Molecular, behavioral, and growth responses of juvenile yellow catfish (Tachysurus fulvidraco) exposed to carbamazepine.

Carbamazepine (CBZ) is an anticonvulsant medication used to treat epilepsy and bipolar disorder. Due to its persistence and low removal rate in wastewater treatment plants, it is frequently detected in the environment, raising concerns regarding its potential adverse effects on aquatic organisms and ecosystems. In this study, we aimed to assess the impact of CBZ on the behavior and growth of juvenile yellow catfish Tachysurus fulvidraco, a native and economically important species in China. Fish were exposed to CBZ at three concentrations of 1, 10, or 100 µg/L for 14 days. The fish exposed to 10 and 100 µg/L of CBZ exhibited decreased feeding, and a significant increase in cannibalistic tendencies was observed in fish exposed to 100 µg/L CBZ. Acetylcholinesterase activity was increased in the brain of fish exposed to 100 µg/L CBZ. CBZ also inhibited the growth of yellow catfish. To better elucidate mechanisms of toxicity, transcriptomics was conducted in both the brain and liver. In the brain, gene networks associated with neurotransmitter dysfunction were altered by CBZ, as well as networks associated with mitochondrial dysfunction and metabolism. In the liver, gene networks associated with the immune system were altered by CBZ. The current study improves comprehension of the sub-lethal effects of CBZ and reveals novel insight into molecular and biochemical pathways disrupted by CBZ, identifying putative key events associated with reduced growth and altered behavior. This study emphasizes the necessity for improved comprehension of the effects of pharmaceutical contaminants on fish at environmentally relevant levels.

Generation and applications of synthetic computed tomography images for neurosurgical planning.

OBJECTIVE: CT and MRI are synergistic in the information provided for neurosurgical planning. While obtaining both types of images lends unique data from each, doing so adds to cost and exposes patients to additional ionizing radiation after MRI has been performed. Cross-modal synthesis of high-resolution CT images from MRI sequences offers an appealing solution. The authors therefore sought to develop a deep learning conditional generative adversarial network (cGAN) which performs this synthesis. METHODS: Preoperative paired CT and contrast-enhanced MR images were collected for patients with meningioma, pituitary tumor, vestibular schwannoma, and cerebrovascular disease. CT and MR images were denoised, field corrected, and coregistered. MR images were fed to a cGAN that exported a "synthetic" CT scan. The accuracy of synthetic CT images was assessed objectively using the quantitative similarity metrics as well as by clinical features such as sella and internal auditory canal (IAC) dimensions and mastoid/clinoid/sphenoid aeration. RESULTS: A total of 92,981 paired CT/MR images obtained in 80 patients were used for training/testing, and 10,068 paired images from 10 patients were used for external validation. Synthetic CT images reconstructed the bony skull base and convexity with relatively high accuracy. Measurements of the sella and IAC showed a median relative error between synthetic CT scans and ground truth images of 6%, with greater variability in IAC reconstruction compared with the sella. Aerations in the mastoid, clinoid, and sphenoid regions were generally captured, although there was heterogeneity in finer air cell septations. Performance varied based on pathology studied, with the highest limitation observed in evaluating meningiomas with intratumoral calcifications or calvarial invasion. CONCLUSIONS: The generation of high-resolution CT scans from MR images through cGAN offers promise for a wide range of applications in cranial and spinal neurosurgery, especially as an adjunct for preoperative evaluation. Optimizing cGAN performance on specific anatomical regions may increase its clinical viability.

Recent advances in microfluidic technology of arterial thrombosis investigations.

Microfluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.

What is the context? To study the mechanism of arterial thrombosis, including the platelet adhesion and aggregation behavior and the coagulation process.Microfluidic technology is commonly used to study thrombosis. Microfluidic technology can simulate the real physiological environment on the microscopic scale in vitro, with high throughput, low cost, and fast speed.As an innovative experimental platform, microfluidic technology has made remarkable progress and has found applications in the fields of biology and medicine.What is new? This review summarizes the different fabrication methods of microfluidics and compares the advantages and disadvantages of these methods. Recent developments in microfluidic integrated systems and modular microfluidic systems have led to more diversified and automated microfluidic chips in the future.The different types and functions of microfluidic models are summarized. Platelet adhesion aggregation and coagulation processes, as well as arterial thrombus-related shear force changes and mechanical behaviors, were investigated by constructing artificial blood vessels and reproducing hemodynamics.Microfluidics can provide a basis for the development of personalized thrombosis treatment strategies. By analyzing the mechanism of action of existing drugs, using microfluidic technology for high-throughput screening of drugs and evaluating drug efficacy, more drug therapy possibilities can be developed.What is the impact?This review utilizes microfluidics to further advance the study of arterial thrombosis, and microfluidics is also expected to play a greater role in the biomedical field in the future.

High arsenic pollution of the eutrophic Lake Taihu and its relationship with iron, manganese, and dissolved organic matter: High-resolution synchronous analysis.

Arsenic (As) is a metalloid that can accumulate in eutrophic lakes and cause adverse health effects to people worldwide. However, the seasonal process and dynamic mechanism for As mobilization in eutrophic lake remains effectively unknown. Here we innovatively used the planar optodes (PO), high-resolution dialysis (HR-Peeper) combined with fluorescence excitation-emission matrix coupled with parallel factor (EEM-PARAFAC) analysis technologies. We synchronously investigate monthly O2, As, iron (Fe), manganese (Mn), and naturally occurring dissolved organic matter (DOM) changes in sediments of Lake Taihu at high resolution in field conditions. We find high As contamination from sediments with 61.88-327.07 µg m-2 d-1 release As fluxes during the algal bloom seasons from May to October 2021. Our results show that an increase in DOM, mainly for humic-like components, resulting in high electron transfer capacity (ETC), promoted the reductive dissolution of Fe and Mn oxides to release As. Partial least square-path modeling (PLS-PM) and random forest modeling analysis identified that Mn oxide reductive dissolution directly accelerated sediments As contamination, which is the crucial factor. Understanding crucial factor controlling As release is especially essential in areas of eutrophic lakes developing effective strategies to manage As-rich eutrophic lake sediments worldwide.

Performance of the digital cell morphology analyzer MC-100i in a multicenter study in tertiary hospitals in China.

BACKGROUND: This study investigated the performance of the MC-100i, a pre-commercial digital morphology analyzer utilizing a convolutional neural network algorithm, in a multicentric setting involving up to 11 tertiary hospitals in China. METHODS: Blood smears were analyzed by MC-100i, verified by morphologists, and manually differentiated. The classification performance on WBCs and RBCs was evaluated by comparing the classification results using different methods. The PLT and PLT clump counting performance was also assessed. The total assay time including hands-on time was evaluated. RESULTS: The agreements between pre- and post-classification were high for normal WBCs (κ > 0.96) and lower for overall abnormal WBCs (κ = 0.90). The post-classification results correlated well with manual differentials for both normal and abnormal WBCs (r > 0.93), except for basophils (r = 0.8480) and atypical lymphocytes (r = 0.8211). The clinical sensitivity and specificity of each RBC abnormality after verification were above 90 % using microscopy reviews as the reference. The PLTs counted by the MC-100i before and after verification correlated well with those measured by the PLT-O mode (r = 0.98). Moreover, PLT clumps were successfully classified by the analyzer in EDTA-dependent pseudothrombocytopenia blood samples. CONCLUSIONS: The MC-100i is an accurate and reliable digital cell morphology analyzer, offering another intelligent option for hematology laboratories.

Micro-Red Blood Cell, Fragmented Red Blood Cell, Platelet Distribution Width, Mean Platelet Volume, and Platelet-Large Cell Ratio on Sysmex XN Series Hematology Analyzers Can Be Used for the Reflex Test of Impedance Platelet Count in Clinical Practice.

CONTEXT.­: Platelet (PLT) counting with impedance (PLT-I) is widely used but has low specificity. PLT counting with fluorescence (PLT-F), tested by the Sysmex XN series with high specificity, can be a complementary method to PLT-I. OBJECTIVE.­: To identify red blood cell (RBC)- and PLT-related parameters as potential influencing factors for PLT-I and establish PLT reflex test rules with PLT-F. DESIGN.­: We prospectively tested both PLT-I and PLT-F in all 3480 samples. In a development data set of 3000 samples, differences between the reflex and nonreflex groups were compared and influencing factors for PLT-I were identified by logistic regression. The area under the receiver operating characteristic (ROC) curve and cutoff values were obtained by ROC curve analysis. Validation was conducted in the remaining 480 samples (validation data set). RESULTS.­: PLT-F showed comparable results with immunoplatelet counting. In logistic regression, increased micro-RBC absolute count (micro-RBC#), fragmented RBC absolute count (FRC#), PLT distribution width (PDW), mean PLT volume (MPV), PLT-large cell ratio (P-LCR), and immature PLT fraction absolute count (IPF#) were influencing factors for PLT-I. In ROC curve analysis, the cutoff values of micro-RBC#, FRC#, PDW, MPV, and P-LCR were 0.64 × 106/µL, 0.082 × 106/µL, 15.40 fL, 11.15 fL, and 33.95%, respectively. The areas under the ROC curve of micro-RBC# and FRC# were 0.77 and 0.79, respectively. CONCLUSIONS.­: Micro-RBC#, FRC#, PDW, MPV, P-LCR, and IPF# were factors affecting PLT-I. Among them, micro-RBC# and FRC# were the most impactful factors. From our study results, micro-RBC#, FRC#, MPV, PDW, and P-LCR can be used to establish reflex test rules for PLT counting in clinical work.

Correlation between tumor invasion and somatostatin receptor subtypes in acromegaly.

OBJECTIVE: The low expression of somatostatin receptor (SSTR) subtypes in somatotropinoma is associated with a poor response to somatostatin analogs (SSAs). However, the correlation between SSTRs and tumor invasion has not yet been clarified. Therefore, the authors aimed to investigate the relationship between SSTRs and tumor invasion, as well as the correlation between tumor invasiveness and pharmacological response to SSAs. METHODS: A total of 102 patients with acromegaly who underwent surgery between December 2016 and December 2021 at the largest pituitary tumor surgery center in southern China were included in this retrospective study. Patients were divided into the noninvasive tumor group (Knosp grades 0-2 and Hardy-Wilson grade I or II) and invasive group (either Knosp grade 3 or 4 or Hardy-Wilson grade III or IV). The positive response to SSAs was defined by the following criteria after at least 3 months of SSA treatment: 1) ≥ 50% reduction or age- and sex-adjusted normal range of insulin-like growth factor-1 (IGF-1) level; 2) ≥ 80% reduction in or normal range of growth hormone (GH) level; or 3) > 20% reduction in tumor volume. The reference for the normal range of age- and sex-adjusted serum IGF-1 levels was derived from a survey of 2791 healthy adults (1339 males and 1452 females) in China. Demographics and clinical characteristics including tumor size, biochemical assessment, expression levels of SSTRs, and response to preoperative SSAs were compared between the invasive group and noninvasive group. Receiver operating characteristic (ROC) curve analysis was performed to assess the association between SSTR2 and tumor invasion. RESULTS: Compared with the noninvasive group, the invasive group presented with a larger tumor size (9.99 ± 10.41 cm3 vs 3.50 ± 4.02 cm3, p < 0.001), relatively lower SSTR2 expression (p < 0.001), and poorer response to SSAs (36.4% vs 91.7%, p < 0.001). In addition, there was a significant negative correlation between SSTR2 mRNA level and tumor size (r = -0.214, p = 0.031). However, there were no statistically significant differences in the expression of SSTR1, SSTR3, and SSTR5 between the groups. ROC analysis revealed that the low SSTR2 mRNA level was closely associated with tumor invasion (area under the curve 0.805, p < 0.0001). CONCLUSIONS: Tumor invasion is negatively correlated with SSTR2 level but is not associated with other SSTR subtypes. Patients with invasive tumors have a poorer response to SSA therapy, which may be due to the low level of SSTR2 expression. Therefore, SSTR2 could be considered as a routine investigative marker for aiding management of postoperative residual tumors.

The toxicological effects of life-cycle exposure to harmful benthic cyanobacteria Oscillatoria on zebrafish growth and reproduction: A comparative study with planktonic Microcystis.

The risks of planktonic cyanobacteria blooms have been the focus of much scientific research, but studies on the ecotoxicological effects of benthic cyanobacteria are lagging. The impacts of cyanobacteria cells on fish populations might be more complex in contrast to purified cyanotoxins or cyanobacteria extracts. This study systematically compared the chronic effects of benthic Oscillatoria sp. (producing cylindrospermopsins) and planktonic Microcystis aeruginosa (producing microcystins) on the growth and reproduction of zebrafish through life-cycle exposure (5- 90 days post fertilization). The results showed that both Oscillatoria sp. and M. aeruginosa exposure caused growth inhibition and fecundity reduction in F0 generation by disrupting sex hormone levels, delayed ovarian and sperm development, and induced pathological lesions in zebrafish gonads. Furthermore, exposure to Oscillatoria sp. or M. aeruginosa in adult zebrafish increased mortality and teratogenicity in F1 embryos (without exposure), indicating a parental transmission effect of developmental toxicity. The difference was that M. aeruginosa exposure led to significant alterations in pathways, such as tissue development, redox processes, and steroid hormone synthesis. In contrast, Oscillatoria sp. exposure primarily disrupted the PPAR signaling pathway, cell adhesion molecules, and lipid transport pathways. Interestingly, the differentially expressed genes revealed that male fish were more sensitive to harmful cyanobacteria than females, whether exposed to Oscillatoria sp. or M. aeruginosa. These findings contribute to a better mechanistic understanding of the chronic toxic effects of distinct types of harmful cyanobacteria, suggesting that the ecological risk of benthic cyanobacteria requires further attention.

Effect of Juvenile Hormone on Worker Behavioral Transition in the Red Imported Fire Ant, Solenopsis invicta (Hymenoptera: Formicidae).

The division of labor among workers is a defining characteristic of social insects and plays a pivotal role in enhancing the competitive advantage of their colony. Juvenile hormone (JH) has long been hypothesized to be the essential driver in regulating the division of labor due to its ability to accelerate behavioral transitions in social insects, such as honeybees. The regulation of behavioral transitions by JH in the red imported fire ant (RIFA), Solenopsis invicta, a typical social pest, is unclear. Through video capture and analysis, we investigated the effects of the juvenile hormone analogue (JHA) methoprene on brood care, phototaxis behavior, and threat responsiveness of RIFA nurse workers. Our results showed that the JHA application significantly reduced the time and frequency of brood care behavior by nurse workers while increasing their walking distance and activity time in the light area. Additionally, the application of JHA made ants become excited, indicating a significant improvement in their activity level (movement distance, time, and speed). Furthermore, it was observed that the application of JHA did not affect the threat responsiveness of nurse workers towards stimuli (nestmates or non-nestmates). Our study demonstrates that the application of JHA reduced brood care behavior and enhanced phototaxis in nurse workers, which may reveal the role of JH in facilitating behavioral transitions in RIFA from intranidal tasks to extranidal activity. This study provides an experimental basis for further elucidating the mechanism underlying the division of labor in social insects.

Top-down effects of filter-feeding fish and bivalves moderate bottom-up effects of nutrients on phytoplankton in subtropical shallow lakes: An outdoor mesocosm study.

Biomanipulation has been widely used in the ecological restoration of eutrophic lakes for decades. However, biomanipulation is prone to failure if external nutrient loads are not reduced. In order to explore the importance of filter-feeding fish and bivalves on algal control, an outdoor mesocosm experiment was conducted using different nutrient concentrations. Four treatments simulating daily loads of nutrients in Lake Taihu were studied: current, two times, and three times average daily loads of nutrients with both fish (Aristichthys nobilis) and Asian clam (Corbicula fluminea) and as a control current daily loads without fish or bivalves. Results showed that stocking of filter-feeding fish and bivalves (80 g m-3 bighead carp; 200 g cm-2 clams) at two times daily nutrient loads could effectively control water column Chl a concentrations and phytoplankton biomass. At higher nutrient concentrations (TN ≥ 260 µg L-1 d-1; TP ≥ 10 µg L-1 d-1), top-down control of filter-feeding fish and bivalves was less effective and bottom-up effects resulted in significant increases of Chl a concentration. Thus, as phytoplankton biomass in freshwater ecosystems is determined by both the top-down effects of predators and the bottom-up effects of nutrients, external loadings should be controlled when filter-feeding fish and bivalves are used for algal control to ensure the efficacy of biomanipulation.

Development and testing of a planktonic index of biotic integrity (P-IBI) for Lake Fuxian, China.

Lake Fuxian has the largest reserves of high-quality water resources in China, and understanding its ecological health status is the basis of its environmental protection. Based on a seasonal field investigation of the plankton community, we established a planktonic index of biotic integrity (P-IBI) evaluation system to assess the lake's ecosystem health. The biological integrity of Lake Fuxian was relatively good during winter and spring, but gradually deteriorated from summer to autumn. Areas with poor biological integrity were mainly distributed near tourist attractions along the lake's west coast. Redundancy analysis (RDA) was performed to explore the relationships between the P-IBI, its selected indicators, and the environmental variables. Water temperature (WT), pH, ammonia nitrogen (NH3-N), and dissolved oxygen (DO) significantly influenced the P-IBI and its selected indicators. NH3-N and DO were significantly positively correlated with the P-IBI, indicating that it could be used as a water quality indicator to indirectly reflect lake biological integrity. We demonstrated that the P-IBI can effectively reflect temporal and spatial variations of biological integrity and could be used as a potential tool to evaluate Lake Fuxian ecosystem health.

Simultaneous increases of filter-feeding fish and bivalves are key for controlling cyanobacterial blooms in a shallow eutrophic lake.

Eutrophication and cyanobacterial blooms have severely affected many freshwater ecosystems. We studied the effects of filter-feeding fish and bivalves on algal populations using a mesocosm experiment and long-term monitoring data from Lake Taihu (China). The mesocosm study, comprised of a two-way factorial design with the clam Corbicula fluminea and the fish Aristichthys nobilis at three biomass levels, resulted in lower chlorophyll a (Chl a) in high fish treatments, but no significant differences in the low and medium fish treatments. Chl a also decreased with an increase in clam biomass in the high fish treatments. Moreover, filter-feeding fish resulted in a decrease in algal sizes (e.g., the colony size of Microcystis aeruginosa was inversely related to fish biomass) which likely increased the filter-feeding efficiency of bivalves. Biomass of filter-feeding fish was found to be a key factor driving the synergistic effects of filter-feeding fish and bivalves in waters dominated by Microcystis colonies. Long-term monitoring revealed increasing trends in Chl a concentration, total fish catch per unit effort (TF-CPUE), and filter-feeding fish (FF-CPUE), and slightly decreasing trends in bivalve biomass and nitrogen to phosphorus ratios (N:P) from 2006 to 2016. Bivalve biomass and N:P were negatively correlated with Chl a, while FF-CPUE was not significantly related to Chl a. The current filter-feeding fish biomass in Lake Taihu is estimated to be too low to drive synergistic algal control effects together with bivalves. Furthermore, the lack of filter feeders in Lake Taihu may lead to top-down control by predators that cannot counteract the bottom-up effects of nutrients on phytoplankton. Collectively, these long-term monitoring and experimental data support the combined use filter-feeding fish and bivalves for managing cyanobacteria blooms in Lake Taihu.

Omics techniques reveal the toxicity mechanisms of three antiepileptic drugs to juvenile zebrafish (Danio rerio) brain and liver.

Epilepsy, a neurological disorder, is characterized by seizures that are an appearance of excessive brain activity and is symptomatically treated with antiepileptic drugs (AEDs). Oxcarbazepine (OCBZ), lamotrigine (LTG), and carbamazepine (CBZ) are widely used AEDs in clinics and are very often detected in aquatic environments. However, neither the sub-lethal effects nor the specific mechanisms of these AEDs' action on the fish are well understood. In this study, juvenile zebrafish were exposed to a sub-lethal concentration (100 µg/L) of OCBZ, LTG, and CBZ for 28 d, after which indicators of oxidative stress (i.e. superoxide dismutase (SOD) activity, catalase (CAT) activity, and malondialdehyde (MDA) level) and neurotoxicity (i.e. acetylcholinesterase (AChE) activity, γ-aminobutyric acid (GABA) level, and glutamic acid (Glu) level) were measured. Brain SOD activity was significantly increased by three AEDs, while brain CAT activity was significantly inhibited by LTG and CBZ. Liver SOD activity was significantly enhanced by CBZ, and liver CAT activity was significantly induced by OCBZ and LTG. Liver MDA level was significantly increased by three AEDs. Brain AChE activity was significantly increased by LTG and CBZ, and brain GABA level was significantly enhanced by three AEDs. However, there were no significant alterations in the levels of MDA and Glu in zebrafish brain. To ascertain mechanisms of AEDs-induced toxicity, brain transcriptomics and liver metabolomics were conducted in zebrafish. The brain transcriptomics results showed that lots of differentially expressed genes (DEGs) were enriched in the sensory system, the immune system, the digestive system, the metabolic processes, and others in three AEDs treated groups. The metabolomics data indicated dysregulation of glycerophospholipid signaling and lipid homeostasis in zebrafish liver after three AEDs exposure. The overall results of this study improve understanding of the sub-lethal effects and potential molecular mechanisms of action of AEDs in fish.

Microbiome dysbiosis occurred in hypertrophic scars is dominated by S. aureus colonization.

Background: The mechanisms of hypertrophic scar formation and its tissue inflammation remain unknown. Methods: We collected 33 hypertrophic scar (HS) and 36 normal skin (NS) tissues, and detected the tissue inflammation and bacteria using HE staining, Gram staining, and transmission electronic microscopy (TEM), in situ hybridization and immunohistochemistry for MCP-1, TNF-α, IL-6 and IL-8. In addition, the samples were assayed by 16S rRNA sequencing to investigate the microbiota diversity in HS, and the correlation between the microbiota and the indices of Vancouver Scar Scale(VSS)score. Results: HE staining showed that a dramatically increased number of inflammatory cells accumulated in HS compared with NS, and an enhanced number of bacteria colonies was found in HS by Gram staining, even individual bacteria could be clearly observed by TEM. In situ hybridization demonstrated that the bacteria and inflammation cells co-localized in the HS tissues, and immunohistochemistry indicated the expression of MCP-1, TNF-α, IL-6, and IL-8 were significantly upregulated in HS than that in NS. In addition, there was a significantly different microbiota composition between HS and NS. At the phylum level, Firmicutes was significantly higher in HS than NS. At the genus level, S. aureus was the dominant species, which was significantly higher in HS than NS, and was strongly correlated with VSS indices. Conclusion: Microbiome dysbiosis, dominated by S. aureus, occurred in HS formation, which is correlated with chronic inflammation and scar formation, targeting the microbiome dysbiosis is perhaps a supplementary way for future scar management.

Using 2-dimensional hand photographs to predict postoperative biochemical remission in acromegaly patients: a transfer learning approach.

Background: The primary treatment goals in acromegaly patients are complete surgical removal of underlying pituitary tumors and biochemical remission. One of the challenges in developing countries is the difficulty in monitoring postoperative biochemical levels in acromegaly patients, particularly those who live in remote areas or regions with limited medical resources. Methods: In an attempt to overcome the abovementioned challenges, we conducted a retrospective study and established a mobile and low-cost method to predict biochemical remission in acromegaly patients after surgery, the efficacy of which was assessed retrospectively using the China Acromegaly Patient Association (CAPA) database. A total of 368 surgical patients from the CAPA database were successfully followed up to obtain their hand photographs. Demographics, baseline clinical characteristics, pituitary tumor features, and treatment details were collated. Postoperative outcome, defined as biochemical remission at the last follow-up timepoint, was assessed. Transfer learning with a new mobile tailored neurocomputing architecture, MobileNetv2, was used to explore the identical features that could be used as predictors of long-term biochemical remission after surgery. Results: As expected, the MobileNetv2-based transfer learning algorithm was shown to predict biochemical remission with statistical accuracies of 0.96 and 0.76 in the training cohort (n=803) and validation cohort (n=200), respectively, and the loss function value was 0.82. Conclusions: Our findings demonstrate the potential of the MobileNetv2-based transfer learning algorithm in predicting biochemical remission for postoperative patients who are at home or live far away from a pituitary or neuroendocrinological treatment center.

A convolutional neural network-based, quantitative complete blood count scattergram-mapping framework promptly screens acute promyelocytic leukemia with high sensitivity.

BACKGROUND: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by its rapidly progressive and fatal clinical course if untreated, although it is curable if treated in a timely manner. Promptly screening patients who have results that are suspicious for APL is vital to overcome early death. METHODS: The authors developed an innovative framework consisting of ResNet-18, a convolutional neural network architecture, with the objective of quantitatively mapping a complete blood count (CBC) scattergram to quickly and robustly indicate a probable susceptibility to APL. Three hundred and twenty scattergrams of the white blood cell differential channel from 51 patients with APL, 510 scattergrams from 105 patients who had non-APL AML, and 320 scattergrams from 320 healthy controls were randomly stratified at a ratio of 4:1 and split into training and testing data sets to accomplish five-fold cross-validation. RESULTS: Both the area under the curve and the average precision of >0.99 were achieved in each fold. Three hundred four of the 320 APL scattergrams (95%) were correctly flagged by the model, which outcompeted the CBC review rules recommended by the International Society of Laboratory Hematology (all p < .001). External validation based on an independent testing data set that included 56 scattergrams from 31 patients with APL, 56 scattergrams from 55 patients with non-APL AML, and 64 scattergrams from 64 healthy controls also confirmed the sensitivity and specificity of the framework. CONCLUSIONS: To the authors' knowledge, their convolutional neural network-based framework is the first to use scattergram output from routine CBC analysis to map suspicious APL early with outstanding sensitivity, specificity, and precision. The authors also describe a new CBC workflow incorporating this framework upstream of the morphologic review, which would provide the earliest flag for APL. PLAIN LANGUAGE SUMMARY: The authors propose an innovative way to visualize complete blood counts (CBCs) by mapping the difference in white blood cell counts using automated CBC analysis to identify potential acute promyelocytic leukemia (APL) using a convolutional neural network (CNN), which can eliminate the potential pitfalls of manual observation. Analyses of an unprecedented, realistic data set validated that the quantitative relationship between the CBC scattergram and an APL abnormality is highly consistent. This is the first study to date focusing on screening for APL using scattergrams of the difference in white blood cell counts from routine CBC tests and has significant clinical relevance. The authors recommend using this method even before analyzing cell images, which could provide the earliest way to screen for APL in a sensitive and accurate way.

Effects of nutrient reduction and habitat heterogeneity on benthic macroinvertebrate assemblages in a large shallow eutrophic lake.

The Taihu Lake ecosystem has been subjected to numerous anthropogenic stressors during the past decades, leading to substantial changes in nutrient dynamics and habitat quality. For instance, the northwestern lake bays receive large amounts of nutrient-rich wastewater and have frequently experienced algal blooms, while the eastern lake region is still dominated by submersed macrophytes. Such changes in environmental characteristics can greatly impact benthic macroinvertebrate communities. We used a 15-year monitoring data series collected by the Taihu Laboratory for Lake Ecosystem Research to examine the spatial and temporal variations of the benthic invertebrate fauna and evaluate its status and trends. We found that three major communities could be distinguished based on taxonomic group composition and abundance, and these corresponded well with three lake habitat types: algal-dominated, macrophyte-dominated, and open-lake zone. An analysis of temporal trends showed major changes in the macroinvertebrates during the study period, largely driven by a lake-wide and significant decline in the abundance of pollution-tolerant taxa. The spatial and temporal variations of macroinvertebrate communities were mainly explained by nutrients (e.g., total nitrogen and ammonium concentrations) and habitat factors (e.g., sediment substrates and macrophyte biomass) as indicated by Random Forests regression, but the major drivers of macroinvertebrate density differed among the three lake zones at the temporal scale. Moreover, our findings suggest that benthic invertebrates were more sensitive to the improvement of the lake's environmental conditions than the pelagic community was. This study provides insights into the responses of macroinvertebrates to ecological dynamics in lakes and highlights the importance of continued monitoring for tracking long-term changes.

Response of zooplankton to nutrient reduction and enhanced fish predation in a shallow eutrophic lake.

As a key link between top-down regulators and bottom-up factors, zooplankton responds sensitively to environmental variations and provides information on the ecological state of freshwater systems. Although the response of zooplankton to anthropogenic pressures and fluctuating natural conditions, such as nutrient loading and climate change, has been extensively examined, findings have varied markedly. The mechanistic basis for the correlation between environmental variability and the zooplankton community is still debated, particularly for subtropical eutrophic lakes. We used two methods to analyze physicochemical and selected biological variables derived from long-term monitoring of Lake Taihu, a subtropical shallow lake in China. We first applied random forest regression to examine how changes in zooplankton were related to a set of environmental variables on interannual time scales. Then we used the results to guide the construction of a conceptual model for piecewise structural equation modeling (pSEM) to quantify more precisely the zooplankton-environment relationship. Zooplanktivorous fish and nutrient concentrations were the most important predictors of long-term trends in zooplankton in RF regression. Intensification of planktivorous fish predation led to a lower zooplankton biomass and smaller individuals through the removal of larger crustaceans. Moreover, suppression of zooplankton can in part be explained by increases in inedible algae, triggered by a combination of reduced nutrient concentrations and weakened grazer control. These results were also confirmed in the pSEM, which further indicated that top-down regulators might be more important than bottom-up factors for the zooplankton community in Lake Taihu. Our results suggest that stocking of filter-feeding fish in the lake did not meet the expectation that they would control algae, but that the use of biomanipulation measures considering both water quality and fishery management seems promising. This study offers insights into how indicator metrics of zooplankton can improve our understanding of the associations between plankton communities and ecosystem alterations.

Transcriptome profiling reveals toxicity mechanisms following sertraline exposure in the brain of juvenile zebrafish (Danio rerio).

Sertraline (SER) is one of the most commonly detected antidepressants in the aquatic environment that can negatively affect aquatic organisms at low concentrations. Despite some knowledge on its acute toxicity to fish, the effects of chronic SER exposure remain poorly understood along with any underlying mechanisms of SER-induced toxicity. To address this knowledge gap, the effects of chronic exposure to three SER concentrations from low to high were investigated in zebrafish. Juvenile zebrafish were exposed to three concentrations of 1, 10, or 100 µg/L of SER for 28 d, after which indicators of oxidative stress and neurotoxicity in the brain were measured. Superoxide dismutase (SOD) activity was significantly enhanced by SER at 1 up to 100 µg/L, and catalase (CAT) activity was significantly induced by SER at 1 or 10 µg/L. The activity of acetylcholinesterase (AChE) was significantly induced by 10 and 100 µg/L of SER, and the serotonin (5-HT) level was significantly increased by all three concentrations of SER. To ascertain mechanisms of SER-induced toxicity, transcriptomics was conducted in the brain of zebrafish following 100 µg/L SER exposure. The molecular signaling pathways connected with circadian system and the immune system were significantly altered in the zebrafish brain. Based on transcriptomic data, the expression levels of six circadian clock genes were measured, and three genes were significantly altered in relative abundance in fish from all experimental treatments with SER, including cryptochrome circadian regulator 2 (cry2), period circadian clock 2 (per2), and period circadian clock 3 (per3). We hypothesize that the circadian system may be related to SER-induced neurotoxicity and oxidative stress in the central nervous system. This study reveals potential mechanisms and key events (i.e., oxidative stress and neurotoxicity) associated with SER-induced toxicity, and improves understanding of the molecular and biochemical pathways putatively perturbed by SER.

Evaluating the effects of aquaculture on the freshwater lake from the perspective of plankton communities: The diversity, co-occurrence patterns and their underlying mechanisms.

Aquaculture has significant impacts on freshwater lakes, but plankton communities, as key components of the microbial food web, are rarely considered when assessing the impacts of aquaculture. Revealing the dynamics of plankton communities, including bacterioplankton, phytoplankton and zooplankton, under anthropological disturbances is critical for predicting the freshwater ecosystem functioning in response to future environmental changes. In the present study, we examined the impacts of aquaculture on water quality, plankton diversity and the co-occurrence patterns within plankton metacommunities in a shallow freshwater lake. The study zones are influenced by the 20-year historical intensive aquaculture, but now they are undergoing either ecological aquaculture or ecological restoration. Our results showed that ecological aquaculture was more efficient in nitrogen removal than ecological restoration. Moreover, lower bacterioplankton diversity but higher phytoplankton and zooplankton diversity were found in the ecological aquaculture and ecological restoration zones compared to the control zone. The lower network connectivity of the plankton metacommunities in the ecological aquaculture and ecological restoration zones indicated the decreasing complexity of potential microbial food web, suggesting a possible lower resistance of the plankton metacommunities to future disturbance. Furthermore, plankton communities of different trophic levels were driven under distinct mechanisms. The bacterioplankton community was primarily affected by abiotic factors, whereas the phytoplankton and zooplankton communities were explained more by trophic interactions. These results revealed the impacts of aquaculture on the plankton communities and their potential interactions, thereby providing fundamental information for better understanding the impacts of aquaculture on freshwater ecosystem functioning.