Miracle-dz/UniFAR-FTUs huggingface dataset:
Deriving Temporal Prototypes from Saliency Map Clusters for the Analysis of Deep-Learning-based Facial Action Unit Classification

Reliably determining the emotional state of a person is a difficult task for both humans as well as machines. Automatic detection and evaluation of facial expressions is particularly important if people are unable to express their emotional state themselves, for example due to cognitive impairments. Identifying the presence of Action Units in a human’s face is a psychologically validated approach of quantifying which emotion is expressed. To automate the detection process of Action Units Neural Networks have been trained. However, the black-box nature of Deep Neural Networks provides no insight on the relevant features identified during the decision process. Approaches of Explainable Artificial Intelligence have to be applied to provide an explanation why the network came to a certain conclusion. In this work "Layer-Wise Relevance Propagation" (LRP) in combination with the meta analysis approach "Spectral Relevance Analysis" (SpRAy) is used to derive temporal prototypes from predictions in video sequences. Temporal prototypes provide an aggregated view on the prediction of the network by grouping together similar frames by considering relevance. Additionally, a specific visualization method for temporal prototypes is presented that highlights the most relevant areas for a prediction of an Action Unit. A quantitative evaluation of our approach shows that temporal prototypes aggregate temporal information well. The proposed method can be used to generate concise visual explanations for a sequence of interpretable saliency maps. Based on the above, this work shall provide the foundation for a new temporal analysis method as well as an explanation approach that is supposed to help researchers and experts to gain a deeper understanding of how the underlying network decides which Action Units are active in a particular emotional state.
Type- and Token-based Word Embeddings in the Digital Humanities

In the general perception of the NLP community, the new dynamic, context-sensitive, token-based embeddings from language models like BERT have replaced the older static, type-based embeddings like word2vec or fastText, due to their better performance. We can show that this is not the case for one area of applications for word embeddings: the abstract representation of the meaning of words in a corpus. This application is especially important for the Computational Humanities, for example in order to show the development of words or ideas. The main contribution of our papers are: 1) We offer a systematic comparison between dynamic and static embeddings in respect to word similarity. 2) We test the best method to convert token embeddings to type embeddings. 3) We contribute new evaluation datasets for word similarity in German. The main goal of our contribution is to make an evidence-based argument that research on static embeddings, which basically stopped after 2019, should be continued not only because it needs less computing power and smaller corpora, but also because for this specific set of applications their performance is on par with that of dynamic embeddings.
Towards Multimodal Computational Humanities. Using CLIP to Analyze Late-Nineteenth Century Magic Lantern Slides

The introduction of the CLIP model signaled a breakthrough in multimodal deep learning. This paper examines whether CLIP can be fruitfully applied to a (binary) classification task in the Humanities. We focus on a historical collection of late-nineteenth century magic lantern slides from the Lucerna database. Based on the available metadata, we evaluate CLIP’s performance on classifying slide images into ‘exterior’ and ‘interior’ categories. We compare the performance of several textual prompts for CLIP to two conventional mono-modal models (textual and visual) which we train and evaluate on the same stratified set of 5,244 magic lantern slides and their captions. We find that the textual and multimodal models achieve a respectable performance ( ∼ 0.80 accuracy) but are still outperformed by a vision model that was fine-tuned to the task ( ∼ 0.89). We flag three methodological issues that might arise from the application of CLIP in the (computational) humanities. First, the lack of (need for) labelled data makes it hard to inspect and/or interpret the performance of the model. Second, CLIP’s zero-shot capability only allows for classification tasks to be simulated, which makes it doubtful if standard metrics can be used to compare its performance to text and/or image models. Third, the lack of effective prompt engineering techniques makes the performance of CLIP (highly) unstable.
Geolocation and Named Entity Recognition in Ancient Texts: A Case Study about Ghewond's Armenian History

We present here a discussion about different methods to perform Named Entity Recognition tasks in order to extract geographic entities from the English translation of an Armenian text of the eighth century. Even though many tools are available and perform quite well with modern English, in this case they are only able to detect a very low percentage of the named geographic places. We compared four existing tools: NLTK and spaCy Python libraries, among the most used for NER tasks, TagMe, an entity linking tool that provide an annotation of found entities with Wikipedia pages, and Flair, a PyTorch library. We set these tools in order to select only geographical entities and we also tried two mixed methods: the best results on our data-set have been obtained by combining Flair and TagMe outputs with geographical clustering.
A Systematic Review of Brainstem Contributions to Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects one in 66 children in Canada. The contributions of changes in the cortex and cerebellum to autism have been studied for decades. However, our understanding of brainstem contributions has only started to emerge more recently. Disruptions of sensory processing, startle response, sensory filtering, sensorimotor gating, multisensory integration and sleep are all features of ASD and are processes in which the brainstem is involved. In addition, preliminary research into brainstem contribution emphasizes the importance of the developmental timeline rather than just the mature brainstem. Therefore, the purpose of this systematic review is to compile histological, behavioral, neuroimaging, and electrophysiological evidence from human and animal studies about brainstem contributions and their functional implications in autism. Moreover, due to the developmental nature of autism, the review pays attention to the atypical brainstem development and compares findings based on age. Overall, there is evidence of an important role of brainstem disruptions in ASD, but there is still the need to examine the brainstem across the life span, from infancy to adulthood which could lead the way for early diagnosis and possibly treatment of ASD.
P300 Event-Related Potentials Mediate the Relationship Between Child Physical Abuse and Externalizing Behavior

The psychophysiological mechanism linking early childhood experiences to behavior problems remains unclear. This study aimed to examine the association of child physical abuse with P300 event-related potentials (ERP), and to test the mediating effect of P300 amplitude and latency in the relationship between child physical abuse and externalizing behaviors. Cross-sectional secondary data were obtained from 155 children (55.5% boys, mean age: 11.28 ± 0.57 years) who participated in the China Jintan Child Cohort Study. Children self-reported maternal and paternal physical abuse and externalizing behaviors, as well as P300 were obtained in 2013. Additionally, parents and teachers reported child externalizing behaviors in preschool in 2007. P300 were recorded during a standard novel auditory oddball task. Path analysis shows that after controlling for child sex, socioeconomic status, area of residence, IQ, and child externalizing behavior in preschool, children exposed to maternal physical abuse exhibited increased novelty P300 amplitude, which links to more externalizing behavior. Novelty P300 amplitude partially mediated the relationship between maternal physical abuse and externalizing behavior. These findings are the first to document the partial mediating effect of P300 amplitude on the abuse-externalizing relationship and are consistent with the view that physical abuse affects the attention bias to novel cues that likely places them at increased risk for the development and maintenance of externalizing behavior.
Effects of SGLT2 Inhibitors on Renal Outcomes in Patients With Chronic Kidney Disease: A Meta-Analysis

Introduction: The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on renal outcomes in patients with chronic kidney disease (CKD) were initially demonstrated in recent trials. However, the magnitude of renal benefits for CKD patients with different baseline features and underlying diseases remains unclear. Method: We systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021 to identify eligible trials. The primary outcome was a composite of worsening kidney function, end-stage kidney disease (ESKD), or renal death. Efficacy and safety outcomes were stratified by baseline features, such as type 2 diabetes, heart failure, atherosclerotic cardiovascular disease, proteinuria, and renal function. Results: A total of nine studies were included. These studies included 25,749 patients with estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2 and 12,863 patients with urine albumin-to-creatinine ratio (UACR) >300 mg/g. SGLT2 inhibitors reduced the risk of the primary renal outcome by 30% in patients with eGFR<60 mL/min/1.73 m2 (HR 0.70, [95% CI 0.58–0.83], I2 = 0.00%) and by 43% in patients with UACR > 300 mg/g (HR 0.57, [95% CI 0.48–0.67], I2 = 16.59%). A similar benefit was observed in CKD patients with type 2 diabetes. SGLT2 inhibitors had no clear effects on renal outcomes in patients with eGFR<60 mL/min/1.73 m2 combined with atherosclerotic cardiovascular disease (HR 0.74, [95% CI 0.51–1.06], I2 = 0.00%). However, they reduced the risk of major renal outcomes by 46% (HR 0.54, [95% CI 0.38–0.76], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease and macroalbuminuria (defined as UACR > 300 mg/g). SGLT2 inhibitors did not significantly reduce the risk of major renal outcomes in CKD patients with heart failure (eGFR<60 mL/min/1.73 m2: HR 0.81, [95% CI 0.47–1.38], I2 = 0.00%; UACR > 300 mg/g: HR 0.66, [95% CI 0.41–1.07], I2 = 0.00%). SGLT2 inhibitors showed consistent renal benefits across different levels of eGFR (P interaction = 0.48). Conclusion: SGLT2 inhibitors significantly reduced the risk of the primary outcome in CKD patients. However, for patients with different features and underlying diseases, there exists differences in the renal protective effect.
Neonatal Isoflurane Does Not Affect Sleep Architecture and Minimally Alters Neuronal Beta Oscillations in Adolescent Rats

General anesthetics are neurotoxic to the developing rodent and primate brains leading to neurocognitive and socio-affective impairment later in life. In addition, sleep patterns are important predictors of cognitive outcomes. Yet, little is known about how anesthetics affect sleep-wake behaviors and their corresponding oscillations. Here we examine how neonatal general anesthesia affects sleep and wake behavior and associated neuronal oscillations. We exposed male and female rat pups to either 6 h of continuous isoflurane or sham anesthesia (compressed air) at the peak of their brain development (postnatal day 7). One cohort of animals was used to examine neurotoxic insult 2 h post-anesthesia exposure. At weaning age, a second cohort of rats was implanted with cortical electroencephalogram electrodes and allowed to recover. During adolescence, we measured sleep architecture (divided into wake, non-rapid eye movement, and rapid eye movement sleep) and electroencephalogram power spectra over a 24 h period. We found that exposure to neonatal isoflurane caused extensive neurotoxicity but did not disrupt sleep architecture in adolescent rats. However, these animals had a small but significant reduction in beta oscillations, specifically in the 12–20 Hz beta 1 range, associated with wake behavior. Furthermore, beta oscillations play a critical role in cortical development, cognitive processing, and homeostatic sleep drive. We speculate that dysregulation of beta oscillations may be implicated in cognitive and socio-affective outcomes associated with neonatal anesthesia.
Trends in Intracranial Glioma Incidence and Mortality in the United States, 1975-2018

Purpose Glioma incidence in the US seems to have stabilized over the past 20 years. It’s also not clear whether changes in glioblastoma incidence are associated with glioma mortality trends. Our study investigated trends in glioma incidence and mortality according to tumor characteristics. Methods This study obtained data from the Surveillance, Epidemiology, and End Results-9 (SEER-9) registries to calculate glioma incidence and mortality trends. Annual percent changes (APC) and 95% CIs were calculated using the Joinpoint program. Results 62,159 patients (34,996 males and 55,424 whites) were diagnosed with glioma during 1975-2018, and 31,922 deaths occurred from 1995-2018. Glioblastoma (32,893 cases) and non-glioblastoma astrocytoma (17,406 cases) were the most common histologic types. During the study period, the incidence of glioma first experienced a significant increase (APC=1.8%, [95% CI, 1.3% to 2.3%]) from 1975 to 1987, and then experienced a slight decrease (APC=-0.4%, [95% CI, -0.5% to -0.3%]) from 1987 to 2018, while the APC was 0.8% for glioblastoma, -2.0% for non-glioblastoma astrocytoma, 1.1% for oligodendroglial tumors, 0.7% for ependymoma and -0.3% for glioma NOS during the study period. Glioblastoma incidence increased for all tumor size and tumor extension except for distant. From 1995 to 2018, glioma mortality declined 0.4% per year (95% CI: -0.6% to -0.2%) but only increased in patients older than 80 years [APC=1.0%, (95% CI, 0.4% to 1.6%)]. Conclusion Significant decline in glioma incidence (1987-2018) and mortality (1995-2018) were observed. Epidemiological changes in non-glioblastoma astrocytoma contributed the most to overall trends in glioma incidence and mortality. These findings can improve understanding of risk factors and guide the focus of glioma therapy.
Dietary Modification for Reproductive Health in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Objective Diet has been reported as the first-line management of polycystic ovary syndrome (PCOS). However, the relationship between diet and fertility in PCOS is still controversial. This meta-analysis aimed to evaluate whether diet could promote reproductive health in women with PCOS while providing evidence-based nutrition advice for clinical practice. Methods Seven databases, including Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of Science, and some Chinese database, were searched up to January 31, 2021. Randomized controlled trials evaluating the effects of diet in women with PCOS were included. Based on a preregistered protocol (PROSPERO CRD42019140454), the systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Two reviewers made study selection, data extraction and bias assessment independently. Risk ratios and mean difference with 95% confidence intervals were assessed by a random-effects model. Statistical heterogeneity within comparisons was evaluated by Cochran’s Q test and quantified by the I-squared (I2 ) statistic. Results Twenty RCTs with 1113 participants were included. Results showed diet significantly related to improved fertility outcomes (increasing clinical pregnancy, ovulation and menstrual regularity rate; reducing miscarriage rate), reproductive endocrine [increasing sex hormone-binding globulin (SHBG); decreasing Anti-Müllerian Hormone (AMH), free androgen index (FAI), total testosterone (T)] and clinical hyperandrogenism (hirsutism assessed by Ferriman-Gallwey score) in PCOS. Specifically, subgroup analyses indicated low-carbohydrate diets were superior in optimizing reproductive outcomes and calorie restriction was critical in ameliorating hyperandrogenism. Additionally, the positive effects were associated with the treatment duration. The longer the duration, the greater the improvement was. Conclusion Overall, diet is an effective intervention for improving fertility health, thus professional and dynamic dietary advice should be offered to all PCOS patients, based on the changeable circumstances, personal needs and expectations of the individuals.
Lessons Learned from Discontinued Clinical Developments in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked condition caused by a deficiency of functional dystrophin protein. Patients experience progressive muscle weakness, cardiomyopathy and have a decreased life expectancy. Standards of care, including treatment with steroids, and multidisciplinary approaches have extended the life expectancy and improved the quality of life of patients. In the last 30 years, several compounds have been assessed in preclinical and clinical studies for their ability to restore functional dystrophin levels or to modify pathways involved in DMD pathophysiology. However, there is still an unmet need with regards to a disease-modifying treatment for DMD and the attrition rate between early-phase and late-phase clinical development remains high. Currently, there are 40 compounds in clinical development for DMD, including gene therapy and antisense oligonucleotides for exon skipping. Only five of them have received conditional approval in one jurisdiction subject to further proof of efficacy. In this review, we present data of another 16 compounds that failed to complete clinical development, despite positive results in early phases of development in some cases. We examine the reasons for the high attrition rate and we suggest solutions to avoid similar mistakes in the future.
Immune Checkpoint Inhibitor and Radiotherapy-Related Pneumonitis: An Informatics Approach to Determine Real-World Incidence, Severity, Management, and Resource Implications

Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials. Similarly, there is a dearth of information on cost impact of symptomatic pneumonitis. Informatics approaches are increasingly being applied to healthcare data for their ability to identify specific patient cohorts efficiently, at scale. We developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT report text to identify cases of ICI and radiotherapy pneumonitis between 1/1/2015 and 31/12/2020. Further data on severity, investigations, medical management were also acquired from the electronic health record. We identified 248 cases of pneumonitis attributable to ICI and/or radiotherapy, of which 139 were symptomatic with CTCAE severity grade 2 or more. The grade ≥2 ICI pneumonitis incidence in our cohort is 5.43%, greater than the all-grade 1.3–2.7% incidence reported in the literature. Time to onset of ICI pneumonitis was also longer in our cohort (mean 4.5 months, range 4 days-21 months), compared to the median 2.7 months (range 9 days−19.2 months) described in the literature. The estimated average healthcare cost of symptomatic pneumonitis is £3932.33 per patient. In this study we use an informatics approach to present new real-world data on the incidence, severity, management, and resource burden of ICI and radiotherapy pneumonitis. To our knowledge, this is the first study to look at real-world incidence and healthcare resource utilisation at the per-patient level in a UK cancer hospital. Improved management of pneumonitis may facilitate prompt continuation of cancer therapy, and improved outcomes for this not insubstantial cohort of patients.
Stimulation of the PD-1 Pathway Decreases Atherosclerotic Lesion Development in Ldlr Deficient Mice

Aim: Signaling through the coinhibitory programmed death (PD)-1/PD-L1 pathway regulates T cell responses and can inhibit ongoing immune responses. Inflammation is a key process in the development of atherosclerosis, the underlying cause for the majority of cardiovascular diseases. Dampening the excessive immune response that occurs during atherosclerosis progression by promoting PD-1/PD-L1 signaling may have a high therapeutic potential to limit disease burden. In this study we therefore aimed to assess whether an agonistic PD-1 antibody can diminish atherosclerosis development. Methods and Results: Ldlr−/− mice were fed a western-type diet (WTD) while receiving 100 μg of an agonistic PD-1 antibody or control vehicle twice a week. Stimulation of the PD-1 pathway delayed the WTD-induced monocyte increase in the circulation up to 3 weeks and reduced T cell activation and proliferation. CD4+ T cell numbers in the atherosclerotic plaque were reduced upon PD-1 treatment. More specifically, we observed a 23% decrease in atherogenic IFNγ-producing splenic CD4+ T cells and a 20% decrease in cytotoxic CD8+ T cells, whereas atheroprotective IL-10 producing CD4+ T cells were increased with 47%. Furthermore, we found an increase in regulatory B cells, B1 cells and associated atheroprotective circulating oxLDL-specific IgM levels in agonistic PD-1-treated mice. This dampened immune activation following agonistic PD-1 treatment resulted in reduced atherosclerosis development (p < 0.05). Conclusions: Our data show that stimulation of the coinhibitory PD-1 pathway inhibits atherosclerosis development by modulation of T- and B cell responses. These data support stimulation of coinhibitory pathways as a potential therapeutic strategy to combat atherosclerosis.