bluuebunny/crossref_metadata_2025_split huggingface dataset:
Size fractionated NET‐Seq reveals a conserved architecture of transcription units around yeast genes
Authors: Xi Shidong , Nguyen Tania , Murray Struan , Lorenz Phil , Mellor Jane 
Published: March 2024

AbstractGenomes from yeast to humans are subject to pervasive transcription. A single round of pervasive transcription is sufficient to alter local chromatin conformation, nucleosome dynamics and gene expression, but is hard to distinguish from background signals. Size fractionated native elongating transcript sequencing (sfNET‐Seq) was developed to precisely map nascent transcripts independent of expression levels. RNAPII‐associated nascent transcripts are fractionation into different size ranges before library construction. When anchored to the transcription start sites (TSS) of annotated genes, the combined pattern of the output metagenes gives the expected reference pattern. Bioinformatic pattern matching to the reference pattern identified 9542 transcription units in Saccharomyces cerevisiae, of which 47% are coding and 53% are noncoding. In total, 3113 (33%) are unannotated noncoding transcription units. Anchoring all transcription units to the TSS or polyadenylation site (PAS) of annotated genes reveals distinctive architectures of linked pairs of divergent transcripts approximately 200nt apart. The Reb1 transcription factor is enriched 30nt downstream of the PAS only when an upstream (TSS −60nt with respect to PAS) noncoding transcription unit co‐occurs with a downstream (TSS +150nt) coding transcription unit and acts to limit levels of upstream antisense transcripts. The potential for extensive transcriptional interference is evident from low abundance unannotated transcription units with variable TSS (median −240nt) initiating within a 500nt window upstream of, and transcribing over, the promoters of protein‐coding genes. This study confirms a highly interleaved yeast genome with different types of transcription units altering the chromatin landscape in distinctive ways, with the potential to exert extensive regulatory control.
Overfitting, Underfitting and General Model Overconfidence and Under-Performance Pitfalls and Best Practices in Machine Learning and AI
Authors: Aliferis Constantin , Simon Gyorgy 
Published: March 2024

AbstractAvoiding over and under fitted analyses (OF, UF) and models is critical for ensuring as high generalization performance as possible and is of profound importance for the success of ML/AI modeling. In modern ML/AI practice OF/UF are typically interacting with error estimator procedures and model selection, as well as with sampling and reporting biases and thus need be considered together in context. The more general situations of over confidence (OC) about models and/or under-performing (UP) models can occur in many subtle and not so subtle ways especially in the presence of high-dimensional data, modest or small sample sizes, powerful learners and imperfect data designs. Because over/under confidence about models are closely related to model complexity, model selection, error estimation and sampling (as part of data design) we connect these concepts with the material of chapters “An Appraisal and Operating Characteristics of Major ML Methods Applicable in Healthcare and Health Science,” “Data Design,” and “Evaluation”. These concepts are also closely related to statistical significance and scientific reproducibility. We examine several common scenarios where over confidence in model performance and/or model under performance occur as well as detailed practices for preventing, testing and correcting them.
Lessons Learned from Historical Failures, Limitations and Successes of AI/ML in Healthcare and the Health Sciences. Enduring Problems, and the Role of Best Practices
Authors: Aliferis Constantin , Simon Gyorgy 
Published: March 2024

AbstractThis chapter covers a variety of cases studies-based incidents and concepts that are valuable for identifying pitfalls, suggesting best practices and supporting their use. Examples include: the Gartner hype cycle; the infamous “AI winters”; limitations of early-stage knowledge representation and reasoning methods; overfitting; using methods not built for the task; over-estimating the value and potential or early and heuristic technology; developing AI disconnected with real-life needs and application contexts; over-interpreting theoretical shortcomings of one algorithm to all algorithms in the class; misinterpreting computational learning theory; failures/shortcomings of literature including technically erroneous information and persistence of incorrect findings; meta research yielding unreliable results; failures/shortcomings of modeling protocols, data and evaluation designs (e.g., competitions); failures/shortcomings of specific projects and technologies; and also contextual factors that may render guidelines themselves problematic. These case studies were often followed by improved technology that overcame various limitations. The case studies reinforce, and demonstrate the value of science-driven practices for addressing enduring and new challenges.
Characterizing, Diagnosing and Managing the Risk of Error of ML & AI Models in Clinical and Organizational Application
Authors: Aliferis Constantin , Ma Sisi , Wang Jinhua , Simon Gyorgy 
Published: March 2024

AbstractThis chapter covers essential practical methods for examining models, reviewing their face validity, and characterizing and managing risk of errors of such models at development and at deployment stages. This chapter also briefly discusses broader methods and best practices for detecting and correcting issues with ML modeling and the emerging concept of debugging ML models and analyses. A “toolkit” for application safety measures is presented.
Regulatory Aspects and Ethical Legal Societal Implications (ELSI)
Authors: Johnson Steven G. , Simon Gyorgy , Aliferis Constantin 
Published: March 2024

AbstractThis chapter reviews the context of regulating AI/ML models, the risk management principles underlying international regulations of clinical AI/ML, the conditions under which health AI/ML models in the U.S. are regulated by the Food and Drug Administration (FDA), and the FDA’s Good Machine Learning Practice (GMLP) principles. The GMLP principles do not offer specific guidance on execution, so we point the Reader to the parts of the book that discuss bringing these principles to practice via concrete best practice recommendations. Intrinsically linked with regulatory aspects are the Ethical, Legal, Social Implications (ELSI) dimensions. The chapter provides an introduction to the nascent field of biomedical AI ethics covering: general AI ELSI studies, AI/ML racial bias, and AI/ML and Health equity principles. Contrary to conventional risks/harms (data security and privacy, adherence to model use as stated in consent), ethical AI/ML involves model effectiveness and harms thatcan exist within the intended scope of consent.On the positive side, in the case of biomedical AI, these risks are in principle measurable and knowable compared to hard-to-quantify risks/harm due to data breaches. The chapter discusses (and gives illustrative examples) of the importance of causality and equivalence classes for practical detection of racial bias in models. The chapter concludes with a series of recommended best practices for promoting health equity and reducing health disparities via the design and use of health AI/ML.
An Appraisal and Operating Characteristics of Major ML Methods Applicable in Healthcare and Health Science
Authors: Simon Gyorgy , Aliferis Constantin 
Published: March 2024

AbstractThis chapter provides an outline of most major biomedical ML methods in a manner suitable for both readers who have not delved into ML before, and readers who may already know about some or all of these methods. The former will find here a useful introduction and review. The latter will find additional insights as we critically revisit the key concepts and add summary guidance on whether and when each technique is applicable (or not) in healthcare and health science problem solving. Toward that end, for each technique, we introduce a “Method Label”, akin to a drug label, which provides distilled information about the techniques at a glance. The method labels present the primary and secondary uses of each technique, provide context of use, describe the principles of operation, and summarize important theoretical and empirical properties.
Foundations of Causal ML
Authors: Kummerfeld Erich , Andrews Bryan , Ma Sisi 
Published: March 2024

AbstractThe present chapter covers the important dimension of causality in ML both in terms of causal structure discovery and causal inference. The vast majority of biomedical ML focuses on predictive modeling and does not address causal methods, their requirements and properties. Yet these are essential for determining and assisting patient-level or healthcare-level interventions toward improving a set of outcomes of interest. Moreover causal ML techniques can be instrumental for health science discovery.
Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) promotes stress granule formation via YBX1 phosphorylation in ovarian cancer
Authors: Mao Shuyu , Xie Chong , Liu Yufeng , Zhao Ye , Li Mengxia , Gao Han , Xiao Yue , Zou Yongkang , Zheng Zhiguo , Gao Ya , Xie Juan , Tian Bing , Wang Liangyan , Hua Yuejin , Xu Hong 
Published: March 2024

AbstractAPE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses. Precise regulation of SGs is pivotal to cell survival, whereas their dysregulation is increasingly linked to diseases. Whether APE1 engages in modulating SG dynamics is worthy of investigation. In this study, we demonstrate that APE1 colocalizes with SGs and promotes their formation. Through phosphoproteome profiling, we discover that APE1 significantly alters the phosphorylation landscape of ovarian cancer cells, particularly the phosphoprofile of SG proteins. Notably, APE1 promotes the phosphorylation of Y-Box binding protein 1 (YBX1) at S174 and S176, leading to enhanced SG formation and cell survival. Moreover, expression of the phosphomutant YBX1 S174/176E mimicking hyperphosphorylation in APE1-knockdown cells recovered the impaired SG formation. These findings shed light on the functional importance of APE1 in SG regulation and highlight the importance of YBX1 phosphorylation in SG dynamics.
On the distribution and diversity of tissue-specific somatic mutations in honey bee (Apis mellifera) drones
Authors: Shultz R. R. , Carey A. , Ragheb K. E. , Robinson J. P. , Harpur B. A. 
Published: March 2024

AbstractSomatic mutations originate from both exogenous (e.g. UV radiation, chemical agents) and endogenous (e.g., DNA replication, defective DNA repair) sources and can have significant impacts on an animal’s reproductive success. This may be especially true for haploid organisms that are susceptible to any deleterious alleles inherited from their parent and any that arise over their lifetime. Unfortunately, little is known about the rate of somatic mutation accumulation across individuals and tissues of haplodiploid animal populations, the functional processes through which they arise, and their distribution across tissues and the genome. Here, we generated short-read whole-genome sequencing data for four tissues of haploid honey bee males. We paired this with estimates of telomere length and tissue-specific DNA content to address three major questions: is there variance in somatic mutational load across haploid individuals and specific tissues therein, does increased DNA content in a tissue contribute to somatic mutational load, and does telomere length correlate with mutational load? Our results suggest that variance in somatic mutational load is better captured across individuals than across tissues, that tissue-specific DNA content is not associated with somatic mutation load, and that variance in telomere length does not correlate with somatic mutation loads across tissues. To our knowledge, this is the first observational study on somatic mutational load in Apoidea and likely Hymenoptera. It serves as a useful advent for additional studies understanding the processes through which haploids tolerate or repair somatic mutations.
Wie viel Digital Public Health steckt in Public-Health-Studiengängen? Eine systematische Modulhandbuchanalyse von Vollzeitstudiengängen an öffentlichen Hochschulen und Universitäten in Deutschland
Authors: Albrecht Joanna , Maaß Laura , Tokgöz Pinar , Hrynyschyn Robert , Wrona Kamil J. , Stark Anna Lea , Dunsche Celina , Fischer Florian , Schmidt Annalena , Schulz Henriette , Hidding Sarah , Dockweiler Christoph 
Published: March 2024

Zusammenfassung
Hintergrund
Fachkräfte für den Bereich Digital Public Health (DiPH) sind für eine erfolgreiche digitale Transformation im Sozial- und Gesundheitswesen notwendig. Unklar ist jedoch, inwiefern im Public-Health-(PH-)Studium DiPH-bezogene Inhalte vermittelt werden.

Methode
Mittels systematischer Modulhandbuchanalyse wurden DiPH-bezogene Inhalte von akkreditierten PH-orientierten Studiengängen öffentlicher Hochschulen und Universitäten in Deutschland analysiert. Über die Plattform „Hochschulkompass“ und Mitgliedsstudiengänge der Deutschen Gesellschaft für Public Health (DGPH) wurden 422 Studiengänge identifiziert. Eingeschlossene Modulhandbücher wurden inhaltsanalytisch mittels MAXQDA ausgewertet.

Ergebnisse
Lediglich 10 Bachelor- und 6 Masterstudiengänge weisen einen inhaltlichen DiPH-Bezug auf. Sie sind in ihren Schwerpunkten heterogen und unterschiedlichen PH-Teilbereichen zuzuordnen („Methoden, Definition, Geschichte und Sozialmedizin“ = 5; „Gesundheitsmanagement“ = 5; „Digital Health“ = 3; „Versorgungsforschung“ = 2; „Gesundheitskommunikation“ = 1). Zwischen dem wissenschaftlich gängigen Verständnis von DiPH und den darauf bezogenen Inhalten in den Modulhandbüchern zeigen sich Unterschiede. Die identifizierten Inhalte fokussieren eher technische und geringfügiger sozial- und gesundheitswissenschaftliche Bereiche.

Diskussion
Die heterogenen Studiengänge mit DiPH-Bezug ermöglichen akademischen PH-Fachkräften eine spezifische Profilierung. Um umfassende Kompetenzen im Bereich DiPH zu erlangen, bedarf es eines weiteren Ausbaus entsprechender Module, die für den jeweiligen Studiengang relevant sind. Die Ergebnisse könnten zur (Weiter‑)Entwicklung geeigneter Module sowie eines DiPH-Kerncurriculums dienen.
Modeling trends and periodic components in geodetic time series: a unified approach
Authors: Kermarrec Gaël , Maddanu Federico , Klos Anna , Proietti Tommaso , Bogusz Janusz 
Published: March 2024

AbstractGeodetic time series are usually modeled with a deterministic approach that includes trend, annual, and semiannual periodic components having constant amplitude and phase-lag. Although simple, this approach neglects the time-variability or stochasticity of trend and seasonal components, and can potentially lead to inadequate interpretations, such as an overestimation of global navigation satellite system (GNSS) station velocity uncertainties, up to masking important geophysical phenomena. In this contribution, we generalize previous methods for determining trends and seasonal components and address the challenge of their time-variability by proposing a novel linear additive model, according to which (i) the trend is allowed to evolve over time, (ii) the seasonality is represented by a fractional sinusoidal waveform process (fSWp), accounting for possible non-stationary cyclical long-memory, and (iii) an additional serially correlated noise captures the short term variability. The model has a state space representation, opening the way for the evaluation of the likelihood and signal extraction with the support of the Kalman filter (KF) and the associated smoothing algorithm. Suitable enhancements of the basic methodology enable handling data gaps, outliers, and offsets. We demonstrate the advantage of our method with respect to the benchmark deterministic approach using both observed and simulated time series and provide a fair comparison with the Hector software. To that end, various geodetic time series are considered which illustrate the ability to capture the time-varying stochastic seasonal signals with the fSWp.
Verhaltenssüchte als neue ICD-11-Diagnosen
Authors: Lindenberg Katajun , Sonnenschein Anke Rebecca 
Published: March 2024

Zusammenfassung
Hintergrund
Die Aufnahme von Störungen durch Verhaltenssüchte in die 11. Revision der International Classification of Diseases and Related Health Problems (ICD-11) durch die Weltgesundheitsorganisation (WHO) ist ein bedeutender Meilenstein in der psychotherapeutischen Versorgung von Betroffenen.

Methode
Die vorliegende Arbeit enthält eine Übersicht über die aktuelle Evidenzlage der neuen ICD-11-Kategorie.

Ergebnisse
Verhaltenssüchte werden zusammen mit Substanzgebrauchsstörungen in der Kategorie „Störungen durch Substanzgebrauch oder Verhaltenssüchte“ klassifiziert. Die Computerspiel- und die Glücksspielstörung werden als eigenständige Diagnosen aufgeführt und können sich sowohl auf online als auch offline ausgeführtes Verhalten beziehen. Die Soziale-Netzwerke-Nutzungsstörung, die Kauf-Shopping-Störung und die Pornografie-Nutzungsstörung werden als „sonstige Störungen durch Verhaltenssüchte“ vorgeschlagen. Behandlungsrelevante Grundlagen der Störungsentstehung umfassen Faktoren des Suchtmittels (insbesondere intermittierende Verstärkungsmechanismen), Faktoren der Person (prädisponierende Variablen sowie kognitive, affektive und exekutive Reaktionen auf suchtbezogene Reize) und Faktoren der Umwelt (Risikofaktoren in relevanten Lebensbereichen sowie die Verfügbarkeit der Suchtmittel). Unterstützungsangebote für Betroffene sind in die Bereiche Beratung, ambulante und stationäre Behandlung sowie Rehabilitation unterteilbar. Therapeutische Ziele und Strategien beinhalten motivationsorientierte Verfahren, behaviorale und kognitive Interventionen, körperorientierte Interventionen, Fertigkeitentrainings und unterstützende Angebote durch Jugendhilfe, Paarberatung, Schulden- und Sozialberatung.

Schlussfolgerung
Der Einzug der Verhaltenssüchte in die ICD-11 ist eine wichtige Grundlage für eine adäquate Versorgung von Betroffenen und ihren Angehörigen.
Welch’s t test is more sensitive to real world violations of distributional assumptions than student’s t test but logistic regression is more robust than either
Authors: Curtis David 
Published: March 2024

AbstractIt has previously been pointed out that Student’s t test, which assumes that samples are drawn from populations with equal standard deviations, can have an inflated Type I error rate if this assumption is violated. Hence it has been recommended that Welch’s t test should be preferred. In the context of carrying out gene-wise weighted burden tests for detecting association of rare variants with psoriasis we observe that Welch’s test performs unsatisfactorily. We show that if the assumption of normality is violated and observations follow a Poisson distribution, then with unequal sample sizes Welch’s t test has an inflated Type I error rate, is systematically biased and is prone to produce extremely low p values. We argue that such data can arise in a variety of real world situations and believe that researchers should be aware of this issue. Student’s t test performs much better in this scenario but a likelihood ratio test based on logistic regression models performs better still and we suggest that this might generally be a preferable method to test for a difference in distributions between two samples.This research has been conducted using the UK Biobank Resource.
Non-femoral focused transaxillary access in TAVI: GARY data analysis and future trends
Authors: Meertens Max M. , Adam Matti , Beckmann Andreas , Ensminger Stephan , Frerker Christian , Seiffert Moritz , Sinning Jan-Malte , Bekeredjian Raffi , Walther Thomas , Beyersdorf Friedhelm , Möllmann Helge , Balaban Ümniye , Eghbalzadeh Kaveh , Rudolph Tanja K. , Bleiziffer Sabine 
Published: March 2024

Abstract
Background
In patients not suitable for transfemoral transcatheter aortic valve implantation (TAVI), several access strategies can be chosen.

Aim
To evaluate the use and patient outcomes of transaxillary (TAx), transapical (TA), and transaortic (TAo) as alternative access for TAVI in Germany; to further evaluate surgical cutdown vs. percutaneous TAx access.

Methods
All patients entered the German Aortic Valve Registry (GARY) between 2011 and 2019 who underwent non-transfemoral TAVI were included in this analysis. Patients with TA, TAo, or TAx TAVI were compared using a weighted propensity score model. Furthermore, a subgroup analysis was performed for TAx regarding the percutaneous or surgical cutdown approach.

Results
Overall, 9686 patients received a non-transfemoral access. A total of 8918 patients (92.1%) underwent TA, 398 (4.1%) TAo, and 370 (3.8%) TAx approaches. Within the TAx subgroup, 141 patients (38.1%) received subclavian cutdown, while 200 (54.1%) underwent a percutaneous approach. The TA patients had a significantly lower 30-day survival than TAx patients (TA 90.92% vs. TAx 95.59%, p = 0.006; TAo 92.22% vs. TAx 95.59%, p = 0.102). Comparing percutaneous and cutdown TAx approaches, no significant differences were seen. However, more vascular complications occurred (TA 1.8%, TAo 2.4%, TAx 12.2%; p < .001), and the hospital length of stay was shorter (TA 12.9 days, TAo 14.1 days, TAx 12 days; p < .001) after TAx access.

Conclusion
It may be reasonable to consider TAx access first in patients not suitable for TF-TAVI, because the 30-day survival was higher compared with TA access and the 1-year survival was higher compared with TAo access. It remains important for the heart teams to offer alternative access modalities for patients not amenable to the standard TF-TAVI approaches.

Graphical Abstract
Early life stress, literacy and dyslexia: an evolutionary perspective
Authors: Kershner John R. 
Published: March 2024

AbstractStress and learning co-evolved in parallel, with their interdependence critical to the survival of the species. Even today, the regulation of moderate levels of stress by the central autonomic network (CAN), especially during pre- and post-natal periods, facilitates biological adaptability and is an essential precursor for the cognitive requisites of learning to read. Reading is a remarkable evolutionary achievement of the human brain, mysteriously unusual, because it is not pre-wired with a genetic address to facilitate its acquisition. There is no gene for reading. The review suggests that reading co-opts a brain circuit centered in the left hemisphere ventral occipital cortex that evolved as a domain-general visual processor. Its adoption by reading depends on the CAN’s coordination of the learning and emotional requirements of learning to read at the metabolic, cellular, synaptic, and network levels. By stabilizing a child’s self-control and modulating the attention network’s inhibitory controls over the reading circuit, the CAN plays a key role in school readiness and learning to read. In addition, the review revealed two beneficial CAN evolutionary adjustments to early-life stress “overloads” that come with incidental costs of school under-performance and dyslexia. A short-term adaptation involving methylation of the FKBP5 and NR3C1 genes is a liability for academic achievement in primary school. The adaptation leading to dyslexia induces alterations in BDNF trafficking, promoting long-term adaptive fitness by protecting against excessive glucocorticoid toxicity but risks reading difficulties by disruptive signaling from the CAN to the attention networks and the reading circuit.