The wooden artifacts from Schöningen's Spear Horizon and their place in human evolution.

Ethnographic records show that wooden tools played a pivotal role in the daily lives of hunter-gatherers including food procurement tools used in hunting (e.g., spears, throwing sticks) and gathering (e.g. digging sticks, bark peelers), as well as, domestic tools (e.g., handles, vessels). However, wood rarely survives in the archeological record, especially in Pleistocene contexts and knowledge of prehistoric hunter-gatherer lifeways is strongly biased by the survivorship of more resilient materials such as lithics and bones. Consequently, very few Paleolithic sites have produced wooden artifacts and among them, the site of Schöningen stands out due to its number and variety of wooden tools. The recovery of complete wooden spears and throwing sticks at this 300,000-y-old site (MIS 9) led to a paradigm shift in the hunter vs. scavenger debate. For the first time and almost 30 y after their discovery, this study introduces the complete wooden assemblage from Schöningen 13 II-4 known as the Spear Horizon. In total, 187 wooden artifacts could be identified from the Spear Horizon demonstrating a broad spectrum of wood-working techniques, including the splitting technique. A minimum of 20 hunting weapons is now recognized and two newly identified artifact types comprise 35 tools made on split woods, which were likely used in domestic activities. Schöningen 13 II-4 represents the largest Pleistocene wooden artifact assemblage worldwide and demonstrates the key role woodworking had in human evolution. Finally, our results considerably change the interpretation of the Pleistocene lakeshore site of Schöningen.

Danish value sets for the EORTC QLU-C10D utility instrument.

PURPOSE: In this study, we developed Danish utility weights for the European Organisation for Research and Treatment of Cancer (EORTC) QLU-C10D, a cancer-specific utility instrument based on the EORTC QLQ-C30. METHODS: Following a standardized methodology, 1001 adult participants from the Danish general population were quota-sampled and completed a cross-sectional web-based survey and discrete choice experiment (DCE). In the DCE, participants considered 16 choice sets constructed from the key 10 dimensions of the QLU-C10D and chose their preferred health state for each one. Utility weights were calculated using conditional logistic regression with correction for non-monotonicity. RESULTS: The sample (n = 1001) was representative of the Danish general population with regard to age and gender. The domains with the largest utility decrements, i.e., the domains with the biggest impact on health utility, were physical functioning (- 0.224), pain (- 0.160), and role functioning (- 0.136). The smallest utility decrements were observed for the domains lack of appetite (- 0.024), sleep disorders (- 0.057), and fatigue (- 0.064). Non-monotonicity of severity levels was observed for the domains sleep disturbances, lack of appetite, and bowel problems. Deviations from monotonicity were not statistically significant. CONCLUSION: The EORTC QLU-C10D is a relatively new multi-attribute utility instrument and is a promising cancer-specific health technology assessment candidate measure. The country-specific Danish utility weights from this study can be used for cost-utility analyses in Danish patients and for comparison with other country-specific utility data.

International validation of two EORTC questionnaires for assessment of health-related quality of life for patients with high-grade non-Hodgkin lymphoma (QLQ-NHL-HG29) and low-grade non-Hodgkin lymphoma (QLQ-NHL-LG20).

BACKGROUND: Health-related quality of life (HRQOL) is a critical aspect to consider when making treatment decisions for patients with non-Hodgkin-lymphoma (NHL). This international study by the European Organisation for Research and Treatment of Cancer (EORTC) tested the psychometric properties of two newly developed measures for patients with high-grade (HG)- and low-grade (LG)-NHL: the EORTC QLQ-NHL-HG29 and the EORTC QLQ-NHL-LG20 to supplement the core questionnaire (EORTC QLQ-C30). METHODS: Overall, 768 patients with HG-NHL (N = 423) and LG-NHL (N = 345) from 12 countries completed the QLQ-C30, QLQ-NHL-HG29/QLQ-NHL-LG20 and a debriefing questionnaire at baseline, and a subset at follow-up for either retest (N = 125/124) or responsiveness to change (RCA; N = 98/49). RESULTS: Confirmatory factor analysis showed an acceptable to good fit of the 29 items of the QLQ-NHL-HG29 on its five scales (symptom burden [SB], neuropathy, physical condition/fatigue [PF], emotional impact [EI], and worries about health/functioning [WH]), and of the 20 items of the QLQ-NHL-LG20 on its four scales (SB, PF, EI, and WH). Completion took on average 10 minutes. Test-retest reliability, convergent validity, known-group comparisons, and RCA find satisfactory results of both measures. A total of 31%-78% of patients with HG-NHL and 22%-73% of patients with LG-NHL reported symptoms and/or worries (e.g., tingling in hands/feet, lack of energy, and worries about recurrence). Patients reporting symptoms/worries had substantially lower HRQOL compared to those without. DISCUSSION: The use of the EORTC QLQ-NHL-HG29 and QLQ-NHL-LG20 questionnaires in clinical research and practice will provide clinically relevant data to better inform treatment decision-making. PLAIN LANGUAGE SUMMARY: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group developed two questionnaires. These questionnaires measure health-related quality of life. The questionnaires are for patients with high-grade or low-grade non-Hodgkin lymphoma. They are called the EORTC QLQ-NHL-HG29 and QLQ-NHL-LG20. The questionnaires are now internationally validated. This study demonstrates that the questionnaires are reliably and valid, which are important aspects of a questionnaire. The questionnaires can now be used in clinical trials and practice. With the information gathered from the questionnaires, patients and clinicians can better evaluate treatments and discuss the best choice for a patient.

Disagreement between mothers' and fathers' rating of health-related quality of life in children with cancer.

PURPOSE: Serial assessment of health condition based on self-report made by children and their proxies has consistently shown a lack of congruence. The study explored the discrepancies between mother's, father's, and children's reports on health-related quality of life (HRQOL) during the first two months of pediatric cancer treatment. METHODS: In this cohort study, children and parents completed the generic and cancer-specific Pediatric Quality-of-Life Inventory (PedsQL) questionnaires at initial diagnosis and in the subsequent months. Evaluation of discrepancies included intraclass correlations between mother-child and father-child dyads at different domain levels. RESULTS: Thirty-six children with a diagnosis of cancer between May 2020 and November 2021 and their parents were included in this study. At diagnosis, mother-child dyads showed better agreement on more domains of the PedsQL Generic Core Scale than father-child dyads; moderate agreement persisted for both parents at subsequent time points on the physical domain. The disease-specific PedsQL Cancer Module revealed moderate and better agreement for mother-child dyads during active cancer therapy. In particular, agreement of mother-child dyads was pronounced for domains such as worry (0.77 [95% CI 0.52-0.89, P < 0.001]), whereas fathers tended to overestimate the child's symptom burden for most of the remaining domains of the PedsQL Cancer Module. CONCLUSION: This cohort study shows that both parent proxy reports can provide valid information on child's HRQOL, but that fathers tend to overestimate, particularly for non-observable domains. Proxy reports derived from mothers more closely agreed with children's HRQOL and might be more weighted, if there is uncertainty between parents.

Usability of Electronic Patient-Reported Outcome Measures for Older Patients With Cancer: Secondary Analysis of Data from an Observational Single Center Study.

BACKGROUND: Patient-reported outcomes are considered the gold standard for assessing subjective health status in oncology patients. Electronic assessment of patient-reported outcomes (ePRO) has become increasingly popular in recent years in both clinical trials and practice. However, there is limited evidence on how well older patients with cancer can complete ePRO assessments. OBJECTIVE: We aimed to investigate how well adult patients with cancer of different age ranges could complete ePRO assessments at home and in a treatment facility and to identify factors associated with the ability to complete questionnaires electronically. METHODS: This retrospective longitudinal single-center study involved survivors of cancer who participated in inpatient rehabilitation. Patients completed ePRO assessments before rehabilitation at home (T1) and after rehabilitation at the facility (T2). We analyzed the rate of patients who could complete the ePRO assessment at T1 and T2, the proportion of patients who required assistance, and the time it took patients to complete standardized questionnaires. Multivariate logistic regression analyses were conducted to identify predictors of ePRO completion rate and the need for assistance. RESULTS: Between 2017 and 2022, a total of 5571 patients were included in this study. Patients had a mean age of 60.3 (SD 12.2) years (range 18 to 93 years), and 1135 (20.3%) of them were classified as geriatric patients (>70 years). While more than 90% (5060/5571) of all patients completed the ePRO assessment, fewer patients in the age group of >70 years (924/1135, 81.4% at T1 vs 963/1135, 84.8% at T2) completed the assessment. Approximately 19% (1056/5571) of patients reported a need for assistance with the ePRO assessment at home, compared to 6.8% (304/4483) at the institution. Patients older than 70 years had a significantly higher need for assistance than those in younger age groups. Moreover, a gender difference was observed, with older women reporting a higher need for assistance than men (71-80 years: women requiring assistance 215/482, 44.6% vs men 96/350, 27.4%; P<.001 and >80 years: women 102/141, 72.3% vs men 57/112, 50.9%; P<.001). On average, patients needed 4.9 (SD 3.20) minutes to remotely complete a 30-item questionnaire (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire) and patients in the older age groups took significantly longer compared to younger age groups. Lower age and higher physical functioning were the clearest predictors for both the ePRO completion rate and the need for assistance in the multivariate regression analysis. CONCLUSIONS: This study's results indicate that ePRO assessment is feasible in older individuals with cancer, but older patients may require assistance (eg, from relatives) to complete home-based assessments. It may be more feasible to conduct assessments in-house in this population. Additionally, it is crucial to carefully consider which resources are necessary and available to support patients in using ePRO devices.

Adherence to Patient-Reported Symptom Monitoring and Subsequent Clinical Interventions for Patients With Multiple Myeloma in Outpatient Care: Longitudinal Observational Study.

BACKGROUND: The use of software to monitor patient-reported outcome measures (PROMs) can improve outcomes for patients with cancer receiving anticancer therapy; however, evidence from applications used in routine clinical practice is lacking. OBJECTIVE: We aimed to investigate adherence to and patient perceptions of a weekly, web-based PROM symptom monitoring program in routine clinical practice for patients with Multiple Myeloma. Moreover, we aimed to capture how clinical alerts prompted by the system influenced clinical care. METHODS: We conducted a single-center longitudinal observational study to evaluate patient adherence to and perceptions of the PROM monitoring software in routine practice. Patients with Multiple Myeloma remotely completed weekly treatment-specific PROMs to monitor key symptoms via a dedicated web-based platform. Alarming symptoms triggered clinical alerts in the application for the treatment team, which could initiate clinical interventions. The primary outcomes were the web-based assessment completion rate and patients' perceptions of the monitoring program, as assessed by an evaluation questionnaire. Moreover, clinical alerts prompted by the system and consequential clinical interventions were analyzed. RESULTS: Between July 2021 and June 2022, a total of 55 patients were approached for participation; 39 patients participated (24, 61% male, mean age 63.2, SD 9.2 years). The median assessment completion rate out of all weekly scheduled assessments was 70.3% (IQR 41.2%-89.6%). Most patients (77%) felt that the health care team was better informed about their health status due to the web-based assessments. Clinical alerts were triggered for 1758 of 14,639 (12%) reported symptoms. For 548 of 1758 (31.2%) alerts, the symptom had been registered before and no further action was required; for 348 of 1758 (19.9%) alerts, telephone consultation and self-management advice sufficed. Higher-level interventions were seldom needed in response to alerts: referral to a doctor or specialist (88/1758, 5% alerts), medication changes (22/1758, 1.3%), scheduling additional diagnostics (9/1758, 0.5%), or unplanned emergency visits (7/1758, 0.4%). Most patients (55%) reported the calls in response to alerts gave them "quite a bit" or "very much" of an added feeling of security during therapy. CONCLUSIONS: Our study shows that high adherence to regular and tailored PROM monitoring can be achieved in routine clinical care. The findings provide valuable insight into how the PROM monitoring program and the clinical alerts and resulting interventions shaped clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT05036863; https://clinicaltrials.gov/study/NCT05036863.

International validation of the EORTC QLQ-CLL17 questionnaire for assessment of health-related quality of life for patients with chronic lymphocytic leukaemia.

Selecting the most appropriate chronic lymphocytic leukaemia (CLL) treatment is challenging. Patient-reported health-related quality of life (HRQoL) is therefore a critical aspect to consider. This international study by the European Organization for Research and Treatment of Cancer (EORTC) tested the psychometric properties of a newly developed measure for CLL patients: the EORTC QLQ-CLL17 to supplement the core questionnaire (EORTC QLQ-C30). Patients with CLL (n = 341) from 12 countries completed the QLQ-C30, QLQ-CLL17 and a debriefing questionnaire. Sociodemographic and clinical data were recorded from medical records. A high percentage (30%-66%) reported symptoms and/or worries (e.g. aches/pains in muscles, lack of energy and worry/fears about health). Confirmatory factor analysis showed an acceptable to good fit of the 17 items on the three scales (i.e. symptom burden, physical condition/fatigue and worries/fears about health and functioning). Completion took on average 8 min. Test-retest and convergent validity was demonstrated. The QLQ-CLL17 differentiated between patients with an Eastern Cooperative Oncology group (ECOG) performance of 0 versus 1-3 (p's < 0.01 and clinically relevant). The newly developed EORTC QLQ-CLL17 will increase sensitivity of HRQoL assessment in patients with CLL. Implementation of this questionnaire both in clinical research and practice will help to generate unique clinically relevant data to better inform CLL treatment decision-making.

CLEP: a hybrid data- and knowledge-driven framework for generating patient representations.

SUMMARY: As machine learning and artificial intelligence increasingly attain a larger number of applications in the biomedical domain, at their core, their utility depends on the data used to train them. Due to the complexity and high dimensionality of biomedical data, there is a need for approaches that combine prior knowledge around known biological interactions with patient data. Here, we present CLinical Embedding of Patients (CLEP), a novel approach that generates new patient representations by leveraging both prior knowledge and patient-level data. First, given a patient-level dataset and a knowledge graph containing relations across features that can be mapped to the dataset, CLEP incorporates patients into the knowledge graph as new nodes connected to their most characteristic features. Next, CLEP employs knowledge graph embedding models to generate new patient representations that can ultimately be used for a variety of downstream tasks, ranging from clustering to classification. We demonstrate how using new patient representations generated by CLEP significantly improves performance in classifying between patients and healthy controls for a variety of machine learning models, as compared to the use of the original transcriptomics data. Furthermore, we also show how incorporating patients into a knowledge graph can foster the interpretation and identification of biological features characteristic of a specific disease or patient subgroup. Finally, we released CLEP as an open source Python package together with examples and documentation. AVAILABILITY AND IMPLEMENTATION: CLEP is available to the bioinformatics community as an open source Python package at https://github.com/hybrid-kg/clep under the Apache 2.0 License. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Usability evaluation of the Computer-Based Health Evaluation System (CHES) eDiary for patients with faecal incontinence: a pilot study.

BACKGROUND: Faecal incontinence (FI) is prevalent in 15-20% of elderly individuals and is frequently monitored in clinical trials and practice. Bowel diaries are the most common way to document FI, but, in clinical practice, are mainly used as paper-based versions. Electronic diaries (eDiaries) offer many potential benefits over paper-based diaries. The aim of this study was to develop and test an eDiary to document FI. METHODS: We migrated a paper FI diary to an eDiary app based on the Computer-based Health Evaluation System (CHES). To assess usability, we conducted functionality and usability tests at two time points in a sample of patients with FI. In the first assessment, the eDiary functionalities were tested, patients completed the System Usability Scale (SUS, range 0-100) and compared the paper diary with the eDiary. We set a threshold for minimum acceptable average usability at 70 points. Patients were then instructed to use the eDiary for 2 days at home and contacted to report on their usage and completed the SUS a second time. RESULTS: We recruited a sample of N = 14 patients to use the eDiary. All patients were able to use all functionalities of the eDiary and only a few patients with lower technological literacy or access to devices (n = 3) needed initial assistance. The mean usability rating given at the first time point was high with 88 points (SD 18, 95% CI 78.2-96.8) and most patients (n = 10) reported they would prefer the eDiary over the paper-based version. Nine patients (n = 9) participated in the follow-up assessment and the mean SUS rating at the second time point was 97 points (SD 7, 95% CI 92.8-100). CONCLUSION: The eDiary showed excellent usability scores for the assessment of FI at both assessments. Generally, patients preferred the eDiary over the paper-based version. We recommend the eDiary for usage with patients who own and use a smartphone and discuss potential solutions for patients with lower technological literacy or access.

The Attitude towards Polypills Questionnaire (APPQ): a phase I-III development and validation study in patients with cerebrovascular disease.

BACKGROUND AND PURPOSE: The polypill approach has been proposed to reduce patients' pill burden, increase medication adherence and lower stroke incidence. However, little is known about patients' attitudes towards polypills for cerebrovascular medication. METHODS: Based on the European Organization for Research and Treatment of Cancer Quality of Life Group questionnaire development guidelines, a questionnaire to measure patients' attitudes towards polypills for the secondary prevention of stroke (phase I-III) was developed. In phase I, issues were generated via literature review and interviews with patients and healthcare professionals. The issues were operationalized into items in phase II. In phase III the questionnaire was validated in a large single-centre sample, and test-retest and internal validity were evaluated. RESULTS: In phase I, 34 relevant issues were identified through literature search and interviews. Pre-testing the questionnaire indicated high applicability and comprehensibility. The final Attitudes towards Polypills Questionnaire was tested in N = 260 patients and showed a two-factor structure. The factors were labelled 'concerns' and 'benefits'. The scales showed acceptable and good internal validity (concerns, Cronbach's α = 0.85; benefits, α = 0.93), but the scales' test-retest validity was ambiguous. On a 0 to 3 rating scale, concerns were rated lower than benefits (mean 1.07, SD 0.69 vs. mean 1.87, SD 0.89). CONCLUSIONS: The Attitudes towards Polypills Questionnaire showed high comprehensibility and content validity to assess German language patients' attitudes towards a polypill medication. Our data and questionnaire may aid the implementation of polypill treatments in clinical practice and can be used in the design of future clinical trials on polypill therapy. Further validation of the questionnaire is advised.

Implementation of daily patient-reported outcome measurements to support children with cancer.

BACKGROUND: Several stakeholders, including patients and health care providers, suggest symptom self-reporting measurements for a more patient-directed cancer control approach. However, services tailored to measure daily reporting and implementing it in clinical care are lacking. This study aimed to evaluate the feasibility and value of daily patient-reported outcome measures (PROMs) by children receiving chemotherapy for cancer. METHODS: Health status was recorded daily with a web-based child-friendly patient portal (ePROtect). Following aspects of feasibility and usability were assessed: (a) the completion rate and time, (b) user feedback on usability and satisfaction, and (c) the performed interventions if moderate to severe symptom deterioration was noted. RESULTS: Twelve children (median age: 7.2 years) were included. A total number of 891 daily reports were collected during the study period; the median percentage of ePROtect completion days was 85.3% (interquartile range [IQR] 64.2-100.0) and 55.9% (IQR 51.9-76.9) for inpatient and outpatient stay, respectively. Mean time to complete the questionnaire was 47.6 seconds. Severe symptoms were reported in 14.7% of measurement time points, which led to prompt health care interventions in 57 cases, including extension of supportive care (n = 37) and pre-emptive inpatient admissions (n = 5). Over 80% of the patients (10/12) and their proxies (16/18) provided feedback with high rating for satisfaction (>90%) and usefulness (>80%) of ePROtect. CONCLUSION: Our study shows that daily symptom monitoring is feasible for all children with newly diagnosed cancer aged 5-18 years. Monitoring offers the opportunity to identify symptoms early and trigger appropriate clinical action.

Estimating seroprevalence of SARS-CoV-2 antibodies using three self-reported symptoms: development of a prediction model based on data from Ischgl, Austria.

We report the development of a regression model to predict the prevalence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) antibodies on a population level based on self-reported symptoms. We assessed participant-reported symptoms in the past 12 weeks, as well as the presence of SARS-CoV-2 antibodies during a study conducted in April 2020 in Ischgl, Austria. We conducted multivariate binary logistic regression to predict seroprevalence in the sample. Participants (n = 451) were on average 47.4 years old (s.d. 16.8) and 52.5% female. SARS-CoV-2 antibodies were found in n = 197 (43.7%) participants. In the multivariate analysis, three significant predictors were included and the odds ratios (OR) for the most predictive categories were cough (OR 3.34, CI 1.70-6.58), gustatory/olfactory alterations (OR 13.78, CI 5.90-32.17) and limb pain (OR 2.55, CI 1.20-6.50). The area under the receiver operating characteristic curve was 0.773 (95% CI 0.727-0.820). Our regression model may be used to estimate the seroprevalence on a population level and a web application is being developed to facilitate the use of the model.

Functional health and symptoms in Spain before and during the COVID-19 pandemic.

BACKGROUND: The impact of the coronavirus disease (COVID-19) pandemic on wellbeing and health has so far been studied using mostly cross-sectional designs. To place recent findings into context, we compared symptoms and functional health status in two independent samples assessed before and during the COVID-19 pandemic. METHODS: Participants were recruited via an online panel using quota sampling. We assessed symptoms, functional health, and global quality of life with the EORTC QLQ-C30 in two general population samples in Spain (collected in July 2019 and April 2020). We also assessed several COVID-19 related variables, such as adherence to social distancing. RESULTS: Data from N = 1010 participants before the pandemic (mean age 47.1 years, 50.5% female) were compared with data from N = 504 participants during the pandemic (mean age 47.1 years, 50.8% female). Participants during the pandemic (vs. before the pandemic) reported lower role functioning and emotional functioning, as well as less symptom burden. A lower degree of social distancing was associated with better functional health and lower symptom burden. CONCLUSION: Our findings indicate an impact of the COVID-19 pandemic on functional health and symptom burden in the Spanish general population. The comparison of before and during the pandemic can be used to benchmark results raised only during the pandemic.

Using the Computer-based Health Evaluation System (CHES) to Support Self-management of Symptoms and Functional Health: Evaluation of Hematological Patient Use of a Web-Based Patient Portal.

BACKGROUND: Patient portals offer the possibility to assess patient-reported outcome measures (PROMs) remotely, and first evidence has demonstrated their potential benefits. OBJECTIVE: In this study, we evaluated patient use of a web-based patient portal that provides patient information and allows online completion of PROMs. A particular focus was on patient motivation for (not) using the portal. The portal was developed to supplement routine monitoring at the Department of Internal Medicine V in Innsbruck. METHODS: We included patients with multiple myeloma and chronic lymphocytic leukemia who were already participating in routine monitoring at the hospital for use of the patient portal. Patients were introduced to the portal and asked to complete questionnaires prior to their next hospital visits. We used system access logs and 3 consecutive semistructured interviews to analyze patient use and evaluation of the portal. RESULTS: Between July 2017 and August 2020, we approached 122 patients for participation in the study, of whom 83.6% (102/122) consented to use the patient portal. Patients were on average 60 (SD 10.4) years old. Of patients providing data at all study time points, 37% (26/71) consistently used the portal prior to their hospital visits. The main reason for not completing PROMs was forgetting to do so in between visits (25/84, 29%). During an average session, patients viewed 5.3 different pages and spent 9.4 minutes logged on to the portal. Feedback from interviews was largely positive with no patients reporting difficulties navigating the survey and 50% of patients valuing the self-management tools provided in the portal. Regarding the portal content, patients were interested in reviewing their own results and reported high satisfaction with the dynamic self-management advice, also reflected in the high number of clicks on those pages. CONCLUSIONS: Patient portals can contribute to patient empowerment by offering sought-after information and self-management advice. In our study, the majority of our patients were open to using the portal. The low number of technical complaints and average time spent in the portal demonstrate the feasibility of our patient portal. While initial interest was high, long-term use was considerably lower and identified as the main area for improvement. In a next step, we will improve several aspects of the patient portal (eg, including a reminder to visit the portal before the next appointment and closer PROM symptom monitoring via an onconurse).

BioKEEN: a library for learning and evaluating biological knowledge graph embeddings.

SUMMARY: Knowledge graph embeddings (KGEs) have received significant attention in other domains due to their ability to predict links and create dense representations for graphs' nodes and edges. However, the software ecosystem for their application to bioinformatics remains limited and inaccessible for users without expertise in programing and machine learning. Therefore, we developed BioKEEN (Biological KnowlEdge EmbeddiNgs) and PyKEEN (Python KnowlEdge EmbeddiNgs) to facilitate their easy use through an interactive command line interface. Finally, we present a case study in which we used a novel biological pathway mapping resource to predict links that represent pathway crosstalks and hierarchies. AVAILABILITY AND IMPLEMENTATION: BioKEEN and PyKEEN are open source Python packages publicly available under the MIT License at https://github.com/SmartDataAnalytics/BioKEEN and https://github.com/SmartDataAnalytics/PyKEEN. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Normative data for the EORTC QLQ-C30 from the Austrian general population.

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is a widely used cancer-specific questionnaire assessing 15 domains of health-related quality of life (HRQoL). Our aim was to facilitate the interpretation of scores on this questionnaire by providing Austrian normative data based on a general population sample. METHODS: The calculation of normative data was based on the EORTC QLQ-C30 data collected from an Austrian general population sample that was part of an international online panel study on the development of European normative data. Data reported herein were stratified and weighted by age and sex. Normative data were calculated for all 15 HRQoL domains of the EORTC QLQ-C30. For precise predictions of EORTC QLQ-C30 scores, a regression model based on sex, age and the presence of health conditions was built. RESULTS: The Austrian sample comprised 1002 Austrian participants (50.1% female, 51.4% when weighted by age and sex based on United Nation statistics). The mean age was 53.7 years (weighted: 47.7 years) and 53.6% (weighted: 47.4%) reported at least one health condition. Men reported better physical (Cohen's d = 0.17) and emotional (Cohen's d = 0.17) functioning as well as less fatigue (Cohen's d = 0.18) and insomnia (Cohen's d = 0.25) compared with women. Younger individuals (< 40 years) reported less dyspnea (Cohen's d = 0.61) and pain (Cohen's d = 0.51), whereas older individuals (≥60 years) reported better emotional functioning (Cohen's d = 0.55). CONCLUSIONS: We present Austrian normative data for the EORTC QLQ-C30. Differences by age and sex are mostly in line with the findings of other European normative studies. The Austrian population sample shows higher HRQoL and lower morbidity compared with other European countries. The normative data in this study will facilitate the interpretation of EORTC QLQ-C30 scores in oncological practice and research at a national and international level (including cross-cultural comparisons).

Microtomography of the Baltic amber tick Ixodes succineus reveals affinities with the modern Asian disease vector Ixodes ovatus.

BACKGROUND: Fossil ticks are extremely rare and Ixodes succineus Weidner, 1964 from Eocene (ca. 44-49 Ma) Baltic amber is one of the oldest examples of a living hard tick genus (Ixodida: Ixodidae). Previous work suggested it was most closely related to the modern and widespread European sheep tick Ixodes ricinus (Linneaus, 1758). RESULTS: Restudy using phase contrast synchrotron x-ray tomography yielded images of exceptional quality. These confirm the fossil's referral to Ixodes Latreille, 1795, but the characters resolved here suggest instead affinities with the Asian subgenus Partipalpiger Hoogstraal et al., 1973 and its single living (and medically significant) species Ixodes ovatus Neumann, 1899. We redescribe the amber fossil here as Ixodes (Partipalpiger) succineus. CONCLUSIONS: Our data suggest that Ixodes ricinus is unlikely to be directly derived from Weidner's amber species, but instead reveals that the Partipalpiger lineage was originally more widely distributed across the northern hemisphere. The closeness of Ixodes (P.) succineus to a living vector of a wide range of pathogens offers the potential to correlate its spatial and temporal position (northern Europe, nearly 50 million years ago) with the estimated origination dates of various tick-borne diseases.

LogicENN: A Neural Based Knowledge Graphs Embedding Model With Logical Rules.

Knowledge graph embedding models have gained significant attention in AI research. The aim of knowledge graph embedding is to embed the graphs into a vector space in which the structure of the graph is preserved. Recent works have shown that the inclusion of background knowledge, such as logical rules, can improve the performance of embeddings in downstream machine learning tasks. However, so far, most existing models do not allow the inclusion of rules. We address the challenge of including rules and present a new neural based embedding model (LogicENN). We prove that LogicENN can learn every ground truth of encoded rules in a knowledge graph. To the best of our knowledge, this has not been proved so far for the neural based family of embedding models. Moreover, we derive formulae for the inclusion of various rules, including (anti-)symmetric, inverse, irreflexive and transitive, implication, composition, equivalence and negation. Our formulation allows to avoid grounding for implication and equivalence relations. Our experiments show that LogicENN outperforms the existing models in link prediction.

A double-pointed wooden throwing stick from Schöningen, Germany: Results and new insights from a multianalytical study.

The site of Schöningen (Germany), dated to ca. 300,000 years ago, yielded the earliest large-scale record of humanly-made wooden tools. These include wooden spears and shorter double-pointed sticks, discovered in association with herbivores that were hunted and butchered along a lakeshore. Wooden tools have not been systematically analysed to the same standard as other Palaeolithic technologies, such as lithic or bone tools. Our multianalytical study includes micro-CT scanning, 3-dimensional microscopy, and Fourier transform infrared spectroscopy, supporting a systematic technological and taphonomic analysis, thus setting a new standard for wooden tool analysis. In illustrating the biography of one of Schöningen's double-pointed sticks, we demonstrate new human behaviours for this time period, including sophisticated woodworking techniques. The hominins selected a spruce branch which they then debarked and shaped into an aerodynamic and ergonomic tool. They likely seasoned the wood to avoid cracking and warping. After a long period of use, it was probably lost while hunting, and was then rapidly buried in mud. Taphonomic alterations include damage from trampling, fungal attack, root damage and compression. Through our detailed analysis we show that Middle Pleistocene humans had a rich awareness of raw material properties, and possessed sophisticated woodworking skills. Alongside new detailed morphometrics of the object, an ethnographic review supports a primary function as a throwing stick for hunting, indicating potential hunting strategies and social contexts including for communal hunts involving children. The Schöningen throwing sticks may have been used to strategically disadvantage larger ungulates, potentially from distances of up to 30 metres. They also demonstrate that the hominins were technologically capable of capturing smaller fast prey and avian fauna, a behaviour evidenced at contemporaneous Middle Pleistocene archaeological sites.

Associations of Age and Sex with the Efficacy of Inpatient Cancer Rehabilitation: Results from a Longitudinal Observational Study Using Electronic Patient-Reported Outcomes.

Cancer rehabilitation is thought to increase the quality of life (QOL) and functioning of cancer survivors. It remains, however, uncertain whether subgroups benefit equally from rehabilitation. We wished to investigate the outcomes of multimodal rehabilitation according to age, sex and functioning. Patients of an Austrian rehabilitation center routinely completed the EORTC QLQ-C30 and the hospital anxiety and depression scale (HADS) questionnaires prior to (T1), and after rehabilitation (T2). To compare the outcomes between age groups (i.e., <40, 41-69, and ≥70 years), sex, and the Norton scale risk status, repeated measures of analyses of variance were calculated. A total of 5567 patients with an average age of 60.7 years were included, of which 62.7% were female. With T1 indicating the cancer survivors' needs, older and high-risk patients reported lower functioning (all p < 0.001) and a higher symptom burden for most scales (all p < 0.05) before rehabilitation. Regardless of age, sex or risk status, the patients showed at a least small to medium improvement during rehabilitation for anxiety, depression, and most functioning and symptom scales. Some between-group differences were observed, none of which being of a relevant effect size as determined with the Cohen's d. In conclusion, QOL is improved by rehabilitation in all patients groups, independently from age, sex, or the risk status.