Miracle-dz/UniFAR-FTUs huggingface dataset:
“Epidermal Eg5 promotes X-ROS dependent paclitaxel neurotoxicity”

Taxanes are chemotherapeutic agents that induce microtubule modifications in cancer cells, resulting in cell cycle modifications and tumor remission. Here we show that paclitaxel, a widely used taxane, also induces microtubule modifications in healthy epidermal keratinocytes leading to chemotherapy-induced peripheral neuropathy (CIPN). Paclitaxel activates the cell cycle regulator, Kinesin-5 (Eg5), which promotes microtubule detyrosination and fasciculation (dfMT). Eg5 loss protects neurons from paclitaxel neurotoxicity, whereas keratinocyte-specific overexpression promotes axon degeneration. In vivo imaging and 3D reconstructions of dfMTs and nuclei, combined with mechanotransduction studies further show that dfMTs constrict keratinocyte nuclei, leading to nuclear Nox-dependent reactive oxygen species (X-ROS) formation upstream of MMP-13 and cutaneous sensory axon degeneration. This new insight facilitates our understanding of chemotherapy side effects and highlights the need for targeted therapies.
The structure of fuzzy fractals generated by an orbital fuzzy iterated function system

Abstract In this article, we present a structure result concerning fuzzy fractals generated by an orbital fuzzy iterated function system ( ( X , d ) , ( f i ) i ∈ I , ( ρ i ) i ∈ I ) \left(\left(X,d),{({f}_{i})}_{i\in I},{\left({\rho }_{i})}_{i\in I}) . Our result involves the following two main ingredients: (a) the fuzzy fractal associated with the canonical iterated fuzzy function system ( ( I N , d Λ ) , ( τ i ) i ∈ I , ( ρ i ) i ∈ I ) \left(\left({I}^{{\mathbb{N}}},{d}_{\Lambda }),{\left({\tau }_{i})}_{i\in I},{\left({\rho }_{i})}_{i\in I}) , where d Λ {d}_{\Lambda } is Baire’s metric on the code space I N {I}^{{\mathbb{N}}} and τ i : I N → I N {\tau }_{i}:{I}^{{\mathbb{N}}}\to {I}^{{\mathbb{N}}} is given by τ i ( ( ω 1 , ω 2 , … ) ) ≔ ( i , ω 1 , ω 2 , … ) {\tau }_{i}\left(\left({\omega }_{1},{\omega }_{2},\ldots )):= \left(i,{\omega }_{1},{\omega }_{2},\ldots ) for every ( ω 1 , ω 2 , … ) ∈ I N \left({\omega }_{1},{\omega }_{2},\ldots )\in {I}^{{\mathbb{N}}} and every i ∈ I i\in I ; (b) the canonical projections of certain iterated function systems associated with the fuzzy fractal under consideration.
Roles and mechanism of IL-11 in vascular diseases

Vascular diseases are the leading cause of morbidity and mortality worldwide. Therefore, effective treatment strategies that can reduce the risk of vascular diseases are urgently needed. The relationship between Interleukin-11 (IL-11) and development of vascular diseases has gained increasing attention. IL-11, a target for therapeutic research, was initially thought to participate in stimulating platelet production. Additional research concluded that IL-11 is effective in treating several vascular diseases. However, the function and mechanism of IL-11 in these diseases remain unknown. This review summarizes IL-11 expression, function, and signal transduction mechanism. This study also focuses on the role of IL-11 in coronary artery disease, hypertension, pulmonary hypertension, cerebrovascular disease, aortic disease, and other vascular diseases and its potential as a therapeutic target. Consequently, this study provides new insight into the clinical diagnosis and treatment of vascular diseases.
Soil chemistry, metabarcoding, and metabolome analyses reveal that a sugarcane—Dictyophora indusiata intercropping system can enhance soil health by reducing soil nitrogen loss

Introduction Greater amounts of fertilizer are applied every year to meet the growing demand for food. Sugarcane is one of the important food sources for human beings. Methods Here, we evaluated the effects of a sugarcane—Dictyophora indusiata (DI) intercropping system on soil health by conducting an experiment with three different treatments: (1) bagasse application (BAS process), (2) bagasse + DI (DIS process), and (3) the control (CK). We then analyzed soil chemistry, the diversity of soil bacteria and fungi, and the composition of metabolites to clarify the mechanism underlying the effects of this intercropping system on soil properties. Results and discussion Soil chemistry analyses revealed that the content of several soil nutrients such as nitrogen (N) and phosphorus (P) was higher in the BAS process than in the CK. In the DIS process, a large amount of soil P was consumed by DI. At the same time, the urease activity was inhibited, thus slowing down the loss of soil in the DI process, while the activity of other enzymes such as β-glucosidase and laccase was increased. It was also noticed that the content of lanthanum and calcium was higher in the BAS process than in the other treatments, and DI did not significantly alter the concentrations of these soil metal ions. Bacterial diversity was higher in the BAS process than in the other treatments, and fungal diversity was lower in the DIS process than in the other treatments. The soil metabolome analysis revealed that the abundance of carbohydrate metabolites was significantly lower in the BAS process than in the CK and the DIS process. The abundance of D(+)-talose was correlated with the content of soil nutrients. Path analysis revealed that the content of soil nutrients in the DIS process was mainly affected by fungi, bacteria, the soil metabolome, and soil enzyme activity. Our findings indicate that the sugarcane–DIS intercropping system can enhance soil health.
Results of haploidentical transplant in patients with donor-specific antibodies: a survey on behalf of the Spanish Group of Hematopoietic Transplant and Cell Therapy

Background Donor-specific antibodies (DSAs) are IgG allo-antibodies against mismatched donor HLA molecules and can cause graft failure (GF) in the setting of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Our aim was to report the experience of the Spanish Group of Hematopoietic Transplant (GETH-TC) in DSA-positive patients who had undergone haplo-HSCT. Methods We conducted a survey of patients who underwent haplo-HSCT in GETH-TC centers between 2012 and 2021. Data were collected on the DSA assay used, monitoring strategy, complement fixation, criteria for desensitization, desensitization strategies and transplant outcomes. Results Fifteen centers from the GETH-TC responded to the survey. During the study period, 1,454 patients underwent haplo-HSCT. Seventy of the transplants were performed in 69 DSA-positive patients, all of whom lacked a suitable alternative donor; 61 (88%) patients were female (90% with prior pregnancies). All patients received post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis. Regarding baseline DSA intensity, 46 (67%) patients presented mean fluorescence intensity (MFI) >5,000, including 21 (30%) with MFI >10,000 and three (4%) with MFI >20,000. Six patients did not receive desensitization treatment, four of them with MFI <5,000. Of 63 patients receiving desensitization treatment, 48 (76%) were tested after desensitization therapy, and a reduction in intensity was confirmed in 45 (71%). Three patients (5%) experienced an increase in MFI after desensitization, two of whom experienced primary GF. Cumulative incidence of neutrophil engraftment at day 28 was 74% in a median of 18 days (IQR, 15─20); six patients died before engraftment due to toxicity or infection and eight patients had primary GF despite desensitization in seven of them. After a median follow-up of 30 months, two-year overall and event-free survival were 46.5% and 39%, respectively. The two-year cumulative incidence of relapse was 16% and non-relapse mortality (NRM) was 43%. Infection was the most frequent cause of NRM, followed by endothelial toxicity. Multivariate analysis identified baseline MFI >20,000 as an independent risk factor for survival and an increase in titers after infusion as an independent risk factor for GF. Conclusions Haplo-HSCT is feasible in DSA-positive patients, with high rates of engraftment after desensitization guided by DSA intensity. Baseline MFI >20,000 and increased intensity after infusion are risk factors for survival and GF.
Transformative experience and informed consent to psychedelic-assisted psychotherapy

Just as psychedelic-assisted psychotherapy (PAP) represents a clinical innovation that may need to be accommodated with corresponding theoretical and methodological innovations, there is growing awareness that the tools, normative frameworks, and standard practices of our clinical ethics may also need to be adapted, renewed, or replaced to accommodate its unusual features. Drawing on L. A. Paul's work on “Transformative Experience,” I argue that the acute and long-term effects that are repeatedly reported following the administration of psychedelic drugs, including in clinical contexts, are epistemically inaccessible at the point of deciding to take them. By virtue of both the so-called “mystical” experiences that frequently arise during PAP, and the long-term shifts to outlooks, values, and priorities that can follow treatment, the processes of decision-making that are normatively expected of patients run aground. If this framing is correct, then prospective patients cannot meet the requirement of understanding that is one of the principal analytic components of informed consent. The role of understanding in supporting two functions of informed consent—avoiding unauthorized trespass against patients and supporting values-aligned decision-making—is explored, and I argue that, while the normative standard for the first function may be met by extant suggestions for enhancing the consenting process for PAP, the latter function remains unattainable. In light of this, the consequences for the ethical preparation of prospective patients are considered.
Accounting for uncertainty in training data to improve machine learning performance in predicting new disease activity in early multiple sclerosis

Introduction Machine learning (ML) has great potential for using health data to predict clinical outcomes in individual patients. Missing data are a common challenge in training ML algorithms, such as when subjects withdraw from a clinical study, leaving some samples with missing outcome labels. In this study, we have compared three ML models to determine whether accounting for label uncertainty can improve a model’s predictions. Methods We used a dataset from a completed phase-III clinical trial that evaluated the efficacy of minocycline for delaying the conversion from clinically isolated syndrome to multiple sclerosis (MS), using the McDonald 2005 diagnostic criteria. There were a total of 142 participants, and at the 2-year follow-up 81 had converted to MS, 29 remained stable, and 32 had uncertain outcomes. In a stratified 7-fold cross-validation, we trained three random forest (RF) ML models using MRI volumetric features and clinical variables to predict the conversion outcome, which represented new disease activity within 2 years of a first clinical demyelinating event. One RF was trained using subjects with the uncertain labels excluded (RFexclude), another RF was trained using the entire dataset but with assumed labels for the uncertain group (RFnaive), and a third, a probabilistic RF (PRF, a type of RF that can model label uncertainty) was trained on the entire dataset, with probabilistic labels assigned to the uncertain group. Results Probabilistic random forest outperformed both the RF models with the highest AUC (0.76, compared to 0.69 for RFexclude and 0.71 for RFnaive) and F1-score (86.6% compared to 82.6% for RFexclude and 76.8% for RFnaive). Conclusion Machine learning algorithms capable of modeling label uncertainty can improve predictive performance in datasets in which a substantial number of subjects have unknown outcomes.
The nature and structure of maternal parenting practices and infant behaviors in U.S. national and international samples

Methods Twenty maternal parenting practices and 15 behaviors of their 5½-month-old infants in a U.S. national sample (N = 360) and 9 international samples (N = 653) were microcoded from videorecords of naturalistic interactions at home and aggregated into domains. Altogether, the samples were recruited from Argentina, Belgium, Brazil, France, Israel, Italy, Japan, Kenya, as well as the United States. Background and Rationale A previous test of three competing models of the nature and structure of the maternal parenting practices supported a hybrid 2 factor/6 domain model as superior to a 1-factor dimensional model and a multi-factor style model: Maternal parenting practices are structured into nurture, physical, social, didactic, material, and language domains undergirded by dyadic and extradyadic factors. Infant behaviors were organized into physical, social, exploration, nondistress vocalization, and distress communication domains. The current study sought to examine links connecting these previously identified maternal domains and factors with infant behavior domains using structural equation models. Results Mothers' dyadic factor is associated with infant social behaviors with mother; and mothers' extradyadic factor and encouragement of infant physical development are associated with infant exploration of their immediate physical environment and physical development. Infant distress communication (and less nondistress vocalization) is associated with more maternal nurturing. Discussion Mothers' parenting practices in the middle of the first year of infant life are commonly structured and adapted to specific needs and developmental tasks of infants. Evaluations of mother-infant interactions with national and international samples permit a wide yet judicious analysis of common vs. specific models of mother-infant relationships.
Association between TRP channels and glutamatergic synapse gene polymorphisms and migraine and the comorbidities anxiety and depression in a Chinese population

Background: Genetic and environmental factors contribute to migraine and the comorbidities of anxiety and depression. However, the association between genetic polymorphisms in the transient receptor potential (TRP) channels and glutamatergic synapse genes with the risk of migraine and the comorbidities of anxiety and depression remain unclear. Methods: 251 migraine patients containing 49 comorbidities with anxiety and 112 with depression and 600 controls were recruited. A customized 48-plex SNPscan kit was used for genotyping 13 SNPs of nine target genes. Logistic regression was conducted to analyze these SNPs’ association with the susceptibility of migraine and comorbidities. The generalized multifactor dimension reduction (GMDR) was applied to analyze the SNP-SNP and gene-environment interactions. The GTEx database was used to examine the effects of the significant SNPs on gene expressions. Results: The TRPV1 rs8065080 and TRPV3 rs7217270 were associated with an increased risk of migraine in the dominant model [ORadj (95% CI): 1.75 (1.09–2.90), p = 0.025; 1.63 (1.02–2.58), p = 0.039, respectively]. GRIK2 rs2227283 was associated with migraine in the edge of significance [ORadj (95% CI) = 1.36 (0.99–1.89), p = 0.062]. In migraine patients, TRPV1 rs222741 was associated with both anxiety risk and depression risk in the recessive model [ORadj (95% CI): 2.64 (1.24–5.73), p = 0.012; 1.97 (1.02–3.85), p = 0.046, respectively]. TRPM8 rs7577262 was associated with anxiety (ORadj = 0.27, 95% CI = 0.10–0.76, p = 0.011). TRPV4 rs3742037, TRPM8 rs17862920 and SLC17A8 rs11110359 were associated with depression in dominant model [ORadj (95% CI): 2.03 (1.06–3.96), p = 0.035; 0.48 (0.23–0.96), p = 0.042; 0.42 (0.20–0.84), p = 0.016, respectively]. Significant eQTL and sQTL signals were observed for SNP rs8065080. Individuals with GRS (Genetic risk scores) of Q4 (14–17) had a higher risk of migraine and a lower risk of comorbidity anxiety than those with Genetic risk scores scores of Q1 (0–9) groups [ORadj (95% CI): 2.31 (1.39–3.86), p = 0.001; 0.28 (0.08–0.88), p = 0.034, respectively]. Conclusion: This study suggests that TRPV1 rs8065080, TRPV3 rs7217270, and GRIK2 rs2227283 polymorphism may associate with migraine risk. TRPV1 rs222741 and TRPM8 rs7577262 may associate with migraine comorbidity anxiety risk. rs222741, rs3742037, rs17862920, and rs11110359 may associate with migraine comorbidity depression risk. Higher GRS scores may increase migraine risk and decrease comorbidity anxiety risk.
Supportive care needs and health-related quality of life in cancer patients receiving palliative care

Objective Cancer patients receiving palliative care experience a variety of impairments in their quality of life (QoL), and have corresponding supportive care needs (SCNs). The aim of this study was to analyze the relationship between SCNs, satisfaction with QoL dimensions, and the perceived importance of these dimensions. Method A sample of 152 cancer patients receiving palliative care were included in this cross-sectional study. Eight dimensions of QoL were defined and assessed concerning SCNs, satisfaction, and subjective importance using a new assessment instrument with five-point scales (range 1–5) for each dimension. Results Among the eight specific domains examined, the greatest SCNs were observed for absence of pain (M = 3.18; SD = 1.29). The patients were least satisfied with their physical functioning (M = 2.60; SD = 0.84), and the dimension social relationships (M = 4.14; SD = 0.72) received the highest perceived importance ratings. The eight dimensions’ SCNs scores were significantly correlated with each other (r between 0.29 and 0.79); the lowest correlations were found for social relationships. The correlations between the satisfaction scores and the SCNs differed from dimension to dimension, with coefficients between −0.32 (absence of pain) and − 0.57 (sleep quality). Conclusion The results show that detriments in QoL do not automatically indicate high levels of SCNs in those dimensions. Health care providers should consider both factors, QoL (as measured with QoL questionnaires) and subjectively expressed SCNs, to optimize their patients’ care regimens.
Grounding and improving assessment in higher education: a way of promoting quality education

Assessment continues to be one of the topics that most concern teachers and most dissatisfies students. In this paper we describe and evaluate the impact of the training course “Grounding and Improving Pedagogical Assessment in Higher Education,” based on a descriptive survey questionnaire, applied in a convenience-selected sample of 31 teachers from a public university in Portugal, who participated in the pedagogical training course. The questionnaire was applied before the beginning of the course (pre-test) and after its completion (post-test). Data were analyzed using statistical procedures that consisted of frequency analysis and non-parametric analysis, using the Mann–Whitney and Wilcoxon tests. The results revealed several changes in teachers’ conceptions of assessment and demonstrated the positive impact of the course, since the comparison of the pre and post-test results showed that relevant changes occurred towards the most current theories of pedagogical assessment, being more significant in the group of teachers without pedagogical training.
Subjective cognitive decline in patients with Parkinson’s disease: an updated review

Cognitive impairment in patients with Parkinson’s disease (PD) worsens the prognosis of PD and increases caregivers’ burden and economic consequences. Recently, subjective cognitive decline (SCD), which refers to self-reported cognitive decline without detectable objective cognitive dysfunction, has been regarded as an at-risk state of mild cognitive impairment (MCI) and a prodromal stage for dementia in Alzheimer’s disease (AD). However, studies on PD-SCD have thus far been scarce, and at present there is no consensus regarding the definition of SCD nor a gold standard as an evaluation tool. The present review aimed to look for an association between PD-SCD and objective cognitive function and found that PD with SCD occurred with brain metabolic changes, which were consistent with early aberrant pathological changes in PD. Moreover, PD patients with SCD were likely to progress to future cognitive impairment. It is necessary to establish a guideline for the definition and evaluation of SCD in PD. A larger sample size and more longitudinal investigations are needed to verify the predictive effectiveness of PD-SCD and to detect earlier subtle cognitive decline before MCI.
Systematic analysis between inflammation-related index and sex hormones in American adults: cross-sectional research based NHANES 2013-2016

Background A series of novel inflammation-related indexes has been confirmed to be efficient indicators of human immune and inflammatory status, with great potential as predictors for a variety of diseases. However, the association between inflammation-related indexes and sex hormones in the general population remained uncertain. Methods We incorporated data from the NHANES 2013-2016 survey of American adults. On the basis of distribution and comparison analysis, we chose to undertake separate analyses of men and women (including premenopausal and postmenopausal groups). Multivariable weighted linear regression models, eXtreme Gradient Boosting (XGBoost) models, generalized linear analysis, stratified models, logistic regression models and sensitivity analysis were utilized to assess the relationships between inflammation-related indexes and sex hormones. Results Total 9372 participants out of 20146 were fitted into our research. We conducted separate gender analysis due to different distribution. Multivariable weighted linear regression indicated every component of the inflammation-related index was negatively correlated with at least one component of the male hormone indexes. However, SII, NLR, PPN, and NC were associated positively with female estradiol. XGBoost identify SII, PLR and NLR were the critical indexes on sex hormones. Inflammation-related indexes was associated with Testosterone deficiency in male and postmenstrual group and associated with Excessive Estradiol in premenstrual group. Finally, the subgroup analysis revealed that the association between sex hormones and inflammatory indicators was prominent in American adults over the age of 60 or those with BMI (>28 kg/m2). Conclusion In all, inflammation-related indexes act as independent risks associated with sex hormone alterations and metabolic disorder in both genders. Using multiple models, we revealed the relative importance of inflammation-related indexes. Subgroup analysis also identified the high-risk population. More prospective and experimental research should be conducted to validate the results.