Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyaluronidase and pH Dual-Responsive Nanoparticles for Targeted Breast Cancer Stem Cells

pH-responsive and CD44 receptor-mediated targeted nanoparticles for eliminating cancer stem cells (CSCs) were developed based on complexes of PEG-poly(β-amino ester) (PEG-PBAE) micelles (PPM) coated with hyaluronic acid (HA) (HA-coated PPM complex, or HPPMc). Thioridazine (Thz) was loaded into HPPMc with a decent drug loading content. The release results of the drug in vitro showed that Thz was released from the HPPMc, which was stimulated by both the acidic pH and specific enzymes. Cytotoxicity studies on mammospheres (MS) revealed that the toxicity potential of Thz-loaded HPPMc (Thz–HPPMc) at pH 5.5 was better than drug solutions. Compared with that at pH 7.4, a higher cellular uptake of a coumarin-6 (C6)-labeled complex at pH 5.5 was observed, which demonstrated that complexes were efficiently taken up in MS. Meanwhile, free HA competitively inhibited the cellular uptake of HPPMc, which revealed that the uptake mechanism was CD44 receptor-mediated endocytosis. Within the acidic endolysosomal environment, the protonation of PBAE facilitated the escape of the complex from the lysosome and releases the drug. The results of in vivo distribution studies and tumor suppression experiments showed that HPMMc could stay in the tumor site of BALB/c nude mice for a longer period of time, and Thz–HPPMc could significantly improve the tumor-suppressing effect. All these results demonstrated the great potential of the multifunctional nanoparticle system for eliminating CSCs.
Continuous High-Dose (6 mg) vs. Low-Dose (3 mg) Intravitreal Ganciclovir for Cytomegalovirus Retinitis After Haploidentical Hematopoietic Stem Cell Transplantation: A Randomized Controlled Study

Purpose: To evaluate the safety and efficacy of continuous high-dose (6 mg) intravitreal ganciclovir injections (IVG) for cytomegalovirus (CMV) retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), and to explore factors that may influence the treatment procedure. Design: Prospective, randomized, single-blinded, positive-controlled, interventional, comparative study. Methods: A total of 22 patients with CMVR (32 eyes) were randomized to either high-dose group (IVG 6 mg weekly) or low-dose group (IVG 3 mg given twice weekly for 2 weeks as induction phase and weekly thereafter as maintenance phase). Patients who were recorded any positive CMV DNAemia or other active CMV diseases and needed systemic anti-CMV treatment during the study period were excluded. The vision outcome, variables of the treatment procedure, and incidence of complication and CMVR recurrence were analyzed and compared. Logistic regression was applied to determine the factors that may have an impact on the treatment process at baseline. Results: Compared to the low-dose group, the high-dose group resulted in a median of two less intravitreal injections (4 vs. 6 times, respectively, P = 0.016), while the rate of vision stability or improvement (81.2 vs. 87.5%), the incidence of complication (6.2 vs. 18.8%), and CMVR recurrence (12.5% vs. 6.2%) were similar (all P > 0.05). No drug-related toxicity was observed. Initial aqueous CMV-DNA load (OR: 6.872, 95% CI: 1.335–35.377, P = 0.021) and extension of lesion (OR: 0.942, 95% CI: 0.897 to .991, P = 0.020), but not dosing regimen (P = 0.162), were predictors of the treatment duration. Conclusions: Continuous high-dose regimen was well tolerated and resulted in less intravitreal injections, with similar vision outcomes and safety profiles. The clinical course of CMVR after Haplo-HSCT was determined by its own nature at baseline and could not be modified by treatment protocols under consistent immune background.
Identifying and Shifting Disempowering Paradigms for Families of Children With Disability Through a System Informed Positive Psychology Approach

Despite the emergence of socio-ecological, strength-based, and capacity-building approaches, care for children with disability remains primarily grounded in a deficit-based perspective. Diagnoses and interventions primarily focus on what children and families cannot do, rather than what might be possible, often undermining the competence, mental health, and functioning of both the children and their families. We first critically examine typical approaches to disability care for families of young children, describe the importance of a systems-informed positive psychology (SIPP) approach to care, and identify the existence of two dominant paradigms, disability is a disadvantage and experts know best. Then, we present a case study investigating families’ experiences with these two paradigms and whether shifts to alternative perspectives could occur through participation in a SIPP-based program co-designed by professionals and families. Of program participants, nine parents and five early intervention professionals participated in two separate focus groups, and ten e-books were randomly selected for review. Thematic analysis of the e-books and focus group data identified two primary themes representing alternative perspectives that arose through the intervention: we will start with our strengths and we’ve got this. Participant comments indicated that they developed a greater sense of hope, empowerment, engagement, and wellbeing, enabled by embedding wellbeing concepts and practices in their routines and communications with their children. We suggest that benefits arose in part from the structure of the program and the development of wellbeing literacy in participants. While care needs to be taken in generalizing the results, the case study provides clear examples of shifts in perspectives that occurred and suggests that the incorporation of SIPP principles within early intervention approaches provides a potential pathway for shifting the problematic paradigms that dominate disability care.
Sensory Experience as a Regulator of Structural Plasticity in the Developing Whisker-to-Barrel System

Cellular structures provide the physical foundation for the functionality of the nervous system, and their developmental trajectory can be influenced by the characteristics of the external environment that an organism interacts with. Historical and recent works have determined that sensory experiences, particularly during developmental critical periods, are crucial for information processing in the brain, which in turn profoundly influence neuronal and non-neuronal cortical structures that subsequently impact the animals’ behavioral and cognitive outputs. In this review, we focus on how altering sensory experience influences normal/healthy development of the central nervous system, particularly focusing on the cerebral cortex using the rodent whisker-to-barrel system as an illustrative model. A better understanding of structural plasticity, encompassing multiple aspects such as neuronal, glial, and extra-cellular domains, provides a more integrative view allowing for a deeper appreciation of how all aspects of the brain work together as a whole.
Association Between Bedtime at Night and Systolic Blood Pressure in Adults in NHANES

Objectives: This study aimed to explore the association between bedtime at night and systolic blood pressure (SBP) in adults. Methods: We conducted a cross-sectional study composed of 7,642 individuals from the National Health and Nutrition Examination Survey (NHANES). Bedtime was defined as the response to the question: “What time do you usually fall asleep on weekdays or workdays? ” SBP was taken using the average of all measured values. Multiple linear regression analyses were done to explore the relationship between bedtime and SBP. Results: The bedtime was changed from categorical variable to continuous variable for data analysis, and a significantly negative association was identified between bedtime and SBP (β, −0.23 [95% CI, −0.43, −0.02]). With the delay of bedtime, the SBP showed a gradual decrease trend, and it was dropped to the lowest at 0:00. After 0:00, the SBP was gradually increased with the delay of sleep time. The stratified analyses showed that in the female group, with the delay of bedtime, the range of SBP was decreased more obviously at 0:00. In the 18–45 year group, bedtime had little effect on SBP. Among ≥45 years old group, this trend was still the same. In the black group, an obvious downward trend was found at 22:00. Conclusion: With the delay of bedtime, the SBP had shown a gradual decrease trend, and it was dropped to the lowest at 0:00. After 0:00, the SBP was gradually increased with the delay of sleep time. Bedtime and SBP showed a U-shaped relationship.
Successional and Intraspecific Variations in Leaf Traits, Spectral Reflectance Indices and Herbivory in a Brazilian Tropical Dry Forest

Leaf traits are good indicators of ecosystem functioning and can affect herbivory and leaf reflectance patterns, allowing a better understanding of changes in environmental conditions, such those observed during forest natural regeneration. The aim of this study was to evaluate the intraspecific variation in leaf traits and their influence on the pattern of herbivory and leaf reflectance in three species distributed along a successional gradient (early, intermediate and late stages) in a tropical dry forest (TDF) in northern Minas Gerais, Brazil. We sampled individuals of the following abundant tree species that occurred in multiple successional stages: Cenostigma pluviosum, Handroanthus ochraceus, and Tabebuia reticulata. We collected 10 leaves from each tree to determine the contents of chlorophyll a, b, and total, carotenoids and water, as well as the percentage of leaf area removed by herbivores and leaf specific mass (LSM). We also measured five spectral reflectance indices (Normalized Difference Vegetation Index-NDVI, Simple Ratio-SR, modified Normalized Difference-nND, modified SR-mSR and Water Index-WI) using a portable spectrometer. Our results showed intraspecific differences in most leaf traits along the successional gradient, suggesting that local adaptation may play an important role in plant community assembly. However, herbivory only differed for H. ochraceus in early and intermediate stages, but it was not affected by the leaf traits considered here. Spectral reflectance indices also differed among successional stage for all species together and for each species separately, except for T. reticulata in intermediate and late stages. Thus, leaf spectral signatures may be an important tool to the remote detection of different successional stages in TDFs, with implications for forest management.
Modeling of Gate Tunable Synaptic Device for Neuromorphic Applications

The emerging memories are great candidates to establish neuromorphic computing challenging non-Von Neumann architecture. Emerging non-volatile resistive random-access memory (RRAM) attracted abundant attention recently for its low power consumption and high storage density. Up to now, research regarding the tunability of the On/Off ratio and the switching window of RRAM devices remains scarce. In this work, the underlying mechanisms related to gate tunable RRAMs are investigated. The principle of such a device consists of controlling the filament evolution in the resistive layer using graphene and an electric field. A physics-based stochastic simulation was employed to reveal the mechanisms that link the filament size and the growth speed to the back-gate bias. The simulations demonstrate the influence of the negative gate voltage on the device current which in turn leads to better characteristics for neuromorphic computing applications. Moreover, a high accuracy (94.7%) neural network for handwritten character digit classification has been realized using the 1-transistor 1-memristor (1T1R) crossbar cell structure and our stochastic simulation method, which demonstrate the optimization of gate tunable synaptic device.
A capacitive immunosensor measurement system with a lock-in amplifier and potentiostatic control by software

We report an elegant small-signal capacitance measurement system for capacitive immunosensors, prototyped around a computer-controlled two-phase lock-in amplifier. Capacitive immunosensors require low-ionic-strength electrolytes for effective antibody-antigen interaction and low dielectric thickness for high sensitivity to phenomena occurring at the insulator-electrolyte interface. The problem of measuring a high intrinsic sensor capacitance in the presence of a modest parasitic cell resistance is overcome by using a potential-sensing electrode close to the electrolyte-dielectric interface for measuring and controlling the stimulus to the intrinsic device. The current phasor through the capacitive sensor is measured after effecting potential control via a software feedback loop and the sensor capacitance calculated. Capacitance can be measured in the range 100 pF to 0.1 µF with an accuracy of ±0.5% at 1 kHz. The technique obviates the need for expensive high-speed potentiostats or impedance analysers for such measurements and can also be used for small-signal admittance measurements in other electrolyte-insulator-semiconductor or electrolyte-insulator-metal systems. The suitability of the proposed measurement system for immunodetection is shown by capacitance measurements on fibronectin-sensitive capacitive immunosensors.
Real and Imagined Smellscapes

The smellscape is the olfactory environment as perceived and understood, consisting of odours and scents from multiple smell sources. To what extent can audiovisual information evoke the smells of a real, complex, and multimodal environment? To investigate smellscape imagination, we compared results from two studies. In the first, onsite participants (N = 15) made a sensory walk through seven locations of an open-air market. In the second, online participants (N = 53) made a virtual walk through the same locations reproduced with audio and video recordings. Responses in the form of free-form verbal annotations, ratings with semantic scales, and a ‘smell wheel’, were analysed for environmental quality, smell source type and strength, and hedonic tone. The degree of association between real and imagined smellscapes was measured through canonical correlation analysis. Hedonic tone, as expressed through frequency counts of keywords in free-form annotations was significantly associated, suggesting that smell sources might generally be correctly inferred from audiovisual information, when such imagination is required. On the other hand, onsite ratings of olfactory quality were not significantly associated with online ratings of audiovisual reproductions, when participants were not specifically asked to imagine smells. We discuss findings in the light of cross-modal association, categorisation, and memory recall of smells.
Microbial Eukaryotes Associated With Sediments in Deep-Sea Cold Seeps

Microbial eukaryotes are key components of the marine food web, but their distribution in deep-sea chemosynthetic ecosystems has not been well studied. Here, high-throughput sequencing of the 18S rRNA gene and network analysis were applied to investigate the diversity, distribution and potential relationships between microbial eukaryotes in samples collected from two cold seeps and one trough in the northern South China Sea. SAR (i.e., Stramenopiles, Alveolata, and Rhizaria) was the predominant group in all the samples, and it was highly affiliated to genotypes with potential symbiotic and parasitic strategies identified from other deep-sea extreme environments (e.g., oxygen deficient zones, bathypelagic waters, and hydrothermal vents). Our findings indicated that specialized lineages of deep-sea microbial eukaryotes exist in chemosynthetic cold seeps, where microbial eukaryotes affiliated with parasitic/symbiotic taxa were prevalent in the community. The biogeographic pattern of the total community was best represented by the intermediate operational taxonomic unit (OTU) category, whose relative abundance ranged 0.01–1% within a sample, and the communities of the two cold seeps were distinct from the trough, which suggests that geographical proximity has no critical impact on the distribution of deep-sea microbial eukaryotes. Overall, this study has laid the foundations for future investigations regarding the ecological function and in situ trophic relationships of microbial eukaryotes in deep-sea ecosystems.
Feasibility, Acceptability, and Preliminary Efficacy of Dignity Therapy in Patients With Early Stage Dementia and Their Family. A Pilot Randomized Controlled Trial

Purpose: Dementia is the major cause for disability and dependence in older people and associated with considerable psychological burden. The aim of this study was to determine the feasibility, acceptability and preliminary efficacy of Dignity Therapy, a brief psychotherapeutic intervention to enhance dignity and reduce psychological burden, in patients with early stage dementia and in their families or close friends. Materials and methods: In this randomized, waitinglist-controlled clinical trial a total of 54 patients with new diagnosis of early stage dementia and 54 study partners (spouses: n = 37; relatives: n = 14; close friends: n = 3) were randomly assigned to immediate treatment (n = 28) or delayed treatment (n = 26) after 3 months waiting. The main outcomes were feasibility: proportion of screened and invited patients who consented participation; Acceptability: number of drop-outs, and satisfaction with treatment; Efficacy: psychological burden (Hospital Anxiety and Depression Scale—HADS), quality of life (WHOQOL-Bref), and sense of dignity (Patient Dignity Inventory—PDI). Results: In total 38.6% of all eligible patients (n = 140) consented and were enrolled. Along the study six participants (11.1%) dropped out. Patients' satisfaction with the treatment was high and with no significant difference between the groups. HADS scores were significantly lower in both groups at the 3-months follow-up (immediate group: mean difference = −2.69, SE = 0.85, P = 0.003; delayed group: mean difference = −1.97, SE = 0.89, P = 0.031). There was no significant group by time interaction effect (F = 0.71; df = 2, 70.3; P = 0.50). PDI scores only decreased significantly (i.e., improvement of dignity) in the immediate group (mean difference = −6.56, SE = 1.63, P < 0.001; delayed group: mean difference = −3.01, SE = 1.69, P = 0.081), but the group by time interaction effect was not statistically significant (F = 2.29; df = 1, 46.8; P = 0.14). Quality of life improved in some respects by the treatment, but the immediate and the delayed group did not differ significantly over time. After pooling patients' data of both groups, Dignity Therapy resulted in significant improvements in almost all outcome measures. Patients' family members/close friends reported high satisfaction with the intervention. Conclusions: Our findings suggest that Dignity Therapy is feasible and highly accepted in patients with early stage dementia. Patients reported significant improvements, however, there was no significant effect of the intervention in the immediate treatment group compared to the delayed group.
Anlotinib Alone or in Combination With Temozolomide in the Treatment of Recurrent High-Grade Glioma: A Retrospective Analysis

Background: Anlotinib is a multi-target anti-angiogenic agent. This retrospective study aimed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide for the treatment of recurrent high-grade glioma. Materials and Methods: The clinical data of patients with recurrent high-grade glioma treated with anlotinib alone or in combination with temozolomide in our cancer center were collected and analyzed. Treatment response was evaluated according to the response assessment for neuro-oncology criteria. Progression-free survival, progression-free survival at 6 months, overall survival, and overall survival at 12 months were evaluated by Kaplan–Meier method and compared by log-rank test. Results: Between August 2019 and December 2020, 31 patients with recurrent high-grade glioma (21 of grade 4 and 10 of grade 3) were enrolled in this study. Seventeen patients received anlotinib alone and 14 received anlotinib plus temozolomide. All patients were heavily treated, the median lines of previous treatments were 2, and the median Karnofsky score was 60. At the data cutoff date, the median progression-free survival was 4.5 months and the progression-free survival at 6 months was 43.5%. The median overall survival was 7.7 months, and the overall survival at 12 months was 26.7%. The progression-free survival at 6 months and the overall survival at 12 months for 21 patients with grade 4 glioma was 40.2 and 27.9%, respectively. The tumor objective response rate was 41.9% in all patients and 33.3% in patients with grade 4 glioma. No grade 3 or worse treatment-related adverse events were recorded during the treatment. Conclusion: Anlotinib alone or in combination with temozolomide showed encouraging efficacy and favorable tolerability in patients with recurrent high-grade glioma who had been heavily treated.
Association of Prescription With Body Composition and Patient Outcomes in Incident Peritoneal Dialysis Patients

Objective: The nutritional status of patients on peritoneal dialysis (PD) is influenced by patient- and disease-related factors and lifestyle. This analysis evaluated the association of PD prescription with body composition and patient outcomes in the prospective incident Initiative for Patient Outcomes in Dialysis–Peritoneal Dialysis (IPOD-PD) patient cohort. Design and Methods: In this observational, international cohort study with longitudinal follow-up of 1,054 incident PD patients, the association of PD prescription with body composition was analyzed by using the linear mixed models, and the association of body composition with death and change to hemodialysis (HD) by means of a competing risk analysis combined with a spline analysis. Body composition was regularly assessed with the body composition monitor, a device applying bioimpedance spectroscopy. Results: Age, time on PD, and the use of hypertonic and polyglucose solutions were significantly associated with a decrease in lean tissue index (LTI) and an increase in fat tissue index (FTI) over time. Competing risk analysis revealed a U-shaped association of body mass index (BMI) with the subdistributional hazard ratio (HR) for risk of death. High LTI was associated with a lower subdistributional HR, whereas low LTI was associated with an increased subdistributional HR when compared with the median LTI as a reference. High FTI was associated with a higher subdistributional HR when compared with the median as a reference. Subdistributional HR for risk of change to HD was not associated with any of the body composition parameters. The use of polyglucose or hypertonic PD solutions was predictive of an increased probability of change to HD, and the use of biocompatible solutions was predictive of a decreased probability of change to HD. Conclusion: Body composition is associated with non-modifiable patient-specific and modifiable treatment-related factors. The association between lean tissue and fat tissue mass and death and change to HD in patients on PD suggests developing interventions and patient counseling to improve nutritional markers and, ultimately, patient outcomes. Study Registration: The study has been registered at Clinicaltrials.gov (NCT01285726).