bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic sinusoidal obstruction syndrome (SOS) associated with checkpoint inhibitor therapy
Authors: Litterio Marianna , Marchetti Nicole , Carubbi Francesco , Tudini Marianna , Mutti Luciano , Ferri Claudio
Published: December 2024

Sinusoidal obstruction syndrome (SOS) is a distinctive and potentially fatal form of hepatic injury that mainly occurs after hematopoietic-stem cell transplantation but also due to many other conditions including drug or toxin exposure. Recently, immune checkpoint inhibitors (ICIs) have revolutionised the treatment of many solid organ malignancies. Furthermore, as their use has become more widespread, rare toxicities have emerged. The difficulty lies in diagnosing these unusual toxicities with an incidence of as low as less than 1% hence defined as SOS. The development of the disease can be rapid and unpredictable. The severe forms of SOS may result in multi-organ dysfunction with a high mortality rate (>80%). We present the case of a patient with metastatic lung adenocarcinoma treated with the ICI pembrolizumab who developed SOS with marked portal hypertension as a rare severe, toxic side effect of immunotherapy. This report highlights the importance of considering SOS in patients who develop liver dysfunction and/or portal hypertension during or after immunotherapy for neoplastic disease. Early identification and severity assessment is crucial in facilitating prompt diagnosis and timely treatment, improving the prognosis of our patients.
Types and causes of speech disorders in children
Authors:   V. O. Sukhomlynskyi Mykolaiv National University, Ruskulis Lilia
Published: December 2024

The article emphasises that the development of children's speech is one of the priorities of preschool education institutions. It is emphasized that in Ukraine there is a large number of children with speech disorders and this trend is growing every year. The article characterises variants of atypical speech formation in ontogeny, indicators by which it is possible to identify problems of speech development in childhood. The types of delay in speech development (delay at the stage of emotional communication, delay at the stage of naming, lack of interest in communication, delay at the stage of ‘baby words’) are analyzed. The general and specific patterns of mental development of a child with a speech disorder are highlighted. The classifications of speech disorders – clinical and pedagogical, psychological and pedagogical and medical (specific disorders of speech and language development) – are studied. The attention is drawn to two groups of speech disorders in children: structural and semantic design of utterance (aphasia and alalia), and phonation design of utterance (dysphonia, tachylalia, bradyalgia, stuttering, dyslalia, rhinolalia, dysarthria). The reasons for the pathology of children's speech are investigated, which include: biological factors (those that affect the fetal development and those that affect during a childbirth), socio-psychological factors (mental derivation of the child: early bilingualism; excessive stimulation of speech development; speech disorders in persons surrounding the child; improper upbringing in the family, etc.), and from the point of view of medical factors – internal (endogenous) and external (exogenous), which may result in ‘mutism’ – a complete refusal to communicate. The factors (traumas) of the postnatal period that affect speech development are considered. It is proved that speech is closely connected with all mental processes – consciousness, thinking, memory, attention and imagination.
Polycultural orientation of future music teachers’ professional training in the educational process of higher educational institutions through the integration of the content of their cultural training in the process of studying specialized disciplines
Authors:   State Institution Luhansk Taras Shevchenko National University, Zipeng Wang
Published: December 2024

The article deals with solving one of the topical issues of modern higher education pedagogy related to the formation of polycultural competence of future music teachers. The aim of the article is to substantiate and identify ways to implement one of the pedagogical conditions for the efficient formation of future music teachers’ polycultural competence – the polycultural orientation of future music teachers’ professional training in the educational process of higher educational institutions through the integration of the content of their cultural training in the process of studying professional disciplines. It was emphasized that the polycultural orientation of the professional training of future music teachers in the educational process of higher education institutions is realized through the integration of the content of their cultural training in the process of studying professional disciplines, because the integration of cultural elements in the study of music subjects contributes to a deeper understanding of students’ diverse cultural contexts and their impact on musical experience. A number of additional polycultural modules were developed and implemented in the educational process of higher educational institutions in the content of some professional disciplines, and an integrated special course “Musical Art as a Polylogue of Cultures” was introduced into the process of professional training of future music teachers. The author concludes that the integration of the content of cultural training into the process of studying professional disciplines allowed students not only to master the technical and theoretical aspects of musical art, but also to understand the deep connections between music and cultural context.
Analytical Model for Compact Star in a Buchdahl Spacetime Consistent with Observational Data
Authors: Malaver Manuel , Iyer Rajan
Published: December 2024

A method is developed to obtain solutions of Einstein field equations for anisotropic charged spheres. This procedure needs to choose a linear relationship between energy density and radial pressure and a metric function proposed for Buchdahl (1959). A new class of solution is obtained and subjected to several physical analyses for realistic models of compact stars. The new solutions in this research are physically reasonable, well-behaved in the interior of the star, which indicates that these new models satisfies important physical conditions as the measure of anisotropy and matching. The models are consistent with the upper limit on the mass of compact stars for PSR J1823-3021G, PSR J1748-2446an and PSR J1518+4904.
‘If You Can, You Should’: Dutch Community Holidays During the Troubles
Authors: Cornelissens Nusi , Milliken Matthew
Published: December 2024

Dutch society was taken aback by the onset of an apparently religious war in Northern Ireland at the end of the 1960s. It responded by initiating community holidays which they targeted at those children who were identified as being most
affected by the Troubles. These community holidays aimed to ameliorate ‘otherisation’ by exposing Catholic and Protestant children to each other in a neutral, peaceful setting. This study examines the context and operation of these community
holidays with a specific focus on three community holidays in the Dutch province of Zeeland between 1973 and 1975, the first of which was organised by Stichting Hulp Noord-Ierland (Foundation Help Northern Ireland, HUNI). The success of this initiative in achieving its aim of reducing prejudice and thereby future violence is assessed through a review of contemporary media material, organisational archives and interviews with witnesses from both the Netherlands and Northern Ireland. The success of the Dutch community holidays in achieving their aim of reducing prejudice and thereby promoting peace is assessed through a review of organisational archives and contemporary media material, alongside interviews with witnesses from both the Netherlands and Northern Ireland.
On Freedom of the Press: The Nevada State Council of Defense Versus William Randolph Hearst
Authors: de la Mer Marlow Janice Price
Published: December 2024

Abstract: During World War I Nevada’s Council of Defense launched a vigorous program that attempted to ban the distribution of antiwar publications, especially William Randolph Hearst’s San Francisco Examiner in Nevada. The move failed in the courts, not because it was an unlawful suppression of free speech, but because it was an unconstitutional attempt by a state to impose a “boycott” interfering with interstate commerce and was also in violation of the 1890 Sherman Antitrust Act.
The Book as Mirror: Embroidered Bindings at the Court of Charles I
Authors: Welch Anna
Published: December 2024

Abstract: Embroidered bindings were an important aspect of the culture of luxury goods associated with the Stuart court, and several surviving examples are associated with Charles I's queen Henrietta Maria, including one in the John Emmerson Collection, State Library Victoria, Melbourne, Australia. Most unusually, this binding can be linked to a group of eight bindings identified to date as the work of one individual or workshop, held in the collections of SLV, the Metropolitan Museum of Art, the Bodleian Libraries, Oxford, and the British Library, London. This article will explore the relationships between these bindings as well as the cultural, gendered, and material history of their production and their reception in seventeenth-century England. Regarding their reception, I will consider the books both as texts to be read in a literal sense, and texts that, as objects, used form as well as iconography to encode directives about female royal behaviour within the richly symbolical and distinctive decorative culture of the Stuart court.
Collecting Early Modern English Books in British Settler Colonies: Contexts, Problems, and Opportunities
Authors: August Hannah , Edelstein Gabriella
Published: December 2024

Abstract: Although it differs from other Australian and New Zealand libraries' rare books collections in several ways, the Emmerson Collection is only the most recent private collection of early modern English books to find a home in a public library in a British settler colony in the South Pacific. In this article, we consider the similarities and differences between the Emmerson Collection and these other named collections of early modern English books in New Zealand and Australia, exploring both the Emmerson's particular affordances and the ways in which all these collections invite scholarly reflection on the relationship between their origins, their content, and their location on colonised land.
Religion and the Rise of Capitalism
Authors: Friedman Benjamin M.
Published: December 2024

Abstract: Based on a presentation at the American Philosophical Society's Member Meeting in April 2023, the central question of this essay is where modern Western economics came from, and why it emerged when and where it did. The author argues that Adam Smith's thinking, indeed the entire Smithian revolution in thinking about what we now call economics, was enabled by what was then a new line of religious thinking in the English-speaking Protestant world – in particular, the turn away from Calvinist notions of depravity and predestination, which took the religious thinking of the English-speaking world beyond the original basis of the Protestant Reformation. This fundamental change in religious thinking enabled the secular thinking of that time and place to take on the more optimistic view of the human character, and the expanded concept of the possibilities for human agency, that underlie modern Western economics.
Compilers of Magic: Greco-Egyptian Magical Handbooks through the Eyes of Their Scribes
Authors: Tovar Sofía Torallas
Published: December 2024

Abstract: Based on a presentation at the American Philosophical Society's Member Meeting in April 2023, this brief essay focuses on how ancient magic was compiled and transmitted. Previous studies of a body of ancient texts on magic focused on their textual and linguistic content. However, a focus on materiality offers new perspectives for the study of the circulation of magical books and the transmission of knowledge through the work of scribes in the production of books. Considering materiality leads to questions such as: How were these books produced? Who produced them and why were specific recipes and prescriptions collected in books? Who were their readers? This large and well-preserved corpus of papyri provides a laboratory to explore scribal experience and the materiality of ancient compilations. It offers, in other words, a window into the transmission of ancient technical knowledge, which may teach us something about magical texts, but also about other fields, like medicine, pharmacology, liturgy, and even cuisine.
Utopia Discovered: The Construction of Accessible Grotto - heaven Landscapes in Song Literature
Authors: Wanmeng Li
Published: December 2024

Article Abstract: The Song dynasty witnessed a significant shift in the literary representation of grotto-heavens—the sacred caves initially worshipped in religious Daoism that symbolized enlightenment and abundance. Prior to the Song dynasty, the poetic depiction of grotto-heavens had largely remained a marginal trope, with the few poems extant on this topic portraying the cavern spaces as alien and forbidden. However, Song literati displayed a newfound interest in celebrating grotto-heavens through their poetry. Using a poetry collection dedicated to the Grand Cleanse Grotto-heaven as a representative case, this article demonstrates that Song poets reimagined the enigmatic Daoist grottos as landscapes accessible to secular literati. Their literary reimagination of grotto-heavens as accessible places illuminates literati attempts to expand their knowledge by drawing inspiration from Daoist treatises, the legacies of earlier literary paragons, and their personal experiences visiting grotto-heaven landscapes.
Trade Unions in my Time – An Intergenerational Discussion
Authors: Bonnin Debby
Published: December 2024

Abstract: This is an edited version of the panel discussion that took place at the Conference '1973 Durban Strikes – Celebrating 50 Years' January 26-28, 2023, held at the Durban University of Technology, Durban. The panel discussion was set for two hours on the first day of the conference; it was followed by questions and debates from the floor. These continued in the first session of the second day. The discussions were recorded, transcribed and then edited by Debby Bonnin. Questions and comments from the floor have been kept anonymous as participants were not asked to give permission for their questions to be published .
Subcycle spectral structures of light-induced states in attosecond transient absorption of helium dressed by an orthogonally polarized laser field
Authors: Du Ling-Ling , Liu He-Chuan , Zhang Hui-Lin , Wang Zhi-Bin , Li Peng-Cheng
Published: December 2024

We present the subcycle spectral structures from attosecond transient absorption spectra of helium by accurately solving the full three-dimensional time-dependent Schrödinger equation in extreme ultraviolet attosecond pulse and an orthogonally polarized infrared (IR) laser field. We discover that the subcycle spectral features associated with the dressed 1snp (n ≥ 4) states and light-induced states, referred to as ns−, nd−, np− and nf−, can be strongly modified or even enhanced when the strength ratio of the orthogonal laser field in two polarized laser directions changes. To understand the spectral evolution of the subcycle structures, we perform calculations of the time-dependent population and time-frequency analysis. The results indicate that more quantum channels can be opened by the attosecond pulse combined with the orthogonally polarized IR laser field, leading to robust absorption spectra of light-induced states. Our theoretical findings predict that the orthogonally polarized laser field is useful for manipulating subcycle transition dynamics in the transient absorption process.
A universal and effective variational method for destriping: application to light-sheet microscopy, FIB-SEM, and remote sensing images
Authors: Rottmayer Niklas , Redenbach Claudia , Fahrbach Florian O.
Published: December 2024

Stripe artifacts are a common problem for various imaging techniques such as light-sheet fluorescence microscopy (LSFM), electron microscopy, and remote sensing. These artifacts are characterized by their elongated shapes, compromised image quality, and impede further analysis. To address the primary challenge of removing the stripe artifacts while preserving the object structures we present an improved variational method for stripe removal with intuitive parametrization. Comparison against previously published methods on images from LSFM, FIB-SEM, and remote sensing by visual inspection and quantitative metrics demonstrates the superior capability of the approach. Based on synthetic LSFM data obtained by simulation of physical light-propagation we enriched our analysis by the comparison of processed images to ground truth data and quantitatively confirmed that our method outperforms existing solutions in terms of improved removal of artifacts and retention of image structures. The open availability of our solution and the flexibility in handling variations in stripe orientation and thickness ensure its broad applicability across diverse imaging scenarios.
Nonlinear and nonlinear-linear hybrid interferometers using coherent and squeezed vacuum states
Authors: Zhang Jian-Dong , Jia Fan , Hou Lili , Wang Shuai
Published: December 2024

Classical and quantum states working in concert play an essential role in high-precision interferometry. In this regard, coherent combined with squeezed vacuum states are the most promising candidate. Here we complement this subject by comparing nonlinear and nonlinear-linear hybrid interferometers with homodyne detection as a readout strategy. For a high-photon coherent state, either of the two interferometers can provide the phase sensitivity approaching the quantum Cramer-Rao bound. Additionally, we discuss the impacts of photon loss during the transmission and readout stages. We find that a nonlinear interferometer is advantageous over a nonlinear-linear hybrid interferometer. With increasing photon number of the coherent state, the maximal tolerable lossy rate ensuring phase sensitivity beyond the shot-noise limit is close to 50%. Our work may deepen the understanding of quantum-enhanced interferometry using nonlinear dynamics.
Generation of programmable GHz burst-mode ultrashort pulses using free-space angular-chirp-enhanced delay
Authors: Wen Xiaoxiao , Zeng Yan , Dong Jiangli , Wang Tianxi , Wei Chiyi , Wei Xiaoming , Wong Kenneth K. Y.
Published: December 2024

In this work, we propose a method for generating programmable GHz burst-mode ultrashort pulses from existing pulse sources with kHz-MHz fundamental repetition rates. It enables flexibly controlling the pulse number and intensity pattern of GHz pulse burst, as well as the repetition rate of the intra-pulses and physical time delay of the pulse. This method leverages an acousto-optic deflector (AOD) with radio-frequency encoded programmability in conjunction with a pair of long non-parallel mirrors, known as free-space angular-chirp-enhanced delay (FACED). The AOD enables real-time programming of the angular difference for aligning with the discrete angular reflection condition of FACED, facilitating the programmable splitting of a single pulse into burst-mode pulses with a GHz repetition rate. The versatility of this burst-mode GHz ultrashort pulses generation technique makes it well-suited for various applications, including material processing and nonlinear imaging.
Generation of 100 W, millijoule-class picosecond laser from a single-stage Yb:YAG dual-crystal bulk amplifier
Authors: Gao Guanguang , Song Jiajun , Peng Yujie , Shen Liya , Zhu Junze , Liu Yinfei , Leng Yuxin
Published: December 2024

We demonstrate a dual-crystal Yb:YAG bulk regenerative amplifier that delivers a hundred-watt average power and millijoule-class pulse energy. The repetition rate of the presented laser is tunable from 50 kHz to 300 kHz, with the highest pulse energy and laser power of 1.9 mJ and 108.9 W, respectively. This presents the highest average power we know of for a single-stage Yb:YAG bulk picosecond laser. Profiting from thermally insensitive dual-crystal regenerative cavity design and the exceptional thermomechanical properties of the Yb:YAG crystals, both the amplification efficiency and beam quality barely deteriorated as pump power increased. The compressed spectral bandwidth and pulse duration are 1.02 nm and 1.45 ps, respectively, with a compression efficiency of 92.7%. The presented laser source could be employed as the pre-pulse for extreme ultraviolet pump source for optical parametric chirped pulse amplifier, or as the front end for high-power thin-disk/Inno-slab lasers.
Analyzing the effect of doping concentration in split-well resonant-phonon terahertz quantum cascade lasers: erratum
Authors: Levy Shiran , Gower Nathalie Lander , Piperno Silvia , Addamane Sadhvikas J. , Reno John L. , Albo Asaf
Published: December 2024

An erratum to correct a mistake in the caption of Fig. 5. [Opt. Express 32, 12040 (2024)] 10.1364/OE.515419. The corrections have no influence on the results and conclusions of the original paper.
3D printing fiber-tip integrated Fabry–Perot interferometers for ultrasensitive RI sensing with an enhanced Vernier effect
Authors: Fan Desheng , Qu Xiwen , Shi Qiang , Luo Yanhua , Chu Yushi , Xiao Gui , Ni Jiasheng , Zhang Wei , Zhang Jianzhong , Peng Gangding
Published: December 2024

An ultrasensitive refractive index (RI) sensing technology based on an enhanced Vernier effect is proposed, which integrates a polymer Fabry–Perot interferometer (FPI) with an open cavity FPI on the tip of a seven-core optical fiber. Interference spectra of the polymer FPI and the open cavity FPI shift to opposite directions as the ambient RI changes, thus leading to the enhanced Vernier effect. Investigations of RI sensitivity and temperature dependence of the proposed fiber sensors are carried out. Taking advantage of the enhanced Vernier effect, we demonstrate a remarkable sensitivity of 19742.86 nm/RIU within the RI range from 1.39 to 1.395. The sensor exhibits substantial advantages such as ease of fabrication, compact structure, high sensitivity, and good repeatability, providing a practical and competitive solution for RI sensing.
Low-complexity 24-h 29-km inter-island real-time FSO communication under strong turbulences
Authors: Guo Meng , Li Bohan , Wang Yifan , Lu Zehui , Xu Dongye , Xiang Qirong , Xiong Lingyi , Li Changjin , Duan Shaoxiang , Yao Yuan , Zhang Hao , Lin Wei , Liu Haifneg , Liu Bo
Published: December 2024

Free space optical communication (FSOC) technology can be used for data transmission between ocean islands as backup wireless communication networks to cope with traffic surges and emergencies. In this paper, we experimentally demonstrate the results of a 24-h real-time single-wavelength 2.5-Gbps FSOC between two islands 29 km apart at a low altitude with low complexity. On–off keying signals generated by field-programmable gate array (FPGA) board and commercial low-cost SFP + optical modules are employed as transceiver signals. At the receiving end, a 250-mm large-aperture Cassegrain telescope and 105-µm multi-mode fibers (MMFs) are utilized to reduce the scintillation index from 1.5 to 0.48 and from 0.55 to 0.25 under strong and weak fluctuations, respectively. The averaged receiving optical power, scintillation index, and average bit rate error (BER) are experimentally observed over a 24-hour period with an averaged transmitting power of 36 dBm. The experimental results show that the proportions reach 93.73% and 99.9% for BER below 1 × 10−6 and 1 × 10−3, respectively.
Design and analysis of an optically efficient and commercially viable OA-HMD
Authors: Mousavi Fard Sayed Sajjad , Farhadian Amir Hossein
Published: December 2024

Off-axis helmet mounted displays (OA-HMDS) are used in various fields, but refractive types are declining in popularity due to poor light transmission and limited spectral range. We propose a solution using efficient polarization converters and a polarizing beam splitters coating (PBS), enhancing optical efficiency with a compact projection module and spherical collimator. Our design offers a monocular field of view of 50° diagonally and features a 10 mm entrance pupil with 76.26 mm eye relief. It operates reliably from -40°C to +70°C achieving a diffraction-limited resolution of 1920 × 1200 wide ultra extended graphics array (WUXGA).
Neural networks with optimized single-neuron adaptation uncover biologically plausible regularization
Authors: Geadah Victor , Horoi Stefan , Kerg Giancarlo , Wolf Guy , Lajoie Guillaume
Published: December 2024

Neurons in the brain have rich and adaptive input-output properties. Features such as heterogeneous f-I curves and spike frequency adaptation are known to place single neurons in optimal coding regimes when facing changing stimuli. Yet, it is still unclear how brain circuits exploit single-neuron flexibility, and how network-level requirements may have shaped such cellular function. To answer this question, a multi-scaled approach is needed where the computations of single neurons and neural circuits must be considered as a complete system. In this work, we use artificial neural networks to systematically investigate single-neuron input-output adaptive mechanisms, optimized in an end-to-end fashion. Throughout the optimization process, each neuron has the liberty to modify its nonlinear activation function parametrized to mimic f-I curves of biological neurons, either by learning an individual static function or via a learned and shared adaptation mechanism to modify activation functions in real-time during a task. We find that such adaptive networks show much-improved robustness to noise and changes in input statistics. Using tools from dynamical systems theory, we analyze the role of these emergent single-neuron properties and argue that neural diversity and adaptation play an active regularization role, enabling neural circuits to optimally propagate information across time. Finally, we outline similarities between these optimized solutions and known coding strategies found in biological neurons, such as gain scaling and fractional order differentiation/integration.
ClustAll: An R package for patient stratification in complex diseases
Authors: Ortega-Legarreta Asier , Palomino-Echeverria Sara , Huergo Estefania , Lagani Vincenzo , Kiani Narsis A. , Rautou Pierre-Emmanuel , Picola Nuria Planell , Tegner Jesper , Gomez-Cabrero David
Published: December 2024

In the era of precision medicine, it is necessary to understand heterogeneity among patients with complex diseases to improve personalized prevention and management strategies. Here, we introduce ClustAll, a Bioconductor package designed for unsupervised patient stratification using clinical data. ClustAll is based on the previously validated methodology ClustAll, a clustering framework that effectively handles intricacies in clinical data, including mixed data types, missing values, and collinearity. Additionally, ClustAll stands out in its ability to identify multiple patient stratifications within the same population while ensuring their robustness. The updated implementation of ClustAll features S4 classes, parallel computing for enhanced computational efficiency, and user-friendly tools for exploring and comparing stratifications against clinical phenotypes. The performance of ClustAll has been validated using two public clinical datasets, confirming its effectiveness in patient stratification and highlighting its potential impact on clinical management. In summary, ClustAll is a powerful tool for patient stratification in personalized medicine.
Tree polynomials identify a link between co-transcriptional R-loops and nascent RNA folding
Authors: Liu Pengyu , Lusk Jacob , Jonoska Nataša , Vázquez Mariel
Published: December 2024

R-loops are a class of non-canonical nucleic acid structures that typically form during transcription when the nascent RNA hybridizes the DNA template strand, leaving the non-template DNA strand unpaired. These structures are abundant in nature and play important physiological and pathological roles. Recent research shows that DNA sequence and topology affect R-loops, yet it remains unclear how these and other factors contribute to R-loop formation. In this work, we investigate the link between nascent RNA folding and the formation of R-loops. We introduce tree-polynomials, a new class of representations of RNA secondary structures. A tree-polynomial representation consists of a rooted tree associated with an RNA secondary structure together with a polynomial that is uniquely identified with the rooted tree. Tree-polynomials enable accurate, interpretable and efficient data analysis of RNA secondary structures without pseudoknots. We develop a computational pipeline for investigating and predicting R-loop formation from a genomic sequence. The pipeline obtains nascent RNA secondary structures from a co-transcriptional RNA folding software, and computes the tree-polynomial representations of the structures. By applying this pipeline to plasmid sequences that contain R-loop forming genes, we establish a strong correlation between the coefficient sums of tree-polynomials and the experimental probability of R-loop formation. Such strong correlation indicates that the pipeline can be used for accurate R-loop prediction. Furthermore, the interpretability of tree-polynomials allows us to characterize the features of RNA secondary structure associated with R-loop formation. In particular, we identify that branches with short stems separated by bulges and interior loops are associated with R-loops.
Adapting to time: Why nature may have evolved a diverse set of neurons
Authors: Habashy Karim G. , Evans Benjamin D. , Goodman Dan F. M. , Bowers Jeffrey S.
Published: December 2024

Brains have evolved diverse neurons with varying morphologies and dynamics that impact temporal information processing. In contrast, most neural network models use homogeneous units that vary only in spatial parameters (weights and biases). To explore the importance of temporal parameters, we trained spiking neural networks on tasks with varying temporal complexity, holding different parameter subsets constant. We found that adapting conduction delays is crucial for solving all test conditions under tight resource constraints. Remarkably, these tasks can be solved using only temporal parameters (delays and time constants) with constant weights. In more complex spatio-temporal tasks, an adaptable bursting parameter was essential. Overall, allowing adaptation of both temporal and spatial parameters enhances network robustness to noise, a vital feature for biological brains and neuromorphic computing systems. Our findings suggest that rich and adaptable dynamics may be the key for solving temporally structured tasks efficiently in evolving organisms, which would help explain the diverse physiological properties of biological neurons.
Neonatal apnea and hypopnea prediction in infants with Robin sequence with neural additive models for time series
Authors: Vetter Julius , Lim Kathleen , Dijkstra Tjeerd M. H. , Dargaville Peter A. , Kohlbacher Oliver , Macke Jakob H. , Poets Christian F.
Published: December 2024

Neonatal apneas and hypopneas present a serious risk for healthy infant development. Treating these adverse events requires frequent manual stimulation by skilled personnel, which can lead to alarm fatigue. This study aims to develop and validate an interpretable model that can predict apneas and hypopneas. Automatically predicting these adverse events before they occur would enable the use of methods for automatic intervention. We propose a neural additive model to predict individual occurrences of neonatal apnea and hypopnea and apply it to a physiological dataset from infants with Robin sequence at risk of upper airway obstruction. The dataset will be made publicly available together with this study. Our proposed model allows the prediction of individual apneas and hypopneas, achieving an average AuROC of 0.80 when discriminating segments of polysomnography recordings starting 15 seconds before the onset of apneas and hypopneas from control segments. Its additive nature makes the model inherently interpretable, which allowed insights into how important a given signal modality is for prediction and which patterns in the signal are discriminative. For our problem of predicting apneas and hypopneas in infants with Robin sequence, prior irregularities in breathing-related modalities as well as decreases in SpO2 levels were especially discriminative. Our prediction model presents a step towards an automatic prediction of neonatal apneas and hypopneas in infants at risk for upper airway obstruction. Together with the publicly released dataset, it has the potential to facilitate the development and application of methods for automatic intervention in clinical practice.
TransferGWAS of T1-weighted brain MRI data from UK Biobank
Authors: Rakowski Alexander , Monti Remo , Lippert Christoph
Published: December 2024

Genome-wide association studies (GWAS) traditionally analyze single traits, e.g., disease diagnoses or biomarkers. Nowadays, large-scale cohorts such as UK Biobank (UKB) collect imaging data with sample sizes large enough to perform genetic association testing. Typical approaches to GWAS on high-dimensional modalities extract predefined features from the data, e.g., volumes of regions of interest. This limits the scope of such studies to predefined traits and can ignore novel patterns present in the data. TransferGWAS employs deep neural networks (DNNs) to extract low-dimensional representations of imaging data for GWAS, eliminating the need for predefined biomarkers. Here, we apply transferGWAS on brain MRI data from UKB. We encoded 36, 311 T1-weighted brain magnetic resonance imaging (MRI) scans using DNN models trained on MRI scans from the Alzheimer’s Disease Neuroimaging Initiative, and on natural images from the ImageNet dataset, and performed a multivariate GWAS on the resulting features. We identified 289 independent loci, associated among others with bone density, brain, or cardiovascular traits, and 11 regions having no previously reported associations. We fitted polygenic scores (PGS) of the deep features, which improved predictions of bone mineral density and several other traits in a multi-PGS setting, and computed genetic correlations with selected phenotypes, which pointed to novel links between diffusion MRI traits and type 2 diabetes. Overall, our findings provided evidence that features learned with DNN models can uncover additional heritable variability in the human brain beyond the predefined measures, and link them to a range of non-brain phenotypes.
The cells are all-right: Regulation of the Lefty genes by separate enhancers in mouse embryonic stem cells
Authors: Taylor Tiegh , Zhu Hongyu Vicky , Moorthy Sakthi D. , Khader Nawrah , Mitchell Jennifer A.
Published: December 2024

Enhancers play a critical role in regulating precise gene expression patterns essential for development and cellular identity; however, how gene-enhancer specificity is encoded within the genome is not clearly defined. To investigate how this specificity arises within topologically associated domains (TAD), we performed allele-specific genome editing of sequences surrounding the Lefty1 and Lefty2 paralogs in mouse embryonic stem cells. The Lefty genes arose from a tandem duplication event and these genes interact with each other in chromosome conformation capture assays which place these genes within the same TAD. Despite their physical proximity, we demonstrate that these genes are primarily regulated by separate enhancer elements. Through CRISPR-Cas9 mediated deletions to remove the intervening chromatin between the Lefty genes, we reveal a distance-dependent dosage effect of the Lefty2 enhancer on Lefty1 expression. These findings indicate a role for chromatin distance in insulating gene expression domains in the Lefty locus in the absence of architectural insulation.
Screening novel antiviral compounds to treat Clostridioides difficile infections
Authors: Stolz Brice J. , Abouelkhair Ahmed A. , Seleem Mohamed N.
Published: December 2024

Clostridioides difficile is a major cause of nosocomial infections, often associated with individuals who have gut dysbiosis from previous antibiotic therapies. C. difficile infections (CDI) have a high recurrence rate and impose significant financial and mortality burdens on the healthcare system. Therefore, novel anti-C. difficile drugs are urgently needed to treat and reduce the severity and recurrence of infection. In this study, we screened a library of 618 antiviral drugs to identify a potential candidate for repurposing as novel anti-C. difficile therapeutics. Following our preliminary screening, we identified 9 novel compounds that inhibited C. difficile at a concentration of 16 μM or lower. Among these, 4 antiviral compounds demonstrated the most potent anti-C. difficile activity against a panel of 15 C. difficile isolates, with minimum inhibitory concentrations (MICs) comparable to the drug of choice, vancomycin. These include rottlerin (MIC50 = 0.25 μg/mL), α-mangostin (MIC50 = 1 μg/mL), dryocrassin ABBA (MIC50 = 1 μg/mL), and obefazimod (MIC50 = 4 μg/mL). All exhibited minimal to no activity against representative members of the human gut microbiota. Interestingly, α-mangostin, a natural xanthone derived from the mangosteen fruit, exhibited strong bactericidal action, clearing a high inoculum of C. difficile in less than an hour. All other drugs exhibited bacteriostatic activity. Given their characteristics, these compounds show great promise as novel treatments for CDI.
Estimating the time of Highly Pathogenic Avian Influenza virus introduction into United States poultry flocks during the 2022/24 epizootic
Authors: Ssematimba Amos , Malladi Sasidhar , Bonney Peter J. , St. Charles Kaitlyn M. , Hutchinson Holden C. , Schoenbaum Melissa , Marusak Rosemary , Culhane Marie R. , Cardona Carol J.
Published: December 2024

Following confirmation of the first case of the ongoing U.S. HPAI H5N1 epizootic in commercial poultry on February 8, 2022, the virus has continued to devastate the U.S. poultry sector and the pathogen has since managed to cross over to livestock and a few human cases have also been reported. Efficient outbreak management benefits greatly from timely detection and proper identification of the pathways of virus introduction and spread. In this study, we used changes in mortality rates as a proxy for HPAI incidence in a layer, broiler and turkey flock together with diagnostic test results to infer within-flock HPAI transmission dynamics. Mathematical modeling techniques, specifically the Approximate Bayesian Computation algorithm in conjunction with a stochastic within-flock HPAI transmission model were used in the analysis. The time window of HPAI virus introduction into the flock (TOI) and the adequate contact rate (ACR) were estimated. Then, using the estimated TOI together with the day when the first HPAI positive sample was collected from the flock, we calculated the most likely time to first positive sample (MTFPS) which reflects the time to HPAI detection. The estimated joint (i.e., all species combined) median of the MTFPS for different flocks was six days, the joint median most likely ACR was 6.8 newly infected birds per infectious bird per day, the joint median R0 was 13 and the joint median number of test days per flock was two. These results were also grouped by species and by epidemic phase and discussed accordingly. We conclude that this findings from this and other related studies are beneficial for the different stakeholders in outbreak management. We recommend that combining TOI analysis with complementary approaches such as phylogenetic analyses is critically important for improved understanding of disease transmission pathways. The estimated parameters can also be used to parametrize mathematical models that can guide the design of surveillance protocols, risk analyses of HPAI spread, and emergency preparedness for HPAI outbreaks.
Suicide methods among Brazilian women from 1980 to 2019: Influence of age, period, and cohort
Authors: Meira Karina Cardoso , Guimarães Raphael Mendonça , Silva Glauber Weder Santos , Jomar Rafael Tavares , Dantas Eder Samuel Oliveira
Published: December 2024

Objective

To analyze the effect of age, period, and cohort on suicides among women by hanging, strangulation, suffocation, firearms, and autointoxication in different Brazilian regions from 1980 to 2019.

Methods

Ecological time-trend study employing estimable functions to estimate APC models, facilitated through the Epi library of the R statistical program, version 4.2.1. Specific rates by age group per 100,00 women and relative risks by period and cohort were estimated using this method.

Results

Between 1980 and 2019, 49,997 suicides among women were reported using the methods under study. Higher suicide rates per 100,000 women were observed in the South using strangulation and suffocation (2.42), while lower firearm suicide rates were observed in the Northeast (0.13). After adjusting the APC model, there was an increase in age-specific rates with advancing age across all regions for suicides by hanging, strangulation, and suffocation. In contrast, suicides by firearms and autointoxication showed a decrease in rates with advancing age. The period effect indicated an increased risk of suicides by hanging, strangulation (RR >1 and p<0.05) in the five-year intervals of the 2000s in the North, Southeast, and South regions. During the same period, there was an increased risk of suicides by autointoxication in the Southeast, South, and Northeast (RR>1, p<0.05). Suicides by firearms exhibited a statistically significant reduction in the risk of death from 2005 to 2019 in the Southeast and South regions, and from 2005 to 2014 in the Northeast and Midwest. The observed increase in the North region was not statistically significant (RR>1, p>0.05). The cohort effect demonstrated an increased risk of suicides by hanging, strangulation in younger cohorts (RR>1, p<0.05), whereas other methods showed an elevated risk in older cohorts relative to the 1950–1954 generation.

Conclusion

The results presented here may suggest changes in suicide method preferences between 1980 and 2019.
Integrated child nutrition, parenting, and health intervention in rural Liberia: A mixed-methods feasibility study
Authors: Isanovic Sejla , Sanoe Musa , Wooten Shelbie , Frongillo Edward A. , Yousafzai Aisha K. , Blake Christine E. , Kanyangarara Mufaro , Swan Melanie , Rodger Nicole , Murray Miriam , Larson Leila M.
Published: December 2024

In Liberia, children are exposed to multiple forms of adversity which can negatively impact their health and development. Research is needed to examine the feasibility and benefits of integrated interventions that can be incorporated into existing health delivery programs to simultaneously address low responsive stimulation, undernutrition, and infection. This study assessed the feasibility of an integrated intervention promoting psychosocial stimulation and improved child feeding by the provision of eggs and fish. The integrated intervention was incorporated into an existing government health program. Thirty female caregiver-child dyads were randomly selected from two rural communities in Liberia. Participants received fortnightly group parenting sessions and weekly eggs and fish designated for child consumption, for four weeks. Trained community health workers delivered the intervention. Assessments were conducted before and after the intervention using quantitative surveys and qualitative interviews. At baseline, we examined the home environment, caregiver-child interactions, diet, and infection control practices. At endline, we assessed the feasibility of the intervention. Descriptive analyses were conducted with quantitative data. Qualitative data were analyzed using conventional content analysis. Baseline findings indicated uncommon responsive parenting, inadequate early learning opportunities, high food insecurity, and high child morbidity. Mixed methods indicators of feasibility, including acceptability, adoption, and fidelity were high. Qualitative data from this feasibility study informed several future modifications to the program, including engaging fathers, supplementing group sessions with home visits, and broadening facilitator eligibility. This integrated intervention is feasible and can be incorporated into existing health programs to support early child development.
Prediction method of sugarcane important phenotype data based on multi-model and multi-task
Authors: Sun Jihong , Sun Chen , Li Zhaowen , Qian Ye , Li Tong
Published: December 2024

The efficacy of generalized sugarcane yield prediction models holds significant implications for global food security. Given that machine learning algorithms often surpass the precision of remote sensing technology, further exploration of machine learning algorithms in the development of sugarcane yield prediction models is imperative. In this study, we employed six key phenotypic traits of sugarcane, specifically plant height, stem diameter, third-node length (internode length), leaf length, leaf width, and field brix, along with eight machine learning methods: logistic regression, linear regression, K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Backpropagation Neural Network (BPNN), Decision Tree, Random Forest, and the XGBoost algorithm. The aim was to establish an intelligent model ensemble for predicting two crucial phenotypic characteristics—stem diameter and plant height—that determine sugarcane yield, ultimately enhancing the overall yield.The experimental findings indicate that the XGBoost algorithm outperforms the other seven algorithms in predicting these significant phenotypic traits of sugarcane. Furthermore, an analysis of the sugarcane intelligent prediction model’s performance under a specialized data environment, incorporating self-prepared data, reveals that the XGBoost algorithm exhibits greater stability. Notably, the data pertaining to these crucial phenotypic traits have a profound impact on the efficacy of the intelligent models. The research demonstrates that a sugarcane yield prediction model ensemble, incorporating multiple intelligent algorithms, can accurately forecast stem diameter and plant height, thereby predicting sugarcane yield. Additionally, this approach, combined with the principles of sugarcane cross-breeding, provides a valuable reference for the artificial breeding of new sugarcane varieties that excel in stem diameter and plant height, bridging a research gap in indirect yield prediction through sugarcane phenotypic traits.