bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mini Nutritional Assessment combined with body fat for detecting the risk of sarcopenia and sarcopenic obesity in metabolic syndrome
Authors: Yen Chi-Hua , Lee Yi-Wen , Chang Wei-Jung , Lin Ping-Ting
Published: February 2024

Malnutrition is a key factor in metabolic syndrome (MS) and sarcopenia, assessing the nutritional status of these patients is a pressing issue. The purpose of this study was to clarify sarcopenia and sarcopenic obesity in patients with MS based on nutritional status. This was a case–control study between MS/non-MS. Body composition was measured by dual-energy X-ray absorptiometry. Muscle function was assessed by handgrip strength, five times sit-to-stand test, gait speed test and short physical performance battery (SPPB). The Mini Nutritional Assessment (MNA) was performed to assess the nutritional status in the participants in this study. Overall, a total of 56 % and 13 % of participants suffered from possible sarcopenia and sarcopenia, respectively. There was a higher rate of possible sarcopenic obesity in the MS group than in the non-MS group (48·9 % v. 24·7 %, P < 0·01), and all the sarcopenia participants in the MS group had sarcopenic obesity. MNA score was significantly associated with sarcopenia status (P < 0·01). The MNA combined with body fat score showed better acceptable discrimination for detecting sarcopenic obesity and sarcopenia in MS (AUC = 0·70, 95 % CI 0·53, 0·86). In summary, there was a higher prevalence of possible sarcopenic obesity in MS, and all the MS patients with sarcopenia had sarcopenic obesity in the present study. We suggest that the MNA should be combined with body fat percentage to assess the nutritional status of MS participants, and it also serves as a good indicator for sarcopenia and sarcopenic obesity in MS.
Consanguinity in northwest Pakistan: evidence of temporal decline
Authors: Malik Sajid , Bibi Anisa , Farid Rubbiya , Khan Sidra , Awan Javaid , Rehman Atta Ur
Published: February 2024

Pakistan has a high burden of hereditary and congenital anomalies and their incidence rate almost doubles against the background of parental consanguinity. Consanguineous unions (CU) are customary in Pakistan and deeply rooted socio-cultural norms favour CU. This study aimed to elucidate the determinants and temporal change in CU in four northwestern populations of Pakistan. In a cross-sectional study, data on marital union types, bio-demographic factors, and paternal consanguinity were collected from 6,323 ever-married individuals in four districts of northwest Pakistan: Haripur, Muzaffarabad, Mansehra, and Shangla. We used descriptive statistics and multivariable logistic regression analysis. The CU were calculated to be 55%, and inbreeding coefficient F (ICF) was estimated to be 0.029. Eight factors, including district, rural origin, age of husband, occupational group of husband, literacy of husband, parental consanguinity, exchange marriage, and extended family type, were found to be significant predictors of consanguinity in the multivariable logistic regression analysis. The rate of consanguinity decreased significantly in the younger age categories of individuals. The rate of CU was seen to be declining over time and in marriages that started ‘before 1980’ and ‘after 2010’, respectively, and there was a decline in ICF from 0.030 to 0.027. These analyses also showed that the literacy rate improved, the average age at marriage increased, and the frequency of exchange marriages decreased over time. This study employs a sizable first-hand dataset to demonstrate a lowering CU rate in northwest Pakistan. It is anticipated that the burden of inherited and congenital anomalies may likely to diminish in the study populations along with the fall in ICF.
There are no shortcuts to theory
Authors: Devezer Berna
Published: February 2024

Almaatouq et al. claim that the integrative experiment design can help “develop a reliable, cohesive, and cumulative theoretical understanding.” I will contest this claim by challenging three underlying assumptions about the nature of scientific theories. I propose that the integrative experiment design should be viewed as an exploratory framework rather than a means to build or evaluate theories.
Discovering the unknown unknowns of research cartography with high-throughput natural description
Authors: Katiyar Tanay , Bonnefon Jean-François , Mehr Samuel A. , Singh Manvir
Published: February 2024

To succeed, we posit that research cartography will require high-throughput natural description to identify unknown unknowns in a particular design space. High-throughput natural description, the systematic collection and annotation of representative corpora of real-world stimuli, faces logistical challenges, but these can be overcome by solutions that are deployed in the later stages of integrative experiment design.
Dimensional versus conceptual incommensurability in the social and behavioral sciences
Authors: Vaynberg Eugene , Hoffman Kate Nicole , Wallis Jacqueline Mae , Weisberg Michael
Published: February 2024

This commentary analyzes the extent to which the incommensurability problem can be resolved through the proposed alternative method of integrative experiment design. We suggest that, although one aspect of incommensurability is successfully addressed (dimensional incommensurability), the proposed design space method does not yet alleviate another major source of discontinuity, which we call conceptual incommensurability.
Getting lost in an infinite design space is no solution
Authors: Gollwitzer Mario , Prager Johannes
Published: February 2024

Almaatouq et al. argue that an “integrative experiment design” approach can help generating cumulative empirical and theoretical knowledge. Here, we discuss the novelty of their approach and scrutinize its promises and pitfalls. We argue that setting up a “design space” may turn out to be theoretically uninformative, inefficient, and even impossible. Designing truly diagnostic experiments provides a better alternative.
Is generalization decay a fundamental law of psychology?
Authors: Mandel David R.
Published: February 2024

Generalizations strengthen in traditional sciences, but in psychology (and social and behavioral sciences, more generally) they decay. This is usually viewed as a problem requiring solution. It could be viewed instead as a law-like phenomenon. Generalization decay cannot be squelched because human behavior is metastable and all behavioral data collected thus far have resulted from a thin sliver of human time.
Design and analysis of a wall-climbing robot with passive compliant mechanisms to adapt variable curvatures walls
Authors: Song Yifeng , Yang Zhenyu , Chang Yong , Yuan Hui , Lin Song
Published: February 2024

Motivated by practical applications of inspection and maintenance, we have developed a wall-climbing robot with passive compliant mechanisms that can autonomously adapt to curved surfaces. At first, this paper presents two failure modes of the traditional wall-climbing robot on the variable curvature wall surface and further introduces the designed passive compliant wall-climbing robot in detail. Then, the motion mechanism of the passive compliant wall-climbing robot on the curved surface is analyzed from stable adsorption conditions, parameter design process, and force analysis. At last, a series of experiments have been carried out on load capability and curved surface adaptability based on a developed principle prototype. The experimental results indicated that the wall-climbing robot with passive compliant mechanisms can effectively promote both adsorption stability and adaptability to variable curvatures.
Measuring Subjective Inequality: Development and Validation of the Perceived Economic Inequality Scale (PEIS)
Authors: Valtorta Roberta Rosa , Vezzoli Michela , Mari Silvia , Durante Federica , Volpato Chiara
Published: February 2024

The main goal of the present research is to develop and validate the Perceived Economic Inequality Scale (PEIS), an instrument measuring individuals’ perceptions of economic inequality at the national level. The study was conducted on a representative sample of the Italian population (N = 1,446, 51% women). The factorial structure of the scale was assessed through cross-validated exploratory-confirmatory factor analyses. To inspect the PEIS psychometric properties, item and correlation analyses were performed. The results showed that the PEIS is a valid and reliable unidimensional measure of perceived economic inequality at the national level. Further support of the PEIS construct validity was provided by the correlation of the scale score with the perceived wage gap and ideological beliefs like the economic system justification, social dominance orientation, meritocratic beliefs, and participants’ political orientation. Crucially, multigroup confirmatory factor analysis supported configural, metric, and scalar invariances of the scale across socio-demographic groups. The PEIS allows researchers to assess the subjective component of economic inequality by also serving as a useful tool for unpacking the psychological correlates of perceived inequality.
Brain tissue- and cell type-specific eQTL Mendelian randomization reveals efficacy of FADS1 and FADS2 on cognitive function
Authors: Wu Xueyan , Jiang Lei , Qi Hongyan , Hu Chunyan , Jia Xiaojing , Lin Hong , Wang Shuangyuan , Lin Lin , Zhang Yifang , Zheng Ruizhi , Li Mian , Wang Tiange , Zhao Zhiyun , Xu Min , Xu Yu , Chen Yuhong , Zheng Jie , Bi Yufang , Lu Jieli
Published: February 2024

Epidemiological studies suggested an association between omega-3 fatty acids and cognitive function. However, the causal role of the fatty acid desaturase (FADS) gene, which play a key role in regulating omega-3 fatty acids biosynthesis, on cognitive function is unclear. Hence, we used two-sample Mendelian randomization (MR) to estimate the gene-specific causal effect of omega-3 fatty acids (N = 114,999) on cognitive function (N = 300,486). Tissue- and cell type-specific effects ofFADS1/FADS2expression on cognitive function were estimated using brain tissue cis-expression quantitative trait loci (cis-eQTL) datasets (GTEx,N ≤ 209; MetaBrain,N ≤ 8,613) and single cell cis-eQTL data (N = 373), respectively. These causal effects were further evaluated in whole blood cis-eQTL data (N ≤ 31,684). A series of sensitivity analyses were conducted to validate MR assumptions. Leave-one-out MR showed aFADSgene-specific effect of omega-3 fatty acids on cognitive function [β = −1.3 × 10−2, 95% confidence interval (CI) (−2.2 × 10−2, −5 × 10−3),P = 2 × 10−3]. Tissue-specific MR showed an effect of increasedFADS1expression in cerebellar hemisphere andFADS2expression in nucleus accumbens basal ganglia on maintaining cognitive function, while decreasedFADS1expression in nine brain tissues on maintaining cognitive function [colocalization probability (PP.H4) ranged from 71.7% to 100.0%]. Cell type-specific MR showed decreasedFADS1/FADS2expression in oligodendrocyte was associated with maintaining cognitive function (PP.H4 = 82.3%, respectively). IncreasedFADS1/FADS2expression in whole blood showed an effect on cognitive function maintenance (PP.H4 = 86.6% and 88.4%, respectively). This study revealed putative causal effect ofFADS1/FADS2expression in brain tissues and blood on cognitive function. These findings provided evidence to prioritizeFADSgene as potential target gene for maintenance of cognitive function.
Engineering stringent genetic biocontainment of yeast with a protein stability switch
Authors: Hoffmann Stefan A. , Cai Yizhi
Published: February 2024

Synthetic biology holds immense promise to tackle key problems in resource use, environmental remediation, and human health care. However, comprehensive safety measures are lacking to employ engineered microorganisms in open-environment applications. Genetically encoded biocontainment systems may solve this issue. Here, we describe such a system based on conditional stability of essential proteins. We used a destabilizing domain degron stabilized by estradiol addition (ERdd). We ERdd-tagged 775 essential genes and screened for strains with estradiol dependent growth. Three genes, SPC110, DIS3 and RRP46, were found to be particularly suitable targets. Respective strains showed no growth defect in the presence of estradiol and strong growth inhibition in its absence. SPC110-ERdd offered the most stringent containment, with an escape frequency of <5×10−7. Removal of its C-terminal domain decreased the escape frequency further to <10−8. Being based on conditional protein stability, the presented approach is mechanistically orthogonal to previously reported genetic biocontainment systems.
Protein structure generation via folding diffusion
Authors: Wu Kevin E. , Yang Kevin K. , van den Berg Rianne , Alamdari Sarah , Zou James Y. , Lu Alex X. , Amini Ava P.
Published: February 2024

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction, directly generating diverse, novel protein structures from neural networks remains difficult. In this work, we present a diffusion-based generative model that generates protein backbone structures via a procedure inspired by the natural folding process. We describe a protein backbone structure as a sequence of angles capturing the relative orientation of the constituent backbone atoms, and generate structures by denoising from a random, unfolded state towards a stable folded structure. Not only does this mirror how proteins natively twist into energetically favorable conformations, the inherent shift and rotational invariance of this representation crucially alleviates the need for more complex equivariant networks. We train a denoising diffusion probabilistic model with a simple transformer backbone and demonstrate that our resulting model unconditionally generates highly realistic protein structures with complexity and structural patterns akin to those of naturally-occurring proteins. As a useful resource, we release an open-source codebase and trained models for protein structure diffusion.
Deceptive orbital confinement at edges and pores of carbon-based 1D and 2D nanoarchitectures
Authors: Piquero-Zulaica Ignacio , Corral-Rascón Eduardo , Diaz de Cerio Xabier , Riss Alexander , Yang Biao , Garcia-Lekue Aran , Kher-Elden Mohammad A. , Abd El-Fattah Zakaria M. , Nobusue Shunpei , Kojima Takahiro , Seufert Knud , Sakaguchi Hiroshi , Auwärter Willi , Barth Johannes V.
Published: February 2024

The electronic structure defines the properties of graphene-based nanomaterials. Scanning tunneling microscopy/spectroscopy (STM/STS) experiments on graphene nanoribbons (GNRs), nanographenes, and nanoporous graphene (NPG) often determine an apparent electronic orbital confinement into the edges and nanopores, leading to dubious interpretations such as image potential states or super-atom molecular orbitals. We show that these measurements are subject to a wave function decay into the vacuum that masks the undisturbed electronic orbital shape. We use Au(111)-supported semiconducting gulf-type GNRs and NPGs as model systems fostering frontier orbitals that appear confined along the edges and nanopores in STS measurements. DFT calculations confirm that these states originate from valence and conduction bands. The deceptive electronic orbital confinement observed is caused by a loss of Fourier components, corresponding to states of high momentum. This effect can be generalized to other 1D and 2D carbon-based nanoarchitectures and is important for their use in catalysis and sensing applications.
Effects of climate and environmental heterogeneity on the phylogenetic structure of regional angiosperm floras worldwide
Authors: Qian Hong , Qian Shenhua , Zhang Jian , Kessler Michael
Published: February 2024

The tendency of species to retain ancestral ecological distributions (phylogenetic niche conservatism) is thought to influence which species from a species pool can persist in a particular environment. Thus, investigating the relationships between measures of phylogenetic structure and environmental variables at a global scale can help understand the variation in species richness and phylogenetic structure in biological assemblages across the world. Here, we analyze a comprehensive data set including 341,846 species in 391 angiosperm floras worldwide to explore the relationships between measures of phylogenetic structure and environmental variables for angiosperms in regional floras across the world and for each of individual continental (biogeographic) regions. We find that the global phylogenetic structure of angiosperms shows clear and meaningful relationships with environmental factors. Current climatic variables have the highest predictive power, especially on phylogenetic metrics reflecting recent evolutionary relationships that are also related to current environmental heterogeneity, presumably because this favors plant speciation in various ways. We also find evidence that past climatic conditions, and particularly refugial conditions, play an important role in determining the phylogenetic structure of regional floras. The relationships between environmental conditions and phylogenetic metrics differ between continents, reflecting the different evolutionary histories of their floras.
A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity
Authors: de Campos-Mata Leire , Trinité Benjamin , Modrego Andrea , Tejedor Vaquero Sonia , Pradenas Edwards , Pons-Grífols Anna , Rodrigo Melero Natalia , Carlero Diego , Marfil Silvia , Santiago César , Raïch-Regué Dàlia , Bueno-Carrasco María Teresa , Tarrés-Freixas Ferran , Abancó Ferran , Urrea Victor , Izquierdo-Useros Nuria , Riveira-Muñoz Eva , Ballana Ester , Pérez Mónica , Vergara-Alert Júlia , Segalés Joaquim , Carolis Carlo , Arranz Rocío , Blanco Julià , Magri Giuliana
Published: February 2024

Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA+ memory B cell, with a broad neutralizing activity against former and new SARS-CoV-2 variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently, 17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in “up” position and blocks the receptor binding motif, as other structurally similar antibodies do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity against all variants tested, probably due to a larger RBD contact area. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future clinical interventions.
Microtubules provide force to promote membrane uncoating in vacuolar escape for a cyto-invasive bacterial pathogen
Authors: Chang Yuen-Yan , Valenzuela Camila , Lensen Arthur , Lopez-Montero Noelia , Sidik Saima , Salogiannis John , Enninga Jost , Rohde John
Published: February 2024

Intracellular bacterial pathogens gain entry to mammalian cells inside a vacuole derived from the host membrane. Some of them escape the bacteria-containing vacuole (BCV) and colonize the cytosol. Bacteria replicating within BCVs coopt the microtubule network to position it within infected cells, whereas the role of microtubules for cyto-invasive pathogens remains obscure. Here, we show that the microtubule motor cytoplasmic dynein-1 and specific activating adaptors are hijacked by the enterobacterium Shigella flexneri. These host proteins were found on infection-associated macropinosomes (IAMs) formed during Shigella internalization. We identified Rab8 and Rab13 as mediators of dynein recruitment and discovered that the Shigella effector protein IpaH7.8 promotes Rab13 retention on moving BCV membrane remnants, thereby facilitating membrane uncoating of the Shigella-containing vacuole. Moreover, the efficient unpeeling of BCV remnants contributes to a successful intercellular spread. Taken together, our work demonstrates how a bacterial pathogen subverts the intracellular transport machinery to secure a cytosolic niche.
Reconfigurable droplet networks
Authors: Sun Shuyi , Li Shuailong , Feng Weixiao , Luo Jiaqiu , Russell Thomas P. , Shi Shaowei
Published: February 2024

Droplet networks stabilized by lipid interfacial bilayers or colloidal particles have been extensively investigated in recent years and are of great interest for compartmentalized reactions and biological functions. However, current design strategies are disadvantaged by complex preparations and limited droplet size. Here, by using the assembly and jamming of cucurbit[8]uril surfactants at the oil-water interface, we show a novel means of preparing droplet networks that are multi-responsive, reconfigurable, and internally connected over macroscopic distances. Openings between the droplets enable the exchange of matter, affording a platform for chemical reactions and material synthesis. Our work requires only a manual compression to construct complex patterns of droplet networks, underscoring the simplicity of this strategy and the range of potential applications.
CDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver
Authors: Hu Alexander J. , Li Wei , Dinh Calvin , Zhang Yongzhao , Hu Jamie K. , Daniele Stefano G. , Hou Xiaoli , Yang Zixuan , Asara John M. , Hu Guo-fu , Farmer Stephen R. , Hu Miaofen G.
Published: February 2024

Increased de novo lipogenesis (DNL) in white adipose tissue is associated with insulin sensitivity. Under both Normal-Chow-Diet and High-Fat-Diet, mice expressing a kinase inactive Cyclin-dependent kinase 6 (Cdk6) allele (K43M) display an increase in DNL in visceral white adipose tissues (VAT) as compared to wild type mice (WT), accompanied by markedly increased lipogenic transcriptional factor Carbohydrate-responsive element-binding proteins (CHREBP) and lipogenic enzymes in VAT but not in the liver. Treatment of WT mice under HFD with a CDK6 inhibitor recapitulates the phenotypes observed in K43M mice. Mechanistically, CDK6 phosphorylates AMP-activated protein kinase, leading to phosphorylation and inactivation of acetyl-CoA carboxylase, a key enzyme in DNL. CDK6 also phosphorylates CHREBP thus preventing its entry into the nucleus. Ablation of runt related transcription factor 1 in K43M mature adipocytes reverses most of the phenotypes observed in K43M mice. These results demonstrate a role of CDK6 in DNL and a strategy to alleviate metabolic syndromes.
Short-term periodic restricted feeding elicits metabolome-microbiome signatures with sex dimorphic persistence in primate intervention
Authors: Yanai Hagai , Park Bongsoo , Koh Hyunwook , Jang Hyo Jung , Vaughan Kelli L. , Tanaka-Yano Mayuri , Aon Miguel , Blanton Madison , Messaoudi Ilhem , Diaz-Ruiz Alberto , Mattison Julie A. , Beerman Isabel
Published: February 2024

Dietary restriction has shown benefits in physiological, metabolic, and molecular signatures associated with aging but is a difficult lifestyle to maintain for most individuals. In mice, a less restrictive diet that allows for cyclical periods of reduced calories mitigates aging phenotypes, yet the effects of such an intervention in a genetically heterogenous, higher-order mammal has not been examined. Here, using middle-aged rhesus macaques matched for age and sex, we show that a regimen of 4 days of low-calorie intake followed by 10 days of ad libitum feeding (4:10 diet) performed in repeating cycles over 12 weeks led to significant loss of weight and fat percentage, despite the free access to food for most of the study duration. We show the 4-day restriction period is sufficient to drive alterations to the serum metabolome characterized by substantial differences in lipid classes. These phenotypes were paralleled by changes in the gut microbiome of restricted monkeys that highlight the involvement of a microbiome-metabolome axis. This regimen shows promising phenotypes, with some sex-dimorphic responses, including residual memory of the diet. As many calorie restriction interventions are difficult to sustain, we propose that this short-term diet may be easier to adhere to and have benefits directly relevant to human aging.
Anticipating regime shifts by mixing early warning signals from different nodes
Authors: Masuda Naoki , Aihara Kazuyuki , MacLaren Neil G.
Published: February 2024

Real systems showing regime shifts, such as ecosystems, are often composed of many dynamical elements interacting on a network. Various early warning signals have been proposed for anticipating regime shifts from observed data. However, it is unclear how one should combine early warning signals from different nodes for better performance. Based on theory of stochastic differential equations, we propose a method to optimize the node set from which to construct an early warning signal. The proposed method takes into account that uncertainty as well as the magnitude of the signal affects its predictive performance, that a large magnitude or small uncertainty of the signal in one situation does not imply the signal’s high performance, and that combining early warning signals from different nodes is often but not always beneficial. The method performs well particularly when different nodes are subjected to different amounts of dynamical noise and stress.
Vessel density on optical coherence tomography angiography is prognostic for future disease course in intermediate uveitis
Authors: Wintergerst Maximilian W. M. , Merten Nicholas R. , Berger Moritz , Terheyden Jan H. , Overbeck Lennart J. , Schmid Matthias , Holz Frank G. , Finger Robert P.
Published: February 2024

As most rare diseases, intermediate uveitis lacks reliable endpoints necessary for randomized clinical trials. Therefore, we investigated longitudinal changes of retinal and choriocapillaris perfusion on optical coherence tomography angiography (OCT-A) in intermediate uveitis and their prognostic value for future best corrected visual acuity (BCVA) and central retinal thickness (CRT). In this retrospective, longitudinal cohort study eyes of patients with intermediate uveitis were imaged by swept-source OCT-A (macula-centered 3 × 3 mm; PLEX Elite 9000, Zeiss) and stratified into clinically stable, worsened and improved based on changes in clinical parameters. Superficial (SRL) and deep retinal layers (DRL) were automatically analyzed for vessel density (VD) and choriocapillaris layer for non-perfused area (CCNPA) using ImageJ. Mixed-effects regression analysis controlling for age, sex, and OCT-A signal strength index (SSI) was used to evaluate the prognostic value of OCT-A parameters. 91 eyes (62 stable, 12 worsened, and 17 improved) were included in the analysis and mean follow-up time was 296 days. Longitudinal changes of VD were different between all three groups (p = 0.002 for SRL and p = 0.017 for DRL). Clinically worsened eyes showed a decrease in VD (− 0.032 ± 0.055 for SRL and − 0.027 ± 0.025 for DRL), whereas clinically improved eyes showed an increase in VD (0.037 ± 0.039 for SRL and 0.001 ± 0.023 for DRL). No difference was found for CCNPA. When controlling for age, sex, and SSI, observed differences held true in clinically worsened eyes for DRL (p = 0.011) and in clinically improved eyes for SRL (p = 0.002). An increase of CCNPA in clinically worsened eyes (p = 0.03) compared to clinically stable and improved eyes was evident. Predictive analysis revealed an association of VD in SRL and DRL at baseline with BCVA at follow-up (p = 0.039 and p = 0.047, respectively) and of VD in SRL at baseline with CRT at follow-up (p = 0.046). Alterations in retinal perfusion on OCT-A in intermediate uveitis are partly reversible and OCT-A VD may serve to predict future BCVA and CRT. Thus, perfusion parameters on OCT-A might aid monitoring and serve as prognostic imaging-biomarker.
Intermetallic and dispersoid structures in AA3104 aluminium alloy during two-step homogenisation
Authors: George S. L. , Magidi-Chicuba L.
Published: February 2024

During homogenisation of the AA3104 cast ingot, a phase transformation of intermetallic particles from β-Al6(Fe,Mn) orthorhombic phase to harder α-Alx(Fe,Mn)3Si2cubic phase occurs. The large constituent intermetallic particles, regardless of phase, assist in the recrystallisation nucleation process through particle stimulated nucleation (PSN). Ultimately, this helps to refine grain size. The sub-micron dispersoids act to impede grain boundary migration through a Zener drag mechanism. For this reason, the dispersoids that form during homogenisation are critical to the recrystallisation kinetics during subsequent rolling, with smaller dispersoids being better suited to instances where the minimisation of recrystallisation is required during hot rolling. This work simulates an industrial two-step homogenisation practice with variations in the peak temperature of the first step between 560 °C and 580 °C. The effect of this temperature variation on the intermetallic particle phase evolution is investigated. The aim is to identify the ideal intermetallic phase balance and the dispersoid structure that are best suited for the minimisation of recrystallisation during hot rolling through maximising Zener drag and maintaining galling resistance. The results indicate a trend where an increase in homogenisation temperature from 560 °C to 580 °C yields, firstly, an increase in the volume fraction of the α-phase particles to greater than 50% of the total volume fraction at both the edge and the centre of the ingot and, secondly, it yields an increased dispersoid size. Thus, a lower temperature homogenisation practice produces a near-ideal combination of intermetallic particle phase distribution, as well as dispersoid size, which is critical for Zener drag and the minimization of recrystallisation during the hot rolling processes.
Multimodal machine learning for modeling infant head circumference, mothers’ milk composition, and their shared environment
Authors: Becker Martin , Fehr Kelsey , Goguen Stephanie , Miliku Kozeta , Field Catherine , Robertson Bianca , Yonemitsu Chloe , Bode Lars , Simons Elinor , Marshall Jean , Dawod Bassel , Mandhane Piushkumar , Turvey Stuart E. , Moraes Theo J. , Subbarao Padmaja , Rodriguez Natalie , Aghaeepour Nima , Azad Meghan B.
Published: February 2024

Links between human milk (HM) and infant development are poorly understood and often focus on individual HM components. Here we apply multi-modal predictive machine learning to study HM and head circumference (a proxy for brain development) among 1022 mother-infant dyads of the CHILD Cohort. We integrated HM data (19 oligosaccharides, 28 fatty acids, 3 hormones, 28 chemokines) with maternal and infant demographic, health, dietary and home environment data. Head circumference was significantly predictable at 3 and 12 months. Two of the most associated features were HM n3-polyunsaturated fatty acid C22:6n3 (docosahexaenoic acid, DHA; p = 9.6e−05) and maternal intake of fish (p = 4.1e−03), a key dietary source of DHA with established relationships to brain function. Thus, using a systems biology approach, we identified meaningful relationships between HM and brain development, which validates our statistical approach, gives credence to the novel associations we observed, and sets the foundation for further research with additional cohorts and HM analytes.
eDNA based bycatch assessment in pelagic fish catches
Authors: Urban Paulina , Jacobsen Magnus Wulff , Bekkevold Dorte , Nielsen Anders , Storr-Paulsen Marie , Nijland Reindert , Nielsen Einar Eg
Published: February 2024

Pelagic fish like herring, sardines, and mackerel constitute an essential and nutritious human food source globally. Their sustainable harvest is promoted by the application of precise, accurate, and cost-effective methods for estimating bycatch. Here, we experimentally test the new concept of using eDNA for quantitative bycatch assessment on the illustrative example of the Baltic Sea sprat fisheries with herring bycatch. We investigate the full pipeline from sampling of production water on vessels and in processing factories to the estimation of species weight fractions. Using a series of controlled mixture experiments, we demonstrate that the eDNA signal from production water shows a strong, seasonally consistent linear relationship with herring weight fractions, however, the relationship is influenced by the molecular method used (qPCR or metabarcoding). In four large sprat landings analyzed, despite examples of remarkable consistency between eDNA and visual reporting, estimates of herring bycatch biomass varied between the methods applied, with the eDNA-based estimates having the highest precision for all landings analyzed. The eDNA-based bycatch assessment method has the potential to improve the quality and cost effectiveness of bycatch assessment in large pelagic fisheries catches and in the long run lead to more sustainable management of pelagic fish as a precious marine resource.
Accelerating thermokarst lake changes on the Qinghai–Tibetan Plateau
Authors: Zhou Guanghao , Liu Wenhui , Xie Changwei , Song Xianteng , Zhang Qi , Li Qingpeng , Liu Guangyue , Li Qing , Luo Bingnan
Published: February 2024

As significant evidence of ice-rich permafrost degradation due to climate warming, thermokarst lake was developing and undergoing substantial changes. Thermokarst lake was an essential ecosystem component, which significantly impacted the global carbon cycle, hydrology process and the stability of the Qinghai–Tibet Engineering Corridor. In this paper, based on Sentinel-2 (2021) and Landsat (1988–2020) images, thermokarst lakes within a 5000 m range along both sides of Qinghai–Tibet Highway were extracted to analyse the spatio-temporal variations. The results showed that the number and area of thermokarst lake in 2021 were 3965 and 4038.6 ha (1 ha = 10,000 m$$^{2}$$

2

), with an average size of 1.0186 ha. Small thermokarst lakes ($$<\,$$

<

1 ha) accounted for 85.65% of the entire lake count, and large thermokarst lakes ($$>\,$$

>

10 ha) occupied for 44.92% of the whole lake area. In all sub-regions, the number of small lake far exceeds 75% of the total lake number in each sub-region. R1 sub-region (around Wudaoliang region) had the maximum number density of thermokarst lakes with 0.0071, and R6 sub-region (around Anduo region) had the minimum number density with 0.0032. Thermokarst lakes were mainly distributed within elevation range of 4300 m–5000 m a.s.l. (94.27% and 97.13% of the total number and size), on flat terrain with slopes less than 3$$^\circ$$

∘

(99.17% and 98.47% of the total number and surface) and in the north, south, and southeast aspects (51.98% and 50.00% of the total number and area). Thermokarst lakes were significantly developed in warm permafrost region with mean annual ground temperature (MAGT) > − 1.5 $$^\circ$$

∘

C, accounting for 47.39% and 54.38% of the total count and coverage, respectively. From 1988 to 2020, in spite of shrinkage or even drain of small portion of thermokarst lake, there was a general expansion trend of thermokarst lake with increase in number of 195 (8.58%) and area of 1160.19 ha (41.36%), which decreased during 1988–1995 (− 702 each year and − 706.27 ha/yr) and then increased during 1995–2020 (184.96–702 each year and 360.82 ha/yr). This significant expansion was attributed to ground ice melting as rising air temperature at a rate of 0.03–0.04 $$^\circ$$

∘

C/yr. Followed by the increasing precipitation (1.76–3.07 mm/yr) that accelerated the injection of water into lake.
Population genetic structure of Aedes aegypti subspecies in selected geographical locations in Sudan
Authors: Abuelmaali Sara A. , Mashlawi Abadi M. , Ishak Intan Haslina , Wajidi Mustafa Fadzil Farid , Jaal Zairi , Avicor Silas Wintuma , Kassim Nur Faeza Abu
Published: February 2024

Although knowledge of the composition and genetic diversity of disease vectors is important for their management, this is limiting in many instances. In this study, the population structure and phylogenetic relationship of the twoAedes aegyptisubspecies namelyAedes aegypti aegypti(Aaa) andAedes aegypti formosus(Aaf) in eight geographical areas in Sudan were analyzed using seven microsatellite markers. Hardy–Weinberg Equilibrium (HWE) for the two subspecies revealed thatAaadeviated from HWE among the seven microsatellite loci, whileAafexhibited departure in five loci and no departure in two loci (A10 and M201). The Factorial Correspondence Analysis (FCA) plots revealed that theAaapopulations from Port Sudan, Tokar, and Kassala clustered together (which is consistent with the unrooted phylogenetic tree),Aaffrom Fasher and Nyala populations clustered together, and Gezira, Kadugli, and Junaynah populations also clustered together. The Bayesian cluster analysis structured the populations into two groups suggesting two genetically distinct groups (subspecies). Isolation by distance test revealed a moderate to strong significant correlation between geographical distance and genetic variations (p = 0.003,r = 0.391). The migration network created using divMigrate demonstrated that migration and gene exchange between subspecies populations appear to occur based on their geographical proximity. The genetic structure of theAe. aegyptisubspecies population and the gene flow among them, which may be interpreted as the mosquito vector's capacity for dispersal, were revealed in this study. These findings will help in the improvement of dengue epidemiology research including information on the identity of the target vector/subspecies and the arboviruses vector surveillance program.
Cuproptosis-related genes predict prognosis and trastuzumab therapeutic response in HER2-positive breast cancer
Authors: Sha Rui , Dong Xinrui , Yan Shanshan , Dai Huijuan , Sun Aijun , You Liuxia , Guo Zongjin
Published: February 2024

Breast cancer is the most common diagnosed cancer, the HER2-positive subtype account for 15% of all breast cancer. HER2-targeted therapy is the mainstay treatment for HER2-positive breast cancer. Cuproptosis is a novel form of programmed cell death, and is caused by mitochondrial lipoylation and destabilization of iron-sulfur proteins triggered by copper, which was considered as a key player in various biological processes. However, the roles of cuproptosis-related genes in HER2-positive breast cancer remain largely unknown. In the present study, we constructed a prognostic prediction model of HER2-positive breast cancer patients using TCGA database. Dysregulated genes for cells resistant to HER2-targeted therapy were analyzed in the GEO dataset. KEGG pathway, GO enrichment and GSEA was performed respectively. The immune landscape of DLAT was analyzed by CIBERSORT algorithm and TIDE algorithm. HER2-positive breast cancer patients with high CRGs risk score showed shorter OS. DLAT was downregulated and correlated with better survival of HER2-positive breast cancer patients (HR = 3.30, p = 0.022). High expressed DLAT was associated with resistant to HER2-targeted therapy. Knocking down DLAT with siRNA increased sensitivity of breast cancer to trastuzumab. KEGG pathway and GO enrichment of DEGs indicated that DLAT participates in various pathways correlated with organelle fission, chromosome segregation, nuclear division, hormone-mediated signaling pathway, regulation of intracellular estrogen receptor signaling pathway, condensed chromosome and PPAR signaling pathway. There was a negative correlation between TIDE and DLAT expression (r = − 0.292, p < 0.001), which means high DLAT expression is an indicator of sensitivity to immunotherapy. In conclusion, our study constructed a four CRGs signature prognostic prediction model and identified DLAT as an independent prognostic factor and associated with resistant to HER2-targeted therapy for HER2-positive breast cancer patients.
Identification of a lipid homeostasis-related gene signature for predicting prognosis, immunity, and chemotherapeutic effect in patients with gastric cancer
Authors: Li Chao , Xiong Zhen , Han Jinxin , Nian Weiqi , Wang Zheng , Cai Kailin , Gao Jinbo , Wang Guobin , Tao Kaixiong , Cai Ming
Published: February 2024

Gastric cancer (GC) is one of the most common and deadliest cancers worldwide. Lipid homeostasis is essential for tumour development because lipid metabolism is one of the most important metabolic reprogramming pathways within tumours. Elucidating the mechanism of lipid homeostasis in GC might significantly improve treatment strategies and patient prognosis. GSE62254 was applied to construct a lipid homeostasis-related gene signature score (HGSscore) by multiple bioinformatic algorithms including weighted gene coexpression network analysis (WGCNA) and LASSO-Cox regression. A nomogram based on HGSscore and relevant clinical characteristics was constructed to predict the survival of patients with GC. TIMER and xCell were used to evaluate immune and stromal cell infiltration in the tumour microenvironment. Correlations between lipid homeostasis-related genes and chemotherapeutic efficacy were analysed in GSCAlite. RT‒qPCR and cell viability assays were applied to verify the findings in this study. HGSscore was constructed based on eighteen lipid homeostasis-related genes that were selected by WGCNA and LASSO-Cox regression. HGSscore was strongly associated with advanced TNM stage and showed satisfactory value in predicting GC prognosis in three independent cohorts. Furthermore, we found that HGSscore was associated with the tumour mutation burden (TMB) and immune/stromal cell infiltration, which are related to GC prognosis, indicating that lipid homeostasis impacts the formation of the tumour microenvironment (TME). With respect to the GSCAlite platform, PLOD2 and TGFB2 were shown to be positively related to chemotherapeutic resistance, while SLC10A7 was a favourable factor for chemotherapy efficacy. Cell viability assays showed that disrupted lipid homeostasis could attenuate GC cell viability. Moreover, RT‒qPCR revealed that lipid homeostasis could influence expression of specific genes. We identified a lipid homeostasis-related gene signature that correlated with survival, clinical characteristics, the TME, and chemotherapeutic efficacy in GC patients. This research provides a new perspective for improving prognosis and guiding individualized chemotherapy for patients with GC.
Increased risk of sudden sensorineural hearing loss in patients with cervical spondylosis
Authors: Liu Chia-Chun , Chen I-Te , Weng Shih-Feng
Published: February 2024

Whether cervical spondylosis (CS) is a risk factor for sudden sensorineural hearing loss (SSNHL) remains unclear. This study used national population-based data to investigate the risk of SSNHL in patients with CS in Taiwan of different ages and sexes. This study used data covering 2 million people in Taiwan, which were obtained from the National Health Insurance Research Database. The data that support the findings of this study are available from National Health Insurance Research Database but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the corresponding authors upon reasonable request and with permission of National Health Insurance Research Database. This retrospective cohort study enrolled 91,587 patients with a newly diagnosed CS between January 2000 and December 2018. Case and control cohorts were matched 1:1 according to age, sex, and comorbidities. SSNHL incidence rate and risk were compared between the groups. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The mean follow-up period was 8.80 (SD = 4.12) and 8.24 (SD = 4.09) years in the CS and control cohorts, respectively. The incidence rate of SSNHL in the CS cohort (85.28 per 100 000 person-years) was 1.49-fold significantly higher than that in the non-CS cohort (57.13 per 100,000 person-years) (95% CI 1.32–1.68, P < .001). After age, sex, and selected comorbidities were adjusted for, CS exhibited an independent risk factor for SSNHL (adjusted HR = 1.52; 95% CI   1.34–1.71, P < .001). An age-stratified analysis in this study demonstrated a strong and highly significant association between CS and SSNHL in patients aged < 35 years (IRR = 2.28, 95% CI   1.18–4.39, P = .013). This large-scale Taiwanese-population-based retrospective study found that CS was associated with an increased risk of SSNHL. Acute hearing loss in patients with CS, particularly at a young age, should be carefully evaluated, and prompt treatment for SSNHL should be initiated.
Thermodynamics and electronic structure of adsorbed and intercalated plumbene in graphene/hexagonal SiC heterostructures
Authors: Brozzesi Simone , Gori Paola , Koda Daniel S. , Bechstedt Friedhelm , Pulci Olivia
Published: February 2024

Graphene-covered hexagonal SiC substrates have been frequently discussed to be appropriate starting points for epitaxial overlayers of Xenes, such as plumbene, or even their deposition as intercalates between graphene and SiC. Here, we investigate, within density functional theory, the plumbene deposition for various layer orderings and substrate terminations. By means of total energy studies we demonstrate the favorization of the intercalation versus the epitaxy for both C-terminated and Si-terminated 4H-SiC substrates. These results are explained in terms of chemical bonding and by means of layer-resolved projected band structures. Our results are compared with available experimental findings.
NDUFS7 variant in dogs with Leigh syndrome and its functional validation in a Drosophila melanogaster model
Authors: Christen Matthias , Gregor Anne , Gutierrez-Quintana Rodrigo , Bongers Jos , Rupp Angie , Penderis Jacques , Shelton G. Diane , Jagannathan Vidhya , Zweier Christiane , Leeb Tosso
Published: February 2024

Two Jack-Russell Terrier × Chihuahua mixed-breed littermates with Leigh syndrome were investigated. The dogs presented with progressive ataxia, dystonia, and increased lactate levels. Brain MRI showed characteristic bilateral symmetrical T2 hyperintense lesions, histologically representing encephalomalacia. Muscle histopathology revealed accumulation of mitochondria. Whole genome sequencing identified a missense variant in a gene associated with human Leigh syndrome, NDUFS7:c.535G > A or p.(Val179Met). The genotypes at the variant co-segregated with the phenotype in the investigated litter as expected for a monogenic autosomal recessive mode of inheritance. We investigated the functional consequences of the missense variant in a Drosophila melanogaster model by expressing recombinant wildtype or mutant canine NDUFS7 in a ubiquitous knockdown model of the fly ortholog ND-20. Neither of the investigated overexpression lines completely rescued the lethality upon knockdown of the endogenous ND-20. However, a partial rescue was found upon overexpression of wildtype NDUFS7, where pupal lethality was moved to later developmental stages, which was not seen upon canine mutant overexpression, thus providing additional evidence for the pathogenicity of the identified variant. Our results show the potential of the fruit fly as a model for canine disease allele validation and establish NDUFS7:p.(Val179Met) as causative variant for the investigated canine Leigh syndrome.