bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying changes in the environmental impact of in-crop herbicide use in Saskatchewan, Canada
Authors: Lika Elisabeta , Sutherland Chelsea , Gleim Savannah , Smyth Stuart J.
Published: March 2024

The sustainable management of herbicides is critical to modern agriculture and the environment. This article examines the evolution and environmental implications of herbicide use in Saskatchewan, Canada, agriculture. It quantifies changes in herbicide use and their environmental impacts by analyzing farm-level herbicide use data from 1991 to 1994 and from 2016 to 2019 through the environmental impact quotient. Results confirm significant reductions in both environmental and toxicological impacts of herbicides used, underlining the pivotal shift from tillage-based weed control to herbicide-resistant cropping systems. The environmental impact of the top five herbicides (glufosinate, glyphosate, clethodim, imazamox, and 2,4-D) used from 2016 to 2019 is 65% lower than that for those herbicides (MCPA, 2,4-D, bromoxynil, diclofop-methyl, and trifluralin) used from 1991 to 1994, with a 45% reduction in the active ingredient applied per acre. Despite increased herbicide use due to more crop acres being seeded, the findings highlight a marked improvement in the sustainability of herbicide use, affirming the importance of technological advancements in agriculture. This research contributes valuable insights into long-term trends in herbicide use, offering a practical framework for informed decisions aligning with sustainable agricultural practices as well as reduced biodiversity impacts.
Sea Otters’ Appetite for Crab Is Helping Strengthen Estuary Banks
Authors: Fritts Rachel
Published: March 2024

Apex predators can have a powerful impact on coastal erosion rates by keeping grazer populations down, but their influence has been largely overlooked.
MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade
Authors: Mukherjee Nabanita , Katsnelson Elizabeth , Brunetti Tonya M. , Michel Kylie , Couts Kasey L. , Lambert Karoline A. , Robinson William A. , McCarter Martin D. , Norris David A. , Tobin Richard P. , Shellman Yiqun G.
Published: March 2024

Immune checkpoint inhibitors (ICIs) are now the first-line treatment for patients with advanced melanoma. Despite promising clinical results, many patients fail to respond to these therapies. BH3 mimetics, a novel class of small molecule inhibitors that bind and inhibit anti-apoptotic members of the BCL2 family proteins such as BCL2 or MCL1, have been very successful in treating hematologic malignancies. However, there are limited studies on the immunomodulatory role of the BH3 mimetics. Several factors contribute to ICI resistance including myeloid-derived suppressor cells (MDSCs) that exert immunosuppressive effects through direct and indirect inhibition of antitumor immunity. Thus, targeting MDSCs to enhance antitumor immunity has the potential to enhance the efficacy of ICIs. In this study, we show that the MCL1 inhibitor S64315 reduces melanoma tumor growth in an immune cell-dependent manner in mice. Specifically, S64315 enhances antitumor immunity by reducing MDSC frequency and by promoting the activity of CD8+T cells. Additionally, human MDSCs are 10 times more sensitive to S64315 than cutaneous melanoma lines. Further, we found that a higher expression of MCL1 is associated with poor survival for patients treated with anti-PD-1. Finally, combining S64315 and anti-PD-1 significantly slowed tumor growth compared to either agent alone. Together, this proof-of-concept study demonstrates the potential of combining an MCL1 inhibitor with anti-PD-1 in the treatment of melanoma. It justifies the further development of next generation MCL1 inhibitors to improve efficacy of ICIs in treating malignant melanoma.
GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer
Authors: Ye Zu , Xu Shengfeng , Shi Yin , Cheng Xueqian , Zhang Yuan , Roy Sunetra , Namjoshi Sarita , Longo Michael A. , Link Todd M. , Schlacher Katharina , Peng Guang , Yu Dihua , Wang Bin , Tainer John A. , Ahmed Zamal
Published: March 2024

Growth factor receptor-bound protein 2 (GRB2) is a cytoplasmic adapter for tyrosine kinase signaling and a nuclear adapter for homology-directed-DNA repair. Here we find nuclear GRB2 protects DNA at stalled replication forks from MRE11-mediated degradation in the BRCA2 replication fork protection axis. Mechanistically, GRB2 binds and inhibits RAD51 ATPase activity to stabilize RAD51 on stalled replication forks. In GRB2-depleted cells, PARP inhibitor (PARPi) treatment releases DNA fragments from stalled forks into the cytoplasm that activate the cGAS–STING pathway to trigger pro-inflammatory cytokine production. Moreover in a syngeneic mouse metastatic ovarian cancer model, GRB2 depletion in the context of PARPi treatment reduced tumor burden and enabled high survival consistent with immune suppression of cancer growth. Collective findings unveil GRB2 function and mechanism for fork protection in the BRCA2-RAD51-MRE11 axis and suggest GRB2 as a potential therapeutic target and an enabling predictive biomarker for patient selection for PARPi and immunotherapy combination.
Area-selective atomic layer deposition on 2D monolayer lateral superlattices
Authors: Park Jeongwon , Kwak Seung Jae , Kang Sumin , Oh Saeyoung , Shin Bongki , Noh Gichang , Kim Tae Soo , Kim Changhwan , Park Hyeonbin , Oh Seung Hoon , Kang Woojin , Hur Namwook , Chai Hyun-Jun , Kang Minsoo , Kwon Seongdae , Lee Jaehyun , Lee Yongjoon , Moon Eoram , Shi Chuqiao , Lou Jun , Lee Won Bo , Kwak Joon Young , Yang Heejun , Chung Taek-Mo , Eom Taeyong , Suh Joonki , Han Yimo , Jeong Hu Young , Kim YongJoo , Kang Kibum
Published: March 2024

The advanced patterning process is the basis of integration technology to realize the development of next-generation high-speed, low-power consumption devices. Recently, area-selective atomic layer deposition (AS-ALD), which allows the direct deposition of target materials on the desired area using a deposition barrier, has emerged as an alternative patterning process. However, the AS-ALD process remains challenging to use for the improvement of patterning resolution and selectivity. In this study, we report a superlattice-based AS-ALD (SAS-ALD) process using a two-dimensional (2D) MoS2-MoSe2 lateral superlattice as a pre-defining template. We achieved a minimum half pitch size of a sub-10 nm scale for the resulting AS-ALD on the 2D superlattice template by controlling the duration time of chemical vapor deposition (CVD) precursors. SAS-ALD introduces a mechanism that enables selectivity through the adsorption and diffusion processes of ALD precursors, distinctly different from conventional AS-ALD method. This technique facilitates selective deposition even on small pattern sizes and is compatible with the use of highly reactive precursors like trimethyl aluminum. Moreover, it allows for the selective deposition of a variety of materials, including Al2O3, HfO2, Ru, Te, and Sb2Se3.
A Protein Misfolding Shaking Amplification-based method for the spontaneous generation of hundreds of bona fide prions
Authors: Eraña Hasier , Sampedro-Torres-Quevedo Cristina , Charco Jorge M. , Díaz-Domínguez Carlos M. , Peccati Francesca , San-Juan-Ansoleaga Maitena , Vidal Enric , Gonçalves-Anjo Nuno , Pérez-Castro Miguel A. , González-Miranda Ezequiel , Piñeiro Patricia , Fernández-Veiga Leire , Galarza-Ahumada Josu , Fernández-Muñoz Eva , Perez de Nanclares Guiomar , Telling Glenn , Geijo Mariví , Jiménez-Osés Gonzalo , Castilla Joaquín
Published: March 2024

Prion diseases are a group of rapidly progressing neurodegenerative disorders caused by the misfolding of the endogenous prion protein (PrPC) into a pathogenic form (PrPSc). This process, despite being the central event underlying these disorders, remains largely unknown at a molecular level, precluding the prediction of new potential outbreaks or interspecies transmission incidents. In this work, we present a method to generate bona fide recombinant prions de novo, allowing a comprehensive analysis of protein misfolding across a wide range of prion proteins from mammalian species. We study more than 380 different prion proteins from mammals and classify them according to their spontaneous misfolding propensity and their conformational variability. This study aims to address fundamental questions in the prion research field such as defining infectivity determinants, interspecies transmission barriers or the structural influence of specific amino acids and provide invaluable information for future diagnosis and therapy applications.
Quantum many-body simulations on digital quantum computers: State-of-the-art and future challenges
Authors: Fauseweh Benedikt
Published: March 2024

Simulating quantum many-body systems is a key application for emerging quantum processors. While analog quantum simulation has already demonstrated quantum advantage, its digital counterpart has recently become the focus of intense research interest due to the availability of devices that aim to realize general-purpose quantum computers. In this perspective, we give a selective overview of the currently pursued approaches, review the advances in digital quantum simulation by comparing non-variational with variational approaches and identify hardware and algorithmic challenges. Based on this review, the question arises: What are the most promising problems that can be tackled with digital quantum simulation? We argue that problems of a qualitative nature are much more suitable for near-term devices then approaches aiming purely for a quantitative accuracy improvement.
Magnetic droplet soliton pairs
Authors: Jiang S. , Chung S. , Ahlberg M. , Frisk A. , Khymyn R. , Le Q. Tuan , Mazraati H. , Houshang A. , Heinonen O. , Åkerman J.
Published: March 2024

We demonstrate magnetic droplet soliton pairs in all-perpendicular spin-torque nano-oscillators (STNOs), where one droplet resides in the STNO free layer (FL) and the other in the reference layer (RL). Typically, theoretical, numerical, and experimental droplet studies have focused on the FL, with any additional dynamics in the RL entirely ignored. Here we show that there is not only significant magnetodynamics in the RL, but the RL itself can host a droplet driven by, and coexisting with, the FL droplet. Both single droplets and pairs are observed experimentally as stepwise changes and sharp peaks in the dc and differential resistance, respectively. While the single FL droplet is highly stable, the coexistence state exhibits high-power broadband microwave noise. Furthermore, micromagnetic simulations reveal that the pair dynamics display periodic, quasi-periodic, and chaotic signatures controlled by applied field and current. The strongly interacting and closely spaced droplet pair offers a unique platform for fundamental studies of highly non-linear soliton pair dynamics.
Acidity-activatable upconversion afterglow luminescence cocktail nanoparticles for ultrasensitive in vivo imaging
Authors: Jiang Yue , Zhao Min , Miao Jia , Chen Wan , Zhang Yuan , Miao Minqian , Yang Li , Li Qing , Miao Qingqing
Published: March 2024

Activatable afterglow luminescence nanoprobes enabling switched “off-on” signals in response to biomarkers have recently emerged to achieve reduced unspecific signals and improved imaging fidelity. However, such nanoprobes always use a biomarker-interrupted energy transfer to obtain an activatable signal, which necessitates a strict distance requisition between a donor and an acceptor moiety (<10 nm) and hence induces low efficiency and non-feasibility. Herein, we report organic upconversion afterglow luminescence cocktail nanoparticles (ALCNs) that instead utilize acidity-manipulated singlet oxygen (1O2) transfer between a donor and an acceptor moiety with enlarged distance and thus possess more efficiency and flexibility to achieve an activatable afterglow signal. After in vitro validation of acidity-activated afterglow luminescence, ALCNs achieve in vivo imaging of 4T1-xenograft subcutaneous tumors in female mice and orthotopic liver tumors in male mice with a high signal-to-noise ratio (SNR). As a representative targeting trial, Bio-ALCNs with biotin modification prove the enhanced targeting ability, sensitivity, and specificity for pulmonary metastasis and subcutaneous tumor imaging via systemic administration of nanoparticles in female mice, which also implies the potential broad utility of ALCNs for tumor imaging with diverse design flexibility. Therefore, this study provides an innovative and general approach for activatable afterglow imaging with better imaging performance than fluorescence imaging.
N-Acetyltransferase 10 represses Uqcr11 and Uqcrb independently of ac4C modification to promote heart regeneration
Authors: Ma Wenya , Tian Yanan , Shi Leping , Liang Jing , Ouyang Qimeng , Li Jianglong , Chen Hongyang , Sun Hongyue , Ji Haoyu , Liu Xu , Huang Wei , Gao Xinlu , Jin Xiaoyan , Wang Xiuxiu , Liu Yining , Yu Yang , Guo Xiaofei , Tian Ye , Yang Fan , Li Faqian , Wang Ning , Cai Benzhi
Published: March 2024

Translational control is crucial for protein production in various biological contexts. Here, we use Ribo-seq and RNA-seq to show that genes related to oxidative phosphorylation are translationally downregulated during heart regeneration. We find that Nat10 regulates the expression of Uqcr11 and Uqcrb mRNAs in mouse and human cardiomyocytes. In mice, overexpression of Nat10 in cardiomyocytes promotes cardiac regeneration and improves cardiac function after injury. Conversely, treating neonatal mice with Remodelin—a Nat10 pharmacological inhibitor—or genetically removing Nat10 from their cardiomyocytes both inhibit heart regeneration. Mechanistically, Nat10 suppresses the expression of Uqcr11 and Uqcrb independently of its ac4C enzyme activity. This suppression weakens mitochondrial respiration and enhances the glycolytic capacity of the cardiomyocytes, leading to metabolic reprogramming. We also observe that the expression of Nat10 is downregulated in the cardiomyocytes of P7 male pig hearts compared to P1 controls. The levels of Nat10 are also lower in female human failing hearts than non-failing hearts. We further identify the specific binding regions of Nat10, and validate the pro-proliferative effects of Nat10 in cardiomyocytes derived from human embryonic stem cells. Our findings indicate that Nat10 is an epigenetic regulator during heart regeneration and could potentially become a clinical target.
The global speciation continuum of the cyanobacterium Microcoleus
Authors: Stanojković Aleksandar , Skoupý Svatopluk , Johannesson Hanna , Dvořák Petr
Published: March 2024

Speciation is a continuous process driven by genetic, geographic, and ecological barriers to gene flow. It is widely investigated in multicellular eukaryotes, yet we are only beginning to comprehend the relative importance of mechanisms driving the emergence of barriers to gene flow in microbial populations. Here, we explored the diversification of the nearly ubiquitous soil cyanobacteriumMicrocoleus. Our dataset consisted of 291 genomes, of which 202 strains and eight herbarium specimens were sequenced for this study. We found thatMicrocoleusrepresents a global speciation continuum of at least 12 lineages, which radiated during Eocene/Oligocene aridification and exhibit varying degrees of divergence and gene flow. The lineage divergence has been driven by selection, geographical distance, and the environment. Evidence of genetic divergence and selection was widespread across the genome, but we identified regions of exceptional differentiation containing candidate genes associated with stress response and biosynthesis of secondary metabolites.
Antiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis
Authors: Gillard Joshua , Suffiotti Madeleine , Brazda Peter , Venkatasubramanian Prashanna B. , Versteegen Pauline , de Jonge Marien I. , Kelly Dominic , Bibi Sagida , Pinto Marta Valente , Simonetti Elles , Babiceanu Mihaela , Kettring Andrew , Teodosio Cristina , de Groot Ronald , Berbers Guy , Stunnenberg Hendrik G. , Schanen Brian , Fenwick Craig , Huynen Martijn A. , Diavatopoulos Dimitri A.
Published: March 2024

Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of the immunological factors that promote durable protection. Here we apply systems vaccinology to investigate antibody responses in adolescents in the Netherlands (N = 14; NL) and the United Kingdom (N = 12; UK) receiving a tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report that early antiviral and interferon gene expression signatures in blood correlate to persistence of pertussis-specific antibody responses. Single-cell analyses of the innate response identified monocytes and myeloid dendritic cells (MoDC) as principal responders that upregulate antiviral gene expression and type-I interferon cytokine production. With public data, we show that Tdap vaccination stimulates significantly lower antiviral/type-I interferon responses than Tdap-IPV, suggesting that IPV may promote antiviral gene expression. Subsequent in vitro stimulation experiments demonstrate TLR-dependent, IPV-specific activation of the pro-inflammatory p38 MAP kinase pathway in MoDCs. Together, our data provide insights into the molecular host response to pertussis booster vaccination and demonstrate that IPV enhances innate immune activity associated with persistent, pertussis-specific antibody responses.
Dynamic feedback bit-level image privacy protection based on chaos and information hiding
Authors: Zhang Jinlong , Wen Heping
Published: March 2024

Bit is the most basic unit of a digital image in the spatial domain, and bit-level encryption is regarded as an important technical means for digital image privacy protection. To address the vulnerability of image privacy protection to cryptographic attacks, in this paper, a bit-level image privacy protection scheme using Zigzag and chain-diffusion is proposed. The scheme uses a combination of Zigzag interleaving scrambling with chaotic sequences and chain-diffusion method images are encrypted at each bit level, while using non-sequential encryption to achieve efficient and secure encryption. To balance security and efficiency, the encryption strategy for each bit layer is weighted. The chaos-based sequences used for encryption depend on the previous hash value, thus the effect of chain-diffusion is achieved. To further enhance the encryption effect, a non-sequential encryption technique by non-linearly rearranging the bit cipher image is employed, so that the attacker cannot crack the protection scheme by analyzing the encrypted image. The ciphertext image hidden by discrete wavelet transform (DWT) also provides efficient encryption, higher level of security and robustness to attacks. This technology provides indistinguishable secret data embedding, making it difficult for attackers to detect or extract hidden information. Experimental results show that this scheme can effectively protect the confidentiality of the image and can resist various common cryptographic attacks. The scheme proposed in this paper is a preferred digital image privacy protection technology, so it has broad application prospects in image secure transmission occasions.
Aryl hydrocarbon receptor suppresses STING-mediated type I IFN expression in triple-negative breast cancer
Authors: Martin Jeffrey C. , da Silva Fernandes Tatiane , Chaudhry Kanita A. , Oshi Masanori , Abrams Scott I. , Takabe Kazuaki , Rosario Spencer R. , Bianchi-Smiraglia Anna
Published: March 2024

Triple-negative breast cancer (TNBC) is one of the most aggressive types of cancer. Despite decades of intense investigation, treatment options remain limited, and rapid recurrence with distant metastases remains a significant challenge. Cancer cell-intrinsic production of cytokines such as type I interferons (IFN-I) is a known potent modulator of response to therapy in many cancers, including TNBC, and can influence therapeutic outcome. Here, we report that, in TNBC systems, the aryl hydrocarbon receptor (AhR) suppresses IFN-I expression via inhibition of STImulator of Interferon Genes (STING), a key mediator of interferon production. Intratumoral STING activity is essential in mediating the efficacy of PARP inhibitors (PARPi) which are used in the treatment of cancers harboring BRCA1 deficiency. We find that, in TNBC cells, PARPi treatment activates AhR in a BRCA1 deficiency-dependent manner, thus suggesting the presence of a negative feedback loop aimed at modulating PARPi efficacy. Importantly, our results indicate that the combined inhibition of PARP and AhR is superior in elevating IFN-I expression as compared to PARPi-alone. Thus, AhR inhibition may allow for enhanced IFN-I production upon PARPi in BRCA1-deficient breast cancers, most of which are of TNBC origin, and may represent a therapeutically viable strategy to enhance PARPi efficacy.
High gain antipodal meander line antenna for point-to-point WLAN/WiMAX applications
Authors: Gad Mohamed M. , Sallam Mai O.
Published: March 2024

This paper introduces a planar antipodal meander line antenna fabricated using RO3003 substrate. The proposed antenna is designed to radiate in the end-fire direction, achieving a maximum measured gain of 10.43 dBi within its working bandwidth, which ranges from 2.24 GHz to 2.7 GHz, covering long-range WLAN/WiMAX applications. A systematic procedure is adopted in the design process to prove its tunability to cover other application requirements in terms of gain and bandwidth. The proposed design steps show that the bandwidth and the gain can independently be controlled by adjusting specific design parameters such as the number of radiators and the scaling factor. The antenna is fine-tuned using sensitivity analysis and parametric study to guarantee optimum operation at the desired bandwidth. Experimental measurements of the fabricated design demonstrate a high degree of correlation with simulations conducted using CST and HFSS. In comparison to other end-fire antennas presented in the literature, the proposed design manifests its capability to provide high gain for WLAN/WiMAX nodes connectivity. The measurements show that the proposed traveling wave antenna exhibits a high radiation efficiency with maximum value of 99.8% at 2.35 GHz. The measured side lobe level is found to be below $$-18$$

-
18

dB and $$-20$$

-
20

dB at 2.45 GHz along the $$E$$
E
- and $$H$$
H
-planes, respectively. Apart from its excellent radiation performance, the antenna is characterized by its low profile and fabrication simplicity.
The clinical relevance of a polygenic risk score for type 2 diabetes mellitus in the Korean population
Authors: Kim Na Yeon , Lee Haekyung , Kim Sehee , Kim Ye-Jee , Lee Hyunsuk , Lee Junhyeong , Kwak Soo Heon , Lee Seunggeun
Published: March 2024

The clinical utility of a type 2 diabetes mellitus (T2DM) polygenic risk score (PRS) in the East Asian population remains underexplored. We aimed to examine the potential prognostic value of a T2DM PRS and assess its viability as a clinical instrument. We first established a T2DM PRS for 5490 Korean individuals using East Asian Biobank data (269,487 samples). Subsequently, we assessed the predictive capability of this T2DM PRS in a prospective longitudinal study with baseline data and data from seven additional follow-ups. Our analysis showed that the T2DM PRS could predict the transition of glucose tolerance stages from normal glucose tolerance to prediabetes and from prediabetes to T2DM. Moreover, T2DM patients in the top-decile PRS group were more likely to be treated with insulin (hazard ratio = 1.69, p value = 2.31E−02) than were those in the remaining PRS groups. T2DM PRS values were significantly high in the severe diabetes subgroup, characterized by insulin resistance and $$\beta$$
β
-cell dysfunction (p value = 0.0012). The prediction models with the T2DM PRS had significantly greater Harrel’s C-indices than did corresponding models without it. By utilizing prospective longitudinal study data and extensive clinical risk factor information, our analysis provides valuable insights into the multifaceted clinical utility of the T2DM PRS.
Effects of macro- and micro-nutrients on momentary and season-long feeding responses by select species of ants
Authors: Renyard Asim , Gooding Claire , Chalissery Jaime M. , Petrov Jonathan , Gries Gerhard
Published: March 2024

Few studies have investigated the relative contribution of specific nutrients to momentary and season-long foraging responses by ants. Using western carpenter ants, Camponotus modoc, and European fire ants, Myrmica rubra, as model species, we: (1) tested preferential consumption of various macro- and micro-nutrients; (2) compared consumption of preferred macro-nutrients; (3) investigated seasonal shifts (late May to mid-September) in nutrient preferences; and (4) tested whether nutrient preferences of C. modoc and M. rubra pertain to black garden ants, Lasius niger, and thatching ants, Formica aserva. In laboratory and field experiments, we measured nutrient consumption by weighing Eppendorf tubes containing aqueous nutrient solutions before and after feeding by ants. Laboratory colonies of C. modoc favored nitrogenous urea and essential amino acids (EAAs), whereas M. rubra colonies favored sucrose. Field colonies of C. modoc and M. rubra preferentially consumed EAAs and sucrose, respectively, with no sustained shift in preferred macro-nutrient over the course of the foraging season. The presence of a less preferred macro-nutrient in a nutrient blend did not diminish the blend’s ‘appeal’ to foraging ants. Sucrose and EAAs singly and in combination were equally consumed by L. niger, whereas F. aserva preferred EAAs. Baits containing both sucrose and EAAs were consistently consumed by the ants studied in this project and should be considered for pest ant control.
Viral genome sequencing to decipher in-hospital SARS-CoV-2 transmission events
Authors: Esser Elisabeth , Schulte Eva C. , Graf Alexander , Karollus Alexander , Smith Nicholas H. , Michler Thomas , Dvoretskii Stefan , Angelov Angel , Sonnabend Michael , Peter Silke , Engesser Christina , Radonic Aleksandar , Thürmer Andrea , von Kleist Max , Gebhardt Friedemann , da Costa Clarissa Prazeres , Busch Dirk H. , Muenchhoff Maximilian , Blum Helmut , Keppler Oliver T. , Gagneur Julien , Protzer Ulrike
Published: March 2024

The SARS-CoV-2 pandemic has highlighted the need to better define in-hospital transmissions, a need that extends to all other common infectious diseases encountered in clinical settings. To evaluate how whole viral genome sequencing can contribute to deciphering nosocomial SARS-CoV-2 transmission 926 SARS-CoV-2 viral genomes from 622 staff members and patients were collected between February 2020 and January 2021 at a university hospital in Munich, Germany, and analysed along with the place of work, duration of hospital stay, and ward transfers. Bioinformatically defined transmission clusters inferred from viral genome sequencing were compared to those inferred from interview-based contact tracing. An additional dataset collected at the same time at another university hospital in the same city was used to account for multiple independent introductions. Clustering analysis of 619 viral genomes generated 19 clusters ranging from 3 to 31 individuals. Sequencing-based transmission clusters showed little overlap with those based on contact tracing data. The viral genomes were significantly more closely related to each other than comparable genomes collected simultaneously at other hospitals in the same city (n = 829), suggesting nosocomial transmission. Longitudinal sampling from individual patients suggested possible cross-infection events during the hospital stay in 19.2% of individuals (14 of 73 individuals). Clustering analysis of SARS-CoV-2 whole genome sequences can reveal cryptic transmission events missed by classical, interview-based contact tracing, helping to decipher in-hospital transmissions. These results, in line with other studies, advocate for viral genome sequencing as a pathogen transmission surveillance tool in hospitals.
Kernel Bayesian nonlinear matrix factorization based on variational inference for human–virus protein–protein interaction prediction
Authors: Ma Yingjun , Zhao Yongbiao , Ma Yuanyuan
Published: March 2024

Identification of potential human–virus protein–protein interactions (PPIs) contributes to the understanding of the mechanisms of viral infection and to the development of antiviral drugs. Existing computational models often have more hyperparameters that need to be adjusted manually, which limits their computational efficiency and generalization ability. Based on this, this study proposes a kernel Bayesian logistic matrix decomposition model with automatic rank determination, VKBNMF, for the prediction of human–virus PPIs. VKBNMF introduces auxiliary information into the logistic matrix decomposition and sets the prior probabilities of the latent variables to build a Bayesian framework for automatic parameter search. In addition, we construct the variational inference framework of VKBNMF to ensure the solution efficiency. The experimental results show that for the scenarios of paired PPIs, VKBNMF achieves an average AUPR of 0.9101, 0.9316, 0.8727, and 0.9517 on the four benchmark datasets, respectively, and for the scenarios of new human (viral) proteins, VKBNMF still achieves a higher hit rate. The case study also further demonstrated that VKBNMF can be used as an effective tool for the prediction of human–virus PPIs.
Mitochondrial DNA mutations in Korean patients with Leber’s hereditary optic neuropathy
Authors: Yang Hee Kyung , Seong Moon-Woo , Hwang Jeong-Min
Published: March 2024

In order to explore the spectrum of mitochondrial DNA (mtDNA) mutations in Korean patients with Leber's hereditary optic neuropathy (LHON), we investigated the spectrum of mtDNA mutations in 145 Korean probands confirmed with the diagnosis of LHON. Total genomic DNA was isolated from the peripheral blood leukocytes of the patients with suspected LHON, and mtDNA mutations were identified by direct sequencing. Analysis of mtDNA mutations revealed seven primary LHON mutations including the nucleotide positions (nps) 11778A (101 probands, 69.2%), 14484C (31 probands, 21.2%), 3460A (5 probands, 3.4%), and G3635A, G3733A, C4171A, and G13051A mutations in one proband each. In addition, two provisional mtDNA mutations at nps T3472C, and G13259A were each found in one proband, respectively. Another provisional mtDNA mutation at np T3394C was found in two probands. In conclusion, the spectrum of mtDNA mutations in Korean patients with LHON may differ from other ethnicities, which is characterized by high prevalence of 11778A and 14484C mutations, and a low prevalence of the 3460A mutation.
Metabolic maturation in the infant urine during the first 3 months of life
Authors: Astono Julie , Poulsen Katrine O. , Larsen Rikke A. , Jessen Emma V. , Sand Chatrine B. , Rasmussen Morten A. , Sundekilde Ulrik K.
Published: March 2024

The infant urine metabolome provides a body metabolic snapshot, and the sample collection can be done without stressing the fragile infant. 424 infant urine samples from 157 infants were sampled longitudinally at 1-, 2-, and 3 months of age. 49 metabolites were detected using proton nuclear magnetic resonance spectroscopy. Data were analyzed with multi- and univariate statistical methods to detect differences related to infant age-stage, gestational age, mother’s pre-pregnancy BMI, C-section, infant birth weight, and infant sex. Significant differences were identified between age-stage (pbonferoni < 0.05) in 30% (15/49) of the detected metabolites. Urine creatinine increased significantly from 1 to 3 months. In addition, myo-inositol, taurine, methionine, and glucose seem to have conserved levels within the individual over time. We calculated a urine metabolic maturation age and found that the metabolic age at 3 months is negatively correlated to weight at 1 year. These results demonstrate that the metabolic maturation can be observed in urine metabolome with implications on infant growth and specifically suggesting that the systematic age effect on creatinine promotes caution in using this as normalization of other urine metabolites.
Loss-of-function variant in spermidine/spermine N1-acetyl transferase like 1 (SATL1) gene as an underlying cause of autism spectrum disorder
Authors: Alayoubi Abdulfatah M. , Iqbal Muhammad , Aman Hassan , Hashmi Jamil A. , Alayadhi Laila , Al-Regaiey Khalid , Basit Sulman
Published: March 2024

Autism spectrum disorder (ASD) is a complicated, lifelong neurodevelopmental disorder affecting verbal and non-verbal communication and social interactions. ASD signs and symptoms appear early in development before the age of 3 years. It is unlikely for a person to acquire autism after a period of normal development. However, we encountered an 8-year-old child who developed ASD later in life although his developmental milestones were normal at the beginning of life. Sequencing the complete coding part of the genome identified a hemizygous nonsense mutation (NM_001367857.2):c.1803C>G; (p.Tyr601Ter) in the gene (SATL1) encoding spermidine/spermine N1-acetyl transferase like 1. Screening an ASD cohort of 28 isolated patients for the SATL1 gene identified another patient with the same variant. Although SATL1 mutations have not been associated with any human diseases, our data suggests that a mutation in SATL1 is the underlying cause of ASD in our cases. In mammals, mutations in spermine synthase (SMS), an enzyme needed for the synthesis of spermidine polyamine, have been reported in a syndromic form of the X-linked mental retardation. Moreover, SATL1 gene expression studies showed a relatively higher expression of SATL1 transcripts in ASD related parts of the brain including the cerebellum, amygdala and frontal cortex. Additionally, spermidine has been characterized in the context of learning and memory and supplementations with spermidine increase neuroprotective effects and decrease age-induced memory impairment. Furthermore, spermidine biosynthesis is required for spontaneous axonal regeneration and prevents α-synuclein neurotoxicity in invertebrate models. Thus, we report, for the first time, that a mutation in the SATL1 gene could be a contributing factor in the development of autistic symptoms in our patients.
In situ gold adsorption experiment at an acidic hot spring using a blue-green algal sheet
Authors: Nozaki Tatsuo , Fukushima Yasuyuki , Okada Satoshi , Takaya Yutaro , Makabe Akiko , Watanabe Masayuki
Published: March 2024

Gold (Au), as one of the most precious metal resources that is used for both industrial products and private ornaments, is a global investment target, and mining companies are making huge investments to discover new Au deposits. Here, we report in situ Au adsorption in an acidic hot spring by a unique adsorption sheet made from blue-green algae with a high preferential adsorption ability for Au. The results of in situ Au adsorption experiments conducted for various reaction times ranging from 0.2 h to 7 months showed that a maximum Au concentration of 30 ppm was adsorbed onto the blue-green algal sheet after a reaction time of 7 months. The Au concentration in the hot spring water was below the detection limit (< 1 ppt); therefore, Au was enriched by preferential adsorption onto the blue-green algal sheet by a factor of more than ~ 3 × 107. Thus, our gold recovery method has a high potential to recover Au even from an Au-poor solution such as hot spring water or mine wastewater with a low impact on the environment.
Helicobacter pylori components increase the severity of metabolic syndrome and its hepatic manifestations induced by a high fat diet
Authors: Tomaszewska Agata , Gonciarz Weronika , Rechcinski Tomasz , Chmiela Magdalena , Kurdowska Anna K. , Krupa Agnieszka
Published: March 2024

The metabolic syndrome, often accompanied by hepatic manifestations, is a high-risk factor for developing cardiovascular disease. Patients with metabolic dysfunction associated with steatohepatic disease (MASDL) are at significant risk of developing coronary artery disease. Atherosclerosis is a systemic inflammatory disorder in which several factors, including dietary or infectious factors, can cause an inflammatory response. Helicobacter pylori (HP) bacteria have been implicated in the progression of proatherogenic vascular endothelial lesions, moreover, our previous study in an experimental in vivo model of Cavia porcellus showed that HP components and high-fat substances acted synergistically in promoting vascular endothelial inflammation, leading to an early onset of a proatherogenic environment. In the present study, our goal was to determine the contribution of HP components to the development of hepatic manifestations of metabolic syndrome in an experimental model. Our results showed that HP infection in animals exposed to a high-fat diet increased oxidative stress and lipid peroxidation, followed by endothelial lipid deposition, impaired endothelial apoptosis, cell lysis, and increased vascular stiffness. Finally, histopathological analysis of liver tissue showed signs of MASLD development in HP-infected animals fed a high-fat diet.
Development of an advanced liquid chromatography–tandem mass spectrometry measurement system for simultaneous sphingolipid analysis
Authors: Uranbileg Baasanjav , Sakai Eri , Kubota Masayuki , Isago Hideaki , Sumitani Masahiko , Yatomi Yutaka , Kurano Makoto
Published: March 2024

Mass spectrometry-based lipidomics approaches offer valuable tools for the detection and quantification of various lipid species, including sphingolipids. The present study aimed to develop a new method to simultaneously detect various sphingolipid species that applies to diverse biological samples. We developed and validated a measurement system by employing a single-column liquid chromatography-mass spectrometry system utilizing a normal-phase separation mode with positive ionization. The measurement system provided precision with a coefficient of variant below 20% for sphingolipids in all types of samples, and we observed good linearity in diluted serum samples. This system can measure the following sphingolipids: sphingosine 1-phosphate (S1P), sphingosine (Sph), dihydroS1P (dhS1P), dihydroSph (dhSph), ceramide 1-phosphate (Cer1P), hexosylceramide (HexCer), lactosylceramide (LacCer), dh-ceramide, deoxy-ceramide, deoxy-dh-ceramide, and sphingomyelin (SM). By measuring these sphingolipids in cell lysates where S1P lyase expression level was modulated, we could observe significant and dynamic modulations of sphingolipids in a comprehensive manner. Our newly established and validated measurement system can simultaneously measure many kinds of sphingolipids in biological samples. It holds great promise as a valuable tool for laboratory testing applications to detect overall modulations of sphingolipids, which have been proposed to be involved in pathogenesis processes in a series of elegant basic research studies.
Development of a density-based topology optimization of homogenized lattice structures for individualized hip endoprostheses and validation using micro-FE
Authors: Müller Patrik , Synek Alexander , Stauß Timo , Steinnagel Carl , Ehlers Tobias , Gembarski Paul Christoph , Pahr Dieter , Lachmayer Roland
Published: March 2024

Prosthetic implants, particularly hip endoprostheses, often lead to stress shielding because of a mismatch in compliance between the bone and the implant material, adversely affecting the implant’s longevity and effectiveness. Therefore, this work aimed to demonstrate a computationally efficient method for density-based topology optimization of homogenized lattice structures in a patient-specific hip endoprosthesis. Thus, the root mean square error (RMSE) of the stress deviations between the physiological femur model and the optimized total hip arthroplasty (THA) model compared to an unoptimized-THA model could be reduced by 81 % and 66 % in Gruen zone (GZ) 6 and 7. However, the method relies on homogenized finite element (FE) models that only use a simplified representation of the microstructural geometry of the bone and implant. The topology-optimized hip endoprosthesis with graded lattice structures was synthesized using algorithmic design and analyzed in a virtual implanted state using micro-finite element (micro-FE) analysis to validate the optimization method. Homogenized FE and micro-FE models were compared based on averaged von Mises stresses in multiple regions of interest. A strong correlation (CCC > 0.97) was observed, indicating that optimizing homogenized lattice structures yields reliable outcomes. The graded implant was additively manufactured to ensure the topology-optimized result’s feasibility.
Preliminary characterization of rectification for transradial prosthetic sockets
Authors: Ngan Calvin C. , Pendse Vishal , Sivasambu Harry , Ouellette Elaine , Ready Neil , Andrysek Jan
Published: March 2024

Achieving proper socket fit is crucial for the effective use of a prosthesis. However, digital socket design lacks standardization and presents a steep learning curve for prosthetists. While research has focused on digital socket design for the lower-limb population, there is a research gap in upper-limb socket design. This study aimed to characterize the design (rectification) process for the transradial socket, specifically the three-quarter Northwestern-style design, towards the development of a more systematic, data-driven socket design approach. Fourteen (n = 14) pairs of unrectified and rectified plaster models were compared. Six common rectification zones were identified through shape analysis, with zones of plaster addition being the most prominent in terms of volume and surface area. A novel 3D vector mapping technique was employed, which revealed that most of the shape changes occurred in the anterior–posterior and proximal–distal directions. Overall, the interquartile range of each rectification zone demonstrated reasonable consistency in terms of volume, surface deviation, and 3D vector representation. The initial findings from this study support the potential for quantitively modelling the transradial socket design process. This opens the door for developing tools for categorizing and predicting socket designs across diverse populations through the application of techniques such as machine learning.
From periphery immunity to central domain through clinical interview as a new insight on schizophrenia
Authors: Krzyściak Wirginia , Szwajca Marta , Śmierciak Natalia , Chrzan Robert , Turek Aleksander , Karcz Paulina , Bryll Amira , Pilecki Maciej , Morava Eva , Ligęzka Anna , Kozicz Tamas , Mazur Paulina , Batko Bogna , Skalniak Anna , Popiela Tadeusz
Published: March 2024

Identifying disease predictors through advanced statistical models enables the discovery of treatment targets for schizophrenia. In this study, a multifaceted clinical and laboratory analysis was conducted, incorporating magnetic resonance spectroscopy with immunology markers, psychiatric scores, and biochemical data, on a cohort of 45 patients diagnosed with schizophrenia and 51 healthy controls. The aim was to delineate predictive markers for diagnosing schizophrenia. A logistic regression model was used, as utilized to analyze the impact of multivariate variables on the prevalence of schizophrenia. Utilization of a stepwise algorithm yielded a final model, optimized using Akaike’s information criterion and a logit link function, which incorporated eight predictors (White Blood Cells, Reactive Lymphocytes, Red Blood Cells, Glucose, Insulin, Beck Depression score, Brain Taurine, Creatine and Phosphocreatine concentration). No single factor can reliably differentiate between healthy patients and those with schizophrenia. Therefore, it is valuable to simultaneously consider the values of multiple factors and classify patients using a multivariate model.
Direct observation of magnetic domain walls in glass-coated submicronic amorphous wires
Authors: Óvári T.-A. , Ababei G. , Stoian G. , Corodeanu S. , Chiriac H. , Lupu N.
Published: March 2024

Results on the magnetic domain walls in rapidly solidified magnetostrictive and non-magnetostrictive amorphous submicronic wires are reported. Utilizing Lorentz transmission electron microscopy (LTEM) for the first time in this context, we have visualized and analyzed the domain walls in such ultra-thin amorphous wires. All the investigated samples display vortex magnetic domain walls, regardless of wire composition or diameter. In non-magnetostrictive wires, the domain walls maintain their structure and symmetry under varying magnetic field conditions. In contrast, magnetostrictive wires show an elongation of their domain walls upon magnetic field application, a response linked to the magnetoelastic coupling between magnetostriction and internal stresses induced during wire preparation. This study advances the understanding of magnetization reversal processes in amorphous submicronic wires. The insights gained are crucial for future developments in miniaturized magnetic devices.
Oral health-related quality of life, adaptation/discomfort during open bite treatment with spurs: complementary analysis from a randomized clinical trial
Authors: Aliaga-Del Castillo Aron , Marañón-Vásquez Guido Artemio , Janson Guilherme , Vilanova Lorena , Miranda Felicia , Massaro Camila , Bellini-Pereira Silvio Augusto , Arriola-Guillén Luis Ernesto , Yatabe Marilia , Ruellas Antonio Carlos , Cevidanes Lucia , Garib Daniela
Published: March 2024

This single-center trial aimed to longitudinally compare the oral health-related quality of life (OHRQOL), adaptation and discomfort during anterior open bite (AOB) treatment with lingual spurs and build-ups (SBU) versus spurs only (S) approaches. Children (7–11 years) with AOB were randomly allocated into two treatment groups (SBU or S). The Child Perception Questionnaire (CPQ8–10) was applied 1 and 12 months after installation of the appliances. Questionnaires evaluating functional adaptation and discomfort during the first month of treatment were also applied. A visual analog scale (VAS) was used in these questionnaires. Generalized mixed models were used for analyzing OHRQOL and discomfort data. Generalized linear models were used to assess adaptation outcomes (α = 0.05). The SBU group included 24 patients (7 males and 17 females; mean age 8.2 years) and the S group included 25 patients (11 males and 14 females; mean age 8.3 years). Regardless of the treatment type, overall OHRQOL scores at 12 months were 0.69 times those recorded at 1 month after the appliances installation (i.e., ~ 31% reduction; exp (β) = 0.69; 95% CI: 0.55, 0.88). A significant interaction between treatment and time was detected for the ‘functional limitations’ domain. For this domain, a significant improvement from the first to the twelfth month was observed in the S group (P < 0.001). Patients in both treatment groups showed similar and easy adaptation to the appliances. Independent of the type of treatment, tongue-related discomfort decreased over time. One week and one month after the appliance’s delivery, the discomfort scores were 0.19 (i.e., ~ 81% reduction; exp (β) = 0.19; 95% CI: 0.13, 0.28; P < 0.001) and 0.02 (i.e., ~ 98% reduction; exp (β) = 0.02; 95% CI: 0.01, 0.07; P < 0.001) times, respectively, those issued immediately after the installation of the appliances. Regardless of treatment type; overall OHRQOL improved from the first to the twelfth month of AOB treatment. The functional limitations score decreased in the S group. Children showed easy adaptation, and their discomfort decreased 1 week after the installation of the appliances.

Trial registration: Clinicaltrials.gov; NCT03702881, date of registration: October 11, 2018.