Combining Automated Organoid Workflows with Artificial Intelligence-Based Analyses: Opportunities to Build a New Generation of Interdisciplinary High-Throughput Screens for Parkinson's Disease and Beyond

Parkinson's disease (PD) is the second most common neurodegenerative disease and primarily characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Despite decades of research and the development of various disease model systems, there is no curative treatment. This could be due to current model systems, including cell culture and animal models, not adequately recapitulating human PD etiology. More complex human disease models, including human midbrain organoids, are maturing technologies that increasingly enable the strategic incorporation of the missing components needed to model PD in vitro. The resulting organoid-based biological complexity provides new opportunities and challenges in data analysis of rich multimodal data sets. Emerging artificial intelligence (AI) capabilities can take advantage of large, broad data sets and even correlate results across disciplines. Current organoid technologies no longer lack the prerequisites for large-scale high-throughput screening (HTS) and can generate complex yet reproducible data suitable for AI-based data mining. We have recently developed a fully scalable and HTS-compatible workflow for the generation, maintenance, and analysis of three-dimensional (3D) microtissues mimicking key characteristics of the human midbrain (called “automated midbrain organoids,” AMOs). AMOs build a reproducible, scalable foundation for creating next-generation 3D models of human neural disease that can fuel mechanism-agnostic phenotypic drug discovery in human in vitro PD models and beyond. Here, we explore the opportunities and challenges resulting from the convergence of organoid HTS and AI-driven data analytics and outline potential future avenues toward the discovery of novel mechanisms and drugs in PD research. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society     

Exercise-based cardiac rehabilitation and parasympathetic function in patients with coronary artery disease: a systematic review and meta-analysis

Clinical Autonomic Research - The effects of exercise-based cardiac rehabilitation (CR) on parasympathetic modulation are controversial. This systematic review and meta-analysis aims to (a)...     

Activation of the NF-kB pathway downregulates TFF-1 in gastric carcinogenesis

Trefoil factor 1 (TFF1) is expressed in the normal superficial epithelium of the stomach and is implicated in the maintenance of gastric epithelial structure and function. During gastric carcinogenesis, in which pro-inflammatory cytokines play a crucial role, its expression level decreases suggesting a role as tumor suppressor factor. We have compared expression of TFF1 in gastric mucosa from cancer patients, in which several degrees of inflammatory infiltrate are present, with that in normal mucosa from non-cancer patients without infiltrating inflammatory cells. TFF1 is less expressed in the superficial gastric epithelium from cancer patients than in that from normal individuals in which the nuclear factor (NF)-κB pathway is not activated. We analyzed TFF1 expression in ex vivo samples of gastric mucosa from cancer patients, and in MKN45 gastric cancer cell line after exposure to proinflammatory cytokines interleukin (IL)-1β or tumor necrosis factor (TNF)-α, that activate the NF-κB pathway. We found that IL-1β and TNF-α activate the NF-κB pathway, as reflected in the nuclear expression of p65 and the activation of p-IκBα, and downregulate TFF1 expression after 1 or 2 h of exposure. Moreover, cells in the superficial gastric epithelium in ex vivo samples co-expressed TFF1/p65 at cellular level, whereas tumor cells did not. In summary, downregulation of TFF1 expression during gastric neoplastic transformation is associated with activation of the NF-κB pathway through IL-1β or TNF-α, but other regulatory mechanisms might also be involved.     

Correction to: Prenatal attachment: Using measurement invariance to test the validity of comparisons across eight culturally diverse countries

Archives of Women's Mental Health - A Correction to this paper has been published: https://doi.org/10.1007/s00737-021-01122-7     

The prevalence and incidence rate of pulmonary arterial hypertension in systemic sclerosis: Systematic review and meta-analysis

The present study aimed to assess the prevalence and incidence rate of pulmonary arterial hypertension (PAH) in Systemic Sclerosis (SSc). The review was undertaken using MEDLINE and SCOPUS from June 1962 to May 2019 and the terms: (“Scleroderma, Systemic”[MesH]) AND “Hypertension, Pulmonary”[MesH]. The Newcastle-Ottawa Scale (NOS) was used for the qualifying assessment. The inverse variance-weighted method was performed. Twenty-four studies were included in the global PAH prevalence study. They comprised data from 9804 SSc patients. The overall PAH prevalence found was 6.4% (95%CI 5%–8.3%). Fourteen studies were included in the PAH prevalence study for lcSSc. They comprised data from 4987 lcSSc patients. The PAH prevalence found in lcSSc was 7.7% (95%CI 5.3%–11.1%). Twelve studies were included in the PAH prevalence study for dcSSc. They comprised data from 1790 dcSSc patients. The PAH prevalence found in dcSSc was 6.3% (95%CI 4.5%–8.9%). Fifteen studies showed PAH incidence of an entire SSc cohort. They comprised data from 5926 SSc patients. The overall PAH incidence found was 18.2 cases per 1000 person-years (95%CI 12–27.4). Eight studies showed PAH incidence for lcSSc. They comprised data from 2721 patients. The overall PAH incidence found in lcSSc was 20.4 cases per 1000 person-years (95%CI 10.1–41.1). Seven studies showed PAH incidence for dcSSc. They comprised data from 942 dcSSc patients. The overall PAH incidence found in dcSSc was 16.6 cases per 1000 person-years (95%CI 8.5–32.1).ConclusionThe overall PAH prevalence found was 6.4% (95%CI 5%–8.3%) and the overall PAH incidence 18.2 cases per 1000 person-years (95%CI 12–27.4).     

Situating language in a minimal social context: how seeing a picture of the speaker’s face affects language comprehension

Natural use of language involves at least two individuals. Some studies have focused on the interaction between senders in communicative situations and how the knowledge about the speaker can bias language comprehension. However, the mere effect of a face as a social context on language processing remains unknown. In the present study, we used event-related potentials to investigate the semantic and morphosyntactic processing of speech in the presence of a photographic portrait of the speaker. In Experiment 1, we show that the N400, a component related to semantic comprehension, increased its amplitude when processed within this minimal social context compared to a scrambled face control condition. Hence, the semantic neural processing of speech is sensitive to the concomitant perception of a picture of the speaker’s face, even if irrelevant to the content of the sentences. Moreover, a late posterior negativity effect was found to the presentation of the speaker’s face compared to control stimuli. In contrast, in Experiment 2, we found that morphosyntactic processing, as reflected in left anterior negativity and P600 effects, is not notably affected by the presence of the speaker’s portrait. Overall, the present findings suggest that the mere presence of the speaker’s image seems to trigger a minimal communicative context, increasing processing resources for language comprehension at the semantic level.