bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil Desiccation Crack Recognition: New Paradigm and Field Application
Authors: Xu Jin‐Jian , Zhang Hao , Tang Chao‐Sheng , Yang Yaowen , Li Lin , Wang Dian‐Long , Liu Bo , Shi Bin
Published: September 2024

Drought‐induced desiccation cracking can trigger several weakening mechanisms in surface soils, which not only potentially create preferential pathways for gravity‐driven flow and contaminant transport, but also contribute to the instability and failure of slopes and earthen structures. With the continuous innovation of artificial intelligence (AI) and the burgeoning emergence of foundation models, soil desiccation crack recognition (SDCR) is currently undergoing a fundamental shift toward a data‐centric paradigm. This study proposes a knowledge‐driven unsupervised framework for SDCR under complicated and volatile field conditions, referred to as U‐CrackNet framework. Pseudo‐labels for crack recognition are generated through a fusion paradigm that combines strong knowledge from the Segment Anything Model (SAM) developed by Meta AI with weak knowledge derived from threshold‐based methods. An innovative low‐parameter and low‐computational semantic segmentation architecture (Lite‐UNet) is proposed to achieve an effective trade‐off between accuracy and inference speed, which facilitates application on portable devices under challenging field environments. Extensive experimental results unequivocally demonstrate the superior performance of the U‐CrackNet framework in recognizing field soil desiccation cracking, surpassing other state‐of‐the‐art methods in both overall and detailed evaluations. The unsupervised and generalized attributes of U‐CrackNet framework hold substantial potential for developing SDCR foundation model, which not only offers an unprecedented level of precision and adaptability in quantification, evaluation, prediction, and decision‐making of soil desiccation crack phenomena, but also provides a novel perspective for unraveling the causal mechanisms underlying observed surface cracking patterns and climate changes.
Two‐Decadal Variability of Lacustrine Groundwater Discharge: Coupled Controls From Weather and Hydrologic Changes
Authors: Sun Xiaoliang , Du Yao , Wu Jing , Xu Jiawen , Tian Hao , Deng Yamin , Gan Yiqun , Wang Yanxin
Published: September 2024

Lacustrine groundwater discharge (LGD) is a vital water and solute source for lakes. However, the understanding of the long‐term temporal variability of LGD remains limited owing to insufficient insights into driving mechanisms, such as climatic and hydrologic changes. In this study, we examined the oxbow lake group in the central Yangtze River (YR) and assessed the LGD rates from 2000 to 2022 using 222Rn combined with meteorological and hydrological data. The findings revealed that groundwater was recharged during the wet season and discharged to the lakes during the dry season. We established a mathematical model to link the LGD rates to the meteorological and hydrological factors of the lakes, which accounted for 98.70% of the LGD rate variance. Using a predictive model combined with meteorological and hydrological data to assess the LGD rate over the past two decades, it was found that in wet years with higher precipitation and higher average YR water levels, the LGD rate was higher. The gradual increase in precipitation during the rising water and wet seasons, along with a slow rise in the YR water levels, will cause the LGD rate to exhibit a slightly increasing trend with fluctuations in the future. This study proposed an innovative approach to investigate the long‐term temporal variation in LGD and identify the weather and hydrological influences on LGD.
An artificial intelligence-assisted digital microfluidic system for multistate droplet control
Authors: Guo Kunlun , Song Zerui , Zhou Jiale , Shen Bin , Yan Bingyong , Gu Zhen , Wang Huifeng
Published: September 2024

Digital microfluidics (DMF) is a versatile technique for parallel and field-programmable control of individual droplets. Given the high level of variability in droplet manipulation, it is essential to establish self-adaptive and intelligent control methods for DMF systems that are informed by the transient state of droplets and their interactions. However, most related studies focus on droplet localization and shape recognition. In this study, we develop the AI-assisted DMF framework μDropAI for multistate droplet control on the basis of droplet morphology. The semantic segmentation model is integrated into our custom-designed DMF system to recognize the droplet states and their interactions for feedback control with a state machine. The proposed model has strong flexibility and can recognize droplets of different colors and shapes with an error rate of less than 0.63%; it enables control of droplets without user intervention. The coefficient of variation (CV) of the volumes of split droplets can be limited to 2.74%, which is lower than the CV of traditional dispensed droplets, contributing to an improvement in the precision of volume control for droplet splitting. The proposed system inspires the development of semantic-driven DMF systems that can interface with multimodal large language models (MLLMs) for fully automatic control.
Therapeutic implications of homologous repair deficiency testing in patients with prostate cancer (Part 2 of 2)
Authors: Serritella Anthony V. , Taylor Amy , Haffner Michael C. , Abida Wassim , Bryce Alan , Karsh Lawrence I. , Tagawa Scott T. , Twardowski Przemyslaw , Armstrong Andrew J. , Lang Joshua M.
Published: September 2024

Background/Objectives

Unfortunately, not all metastatic castration-resistant prostate cancer (mCRPC) patients receive available life-prolonging systemic therapies, emphasizing the need to optimize mCRPC treatment selections. Better guidelines are necessary to determine genetic testing for prostate cancer.

Subjects/Methods

In this two-part expert opinion-based guide, we provide an expert consensus opinion on the utilization of germline and somatic testing to detect HRR alterations in patients with mCRPC. This guide was developed by a multidisciplinary expert panel that convened in 2023-2024, including representatives from medical oncology, urology, radiation oncology, pathology, medical genomics, and basic science.

Results/Conclusions

In this second part, we highlight how genetic testing can lead to improved, life-prolonging mCRPC therapeutic strategies based on a review of the recent phase III trials and subsequent regulatory approvals for PARP inhibitors in mCRPC.
Catalytic undirected methylation of unactivated C(sp3)−H bonds suitable for complex molecules
Authors: Tan Jin-Fay , Kang Yi Cheng , Hartwig John F.
Published: September 2024

In pharmaceutical discovery, the “magic methyl” effect describes a substantial improvement in the pharmacological properties of a drug candidate with the incorporation of methyl groups. Therefore, to expedite the synthesis of methylated drug analogs, late-stage, undirected methylations of C(sp3)−H bonds in complex molecules would be valuable. However, current methods for site-selective methylations are limited to activated C(sp3)−H bonds. Here we describe a site-selective, undirected methylation of unactivated C(sp3)−H bonds, enabled by photochemically activated peroxides and a nickel(II) complex whose turnover is enhanced by an ancillary ligand. The methodology displays compatibility with a wide range of functional groups and a high selectivity for tertiary C−H bonds, making it suitable for the late-stage methylation of complex organic compounds that contain multiple alkyl C−H bonds, such as terpene natural products, peptides, and active pharmaceutical ingredients. Overall, this method provides a synthetic tool to explore the “magic methyl” effect in drug discovery.
Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum
Authors: Wenqiang Du , Novin Ashkan , Liu Yamin , Afzal Junaid , Suhail Yasir , Liu Shaofei , Gavin Nicole R. , Jorgensen Jennifer R. , Morosky Christopher M. , Figueroa Reinaldo , Schmidt Tannin A. , Sanders Melinda , Brewer Molly A. , Kshitiz
Published: September 2024

Scar tissue formation is a hallmark of wound repair in adults and can chronically affect tissue architecture and function. To understand the general phenomena, we sought to explore scar-driven imbalance in tissue homeostasis caused by a common, and standardized surgical procedure, the uterine scar due to cesarean surgery. Deep uterine scar is associated with a rapidly increasing condition in pregnant women, placenta accreta spectrum (PAS), characterized by aggressive trophoblast invasion into the uterus, frequently necessitating hysterectomy at parturition. We created a model of uterine scar, recapitulating PAS-like invasive phenotype, showing that scar matrix activates mechanosensitive ion channel, Piezo1, through glycolysis-fueled cellular contraction. Piezo1 activation increases intracellular calcium activity and Protein kinase C activation, leading to NF-κB nuclear translocation, and MafG stabilization. This inflammatory transformation of decidua leads to production of IL-8 and G-CSF, chemotactically recruiting invading trophoblasts towards scar, initiating PAS. Our study demonstrates aberrant mechanics of scar disturbs stroma-epithelia homeostasis in placentation, with implications in cancer dissemination.
Telomere-to-telomere assemblies of cattle and sheep Y-chromosomes uncover divergent structure and gene content
Authors: Olagunju Temitayo A. , Rosen Benjamin D. , Neibergs Holly L. , Becker Gabrielle M. , Davenport Kimberly M. , Elsik Christine G. , Hadfield Tracy S. , Koren Sergey , Kuhn Kristen L. , Rhie Arang , Shira Katie A. , Skibiel Amy L. , Stegemiller Morgan R. , Thorne Jacob W. , Villamediana Patricia , Cockett Noelle E. , Murdoch Brenda M. , Smith Timothy P. L.
Published: September 2024

Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. Here, we assemble complete and gapless telomere to telomere (T2T) Y chromosomes for these species. We find that the pseudo-autosomal regions are similar in length, but the total chromosome size is substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity is accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 19MYA. The centromeres also differ dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosomes have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.
Mechanical force regulates ligand binding and function of PD-1
Authors: Li Kaitao , Cardenas-Lizana Paul , Lyu Jintian , Kellner Anna V. , Li Menglan , Cong Peiwen , Watson Valencia E. , Yuan Zhou , Ahn Eunseon , Doudy Larissa , Li Zhenhai , Salaita Khalid , Ahmed Rafi , Zhu Cheng
Published: September 2024

Despite the success of PD-1 blockade in cancer therapy, how PD-1 initiates signaling remains unclear. Soluble PD-L1 is found in patient sera and can bind PD-1 but fails to suppress T cell function. Here, we show that PD-1 function is reduced when mechanical support on ligand is removed. Mechanistically, cells exert forces to PD-1 and prolong bond lifetime at forces <7 pN (catch bond) while accelerate dissociation at forces >8pN (slip bond). Molecular dynamics of PD-1–PD-L2 complex suggests force may cause relative rotation and translation between the two molecules yielding distinct atomic contacts not observed in the crystal structure. Compared to wild-type, PD-1 mutants targeting the force-induced distinct interactions maintain the same binding affinity but suppressed/eliminated catch bond, lowered rupture force, and reduced inhibitory function. Our results uncover a mechanism for cells to probe the mechanical support of PD-1–PD-Ligand bonds using endogenous forces to regulate PD-1 signaling.
Spatial organization of adenylyl cyclase and its impact on dopamine signaling in neurons
Authors: Ripoll Léa , Li Yong , Dessauer Carmen W. , von Zastrow Mark
Published: September 2024

The cAMP cascade is increasingly recognized to transduce physiological effects locally through spatially limited cAMP gradients. However, little is known about how adenylyl cyclase enzymes that initiate cAMP gradients are localized. Here we address this question in physiologically relevant striatal neurons and investigate how AC localization impacts downstream signaling function. We show that the major striatal AC isoforms are differentially sorted between ciliary and extraciliary domains of the plasma membrane, and that one isoform, AC9, is uniquely concentrated in endosomes. We identify key sorting determinants in the N-terminal cytoplasmic domain responsible for isoform-specific localization. We further show that AC9-containing endosomes accumulate activated dopamine receptors and form an elaborately intertwined network with juxtanuclear PKA stores bound to Golgi membranes. Finally, we provide evidence that endosomal localization enables AC9 to selectively elevate PKA activity in the nucleus relative to the cytoplasm. Together, these results reveal a precise spatial landscape of the cAMP cascade in neurons and a key role of AC localization in directing downstream PKA signaling to the nucleus.
Cooperative chemoenzymatic and biocatalytic cascades to access chiral sulfur compounds bearing C(sp3)–S stereocentres
Authors: Zhao Fei , Mattana Ariane , Alam Ruqaiya , Montgomery Sarah L. , Pandya Akash , Manetti Fabrizio , Dominguez Beatriz , Castagnolo Daniele
Published: September 2024

Biocatalysis has been widely employed for the generation of carbon-carbon/heteroatom stereocentres, yet its application in chiral C(sp3)–S bond construction is rare and limited to enzymatic kinetic resolutions. Herein, we describe the enantioselective construction of chiral C(sp3)–S bonds through ene-reductase biocatalyzed conjugate reduction of prochiral vinyl sulfides. A series of cooperative sequential/concurrent chemoenzymatic and biocatalytic cascades have been developed to access a broad range of chiral sulfides, including valuable β-hydroxysulfides bearing two adjacent C(sp3)–S and C(sp3)–O stereocentres, in a stereoconvergent manner with good to excellent yields (up to 96%) and enantioselectivities (up to >99% ee). Notably, this biocatalytic strategy allows to overcome the long-standing shortcomings of catalyst poisoning and C(sp2)/C(sp3)–S bond cleavage faced in transition-metal-catalyzed hydrogenation of vinyl sulfides. Finally, the potential of this methodology is also exemplified by its broader application in the stereoconvergent assembly of chiral C(sp3)–N/O/Se bonds with good to excellent enantioselctivities.
Impact of six-month COVID-19 travel moratorium on Plasmodium falciparum prevalence on Bioko Island, Equatorial Guinea
Authors: Hergott Dianna E. B. , Guerra Carlos A. , García Guillermo A. , Mba Eyono Jeremías Nzamío , Donfack Olivier T. , Iyanga Marcos Mbulito , Nguema Avue Restituto Mba , Abeso Nsegue Crisantos Nsue , Ondo Mifumu Teresa Ayingono , Rivas Matilde Riloha , Phiri Wonder P. , Murphy Sean C. , Guthrie Brandon L. , Smith David L. , Balkus Jennifer E.
Published: September 2024

Importation of malaria infections is a suspected driver of sustained malaria prevalence on areas of Bioko Island, Equatorial Guinea. Quantifying the impact of imported infections is difficult because of the dynamic nature of the disease and complexity of designing a randomized trial. We leverage a six-month travel moratorium in and out of Bioko Island during the initial COVID-19 pandemic response to evaluate the contribution of imported infections to malaria prevalence on Bioko Island. Using a difference in differences design and data from island wide household surveys conducted before (2019) and after (2020) the travel moratorium, we compare the change in prevalence between areas of low historical travel to those with high historical travel. Here, we report that in the absence of a travel moratorium, the prevalence of infection in high travel areas was expected to be 9% higher than observed, highlighting the importance of control measures that target imported infections.
Doping strategy in metavalently bonded materials for advancing thermoelectric performance
Authors: Liu Ming , Guo Muchun , Lyu Haiyan , Lai Yingda , Zhu Yuke , Guo Fengkai , Yang Yueyang , Yu Kuai , Dong Xingyan , Liu Zihang , Cai Wei , Wuttig Matthias , Yu Yuan , Sui Jiehe
Published: September 2024

Metavalent bonding is a unique bonding mechanism responsible for exceptional properties of materials used in thermoelectric, phase-change, and optoelectronic devices. For thermoelectrics, the desired performance of metavalently bonded materials can be tuned by doping foreign atoms. Incorporating dopants to form solid solutions or second phases is a crucial route to tailor the charge and phonon transport. Yet, it is difficult to predict if dopants will form a secondary phase or a solid solution, which hinders the tailoring of microstructures and material properties. Here, we propose that the solid solution is more easily formed between metavalently bonded solids, while precipitates prefer to exist in systems mixed by metavalently bonded and other bonding mechanisms. We demonstrate this in a metavalently bonded GeTe compound alloyed with different sulfides. We find that S can dissolve in the GeTe matrix when alloyed with metavalently bonded PbS. In contrast, S-rich second phases are omnipresent via alloying with covalently bonded GeS and SnS. Benefiting from the reduced phonon propagation and the optimized electrical transport properties upon doping PbS in GeTe, a high figure-of-merit ZT of 2.2 at 773 K in (Ge0.84Sb0.06Te0.9)(PbSe)0.05(PbS)0.05 is realized. This strategy can be applied to other metavalently bonded materials to design properties beyond thermoelectrics.
Strongly deleterious mutations influence reproductive output and longevity in an endangered population
Authors: Hasselgren Malin , Dussex Nicolas , von Seth Johanna , Angerbjörn Anders , Dalén Love , Norén Karin
Published: September 2024

Inbreeding depression has been documented in various fitness traits in a wide range of species and taxa, however, the mutational basis is not yet well understood. We investigate how putatively deleterious variation influences fitness and is shaped by individual ancestry by re-sequencing complete genomes of 37 individuals in a natural arctic fox (Vulpes lagopus) population subjected to both inbreeding depression and genetic rescue. We find that individuals with high proportion of homozygous loss of function genotypes (LoFs), which are predicted to exert a strong effect on fitness, generally have lower lifetime reproductive success and live shorter lives compared with individuals with lower proportion of LoFs. We also find that juvenile survival is negatively associated with the proportion of homozygous missense genotypes and positively associated with genome wide heterozygosity. Our results demonstrate that homozygosity of strongly and moderately deleterious mutations can be an important cause of trait specific inbreeding depression in wild populations, and mark an important step towards making more informed decisions using applied conservation genetics.
Taxometer: Improving taxonomic classification of metagenomics contigs
Authors: Kutuzova Svetlana , Nielsen Mads , Piera Pau , Nissen Jakob Nybo , Rasmussen Simon
Published: September 2024

For taxonomy based classification of metagenomics assembled contigs, current methods use sequence similarity to identify their most likely taxonomy. However, in the related field of metagenomic binning, contigs are routinely clustered using information from both the contig sequences and their abundance. We introduce Taxometer, a neural network based method that improves the annotations and estimates the quality of any taxonomic classifier using contig abundance profiles and tetra-nucleotide frequencies. We apply Taxometer to five short-read CAMI2 datasets and find that it increases the average share of correct species-level contig annotations of the MMSeqs2 tool from 66.6% to 86.2%. Additionally, it reduce the share of wrong species-level annotations in the CAMI2 Rhizosphere dataset by an average of two-fold for Metabuli, Centrifuge, and Kraken2. Futhermore, we use Taxometer for benchmarking taxonomic classifiers on two complex long-read metagenomics data sets where ground truth is not known. Taxometer is available as open-source software and can enhance any taxonomic annotation of metagenomic contigs.
Engineered allogeneic T cells decoupling T-cell-receptor and CD3 signalling enhance the antitumour activity of bispecific antibodies
Authors: Kapetanovic Edo , Weber Cédric R. , Bruand Marine , Pöschl Daniel , Kucharczyk Jakub , Hirth Elisabeth , Dietsche Claudius , Khan Riyaz , Wagner Bastian , Belli Olivier , Vazquez-Lombardi Rodrigo , Castellanos- Rueda Rocío , Di Roberto Raphael B. , Kalinka Kevin , Raess Luca , Ly Kevin , Rai Shivam , Dittrich Petra S. , Platt Randall J. , Oricchio Elisa , Reddy Sai T.
Published: September 2024

Bispecific antibodies (biAbs) used in cancer immunotherapies rely on functional autologous T cells, which are often damaged and depleted in patients with haematological malignancies and in other immunocompromised patients. The adoptive transfer of allogeneic T cells from healthy donors can enhance the efficacy of biAbs, but donor T cells binding to host-cell antigens cause an unwanted alloreactive response. Here we show that allogeneic T cells engineered with a T-cell receptor that does not convert antigen binding into cluster of differentiation 3 (CD3) signalling decouples antigen-mediated T-cell activation from T-cell cytotoxicity while preserving the surface expression of the T-cell-receptor–CD3 signalling complex as well as biAb-mediated CD3 signalling and T-cell activation. In mice with CD19+ tumour xenografts, treatment with the engineered human cells in combination with blinatumomab (a clinically approved biAb) led to the recognition and clearance of tumour cells in the absence of detectable alloreactivity. Our findings support the development of immunotherapies combining biAbs and ‘off-the-shelf’ allogeneic T cells.
Feasible deployment of carbon capture and storage and the requirements of climate targets
Authors: Kazlou Tsimafei , Cherp Aleh , Jewell Jessica
Published: September 2024

Climate change mitigation requires the large-scale deployment of carbon capture and storage (CCS). Recent plans indicate an eight-fold increase in CCS capacity by 2030, yet the feasibility of CCS expansion is debated. Using historical growth of CCS and other policy-driven technologies, we show that if plans double between 2023 and 2025 and their failure rates decrease by half, CCS could reach 0.37 GtCO2 yr−1 by 2030—lower than most 1.5 °C pathways but higher than most 2 °C pathways. Staying on-track to 2 °C would require that in 2030–2040 CCS accelerates at least as fast as wind power did in the 2000s, and that after 2040, it grows faster than nuclear power did in the 1970s to 1980s. Only 10% of mitigation pathways meet these feasibility constraints, and virtually all of them depict <600 GtCO2 captured and stored by 2100. Relaxing the constraints by assuming no failures of CCS plans and growth as fast as flue-gas desulfurization would approximately double this amount.
Climate variability shifts the vertical structure of phytoplankton in the Sargasso Sea
Authors: Viljoen Johannes J. , Sun Xuerong , Brewin Robert J. W.
Published: September 2024

Marine phytoplankton are essential to ocean biogeochemical cycles. However, our understanding of changes in phytoplankton rely largely on satellite data, which can only assess changes in surface phytoplankton. How climate variability is impacting their vertical structure remains unclear. Here we use 33 years’ worth of data from the Sargasso Sea to show distinct seasonal and long-term phytoplankton climate responses in the surface mixed layer compared with the subsurface. Seasonally, the surface community alters their carbon-to-chlorophyll ratio without changing their carbon biomass, whereas the chlorophyll a and carbon of the subsurface community covaries with no change in their carbon-to-chlorophyll ratio. Over the last decade, the subsurface phytoplankton biomass has increased in response to warming, whereas the surface phytoplankton have altered their carbon-to-chlorophyll ratio with minimal change in their carbon biomass. Given that satellites can only view the surface ocean, sustained subsurface monitoring is required to provide a full understanding of how phytoplankton are responding to climate change.
Genomic and fitness consequences of a near-extinction event in the northern elephant seal
Authors: Hoffman Joseph I. , Vendrami David L. J. , Hench Kosmas , Chen Rebecca S. , Stoffel Martin A. , Kardos Marty , Amos William , Kalinowski Jörn , Rickert Daniel , Köhrer Karl , Wachtmeister Thorsten , Goebel Mike E. , Bonin Carolina A. , Gulland Frances M. D. , Dasmahapatra Kanchon K.
Published: September 2024

Understanding the genetic and fitness consequences of anthropogenic bottlenecks is crucial for biodiversity conservation. However, studies of bottlenecked populations combining genomic approaches with fitness data are rare. Theory predicts that severe bottlenecks deplete genetic diversity, exacerbate inbreeding depression and decrease population viability. However, actual outcomes are complex and depend on how a species’ unique demography affects its genetic load. We used population genetic and veterinary pathology data, demographic modelling, whole-genome resequencing and forward genetic simulations to investigate the genomic and fitness consequences of a near-extinction event in the northern elephant seal. We found no evidence of inbreeding depression within the contemporary population for key fitness components, including body mass, blubber thickness and susceptibility to parasites and disease. However, we detected a genomic signature of a recent extreme bottleneck (effective population size = 6; 95% confidence interval = 5.0–7.5) that will have purged much of the genetic load, potentially leading to the lack of observed inbreeding depression in our study. Our results further suggest that deleterious genetic variation strongly impacted the post-bottleneck population dynamics of the northern elephant seal. Our study provides comprehensive empirical insights into the intricate dynamics underlying species-specific responses to anthropogenic bottlenecks.
Dataset from a human-in-the-loop approach to identify functionally important protein residues from literature
Authors: Vollmar Melanie , Tirunagari Santosh , Harrus Deborah , Armstrong David , Gáborová Romana , Gupta Deepti , Afonso Marcelo Querino Lima , Evans Genevieve , Velankar Sameer
Published: September 2024

We present a novel system that leverages curators in the loop to develop a dataset and model for detecting structure features and functional annotations at residue-level from standard publication text. Our approach involves the integration of data from multiple resources, including PDBe, EuropePMC, PubMedCentral, and PubMed, combined with annotation guidelines from UniProt, and LitSuggest and HuggingFace models as tools in the annotation process. A team of seven annotators manually curated ten articles for named entities, which we utilized to train a starting PubmedBert model from HuggingFace. Using a human-in-the-loop annotation system, we iteratively developed the best model with commendable performance metrics of 0.90 for precision, 0.92 for recall, and 0.91 for F1-measure. Our proposed system showcases a successful synergy of machine learning techniques and human expertise in curating a dataset for residue-level functional annotations and protein structure features. The results demonstrate the potential for broader applications in protein research, bridging the gap between advanced machine learning models and the indispensable insights of domain experts.
A starfish-inspired 4D self-healing morphing structure
Authors: Raman  , Labisch Susanna , Dirks Jan-Henning
Published: September 2024

Inspired by the starfish's unique ability to achieve flexibility and posture-holding with minimal energy expenditure, we present a novel bioinspired morphing structure. Our two-component design, consisting of a thermoplastic mesh and elastomeric jacket, effectively mimics the functions of the starfish's ossicles, mutable collagenous tissues, and derma. This structure exhibits a remarkable combination of self-healing, time-dependent shape memory, and self-posture-holding properties. Systematic variations in mesh geometry demonstrate precise control over structural stiffness and thermal response, enabling customization for specific applications. The structure's scalability and ease of fabrication further enhance its adaptability. We experimentally demonstrate the potential of our biomimetic morphing structure using several prototypes. This work lays the foundation for developing a new type of versatile morphing structures with applications in diverse fields, including robotics, biomedical devices, and adaptive structures.
The use of accelerometers to assess upper limb function in patients with obstetric brachial plexus palsy
Authors: Leypold Tim , Bahm Jörg , Schäfer Benedikt , Beier Justus P. , Disselhorst-Klug Catherine , Fonseca-Höflinger Ligia C.
Published: September 2024

For half a century, the Mallet Scale (MS) has been utilized to assess upper limb function in patients with obstetric brachial plexus palsy (OBPP). However, the correct use of the MS requires trained personnel and the MS does not measure compensatory movements. For this reason, new methods are needed to compensate for these weaknesses. This study introduces an innovative method for objective functional motion analysis using accelerometers to measure upper limb movements in thirty patients with obstetric brachial plexus lesions. Five triaxial accelerometers were positioned on the chest and each upper limb. They recorded acceleration signals during repetitive everyday tasks: hand-to-mouth (HM), hand-to-neck (HN), and hand-to-spine (HS). From these signals, 54 features were extracted and subjected to linear correlation tests to identify 5 suitable features. An algorithm was then developed to categorize patients into five groups and compute an individual movement performance score (iMPScore) assessing the patient’s upper extremity function. By using the iMPScore more than 75% of all participants have been classified correctly with respect to their MS category. Identification of MS I category patients in general and assessing upper extremity function of MS I to III in HS tasks were most challenging. We conclude that the introduced approach is a valuable tool for gauging movement limitation of upper limbs in patients with obstetric brachial plexus palsy. Compared to other clinically established methods, it becomes possible to record and even quantify the extent of compensatory movements. In this way, an objective, user- and patient-friendly method is offered, which supports significantly physicians and therapists in their evaluation of OBPP.
Terahertz conductivity mapping of thin films on smart textiles
Authors: Jäckel Alexander , Hupfer Maximilian L. , Castro-Camus Enrique , Mittleman Daniel M. , Schmidl Gabriele , Gawlik Annett , Plentz Jonathan , Koch Martin
Published: September 2024

Smart textiles that promise to become sensors and actuators for multiple applications are an active area of research. Conductive textiles formed by coating a fabric with a conductive film will play a key role in such applications. Here we present contactless mapping of the terahertz (THz) conductivity of thin conductive films deposited on textiles. These conductivity maps enable non-destructive assessment of the conductivity of such layers and therefore the identification and localization of non-uniformities in local conductivity. The THz measurements are quantitatively consistent with four-point probe measurements of the same areas.
Promotion focus, but not prevention focus of teachers and students matters when shifting towards technology-based instruction in schools
Authors: Hoch Emely , Scheiter Katharina , Sassenberg Kai
Published: September 2024

Implementing technology-enhanced learning and teaching in schools causes major changes for both teachers and students. Research in other fields shows that individuals’ regulatory orientation (i.e., promotion and prevention focus) predicts how people deal with such fundamental changes. Our research ties in with a school trial where classes were equipped with tablets, yielding a shift from predominantly analog to technology-enhanced learning and teaching. In this context, we investigated whether the regulatory orientation of teachers (N = 109) and students (N = 1,127) related to how they dealt with this change. As expected, teachers with a stronger promotion focus were more likely to perceive the changing teaching situation as a (positively connotated) challenge and to intend to use the tablets in class. Further, students with a strong promotion focus when tablet-based teaching was introduced showed higher technology-related self-efficacy and higher motivation to use digital devices after a few months of using tablets in class. Prevention focus was unrelated to teachers’ and students’ attitudes, behavioral intentions, or motivation. Thus, the concept of regulatory orientation helps explain how teachers and students respond to changes in school, whereby particularly promotion focus appears to be relevant for change processes due to digital transformation in education.
Dynamics of a single cavitation bubble near an oscillating boundary
Authors: Sagar Hemant J. , Lin Yuxing , Moctar Ould el
Published: September 2024

Cavitation and its effects are well investigated, especially single bubble cavitation and its collapse near rigid and elastic boundaries. In our current article, we investigated novel experiments of a single cavitation bubble near an oscillatory boundary. We generated the cavitation bubble by laser focusing in water. A flat glass plate was fixed to the shaft of the magnetostriction oscillator coil. We investigated the dynamics of bubbles at two relative wall distances (ratio of the distance between the bubble center and plate surface to the maximum radius of the bubble) of the bubble from the glass plate in combination with four modes of oscillation. Each mode has specific frequency and amplitude of oscillation. The high-speed camera captured the dynamics of the bubble using the back-illumination method with a framing rate of 120Kfps and simultaneously we used an optical CMOS sensor to measure the oscillation of the glass plate. We presented a clear comparison among the bubble dynamics near stationary and oscillating plates with parameters such as oscillating modes and direction. We correlated the dynamics of the bubble with the motion of the plate. In addition, we highlighted the differences including the characteristics of bubble shape and jetting that occurred during the collapse phase. The comparison of the time histories of the bubble’s equivalent size postulated that the bubble’s collapse times vary significantly in some cases compared to the bubble’s dynamics near the stationary plate. In all cases, we noticed the shortening of the bubble’s collapsing time, i.e. accelerated collapses. In our findings, we noticed a collapse times reduction of about 4–15%. Our finding signifies the importance of introducing the oscillation of the boundaries to obtain effective energy concentration over the time during the collapse. Our study also suggests that forced oscillation of boundaries is undesirable for destructive cavitation effects. The method we suggested for the manipulation of bubble dynamics holds potential for enhancing the efficiency of applications such as lithotripsy in biomedical devices, actuation and micro pumping in microfluidic devices, and effective semiconductor surface cleaning. Not but least, obtained results can be used as benchmark in future for validating numerical methods.
Damaging mutations in liver X receptor-α are hepatotoxic and implicate cholesterol sensing in liver health
Authors: Lockhart Sam M. , Muso Milan , Zvetkova Ilona , Lam Brian Y. H. , Ferrari Alessandra , Schoenmakers Erik , Duckett Katie , Leslie Jack , Collins Amy , Romartínez-Alonso Beatriz , Tadross John A. , Jia Raina , Gardner Eugene J. , Kentistou Katherine , Zhao Yajie , Day Felix , Mörseburg Alexander , Rainbow Kara , Rimmington Debra , Mastantuoni Matteo , Harrison James , Nus Meritxell , Guma’a Khalid , Sherratt-Mayhew Sam , Jiang Xiao , Smith Katherine R. , Paul Dirk S. , Jenkins Benjamin , Koulman Albert , Pietzner Maik , Langenberg Claudia , Wareham Nicholas , Yeo Giles S. , Chatterjee Krishna , Schwabe John , Oakley Fiona , Mann Derek A. , Tontonoz Peter , Coll Anthony P. , Ong Ken , Perry John R. B. , O’Rahilly Stephen
Published: September 2024

Liver X receptor-α (LXRα) regulates cellular cholesterol abundance and potently activates hepatic lipogenesis. Here we show that at least 1 in 450 people in the UK Biobank carry functionally impaired mutations in LXRα, which is associated with biochemical evidence of hepatic dysfunction. On a western diet, male and female mice homozygous for a dominant negative mutation in LXRα have elevated liver cholesterol, diffuse cholesterol crystal accumulation and develop severe hepatitis and fibrosis, despite reduced liver triglyceride and no steatosis. This phenotype does not occur on low-cholesterol diets and can be prevented by hepatocyte-specific overexpression of LXRα. LXRα knockout mice exhibit a milder phenotype with regional variation in cholesterol crystal deposition and inflammation inversely correlating with steatosis. In summary, LXRα is necessary for the maintenance of hepatocyte health, likely due to regulation of cellular cholesterol content. The inverse association between steatosis and both inflammation and cholesterol crystallization may represent a protective action of hepatic lipogenesis in the context of excess hepatic cholesterol.
Bio-inspired autonomy in soft robots
Authors: van Laake Lucas Carolus , Overvelde Johannes Tesse Bastiaan
Published: September 2024

Soft robotic actuation concepts meet and sometimes exceed their natural counterparts. In contrast, artificially recreating natural levels of autonomy is still an unmet challenge. Here, we come to this conclusion after defining a measure of energy- and control-autonomy and classifying a representative selection of soft robots. We argue that, in order to advance the field, we should focus our attention on interactions between soft robots and their environment, because in nature autonomy is also achieved in interdependence. If we better understand how interactions with an environment are leveraged in nature, this will enable us to design bio-inspired soft robots with much greater autonomy in the future.
Addressing challenges in speaker anonymization to maintain utility while ensuring privacy of pathological speech
Authors: Tayebi Arasteh Soroosh , Arias-Vergara Tomás , Pérez-Toro Paula Andrea , Weise Tobias , Packhäuser Kai , Schuster Maria , Noeth Elmar , Maier Andreas , Yang Seung Hee
Published: September 2024

Background

Integration of speech into healthcare has intensified privacy concerns due to its potential as a non-invasive biomarker containing individual biometric information. In response, speaker anonymization aims to conceal personally identifiable information while retaining crucial linguistic content. However, the application of anonymization techniques to pathological speech, a critical area where privacy is especially vital, has not been extensively examined.

Methods

This study investigates anonymization’s impact on pathological speech across over 2700 speakers from multiple German institutions, focusing on privacy, pathological utility, and demographic fairness. We explore both deep-learning-based and signal processing-based anonymization methods.

Results

We document substantial privacy improvements across disorders—evidenced by equal error rate increases up to 1933%, with minimal overall impact on utility. Specific disorders such as Dysarthria, Dysphonia, and Cleft Lip and Palate experience minimal utility changes, while Dysglossia shows slight improvements. Our findings underscore that the impact of anonymization varies substantially across different disorders. This necessitates disorder-specific anonymization strategies to optimally balance privacy with diagnostic utility. Additionally, our fairness analysis reveals consistent anonymization effects across most of the demographics.

Conclusions

This study demonstrates the effectiveness of anonymization in pathological speech for enhancing privacy, while also highlighting the importance of customized and disorder-specific approaches to account for inversion attacks.
Measured and genetically predicted protein levels and cardiovascular diseases in UK Biobank and China Kadoorie Biobank
Authors: Lind Lars , Mazidi Mohsen , Clarke Robert , Bennett Derrick A. , Zheng Rui
Published: September 2024

Several large-scale studies have measured plasma levels of the proteome in individuals with cardiovascular diseases (CVDs)1–7. However, since the majority of such proteins are interrelated2, it is difficult for observational studies to distinguish which proteins are likely to be of etiological relevance. Here we evaluate whether plasma levels of 2,919 proteins measured in 52,164 UK Biobank participants are associated with incident myocardial infarction, ischemic stroke or heart failure. Of those proteins, 126 were associated with all three CVD outcomes and 118 were associated with at least one CVD in the China Kadoorie Biobank. Mendelian randomization and colocalization analyses indicated that genetically determined levels of 47 and 18 proteins, respectively, were associated with CVDs, including FGF5, PROCR and FURIN. While the majority of protein–CVD observational associations were noncausal, these three proteins showed evidence to support potential causality and are therefore promising targets for drug treatment for CVD outcomes.
Proteome-wide copy-number estimation from transcriptomics
Authors: Sweatt Andrew J , Griffiths Cameron D , Groves Sarah M , Paudel B Bishal , Wang Lixin , Kashatus David F , Janes Kevin A
Published: September 2024

Protein copy numbers constrain systems-level properties of regulatory networks, but proportional proteomic data remain scarce compared to RNA-seq. We related mRNA to protein statistically using best-available data from quantitative proteomics and transcriptomics for 4366 genes in 369 cell lines. The approach starts with a protein’s median copy number and hierarchically appends mRNA–protein and mRNA–mRNA dependencies to define an optimal gene-specific model linking mRNAs to protein. For dozens of cell lines and primary samples, these protein inferences from mRNA outmatch stringent null models, a count-based protein-abundance repository, empirical mRNA-to-protein ratios, and a proteogenomic DREAM challenge winner. The optimal mRNA-to-protein relationships capture biological processes along with hundreds of known protein-protein complexes, suggesting mechanistic relationships. We use the method to identify a viral-receptor abundance threshold for coxsackievirus B3 susceptibility from 1489 systems-biology infection models parameterized by protein inference. When applied to 796 RNA-seq profiles of breast cancer, inferred copy-number estimates collectively re-classify 26–29% of luminal tumors. By adopting a gene-centered perspective of mRNA–protein covariation across different biological contexts, we achieve accuracies comparable to the technical reproducibility of contemporary proteomics.
Prediction of the 3D cancer genome from whole-genome sequencing using InfoHiC
Authors: Lee Yeonghun , Park Sung-Hye , Lee Hyunju
Published: September 2024

The 3D genome prediction in cancer is crucial for uncovering the impact of structural variations (SVs) on tumorigenesis, especially when they are present in noncoding regions. We present InfoHiC, a systemic framework for predicting the 3D cancer genome directly from whole-genome sequencing (WGS). InfoHiC utilizes contig-specific copy number encoding on the SV contig assembly, and performs a contig-to-total Hi-C conversion for the cancer Hi-C prediction from multiple SV contigs. We showed that InfoHiC can predict 3D genome folding from all types of SVs using breast cancer cell line data. We applied it to WGS data of patients with breast cancer and pediatric patients with medulloblastoma, and identified neo topologically associating domains. For breast cancer, we discovered super-enhancer hijacking events associated with oncogenic overexpression and poor survival outcomes. For medulloblastoma, we found SVs in noncoding regions that caused super-enhancer hijacking events of medulloblastoma driver genes (GFI1, GFI1B, and PRDM6). In addition, we provide trained models for cancer Hi-C prediction from WGS at https://github.com/dmcb-gist/InfoHiC, uncovering the impacts of SVs in cancer patients and revealing novel therapeutic targets.
Mutation in the mitochondrial chaperone TRAP1 leads to autism with more severe symptoms in males
Authors: Rydzanicz Małgorzata , Kuzniewska Bozena , Magnowska Marta , Wójtowicz Tomasz , Stawikowska Aleksandra , Hojka Anna , Borsuk Ewa , Meyza Ksenia , Gewartowska Olga , Gruchota Jakub , Miłek Jacek , Wardaszka Patrycja , Chojnicka Izabela , Kondrakiewicz Ludwika , Dymkowska Dorota , Puścian Alicja , Knapska Ewelina , Dziembowski Andrzej , Płoski Rafał , Dziembowska Magdalena
Published: September 2024

There is increasing evidence of mitochondrial dysfunction in autism spectrum disorders (ASD), but the causal relationships are unclear. In an ASD patient whose identical twin was unaffected, we identified a postzygotic mosaic mutation p.Q639* in the TRAP1 gene, which encodes a mitochondrial chaperone of the HSP90 family. Additional screening of 176 unrelated ASD probands revealed an identical TRAP1 variant in a male patient who had inherited it from a healthy mother. Notably, newly generated knock-in Trap1 p.Q641* mice display ASD-related behavioral abnormalities that are more pronounced in males than in females. Accordingly, Trap1 p.Q641* mutation also resulted in sex-specific changes in synaptic plasticity, the number of presynaptic mitochondria, and mitochondrial respiration. Thus, the TRAP1 p.Q639* mutation is the first example of a monogenic ASD caused by impaired mitochondrial protein homeostasis.
The effect of volume loading on the extrusion of bimodal glass bead mixtures
Authors: Lawrence Joseph R. , Lipic Hugh R. , Manship Timothy D. , Son Steven F.
Published: September 2024

Additive manufacturing has provided new methods for generating complex geometries of composite energetic materials. Additive manufacturing of ammonium-perchlorate composite propellants through direct-ink-write experiences extrusion limitations due to the high viscosities of highly solids loaded propellants. Vibration-assisted printing (VAP) was developed as a method to extend the extrudability limits and extrusion speeds observed with direct-ink-write systems. This study compares the mass flowrates and extrudability limits for bimodal mixtures of glass beads and hydroxyl-terminated polybutadiene (HTPB) binder for both VAP and direct-ink-write printing as a function of volume percent solids loading. The VAP system was able to print higher volume loadings and significantly higher mass flowrate than the direct-ink-write system. The bimodal glass bead mixtures were also compared to a previous study that focused on the extrusion of monomodal glass beads/HTPB mixtures. Interestingly, bimodal mixtures were shown to extrude quicker than monomodal mixtures at all volume loadings and across both printing systems.
Paper-based colorimetric sensor using a single-atom nanozyme for the ultrasensitive detection of Cr(vi) in short-necked clams
Authors: Wu Shuo , Khan Muhammad Arif , Zhang Lifan , Zhao Hongbin , Huang Tianzeng , Cao Hongmei , Ye Daixin
Published: September 2024

A schematic of the preparation and application of a paper-based colorimetric sensor using Fe–N–C for the detection of Cr(vi) in short-necked clams.