Miracle-dz/UniFAR-FTUs huggingface dataset:
Recent advances in understanding neuronal diversity and neural circuit complexity across different brain regions using single-cell sequencing

Neural circuits are characterized as interconnecting neuron networks connected by synapses. Some kinds of gene expression and/or functional changes of neurons and synaptic connections may result in aberrant neural circuits, which has been recognized as one crucial pathological mechanism for the onset of many neurological diseases. Gradual advances in single-cell sequencing approaches with strong technological advantages, as exemplified by high throughput and increased resolution for live cells, have enabled it to assist us in understanding neuronal diversity across diverse brain regions and further transformed our knowledge of cellular building blocks of neural circuits through revealing numerous molecular signatures. Currently published transcriptomic studies have elucidated various neuronal subpopulations as well as their distribution across prefrontal cortex, hippocampus, hypothalamus, and dorsal root ganglion, etc. Better characterization of brain region-specific circuits may shed light on new pathological mechanisms involved and assist in selecting potential targets for the prevention and treatment of specific neurological disorders based on their established roles. Given diverse neuronal populations across different brain regions, we aim to give a brief sketch of current progress in understanding neuronal diversity and neural circuit complexity according to their locations. With the special focus on the application of single-cell sequencing, we thereby summarize relevant region-specific findings. Considering the importance of spatial context and connectivity in neural circuits, we also discuss a few published results obtained by spatial transcriptomics. Taken together, these single-cell sequencing data may lay a mechanistic basis for functional identification of brain circuit components, which links their molecular signatures to anatomical regions, connectivity, morphology, and physiology. Furthermore, the comprehensive characterization of neuron subtypes, their distributions, and connectivity patterns via single-cell sequencing is critical for understanding neural circuit properties and how they generate region-dependent interactions in different context.
Body mass index affecting ticagrelor monotherapy vs. ticagrelor with aspirin in patients with acute coronary syndrome: A pre-specified sub-analysis of the TICO randomized trial

Background Although ticagrelor monotherapy after 3-month dual antiplatelet therapy (DAPT) results in a significantly greater net clinical benefit over that with ticagrelor-based 12-month DAPT in patients with acute coronary syndrome (ACS), it remains uncertain whether this effect is dependent on body mass index (BMI). We aimed to evaluate the BMI-dependent effect of these treatment strategies on clinical outcomes. Methods This was a pre-specified subgroup analysis from the TICO trial (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus-eluting Stent for Acute Coronary Syndrome), evaluating the interaction between BMI and treatment strategies for the primary outcome [composite of major bleeding and adverse cardiac and cerebrovascular events (MACCE): death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization]. The secondary outcomes were major bleeding and MACCE. Results Based on a pre-specified BMI threshold of 25 kg/m2, 3,056 patients were stratified. Patients with BMI <25 kg/m2 had a higher risk of primary and secondary outcomes than those with BMI ≥25 kg/m2. Regardless of the BMI subgroup, the effects of ticagrelor monotherapy after 3-month DAPT on the primary outcome (pint = 0.61), major bleeding (pint = 0.76), and MACCE (pint = 0.80) were consistent without significant interaction compared with ticagrelor-based 12-month DAPT. The treatment effects according to the BMI quartiles and age, sex, and diabetic status were also consistent without significant interaction. Conclusion The BMI-dependent impact of ticagrelor monotherapy after 3-month DAPT compared with 12-month DAPT on clinical outcomes was not heterogeneous in patients with ACS. Clinical Trial Registration [www.ClinicalTrials. gov], identifier [NCT02494895].
Increased NOX2 expression in astrocytes leads to eNOS uncoupling through dihydrofolate reductase in endothelial cells after subarachnoid hemorrhage

Introduction Endothelial nitric oxide synthase (eNOS) uncoupling plays a significant role in acute vasoconstriction during early brain injury (EBI) after subarachnoid hemorrhage (SAH). Astrocytes in the neurovascular unit extend their foot processes around endothelia. In our study, we tested the hypothesis that increased nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression in astrocytes after SAH leads to eNOS uncoupling. Methods We utilized laser speckle contrast imaging for monitoring cortical blood flow changes in mice, nitric oxide (NO) kits to measure the level of NO, and a co-culture system to study the effect of astrocytes on endothelial cells. Moreover, the protein levels were assessed by Western blot and immunofluorescence staining. We used CCK-8 to measure the viability of astrocytes and endothelial cells, and we used the H2O2 kit to measure the H2O2 released from astrocytes. We used GSK2795039 as an inhibitor of NOX2, whereas lentivirus and adeno-associated virus were used for dihydrofolate reductase (DHFR) knockdown in vivo and in vitro. Results The expression of NOX2 and the release of H2O2 in astrocytes are increased, which was accompanied by a decrease in endothelial DHFR 12 h after SAH. Moreover, the eNOS monomer/dimer ratio increased, leading to a decrease in NO and acute cerebral ischemia. All of the above were significantly alleviated after the administration of GSK2795039. However, after knocking down DHFR both in vivo and in vitro, the protective effect of GSK2795039 was greatly reversed. Discussion The increased level of NOX2 in astrocytes contributes to decreased DHFR in endothelial cells, thus aggravating eNOS uncoupling, which is an essential mechanism underlying acute vasoconstriction after SAH.
Two-level mixed-effects height to crown base model for moso bamboo (Phyllostachys edulis) in Eastern China

Height to crown base (HCB) is an important predictor variable for forest growth and yield models and is of great significance for bamboo stem utilization. However, existing HCB models built so far on the hierarchically structured data are for arbor forests, and not applied to bamboo forests. Based on the fitting of data acquired from 38 temporary sample plots of Phyllostachys edulis forests in Yixing, Jiangsu Province, we selected the best HCB model (logistic model) from among six basic models and extended it by integrating predictor variables, which involved evaluating the impact of 13 variables on HCB. Block- and sample plot-level random effects were introduced to the extended model to account for nested data structures through mixed-effects modeling. The results showed that bamboo height, diameter at breast height, total basal area of all bamboo individuals with a diameter larger than that of the subject bamboo, and canopy density contributed significantly more to variation in HCB than other variables did. Introducing two-level random effects resulted in a significant improvement in the accuracy of the model. Different sampling strategies were evaluated for response calibration (model localization), and the optimal strategy was identified. The prediction accuracy of the HCB model was substantially improved, with an increase in the number of bamboo samples in the calibration. Based on our findings, we recommend the use of four randomly selected bamboo individuals per sample to provide a compromise between measurement cost, model use efficiency, and prediction accuracy.
Evaluation of a clinical method for selective electrode deactivation in cochlear implant programming

Background Cochlear implants are a neural prosthesis used to restore the perception of hearing in individuals with severe-to-profound hearing loss by stimulating the auditory nerve with electrical current through a surgically implanted electrode array. The integrity of the interface between the implanted electrode array and the auditory nerve contributes to the variability in outcomes experienced by cochlear implant users. Strategies to identify and eliminate poorly encoding electrodes have been found to be effective in improving outcomes with the device, but application is limited in a clinical setting. Objective The purpose of this study was to evaluate a clinical method used to identify and selectively deactivate cochlear implants (CI) electrodes related to poor electrode-neural interface. Methods Thirteen adult CI users participated in a pitch ranking task to identify indiscriminate electrode pairs. Electrodes associated with indiscriminate pairs were selectively deactivated, creating an individualized experimental program. Speech perception was evaluated in the baseline condition and with the experimental program before and after an acclimation period. Participant preference responses were recorded at each visit. Results Statistically significant improvements using the experimental program were found in at least one measure of speech perception at the individual level in four out of 13 participants when tested before acclimation. Following an acclimation period, ten out of 13 participants demonstrated statistically significant improvements in at least one measure of speech perception. Statistically significant improvements were found with the experimental program at the group level for both monosyllabic words (p = 0.006) and sentences in noise (p = 0.020). Additionally, ten participants preferred the experimental program prior to the acclimation period and eleven preferred the experimental program following the acclimation period. Conclusion Results from this study suggest that electrode deactivation may yield improvement in speech perception following an acclimation period. A majority of CI users in our study reported a preference for the experimental program. This method proved to be a suitable clinical strategy for identifying and deactivating poorly encoding electrodes in adult CI users.
Acute exercise and high-glucose ingestion elicit dynamic and individualized responses in systemic markers of redox homeostasis

Background Biomarkers of oxidation-reduction (redox) homeostasis are commonly measured in human blood to assess whether certain stimuli (e.g., high-glucose ingestion or acute exercise) lead to a state of oxidative distress (detrimental to health) or oxidative eustress (beneficial to health). Emerging research indicates that redox responses are likely to be highly individualized, yet few studies report individual responses. Furthermore, the effects of complex redox stimuli (e.g., high-glucose-ingestion after exercise) on redox homeostasis remains unclear. We investigated the effect of acute exercise (oxidative eustress), high-glucose ingestion (oxidative distress), and high-glucose ingestion after exercise (both oxidative eu/distress), on commonly measured redox biomarkers in serum/plasma. Methods In a randomized crossover fashion, eight healthy men (age: 28 ± 4 years; BMI: 24.5 ± 1.5 kg/m2 [mean ± SD]) completed two separate testing conditions; 1) consumption of a high-glucose mixed-nutrient meal (45% carbohydrate [1.1 g glucose.kg-1], 20% protein, and 35% fat) at rest (control trial), and 2) consumption of the same meal 3 h and 24 h after 1 h of moderate-intensity cycling exercise (exercise trial). Plasma and serum were analyzed for an array of commonly studied redox biomarkers. Results Oxidative stress and antioxidant defense markers (hydrogen peroxide, 8-isoprostanes, catalase, superoxide dismutase, and nitrate levels) increased immediately after exercise (p < 0.05), whereas nitric oxide activity and thiobarbituric acid reactive substances (TBARS) remained similar to baseline (p > 0.118). Nitric oxide activity and nitrate levels decreased at 3 h post-exercise compared to pre-exercise baseline levels. Depending on when the high-glucose mixed nutrient meal was ingested and the postprandial timepoint investigated, oxidative stress and antioxidant defense biomarkers either increased (hydrogen peroxide, TBARS, and superoxide dismutase), decreased (hydrogen peroxide, 8-isoprostanes, superoxide dismutase, nitric oxide activity, nitrate, and nitrite), or remained similar to pre-meal baseline levels (hydrogen peroxide, 8-isoprostanes, TBARS, catalase, superoxide dismutase and nitrite). Redox responses exhibited large inter-individual variability in the magnitude and/or direction of responses. Conclusion Findings highlight the necessity to interpret redox biomarkers in the context of the individual, biomarker measured, and stimuli observed. Individual redox responsiveness may be of physiological relevance and should be explored as a potential means to inform personalized redox intervention.
Discriminative analysis of schizophrenia patients using graph convolutional networks: A combined multimodal MRI and connectomics analysis

Introduction Recent studies in human brain connectomics with multimodal magnetic resonance imaging (MRI) data have widely reported abnormalities in brain structure, function and connectivity associated with schizophrenia (SZ). However, most previous discriminative studies of SZ patients were based on MRI features of brain regions, ignoring the complex relationships within brain networks. Methods We applied a graph convolutional network (GCN) to discriminating SZ patients using the features of brain region and connectivity derived from a combined multimodal MRI and connectomics analysis. Structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 140 SZ patients and 205 normal controls. Eighteen types of brain graphs were constructed for each subject using 3 types of node features, 3 types of edge features, and 2 brain atlases. We investigated the performance of 18 brain graphs and used the TopK pooling layers to highlight salient brain regions (nodes in the graph). Results The GCN model, which used functional connectivity as edge features and multimodal features (sMRI + fMRI) of brain regions as node features, obtained the highest average accuracy of 95.8%, and outperformed other existing classification studies in SZ patients. In the explainability analysis, we reported that the top 10 salient brain regions, predominantly distributed in the prefrontal and occipital cortices, were mainly involved in the systems of emotion and visual processing. Discussion Our findings demonstrated that GCN with a combined multimodal MRI and connectomics analysis can effectively improve the classification of SZ at an individual level, indicating a promising direction for the diagnosis of SZ patients. The code is available at https://github.com/CXY-scut/GCN-SZ.git.
Efficacy of concurrent radiotherapy in patients with locally advanced rectal cancer and synchronous metastasis receiving systemic therapy

Background Neoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment for patients with nonmetastatic locally advanced rectal cancer (LARC). However, for patients with LARC and synchronous metastasis, the optimal treatment strategy and sequence remain inconclusive. In the present study, we evaluated the efficacy and safety of concurrent radiotherapy in patients with de novo metastatic rectal cancer who received chemotherapy and targeted therapy. Methods We retrospectively reviewed the data of 63 patients with LARC and synchronous metastasis who received intensive therapy at the study hospital between April 2015 and November 2018. The included patients were divided into two groups: RT-CT, those who received systemic chemotherapy with targeted therapy and concurrent radiotherapy (for primary rectal cancer), and CT, those who received only systemic chemotherapy with targeted therapy. Results Treatment response was better in the RT-CT group than in the CT group. The rate of primary tumor resection (PTR) was higher in the RT-CT group than in the CT group (71.4% and 42.9%, respectively; P = .0286). The RT-CT group exhibited considerably longer local recurrence-free survival (P = .0453) and progression-free survival (PFS; from 13.3 to 22.5 months) than did the CT group (P = .0091); however, the groups did not differ in terms of overall survival (OS; P = .49). Adverse events were almost similar between the groups, except frequent diarrhea, the prevalence of which was higher in the RT-CT group than in the CT group (59.5% and 23.8%, respectively; P = .0075). Conclusions In the era of biologics, radiotherapy may increase the resectability of primary rectal tumors, reducing the risk of locoregional failure and prolonging PFS. Concurrent pelvic radiotherapy may not substantially improve OS, which is indicated by metastasis. Hence, the resection of the distant metastases may be essential for improving long-term OS. To further determine the efficacy of concurrent radiotherapy, additional prospective, randomized studies must combine preoperative pelvic radiotherapy with PTR and metastectomy to treat patients with stage IV LARC.
Cell-based meat: The molecular aspect

Cellular agriculture is one of the evolving fields of translational biotechnology. The emerging science aims to improve the issues related to sustainable food products and food security, reduce greenhouse gas emissions and provide animal wellbeing by circumventing livestock farming through cell-based meat (CBM) production. CBM exploits cell culture techniques and biomanufacturing methods by manipulating mammalian, avian, and fish cell lines. The cell-based products ought to successfully meet the demand for nutritional protein products for human consumption and pet animals. However, substantial advancement and modification are required for manufacturing CBM and related products in terms of cost, palatability, consumer acceptance, and safety. In order to achieve high-quality CBM and its production with high yield, the molecular aspect needs a thorough inspection to achieve good laboratory practices for commercial production. The current review discusses various aspects of molecular biology involved in establishing cell lines, myogenesis, regulation, scaffold, and bioreactor-related approaches to achieve the target of CBM.
Welfare implications on management strategies for rearing dairy calves: A systematic review. Part 1–feeding management

Introduction Calves are very susceptible to stress in the early stages of life, and it is necessary to ensure maximum welfare. Feeding management has been identified as a major risk factor for calf health and welfare at this stage. However, the management protocol for calf rearing and its impact on animal welfare is unclear. A systematic review of different management strategies for rearing dairy calves according to the three spheres of animal welfare was conducted using an electronic search strategy. In this review, management strategies were studied to identify scientific gaps, to know the welfare problems of these animals in order to prioritize actions and future research and to study the interpretive approach of this management from the three welfare spheres. Methods A protocol was used to analyze and extract information from the studies. Of the 1,783 publications screened, only 351 met the inclusion criteria for the management or welfare of calves' items. Results The publications identified in the search can be divided into two main groups feeding and socialization, based on the main topic of the publication. The main topics that emerged from the search in the feeding management group were milk replacer, colostrum, and weaning, divided into the three main areas of biological functioning and health, natural life and affective states or cognitive judgement. Discussion The main issues to be addressed were the different types of feed consumed by animals from birth to weaning and the weaning management. It has been found that the most researched issues are colostrum and solid starter feed management. Unresolved issues were highlighted, such as the lack of a clear protocol for the administration of milk replacers to reduce hunger and the best management of weaning to reduce stress.
Design strategy and mechanism of nitrite oxidation suppression of elevated loading rate partial nitritation system

There is a current need for a low operational intensity, effective and small footprint system to achieve stable partial nitritation for subsequent anammox treatment at mainstream municipal wastewaters. This research identifies a unique design strategy using an elevated total ammonia nitrogen (TAN) surface area loading rate (SALR) of 5 g TAN/m2.d to achieve cost-effective, stable, and elevated rates of partial nitritation in a moving bed biofilm reactor (MBBR) system under mainstream conditions. The elevated loaded partial nitritation MBBR system achieves a TAN surface area removal rate (SARR) of 2.01 ± 0.07 g TAN/m2.d and NO2−-N: NH4+-N stoichiometric ratio of 1.15:1, which is appropriate for downstream anammox treatment. The elevated TAN SALR design strategy promotes nitrite-oxidizing bacteria (NOB) activity suppression rather than a reduction in NOB population as the reason for the suppression of nitrite oxidation in the mainstream elevated loaded partial nitritation MBBR system. NOB activity is limited at an elevated TAN SALR likely due to thick biofilm embedding the NOB population and competition for dissolved oxygen (DO) with ammonia-oxidizing bacteria for TAN oxidation to nitrite within the biofilm structure, which ultimately limits the uptake of DO by NOB in the system. Therefore, this design strategy offers a cost-effective and efficient alternative for mainstream partial nitritation MBBR systems at water resource recovery facilities.
Reducing milking frequency from 3 to 2 times daily in early lactation: effects on milk production, health and body condition

Abstract The objective of this experiment was to investigate the effect of reducing early lactation milking frequency on milk yield and persistency through lactation and early lactation fat mobilization, measured by body condition score (BCS) and BHB in milk. We hypothesized that milking cows twice per day in early lactation before milking them 3 times per day for the remaining lactation would cause less fat mobilization in early lactation, a lower peak milk yield but improved persistency throughout lactation compared with milking cows 3 times per day for the entire lactation. The experiment took place on 2 commercial dairy farms in Denmark. All cows calving in a period of nine months (n = 239) in their current first and later parities were randomly allocated at dry-off to 1 of 3 treatments based on expected calving date. The treatments were (1) cows milked 2 times per day for 1 week after calving, (2) cows milked 2 times per day for 4 weeks after calving and (3) cows milked 2 times per day for 7 weeks after calving. All cows were then milked 3 times per day for the remaining lactation. Milk yield peaked 3.3 and 3.6 d later and milk yield persistency improved with 18 and 19 g per day when cows were milked 2 times per day for 4 and 7 weeks, respectively, compared with milking 2 times per day for 1 week after calving. We found a significant highest milk BHB in treatment 2, but the underlying effect of milking cows 2 times per day for 4 weeks compared with 1 or 7 weeks was unclear. In conclusion, we did not confirm our hypothesis that milking cows 2 times per day compared to 3 times in early lactation would reduce fat mobilization and reduce peak yield. We did, however, find an improved milk yield persistency, which partially offset a numerical reduction in peak yield, and hence there was no significant effect of reducing early lactation milking frequency on total lactation (305 DIM) milk yield.