bluuebunny/crossref_metadata_2025 huggingface dataset:
Sheep fatigue during transport: Lost in translation?
Authors: Colitti Katia , Mitchell Malcolm , Langford Fritha
Published: March 2024

Although sheep are commonly transported long distances, and sheep welfare during transport is a topic of research and policy discussion, the subject of their fatigue during transport has been under-researched. The current qualitative study, focused on the EU and UK, aimed to critically analyse stakeholder views on issues relating to sheep fatigue, including behavioural indications of fatigue, the interplay between fatigue and other factors, and the practicalities of identifying fatigue in commercial transport conditions. Insight into stakeholder perceptions of these issues could contribute to the body of knowledge regarding sheep fatigue during transport, potentially playing a part in future efforts to improve fatigue understanding and detection. Eighteen experts from different stakeholder groups were interviewed. Reflexive thematic analysis of interview data yielded four themes and three sub-themes. The first theme, “Let’s anthropomorphise it a little bit”, underscores the pervasiveness of anthropomorphism and suggests using it in a conscious and deliberate way to drive stakeholder engagement and policy change. The second theme, “We think that they’re like we are and they’re not”, cautions against wholesale transfer of human experiences to animals. The third theme, ‘See the whole animal’, advocates using Qualitative Behaviour Analysis (QBA), proven reliable in other contexts, to deepen and enrich our current understanding of fatigue. The fourth theme, ‘Fatigue “never comes up”’, highlights the fact that fatigue is rarely if ever discussed in the context of sheep transport. These themes suggest several avenues for future research, including developing QBA-based assessments for fatigue to improve welfare during transport.
More than Just a Business: Recasting Literary Publishing in Postwar Germany, 1945–1949
Authors: Stokes Anne , Stokes Ray
Published: March 2024

Like other creative industries emerging in mid-1945 from 12 years of Nazi rule, including six years of war, German publishing was ideologically suspect, internationally isolated, and insular. By the 1950s, however, the book trade in the two German successor states was once again varied and vibrant. And it was also tightly integrated into the international publishing business, within which it had become an increasingly active and important presence. This article analyzes the development of the German book publishing industry during the Allied occupation, 1945-1949, through the lens of knowledge transfer. It was a time during which capital-starved German publishers harnessed the political and ideological objectives of the occupiers and their prewar contacts to achieve their own commercial and cultural ambitions, including taking initial steps toward internationalization. The focus is on literary fiction, a genre that constituted a minority of all published output in the postwar period, but which also included all top bestsellers. Literature in translation, moreover, accounted for a substantial proportion of those bestselling books, and at the same time represented a key vehicle for internationalization. Two case studies, one drawn from the Soviet zone of occupation, the later East Germany, and one from the western zones that came to be dominated by the Americans, the later West Germany, illustrate two different, yet remarkably similar paths through which this interplay of ideological alignment and commerce played out among a range of actors and laid the basis for the subsequent development of the industry.
Humanitarian and Youth Activism across Time and Space
Authors: Brewis Georgina
Published: March 2024

This essay engages with Daniel Laqua's book Activism across Borders since 1870: Causes, Campaigns and Conflicts in and beyond Europe (London, 2023) from the perspective of a historian of both humanitarianism and youth. This short reflection therefore focuses primarily on the book's engagement with the topic of humanitarianism, before discussing an understated, albeit important, cross-cutting theme of the book: the significance of youth in transnational activism. It highlights a number of features of Laqua's book, for instance the merits of adopting a broad chronological approach. At the same time, the essay also uses the space to present a number of reflections on activism, from questions about the generational appeal of particular causes to the way in which particular figures might spark activism. It ends with some thoughts about the source base used to write such histories of activism.
A Mid‐Lithospheric Discontinuity Detected Beneath 155 Ma Western Pacific Seafloor Using Sp Receiver Functions
Authors: Chen K.‐X. , Forsyth D. W. , Fischer K. M.
Published: March 2024

This study probes the lithosphere‐asthenosphere system beneath 155 Ma Pacific seafloor using teleseismic S‐to‐p receiver functions at the Pacific Lithosphere Anisotropy and Thickness Experiment project ocean‐bottom‐seismometers. Within the lithosphere, a significant velocity decrease at 33–50 km depth is observed. This mid‐lithospheric discontinuity is consistent with the velocity contrast between the background mantle and thin, trapped layers of crystallized partial melt, in the form of either dolomite or garnet granulite. These melts possibly originated from deeper asthenospheric melting beneath the flanks of spreading centers, and were transported within the cooling lithosphere. A positive velocity increase of 3%–6% is observed at 130–155 km depth and is consistent with the base of a layer with partial melt in the asthenosphere. A shear velocity decrease associated with the lithosphere‐asthenosphere boundary at 95–115 km depth is permitted by the data, but is not required.
Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential
Authors: Xiao Yu-Ling , Gong Yue , Qi Ying-Jia , Shao Zhi-Ming , Jiang Yi-Zhou
Published: March 2024

Diet, serving as a vital source of nutrients, exerts a profound influence on human health and disease progression. Recently, dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases, autoimmune diseases, cardiovascular diseases, and metabolic disorders. These interventions have demonstrated substantial potential in modulating metabolism, disease trajectory, and therapeutic responses. Metabolic reprogramming is a hallmark of malignant progression, and a deeper understanding of this phenomenon in tumors and its effects on immune regulation is a significant challenge that impedes cancer eradication. Dietary intake, as a key environmental factor, can influence tumor metabolism. Emerging evidence indicates that dietary interventions might affect the nutrient availability in tumors, thereby increasing the efficacy of cancer treatments. However, the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is complex. Despite encouraging results, the mechanisms underlying diet-based therapeutic strategies remain largely unexplored, often resulting in underutilization in disease management. In this review, we aim to illuminate the potential effects of various dietary interventions, including calorie restriction, fasting-mimicking diet, ketogenic diet, protein restriction diet, high-salt diet, high-fat diet, and high-fiber diet, on cancer and the aforementioned diseases. We explore the multifaceted impacts of these dietary interventions, encompassing their immunomodulatory effects, other biological impacts, and underlying molecular mechanisms. This review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.
The pancancer overexpressed NFYC Antisense 1 controls cell cycle mitotic progression through in cis and in trans modes of action
Authors: Pandini Cecilia , Pagani Giulia , Tassinari Martina , Vitale Emanuele , Bezzecchi Eugenia , Saadeldin Mona Kamal , Doldi Valentina , Giannuzzi Giuliana , Mantovani Roberto , Chiara Matteo , Ciarrocchi Alessia , Gandellini Paolo
Published: March 2024

Antisense RNAs (asRNAs) represent an underappreciated yet crucial layer of gene expression regulation. Generally thought to modulate their sense genes in cis through sequence complementarity or their act of transcription, asRNAs can also regulate different molecular targets in trans, in the nucleus or in the cytoplasm. Here, we performed an in-depth molecular characterization of NFYCAntisense1 (NFYC-AS1), the asRNA transcribed head-to-head to NFYC subunit of the proliferation-associated NF-Y transcription factor. Our results show that NFYC-AS1 is a prevalently nuclear asRNA peaking early in the cell cycle. Comparative genomics suggests a narrow phylogenetic distribution, with a probable origin in the common ancestor of mammalian lineages. NFYC-AS1 is overexpressed pancancer, preferentially in association with RB1 mutations. Knockdown of NFYC-AS1 by antisense oligonucleotides impairs cell growth in lung squamous cell carcinoma and small cell lung cancer cells, a phenotype recapitulated by CRISPR/Cas9-deletion of its transcription start site. Surprisingly, expression of the sense gene is affected only when endogenous transcription of NFYC-AS1 is manipulated. This suggests that regulation of cell proliferation is at least in part independent of the in cis transcription-mediated effect on NFYC and is possibly exerted by RNA-dependent in trans effects converging on the regulation of G2/M cell cycle phase genes. Accordingly, NFYC-AS1-depleted cells are stuck in mitosis, indicating defects in mitotic progression. Overall, NFYC-AS1 emerged as a cell cycle-regulating asRNA with dual action, holding therapeutic potential in different cancer types, including the very aggressive RB1-mutated tumors.
The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial
Authors: Hsiehchen David , Beg Muhammad S. , Kainthla Radhika , Lohrey Jay , Kazmi Syed M. , Khosama Leticia , Maxwell Mary Claire , Kline Heather , Katz Courtney , Hassan Asim , Kubota Naoto , Siglinsky Ellen , Pillai Anil K. , Youssoufian Hagop , Mockbee Colleen , Culm Kerry , Uhlik Mark , Benjamin Laura , Brekken Rolf A. , Ahn Chul , Singal Amit G. , Zhu Hao , Hoshida Yujin , Yopp Adam C.
Published: March 2024

Immune checkpoint inhibitors targeting PD-1/L1 have modest efficacy in hepatocellular carcinoma as single agents. Targeting membranous phosphatidylserine may induce pro-inflammatory and -immune stimulating effects that enhance immunotherapy activity. This hypothesis was tested in a single-arm phase 2 trial evaluating frontline bavituximab, a phosphatidylserine targeting antibody, plus pembrolizumab (anti-PD-1) in patients with unresectable hepatocellular carcinoma (NCT03519997). The primary endpoint was investigator-assessed objective response rate among evaluable patients, and secondary end points included progression-free survival, incidence of adverse events, overall survival, and duration of response. Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3–11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response. These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the pre-treatment tumor microenvironment.
Energy system for evaluation of modification methods on energy transfer efficiency and optimization of membranes
Authors: Li Tian , Zhou Hong , Ding Wei , Wang Jinjun , Zhang Tiancheng
Published: March 2024

Saving energy is crucial for utilizing membrane technology, but there is no energy parameter for understanding the relationships among membrane performance and energy. Here, φ is defined as the energy transfer efficiency of the membrane, and its numerical expression of membrane performance is poor (e.g., in the range of 10−23). The method of modifying membranes is a crucial determinant for developing membrane science, but researchers using current parameters to evaluate modification methods might lead to erroneous conclusions. Hence, the newly established system θ is used to analyze the influence of different modification methods on energy consumption, which not only establish the relationship between different modification methods but also provide the research routes for future optimization methods. The main conclusions are as follows: (1) The current modification methods influence on the energy transfer efficiency of the pristine membrane by about 0.4902–3.278 × 104 times; (2) Using scientific data certifies that the modified support layer of the membranes is a more effective method for reducing the energy consumption than the modified activity layer of the membranes; (3) The establishment of this system provides data support for analyzing the advantages and disadvantages of modification methods, and provides guidance for how to optimize the modification methods of membranes. Therefore, this study not only fills key knowledge gaps in membrane science, but also provides theoretical support for how to optimize membrane modification methods.
Bone scan findings of Paget’s disease of bone in patients with VCP Multisystem Proteinopathy 1
Authors: Columbres Rod Carlo Agram , Din Sarosh , Gibbs Liliane , Kimonis Virginia
Published: March 2024

Multisystem Proteinopathy 1 (MSP1) disease is a rare genetic disorder caused by mutations in the Valosin-Containing Protein (VCP) gene with clinical features of inclusion body myopathy (IBM), frontotemporal dementia (FTD), and Paget’s disease of bone (PDB). We performed bone scan imaging in twelve patients (6 females, 6 males) with confirmed VCP gene mutation six (50%) of which has myopathy alone, four (33%) with both PDB and myopathy, and two (15%) were presymptomatic carriers. We aim to characterize the PDB in diagnosed individuals, and potentially identify PDB in the myopathy and presymptomatic groups. Interestingly, two patients with previously undiagnosed PDB had positive diagnostic findings on the bone scan and subsequent radiograph imaging. Among the individuals with PDB, increased radiotracer uptake of the affected bones were of typical distribution as seen in conventional PDB and those reported in other MSP1 cohorts which are the thoracic spine and ribs (75%), pelvis (75%), shoulder (75%) and calvarium (15%). Overall, we show that technetium-99m bone scans done at regular intervals are a sensitive screening tool in patients with MSP1 associated VCP variants at risk for PDB. However, diagnostic confirmation should be coupled with clinical history, biochemical analysis, and skeletal radiographs to facilitate early treatment and prevention complications, acknowledging its limited specificity.
Pulmonary vascular reactivity in growth restricted fetuses using computational modelling and machine learning analysis of fetal Doppler waveforms
Authors: Vellvé Kilian , Garcia-Canadilla Patricia , Nogueira Mariana , Youssef Lina , Arranz Angela , Nakaki Ayako , Boada David , Blanco Isabel , Faner Rosa , Figueras Francesc , Agustí Àlvar , Gratacós Eduard , Crovetto Francesca , Bijnens Bart , Crispi Fàtima
Published: March 2024

The aim of this study was to investigate the pulmonary vasculature in baseline conditions and after maternal hyperoxygenation in growth restricted fetuses (FGR). A prospective cohort study of singleton pregnancies including 97 FGR and 111 normally grown fetuses was carried out. Ultrasound Doppler of the pulmonary vessels was obtained at 24–37 weeks of gestation and data were acquired before and after oxygen administration. After, Machine Learning (ML) and a computational model were used on the Doppler waveforms to classify individuals and estimate pulmonary vascular resistance (PVR). Our results showed lower mean velocity time integral (VTI) in the main pulmonary and intrapulmonary arteries in baseline conditions in FGR individuals. Delta changes of the main pulmonary artery VTI and intrapulmonary artery pulsatility index before and after hyperoxygenation were significantly greater in FGR when compared with controls. Also, ML identified two clusters: A (including 66% controls and 34% FGR) with similar Doppler traces over time and B (including 33% controls and 67% FGR) with changes after hyperoxygenation. The computational model estimated the ratio of PVR before and after maternal hyperoxygenation which was closer to 1 in cluster A (cluster A 0.98 ± 0.33 vs cluster B 0.78 ± 0.28, p = 0.0156). Doppler ultrasound allows the detection of significant changes in pulmonary vasculature in most FGR at baseline, and distinct responses to hyperoxygenation. Future studies are warranted to assess its potential applicability in the clinical management of FGR.
A comparative study of 11 non-linear regression models highlighting autoencoder, DBN, and SVR, enhanced by SHAP importance analysis in soybean branching prediction
Authors: Zhou Wei , Yan Zhengxiao , Zhang Liting
Published: March 2024

To explore a robust tool for advancing digital breeding practices through an artificial intelligence-driven phenotype prediction expert system, we undertook a thorough analysis of 11 non-linear regression models. Our investigation specifically emphasized the significance of Support Vector Regression (SVR) and SHapley Additive exPlanations (SHAP) in predicting soybean branching. By using branching data (phenotype) of 1918 soybean accessions and 42 k SNP (Single Nucleotide Polymorphism) polymorphic data (genotype), this study systematically compared 11 non-linear regression AI models, including four deep learning models (DBN (deep belief network) regression, ANN (artificial neural network) regression, Autoencoders regression, and MLP (multilayer perceptron) regression) and seven machine learning models (e.g., SVR (support vector regression), XGBoost (eXtreme Gradient Boosting) regression, Random Forest regression, LightGBM regression, GPs (Gaussian processes) regression, Decision Tree regression, and Polynomial regression). After being evaluated by four valuation metrics: R2 (R-squared), MAE (Mean Absolute Error), MSE (Mean Squared Error), and MAPE (Mean Absolute Percentage Error), it was found that the SVR, Polynomial Regression, DBN, and Autoencoder outperformed other models and could obtain a better prediction accuracy when they were used for phenotype prediction. In the assessment of deep learning approaches, we exemplified the SVR model, conducting analyses on feature importance and gene ontology (GO) enrichment to provide comprehensive support. After comprehensively comparing four feature importance algorithms, no notable distinction was observed in the feature importance ranking scores across the four algorithms, namely Variable Ranking, Permutation, SHAP, and Correlation Matrix, but the SHAP value could provide rich information on genes with negative contributions, and SHAP importance was chosen for feature selection. The results of this study offer valuable insights into AI-mediated plant breeding, addressing challenges faced by traditional breeding programs. The method developed has broad applicability in phenotype prediction, minor QTL (quantitative trait loci) mining, and plant smart-breeding systems, contributing significantly to the advancement of AI-based breeding practices and transitioning from experience-based to data-based breeding.
Palaeoproteomic investigation of an ancient human skeleton with abnormal deposition of dental calculus
Authors: Uchida-Fukuhara Yoko , Shimamura Shigeru , Sawafuji Rikai , Nishiuchi Takumi , Yoneda Minoru , Ishida Hajime , Matsumura Hirofumi , Tsutaya Takumi
Published: March 2024

Detailed investigation of extremely severe pathological conditions in ancient human skeletons is important as it could shed light on the breadth of potential interactions between humans and disease etiologies in the past. Here, we applied palaeoproteomics to investigate an ancient human skeletal individual with severe oral pathology, focusing our research on bacterial pathogenic factors and host defense response. This female skeleton, from the Okhotsk period (i.e., fifth to thirteenth century) of Northern Japan, poses relevant amounts of abnormal dental calculus deposition and exhibits oral dysfunction due to severe periodontal disease. A shotgun mass-spectrometry analysis identified 81 human proteins and 15 bacterial proteins from the calculus of the subject. We identified two pathogenic or bioinvasive proteins originating from two of the three “red complex” bacteria, the core species associated with severe periodontal disease in modern humans, as well as two additional bioinvasive proteins of periodontal-associated bacteria. Moreover, we discovered defense response system-associated human proteins, although their proportion was mostly similar to those reported in ancient and modern human individuals with lower calculus deposition. These results suggest that the bacterial etiology was similar and the host defense response was not necessarily more intense in ancient individuals with significant amounts of abnormal dental calculus deposition.
Evidence for disrupted copper availability in human spinal cord supports CuII(atsm) as a treatment option for sporadic cases of ALS
Authors: Hilton James B. W. , Kysenius Kai , Liddell Jeffrey R. , Mercer Stephen W. , Paul Bence , Beckman Joseph S. , McLean Catriona A. , White Anthony R. , Donnelly Paul S. , Bush Ashley I. , Hare Dominic J. , Roberts Blaine R. , Crouch Peter J.
Published: March 2024

The copper compound CuII(atsm) has progressed to phase 2/3 testing for treatment of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). CuII(atsm) is neuroprotective in mutant SOD1 mouse models of ALS where its activity is ascribed in part to improving availability of essential copper. However, SOD1 mutations cause only ~ 2% of ALS cases and therapeutic relevance of copper availability in sporadic ALS is unresolved. Herein we assessed spinal cord tissue from human cases of sporadic ALS for copper-related changes. We found that when compared to control cases the natural distribution of spinal cord copper was disrupted in sporadic ALS. A standout feature was decreased copper levels in the ventral grey matter, the primary anatomical site of neuronal loss in ALS. Altered expression of genes involved in copper handling indicated disrupted copper availability, and this was evident in decreased copper-dependent ferroxidase activity despite increased abundance of the ferroxidases ceruloplasmin and hephaestin. Mice expressing mutant SOD1 recapitulate salient features of ALS and the unsatiated requirement for copper in these mice is a biochemical target for CuII(atsm). Our results from human spinal cord indicate a therapeutic mechanism of action for CuII(atsm) involving copper availability may also be pertinent to sporadic cases of ALS.
Antagonistic properties against Fusarium sporotrichioides and glycosylation of HT-2 and T-2 toxins by selected Trichoderma strains
Authors: Modrzewska Marta , Popowski Dominik , Błaszczyk Lidia , Stępień Łukasz , Urbaniak Monika , Bryła Marcin , Cramer Benedikt , Humpf Hans-Ulrich , Twarużek Magdalena
Published: March 2024

The present study assessed the ability of Trichoderma to combat F. sporotrichioides, focusing on their antagonistic properties. Tests showed that Trichoderma effectively inhibited F. sporotrichioides mycelial growth, particularly with T. atroviride strains. In co-cultures on rice grains, Trichoderma almost completely reduced the biosynthesis of T-2 and HT-2 toxins by Fusarium. T-2 toxin-α-glucoside (T-2-3α-G), HT-2 toxin-α-glucoside (HT-2-3α-G), and HT-2 toxin-β-glucoside (HT-2-3β-G) were observed in the common culture medium, while these substances were not present in the control medium. The study also revealed unique metabolites and varying metabolomic profiles in joint cultures of Trichoderma and Fusarium, suggesting complex interactions. This research offers insights into the processes of biocontrol by Trichoderma, highlighting its potential as a sustainable solution for managing cereal plant pathogens and ensuring food safety.
Automatically listing senior members of departments as co-authors is highly prevalent in health sciences: meta-analysis of survey research
Authors: Meursinge Reynders Reint A. , Cavagnetto Davide , ter Riet Gerben , Di Girolamo Nicola , Malički Mario
Published: March 2024

A systematic review with meta-analysis was conducted to assess the prevalence of automatically listing (a) senior member(s) of a department as co-author(s) on all submitted articles in health sciences and the prevalence of degrees of support on a 5-point justification scale. Survey research was searched in PubMed, Lens.org, and Dimensions.ai. until January 5 2023. We assessed the methodological quality of studies and conducted quantitative syntheses. We identified 15 eligible surveys, that provided 67 results, all of which were rated as having low quality. A pooled estimate of 20% [95% CI 16–25] (10 surveys, 3619 respondents) of researchers in various health sciences reported that a senior member of their department was automatically listed as an author on all submitted articles. Furthermore, 28% [95% CI 22–34] of researchers (10 surveys, 2180 respondents) felt that this practice was ‘never’, 24% [95% CI 22–27] ‘rarely’, 25% [95% CI 23–28] ‘sometimes’, 13% [95% CI 9–17] ‘most of the time’, and 8% [95% CI 6–9] ‘always justified’. The practice of automatically assigning senior members of departments as co-authors on all submitted manuscripts may be common in the health sciences; with those admitting to this practice finding it unjustified in most cases.

Registration of the protocol The protocol was registered in Open Science Framework. Link: https://osf.io/4eywp/.
Novel theory and potential applications of central diastolic pressure decay time constant
Authors: Bikia Vasiliki , Segers Patrick , Rovas Georgios , Anagnostopoulos Sokratis , Stergiopulos Nikolaos
Published: March 2024

Central aortic diastolic pressure decay time constant ($${\uptau }$$
τ
) is according to the two-element Windkessel model equal to the product of total peripheral resistance ($$R$$
R
) times total arterial compliance ($$C$$
C
). As such, it is related to arterial stiffness, which has considerable pathophysiological relevance in the assessment of vascular health. This study aimed to investigate the relationship of the constant $${\uptau }$$
τ
with the product $$T\frac{MBP}{{cPP}}$$

T

MBP

cPP

, given by heart period ($$T$$
T
) times the ratio of mean blood pressure (MBP) to central pulse pressure ($$cPP$$

cPP

). The relationship was derived by performing linear fitting on an in silico population of n1 = 3818 virtual subjects, and was subsequently evaluated on in vivo data (n2 = 2263) from the large Asklepios study. The resulted expression was found to be $${\uptau } = k^{\prime}T\frac{MBP}{{cPP}},$$

τ
=

k
′

T

MBP

cPP

,

with $$k^{\prime} = 0.7$$

k
′

=
0.7

(R2 = 0.9). The evaluation of the equation on the in vivo human data reported high agreement between the estimated and reference $${\uptau }$$
τ
values, with a correlation coefficient equal to 0.94 and a normalized RMSE equal to 5.5%. Moreover, the analysis provided evidence that the coefficient $$k^{\prime}$$

k
′

is age- and gender-independent. The proposed formula provides novel theoretical insights in the relationship between $${\uptau }$$
τ
and central blood pressure features. In addition, it may allow for the evaluation of $${\uptau }$$
τ
without the need for acquiring the entire central blood pressure wave, especially when an approximation of the $$cPP$$

cPP

is feasible. This study adds to the current literature by contributing to the accessibility of an additional biomarker, such as the central diastolic pressure decay time constant, for the improved assessment of vascular ageing.
CTX-M-127 with I176F mutations found in bacteria isolates from Bangladeshi circulating banknotes
Authors: Ali Md. Zannat , Srinivasan Sankaranarayanan , Akter Selina
Published: March 2024

Extended-spectrum beta-lactamase (ESBL)-producing organisms are widely recognized as clinically relevant causes of difficult-to-treat infections. CTX-M has formed a rapidly growing family distributed worldwide among a wide range of clinical bacteria, particularly members of Enterobacteriaceae. Circulating banknotes, exchanged daily among people, pose a potential vehicle for transmitting multidrug resistance. We screened for ESBL-carrying bacteria in the present study and reported CTX-M mutations in Bangladesh's banknotes. We sequenced the genes and performed homology modeling using the Swiss model with CTX-M-15 (4HBT) as a template. Then, we performed molecular docking of mecillinam with the template and the generated model using Autodock 4.2 (Release 4.2.6). After docking, we visually inspected the complexes built using Autodock tools for polar contacts and pi-pi interactions in PyMOL 2.5.4. Our partially sequenced blaCTX-M was related to blaCTX-M-10 and blaCTX-M-15. We observed multiple single-nucleotide substitution mutations, i.e., G613T (silent mutation), A626T (I176F), and A503G (N135D). Homology modeling showed high similarity when the model was superimposed over the template. The orientation of Asn (135) in the template and Asp (135) in the model does not show a significant difference. Likewise, Ile (176) in the template and Phe (176) in the model offer the same orientation. Our generated model could bind to Lys237, Ser240, and Asp135 residues with the lowest binding energy on docking. Our predicted binding of the mecillinam to the mutated D-135 residue in the model indicates contributions and supports previous reports proposing CTX-M-15 to CTX-M-127 mutational conversion on the mecillinum resistance phenotype.
Belt electrode tetanus muscle stimulation reduces denervation-induced atrophy of rat multiple skeletal muscle groups
Authors: Uno Hiroyuki , Kamiya Shohei , Akimoto Ryuji , Hosoki Katsu , Tadano Shunta , Isemura Mako , Kouzaki Karina , Tamura Yuki , Kotani Takaya , Nakazato Koichi
Published: March 2024

Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to contract multiple muscle groups simultaneously. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly through mitochondrial biosynthesis. This study examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for one week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague–Dawley rats using belt electrodes attached to both ankle joints. After acute stimulation, a significant decrease in the glycogen content was observed in the left and right TA and GAS, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN + electrically stimulated with B-SES (DEN + ES) groups. After seven days of treatment, the wet weight (n = 8–11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN + ES groups compared with that in the CON group. The DEN + ES group showed significantly higher muscle weight and CSA than those in the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial biogenesis is a critical event in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 18S (n = 6) levels in the DEN + ES group were higher than those in the DEN group, even though RNA-seq showed that the ribosome biogenesis pathway was reduced by electrical stimulation. The mRNA levels of the muscle proteolytic molecules atrogin-1 and MuRF1 were significantly higher in DEN than those in CONT. However, they were more suppressed in DEN + ES than those in DEN. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes effectively reduced denervation-induced atrophy in multiple muscle groups. Furthermore, ribosomal biosynthesis plays a vital role in this phenomenon.
Characterization of the complete chloroplast genome of Wolffia arrhiza and comparative genomic analysis with relative Wolffia species
Authors: Park Halim , Park Jin Hwa , Kang Yang Jae
Published: March 2024

Lemnoideae, commonly referred to as the duckweed, are aquatic plants found worldwide. Wolffia species are known for their extreme reduction in size and complexity, lacking both roots and leaves, and they hold the distinction of being the smallest plants among angiosperms. Interestingly, it belongs to the Araceae family, despite its apparent morphological differences from land plants in the same family. Traditional morphological methods have limitations in classifying these plants, making molecular-level information essential. The chloroplast genome of Wolffia arrhiza is revealed that a total length of 169,602 bp and a total GC content of 35.78%. It follows the typical quadripartite structure, which includes a large single copy (LSC, 92,172 bp) region, a small single copy (SSC, 13,686 bp) region, and a pair of inverted repeat (IR, 31,872 bp each) regions. There are 131 genes characterized, comprising 86 Protein-Coding Genes, 37 Transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Moreover, 48 simple sequence repeats and 32 long repeat sequences were detected. Comparative analysis between W. arrhiza and six other Lemnoideae species identified 12 hotspots of high nucleotide diversity. In addition, a phylogenetic analysis was performed using 14 species belonging to the Araceae family and one external species as an outgroup. This analysis unveiled W. arrhiza and Wolffia globosa as closely related sister species. Therefore, this research has revealed the complete chloroplast genome data of W. arrhiza, offering a more detailed understanding of its evolutionary position and phylogenetic categorization within the Lemnoideae subfamily.
The crossing of two unwound transmembrane regions that is the hallmark of the NhaA structural fold is critical for antiporter activity
Authors: Rimon Abraham , Amartely Hadar , Padan Etana
Published: March 2024

Cell pH and Na+ homeostasis requires Na+/H+ antiporters. The crystal structure of NhaA, the main Escherichia coli Na+/H+ antiporter, revealed a unique NhaA structural fold shared by prokaryotic and eukaryotic membrane proteins. Out of the 12 NhaA transmembrane segments (TMs), TMs III–V and X–XII are topologically inverted repeats with unwound TMs IV and XI forming the X shape characterizing the NhaA fold. We show that intramolecular cross-linking under oxidizing conditions of a NhaA mutant with two Cys replacements across the crossing (D133C-T340C) inhibits antiporter activity and impairs NhaA-dependent cell growth in high-salts. The affinity purified D133C-T340C protein binds Li+ (the Na+ surrogate substrate of NhaA) under reducing conditions. The cross-linking traps the antiporter in an outward-facing conformation, blocking the antiport cycle. As many secondary transporters are found to share the NhaA fold, including some involved in human diseases, our data have importance for both basic and clinical research.
Identification of redox activators for continuous reactivation of glyoxal oxidase from Trametes versicolor in a two-enzyme reaction cascade
Authors: Alpdağtaş Saadet , Jankowski Nina , Urlacher Vlada B. , Koschorreck Katja
Published: March 2024

Glyoxal oxidases, belonging to the group of copper radical oxidases (CROs), oxidize aldehydes to carboxylic acids, while reducing O2 to H2O2. Their activity on furan derivatives like 5-hydroxymethylfurfural (HMF) makes these enzymes promising biocatalysts for the environmentally friendly synthesis of the bioplastics precursor 2,5-furandicarboxylic acid (FDCA). However, glyoxal oxidases suffer from inactivation, which requires the identification of suitable redox activators for efficient substrate conversion. Furthermore, only a few glyoxal oxidases have been expressed and characterized so far. Here, we report on a new glyoxal oxidase from Trametes versicolor (TvGLOX) that was expressed at high levels in Pichia pastoris (reclassified as Komagataella phaffii). TvGLOX was found to catalyze the oxidation of aldehyde groups in glyoxylic acid, methyl glyoxal, HMF, 2,5-diformylfuran (DFF) and 5-formyl-2-furancarboxylic acid (FFCA), but barely accepted alcohol groups as in 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), preventing formation of FDCA from HMF. Various redox activators were tested for TvGLOX reactivation during catalyzed reactions. Among them, a combination of horseradish peroxidase and its substrate 2,2′-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS) most efficiently reactivated TvGLOX. Through continuous reactivation of TvGLOX in a two-enzyme system employing a recombinant Moesziomyces antarcticus aryl-alcohol oxidase (MaAAO) almost complete conversion of 8 mM HMF to FDCA was achieved within 24 h.
Reconfigurable optical logic in silicon platform
Authors: Ruhul Fatin M. A. , Gostimirovic Dusan , Ye Winnie N.
Published: March 2024

In this paper, we present a novel, scalable, and reconfigurable optical switch that performs multiple computational logic functions simultaneously. The free-carrier depletion effect is used to perform non-volatile switching operations due to its high speed and low power consumption. We adopt the concept of optical memory using a phase-change material to realize the non-volatile reconfigurability without a constant power supply, in addition to providing a large operating bandwidth required for reconfigurability. The proposed reconfigurable optical logic architecture is realized in a compact microdisk resonator configuration, utilizing both the carrier-depletion-based modulation and phase-change optical memory. This is the first time these two modulation schemes are implemented in the same optical microdisk for the purpose of reconfigurable optical logic.
Association between glycemic variability and short-term mortality in patients with acute kidney injury: a retrospective cohort study of the MIMIC-IV database
Authors: Guo Yifan , Qiu Yue , Xue Taiqi , Zhou Yi , Yan Pu , Liu Shiyi , Liu Shiwei , Zhao Wenjing , Zhang Ning
Published: March 2024

Acute kidney injury (AKI) represents a significant challenge to global public health problem and is associated with poor outcomes. There is still considerable debate about the effect of mean blood glucose (MBG) and coefficient of variation (CV) of blood glucose on the short-term mortality of AKI patients. This retrospective cohort study aimed to explore the association between glycemic variability and short-term mortality in patients with AKI. Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were analyzed, including 6,777 adult AKI patients. MBG and CV on the first day of ICU admission were calculated to represent the overall glycemic status and variability during the ICU stay in AKI patients. The primary outcome indicator was ICU 30-day mortality of AKI patients. Multivariate Cox regression analysis and smoothed curve fitting were used to assess the relationship between blood glucose levels and mortality. Eventually, the ICU 30-day mortality rate of AKI patients was 23.5%. The increased MBG and CV were significantly correlated with ICU 30-day mortality (hazards ratio (HR) = 1.20, 95% confidence interval (CI) 1.14–1.27; HR = 1.08, 95% CI 1.03–1.13). The smoothed curve fitting showed a U-shaped relationship between MBG on the first day of ICU admission and ICU 30-day mortality (inflection point = 111.3 mg/dl), while CV had a linear relationship with 30-day ICU mortality. Thus, we conclude that MBG and CV were significantly associated with short-term mortality in intensive care patients with AKI. Tighter glycemic control may be an effective measure to improve the prognosis of patients with AKI.
The role of the pulmonary veins on left atrial flow patterns and thrombus formation
Authors: Mill Jordi , Harrison Josquin , Saiz-Vivo Marta , Albors Carlos , Morales Xabier , Olivares Andy L. , Iriart Xavier , Cochet Hubert , Noailly Jerome , Sermesant Maxime , Camara Oscar
Published: March 2024

Atrial fibrillation (AF) is the most common human arrhythmia, forming thrombi mostly in the left atrial appendage (LAA). However, the relation between LAA morphology, blood patterns and clot formation is not yet fully understood. Furthermore, the impact of anatomical structures like the pulmonary veins (PVs) have not been thoroughly studied due to data acquisition difficulties. In-silico studies with flow simulations provide a detailed analysis of blood flow patterns under different boundary conditions, but a limited number of cases have been reported in the literature. To address these gaps, we investigated the influence of PVs on LA blood flow patterns and thrombus formation risk through computational fluid dynamics simulations conducted on a sizeable cohort of 130 patients, establishing the largest cohort of patient-specific LA fluid simulations reported to date. The investigation encompassed an in-depth analysis of several parameters, including pulmonary vein orientation (e.g., angles) and configuration (e.g., number), LAA and LA volumes as well as their ratio, flow, and mass-less particles. Our findings highlight the total number of particles within the LAA as a key parameter for distinguishing between the thrombus and non-thrombus groups. Moreover, the angles between the different PVs play an important role to determine the flow going inside the LAA and consequently the risk of thrombus formation. The alignment between the LAA and the main direction of the left superior pulmonary vein, or the position of the right pulmonary vein when it exhibits greater inclination, had an impact to distinguish the control group vs. the thrombus group. These insights shed light on the intricate relationship between PV configuration, LAA morphology, and thrombus formation, underscoring the importance of comprehensive blood flow pattern analyses.
Validation of anterior ankle soft tissue dynamics and shear modulus for anterior ankle impingement syndrome after ankle fracture surgery
Authors: Osanami Haruki , Akuzawa Hiroshi , Sakamoto Kodai , Yokota Hirotake , Hirabayashi Ryo , Sekine Chie , Ishigaki Tomonobu , Edama Mutsuaki
Published: March 2024

Anterior ankle impingement syndrome (AAIS) has been reported to account for a high percentage of complications following ankle fracture surgery. The soft tissue etiology of AAIS is thought to be thickening and inflammation of the anterior ankle soft tissues intervening anteriorly at the tibiotalar joint, causing pain and functional limitation during dorsiflexion. However, the effects of anterior ankle soft tissue dynamics and stiffness on AAIS have yet to be clarified. This study aimed to determine the relationship between AAIS and the anterior ankle soft tissue thickness change ratio and shear modulus using ultrasonography (US). The participants were 20 patients with ankle joint fractures (AO classification A, B) who had undergone open reduction and internal fixation and 20 healthy adults. The evaluation periods were 3 months and 6 months postoperatively. US was used to delineate the tibialis anterior tendon, extensor hallucis longus tendon, and the extensor digitorum longus tendon over the talus and tibia on a long-axis image. Anterior ankle soft tissue thickness was measured as the shortest distance from the most convex part of the talus to the tendon directly above it. The Anterior ankle soft tissue thickness change ratio was determined by dividing the value at 0° dorsiflexion by the value at 10° plantarflexion. The same images as for the anterior soft tissue thickness measurement were drawn for the shear modulus measurement, and the average shear modulus (kPa) was calculated using shear-wave elastography. There was no significant difference in the thickness change ratio between the postoperative and healthy groups. Compared with the healthy group, the shear modulus was significantly higher at 3 and 6 months in the postoperative group (p < 0.01). The shear elastic modulus at 6-month postoperative group was significantly lower than at 3-month postoperative group (p < 0.01). Anterior ankle joint soft tissue stiffness may increase after surgery for an ankle fracture.
From peak to plummet: impending decline of the warm Arctic-cold continents phenomenon
Authors: Hong Yungi , Wang S.-Y. Simon , Son Seok-Woo , Jeong Jee-Hoon , Kim Sang-Woo , Kim Baekmin , Kim Hyungjun , Yoon Jin-Ho
Published: March 2024

This study assesses the projected trajectory of Warm Arctic-Cold Continent (WACC) events in East Asia and North America through large ensemble simulation for the upcoming decades. It analyses the evolution of the geographical boundaries of threshold cold temperatures, revealing a significant northward shift as a sign of global warming’s impact on the southward advancement of Arctic cold air. While validating the intensification of the WACC phenomenon until the 2020 s, echoing earlier studies, the findings indicate a marked decrease beginning in the 2030s. If warming is not curbed, this shift suggests a critical modification in the WACC pattern, prompting a re-evaluation of existing theories and models for extreme winter weather events. The results have major implications, spurring communities impacted by WACC to anticipate future changes and encouraging the climate forecasting community to update conceptual models for improved adaptation and mitigation approaches.
Modeling multiple sclerosis using mobile and wearable sensor data
Authors: Gashi Shkurta , Oldrati Pietro , Moebus Max , Hilty Marc , Barrios Liliana , Ozdemir Firat ,   PHRT Consortium, Kana Veronika , Lutterotti Andreas , Rätsch Gunnar , Holz Christian
Published: March 2024

Multiple sclerosis (MS) is a neurological disease of the central nervous system that is the leading cause of non-traumatic disability in young adults. Clinical laboratory tests and neuroimaging studies are the standard methods to diagnose and monitor MS. However, due to infrequent clinic visits, it is fundamental to identify remote and frequent approaches for monitoring MS, which enable timely diagnosis, early access to treatment, and slowing down disease progression. In this work, we investigate the mostreliable,clinically useful, andavailablefeatures derived from mobile and wearable devices as well as their ability to distinguish people with MS (PwMS) from healthy controls, recognize MS disability and fatigue levels. To this end, we formalize clinical knowledge and derive behavioral markers to characterize MS. We evaluate our approach on a dataset we collected from 55 PwMS and 24 healthy controls for a total of 489 days conducted in free-living conditions. The dataset containswearable sensor data– e.g., heart rate – collected using an arm-worn device,smartphone data– e.g., phone locks – collected through a mobile application,patient health records– e.g., MS type – obtained from the hospital, andself-reports– e.g., fatigue level – collected using validated questionnaires administered via the mobile application. Our results demonstrate the feasibility of using features derived from mobile and wearable sensors to monitor MS. Our findings open up opportunities for continuous monitoring of MS in free-living conditions and can be used to evaluate and guide the effectiveness of treatments, manage the disease, and identify participants for clinical trials.