Miracle-dz/UniFAR-FTUs huggingface dataset:
Circadian Strain, Light Exposure, and Depressive Symptoms in Rural Communities of Southern Brazil

Irregular light–dark cycles and circadian/sleep disturbances have been suggested as risk or co-occurring factors in depression. Among a set of metrics developed to quantify strain on the circadian system, social jetlag (SJL) has been put forward as a measure of the discrepancy between biological and social clocks. Here, we approached the question on whether light exposure and SJL would also be associated with depressive symptoms in Quilombola communities in Southern Brazil. These rural communities are void of potential confounders of modern lifestyles and show low levels of SJL. 210 Quilombolas (age range 16–92; 56% women) were asked about their sleep times and light exposure using the Munich ChronoType Questionnaire (MCTQ). The Beck Depression Inventory (BDI) was used to assess depressive symptoms. Additionally, we analyzed 7-day actimetry recordings in 124 subjects. BDI scores higher than 10 (having clinically significant depressive symptoms; controlled for age and sex in the multivariate analysis) were positively associated with SJL >1 h and negatively associated with median light exposure during the day, especially in the morning from 8:00 to 10:00. Our results suggest that low light exposure during the day, and higher levels of SJL are associated with depressive symptoms; longitudinal and experimental studies are needed to understand the underlying mechanisms. Nevertheless, we highlight the potential of treatment strategies aimed at decreasing circadian strain and insufficient light exposure, which are suggested as areas of further research in Psychiatry.
Chimeric Antigen Receptor T-Cell Therapy in Paediatric B-Cell Precursor Acute Lymphoblastic Leukaemia: Curative Treatment Option or Bridge to Transplant?

Chimeric antigen receptor T-cell therapy (CAR-T) targeting CD19 has been associated with remarkable responses in paediatric patients and adolescents and young adults (AYA) with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). Tisagenlecleucel, the first approved CD19 CAR-T, has become a viable treatment option for paediatric patients and AYAs with BCP-ALL relapsing repeatedly or after haematopoietic stem cell transplantation (HSCT). Based on the chimeric antigen receptor molecular design and the presence of a 4-1BB costimulatory domain, tisagenlecleucel can persist for a long time and thereby provide sustained leukaemia control. “Real-world” experience with tisagenlecleucel confirms the safety and efficacy profile observed in the pivotal registration trial. Recent guidelines for the recognition, management and prevention of the two most common adverse events related to CAR-T — cytokine release syndrome and immune-cell–associated neurotoxicity syndrome — have helped to further decrease treatment toxicity. Consequently, the questions of how and for whom CD19 CAR-T could substitute HSCT in BCP-ALL are inevitable. Currently, 40–50% of R/R BCP-ALL patients relapse post CD19 CAR-T with either CD19− or CD19+ disease, and consolidative HSCT has been proposed to avoid disease recurrence. Contrarily, CD19 CAR-T is currently being investigated in the upfront treatment of high-risk BCP-ALL with an aim to avoid allogeneic HSCT and associated treatment-related morbidity, mortality and late effects. To improve survival and decrease long-term side effects in children with BCP-ALL, it is important to define parameters predicting the success or failure of CAR-T, allowing the careful selection of candidates in need of HSCT consolidation. In this review, we describe the current clinical evidence on CAR-T in BCP-ALL and discuss factors associated with response to or failure of this therapy: product specifications, patient- and disease-related factors and the impact of additional therapies given before (e.g., blinatumomab and inotuzumab ozogamicin) or after infusion (e.g., CAR-T re-infusion and/or checkpoint inhibition). We discuss where to position CAR-T in the treatment of BCP-ALL and present considerations for the design of supportive trials for the different phases of disease. Finally, we elaborate on clinical settings in which CAR-T might indeed replace HSCT.
Seasonal Amplitude of Water Storage Variations of the Yangtze–Huai Plain Lake Group: Implicaion for Floodwater Storage Capacity

Lakes are of significant importance in regulating floods and providing water sources. The seasonal water storage variations for the plain lake group in the Yangtze–Huai River Basin (YHRB) are significant for alleviating flood pressure and regulating runoff. However, to date, the seasonal amplitude of lake water storage variations and its capacity of buffering floodwater in the YHRB is not quantified well and remains to be investigated comprehensively. To advance the understanding of such a critical scientific issue, the water level data of the plain lake group (area>100 km2, 29 lakes) in the YHRB is collected from multi-source data between 1990 and 2020. Using lake inundation area obtained from Global Surface Water and water level variations, water storage dynamics for the plain lake group are quantified. Furthermore, this study also uses the Gravity Recovery and Climate Experiment (GRACE) products to analyze the terrestrial water storage anomalies (TWSA) in the whole basin. The results indicate that the seasonal amplitude of water level change and water storage variation of the plain lake group are 2.80 ± 0.71 m and 37.38 ± 14.19 Gt, respectively. Poyang and Dongting Lakes, two lakes that maintain the natural connection with the Yangtze River, have the most substantial seasonal amplitude in the hydrological situation. The amplitude in water level and water storage in Poyang Lake is 9.53 ± 2.02 m and 14.13 ± 5.54 Gt respectively, and that in Dongting Lake is 7.39 ± 1.29 m and 7.31 ± 3.42 Gt respectively. The contribution of seasonal variation of water storage for large plain lakes to TWSA in the YHRB is approximately 33.25%, fully reflecting these lake’s imperative position in the YHRB. This study is expected to enhance the scientific understanding of the seasonal hydrologic regime for the large lakes in the YHRB and contribute to the management of flood risks and water resources in East China.
Genomic Analysis Uncovers Immune Microenvironment Characteristics and Drug Sensitivity of Ferroptosis in Breast Cancer Brain Metastasis

Background: The role of ferroptosis in breast cancer brain metastasis (BCBM) is unclear. This study aimed to explore the ferroptosis-related genes (FRG) relations with the tumor microenvironment, as well as evaluate their values in predicting survival and drug sensitivity in patients with BCBM. Materials and Methods: Genes expression and clinical data were downloaded from Gene Expression Omnibus (GEO). Univariate and multivariate Cox regression analyses were performed to explore the independent prognostic factors. Consensus cluster principal component analysis (PCA) was used to establish the ferroptosis score. Immunological signatures were analyzed by the single-sample gene set enrichment analysis (ssGSEA). Drug sensitivity was evaluated through the estimated half-maximal inhibitory concentration (IC50). Finally, results were validated in external cohorts. Results: Fourteen significantly different FRG were identified between breast cancer (BC) and BCBM tissues. Survival analysis demonstrated HMOX1, PEBP1, KEAP1, and LPCAT3 were significantly associated with overall survival (OS) and relapse-free survival (RFS) (all p < 0.05). High ferroptosis score was correlated with iron ion homeostasis, iron metabolism, higher stromal cells and immune cells scores. Patients with high- and low-ferroptosis scores were characterized by different drug sensitivities. Following external validations, the ferroptosis had distinct expression profiles between the BC and BCBM, and could serve as biomarkers for OS and drug response. Conclusion: Our findings suggested that ferroptosis may be involved in the process of BCBM, and ferroptosis could serve as prognostic biomarkers. Evaluation of ferroptosis may deepen our understanding about the tumor microenvironment, and could help clinicians to make individualized therapy.
Influence of the Location of a Decision Cue on the Dynamics of Pupillary Light Response

The pupils of the eyes reflexively constrict in light and dilate in dark to optimize retinal illumination. Non-visual cognitive factors, like attention, arousal, decision-making, etc., also influence pupillary light response (PLR). During passive viewing, the eccentricity of a stimulus modulates the pupillary aperture size driven by spatially weighted corneal flux density (CFD), which is the product of luminance and the area of the stimulus. Whether the scope of attention also influences PLR remains unclear. In this study, we contrasted the pupil dynamics between diffused and focused attentional conditions during decision-making, while the global CFD remained the same in the two conditions. A population of 20 healthy humans participated in a pair of forced choice tasks. They distributed attention to the peripheral decision cue in one task, and concentrated at the center in the other to select the target from four alternatives for gaze orientation. The location of this cue did not influence participants’ reaction time (RT). However, the magnitude of constriction was significantly less in the task that warranted attention to be deployed at the center than on the periphery. We observed similar pupil dynamics when participants either elicited or canceled a saccadic eye movement, which ruled out pre-saccadic obligatory attentional orientation contributing to PLR. We further addressed how the location of attentional deployment might have influenced PLR. We simulated a biomechanical model of PLR with visual stimulation of different strengths as inputs corresponding to the two attentional conditions. In this homeomorphic model, the computational characteristic of each element was derived from the physiological and/or mechanical properties of the corresponding biological element. The simulation of this model successfully mimicked the observed data. In contrast to common belief that the global ambient luminosity drives pupillary response, the results of our study suggest that the effective CFD (eCFD) determined via the luminance multiplied by the size of the stimulus at the location of deployed attention in the visual space is critical for the magnitude of pupillary constriction.
Conservation Agriculture Affects Grain and Nutrient Yields of Maize (Zea Mays L.) and Can Impact Food and Nutrition Security in Sub-Saharan Africa

Maize is a major staple and plays an essential role in food and nutrition security in Sub-Saharan Africa (SSA). Conservation agriculture (CA), a climate-smart agriculture practise based on minimum soil disturbance, crop residue retention, and crop diversification, has been widely advocated but without extensive research on the impact it may have on maize nutrient composition, and food and nutrition security. This study assessed the grain yield, macro- and micronutrient mineral content, and nutrient yield of eight maize varieties grown in Malawi, and how these are affected by CA practises over two seasons. The minerals were analysed by inductively coupled plasma (ICP) coupled to optical emission spectroscopy (OES) and to mass spectroscopy (MS). Grain yield and Se content differed among the varieties, while C, N, Fe, K, Mg, Mn, P, and Zn were similar. The local variety Kanjerenjere showed lowest grain and nutrient yields. The open-pollinated varieties (OPVs) concentrated more minerals than the F1 hybrids, but the latter showed higher yields for both grain and nutrients. Typical consumption of the eight maize varieties could fully meet the protein and Mg dietary reference intake (DRIs) of Malawian children (1–3 years), as well as Mg and Mn needs of adult women (19–50 years), but their contribution to dietary requirements was low for Fe (39–41%) and K (13–21%). The trials showed that CA increased grain yield (1.2- to 1.8-fold) and Se content (1.1- to 1.7-fold), but that it had no effect on C, K, Mg, P, and Zn, and that N (1.1- to 1.2-fold), Mn (1.1- to 1.8-fold), and Fe (1.3- to 3.4-fold) were reduced. The high increase in grain yield under CA treatments resulted in increased yields of protein and Se, no effect on the yields of K, Mg, Mn, P, Zn, and reduced Fe yield. Conservation agriculture could contribute in reducing the risk of Se deficiency in Malawian women and children but exacerbates the risk of Fe deficiency. A combination of strategies will be needed to mitigate some of the foreseen effects of climate change on agriculture, and food and nutrition security, and improve nutrient intake.
Experimental Evolution Expands the Breadth of Adaptation to an Environmental Gradient Correlated With Genome Reduction

Whether and how adaptive evolution adjusts the breadth of adaptation in coordination with the genome are essential issues for connecting evolution with ecology. To address these questions, experimental evolution in five Escherichia coli strains carrying either the wild-type genome or a reduced genome was performed in a defined minimal medium (C0). The ancestral and evolved populations were subsequently subjected to fitness and chemical niche analyses across an environmental gradient with 29 combinations of eight chemical components of the minimal medium. The results showed that adaptation was achieved not only specific to the evolutionary condition (C0), but also generally, to the environmental gradient; that is, the breadth of adaptation to the eight chemical niches was expanded. The magnitudes of the adaptive improvement and the breadth increase were both correlated with genome reduction and were highly significant in two out of eight niches (i.e., glucose and sulfate). The direct adaptation-induced correlated adaptation to the environmental gradient was determined by only a few genome mutations. An additive increase in fitness associated with the stepwise fixation of mutations was consistently observed in the reduced genomes. In summary, this preliminary survey demonstrated that evolution finely tuned the breadth of adaptation correlated with genome reduction.
Reduction of Genetic Variation When Far From the Niche Centroid: Prediction for Mangrove Species

The niche-centroid hypothesis states that populations that are distributed near the centroid of the species' ecological niche will have higher fitness-related attributes, such as population abundance and genetic diversity than populations near the edges of the niche. Empirical evidence based on abundance and, more recently, genetic diversity data support this hypothesis. However, there are few studies that test this hypothesis in coastal species, such as mangroves. Here, we focused on the black mangrove Avicennia germinans. We combined ecological, heterozygosity, and allelic richness information from 1,419 individuals distributed in 40 populations with three main goals: (1) test the relationship between distance to the niche centroid and genetic diversity, (2) determine the set of environmental variables that best explain heterozygosity and allelic richness, and (3) predict the spatial variation in genetic diversity throughout most of the species' natural geographic range. We found a strong correlation between the distance to the niche centroid and both observed heterozygosity (Ho; ρ2 = 0.67 P < 0.05) and expected heterozygosity (He; ρ2 = 0.65, P < 0.05). The niche variables that best explained geographic variation in genetic diversity were soil type and precipitation seasonality. This suggests that these environmental variables influence mangrove growth and establishment, indirectly impacting standing genetic variation. We also predicted the spatial heterozygosity of A. germinans across its natural geographic range in the Americas using regression model coefficients. They showed significant power in predicting the observed data (R2 = 0.65 for Ho; R2 = 0.60 for He), even when we considered independent data sets (R2= 0.28 for Ho; R2 = 0.25 for He). Using this approach, several genetic diversity estimates can be implemented and may take advantage of population genomics to improve genetic diversity predictions. We conclude that the level of genetic diversity in A. germinans is in agreement with expectations of the niche-centroid hypothesis, namely that the highest heterozygosity and allelic richness (the basic genetic units for adaptation) are higher at locations of high environmental suitability. This shows that this approach is a potentially powerful tool in the conservation and management of this species, including for modelling changes in the face of climate change.
Discretization and perturbations in the simulation of localized turbulence in a pipe with a sudden expansion

Abstract At low Reynolds numbers, the flow through a pipe with a sudden expansion is characterized by the localized occurrence of flow instabilities, with the formation of a so-called turbulence puff. In the literature, physical experiments typically predict earlier occurrence of turbulence than computational fluid dynamics simulations. However, the behaviour of ‘natural’ transition to turbulence without perturbations, and the dependence of transition to turbulence on perturbations, are not yet fully understood, particularly for the simulations. The purpose of the present study is therefore to investigate this flow, including possible sources of perturbation in numerical simulations, and to evaluate their effect on transition to turbulence. Through the exploration of different flow rates, numerical settings and inlet perturbation amplitudes, and by evaluating coarse and refined simulations, insights into low-Reynolds-number transitional turbulent flows are obtained. The turbulence kinetic energy budget of the turbulence puff or slug characteristic of this flow is also evaluated. In conclusion, even when perturbations are not intentionally added, there can still be significant sources of numerical perturbation and error that trigger turbulence in simulations, but perturbations will need to be added in refined simulations in order to produce turbulence. Finally, the results agree with the notion that there may not be a scenario where the flow transitions naturally to turbulence without any perturbation.
Dynamic APACHE II Score to Predict the Outcome of Intensive Care Unit Patients

Objective This study aims to evaluate the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) II score on different days in predicting the mortality of critically ill patients to identify the best time point for the APACHE II score. Methods The demographic and clinical data are retrieved from the Medical Information Mart for Intensive Care (MIMIC)-IV dataset. APACHE II scores on days 1, 2, 3, 5, 7, 14, and 28 of hospitalization are calculated, and their performance is evaluated using the area under the receiver operating characteristic (AUROC) analysis. The cut-off for defining the high risk of mortality is determined using Youden's index. The APACHE II score on day 3 is the best time point to predict hospital mortality of ICU patients. The Hosmer-Lemeshow goodness-of-fit test is then applied to evaluate the calibration of the day 3 APACHE II score. Results We recruited 6,374 eligible subjects from the MIMIC-IV database. Day 3 is the optimal time point for obtaining the APACHE II score to predict the hospital mortality of patients. The best cut-off for day 3 APACHE II score is 17. When APACHE II score ≥17, the sensitivity for the non-survivors and survivors is 92.8 and 82.2%, respectively, and the positive predictive value (PPV) is 23.1%. When APACHE II socre <17, the specificity for non-survivors and survivors is 90.1 and 80.2%, respectively, and the negative predictive value (NPV) is 87.8%. When day-3 APACHE II is used to predict the hospital mortality, the AUROC is 0.743 (P <0.001). In the ≥17 group, the sensitivity of non-survivors and survivors is 92.2 and 81.3%, respectively, and the PPV is 30.3%. In the <17 group, the specificity of non-survivors and survivors is 100.0 and 80.2%, respectively, and the NPV is 81.6%. The Hosmer-Lemeshow test indicated day-3 APACHE II has a high predicting the hospital mortality (X2 = 6.198, P = 0.625, consistency = 79.4%). However, the day-1 APACHE II has a poor calibration in predicting the hospital mortality rate (X 2 = 294.898, P <0.001). Conclusion Day-3 APACHE II score is an optimal biomarker to predict the outcomes of ICU patients; 17 is the best cut-off for defining patients at high risk of mortality.
Partial and Radical Nephrectomy Provides Equivalent Oncologic Outcomes in pT3a Renal Cell Carcinoma: A Population-Based Study

Purpose To compare the cause-specific survival (CSS) and overall survival (OS) of patients with localized T3a renal cell carcinoma (RCC) after partial nephrectomy (PN) or radical nephrectomy (RN). Methods We obtained the demographic and clinicopathological data of 7,127 patients with localized T3a RCC and who underwent PN or RN from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were divided into fat invasion cohort and venous invasion cohort for subsequent analysis. Kaplan–Meier analysis (KMA) and univariate and multivariate Cox proportional hazards regression analyses were used to evaluate the effects of PN or RN on OS and CSS. Meanwhile, 65 cases with clinical T1 (cT1) RCC upstaged to pathological T3a (pT3a) who were treated in Tongji Hospital (TJH) from 2011 to 2020 and underwent PN or RN were identified. Results In the study cohort, 2,085 (29.3%) patients died during the 1–172 months’ follow-up, of whom 1,155 (16.2%) died of RCC. In the two cohorts of fat invasion and venous invasion, KMA indicated that the PN group had favorable survival (p < 0.001). However, after propensity score matching (PSM), univariate and multivariate Cox regression analyses showed that the PN and RN groups had comparable CSS in the fat invasion cohort (p = 0.075) and the venous invasion cohort (p = 0.190). During 1–104 months of follow-up, 9 cases in the Tongji cohort had disease recurrence. There was no significant difference in recurrence-free survival between the RN group and the PN group (p = 0.170). Conclusions Our analysis showed that after balancing these factors, patients with localized pT3a RCC receiving PN or RN can achieve comparable oncologic outcomes. PN is safe for selected T3a patients.
The Role of the Microbiota in Regeneration-Associated Processes

The microbiota, the set of microorganisms associated with a particular environment or host, has acquired a prominent role in the study of many physiological and developmental processes. Among these, is the relationship between the microbiota and regenerative processes in various organisms. Here we introduce the concept of the microbiota and its involvement in regeneration-related cellular events. We then review the role of the microbiota in regenerative models that extend from the repair of tissue layers to the regeneration of complete organs or animals. We highlight the role of the microbiota in the digestive tract, since it accounts for a significant percentage of an animal microbiota, and at the same time provides an outstanding system to study microbiota effects on regeneration. Lastly, while this review serves to highlight echinoderms, primarily holothuroids, as models for regeneration studies, it also provides multiple examples of microbiota-related interactions in other processes in different organisms.