Polypharmacy, most often defined as the simultaneous consumption of five or more drugs at once, is a prevalent phenomenon in the older population. Some of these polypharmacies, deemed inappropriate, may be associated with adverse health outcomes such as death or hospitalization. Considering the combinatorial nature of the problem as well as the size of claims database and the cost to compute an exact association measure for a given drug combination, it is impossible to investigate every possible combination of drugs. Therefore, we propose to optimize the search for potentially inappropriate polypharmacies (PIPs). To this end, we propose the OptimNeuralTS strategy, based on Neural Thompson Sampling and differential evolution, to efficiently mine claims datasets and build a predictive model of the association between drug combinations and health outcomes. We benchmark our method using two datasets generated by an internally developed simulator of polypharmacy data containing 500 drugs and 100 000 distinct combinations. Empirically, our method can detect up to 33\% of PIPs while maintaining an average precision score of 99\% using 10 000 time steps.

The number of international benchmarking competitions is steadily increasing in various fields of machine learning (ML) research and practice. So far, however, little is known about the common practice as well as bottlenecks faced by the community in tackling the research questions posed. To shed light on the status quo of algorithm development in the specific field of biomedical imaging analysis, we designed an international survey that was issued to all participants of challenges conducted in conjunction with the IEEE ISBI 2021 and MICCAI 2021 conferences (80 competitions in total). The survey covered participants' expertise and working environments, their chosen strategies, as well as algorithm characteristics. A median of 72% challenge participants took part in the survey. According to our results, knowledge exchange was the primary incentive (70%) for participation, while the reception of prize money played only a minor role (16%). While a median of 80 working hours was spent on method development, a large portion of participants stated that they did not have enough time for method development (32%). 25% perceived the infrastructure to be a bottleneck. Overall, 94% of all solutions were deep learning-based. Of these, 84% were based on standard architectures. 43% of the respondents reported that the data samples (e.g., images) were too large to be processed at once. This was most commonly addressed by patch-based training (69%), downsampling (37%), and solving 3D analysis tasks as a series of 2D tasks. K-fold cross-validation on the training set was performed by only 37% of the participants and only 50% of the participants performed ensembling based on multiple identical models (61%) or heterogeneous models (39%). 48% of the respondents applied postprocessing steps.

Causal disentanglement seeks a representation of data involving latent variables that relate to one another via a causal model. A representation is identifiable if both the latent model and the transformation from latent to observed variables are unique. In this paper, we study observed variables that are a linear transformation of a linear latent causal model. Data from interventions are necessary for identifiability: if one latent variable is missing an intervention, we show that there exist distinct models that cannot be distinguished. Conversely, we show that a single intervention on each latent variable is sufficient for identifiability. Our proof uses a generalization of the RQ decomposition of a matrix that replaces the usual orthogonal and upper triangular conditions with analogues depending on a partial order on the rows of the matrix, with partial order determined by a latent causal model. We corroborate our theoretical results with a method for causal disentanglement that accurately recovers a latent causal model.

平行操纵器的配置歧管比串行操纵器表现出更多的非线性。从定性上讲，它们可以看到额外的褶皱。通过将这种歧管投射到工程相关性的空间上，例如输出工作区或输入执行器空间，这些折叠式的边缘呈现出表现非滑动行为的边缘。例如，在五杆链接的全局工作空间边界内显示了几个局部工作空间边界，这些边界仅限于该机制的某些输出模式。当专门研究这些投影而不是配置歧管本身时，这种边界的存在在输入和输出投影中都表现出来。特别是，非对称平行操纵器的设计已被其输入和输出空间中的外来投影所困扰。在本文中，我们用半径图表示配置空间，然后通过使用同型延续来量化传输质量来解决每个边缘。然后，我们采用图路径计划器来近似于避免传输质量区域的配置点之间的大地测量。我们的方法会自动生成能够在非邻居输出模式之间过渡的路径，该运动涉及示波多个工作空间边界（局部，全局或两者）。我们将技术应用于两个非对称五杆示例，这些示例表明如何通过切换输出模式来选择工作空间的传输属性和其他特征。

跨学科的一个重要问题是发现产生预期结果的干预措施。当可能的干预空间很大时，需要进行详尽的搜索，需要实验设计策略。在这种情况下，编码变量之间的因果关系以及因此对系统的影响，对于有效地确定理想的干预措施至关重要。我们开发了一种迭代因果方法来识别最佳干预措施，这是通过分布后平均值和所需目标平均值之间的差异来衡量的。我们制定了一种主动学习策略，该策略使用从不同干预措施中获得的样本来更新有关基本因果模型的信念，并确定对最佳干预措施最有用的样本，因此应在下一批中获得。该方法采用了因果模型的贝叶斯更新，并使用精心设计的，有因果关系的收购功能优先考虑干预措施。此采集函数以封闭形式进行评估，从而有效优化。理论上以信息理论界限和可证明的一致性结果在理论上基于理论上的算法。我们说明了综合数据和现实世界生物学数据的方法，即来自worturb-cite-seq实验的基因表达数据，以识别诱导特定细胞态过渡的最佳扰动；与几个基线相比，观察到所提出的因果方法可实现更好的样品效率。在这两种情况下，我们都认为因果知情的采集函数尤其优于现有标准，从而允许使用实验明显更少的最佳干预设计。

由多种因素引起的组织学图像的染色变化不仅是病理学家的视觉诊断，而且是细胞分割算法的挑战。为了消除颜色变化，已经提出了许多染色归一化方法。但是，大多数是为苏木精和曙红染色图像而设计的，并且在免疫组织化学染色图像上表现不佳。当前的细胞分割方法系统地将染色归一化作为预处理步骤，但是尚未定量研究颜色变化带来的影响。在本文中，我们制作了五组具有不同颜色的Neun染色图像。我们应用了一种深度学习的图像录制方法来在组织学图像组之间执行色彩转移。最后，我们改变了分割集的颜色，并量化了颜色变化对细胞分割的影响。结果证明了在后续分析之前必须进行颜色归一化的必要性。

在嘈杂和致密的荧光显微镜数据中跟踪胚胎的所有核是一项具有挑战性的任务。我们建立在最新的核跟踪方法的基础上，该方法结合了弱监督的学习，从一小部分核中心点注释与整数线性程序（ILP）结合了最佳的细胞谱系提取。我们的工作专门解决了秀丽隐杆线虫胚胎记录的以下具有挑战性的特性：（1）与其他生物的基准记录相比，许多细胞分裂以及（2）很容易被误认为是细胞核的极性体。为了应付（1），我们设计并纳入了学习的细胞分裂检测器。为了应付（2），我们采用了学到的极性身体探测器。我们进一步提出了通过结构化的SVM调整自动化的ILP权重，从而减轻了对各自的网格搜索进行乏味的手动设置的需求。我们的方法的表现优于Fluo-N3DH-CE胚胎数据集上细胞跟踪挑战的先前领导者。我们报告了另外两个秀丽隐杆线虫数据集的进一步广泛的定量评估。我们将公开这些数据集作为未来方法开发的扩展基准。我们的结果表明，我们的方法产生了可观的改进，尤其是在分区事件检测的正确性以及完全正确的轨道段的数量和长度方面。代码：https：//github.com/funkelab/linajea

图像注册可用于量化前列腺癌患者纵向MR图像的形态变化。本文描述了改善基于学习的注册算法的发展，对于这种挑战性的临床应用程序通常具有高度可变但有限的培训数据。首先，我们报告说，潜在空间可以聚集到一个比在经过训练的注册网络深层瓶颈特征的瓶颈特征中通常发现的尺寸空间要低得多。基于此观察结果，我们提出了一种层次量化方法，使用具有约束大小的共同训练的词典来离散学习的特征向量，以改善注册网络的概括。此外，在潜在的量化空间中，独立优化了一种新颖的协作词典，以合并其他先验信息，例如对腺体或其他感兴趣的区域的分割。根据来自86名前列腺癌患者的216张真实临床图像，我们显示了这两个组件的功效。从腺体上的骰子和相应地标的目标登记误差方面，获得了统计学意义的提高注册精度，后者的实现了5.46毫米，而没有量化的基线提高了28.7 \％。实验结果还表明，在训练数据和测试数据之间，性能的差异确实被最小化了。

学习异质治疗效果（HTE）是许多领域的重要问题。大多数现有方法都使用单个治疗组和单个结果指标来考虑设置。但是，在许多现实世界中，实验始终如一 - 例如，在互联网公司中，每天进行A/B测试，以衡量许多感兴趣的不同指标的潜在变化的影响。我们表明，即使一个分析师在一个实验中仅关心HTES来实现一个指标，也可以通过共同分析所有数据来利用交叉实验和交叉结果度量相关性来大大提高精度。我们在张量分解框架中对这个想法进行形式化，并提出了一个简单且可扩展的模型，我们称之为低级或LR-LR-LERNER。合成数据和实际数据的实验表明，LR-LEARNER可以比独立的HTE估计更精确。

In this review, we discuss approaches for learning causal structure from data, also called causal discovery. In particular, we focus on approaches for learning directed acyclic graphs (DAGs) and various generalizations which allow for some variables to be unobserved in the available data. We devote special attention to two fundamental combinatorial aspects of causal structure learning. First, we discuss the structure of the search space over causal graphs. Second, we discuss the structure of equivalence classes over causal graphs, i.e., sets of graphs which represent what can be learned from observational data alone, and how these equivalence classes can be refined by adding interventional data.