = 0.64, P = 0.17). Conclusions In this multicenter study, we report incidence and predictors of subtype switching, the risk of which varies considerably by baseline subtype. Switches can have clinical implications for prognosis and treatment choice.
Effects of supporting patients with dementia: A study with dyads.

PURPOSE This study aimed to examine the factors associated with the development of higher burden in informal caregivers of patients with dementia, using dyadic data. DESIGN AND METHODS Seventy-two dyads of patients with dementia and their informal caregivers were assessed, the former in terms of behavioral-psychological symptoms and autonomy, the latter in terms of burden and individual needs. FINDINGS Caregivers at risk for developing higher burden are those who are female, whose care recipient present psychiatric symptoms and lower autonomy, and those who recognize the need for more information/support. PRACTICE IMPLICATIONS Interventions should offer caregivers the tools to provide care, maintaining their psychological well-being. Interventions should target not only common aspects of caregiver burden but also the specificities of caring for a person with dementia.
Fast syntax in the brain: Electrophysiological evidence from the rapid parallel visual presentation paradigm (RPVP).

In 2 ERP experiments participants read 4-word sequences presented for 200 ms (RPVP paradigm) and were required to decide whether the word sequences were grammatical or not. In Experiment 1, the word sequence consisted of either a grammatically correct sentence (e.g., she can sing now) or an ungrammatical scrambled sequence (e.g., sing can now she). A reduced N400 effect was obtained in the grammatically correct sequences compared to the ungrammatical sequences. In Experiment 2, the critical comparison was between 2 types of ungrammatical sequences: transposed-word sequences (e.g., you that read wrong, transposing 2 adjacent central words can form a grammatical sequence) and control sequences (e.g., you that read worry, transposing any 2 adjacent central words still forms an ungrammatical sequence). An N400 reduction was observed in the transposed-word sequences relative to the control sequences. We interpret these N400 effects as evidence that an elementary syntactic representation can be rapidly constructed on the basis of parallel processing of word identities and their parts-of-speech. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Neuroendocrinology and neurobiology of sebaceous glands

The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro‐regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α‐melanocyte‐stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro‐autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin‐mediated or facial paresis‐associated reduction of human sebum secretion suggests that cutaneous nerve‐derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.
Attitude of University Students towards the Use of Institutional Repositories

The continuous advancement in ICT leads to the development of institutional repositories (IRs) as tools for managing the institutional information resources in digital format. Attitude is one of the major factors determining the use of institutional repositories (IRs). This study investigated the attitude of university students towards the use of IRs. The study focused on the deployment of IRs as a scholarly communication tool among students in academic environment. The study employed descriptive survey research design. Questionnaire was used to collect data from 500 undergraduate and postgraduate students of Federal University of Technology Akure (FUTA) for the study. Simple random sampling technique was adopted. Descriptive statistics was used to analyse the data with two hypotheses tested at 0.05level of significance. Criterion mean was placed at 2.0. The major findings of the study were: the attitude of university students towards the use of IRs was positive; university students used IRs for assignment; reading of articles and; development of collaborative research. The extent of usage of IRs by university students was high. The result of the hypotheses revealed that there was significant relationship between attitude and use of IRs by students, and there was no significant difference between undergraduate and postgraduate students' use of IRs. The study concluded that the university should update the contents of its IRs in order to encourage the students to improve their attitude the more towards the use of the IRs.
Electrostatically driven complex coacervation and amyloid aggregation of tau are independent processes with overlapping conditions.

Amyloid aggregation of the microtubule binding protein tau is a hallmark of many neurodegenerative diseases. Recently, tau has been found to undergo liquid-liquid phase separation (LLPS) by an electrostatically driven complex coacervation (CC) mechanism near physiological conditions. Although LLPS and aggregation have been shown to simultaneously occur under certain common conditions, it is unclear whether LLPS promotes aggregation of tau, or whether they are two independent processes. In this study, we address this question by combining multiple biochemical and biophysical assays in vitro. We investigate the impacts of LLPS-CC on cofactor-induced tau aggregation by evaluating the conformation of tau, kinetics of aggregation and fibril quantity. We showed that none of these properties are influenced directly by LLPS-CC, and that LLPS-CC and cofactor-induced aggregation of tau merely occur under overlapping conditions of enhanced intermolecular interactions and localization, but are two independent processes. We furthermore showed that tau LLPS can be driven by non-electrostatic interaction using high salt concentrations. In these conditions, LLPS strongly correlated with increased aggregation propensity. Whether LLPS of tau formed under different conditions or of different constituents may actively promote aggregation of tau remains an open question, but this study shows that the readily accessible electrostatically driven condensation of tau into LLPS in and of itself is not sufficient to promote aggregation.
Active Commuting, Physical Activity, and Sedentary Behaviors in Children and Adolescents from Spain: Findings from the ANIBES Study

Active commuting (AC) has been proposed as a great opportunity to increase physical activity level (PA) in children and adolescents. The aim of the present study is to determine the associations between AC (walk and cycle commuting) and non-AC (motor vehicle commuting) with PA levels, and with AC and sedentarism in Spanish children and adolescents. A representative Spanish sample of 424 children and adolescents (38% females) was involved in the ANIBES (Anthropometry, Dietary Intake and Lifestyle in Spain) Study in 2013. Data on the levels of AC, non-AC, PA, and sedentarism were obtained using the International Physical Activity Questionnaire for adolescents. Stepwise backward univariate generalized linear and linear regression models were performed. In girls, walking was associated with playground PA, moderate PA, and moderate to vigorous PA (MVPA) (β = 0.007, p < 0.05; both β = 0.007, p < 0.01), respectively. In boys, walking was associated with all PA levels (p < 0.05); while cycling was related to moderate PA and MVPA (both β = 0.007, p < 0.05). A negative significant association was observed between AC and time spent studying without Internet use in boys (β = −0.184, p < 0.05). Commuting by walking contributes to increased daily PA in both sexes, whereas cycling was only related to moderate PA and MVPA in boys. Sedentary behaviors are not related to AC, but studying without Internet use was negatively associated with AC in boys.
Comparative performance evaluation of different HPV tests and triaging strategies using self‐samples and feasibility assessment of thermal ablation in ‘colposcopy and treat’ approach: A population‐based study in rural China

Human papillomavirus (HPV) test, self‐sampling and thermal ablation for cervical intraepithelial neoplasia (CIN) have been developed separately to increase screening coverage and treatment compliance of cervical cancer screening programmes. A large‐scale study in rural China screened 9,526 women with their combinations to explore the optimal cervical cancer‐screening cascade in the real‐world. Participants received careHPV and polymerase chain reaction (PCR) HPV tests on self‐collected samples. Women positive on either HPV test underwent colposcopy, biopsy and thermal ablation in a single visit. Samples positive on either HPV test were retested for genotyping. Absolute and relative performance of HPV tests, triage strategies, ‘colposcopy and thermal ablation’ approach were statistically evaluated. PCR HPV test detected 33.3% more CIN grade two or worse (CIN2+) at a cost of 28.1% more colposcopies compared to careHPV. Sensitivities of PCR HPV and careHPV tests to detect CIN2+ were 96.7 and 72.5%. Specificities for the same disease outcome were 82.1 and 86.0%. Triaging HPV‐positive women with HPV16/18 genotyping considerably improved the positive predictive value for CIN2+ (4.8–5.0 to 18.2–19.2%). Ninety‐six women positive on HPV and having abnormal colposcopy were eligible for thermal ablation and all accepted same‐day treatment, contributing to 64.6% being treated appropriately (CIN1+ on histopathology), which reached up to 84.8% among women positive on HPV 16/18 triage. No serious side‐effects/complications were reported. The combination of PCR HPV test followed by HPV 16/18 triaging on self‐collected samples and colposcopy of triage positive women followed by immediate thermal ablation might be the appropriate screening cascade for rural China.
Harm Perceptions of E-cigarettes Among Smokers With and Without Mental Health Conditions in England: A Cross-Sectional Population Survey

Abstract Introduction E-cigarettes (ECs) may benefit smokers with mental health conditions who are more likely to smoke, and smoke more heavily, than those without mental health conditions. This could be undermined if harm misperceptions in this group are high as is the case in the general population. This study aimed to assess EC harm perceptions relative to cigarettes as a function of mental health status and a variety of characteristics. Methods Data were collected from 6531 current smokers in 2016/2017 in household surveys of representative samples of adults. The associations of mental health status (self-reported mental health condition and past year treatment), smoking and EC use characteristics, and characteristics relating to use of potential information sources with harm perceptions of ECs relative to cigarettes (measured by correct response “less harmful” vs. wrong responses “more harmful,” “equally harmful,” “don’t know”) were analyzed with logistic regression. Results A similar proportion of smokers without mental health conditions (61.5%, 95% CI 60.1–62.9) and with mental health conditions (both with [61.3%, 95% confidence interval [CI] 58.7–63.8] and without past year treatment [61.5%, 95% CI 58.1–64.7]) held inaccurate EC harm perceptions (all P > 0.05). Being female, nonwhite, aged 25–34 compared with 16–24, from lower social grades (C2, D, and E), not having post-16 qualifications, no EC experience, a daily smoker, unmotivated to quit <1 month, non-internet user and non-broadsheet reader were all associated with more inaccurate harm perceptions (all p < .05). Conclusions The majority of smokers in England have inaccurate harm perceptions of ECs regardless of mental health status. Implications This study is the first to use a nationally representative sample in order to investigate whether smokers with and without mental health conditions differ with regard to harm perceptions of ECs. Findings show that the majority of smokers in England hold inaccurate harm perceptions of ECs, and this does not differ as a function of mental health status. A number of characteristics associated with disadvantaged groups were significantly associated with inaccurate harm perceptions. These findings highlight the need to improve awareness and understanding among disadvantaged groups regarding the relative harms of ECs compared with tobacco.
Computational Modeling of the Food and Drug Administration's Benchmark Centrifugal Blood Pump.

In order to simulate hemodynamics within centrifugal blood pumps and to predict pump hemolysis, CFD simulations must be thoroughly validated against experimental data. They must also account for and accurately model the specific working fluid in the pump, whether that is a blood-analog solution to match an experimental PIV study or animal blood in a hemolysis experiment. Therefore, the FDA benchmark centrifugal blood pump and its database of experimental PIV and hemolysis data were used to thoroughly validate CFD simulations of the same blood pump. A Newtonian blood model was first used to compare to the PIV data with a blood analog fluid while hemolysis data was compared using a power-law hemolysis model fit to porcine blood data. A viscoelastic blood model was then incorporated into the CFD solver to investigate the importance of modeling blood's viscoelasticity in centrifugal pumps. The established computational framework, including a dynamic rotating mesh, animal blood specific fluid properties and hemolysis modeling, and a k-ω SST turbulence model, was shown to more accurately predict pump pressure heads, velocity fields, and hemolysis compared to previously published CFD studies of the FDA centrifugal pump. The CFD simulations were able to match the FDA pressure and hemolysis data for multiple pump operating conditions, with the CFD results being within the standard deviations of the experimental results. While CFD radial velocity profiles between the impeller blades also compared well to the PIV velocity results, more work is still needed to address the large variability among both experimental and computational predictions of velocity in the diffuser outlet jet. Small differences were observed between the Newtonian and viscoelastic blood models in pressure head and hemolysis at the higher flow rate cases (FDA Conditions 4 and 5) but were more significant at lower flow rate and pump impeller speeds (FDA Condition 1). These results suggest that the importance of accounting for blood's viscoelasticity may be dependent on the specific blood pump operating conditions. This detailed computational framework with improved modeling techniques and an extensive validation procedure will be used in future CFD studies of centrifugal blood pumps to aid in device design and predictions of their biological responses.