Development of deep learning applications for the automated extraction of chemical information from scientific literature

This dissertation focuses on developing deep learning applications for extracting chemical information from scientific literature, particularly targeting the automated recognition of molecular structures in images. DECIMER Segmentation, a novel application, employs a Mask Region-based Convolutional Neural Network (MRCNN) model to segment chemical structures in documents, aided by a mask expansion algorithm, marking a significant advancement in processing chemical literature. The Optical Chemical Structure Recognition (OCSR) tool DECIMER Image Transformer uses an encoder-decoder architecture to convert chemical structure depictions into the machine-readable SMILES format. The model has been trained on over 450 million pairs of images and SMILES representations. Its ability to interpret various depiction styles, including hand-drawn structures, sets a new standard in OCSR. To artificially generate large and diverse OCSR training datasets using multiple cheminformatics toolkits, RanDepict was developed. The diversification of training data ensures robust model generalisation across different chemical structure depictions. A unique dataset of hand-drawn molecule images was created to evaluate the model's performance in interpreting these challenging depictions. This dataset further contributes to the understanding of automated structure recognition from diverse styles. The integration of these technologies led to the creation of DECIMER.ai, an open-source web application that combines segmentation and interpretation tools, allowing users to extract and process chemical information from literature efficiently. The work concludes with a discussion on the significance of open data in advancing molecular informatics, highlighting the potential to broader chemical research domains. By adhering to FAIR data standards and open-source principles, the tools developed for this dissertation are designed for adaptability and future development within the community

Epistatic effects on carcass composition and meat quality in pigs

The analysis of epistasis is not yet a routine, but it has been shown by few studies in livestock animals that interaction effects contribute with considerable proportions to the phenotypic variance. Therefore the objective of this study was to evaluate the importance of epistatic effects in the Bonn Duroc × Pietrain resource population (DuPi) for carcass composition and meat quality traits. This population was investigated so far for single quantitative trait loci (QTL) considering additive, dominance and imprinting effects. In the first approach, 585 F2 pigs of DuPi were used to perform a two dimensional QTL scan. All animals were genotyped using 125 genetic markers (microsatellites and SNP) spread across the 18 pig autosomes. Phenotypic information for 26 carcass composition and meat quality traits was available for all F2 animals. Linkage analysis was performed in a two-step procedure using a maximum likelihood approach implemented in the QxPak program. A number of 56 interacting QTL was observed for 19 different traits. These interacting QTL pairs explained up to 8% of the phenotypic variance. Based on these results a variety of networks among chromosomal regions throughout the porcine genome were identified. Moreover, considering interactions between loci allowed to detect several novel QTL and trait-specific relationships of loci within and across chromosomes. In a second step the causes of an epistatic QTL pair between Sus scrofa chomsosome (SSC) 8 and 15 influencing pH value 1 h post mortem in M. long. dorsi were investigated. Gene expression data was obtained from loin tissue of 74 F2 which were selected from 585 animals. Gene expression profiles, genotypes and phenotypes of these pigs were investigated jointly applying three alternative models. Method A considered the phenotypic differences in pH values between groups of pigs with extreme values. Method B was based on differences between the genotype combinations of relevant epistatic QTL pairs between SSC8 and SSC15. Finally, method C was a linear model comprising the epistatic QTL genotypes as fixed effects. Overall method A, B and C revealed 1182, 480 and 1823 differentially expressed or associated genes, respectively. By means of a functional analysis it was possible to set up networks which contained mainly interactions between genes located within the specific regions on SSC8 and SSC15 and allowed a meaningful biological discussion. Expression QTL (eQTL) analyses were performed for functional and positional transcripts in order to assume regulations patterns. This approach showed that combining phenotype, genotype and transcriptome data helped to uncover the involved molecules of observed epistasis. In conclusion, this study revealed the importance of epistasis for the expression of complex traits. Furthermore, it was possible to uncover potential biological causes of observed epistatic QTL pairs applying different statistical models as well as bioinformatic tools.Epistatische Effekte auf die Schlachtkörperzusammensetzung und Fleischqualität beim Schwein Epistasie wird bisher nur selten in Untersuchungen komplexer Merkmale berücksichtigt. Dabei wurde bereits in einer Vielzahl von Studien gezeigt, dass die zu beobachtenden Variationen von quantitativen Merkmalen nicht alleine durch additive Effekte erklärt werden können. Daher war das Ziel dieser Studie, die Bedeutung von epistatischen Effekten auf Schlachtkörper- und Fleischqualitätsmerkmale innerhalb der Bonner Duroc × Piétain Ressourcenpopulation (DuPi) zu untersuchen. Bisherige Studien in der DuPi Population berücksichtigten nur einfache Quantitative Trait Loci (QTL), die additive, Dominanz oder Imprintingeffekte beinhalteten. In der ersten Analyse wurden 585 Schweine der F2-Generation verwendet um epistatische QTL Paare zu identifizieren. Diese Tiere sind mit 125 genetischen Markern genotypisiert worden, die sich gleichmäßig über alle 18 Autosomen verteilten. Als phänotypische Informationen wurden 26 verschiedene Schlachtkörper- und Fleischqualitätsmerkmale erfasst. Die Koppelungsanalyse wurde in einer zweistufigen Prozedur innerhalb des Programms Qxpak, basierend auf einem Maximum Likelihood Ansatzes, durchgeführt. Insgesamt konnten 56 interagierende QTL für 19 verschiedene Merkmale beobachtet werden. Für Schlachtkörpermerkmale konnten 17 und für Fleischqualitätsmerkmale 39 epistatische QTL Paare identifiziert werden. Diese interagierenden QTL Paare erklärten bis zu 8% der phänotypischen Varianz. Auf Grundlage dieser Ergebnisse konnten verschiedene Netzwerkstrukturen zwischen den verschiedenen Chromosomensegmenten identifiziert werden. Die Berücksichtigung der Beziehung zwischen zwei Genorten ermöglichte es einige neue QTL zu identifizieren, sowie merkmalsbezogene Beziehungen innerhalb eines Chromosoms und zwischen Chromosomen zu charakterisieren. In einer zweiten Untersuchung wurde versucht, die biologischen Gründe des epistatischen QTL Paares zwischen den porcinen Chromosomen (SSC) 8 und 15 aufzuklären. Für die Analyse standen die Muskeltranskriptionsprofile von 74 ausgewählten F2 Tieren der DuPi Population zur Verfügung. Die Interaktion zwischen SSC8 und 15 war assoziiert mit früh post mortalem pH Wert im M. long. dorsi. Genexpressionsprofile, Genotypen und Phänotypen dieser Tiere wurden mit drei verschiedenen statistischen Ansätzen und Modellen untersucht. Methode A berücksichtigte phänotypische Unterschiede des pH Wertes zwischen zwei Tiergruppen mit extremen Werten, Methode B basierte auf den Unterschieden zwischen den Genotypgruppen des relevanten epistatischen QTL Paares und Methode C berücksichtigte die Genotypen des epistatischen QTL Paares als fixen Effekt innerhalb eines linearen Modells. Insgesamt ließen sich mit Methode A, B und C 1182 und 480 unterschiedlich exprimierte Gene sowie 1823 linear assoziierte Gene identifizieren. Durch funktionale Analysen war es möglich Netzwerke zu erstellen, die nur Gene beinhalteten, die innerhalb der epistatischen Regionen lagen. Die daraus erzielten Ergebnisse erlaubten eine biologisch sinnvolle Diskussion möglicher Kandidatengene der epistatischen Regionen. Des Weiteren wurden Expressions-QTL Analysen durchgeführt um eine Aussage über die Genregulation zu treffen. Schlussfolgernd konnte gezeigt werden, dass Epistasie eine bedeutende Rolle bei der Ausprägung von komplexen Merkmalen beim Schwein hat. Es war des Weiteren möglich biologische Ursachen beobachteter epistatischer Beziehungen mit Hilfe verschiedener statistischer Methoden zu identifizieren

Acupuncture randomized trials (ART) in patients with chronic low back pain and osteoarthritis of the knee - Design and protocols

Background: We report on the study design and protocols of two randomized controlled trials (Acupuncture Randomized Trials = ART) that investigate the efficacy of acupuncture in the treatment of chronic low back pain and osteoarthritis of the knee, respectively. Objective: To investigate whether acupuncture is more efficacious than (a) no treatment or (b) minimal acupuncture in the treatment of low back pain and osteoarthritis. Design: Two randomized, controlled, multicenter trials with three treatment arms and a total follow-up time of 52 weeks. Setting: 30 practitioners and outpatient units in Germany specialized in acupuncture treatment. Patients: 300 patients will be included in each study. In the low back pain trial, patients will be included according to clinical diagnosis. In the osteoarthritis pain trial, patients will be included according to the American College of Rheumatology criteria. Interventions: Patients are randomly assigned to receive either (1) semi-standardized acupuncture (150 patients), (2) minimal acupuncture at non-acupuncture points (75 patients), or (3) no treatment for two months followed by semi-standardized acupuncture (75 patients, waiting list control). Acupuncture treatment consists of 12 sessions per patient over a period of 8 weeks. Main Outcome Measure: The main outcome measure is the difference between baseline and the end of the 8-week treatment period in the following parameters: pain intensity as measured by a visual analogue scale (VAS; 0-100 mm) in the low back pain trial and by the Western Ontario and McMaster Universities Osteoarthritis Score (WOMAC) in the osteoarthritis trial. Outlook: The results of these two studies (available in 2004) will provide health care providers and policy makers with the information needed to make scientifically sound assessments of acupuncture therapy

Acupuncture in Seasonal Allergic Rhinitis (ACUSAR) - Design and Protocol of a Randomised Controlled Multi-Centre Trial

Background: We report on the study design and protocol of a randomised controlled trial (Acupuncture in Seasonal Allergic Rhinitis, ACUSAR) that investigates the efficacy of acupuncture in the treatment of seasonal allergic rhinitis (SAR). Objective: To investigate whether acupuncture is non-inferior or superior to (a) penetrating sham acupuncture and (b) rescue medication in the treatment of SAR. Design: 3-armed, randomised controlled multi-centre trial with a total follow-up time of 16 weeks in the 1st year and 8 weeks in the 2nd year. Setting: 41 physicians in 37 out-patient units in Germany specialised in acupuncture treatment. Patients: 400 seasonal allergic rhinitis patients with clinical symptoms and test-positive (skin-prick test and/or specific IgE) to both birch and grass pollen. Interventions: Patients will be randomised in a 2:1:1 ratio to one of three groups: (a) semi-standardised acupuncture plus rescue medication (cetirizine); (b) penetrating sham acupuncture at non-acupuncture points plus rescue medication; or (c) rescue medication alone for 8 weeks (standard treatment group). Acupuncture and sham acupuncture will consist of 12 treatments per patient over 8 weeks. Main Outcome Measures: Average means of the Rhinitis Quality of Life Questionnaire (RQLQ) overall score and the Rescue Medication Score (RMS) between weeks 6 and 8 in the first year, adjusted for baseline values. Outlook: The results of this trial available in 2011 will have a major impact on the decision of whether acupuncture should be considered as a therapeutic option in the treatment of SAR

Prophylactic Acupuncture Treatment during Chemotherapy in Patients with Breast Cancer – Results of a Qualitative Study nested in a Randomized Pragmatic Trial

Background: In a randomized controlled trial, compared with standard care alone in breast cancer, acupuncture as a prophylactic treatment did not show better quality of life or fewer side effects of chemotherapy (NCT01727362 [clinicaltrials.gov]). The aim of the qualitative part of this mixed methods study was to better understand the subjective perspectives of the patients regarding quality of life during chemotherapy and the perceived effects of acupuncture. Methods: In a nested retrospective qualitative study, semi-structured telephone interviews were conducted with 5 responders and 5 non-responders (defined by the outcome of the primary parameter FACT-B) who were randomly selected from both study arms. The interviews were digitally recorded, pseudonymized, transcribed, and then deductively and inductively analyzed according to Qualitative Content Analysis using MAXQDA® software. Results: A total of 20 patients were included in the qualitative part of the study. In both groups, most women stated that their quality of life was surprisingly better than what they had expected before starting the chemotherapy. All patients of the acupuncture group experienced the acupuncture treatments as relaxing and beneficial, mentioning a friendly setting, and empathic attitude of the therapist. Most of these patients stated that the acupuncture treatment reduced chemotherapy-induced side effects. The patients reported that acupuncture was supportive for coping with the disease in a salutogenic way. For all patients, finding strategies to cope with life-threatening cancer and the side effects of chemotherapy was essential, for example, keeping a positive attitude toward life, selecting social contacts, and staying active as much as possible. Conclusions: Patients in the acupuncture group reported positive effects on psychological and physical well-being after receiving the study intervention. For all patients, having coping strategies for cancer seemed to be more important than reducing side effects. Therefore, further studies should focus more on coping strategies and reducing acute side effects

Experiences and Perceived Effects of Rosary Praying: A Qualitative Study

The aim of this study is to explore experiences and perceived effects of the Rosary on issues around health and well-being, as well as on spirituality and religiosity. A qualitative study was conducted interviewing ten Roman Catholic German adults who regularly practiced the Rosary prayer. As a result of using a tangible prayer cord and from the rhythmic repetition of prayers, the participants described experiencing stability, peace and a contemplative connection with the Divine, with Mary as a guide and mediator before God. Praying the Rosary was described as helpful in coping with critical life events and in fostering an attitude of acceptance, humbleness and devotion

Learning to Establish a Therapeutic Doctor-Patient Communication: German and Israeli Medical Students Experiencing Integrative Medicine’s Skills

The doctors’ clinical time collides with the increasing of the use of telecare technologies in our digital era, reducing the actual doctor-patient interaction and the potential to engage with therapeutic doctor-patient communication. In our qualitative study, we followed a collaborative German-Israeli project that trained medical students to use complementary and integrative medicine (CIM) methods in order to improve doctor-patient communication. Interviews with the participants and participatory observation revealed the ways the mentors taught CIM methods, the meaning of therapuitic doctor-patient communication and how the students learned and implemented these skills in different ways. Our findings show that students expand their communication channels and skills, notice their own somatic-sensory states, and engage with somatic knowledge in different interactions. Our findings correspond with, and signify the intercorporeal space of doctor-patient interaction in the way in which doctors’ and patients’ soma-sensual aspects are interact, influence each another, and enable therapeutic communication

Complementary and Integrative Medicine in Nursing Homes: Results of a Cross-Sectional Study in Residents and Caregivers

Objective: Some nursing homes for the elderly in Germany integrate complex complementary and integrative medicine interventions in the form of hydrotherapy, herbal and mind-body therapies, physical activities, and healthy eating, known as Kneipp therapy (KT), in care. This pilot study explored health- and work-related characteristics and acceptance of KT amongst residents and caregivers. Methods: Within a mixed-methods cross-sectional study in nursing homes who had integrated KT, we assessed work ability, psychosocial burden at work and health-related quality of life of caregivers, as well as a broad selection of health-related data of residents by questionnaires and assessments. Data were analyzed descriptively. Results: The data from 29 female caregivers (42.0 ± 11.7 years) and 64 residents (83.2 ± 8.1 years) were analyzed. Both caregivers (96%) and residents (89%) considered KT to be beneficial for health and well-being. Ninety percent of the caregivers indicated an improved relationship to residents since implementing KT. Caregivers showed a good work ability and quality of life. Residents attained remarkable ratings in social relation and affect-related aspects of quality of life. Conclusion: The results of this cross-sectional study indicate a high acceptance of integrating KT by residents and caregivers. The effectiveness and safety of KT should be explored in further comparative studies.Hintergrund: Einige Senioreneinrichtungen in Deutschland integrieren die Kombination aus Hydrotherapie, Phytotherapie, Ordnungstherapie, Bewegung und gesunder Ernährung als Kneipp-Therapie (KT) in die Pflege und Betreuung von Bewohnern. Diese Pilotstudie zielte darauf ab, gesundheits- und arbeitsbezogene Charakte­ristika und die Akzeptanz von KT bei Bewohnern und ­Mitarbeitern dieser Pflegeeinrichtungen zu untersuchen. Methoden: Im Rahmen einer Mixed-Methods-Querschnittsstudie in vier Senioreneinrichtungen, die KT integrierten, wurden unter anderem die Arbeitsfähigkeit, die psychosoziale Belastung am Arbeitsplatz und die gesundheitsbezogene Lebensqualität der Pflegekräfte sowie eine breite Auswahl an gesundheitsbezogenen Daten und die Lebensqualität der Bewohner durch Fragebögen erhoben. Alle Daten wurden deskriptiv analysiert. Ergebnisse: Es wurden die Daten von 29 Mitarbeiterinnen (42,0 ± 11,7 Jahre) und 64 Bewohnern (83,2 ± 8,1 Jahre) analysiert. Sowohl die Pflegekräfte (96%) als auch die Bewohner (89%) betrachteten KT als vorteilhaft für die Gesundheit und das Wohlbefinden. Ausserdem gaben 90% der Mitarbeiterinnen eine verbesserte Beziehung zu den Bewohnern seit der Einführung von KT an. Die Mitarbeiterinnen zeigten eine gute Arbeitsfähigkeit und Lebensqua­lität. Die Bewohner zeigten gute Bewertungen von Aspekten der Lebensqualität, die mit sozialer Beziehung und Affekt zusammenhängen. Fazit: Die Ergebnisse zeigen, dass KT in den untersuchten Senioreneinrichtungen von den Bewohnern und Betreuern gut angenommen wurde. Die spezifische Wirksamkeit und Sicherheit von KT sollten in weiteren vergleichenden Studien untersucht werden