InClust+: the deep generative framework with mask modules for multimodal data integration, imputation, and cross-modal generation.

BACKGROUND: With the development of single-cell technology, many cell traits can be measured. Furthermore, the multi-omics profiling technology could jointly measure two or more traits in a single cell simultaneously. In order to process the various data accumulated rapidly, computational methods for multimodal data integration are needed. RESULTS: Here, we present inClust+, a deep generative framework for the multi-omics. It's built on previous inClust that is specific for transcriptome data, and augmented with two mask modules designed for multimodal data processing: an input-mask module in front of the encoder and an output-mask module behind the decoder. InClust+ was first used to integrate scRNA-seq and MERFISH data from similar cell populations, and to impute MERFISH data based on scRNA-seq data. Then, inClust+ was shown to have the capability to integrate the multimodal data (e.g. tri-modal data with gene expression, chromatin accessibility and protein abundance) with batch effect. Finally, inClust+ was used to integrate an unlabeled monomodal scRNA-seq dataset and two labeled multimodal CITE-seq datasets, transfer labels from CITE-seq datasets to scRNA-seq dataset, and generate the missing modality of protein abundance in monomodal scRNA-seq data. In the above examples, the performance of inClust+ is better than or comparable to the most recent tools in the corresponding task. CONCLUSIONS: The inClust+ is a suitable framework for handling multimodal data. Meanwhile, the successful implementation of mask in inClust+ means that it can be applied to other deep learning methods with similar encoder-decoder architecture to broaden the application scope of these models.

Engineering Streptomyces sp. CPCC 204095 for the targeted high-level production of isatropolone A by elucidating its pathway-specific regulatory mechanism.

BACKGROUND: Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs. RESULTS: Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield-980.8 mg/L of isatropolone A-achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date. CONCLUSION: In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.

Study of clinical traits and systemic immune inflammation index assessments in patients with endogenous endophthalmitis over the last ten years.

PURPOSE: The clinical aspects and prognosis of eyes with endogenous endophthalmitis were compared over the last ten years. The occurrence and progression of endophthalmitis are linked to the systemic immune inflammation index (SII) and clinical features. METHODS: The study comprised patients with endogenous endophthalmitis and 64 patients without endophthalmitis who were treated at Hebei Province Eye Hospital in the last ten years. According to the prognostic visual acuity, patients with endophthalmitis were split into two groups: Group A and Group B. Underlying disease (hypertension, diabetes, tuberculosis), infection risk (liver abscess, urinary tract infection, and recent abdominal surgery), signs and symptoms, and complete blood count were among the evaluation parameters (neutrophil count, lymphocyte count, monocyte count, platelet count, red blood cell distribution width). The NLR, PLR, MLR, and SII values were calculated. A nonparametric test was used to examine the clinical features and complete blood count results of patients in each group. To determine the parameters linked to endophthalmitis progression, researchers used principal component and ordinal logistic regression analyses. RESULTS: The study comprised a total of 25 eyes and 22 individuals with endogenous endophthalmitis. Infectious bacteria included Staphylococcus aureus, Micrococcus luteus, Staphylococcus hemolyticus, and so on. The visual acuity of the affected eye ranged from 2.7 (1.55, 2.7) LogMAR to 1.22 (0.6, 2.7) LogMAR during the 6-month to 8-year follow-up period. The neutrophil, monocyte, and PLT counts, NLR, PLR, and SII values and other markers were considerably higher in Groups A and B than in the control group. The likelihood model of the SII and sex, age, onset time, diabetes, hypertension, monocyte count, and red blood cell distribution was the best, and its increase was strongly connected with the occurrence and progression of endophthalmitis, according to ordinal regression analysis. CONCLUSION: Patients with endophthalmitis had significantly higher blood neutrophil, monocyte, and PLT counts and SII, NLR, PLR, and MLR values. The SII can be employed as a biomarker for predicting endophthalmitis severity and prognosis.

Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage of both eyes after COVID-19 infection: a case report.

BACKGROUND: Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage is commonly observed in myopia with tilted optic disc. It presents with typical features on the fundus and follows a self-limiting course. However, due to its complex etiology, clinicians sometimes lack sufficient understanding of it which can easily lead to misdiagnosis or overtreatment. In this case report, we describe a rare case of intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage in both eyes. CASE PRESENTATION: An 18-year-old female who has no past medical history experienced sudden black shadow blocking of her right eye in the right eye for the past 2 days after a 5-day history of COVID-19 infection. The best corrected visual acuity is 0.5 in the right eye and 0.6 in the left eye. Optical coherence tomography (OCT) showed tilted optic discs in both eyes, bulged nasal optic discs, and the presence of strong reflective material under the parafoveal retina of the optic discs. Fundus fluorescein angiography (FFA) showed subretinal fluorescence occlusion above and nasolateral to the optic disc in the right eye, with hypofluorescence below the optic disc; the subretinal below the optic disc was obscured by vitreous hemorrhage; hypofluorescence was seen in the optic disc region of the left eye.COVID-19 antigen was positive. The patient was in the early stage of the third COVID-19 infection when the disease occurred. We speculate that it may be related to it. After 5 months of conservative treatment, the patient's hemorrhage disappeared in both eyes and her best corrected visual acuity returned to normal. CONCLUSIONS: Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage usually occurs in myopia with tilted optic disc. In most patients, the cause of the bleeding is unknown, but it can gradually resolve under clinical observation or conservative treatment.

Effectiveness of a Biofeedback Intervention Targeting Mental and Physical Health Among College Students Through Speech and Physiology as Biomarkers Using Machine Learning: A Randomized Controlled Trial.

Biofeedback therapy is mainly based on the analysis of physiological features to improve an individual's affective state. There are insufficient objective indicators to assess symptom improvement after biofeedback. In addition to psychological and physiological features, speech features can precisely convey information about emotions. The use of speech features can improve the objectivity of psychiatric assessments. Therefore, biofeedback based on subjective symptom scales, objective speech, and physiological features to evaluate efficacy provides a new approach for early screening and treatment of emotional problems in college students. A 4-week, randomized, controlled, parallel biofeedback therapy study was conducted with college students with symptoms of anxiety or depression. Speech samples, physiological samples, and clinical symptoms were collected at baseline and at the end of treatment, and the extracted speech features and physiological features were used for between-group comparisons and correlation analyses between the biofeedback and wait-list groups. Based on the speech features with differences between the biofeedback intervention and wait-list groups, an artificial neural network was used to predict the therapeutic effect and response after biofeedback therapy. Through biofeedback therapy, improvements in depression (p = 0.001), anxiety (p = 0.001), insomnia (p = 0.013), and stress (p = 0.004) severity were observed in college-going students (n = 52). The speech and physiological features in the biofeedback group also changed significantly compared to the waitlist group (n = 52) and were related to the change in symptoms. The energy parameters and Mel-Frequency Cepstral Coefficients (MFCC) of speech features can predict whether biofeedback intervention effectively improves anxiety and insomnia symptoms and treatment response. The accuracy of the classification model built using the artificial neural network (ANN) for treatment response and non-response was approximately 60%. The results of this study provide valuable information about biofeedback in improving the mental health of college-going students. The study identified speech features, such as the energy parameters, and MFCC as more accurate and objective indicators for tracking biofeedback therapy response and predicting efficacy. Trial Registration ClinicalTrials.gov ChiCTR2100045542.

Development of Genome-Wide Intron Length Polymorphism (ILP) Markers in Tea Plant (Camellia sinensis) and Related Applications for Genetics Research.

The market value of tea is largely dependent on the tea species and cultivar. Therefore, it is important to develop efficient molecular markers covering the entire tea genome that can be used for the identification of tea varieties, marker-assisted breeding, and mapping important quantitative trait loci for beneficial traits. In this study, genome-wide molecular markers based on intron length polymorphism (ILP) were developed for tea trees. A total of 479, 1393, and 1342 tea ILP markers were identified using the PCR method in silico from the 'Shuchazao' scaffold genome, the chromosome-level genome of 'Longjing 43', and the ancient tea DASZ chromosome-level genome, respectively. A total of 230 tea ILP markers were used to amplify six tea tree species. Among these, 213 pairs of primers successfully characterize products in all six species, with 112 primer pairs exhibiting polymorphism. The polymorphism rate of primer pairs increased with the improvement in reference genome assembly quality level. The cross-species transferability analysis of 35 primer pairs of tea ILP markers showed an average amplification rate of 85.17% through 11 species in 6 families, with high transferability in Camellia reticulata and tobacco. We also used 40 pairs of tea ILP primers to evaluate the genetic diversity and population structure of C. tetracocca with 176 plants from Puan County, Guizhou Province, China. These genome-wide markers will be a valuable resource for genetic diversity analysis, marker-assisted breeding, and variety identification in tea, providing important information for the tea industry.

Radiomics nomograms based on R2* mapping and clinical biomarkers for staging of liver fibrosis in patients with chronic hepatitis B: a single-center retrospective study.

OBJECTIVES: To investigate the value of R2* mapping-based radiomics nomograms in staging liver fibrosis in patients with chronic hepatitis B. METHODS: Between January 2020 and December 2020, 151 patients with chronic hepatitis B were randomly divided into training (n = 103) and validation (n = 48) cohorts. From January to February 2021, 58 patients were included in a test cohort. Radiomics features were selected using the interclass correlation coefficient and least absolute shrinkage and selection operator method. Three radiomics nomograms, combining the radiomics score (Radscore) derived from R2* mapping and clinical variables, were used for staging significant and advanced fibrosis, and cirrhosis. Performance of the model was evaluated using the AUC. The utility and clinical benefits were evaluated using the continuous net reclassification index (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). RESULTS: The Radscore calculated by 12 radiomics features and independent factors (laminin and platelet) of advanced fibrosis were used to construct the radiomics nomograms. In the test cohort, the AUCs of the radiomics nomograms for staging significant fibrosis, advanced fibrosis, and cirrhosis were 0.738 (95% confidence interval [CI]: 0.604-0.872), 0.879 (95% CI: 0.779-0.98), and 0.952 (95% CI: 0.878-1), respectively. NRI, IDI, and DCA confirmed that radiomics nomograms demonstrated varying degrees of clinical benefit and improvement for advanced fibrosis and cirrhosis, but not for significant fibrosis. CONCLUSIONS: Radiomics nomograms combined with R2* mapping-based Radscore, laminin, and platelet have value in staging advanced fibrosis and cirrhosis but limited value for staging significant fibrosis. KEY POINTS: • Laminin and platelets were independent predictors of advanced fibrosis. • Radiomics analysis based on R2* mapping was beneficial for evaluating advanced fibrosis and cirrhosis. • It was difficult to distinguish significant fibrosis using a radiomics nomogram, which is possibly due to the complex pathological microenvironment of chronic liver diseases.

Dynamics of C(3P) + OH(X 2Π) reaction on the new global HCO(X2A') potential energy surface.

A precise analytical potential energy surface (PES) of HCO(X2A') is fitted from a great quantity of ab initio energy points computed with the multi-reference configuration interaction method and aug-cc-pV(Q/5)Z basis sets. The whole energy points extrapolated to the complete basis set limit are fitted by the many-body expansion formula. The calculated topographic characteristics are analyzed and compared with the existing work to prove the precision of the present HCO(X2A') PES. By utilizing the time-dependent wave packet and quasi-classical trajectory methods, the reaction probabilities, integral cross sections, and rate constants are computed. The results are compared in detail with the former results carried out on the other PES. Moreover, the provided information on stereodynamics leads to an in-depth understanding of the role of collision energy in product distribution.

A study on the rapid diagnosis of chronic heart failure by measuring the difference in pulse oxygen saturation before and after arm compression.

BACKGROUND: Clinically, the pulse oxygen saturation of patients with chronic heart failure does not decrease significantly, and the clinical manifestations of labor-related dyspnea are not typical. As such, it is difficult to make a rapid diagnosis. OBJECTIVE: To investigate changes in pulse oxygen saturation in patients with chronic heart failure and examine the relationship between B-type natriuretic peptide (BNP) and normal pulse oxygen saturation. METHODS: A total of 80 hospitalized patients with chronic heart failure and increased BNP were randomly selected as the study group; the family members of 60 patients without dyspnea were randomly selected as the control group. The researchers measured the value of pulse oxygen saturation before and after upper arm compression, calculating the difference and analyzing the correlation between this difference and BNP values. The data were statistically analyzed using the SPSS Statistics 17.0 program. RESULTS: The decrease in pulse oxygen saturation in the study group was greater than in the control group; the decrease in pulse oxygen saturation of patients with chronic heart failure positively correlated with BNP. CONCLUSION: The value of pulse oxygen saturation in patients with chronic heart failure decreased more than in the control group, and this difference positively correlated with BNP. The measurement of pulse oxygen saturation before and after upper arm compression is a simple and effective method for diagnosing and evaluating chronic heart failure.

CHARACTERIZATION OF MACULAR NEOVASCULARIZATION IN BIETTI CRYSTALLINE DYSTROPHY USING MULTIMODAL IMAGING MODALITIES.

PURPOSE: To characterize the clinical features of macular neovascularization (MNV) secondary to Bietti crystalline dystrophy. METHODS: The imaging data of 157 eyes in 79 patients with Bietti crystalline dystrophy were retrospectively reviewed. 12 individuals (19 eyes) were found to have MNVs. Multimodal retinal imaging was used to evaluate the features of MNVs and the primary chorioretinopathy. RESULTS: The MNV lesions were shown as typical type 2 MNVs with subretinal hyperreflective material (SHRM), and usually detected along the borders of the retinal pigment epithelium/choriocapillaris dropout. The active MNVs were noted in earlier stages of Bietti crystalline dystrophy, while the activity was observed to be reduced in advanced cases. On spectral domain optical coherence tomography, the outer retinal structures were demonstrated to be partially preserved above the SHRMs compared with the extensive atrophy contiguously. Fibrotic scaring of the MNVs was commonly observed and arteriolarization was usually shown within the scars. CONCLUSION: MNV was demonstrated to be a common complication secondary to Bietti crystalline dystrophy. The lesions were typical type 2 MNV of varied activities possibly associated with the degrees of the primary degeneration. Choriocapillaris hypoperfusion may participate in MNV development.

Stellate nonheritable idiopathic foveomacular retinoschisis in juveniles: case report.

BACKGROUND: Stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) is a rare type of retinoschisis with a spoke-like splitting that occurs in the outer plexus layer. We present a case of stellate nonhereditary idiopathic foveomacular retinoschisis in a juvenile, in which two eyes show different development trends and macular retinoschisis could be associated with mechanical force in the Henle fibre layer. The removal of mechanical force can partially restore vision. CASE PRESENTATION: A 14-year-old girl with bilateral SNIFR was diagnosed and followed up with spectral-domain optical coherence tomography (SD-OCT). During the two follow-up visits, vitreous adhesion was released in the left eye, and visual acuity improved. Neuroepithelial detachment was aggravated in the right eye, and visual acuity decreased. Therefore, vitrectomy was performed on the right eye. After surgery, the patient's retina was reattached, and her vision was partially restored. CONCLUSIONS: We reported a juvenile with bilateral SNIFR. Each of her eyes showed different development trends, so we adopted different treatment methods for each eye. Vitrectomy was performed on the patient to address progressive vision loss, which improved the patient's vision. It was further confirmed that the Henle layer of SNIFR patients was susceptible to posterior vitreous membrane adhesion.

Binding selectivity-dependent molecular mechanism of inhibitors towards CDK2 and CDK6 investigated by multiple short molecular dynamics and free energy landscapes.

Understanding selectivity-dependent molecular mechanism of inhibitors towards CDK2 over CDK6 is prominent for improving drug design towards the CDK family. Multiple short molecular dynamics (MD) simulations combined with MM-GBSA approach are adopted to investigate molecular mechanism on binding selectivity of inhibitors X64, X3A, and 4 AU to CDK2 and CDK6. The RMSF analysis and calculations of molecular surface areas indicate that local structural and global flexibility of CDK6 are stronger than that of CDK2. Based on dynamics cross-correlation maps (DCCMs), motion modes of CDK2 and CDK6 produce difference due to associations of X64, X3A, and 4 AU. The calculated binding free energies (BFEs) demonstrate that the compensation between binding enthalpy and entropy of X64, X34, and 4 AU is a key force driving selectivity of inhibitors towards CDK2 over CDK6. This work provides valuable information for designing highly selective inhibitors towards CDK2 and CDK6 and further promotes identification of efficient anticancer drugs in the future.

Changes in group counseling engagement and conflict and growth in emotional cultivation for children and adolescents.

Group climate is an important factor in group counseling and psychotherapy process and outcome research. The current investigation examined group climate changes (from early to late sessions) at the within-group (i.e., group members) and between-group (i.e., group-as-a-whole) levels in predicting changes in group members' emotional cultivation in group counseling. A total of 236 Taiwanese children and adolescents across 41 groups participated in this study. Members' ratings of group climate (i.e., engagement and conflict) were partitioned into within-group and between-group components, and polynomial regression with response surface analysis was used to examine the association between changes in group engagement and conflict (at the member- and group-level) from early to late group sessions on changes in emotional cultivation. Results supported the theoretical hypothesis that when a group-as-a-whole reported increasing engagement from early to late group sessions, relative to other groups (i.e., between-group effect), members of that group experienced greater growth in emotional cultivation. Results also indicated that group members reported greater growth in emotional cultivation when there was consistent and high engagement or consistent and low conflict from early to late group sessions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Characteristics and Outcomes of Electric Bicycle-Related Open-Globe Injuries in a Tertiary Hospital in North China.

BACKGROUND: The aim was to describe the characteristics and outcomes of patients treated for electric bicycle-related open-globe injuries (OGIs). METHODS: A retrospective chart review of all patients who presented with electric bicycle-related OGIs was performed at the Hebei Eye Hospital in North China between January 2012 and December 2018. Demographic data, injury type, presenting clinical examination findings, best-corrected visual acuity (BCVA), secondary ocular complications, necessary surgical procedures and long-term outcome data were recorded. RESULTS: Twenty-six patients with electric bicycle-related OGIs met the inclusion criteria and were enrolled in the study. Eighteen of the 26 patients (69.2%) were males. the average age of these patients was 44.0 years old. The injuries peaked in winter in the hour between 15:00 and 20:00. Among the patients, 23 (88.5%) were farm workers, 2 (7.7%) were industrial workers, 1 (3.8%) was student. The types of OGIs were 23 ruptures (88.5%), 3 penetrating injuries (11.5%). Data on zone of injuries included 1 zone I injuries (3.8%), 12 zone II injuries (46.2%), 13 zone III injuries (50.0%). Nine eyes (34.6%) had traumatic cataract, 24 eyes (92.3%) had vitreous hemorrhage, 20 eyes (79.9%) had retinal detachment, 19 eyes (73.1%) had choroidal detachment. Ten eyes (38.4%) had hand motion or worse vision at final follow-up. four eyes (15.4%) which had injuries involving all 3 zones resulted in enucleation or evisceration. With respect to BCVA, the initial BCVA was 2.7±0.3 and the final BCVA was 2.0±0.7, indicating that the patients' BCVA was significantly improved by surgery ( t =4.3, P <0.001). CONCLUSIONS: Electric bicycle-related OGIs may have severe consequences. Modern surgical techniques can increase the rate of globe salvage although final vision remains poor. Therefore, increased awareness, proposed policies and suggestions should focus on regulating the use of electric bicycles and reinforcing laws and regulations to improve safety and prevent injuries.

PNPLA3-I148M Variant Promotes the Progression of Liver Fibrosis by Inducing Mitochondrial Dysfunction.

Patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism (I148M) is strongly associated with non-alcoholic steatohepatitis and advanced fibrosis; however, the underlying mechanisms remain largely unknown. In this study, we investigated the effect of PNPLA3-I148M on the activation of hepatic stellate cell line LX-2 and the progression of liver fibrosis. Immunofluorescence staining and enzyme-linked immunosorbent assay were used to detect lipid accumulation. The expression levels of fibrosis, cholesterol metabolism, and mitochondria-related markers were measured via real-time PCR or western blotting. Electron microscopy was applied to analyze the ultrastructure of the mitochondria. Mitochondrial respiration was measured by a Seahorse XFe96 analyzer. PNPLA3-I148M significantly promoted intracellular free cholesterol aggregation in LX-2 cells by decreasing cholesterol efflux protein (ABCG1) expression; it subsequently induced mitochondrial dysfunction characterized by attenuated ATP production and mitochondrial membrane potential, elevated ROS levels, caused mitochondrial structural damage, altered the oxygen consumption rate, and decreased the expression of mitochondrial-function-related proteins. Our results demonstrated for the first time that PNPLA3-I148M causes mitochondrial dysfunction of LX-2 cells through the accumulation of free cholesterol, thereby promoting the activation of LX-2 cells and the development of liver fibrosis.

Deciphering Selectivity Mechanism of BRD9 and TAF1(2) toward Inhibitors Based on Multiple Short Molecular Dynamics Simulations and MM-GBSA Calculations.

BRD9 and TAF1(2) have been regarded as significant targets of drug design for clinically treating acute myeloid leukemia, malignancies, and inflammatory diseases. In this study, multiple short molecular dynamics simulations combined with the molecular mechanics generalized Born surface area method were employed to investigate the binding selectivity of three ligands, 67B, 67C, and 69G, to BRD9/TAF1(2) with IC50 values of 230/59 nM, 1400/46 nM, and 160/410 nM, respectively. The computed binding free energies from the MM-GBSA method displayed good correlations with that provided by the experimental data. The results indicate that the enthalpic contributions played a critical factor in the selectivity recognition of inhibitors toward BRD9 and TAF1(2), indicating that 67B and 67C could more favorably bind to TAF1(2) than BRD9, while 69G had better selectivity toward BRD9 over TAF1(2). In addition, the residue-based free energy decomposition approach was adopted to calculate the inhibitor-residue interaction spectrum, and the results determined the gatekeeper (Y106 in BRD9 and Y1589 in TAF1(2)) and lipophilic shelf (G43, F44, and F45 in BRD9 and W1526, P1527, and F1528 in TAF1(2)), which could be identified as hotspots for designing efficient selective inhibitors toward BRD9 and TAF1(2). This work is also expected to provide significant theoretical guidance and insightful molecular mechanisms for the rational designs of efficient selective inhibitors targeting BRD9 and TAF1(2).

scCapsNet-mask: an updated version of scCapsNet with extended applicability in functional analysis related to scRNA-seq data.

BACKGROUND: With the rapid accumulation of scRNA-seq data, more and more automatic cell type identification methods have been developed, especially those based on deep learning. Although these methods have reached relatively high prediction accuracy, many issues still exist. One is the interpretability. The second is how to deal with the non-standard test samples that are not encountered in the training process. RESULTS: Here we introduce scCapsNet-mask, an updated version of scCapsNet. The scCapsNet-mask provides a reasonable solution to the issues of interpretability and non-standard test samples. Firstly, the scCapsNet-mask utilizes a mask to ease the task of model interpretation in the original scCapsNet. The results show that scCapsNet-mask could constrain the coupling coefficients, and make a one-to-one correspondence between the primary capsules and type capsules. Secondly, the scCapsNet-mask can process non-standard samples more reasonably. In one example, the scCapsNet-mask was trained on the committed cells, and then tested on less differentiated cells as the non-standard samples. It could not only estimate the lineage bias of less differentiated cells, but also distinguish the development stages more accurately than traditional machine learning models. Therefore, the pseudo-temporal order of cells for each lineage could be established. Following these pseudo-temporal order, lineage specific genes exhibit a gradual increase expression pattern and stem cell associated genes exhibit a gradual decrease expression pattern. In another example, the scCapsNet-mask was trained on scRNA-seq data, and then used to assign cell type in spatial transcriptomics that may contain non-standard sample of doublets. The results show that the scCapsNet-mask not only restored the spatial map but also identified several non-standard samples of doublet. CONCLUSIONS: The scCapsNet-mask offers a suitable solution to the challenge of interpretability and non-standard test samples. By adding a mask, it has the advantages of automatic processing and easy interpretation compared with the original scCapsNet. In addition, the scCapsNet-mask could more accurately reflect the composition of non-standard test samples than traditional machine learning methods. Therefore, it can extend its applicability in functional analysis, such as fate bias prediction in less differentiated cells and cell type assignment in spatial transcriptomics.

Second fertility-sparing surgery and fertility-outcomes in patients with recurrent borderline ovarian tumors.

BACKGROUND: At the time of recurrence, many borderline ovarian tumor (BOT) patients are still young with fertility needs. The purpose of this study is to evaluate the reproductive outcomes and recurrence rate of second fertility-sparing surgery (FSS) in women with recurrent BOTs. METHODS: Seventy-eight women of childbearing age diagnosed with recurrent BOTs from November 2009 to 2020 whose primary treatment was FSS were included. RESULTS: The FIGO stage I disease accounted for 46.2% and serous BOT accounted for 87.2% in the study group. Forty-seven patients underwent second FSS, and the remaining 31 underwent radical surgery (RS). Seventeen patients relapsed again after second surgery, but no malignant transformation and tumor-associated deaths were reported. Compared to FIGO stage I, the FIGO stage III tumors were more likely to relapse, but there was no statistical difference in pregnancy rate among patients with different stages. In the second FSS group, recurrence rate was higher in patients who underwent oophorocystectomy compared to patients with unilateral salpingo-oophorectomy (USO), but the pregnancy rate was similar. There was no significant difference in postoperative recurrence risk between USO and RS. The recurrence rate was not associated with operative route (laparoscopy or laparotomy), or lymphadenectomy, or postoperative chemotherapy. Among the 32 patients who tried to conceive, the pregnancy rate was 46.9% and live birth rate was 81.3%. CONCLUSION: Unilateral salpingo-oophorectomy is a safe procedure for FIGO stage I recurrent BOT patients with fertility needs, and can achieve a high postoperative pregnancy rate and live birth rate.

Unpacking leader responsiveness effects of emotional cultivation groups: Using the variance partitioning method.

Theoretically, group leaders can play a significant role in contributing to the effectiveness of group counseling intervention. However, very few studies have examined the group leader's effects on the client-rated group counseling outcomes. We hypothesized that responsive group leaders who were caring, understanding, and respectful could serve as safe havens and secure bases to facilitate their group members' social and emotional cultivation. The current investigation examined the effects of leader responsiveness on group members' social-emotional cultivation (SEC). A total of 307 Taiwanese children and adolescent clients across 53 groups participated in an eight-session emotional cultivation group intervention. There were five time points of data collection (i.e., preintervention, third group session, sixth group session, postintervention, and a 4-week follow-up), and the variance partitioning method was used to partition longitudinal data into within-member, within-group, and between-group variance components. The results of hierarchical linear modeling revealed that the group leader's responsiveness significantly predicted group members' SEC at each of the three levels of analysis: Individual members had greater change in SEC when (a) they perceived higher leader responsiveness in a time period compared to the average rating of leader responsiveness across all time periods, (b) they perceived higher leader responsiveness compared to the average rating of leader responsiveness across all members in the same group, and (c) the group-as-a-whole perceived higher leader responsiveness than the average rating of leader responsiveness across all groups. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

[Noradrenaline modulates the spontaneous firing activities of Purkinje cells via α2-adrenergic receptor in mouse cerebellar cortex].

Cerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear. Therefore, in the present study, we examined the mechanism underlying the increasing effect of NA on SS firing of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods. GABAA receptor was blocked by 100 µmol/L picrotoxin in the whole process. In vivo results showed that NA significantly reduced the number of spikelets of spontaneous CS and enhanced the discharge frequency of SS, but did not affect the discharge frequency of CS. In vitro experiments showed that NA reduced the number of CS spikelets and after hyperpolarization potential (AHP) induced by electrical stimulation, and increased the discharge frequency of SS. NA also reduced the amplitude of excitatory postsynaptic current (EPSC) of parallel fiber (PF)-PC and significantly increased the paired-pulse ratio (PPR). Application of yohimbine, an antagonist of α2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The α2-AR agonist, UK14304, also increased the frequency of SS. The ß-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABAA receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating α2-AR, inhibit CS activity and reduce AHP, thus enhancing the SS discharge frequency of PC. This result suggests that NA neurons of locus coeruleus can finely regulate PC signal output by regulating CF-PC synaptic transmission.