UNASSIGNED: Revealing the role of anoikis resistance plays in CRC is significant for CRC diagnosis and treatment. This study integrated the CRC anoikis-related key genes (CRC-AKGs) and established a novel model for improving the efficiency and accuracy of the prognostic evaluation of CRC.
UNASSIGNED: CRC-ARGs were screened out by performing differential expression and univariate Cox analysis. CRC-AKGs were obtained through the LASSO machine learning algorithm and the LASSO Risk-Score was constructed to build a nomogram clinical prediction model combined with the clinical predictors. In parallel, this work developed a web-based dynamic nomogram to facilitate the generalization and practical application of our model.
UNASSIGNED: We identified 10 CRC-AKGs and a risk-related prognostic Risk-Score was calculated. Multivariate COX regression analysis indicated that the Risk-Score, TNM stage, and age were independent risk factors that significantly associated with the CRC prognosis(p < 0.05). A prognostic model was built to predict the outcome with satisfied accuracy (3-year AUC = 0.815) for CRC individuals. The web interactive nomogram (https://yuexiaozhang.shinyapps.io/anoikisCRC/) showed strong generalizability of our model. In parallel, a substantial correlation between tumor microenvironment and Risk-Score was discovered in the present work.
UNASSIGNED: This study reveals the potential role of anoikis in CRC and sets new insights into clinical decision-making in colorectal cancer based on both clinical and sequencing data. Also, the interactive tool provides researchers with a user-friendly interface to input relevant clinical variables and obtain personalized risk predictions or prognostic assessments based on our established model.

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A common research protocol in cognitive neuroscience is to train subjects to perform deliberately designed experiments while recording brain activity, with the aim of understanding the brain mechanisms underlying cognition. However, how the results of this protocol of research can be applied in technology is seldom discussed. Here, I review the studies on time processing of the brain as examples of this research protocol, as well as two main application areas of neuroscience (neuroengineering and brain-inspired artificial intelligence). Time processing is a fundamental dimension of cognition, and time is also an indispensable dimension of any real-world signal to be processed in technology. Therefore, one may expect that the studies of time processing in cognition profoundly influence brain-related technology. Surprisingly, I found that the results from cognitive studies on timing processing are hardly helpful in solving practical problems. This awkward situation may be due to the lack of generalizability of the results of cognitive studies, which are under well-controlled laboratory conditions, to real-life situations. This lack of generalizability may be rooted in the fundamental unknowability of the world (including cognition). Overall, this paper questions and criticizes the usefulness and prospect of the abovementioned research protocol of cognitive neuroscience. I then give three suggestions for future research. First, to improve the generalizability of research, it is better to study brain activity under real-life conditions instead of in well-controlled laboratory experiments. Second, to overcome the unknowability of the world, we can engineer an easily accessible surrogate of the object under investigation, so that we can predict the behavior of the object under investigation by experimenting on the surrogate. Third, the paper calls for technology-oriented research, with the aim of technology creation instead of knowledge discovery.

BACKGROUND: Deep learning has been increasingly investigated for assisting clinical in vitro fertilization (IVF). The first technical step in many tasks is to visually detect and locate sperm, oocytes, and embryos in images. For clinical deployment of such deep learning models, different clinics use different image acquisition hardware and different sample preprocessing protocols, raising the concern over whether the reported accuracy of a deep learning model by one clinic could be reproduced in another clinic. Here we aim to investigate the effect of each imaging factor on the generalizability of object detection models, using sperm analysis as a pilot example.
METHODS: Ablation studies were performed using state-of-the-art models for detecting human sperm to quantitatively assess how model precision (false-positive detection) and recall (missed detection) were affected by imaging magnification, imaging mode, and sample preprocessing protocols. The results led to the hypothesis that the richness of image acquisition conditions in a training dataset deterministically affects model generalizability. The hypothesis was tested by first enriching the training dataset with a wide range of imaging conditions, then validated through internal blind tests on new samples and external multi-center clinical validations.
RESULTS: Ablation experiments revealed that removing subsets of data from the training dataset significantly reduced model precision. Removing raw sample images from the training dataset caused the largest drop in model precision, whereas removing 20x images caused the largest drop in model recall. by incorporating different imaging and sample preprocessing conditions into a rich training dataset, the model achieved an intraclass correlation coefficient (ICC) of 0.97 (95% CI: 0.94-0.99) for precision, and an ICC of 0.97 (95% CI: 0.93-0.99) for recall. Multi-center clinical validation showed no significant differences in model precision or recall across different clinics and applications.
CONCLUSIONS: The results validated the hypothesis that the richness of data in the training dataset is a key factor impacting model generalizability. These findings highlight the importance of diversity in a training dataset for model evaluation and suggest that future deep learning models in andrology and reproductive medicine should incorporate comprehensive feature sets for enhanced generalizability across clinics.

Major depressive disorder (MDD) is a serious and heterogeneous psychiatric disorder that needs accurate diagnosis. Resting-state functional MRI (rsfMRI), which captures multiple perspectives on brain structure, function, and connectivity, is increasingly applied in the diagnosis and pathological research of MDD. Different machine learning algorithms are then developed to exploit the rich information in rsfMRI and discriminate MDD patients from normal controls. Despite recent advances reported, the MDD discrimination accuracy has room for further improvement. The generalizability and interpretability of the discrimination method are not sufficiently addressed either. Here, we propose a machine learning method (MFMC) for MDD discrimination by concatenating multiple features and stacking multiple classifiers. MFMC is tested on the REST-meta-MDD data set that contains 2428 subjects collected from 25 different sites. MFMC yields 96.9% MDD discrimination accuracy, demonstrating a significant improvement over existing methods. In addition, the generalizability of MFMC is validated by the good performance when the training and testing subjects are from independent sites. The use of XGBoost as the meta classifier allows us to probe the decision process of MFMC. We identify 13 feature values related to 9 brain regions including the posterior cingulate gyrus, superior frontal gyrus orbital part, and angular gyrus, which contribute most to the classification and also demonstrate significant differences at the group level. The use of these 13 feature values alone can reach 87% of MFMC\'s full performance when taking all feature values. These features may serve as clinically useful diagnostic and prognostic biomarkers for MDD in the future.

Three-dimensional lake hydrodynamic model is a powerful tool widely used to assess hydrological condition changes of lake. However, its computational cost becomes problematic when forecasting the state of large lakes or using high-resolution simulation in small-to-medium size lakes. One possible solution is to employ a data-driven emulator, such as a deep learning (DL) based emulator, to replace the original model for fast computing. However, existing DL-based emulators are often black-box and data-dependent models, causing poor interpretability and generalizability in practical applications. In this study, a data-driven emulator is established using deep neural network (DNN) to replace the original model for fast computing of three-dimensional lake hydrodynamics. Then, the Koopman operator and transfer learning (TL) are employed to enhance the interpretability and generalizability of the emulator. Finally, the generalizability of DL-based emulators is comprehensively analyzed through linear regression and correlation analysis. These methods are tested against an existing hydrodynamic model of Lake Zurich (Switzerland) whose data was provided by an open-source web-based platform called Meteolakes/Alplakes. According to the results, (1) The DLEDMD offers better interpretability than DNN because its Koopman operator reveals the linear structure behind the hydrodynamics; (2) The generalization of the DL-based emulators in three-dimensional lake hydrodynamics are influenced by the similarity between the training and testing data; (3) TL effectively improves the generalizability of the DL-based emulators.

Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity-variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity-estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs-indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis.

Collaborative efforts to directly replicate empirical studies in the medical and social sciences have revealed alarmingly low rates of replicability, a phenomenon dubbed the \'replication crisis\'. Poor replicability has spurred cultural changes targeted at improving reliability in these disciplines. Given the absence of equivalent replication projects in ecology and evolutionary biology, two inter-related indicators offer the opportunity to retrospectively assess replicability: publication bias and statistical power. This registered report assesses the prevalence and severity of small-study (i.e., smaller studies reporting larger effect sizes) and decline effects (i.e., effect sizes decreasing over time) across ecology and evolutionary biology using 87 meta-analyses comprising 4,250 primary studies and 17,638 effect sizes. Further, we estimate how publication bias might distort the estimation of effect sizes, statistical power, and errors in magnitude (Type M or exaggeration ratio) and sign (Type S). We show strong evidence for the pervasiveness of both small-study and decline effects in ecology and evolution. There was widespread prevalence of publication bias that resulted in meta-analytic means being over-estimated by (at least) 0.12 standard deviations. The prevalence of publication bias distorted confidence in meta-analytic results, with 66% of initially statistically significant meta-analytic means becoming non-significant after correcting for publication bias. Ecological and evolutionary studies consistently had low statistical power (15%) with a 4-fold exaggeration of effects on average (Type M error rates = 4.4). Notably, publication bias reduced power from 23% to 15% and increased type M error rates from 2.7 to 4.4 because it creates a non-random sample of effect size evidence. The sign errors of effect sizes (Type S error) increased from 5% to 8% because of publication bias. Our research provides clear evidence that many published ecological and evolutionary findings are inflated. Our results highlight the importance of designing high-power empirical studies (e.g., via collaborative team science), promoting and encouraging replication studies, testing and correcting for publication bias in meta-analyses, and adopting open and transparent research practices, such as (pre)registration, data- and code-sharing, and transparent reporting.

Objective. Mind-wandering is a mental phenomenon where the internal thought process disengages from the external environment periodically. In the current study, we trained EEG classifiers using convolutional neural networks (CNNs) to track mind-wandering across studies.Approach. We transformed the input from raw EEG to band-frequency information (power), single-trial ERP (stERP) patterns, and connectivity matrices between channels (based on inter-site phase clustering). We trained CNN models for each input type from each EEG channel as the input model for the meta-learner. To verify the generalizability, we used leave-N-participant-out cross-validations (N= 6) and tested the meta-learner on the data from an independent study for across-study predictions.Main results. The current results show limited generalizability across participants and tasks. Nevertheless, our meta-learner trained with the stERPs performed the best among the state-of-the-art neural networks. The mapping of each input model to the output of the meta-learner indicates the importance of each EEG channel.Significance. Our study makes the first attempt to train study-independent mind-wandering classifiers. The results indicate that this remains challenging. The stacking neural network design we used allows an easy inspection of channel importance and feature maps.

The spatial heterogeneity of landslide influencing factors is the main reason for the poor generalizability of the susceptibility evaluation model. This study aimed to construct a comprehensive explanatory framework for landslide susceptibility evaluation models based on the SHAP (SHapley Additive explanation)-XGBoost (eXtreme Gradient Boosting) algorithm, analyze the regional characteristics and spatial heterogeneity of landslide influencing factors, and discuss the heterogeneity of the generalizability of the models under different landscapes. Firstly, we selected different regions in typical mountainous hilly region and constructed a geospatial database containing 12 landslide influencing factors such as elevation, annual average rainfall, slope, lithology, and NDVI through field surveys, satellite images, and a literature review. Subsequently, the landslide susceptibility evaluation model was constructed based on the XGBoost algorithm and spatial database, and the prediction results of the landslide susceptibility evaluation model were explained based on regional topography, geology, and hydrology using the SHAP algorithm. Finally, the model was generalized and applied to regions with both similar and very different topography, geology, meteorology, and vegetation, to explore the spatial heterogeneity of the generalizability of the model. The following conclusions were drawn: the spatial distribution of landslides is heterogeneous and complex, and the contribution of each influencing factor on the occurrence of landslides has obvious regional characteristics and spatial heterogeneity. The generalizability of the landslide susceptibility evaluation model is spatially heterogeneous and has better generalizability to regions with similar regional characteristics. Further explanation of the XGBoost landslide susceptibility evaluation model using the SHAP method allows quantitative analysis of the differences in how much various factors contribute to disasters due to spatial heterogeneity, from the perspective of global and local evaluation units. In summary, the integrated explanatory framework based on the SHAP-XGBoost model can quantify the contribution of influencing factors on landslide occurrence at both global and local levels, which is conducive to the construction and improvement of the influencing factor system of landslide susceptibility in different regions. It can also provide a reference for predicting potential landslide hazard-prone areas and for Explainable Artificial Intelligence (XAI) research.