julilili42/papers huggingface dataset:
Post-Hoc Explanations Fail to Achieve their Purpose in Adversarial Contexts
2022-06-20

Existing and planned legislation stipulates various obligations to provide\\ninformation about machine learning algorithms and their functioning, often\\ninterpreted as obligations to "explain". Many researchers suggest using\\npost-hoc explanation algorithms for this purpose. In this paper, we combine\\nlegal, philosophical and technical arguments to show that post-hoc explanation\\nalgorithms are unsuitable to achieve the law's objectives. Indeed, most\\nsituations where explanations are requested are adversarial, meaning that the\\nexplanation provider and receiver have opposing interests and incentives, so\\nthat the provider might manipulate the explanation for her own ends. We show\\nthat this fundamental conflict cannot be resolved because of the high degree of\\nambiguity of post-hoc explanations in realistic application scenarios. As a\\nconsequence, post-hoc explanation algorithms are unsuitable to achieve the\\ntransparency objectives inherent to the legal norms. Instead, there is a need\\nto more explicitly discuss the objectives underlying "explainability"\\nobligations as these can often be better achieved through other mechanisms.\\nThere is an urgent need for a more open and honest discussion regarding the\\npotential and limitations of post-hoc explanations in adversarial contexts, in\\nparticular in light of the current negotiations of the European Union's draft\\nArtificial Intelligence Act.\\n
Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies
2022-06-20

Abstract Background Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. Methods Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2–like, HER2-enriched–like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided. Results Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2–like, and HER2-enriched–like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity &amp;lt; .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity &amp;lt; .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like. Conclusions This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.
Fat Distribution Patterns and Future Type 2 Diabetes
2022-06-20

Fat accumulation in the liver, pancreas, skeletal muscle, and visceral bed relates to type 2 diabetes (T2D). However, the distribution of fat among these compartments is heterogenous and whether specific distribution patterns indicate high T2D risk is unclear. We therefore investigated fat distribution patterns and their link to future T2D. From 2,168 individuals without diabetes who underwent computed tomography in Japan, this case-cohort study included 658 randomly selected individuals and 146 incident cases of T2D over 6 years of follow-up. Using data-driven analysis (k-means) based on fat content in the liver, pancreas, muscle, and visceral bed, we identified four fat distribution clusters: hepatic steatosis, pancreatic steatosis, trunk myosteatosis, and steatopenia. In comparisons with the steatopenia cluster, the adjusted hazard ratios for incident T2D were 4.02 (95% CI 2.27–7.12) for the hepatic steatosis cluster, 3.38 (1.65–6.91) for the pancreatic steatosis cluster, and 1.95 (1.07–3.54) for the trunk myosteatosis cluster. The clusters were replicated in 319 German individuals without diabetes who underwent MRI and metabolic phenotyping. The distribution of the glucose area under the curve across the four clusters found in Germany was similar to the distribution of T2D risk across the four clusters in Japan. Insulin sensitivity and insulin secretion differed across the four clusters. Thus, we identified patterns of fat distribution with different T2D risks presumably due to differences in insulin sensitivity and insulin secretion.
German AI Start-Ups and “AI Ethics”: Using A Social Practice Lens for Assessing and Implementing Socio-Technical Innovation
2022-06-20

The current AI ethics discourse focuses on developing computational interpretations of ethical concerns, normative frameworks, and concepts for socio-technical innovation. There is less emphasis on understanding how AI practitioners themselves understand ethics and socially organize to operationalize ethical concerns. This is particularly true for AI start-ups, despite their significance as a conduit for the cultural production of innovation and progress, especially in the US and European context.
Multiple Social and Academic Achievement Goals: Students’ Goal Profiles and Their Linkages
2022-06-20

Students' engagement in class stems from academic and social motivations, which can be expressed through their academic and social achievement goals. Using a person-centered approach, we investigated the configurations of academic and social achievement goals and their relevance for aspects of students' academic (achievement, self-concept, goal structures) and social life (bullying, belonging). We relied on data from 1,759 Austrian secondary students. Latent profile analyses based on the students' academic mastery, performance-approach, and performance-avoidance goals as well as social development, social demonstration-approach, and social demonstration-avoidance goals were conducted. Relations to aspects of students' social and academic life were investigated through structural equation modeling. We identified five profiles that were each differentially associated with these variables: (a) weak pursuit of all goals, (b) strong mastery and development but weak performance and demonstration goals, (c) strong mastery and development but moderate performance and demonstration goals, (d) strong mastery and strong performance goals paired with strong social development, demonstration-approach, and demonstration-avoidance goals. Findings from additional variable-centered analyses indicated that while profile analyses are helpful to explain how academic and social goals are combined within individuals, researchers primarily interested in explaining differences in students' academic and social functioning might derive clearer results through variable-centered approaches.
Learning to Limit Data Collection via Scaling Laws: A Computational Interpretation for the Legal Principle of Data Minimization
2022-06-20

Modern machine learning systems are increasingly characterized by extensive personal data collection, despite the diminishing returns and increasing societal costs of such practices. Yet, data minimisation is one of the core data protection principles enshrined in the European Union's General Data Protection Regulation ('GDPR') and requires that only personal data that is adequate, relevant and limited to what is necessary is processed. However, the principle has seen limited adoption due to the lack of technical interpretation.
Predictors of post-stroke delirium incidence and duration: Results of a prospective observational study using high-frequency delirium screening
2022-06-20

Background: Post-stroke delirium (PSD) is a modifiable predictor for worse outcome in stroke. Knowledge of its risk factors would facilitate clinical management of affected patients, but recently updated national guidelines consider available evidence insufficient. Aims: The study aimed to establish risk factors for PSD incidence and duration using high-frequency screening. Methods: We prospectively investigated patients with ischemic stroke admitted within 24 h. Patients were screened twice daily for the presence of PSD throughout the treatment period. Sociodemographic, treatment-related, and neuroimaging characteristics were evaluated as predictors of either PSD incidence (odds ratios (OR)) or duration (PSD days/unit of the predictor, b), using logistic and linear regression models, respectively. Results: PSD occurred in 55/141 patients (age = 73.8 ± 10.4 years, 61 female, National Institutes of Health Stroke Scale (NIHSS) = 6.4 ± 6.5). Age (odds ratio (OR) = 1.06 (95% confidence interval (CI): 1.02–1.10), b = 0.08 (95% CI = 0.04–0.13)), and male gender ( b = 0.99 (95% CI = 0.05–1.93)) were significant non-modifiable risk factors. In a multivariable model adjusted for age and gender, presence of pain (OR &lt; sub &gt; mvar &lt;/sub &gt;= 1.75 (95% CI = 1.12–2.74)), urinary catheter (OR &lt; sub &gt; mvar &lt;/sub &gt; = 3.16 (95% CI = 1.10–9.14)) and post-stroke infection (PSI; OR &lt; sub &gt; mvar &lt;/sub &gt; = 4.43 (95% CI = 1.09–18.01)) were predictors of PSD incidence. PSD duration was impacted by presence of pain ( b &lt; sub &gt; mvar &lt;/sub &gt;= 0.49 (95% CI = 0.19–0.81)), urinary catheter ( b &lt; sub &gt; mvar &lt;/sub &gt; = 1.03 (95% CI = 0.01–2.07)), intravenous line ( b &lt; sub &gt; mvar &lt;/sub &gt;= 0.36 (95% CI = 0.16–0.57)), and PSI ( b &lt; sub &gt; mvar &lt;/sub &gt;= 1.60 (95% CI = 0.42–2.78)). PSD (OR = 3.53 (95% CI = 1.48–5.57)) and PSI (OR = 5.29 (95% CI = 2.92–7.66)) independently predicted inferior NIHSS at discharge. Insular and basal ganglia lesions increased the PSD risk about four- to eight-fold. Discussion/Conclusion: This study identified modifiable risk factors, the management of which might reduce the negative impact PSD has on outcome.
In Vivo Inhibition of TRPC6 by SH045 Attenuates Renal Fibrosis in a New Zealand Obese (NZO) Mouse Model of Metabolic Syndrome
2022-06-20

Metabolic syndrome is a significant worldwide public health challenge and is inextricably linked to adverse renal and cardiovascular outcomes. The inhibition of the transient receptor potential cation channel subfamily C member 6 (TRPC6) has been found to ameliorate renal outcomes in the unilateral ureteral obstruction (UUO) of accelerated renal fibrosis. Therefore, the pharmacological inhibition of TPRC6 could be a promising therapeutic intervention in the progressive tubulo-interstitial fibrosis in hypertension and metabolic syndrome. In the present study, we hypothesized that the novel selective TRPC6 inhibitor SH045 (larixyl N-methylcarbamate) ameliorates UUO-accelerated renal fibrosis in a New Zealand obese (NZO) mouse model, which is a polygenic model of metabolic syndrome. The in vivo inhibition of TRPC6 by SH045 markedly decreased the mRNA expression of pro-fibrotic markers (Col1α1, Col3α1, Col4α1, Acta2, Ccn2, Fn1) and chemokines (Cxcl1, Ccl5, Ccr2) in UUO kidneys of NZO mice compared to kidneys of vehicle-treated animals. Renal expressions of intercellular adhesion molecule 1 (ICAM-1) and α-smooth muscle actin (α-SMA) were diminished in SH045- versus vehicle-treated UUO mice. Furthermore, renal inflammatory cell infiltration (F4/80+ and CD4+) and tubulointerstitial fibrosis (Sirius red and fibronectin staining) were ameliorated in SH045-treated NZO mice. We conclude that the pharmacological inhibition of TRPC6 might be a promising antifibrotic therapeutic method to treat progressive tubulo-interstitial fibrosis in hypertension and metabolic syndrome.
Multicenter dose-escalation Phase I trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for appendiceal and colorectal peritoneal metastases: rationale and design
2022-06-20

Abstract Objectives Peritoneal metastasis (PM) from appendiceal cancer or colorectal cancer (CRC) has significant morbidity and limited survival. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a minimally invasive approach to treat PM. We aim to conduct a dose-escalation trial of mitomycin C (MMC)-PIPAC combined with systemic chemotherapy (FOLFIRI) in patients with PM from appendiceal cancer or CRC. Methods This is a multicenter Phase I study of MMC-PIPAC (NCT04329494). Inclusion criteria include treatment with at least 4 months of first- or second-line systemic chemotherapy with ineligibility for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Exclusion criteria are: progression on chemotherapy; extraperitoneal metastases; systemic chemotherapy intolerance; bowel obstruction; or poor performance status (ECOG&gt;2). Escalating MMC-PIPAC doses (7–25 mg/m 2 ) will be administered in combination with standard dose systemic FOLFIRI. Safety evaluation will be performed on 15 patients (dose escalation) and six expansion patients: 21 evaluable patients total. Results The primary endpoints are recommended MMC dose and safety of MMC-PIPAC with FOLFIRI. Secondary endpoints are assessment of response (by peritoneal regression grade score; Response Evaluation Criteria in Solid Tumors [RECIST 1.1], and peritoneal carcinomatosis index), progression free survival, overall survival, technical failure rate, surgical complications, conversion to curative-intent CRS-HIPEC, patient-reported outcomes, and functional status. Longitudinal blood and tissue specimens will be collected for translational correlatives including pharmacokinetics, circulating biomarkers, immune profiling, and single-cell transcriptomics. Conclusions This Phase I trial will establish the recommended dose of MMC-PIPAC in combination with FOLFIRI. Additionally, we expect to detect an early efficacy signal for further development of this therapeutic combination.
A Novel 2-Metagene Signature to Identify High-Risk HNSCC Patients amongst Those Who Are Clinically at Intermediate Risk and Are Treated with PORT
2022-06-20

(1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are biologically at high risk for the development of loco–regional recurrences after postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors may benefit from additional concurrent chemotherapy. In this matched-pair study, we aimed to identify a corresponding predictive gene signature. (2) Methods: Gene expression analysis was performed on a multicenter retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients who were treated with PORT alone. Propensity score analysis was used to identify matched patient pairs from both cohorts. From differential gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 matched patient pairs were selected. We identified a 2-metagene signature that stratified patients into risk groups in both cohorts. The comparison of the high-risk patients between the two types of treatment showed higher loco–regional control (LRC) after treatment with PORT-C (p &lt; 0.001), which was confirmed by a significant interaction term in Cox regression (p = 0.027), i.e., the 2-metagene signature was indicative for the type of treatment. (4) Conclusion: We have identified a novel gene signature that may be helpful to identify patients with high-risk HNSCC amongst those at intermediate clinical risk treated with PORT, who may benefit from additional concurrent chemotherapy.
Novel OPN1LW/OPN1MW Exon 3 Haplotype-Associated Splicing Defect in Patients with X-Linked Cone Dysfunction
2022-06-20

Certain combinations of common variants in exon 3 of OPN1LW and OPN1MW, the genes encoding the apo-protein of the long- and middle-wavelength sensitive cone photoreceptor visual pigments in humans, induce splicing defects and have been associated with dyschromatopsia and cone dysfunction syndromes. Here we report the identification of a novel exon 3 haplotype, G-C-G-A-T-T-G-G (referring to nucleotide variants at cDNA positions c.453, c.457, c.465, c.511, c.513, c.521, c.532, and c.538) deduced to encode a pigment with the amino acid residues L-I-V-V-A at positions p.153, p.171, p.174, p.178, and p.180, in OPN1LW or OPN1MW or both in a series of seven patients from four families with cone dysfunction. Applying minigene assays for all observed exon 3 haplotypes in the patients, we demonstrated that the novel exon 3 haplotype L-I-V-V-A induces a strong but incomplete splicing defect with 3–5% of residual correctly spliced transcripts. Minigene splicing outcomes were similar in HEK293 cells and the human retinoblastoma cell line WERI-Rb1, the latter retaining a cone photoreceptor expression profile including endogenous OPN1LW and OPN1MW gene expression. Patients carrying the novel L-I-V-V-A haplotype presented with a mild form of Blue Cone Monochromacy or Bornholm Eye Disease-like phenotype with reduced visual acuity, reduced cone electroretinography responses, red-green color vision defects, and frequently with severe myopia.
Following negative search instructions: the role of visual context
2022-06-20

Abstract One typical use of negation is to refer to exceptions. In a visual display showing several similar items (majority) and one exception, referring to the exception by negating the majority should therefore be pragmatically felicitous. We investigated whether comprehenders are sensitive to these pragmatic aspects when processing negative sentences and having to identify the according items in the visual display. In Experiment 1, participants read affirmative and negative sentences referring to either the exception or the majority object in strongly biased displays. Additionally, unbiased displays were implemented, showing equal numbers of objects of each type. Identification times of the correct referent were shorter with the biased display independent of sentence polarity. Also, picking the exceptional item in the biased display was faster than picking a majority item, independent of sentence polarity. Thus, participants did not specifically profit from pragmatically felicitous conditions when processing negation. Critically, in the biased displays, the exceptional object was highly salient, which might have initially drawn the participant’s attention to this object, resulting in a general speed-up. Therefore, in Experiment 2, we used a biased display with reduced saliency of the exceptional object. Again negation did not result in a specific speed-up due to pragmatically correct negation use. Thus, negation does not seem to facilitate the identification of an exceptional object.
Effect of orlistat during individualized comprehensive life-style intervention on visceral fat in overweight or obese PCOS patients
2022-06-20

<b>Objective</b>To investigate the effect of orlistat combined with drospirenone/ethinylestradiol tablets (DRSP/EE) on the visceral fat area (VFA) compared to DRSP/EE-alone in overweight or obese patients with polycystic ovary syndrome (PCOS).<b>Methods</b>90 PCOS patients [body mass index (BMI) ≥24kg/m<sup>2</sup>] were recruited for a prospective, open-label, 1:2 paired 3-monthly study. All were included during the per-protocol defined recruitment time and numbered according to the entry-order: group-1: No.1-60, orlistat plus DRSP/EE; group-2: No.61-90, DRSP/EE-alone. Both groups received the same comprehensive intervention in terms of individualized, standardized management and lifestyle monitoring such as diet and exercise. Primary study-endpoint was VFA, secondary endpoints were anthropometric indices, sex hormones and glucolipid metabolism. Within- and between-group analyses were performed.<b>Results</b>VFA [cm<sup>2</sup>] in group-1 after treatment decreased significantly (<i>p</i> = 0.001), and the between-group comparison was highly significant (<i>p =</i> 0.001). Body weight, hip circumference (HC), BMI, body fat (BF), free testosterone (FT) and low-density lipoprotein-cholesterol (LDL-C) significantly decreased in both groups (within-group analysis); the decrease in group-1 was significantly greater than in group-2 (<i>p</i> < 0.05). Systolic and diastolic blood pressure (SBP/DBP) and fasting plasma glucose (FPG) in group-1 were significantly decreased, significantly more in group-1 than in group-2 (<i>p</i> < 0.05).<b>Conclusion</b>This study is the first to investigate the effect of orlistat combined with DRSP/EE in overweight or obese PCOS patients compared with using DRSP/EE-alone. Orlistat combined with DRSP/EE was better than using DRSP/EE-alone in reducing VFA, body weight, FT, BP and FPG, which provides evidence for the choice of rational drug use in clinical practice.
The Sensorium competition on predicting large-scale mouse primary visual cortex activity
2022-06-20

The neural underpinning of the biological visual system is challenging to study experimentally, in particular as the neuronal activity becomes increasingly nonlinear with respect to visual input. Artificial neural networks (ANNs) can serve a variety of goals for improving our understanding of this complex system, not only serving as predictive digital twins of sensory cortex for novel hypothesis generation in silico, but also incorporating bio-inspired architectural motifs to progressively bridge the gap between biological and machine vision. The mouse has recently emerged as a popular model system to study visual information processing, but no standardized large-scale benchmark to identify state-of-the-art models of the mouse visual system has been established. To fill this gap, we propose the Sensorium benchmark competition. We collected a large-scale dataset from mouse primary visual cortex containing the responses of more than 28,000 neurons across seven mice stimulated with thousands of natural images, together with simultaneous behavioral measurements that include running speed, pupil dilation, and eye movements. The benchmark challenge will rank models based on predictive performance for neuronal responses on a held-out test set, and includes two tracks for model input limited to either stimulus only (Sensorium) or stimulus plus behavior (Sensorium+). We provide a starting kit to lower the barrier for entry, including tutorials, pre-trained baseline models, and APIs with one line commands for data loading and submission. We would like to see this as a starting point for regular challenges and data releases, and as a standard tool for measuring progress in large-scale neural system identification models of the mouse visual system and beyond.