bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of gas control lane of 9# coal seam in Wuhushan Mine based on layer layout optimization
Authors: Zhang Chun , Qian Xianju
Published: October 2024

In order to address the issue of gas over limit in the upper corner of the working face of the 9# coal seam in Wuhushan Mine, a series of theoretical and numerical simulation analyses were conducted to evaluate the optimal configuration for the gas control lane of the 9# coal seam. In accordance with the "O" circle theory and the lithology of the overlying rock strata of the 9# coal seam, the height range of the fallout zone and fissure zone in the working face mining area was determined by employing empirical formulas. The change rule and distribution characteristics of the porosity of the fissure zone and the fall zone in the mining area were analyzed based on the characteristics of rock movement and fall. The determination method was also provided. The numerical simulation software was employed to simulate and analyze the gas concentration field in the air-mining zone under conditions of no extraction and six distinct layer positions of the gas control lane. The optimal layer position of the gas control lane in the 9# coal seam was determined and subsequently implemented in the field. The results demonstrate that the overlying rock layer in the 9# coal seam exhibits a height range of 6.86 ~ 11.26 m, while the fissure zone displays a height range of 30.11 ~ 41.31 m. When the gas control road is situated in close proximity to the working face, the gas concentration field exhibits a markedly low concentration. When the distance between the gas control lane and the return airway of the working face is 20 m and the distance from the top of the coal seam is 20 m, the gas concentration in the upper corner and the return airway is 0.35% and 0.26%, respectively. These values are close to the lowest concentration observed in the layout scheme. Additionally, the gas extraction concentration and the pure volume of the gas control lane are 23.7% and 38.3 m3 min−1, respectively. These values represent the highest concentrations observed in the various layout schemes. The application of the gas management lane in the field, based on the numerical simulation results, demonstrated a successful extraction effect, which was consistent with the numerical simulation results. This effectively managed the issue of an over-limit of gas in the upper corner of the working face of the 9# coal seam.
The effects of RT-qPCR standards on reproducibility and comparability in monitoring SARS-CoV-2 levels in wastewater
Authors: Juutinen Aapo , Tiwari Ananda , Hokajärvi Anna-Maria , Luomala Oskari , Kolehmainen Aleksi , Nurmi Eveliina , Salmivirta Elisa , Pitkänen Tarja , Lipponen Anssi
Published: October 2024

Reverse transcription-quantitative PCR (RT-qPCR) is widely used for monitoring viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in wastewater. Various materials, including plasmid DNA, synthetic nucleic acids, PCR amplicons, genomic DNA, and cDNA, are currently used for SARS-CoV-2 quantification by generating standard curves. We assessed three common standards on quantifying SARS-CoV-2 RNA across nine wastewater treatment plants in Finland, as part of the national wastewater surveillance effort. We pairwise compared RT-qPCR results from 148 wastewater samples, using both IDT (#10006625, IDT, USA) and CODEX standards (#SC2-RNAC-1100, CODEX DNA), and 179 samples using both IDT and EURM019 standards (#EURM-019, European Commission, Joint Research Centre) in our assessment. Amongst the tested standards, the CODEX standard consistently yielded more stable results than either the IDT or EURM019 standards. We found that SARS-CoV-2 levels were higher with the IDT standard (4.36 Log10 GC/100 mL) compared to the CODEX standard (4.05 Log10 GC/100 mL). Similarly, quantification using the IDT standard was higher (5.27 Log10 GC/100 mL) than values obtained with the EURM019 (4.81 Log10 GC/100 mL). SARS-CoV-2 RNA quantified with IDT and CODEX standards exhibited stronger concordance (Spearman’s correlation rho median of 0.79) compared to those quantified with IDT and EURM019 standards (rho median of 0.59). This study highlights the significant impact of standard material selection on SARS-CoV-2 RNA quantification, emphasizing the need for harmonization in standard material.
A high voltage gain solid-state transformer for integration of renewable energy and AC sources
Authors: Hashemzadeh Seyed Majid , Al-Hitmi Mohammed A. , Islam Shirazul , Iqbal Atif , Aghaei Hadi , Hosseini Seyed Hossein , Babaei Ebrahim
Published: October 2024

This paper introduces a novel high-voltage gain topology for a solid-state transformer, integrating a DC-DC converter and dual active bridge converters. The proposed design features three DC links operating at different voltage levels. The first DC link connects to a single-switch high step-up DC-DC converter, while the second DC link interfaces with an AC source via a rectifier, allowing the use of both DC and AC inputs. A high-frequency transformer ensures galvanic isolation between the sources and the third DC link. The DC-DC converter employs coupled inductors and voltage multiplier cells, offering distinct advantages such as a high voltage gain, reduced voltage stress on semiconductors, and minimized current ripple. These features make the topology highly suitable for transferring power from renewable energy sources, such as photovoltaic panels, to a high-voltage DC link in microgrid or nanogrid applications. The novelty lies in the combination of multiple voltage levels, high-frequency isolation, and the ability to handle both DC and AC inputs efficiently. An experimental prototype, delivering 620 W with a 25 V DC input and 110 V AC input, is built, and the results validate the converter’s effectiveness.
Grating-based phase-contrast computed tomography for breast tissue at an inverse compton source
Authors: Berthe Daniel , Heck Lisa , Resch Sandra , Dierolf Martin , Brantl Johannes , Günther Benedikt , Petrich Christian , Achterhold Klaus , Pfeiffer Franz , Grandl Susanne , Hellerhoff Karin , Herzen Julia
Published: October 2024

The introduction of mammography screening programs has significantly reduced breast cancer mortality rates. Nevertheless, some lesions remain undetected, especially in dense breast tissue. Studies have shown that phase-contrast imaging can improve breast cancer diagnosis by increasing soft tissue contrast. Furthermore, grating-based phase-contrast imaging enables the simultaneous acquisition of absorption, phase-contrast, and scattering, so-called dark-field images. The latter allows the classification of microcalcifications. In addition, breast computed tomography (BCT) systems can identify and discriminate overlapping but clinically relevant structures. This study investigates the benefit of combining grating-based phase-contrast with BCT. We explore the potential of grating-based phase-contrast breast computed tomography (gbpc-BCT) with a breast phantom and a freshly dissected fibroadenoma. Improved image contrast could be achieved with radiation doses comparable to those used in clinical BCT.
Identification of diagnostic markers pyrodeath-related genes in non-alcoholic fatty liver disease based on machine learning and experiment validation
Authors: Lei Liping , Li Jixue , Liu Zirui , Zhang Dongdong , Liu Zihan , Wang Qing , Gao Yi , Mo Biwen , Li Jiangfa
Published: October 2024

Non-alcoholic fatty liver disease (NAFLD) poses a global health challenge. While pyroptosis is implicated in various diseases, its specific involvement in NAFLD remains unclear. Thus, our study aims to elucidate the role and mechanisms of pyroptosis in NAFLD. Utilizing data from the Gene Expression Omnibus (GEO) database, we analyzed the expression levels of pyroptosis-related genes (PRGs) in NAFLD and normal tissues using the R data package. We investigated protein interactions, correlations, and functional enrichment of these genes. Key genes were identified employing multiple machine learning techniques. Immunoinfiltration analyses were conducted to discern differences in immune cell populations between NAFLD patients and controls. Key gene expression was validated using a cell model. Analysis of GEO datasets, comprising 206 NAFLD samples and 10 controls, revealed two key PRGs (TIRAP, and GSDMD). Combining these genes yielded an area under the curve (AUC) of 0.996 for diagnosing NAFLD. In an external dataset, the AUC for the two key genes was 0.825. Nomogram, decision curve, and calibration curve analyses further validated their diagnostic efficacy. These genes were implicated in multiple pathways associated with NAFLD progression. Immunoinfiltration analysis showed significantly lower numbers of various immune cell types in NAFLD patient samples compared to controls. Single sample gene set enrichment analysis (ssGSEA) was employed to assess the immune microenvironment. Finally, the expression of the two key genes was validated in cell NAFLD model using qRT-PCR. We developed a prognostic model for NAFLD based on two PRGs, demonstrating robust predictive efficacy. Our findings enhance the understanding of pyroptosis in NAFLD and suggest potential avenues for therapeutic exploration.
Running in mice increases the expression of brain hemoglobin-related genes interacting with the GH/IGF-1 system
Authors: Walser Marion , Karlsson Lars , Motalleb Reza , Isgaard Jörgen , Kuhn H. Georg , Svensson Johan , Åberg N. David
Published: October 2024

The beneficial effects of exercise are partly mediated via local or systemic functions of the insulin-like growth factor-1 (IGF-1) system. As IGF-1 increases local brain hemoglobin beta (Hbb) transcripts, we hypothesized that exercise could have similar effects. Mice were single-housed with free access to running wheels for seven days. After sacrifice and saline perfusion, the expression of 13 genes was quantified using real-time quantitative polymerase chain reaction (RT-qPCR) in three brain regions: the prefrontal cortex, motor cortex, and hippocampus. In addition, plasma insulin, glucose, homeostatic model assessment of IR (HOMA-IR), C-peptide, and IGF-1 were investigated. We show that hemoglobin-related transcripts (Hbb and 5’-aminolevulinate synthase 2 [Alas2]) increased 46–63% in the running group, while IGF-1-related genes [Igf1 / growth hormone receptor (Ghr)] decreased slightly (7%). There were also moderate to large correlations between Hbb- and IGF-1-related genes in the running group but not in the sedentary group. HOMA-IR, plasma glucose, and insulin changed marginally and non-significantly, but there was a trend toward an increase in plasma-IGF-1 in the running group. In conclusion, seven days of running increased Hbb-related transcripts in three brain regions. Hbb-related transcripts correlated with components of the brain IGF-1 system only in the running group.
Mapping the energy-momentum dispersion of hBN excitons and hybrid plasmons in hBN-WSe2 heterostructures
Authors: Nerl Hannah C. , Guerrero-Felipe Juan Pablo , Valencia Ana M. , Elyas Khairi Fahad , Höflich Katja , Koch Christoph T. , Cocchi Caterina
Published: October 2024

Heterostructures obtained by combining two-dimensional (2D) sheets are widely investigated as a platform for designing new materials with customised characteristics. Transition metal dichalcogenides (TMDCs) are often combined with hexagonal boron nitride (hBN) to enhance their excitonic resonances. However, little is known about how stacking affects excitons and plasmons in TMDCs or their mutual interactions. Here, we combine momentum-resolved electron energy-loss spectroscopy with first-principles calculations to study the energy-momentum dispersion of plasmons in multi-layer WSe2-hBN heterostructures as well as in their isolated components. The dispersion of the high-momentum excitons of hBN, alone and in combination with WSe2, is mapped across the entire Brillouin zone. Signatures of hybridisation in the plasmon resonances and some of the excitons suggest that the contribution of hBN cannot be neglected when interpreting the response of such a heterostructure. The consequences of using hBN as an encapsulant for TMDCs are also discussed.
Water-surface photovoltaic systems have affected water physical and chemical properties and biodiversity
Authors: Yang Sen , Zhang Youzheng , Tian Defeng , Liu Zekang , Ma Zhijun
Published: October 2024

The implementation of water-surface photovoltaic systems as a source of renewable power has expanded rapidly worldwide in recent decades. Water-surface photovoltaic avoids negative impacts on terrestrial ecosystems, while the impacts on aquatic physical and chemical properties and biodiversity are unclear. To understand the ecological and environmental impacts of water-surface photovoltaic systems, here we conducted a field survey on water physical and chemical properties, plankton and bird communities of 26 water-surface photovoltaic systems in the Yangtze River basin in China during the winter and summer of 2022. We found that water-surface photovoltaic systems decreased water temperature, dissolved oxygen saturation and uncovered area of the water surface, which caused a reduction in plankton species and individual density, altering the community composition. Water-surface photovoltaic systems also caused an overall decrease in bird diversity and changed bird community compositions. These findings suggested that water-surface photovoltaic systems have impacts on the water environment and ecology. Since water-surface photovoltaic systems will continue to expand in the future, our results emphasize that rational planning is critical for the sustainable development of water-surface photovoltaic systems and the protection of the aquatic environment and biodiversity.
Advancing continuous flow techniques in effective trimethoprim oxidation: combatting bacterial resistance in wastewater
Authors: Marques Diana L. , Piccirillo Giusi , Rodrigues Fábio M. S. , Aroso Rafael T. , Dias Lucas D. , da Silva Gabriela J. , Calvete Mário J. F. , Pereira Mariette M.
Published: October 2024

An innovative fixed-bed reactor using covalently immobilized Mn(iii)-porphyrin on silica gel for continuous flow catalytic degradation of trimethoprim is described. The system uses H2O2 as a green oxidant for efficient eco-friendly water treatment.
Investigating Ni nanoparticles on CeO2 for methane dissociation: a comparative study of theoretical calculations and experimental insights
Authors: Fujisaki Takaya , Tsuji Yuta , Tu Phuc Hoan , Doan Tin Chanh Duc , Rivera Rocabado David S. , Staykov Aleksandar Tsekov , Yashiro Keiji , Shiratori Yusuke
Published: October 2024

CeO2 supported with Ni nanoparticles has emerged as a promising catalyst for enhancing the efficiency of dry reforming of methane (DRM) reaction.
Impact of pH on the fabrication of egg white reinforced soy protein composite microgels for gastrointestinal delivery purposes
Authors: Liu Feng , Liu Yi , Zhang Suyun , Liu Gang , Ritzoulis Christos , Zhang Yue
Published: October 2024

Protein molecules such as soy protein isolate (SPI) and egg white (EW) are highly promising materials for developing hydrogels (especially micro/nanogels) for the encapsulation, protection and controlled release of bioactive substances.
Engineering high-valence nickel sites in Ni3S2/Ni3Se2 architectures enabling urea-assisted hydrogen evolution reactions
Authors: Ai Taotao , Bai Miaomiao , Bao Weiwei , Han Jie , Wei Xueling , Zou Xiangyu , Hou Jungang , Zhang Lizhai , Deng Zhifeng , Zhang Yuxin
Published: October 2024

Bifunctional Ni3S2@Ni3Se2 electrocatalysts were constructed for urea-assisted hydrogen evolution. In the HER/UOR two-electrode system, the heterogeneous interface modulates the electronic structure and thus improves the catalytic performance.
Fundamental studies of laser ablation ICPMS using a nitrogen plasma source and helium, argon and nitrogen as carrier gas
Authors: Käser Dylan , Kägi Ralf , Hattendorf Bodo , Günther Detlef
Published: October 2024

Nitrogen as alternative carrier gas for LA-ICPMS showed similar sensitivities and quantification capabilities as using helium in combination with a N2 plasma. The role of the gas and of the ablation cell design on the aerosol structure was studied.
Tandem NiO–Ni(OH)2/VS2 nanosheets: a robust photocatalyst for hydrogen evolution
Authors: NourEldien Mona S. , Nassar Mostafa Y. , Ibrahim Islam M. , Aly Hisham M.
Published: October 2024

Hydrogen is a viable sustainable alternative to fossil fuels, with photocatalysis enhancing its production efficiency and supporting environmental sustainability.
Construction of an ultrathin multi-functional polymer electrolyte for safe and stable all-solid-state batteries
Authors: Zhang Youjia , Cheng Tianhui , Gao Shilun , Ding Hang , Li Zhenxi , Li Lin , Yang Dandan , Yang Huabin , Cao Peng-Fei
Published: October 2024

An ultrathin, flexible and mechanical robust solid polymer electrolyte based on a rationally designed polymer network is developed.
Shape-controlled, water-assisted synthesis of 2D luminescent CsPb2Br5 perovskite microcrystals for highly responsive UV detectors
Authors: Ray Dipayan , Saini Ankush , Kumar Ankit , Kumar Sumit , Bag Monojit , Kar Prasenjit
Published: October 2024

Water-assisted, growth-controlled synthesis of CsPb2Br5 microcrystals for fast responsive UV-detectors.
HSAB theory guiding electrophilic substitution reactions of o-carborane
Authors: Wang Yan , Li Yi-Ge , Chen Feijing , Ma Yan-Na , Chen Xuenian
Published: October 2024

Herein, we systematically compared the reactivity of o-carborane and benzene toward different electrophiles and explained the results with the HSAB principle.
Hydrogel-stabilized supercooled salt hydrates for seasonal storage and controlled release of solar-thermal energy
Authors: Liu Yizhe , Li Xiaoxiang , Xu Yangzhe , Fu Benwei , Song Chengyi , Shang Wen , Tao Peng , Deng Tao
Published: October 2024

Hydrogel networks boost supercooling and thermal cycling stability of salt hydrates, which in turn enables seasonal room-temperature storage and controlled release of solar-thermal energy.
Hydrophilic conjugated polymer additives in fullerene-heterojunction photocatalytic systems for efficient photocatalytic hydrogen evolution
Authors: Tian Li , Guo Shukui , Feng Lingwei , Wang Jichao , Wang Airong , Cui Cheng-xing
Published: October 2024

A novel fullerene-heterojunction photocatalytic system (fullerene-HP) is developed by simply rapid oscillation and rotary evaporation without surfactant. An effective hydrogen evolution activity in the fullerene-HP is achieved with 5% P4EOBDT-TTE.
Thermal optimization of PCM‐based heat sink using fins: A combination of CFD, genetic algorithms, and neural networks
Authors: Bahrami Hamid‐Reza , Saberi Mehdi
Published: October 2024

Sustainable development requires focusing on renewable energy, such as solar power, due to the limited availability of fossil fuels. Solar energy, available only during daylight, can be stored in thermal batteries using phase change materials (PCM). However, PCM has low thermal conductivity, slowing its melting process. Fins have been added to enhance heat diffusion, but their optimal design requires further study. This research examines an annular chamber with fixed inner and outer wall temperatures and explores fin configurations. Two series of evenly spaced fins (four and five) were analyzed, with melting times calculated using CFD simulations. Larger fins reduce melting time but limit PCM storage. Effectiveness, defined as the PCM space over melting time, was used to evaluate performance. Higher boundary temperatures decreased melting time but did not always increase effectiveness. The study also used artificial neural networks (ANN) combined with a genetic algorithm to predict optimal conditions. The configuration with five fins, a 90°C boundary temperature, a fin length of 45 mm, and a thickness of 5.4 mm achieved the highest effectiveness of 4.7, showing that smaller fins at lower temperatures are more efficient.
The rotational disruption of porous dust aggregates from ab initio kinematic calculations
Authors: Reissl Stefan , Nguyen Philipp , Jordan Lucas M. , Klessen Ralf S.
Published: October 2024

Context. The size of dust grains in the interstellar medium follows a distribution where most of the dust mass is made up of smaller grains. However, the redistribution from larger grains towards smaller sizes, especially by means of rotational disruption, is still poorly understood.

Aims. We aim to study the dynamics of porous grain aggregates undergoing an accelerated rotation, namely, a spin-up process that rapidly increases the angular velocity of the aggregate. In particular, we aim to determine the deformation of the grains and the maximal angular velocity up to the rotational disruption event by caused by centrifugal forces.

Methods. We precalculated the porous grain aggregate by means of ballistic aggregation analogous to the interstellar dust as input for subsequent numerical simulations. We performed three-dimensional (3D) N-body simulations, mimicking the radiative torque spin-up process up to the point where the grain aggregates become rotationally disrupted.

Results. Our simulations results are in agreement with theoretical models predicting a characteristic angular velocity, ωdisr, on the order of 108–109 rad s−1, where grains become rotationally disrupted. In contrast to theoretical predictions, we show that for large porous grain aggregates (⪆300 nm), the ωdisr values do not strictly decline. Instead, they reach a lower asymptotic value. Hence, such grains can withstand an accelerated rotation more efficiently up to a factor of 10 because the displacement of mass by centrifugal forces and the subsequent mechanical deformation supports the buildup of new connections within the aggregate. Furthermore, we report that the rapid rotation of grains deforms an ensemble with initially 50:50 prolate and oblate shapes, respectively, preferentially into oblate shapes. Finally, we present a best-fit formula to predict the average rotational disruption of an ensemble of porous dust aggregates dependent on the internal grain structure, total number of monomers, and applied material properties.
Strong Balmer break objects at z ∼ 7–10 uncovered with JWST
Authors: Kuruvanthodi A. , Schaerer D. , Marques-Chaves R. , Korber D. , Weibel A. , Oesch P. A. , Roberts-Borsani G.
Published: October 2024

We report the discovery of robust spectroscopically confirmed Balmer break (BB) galaxies and candidates, with secure spectroscopic redshifts 7.1 ≤ z ≤ 9.6, from publicly available James Webb Space Telescope (JWST) extra-galactic photometric and spectroscopic surveys. To achieve this, we used dedicated filters probing the BB and inspected the objects with NIRSpec spectroscopy. We have recovered the previously known objects with strong BBs and here reveal 10−11 new objects with clear BBs, thus tripling the number of spectroscopically confirmed galaxies with a BB at z > 7. Approximately half of them show a pure BB and no signs of recent star formation, whereas the other half show BB and emission lines, most likely indicating galaxies whose star formation ceased earlier and has restarted recently. Overall, we find that ∼10 − 20% of all galaxies from our sample show signatures of an evolved stellar population. Furthermore, we find that the strength of the BB does not significantly depend on the rest-UV and rest-optical brightness of these sources. In short, our work confirms that photometry alone has the potential to measure BB strengths and to identify evolved stellar populations at high redshift, and that such objects may be more frequent than previously thought. The presence of galaxies with a range of break strengths and the joint presence of BB and emission lines indicate a bursty nature of the star formation in the early Universe.
Schuleingangsuntersuchungen in der ehemaligen Deutschen
Demokratischen Republik (DDR) von 1949 bis 1989 – Eine orientierende Übersicht
zur formalen und inhaltlichen Durchführung
Authors: Knüppel Clara Maria , Stich Heribert
Published: October 2024

Ziel der Studie Zusammenfassende Darstellung der formalen und inhaltlichen
Einschulungspraxis von Schuleingangsuntersuchungen (SEU) in der Deutschen
Demokratischen Republik (DDR).

Methoden Durch eine systematische Literatursichtung auf konventioneller
und internetbasierter Grundlage wurden nach ausgewählten Suchbegriffen
Fachpublikationen und themenbezogene Originaldokumente zielgerichtet verfügbar
gemacht, um wesentliche Merkmale von SEU in der DDR zu erfassen und in einem
Gesamtkontext darzustellen.

Ergebnisse In der DDR erfolgte im Alter von 6 Jahren die regelrechte
Einschulung, wobei deren Durchführungspraxis während der 1950er und 1960er Jahre
formal und inhaltlich uneinheitlich ausgestaltet war. Auf der Grundlage
verpflichtender Reihenuntersuchungen hatte damals die medizinische
Reihenuntersuchung für die Altersgruppe der 5- bis 6-jährigen Kinder formale
Gültigkeit als SEU. Fallbezogen führten die zuständigen Kinderärzte ergänzende,
nicht standardisierte Entwicklungstests durch. Unter anderem durch die
zunehmende Versorgungsdichte mit Kindergärten in der DDR wurde dem dortigen
Fachpersonal ab den 1970er Jahren eine stärkere Einbindung bei der Beurteilung
beschulungsrelevanter Kompetenzen bei Vorschulkindern zugedacht. Daneben gewann
die Reihenuntersuchung für 4- bis 5-jährige Kinder für entwicklungsdiagnostische
Belange zusätzlich an Relevanz. Während anfangs noch diverse Testverfahren
Anwendung fanden, entwickelte sich ab den 1970er Jahren ein standardisiertes
Instrumenteninventar zur Einschätzung der Lernfähigkeit, Denkentwicklung und
Sprachentwicklung sukzessiv heraus. Durch beide zeitlich gestaffelten SEU
konnten im Bedarfsfall frühzeitige Förderungsmaßnahmen bei
entwicklungsverzögerten Kindern ergriffen werden, sodass diesen betroffenen
Kindern adäquate Entwicklungs- und Bildungschancen eröffnet werden konnten. Im
Gefolge dieser Konzeption fand auch eine sich intensivierende, teilweise
informelle Kooperation zwischen dem Fachpersonal in den Kindergärten, den
Kinderärzten, den Eltern und den Schulleitungen statt.

Schlussfolgerung Insgesamt kann festgehalten werden, dass die SEU in der
DDR ab den 1970er Jahren auf ein fachlich durchdachtes Gesamtkonzept basierten.
Zur damaligen Zeit war diese standardisierte, gestaffelte und multidisziplinäre
Vorgehensweise in der DDR der Einschulungspraxis in Westdeutschland methodisch
überlegen.
Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency
Authors: Blanco Elena , Camps Carme , Bahal Sameer , Kerai Mohit D. , Ferla Matteo P. , Rochussen Adam M. , Handel Adam E. , Golwala Zainab M. , Spiridou Goncalves Helena , Kricke Susanne , Klein Fabian , Zhang Fang , Zinghirino Federica , Evans Grace , Keane Thomas M. , Lizot Sabrina , Kusters Maaike A.A. , Iro Mildred A. , Patel Sanjay V. , Morris Emma C. , Burns Siobhan O. , Radcliffe Ruth , Vasudevan Pradeep , Price Arthur , Gillham Olivia , Valdebenito Gabriel E. , Stewart Grant S. , Worth Austen , Adams Stuart P. , Duchen Michael , André Isabelle , Adams David J. , Santili Giorgia , Gilmour Kimberly C. , Holländer Georg A. , Davies E. Graham , Taylor Jenny C. , Griffiths Gillian M. , Thrasher Adrian J. , Dhalla Fatima , Kreins Alexandra Y.
Published: October 2024

The importance of calcium (Ca2+) as a second messenger in T cell signaling is exemplified by genetic deficiencies of STIM1 and ORAI1, which abolish store-operated Ca2+ entry (SOCE) resulting in combined immunodeficiency (CID). We report five unrelated patients with de novo missense variants in ITPR3, encoding a subunit of the inositol 1,4,5-trisphosphate receptor (IP3R), which forms a Ca2+ channel in the endoplasmic reticulum (ER) membrane responsible for the release of ER Ca2+ required to trigger SOCE, and for Ca2+ transfer to other organelles. The patients presented with CID, abnormal T cell Ca2+ homeostasis, incompletely penetrant ectodermal dysplasia, and multisystem disease. Their predominant T cell immunodeficiency is characterized by significant T cell lymphopenia, defects in late stages of thymic T cell development, and impaired function of peripheral T cells, including inadequate NF-κB- and NFAT-mediated, proliferative, and metabolic responses to activation. Pathogenicity is not due to haploinsufficiency, rather ITPR3 protein variants interfere with IP3R channel function leading to depletion of ER Ca2+ stores and blunted SOCE in T cells.
Causal relationships between diseases mined from the literature improve the use of polygenic risk scores
Authors: Toonsi Sumyyah , Gauran Iris Ivy , Ombao Hernando , Schofield Paul N , Hoehndorf Robert
Published: October 2024

Motivation

Identifying causal relations between diseases allows for the study of shared pathways, biological mechanisms, and inter-disease risks. Such causal relations can facilitate the identification of potential disease precursors and candidates for drug re-purposing. However, computational methods often lack access to these causal relations. Few approaches have been developed to automatically extract causal relationships between diseases from unstructured text, but they are often only focused on a small number of diseases, lack validation of the extracted causal relations, or do not make their data available.

Results

We automatically mined statements asserting a causal relation between diseases from the scientific literature by leveraging lexical patterns. Following automated mining of causal relations, we mapped the diseases to the International Classification of Diseases (ICD) identifiers to allow the direct application to clinical data. We provide quantitative and qualitative measures to evaluate the mined causal relations and compare to UK Biobank diagnosis data as a completely independent data source. The validated causal associations were used to create a directed acyclic graph that can be used by causal inference frameworks. We demonstrate the utility of our causal network by performing causal inference using the do-calculus, using relations within the graph to construct and improve polygenic risk scores, and disentangle the pleiotropic effects of variants.

Availability and implementation

The data are available through https://github.com/bio-ontology-research-group/causal-relations-between-diseases.
Improving ncRNA family prediction using multi-modal contrastive learning of sequence and structure
Authors: Xu Ruiting , Li Dan , Yang Wen , Wang Guohua , Li Yang
Published: October 2024

Motivation

Recent advancements in high-throughput sequencing technology have significantly increased the focus on non-coding RNA (ncRNA) research within the life sciences. Despite this, the functions of many ncRNAs remain poorly understood. Research suggests that ncRNAs within the same family typically share similar functions, underlining the importance of understanding their roles. There are two primary methods for predicting ncRNA families: biological and computational. Traditional biological methods are not suitable for large-scale data prediction due to the significant human and resource requirements. Concurrently, most existing computational methods either rely solely on ncRNA sequence data or are exclusively based on the secondary structure of ncRNA molecules. These methods fail to fully utilize the rich multimodal information available from ncRNAs, thereby preventing them from learning more comprehensive and in-depth feature representations.

Results

To tackle these problems, we proposed MM-ncRNAFP, a multi-modal contrastive learning framework for ncRNA family prediction. We first used a pre-trained language model to encode the primary sequences of a large mammalian ncRNA dataset. Then, we adopted a contrastive learning framework with an attention mechanism to fuse the secondary structure information obtained by graph neural networks. The MM-ncRNAFP method can effectively fuse multi-modal information. Experimental comparisons with several competitive baselines demonstrated that MM-ncRNAFP can achieve more comprehensive representations of ncRNA features by integrating both sequence and structural information. This integration significantly enhances the performance of ncRNA family prediction. Ablation experiments and qualitative analyses were performed to verify the effectiveness of each component in our model. Moreover, since our model is pre-trained on a large amount of ncRNA data, it has the potential to bring significant improvements to other ncRNA-related tasks.

Availability and implementation

MM-ncRNAFP and the datasets are available at https://github.com/xuruiting2/MM-ncRNAFP.
Detection and quantification of introgression using Bayesian inference based on conjugate priors
Authors: Pfeifer Bastian , Kapan Durrell D , Herzog Sereina A
Published: October 2024

Introgression (the flow of genes between species) is a major force structuring the evolution of genomes, potentially providing raw material for adaptation. Here, we present a versatile Bayesian model selection approach for detecting and quantifying introgression, df-BF, that builds upon the recently published distance-based df statistic. Unlike df, df-BF accounts for the number of variant sites within a genomic region. The underlying model parameter of our df-BF method, here denoted as dfθ, accurately quantifies introgression, and the corresponding Bayes Factors (df-BF) enables weighing the strength of evidence for introgression. To ensure fast computation, we use conjugate priors with no need for computationally demanding MCMC iterations. We compare our method with other approaches including df, fd, Dp, and Patterson’s D using a wide range of coalescent simulations. Furthermore, we showcase the applicability of df-BF and dfθ using whole-genome mosquito data. Finally, we integrate the new method into the powerful genomics R-package PopGenome.

Availability and implementation

The presented methods are implemented within the R-package PopGenome (https://github.com/pievos101/PopGenome) and the simulation as the application results can be reproduced from the source code available from a dedicated GitHub repository (https://github.com/pievos101/Introgression-Simulation).
A conceptual classification scheme of invasion science
Authors: Musseau Camille L , Bernard-Verdier Maud , Heger Tina , Skopeteas Leonidas H , Strasiewsky David , Mietchen Daniel , Jeschke Jonathan M
Published: October 2024

In the era of big data and global biodiversity decline, there is a pressing need to transform data and information into findable and actionable knowledge. We propose a conceptual classification scheme for invasion science that goes beyond hypothesis networks and allows to organize publications and data sets, guide research directions, and identify knowledge gaps. Combining expert knowledge with literature analysis, we identified five major research themes in this field: introduction pathways, invasion success and invasibility, impacts of invasion, managing biological invasions, and meta-invasion science. We divided these themes into 10 broader research questions and linked them to 39 major hypotheses forming the theoretical foundation of invasion science. As artificial intelligence advances, such classification schemes will become important references for organizing scientific information. Our approach can be extended to other research fields, fostering cross-disciplinary connections to leverage the scientific knowledge needed to address Anthropocene challenges.
Carcinoid syndrome presenting as diffuse violaceous cutaneous flushing
Authors: Chen Meiqing , Gao Lujuan
Published: October 2024

We report a rare case of carcinoid syndrome presenting as deep red to violaceous erythema and diarrhoea. Early diagnosis and treatment by multidisciplinary team is crucial in improving prognosis and outcomes.
MBNL deficiency in motor neurons disrupts neuromuscular junction maintenance and gait coordination
Authors: Frison-Roche Charles , Demier Célia Martin , Cottin Steve , Lainé Jeanne , Arandel Ludovic , Halliez Marius , Lemaitre Mégane , Lornage Xavière , Strochlic Laure , Swanson Maurice S , Martinat Cécile , Messéant Julien , Furling Denis , Rau Frédérique
Published: October 2024

Muscleblind-like proteins (MBNLs) are a family of RNA-binding proteins that play essential roles in the regulation of RNA metabolism. Beyond their canonical role in RNA regulation, MBNL proteins have emerged as key players in the pathogenesis of myotonic dystrophy type 1. In myotonic dystrophy type 1, sequestration of MBNL proteins by expansion of the CUG repeat RNA leads to functional depletion of MBNL, resulting in deregulated alternative splicing and aberrant RNA processing, which underlie the clinical features of the disease.

Although attention on MBNL proteins has focused on their functions in skeletal muscle, new evidence suggests that their importance extends to motor neurons (MNs), pivotal cellular components in the control of motor skills and movement. To address this question, we generated conditional double-knockout (dKO) mice, in which Mbnl1 and Mbnl2 were specifically deleted in motor neurons (MN-dKO). Adult MN-dKO mice develop gait coordination deficits associated with structural and ultrastructural defects in the neuromuscular junction, indicating that MBNL activity in MNs is crucial for the maintenance of the neuromuscular junction. In addition, transcriptome analysis performed on the spinal cord of MN-dKO mice identified mis-splicing events in genes associated with synaptic transmission and neuromuscular junction homeostasis.

In summary, our results highlight the complex roles and regulatory mechanisms of MBNL proteins in MNs for muscle function and locomotion. This work provides valuable insights into fundamental aspects of RNA biology and offers promising avenues for therapeutic intervention in myotonic dystrophy type 1 and in a range of diseases associated with RNA dysregulation.
Environmental sustainability in dermatological surgery. Part 1: reducing carbon intensity
Authors: Ali Fatima ,   BSDS Sustainability Subgroup Collaborative, Ali Fatima , Abbott Rachel , Wernham Aaron , Nikookam Yasmin , Hunt William , Holloran Sophie , Chaolin Catriona , Ang Eshen , Charalambides Maria , Lowe Ashima , Brindley Luke , Bower Christopher , Varma Sandeep , Lam Minh , Veitch David , Recica Hilmi , Woo Wen Ai , Tso Simon , Doyle Claire , Wernham Aaron , Abbott Rachel
Published: October 2024

This two-part review addresses the pressing need for environmental sustainability in dermatological surgery, driven by the National Health Service’s commitment to net-zero emissions. Part 1 focuses on strategies to reduce the carbon intensity of dermatological procedures by adopting low-carbon alternatives and optimizing operational resource usage. Key strategies for a system-wide reduction in environmental impact include leveraging local suppliers to reduce transport emissions, streamlining care models, promoting efficient waste management and using mindful prescribing practices. Another aspect is integrating sustainability into dermatological education while minimizing the carbon footprint of surgical education. Additionally, the review provides a comprehensive overview of optimizing resource use in dermatological surgery, focusing on efficient management of consumables, equipment and energy. This includes recycling, waste segregation, transitioning to reusable personal protective equipment and surgical instruments, and applying energy-saving and sustainable water use practices. By implementing these strategies, dermatological surgery can significantly reduce its environmental impact while upholding high standards of patient care.
Recurrent balanoposthitis and oral blistering in a young man
Authors: Chung Jenny G , Gupta Garima , Wilsher Mark J , Mee John B , Setterfield Jane , Bunker Christopher B
Published: October 2024

A 35-year-old man presented with a clinical history of recurrent blisters on the genital skin and oral mucosa. Lesions had started 3 years previously on the glans penis, with painful swelling, blistering and sloughing and a 2-year history of alternating activity/remitting symptoms. In the past year, painless blisters had developed on his hard palate. He had experienced painful eyes for 3 years.
Image classification with deconvolution operation and augmentation
Authors: Kumar Sarkar Nayan , Marjit Singh Moirangthem , Nandi Utpal
Published: October 2024

Several image classification approaches have been evolved over the years utilizing convolutional neural network (CNN). In convolution operation of CNN, the shifting of kernels to overlapping regions of the image learns redundant data as the images are strongly correlated in reality. The redundant data make the neural network training a challenging task. Again, Deep Learning methods evaluated on small dataset yields degraded performance. To deal with these issues, a proposal is made in this paper that uses deconvolution operation to minimize correlations from images and data augmentation technique to increase the size of datasets. Plant Village, Tomato, and Covid-19 datasets were used for evaluating the performance of the proposed method. 70% of the datasets were used for training, 10% for validation, and 20% for testing purposes. The CIFAR10, MNIST, and Mini-ImageNet datasets were also considered for performance evaluation. The proposed method performed better than other existing methods in terms of classification accuracy.
Behavioral repeatability in dung beetles is not limited to subsocial and sexual horn dimorphic species: the case of Geotrupes mutator (Coleoptera, Geotrupidae)
Authors: Natta Gianluca , Roggero Angela , Zanon Alice , Fiorito Alessandro , Laini Alex , Rolando Antonio , Palestrini Claudia
Published: October 2024

The study of temperament and behavioral syndromes in insects is still in its early stage, and research conducted to date has mainly focused on locomotor activity and thanatosis. Dung beetles have been the subject of extensive behavioral studies; however, very few studies have addressed the expression of temperament. Those doing so only looked at subsocial and sexual horn dimorphic species, suggesting subsociality and/or sexual horn-dimorphism as possible facilitators of temperament expression. To test this assumption, we conducted a temperament study in a hornless, non-subsocial species, namely Geotrupes mutator (Marsham, 1802). We set up laboratory tests to evaluate 3 behaviors (activity, thanatosis, and distress calls) through the measurement of 7 distinct behavioral traits (3 activity-, 1 thanatosis-, and 3 call-related traits). We found high levels of individual repeatability in all activity- and thanatosis-related traits. We also identified behavioral differences between individuals, which may reflect differences in temperament. Statistical analyses revealed a negative correlation between activity and thanatosis. These results show that the temperament and behavioral syndromes related to activity and thanatosis may also be expressed in dung beetle species that are neither subsocial nor sexual horn dimorphic. By contrast, we only found one of 3 sound-related traits tested (frequency) to be clearly repeatable. Males and females presented a different structure of the stridulatory apparatus, suggesting that morphology may affect the frequency of sounds emitted. These results indicate that certain sound traits might not be good descriptors of individual temperament revealing the need for future research addressing the role of bioacoustics.
Polygenic risk, aspirin, and primary prevention of coronary artery disease
Authors: Yu Chenglong , Natarajan Pradeep , Patel Aniruddh P , Bhatia Harpreet S , Khera Amit V , Neumann Johannes T , Tsimikas Sotirios , Wolfe Rory , Nicholls Stephen J , Reid Christopher M , Zoungas Sophia , Tonkin Andrew M , McNeil John J , Lacaze Paul
Published: October 2024

Aims

Recent aspirin primary prevention trials failed to identify a net benefit of aspirin for preventing cardiovascular disease vs. the harms of bleeding. This study aimed to investigate whether a high-risk subgroup, individuals with elevated genetic predisposition to coronary artery disease (CAD), might derive more benefit than harm with aspirin, compared to those with lower genetic risk.

Methods and results

We performed genetic risk stratification of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial using a CAD polygenic risk score (GPSMult). For 12 031 genotyped participants (5974 aspirin, 6057 placebo) overall, we stratified them by GPSMult quintiles (q1–5), then examined risk of CAD (composite of myocardial infarction and coronary heart disease death) and bleeding events using Cox models. During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin vs. placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk [adjusted Hazard ratio (aHR) = 1.30 (1.06–1.61), P = 0.01] but no significant CAD reduction [aHR = 0.84 (0.64–1.09), P = 0.19]. However, among the highest quintile of polygenic risk (q5, top 20% of the GPSMult distribution), there was a 47% reduction in risk of CAD events with aspirin [aHR = 0.53 (0.31–0.90), P = 0.02] without increased bleeding risk [aHR = 1.05 (0.60–1.82), P = 0.88]. Interaction between the GPSMult and aspirin was significant for CAD (q5 vs. q1, P = 0.02) but not bleeding (P = 0.80).

Conclusion

The balance between net benefit and harm on aspirin in the primary prevention setting shifts favourably in individuals with an elevated genetic predisposition.
Discovering genotype–phenotype relationships with machine learning and the Visual Physiology Opsin Database (VPOD)
Authors: Frazer Seth A , Baghbanzadeh Mahdi , Rahnavard Ali , Crandall Keith A , Oakley Todd H
Published: October 2024

Background

Predicting phenotypes from genetic variation is foundational for fields as diverse as bioengineering and global change biology, highlighting the importance of efficient methods to predict gene functions. Linking genetic changes to phenotypic changes has been a goal of decades of experimental work, especially for some model gene families, including light-sensitive opsin proteins. Opsins can be expressed in vitro to measure light absorption parameters, including λmax—the wavelength of maximum absorbance—which strongly affects organismal phenotypes like color vision. Despite extensive research on opsins, the data remain dispersed, uncompiled, and often challenging to access, thereby precluding systematic and comprehensive analyses of the intricate relationships between genotype and phenotype.

Results

Here, we report a newly compiled database of all heterologously expressed opsin genes with λmax phenotypes that we call the Visual Physiology Opsin Database (VPOD). VPOD_1.0 contains 864 unique opsin genotypes and corresponding λmax phenotypes collected across all animals from 73 separate publications. We use VPOD data and deepBreaks to show regression-based machine learning (ML) models often reliably predict λmax, account for nonadditive effects of mutations on function, and identify functionally critical amino acid sites.

Conclusion

The ability to reliably predict functions from gene sequences alone using ML will allow robust exploration of molecular-evolutionary patterns governing phenotype, will inform functional and evolutionary connections to an organism’s ecological niche, and may be used more broadly for de novo protein design. Together, our database, phenotype predictions, and model comparisons lay the groundwork for future research applicable to families of genes with quantifiable and comparable phenotypes.