bluuebunny/crossref_metadata_2025 huggingface dataset:
Uni-Fold MuSSe: De Novo Protein Complex Prediction with Protein Language Models
Authors: Zhu Jinhua , He Zhenyu , Li Ziyao , Ke Guolin , Zhang Linfeng
Published: February 2023

Abstract

Accurately solving the structures of protein complexes is crucial for understanding and further modifying biological activities. Recent success of AlphaFold and its variants shows that deep learning models are capable of accurately predicting protein complex structures, yet with the painstaking effort of homology search and pairing. To bypass this need, we present Uni-Fold MuSSe (Multimer with Single Sequence inputs), which predicts protein complex structures from their primary sequences with the aid of pre-trained protein language models. Specifically, we built protein complex prediction models based on the protein sequence representations of ESM-2, a large protein language model with 3 billion parameters. In order to adapt the language model to inter-protein evolutionary patterns, we slightly modified and further pre-trained the language model on groups of protein sequences with known interactions. Our results highlight the potential of protein language models for complex prediction and suggest room for improvements.
Structural Optimization of siRNA Conjugates for Albumin Binding Achieves Effective MCL1-Targeted Cancer Therapy
Authors: Hoogenboezem Ella N. , Patel Shrusti S. , Cavnar Ashley B. , Lo Justin H. , Babb Lauren M. , Francini Nora , Patil Prarthana , Colazo Juan M. , Michell Danielle L. , Sanchez Violeta M. , McCune Joshua T. , Ma Jinqi , DeJulius Carlisle R. , Lee Linus H. , Rosch Jonah C. , Allen Ryan M. , Stokes Larry D. , Hill Jordan L. , Vickers Kasey C. , Cook Rebecca S. , Duvall Craig L.
Published: February 2023

The high potential for therapeutic application of siRNAs to silence traditionally undruggable oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, siRNAs were optimized forin situbinding to albumin through C18 lipid modifications to improve pharmacokinetics and tumor delivery. Systematic variation of siRNA conjugates revealed a lead structure with divalent C18lipids each linked through three repeats of hexaethylene glycol connected by phosphorothioate bonds. Importantly, we discovered that locating the branch site of the divalent lipid structure proximally (adjacent to the RNA) rather than at a more distal site (after the linker segment) promotes association with albumin, while minimizing self-assembly and lipoprotein association. Comparison to higher albumin affinity (diacid) lipid variants and siRNA directly conjugated to albumin underscored the importance of conjugate hydrophobicity and reversibility of albumin binding for siRNA delivery and bioactivity in tumors. The lead conjugate increased tumor siRNA accumulation 12-fold in orthotopic mouse models of triple negative breast cancer over the parent siRNA. When applied for silencing of the anti-apoptotic oncogene MCL-1, this structure achieved approximately 80% MCL1 silencing in orthotopic breast tumors. Furthermore, application of the lead conjugate structure to target MCL1 yielded better survival outcomes in three independent, orthotopic, triple negative breast cancer models than an MCL1 small molecule inhibitor. These studies provide new structure-function insights on optimally leveraging siRNA-lipid conjugate structures that associatein situwith plasma albumin for molecular-targeted cancer therapy.
Aging-related changes in expression and function of glutamate transporters in rat spinal cord astrocytes
Authors: Sharan Shiksha , Tewari Bhanu Prakash , Joshi Preeti G.
Published: February 2023

Astrocytes are abundant and heterogeneous cell types in the CNS [1]. They promote neuronal health and survival and protect neurons from glutamate-induced excitotoxicity. In the spinal cord, astrocytes are present in both the dorsal horn (DH) and ventral horns (VH). However, only motor neurons in the VH are highly vulnerable to glutamate excitotoxicity. We hypothesize that the preferential vulnerability of motor neurons may underlie their spatial confinement to the VH, where astrocytes are differentially equipped with glutamate-handling machinery. With aging, glutamate excitotoxicity increases, suggesting compromised astrocytic glutamate handling. We tested our hypotheses by comparing astrocytic morphology, expression of glutamate transporters, and glutamate uptake function in the DH and VH using immunohistochemical staining, western blotting, and whole-cell patch-clamp electrophysiology. We found a global reduction in the numerical density and astroglial coverage in the spinal cord, with a prominent decline in the VH with aging. Astrocytic glutamate transporters, Excitatory amino acid transporter 1 (EAAT1) and Excitatory amino acid transporter 2 (EAAT2), show an overall reduction in expression with aging, with a more progressive decrease in the VH than DH. We performed whole-cell patch-clamp studies on DH and VH astrocytes to assess the functional outcome of the altered expression of EAATs with aging. Both VH and DH astrocytes showed a dramatic decline in glutamate uptake currents with aging, suggesting compromised glutamate handling in aging astrocytes. Our study suggests that astrocytes in the DH and VH undergo differential changes with aging, exhibiting compromised glutamate handling properties, which may be one of the key contributors to the late onset of neurodegenerative disorders.
Psychophysical measurement of perceived motion flow of naturalistic scenes
Authors: Yang Yung-Hao , Fukiage Taiki , Sun Zitang , Nishida Shin’ya
Published: February 2023

The neural and computational mechanisms underlying visual motion perception have been extensively investigated over several decades, but most studies have used simple artificial stimuli such as random-dot kinematograms. Thus, it remains difficult to predict how human observers perceive optical flows in complex natural scenes. Here, we report a novel method to measure, psychophysically, optical flows perceived by human observers watching naturalistic movies, and to reveal the characteristics of human motion perception via comparison of the measured perceived flow to the ground truths and model predictions. We selected movie clips from the MPI Sintel Flow Dataset, which contains open-source computer graphics animations with ground truths. To measure the perceived vectors at a spatiotemporal point, we flashed a small dot during presentation of a brief clip and asked the observers to adjust the speed and direction of a matching random-noise stimulus, to reproduce the vector at the flashed point. The proposed method adequately estimated perceived flow, and the estimated perceived vector also indicated flow illusions, i.e., consistent deviations from the ground truths, in various ways, depending on the stimulus patterns. Comparisons with the predictions of biologically motivated models and machine vision algorithms indicated that some flow illusions were attributable to lower-level factors such as spatiotemporal pooling and signal loss, but others reflected higher-level computations including coordinate transformations that cannot be precisely predicted by existing flow estimation models. Psychophysical measurement of the optical flows that humans perceive in realistic environments constitutes a promising paradigm for advancing our understanding of visual motion perception.

Significance Statement

The basic approach to studying human vision is to analyze relationships among subjective perceptual experiences, responses of neural mechanisms, and predictions of computational models. Recent technical advances have enabled researchers to access large-scale neuronal responses and model predictions for complex sensory inputs. The data on human visual perception, however, cannot be easily scaled up. Accurate measurement of rich visual experiences when viewing natural scenes remains challenging. We thus devised a novel psychophysical method to measure optical motion flows perceived by humans. We successfully visualized human-perceived flows of complex naturalistic movies and show, for the first time, ways in which human-perceived naturalistic flows agree with, and deviate from, the physical ground truths and the predictions of various visual motion models.
Predicting CIN rates from single-cell whole genome sequencing data using anin silicomodel
Authors: Bakker Bjorn , Schubert Michael , Bolhaqueiro Ana C.F. , Kops Geert J.P.L. , Spierings Diana. C.J. , Foijer Floris
Published: February 2023

Chromosomal instability (CIN) drives the formation of karyotype aberrations in cancer cells and is a major contributor to intra-tumour heterogeneity, metastasis, and therapy resistance. Understanding how CIN contributes to tumour karyotype evolution requires quantification of CIN rates in primary tumours. Single-cell sequencing-based technologies enable the detection of karyotype heterogeneity, however deducing the actual CIN rates that underlie intra-tumour heterogeneity is still complicated. We have developed anin-silicomodel, calledCINsim, to simulate the karyotype dynamics and validated our model in a murine mouse model for T-cell lymphoma (T-ALL) in which CIN is introduced by mutation of the Mps1 spindle assembly checkpoint protein.CINsimcan simulate karyotype evolution within physiologically relevant timescales, across a range of CIN rates, and across a range of karyotype-imposed survival and proliferation effects. We find thatCINsimcan accurately predict the CIN rates in chromosomal instable mouse T-ALLs as well as in human colon cancer organoids as observed by live-cell time-lapse imaging. We conclude thatCINsimis a powerful tool to estimate CIN rates from static single-cell DNA sequencing data by finding the most likely path from euploid founder cell to a heterogeneous tumour cell population.
Disentangled deep generative models reveal coding principles of the human face processing network
Authors: Soulos Paul , Isik Leyla
Published: February 2023

Despite decades of research, much is still unknown about the computations carried out in the human face processing network. Recently deep networks have been proposed as a computational account of human visual processing, but while they provide a good match to neural data throughout visual cortex, they lack interpretability. We introduce a method for interpreting brain activity using a new class of deep generative models, disentangled representation learning models, which learn a low-dimensional latent space that “disentangles” different semantically meaningful dimensions of faces, such as rotation, lighting, or hairstyle, in an unsupervised manner by enforcing statistical independence between dimensions. We find that the majority of our model’s learned latent dimensions are interpretable by human raters. Further, these latent dimensions serve as a good encoding model for human fMRI data. We next investigated the representation of different latent dimensions across face-selective voxels. We find a gradient from low- to high-level face feature representations along posterior to anterior face-selective regions, corroborating prior models of human face recognition. Interestingly, though, we find no spatial segregation between identity-relevant and irrelevant face features. Finally, we provide new insight into the few “entangled” (uninterpretable) dimensions in our model by showing that they match responses across the ventral stream and carry significant information about facial identity. Disentangled face encoding models provide an exciting alternative to standard “black box” deep learning approaches for modeling and interpreting human brain data.
Tumor Niche Network-Defined Subtypes Predict Immunotherapy Response of Esophageal Squamous Cell Cancer
Authors: Ko Kyung-Pil , Zhang Shengzhe , Huang Yuanjian , Kim Bongjun , Zou Gengyi , Jun Sohee , Zhang Jie , Martin Cecilia , Dunbar Karen J. , Efe Gizem , Rustgi Anil K. , Zhang Haiyang , Nakagawa Hiroshi , Park Jae-Il
Published: February 2023

Despite the promising outcomes of immune checkpoint blockade (ICB), resistance to ICB presents a new challenge. Therefore, selecting patients for specific ICB applications is crucial for maximizing therapeutic efficacy. Herein we curated 69 human esophageal squamous cell cancer (ESCC) patients’ tumor microenvironment (TME) single-cell transcriptomic datasets to subtype ESCC. Integrative analyses of the cellular network transcriptional signatures of T cells, myeloid cells, and fibroblasts define distinct ESCC subtypes characterized by T cell exhaustion, Interferon (IFN) a/b signaling, TIGIT enrichment, and specific marker genes. Furthermore, this approach classifies ESCC patients into ICB responders and non-responders, as validated by liquid biopsy single-cell transcriptomics. Our study stratifies ESCC patients based on TME transcriptional network, providing novel insights into tumor niche remodeling and predicting ICB responses in ESCC patients.
Classification of dog breeds using convolutional neural network models and support vector machine
Authors: Cui Ying , Tang Bixia , Wu Gangao , Li Lun , Zhang Xin , Du Zhenglin , Zhao Wenming
Published: February 2023

Convolutional neural network (CNN) has been widely used for fine-grained image classification, which has proven to be an effective approach for the classification and identification of specific species. For breed classification of dog, there are several proposed methods based on dog images, however, the highest accuracy rate for dogs (about 93%) is still below expectations compared to other animals or plants (more than 95% on birds and more than 97% on flowers). In this study, we used the Stanford Dog Dataset, combined image features from four CNN models, filtered the features using principal component analysis (PCA) and gray wolf optimization algorithm (GWO), and then classified the features with support vector machine (SVM). Eventually, the classification accuracy rate reached 95.24% for 120 breeds and 99.34% for 76 selected breeds, respectively, demonstrating a significant improvement over existing methods using the same Stanford Dog Dataset. It is expected that our proposed method will further serve as a fundamental framework for accurate classification of a wider range of species.
Specialized actin nanoscale layers control focal adhesion turnover
Authors: Kumari Reena , Ven Katharina , Chastney Megan , Peränen Johan , Aaron Jesse , Almeida-Souza Leonardo , Kremneva Elena , Poincloux Renaud , Chew Teng-Leong , Gunning Peter W. , Ivaska Johanna , Lappalainen Pekka
Published: February 2023

Focal adhesions (FAs) connect inner workings of the cell to the extracellular matrix to control cell adhesion, migration, and mechanosensing1,2. Previous studies demonstrated that FAs contain three vertical layers, which connect extracellular matrix to the cytoskeleton3,4,5. However, cellular processes rely on precisely-regulated FA turnover, but the molecular machineries that control FA assembly and disassembly have remained elusive. By using super-resolution iPALM microscopy, we identified two unprecedented nanoscale layers within FAs, specified by actin filaments bound to tropomyosin isoforms Tpm1.6 and Tpm3.2. The Tpm1.6-actin filaments beneath the previously identified ‘actin-regulatory layer’ are critical for adhesion maturation and controlled cell motility, whereas the Tpm3.2-actin filament layer towards the bottom of FA facilitates adhesion disassembly. Mechanistically, Tpm3.2 stabilizes KANK-family proteins at adhesions, and hence targets microtubule plus-ends to FAs to catalyse their disassembly. Loss of Tpm3.2 leads to disorganized microtubule network, abnormally stable FAs, and defects in tail retraction during cell migration. Thus, FAs are composed of at least three distinct actin filament layers, each having specific roles in coupling of adhesion to the cytoskeleton, or in controlling adhesion dynamics. In a broader context, these findings demonstrate how distinct actin filament populations can co-exist and perform specific functions within a defined cellular compartment.
Multivariate Residualization in Medical Imaging Analysis
Authors: Donovan Kevin , Tustison Nicholas J , Linn Kristin A. , Shinohara Russell T. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2023

Nuisance variables in medical imaging research are common, complicating association and prediction studies based on image data. Medical image data are typically high dimensional, often consisting of many highly correlated features. As a result, computationally efficient and robust methods to address nuisance variables are difficult to implement. By-region univariate residualization is commonly used to remove the influence of nuisance variables, as are various extensions. However, these methods neglect multivariate properties and may fail to fully remove influence related to the joint distribution of these regions. Some methods, such as functional regression and others, do consider multivariate properties when controlling for nuisance variables. However, the utility of these methods is limited for data with many image regions due to computational and model complexity. We develop a multivariate residualization method to estimate the association between the image and nuisance variable using a machine learning algorithm and then compute the orthogonal projection of each subject’s image data onto this space. We illustrate this method’s performance in a set of simulation studies and apply it to data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
Barley shows reduced Fusarium Head Blight under drought and modular expression of differential expressed genes under combined stress
Authors: Hoheneder Felix , Steidele Christina E. , Messerer Maxim , Mayer Klaus , Köhler Nikolai , Wurmser Christine , Heß Michael , Gigl Michael , Dawid Corinna , Stam Remco , Hückelhoven Ralph
Published: February 2023

Plants often face simultaneous abiotic and biotic stress conditions. However, physiological and transcriptional responses of plants under combined stress situations are little understood. Spring barley is susceptible to Fusarium Head Blight (FHB), which is strongly affected by weather conditions. We therefore studied the potential influence of drought on FHB severity and responses in three differently susceptible spring barley varieties and found strongly reduced FHB severity in susceptible varieties under drought. Quantity of differentially expressed genes (DEGs) and strength of transcriptomic regulation reflected the concentration of physiological stress markers such as abscisic acid or fungal DNA contents. Infection-related gene expression associated rather with susceptibility than resistance. Weighted gene correlation network analysis uncovered 18 modules of co-expressed genes, which reflect the pathogen or drought response in the used varieties. A generally infection-related module contained co-expressed genes for defence, programmed cell death and mycotoxin-detoxification indicating that diverse genotypes use a similar defence strategy towards FHB albeit with different success. Further DEGs showed co-expression in drought or genotype-associated modules correlating with measured phytohormones or the osmolyte proline. The combination of drought stress with infection lead to highest numbers of DEGs and provoked a modular composition of single stress responses rather than a specific transcriptional readout.

Highlight

Co-expression network analysis reveals association of physiological stress markers and gene expression modules under biotic and abiotic stress
Accelerating crystal structure determination with iterative AlphaFold prediction
Authors: Terwilliger Thomas C. , Afonine Pavel V. , Liebschner Dorothee , Croll Tristan I. , McCoy Airlie J. , Oeffner Robert D. , Williams Christopher J. , Poon Billy K. , Richardson Jane S. , Read Randy J. , Adams Paul D.
Published: February 2023

Experimental structure determination can be accelerated with artificial intelligence (AI)-based structure-prediction methods such as AlphaFold. Here, an automatic procedure requiring only sequence information and crystallographic data is presented that uses AlphaFold predictions to produce an electron-density map and a structural model. Iterating through cycles of structure prediction is a key element of this procedure: a predicted model rebuilt in one cycle is used as a template for prediction in the next cycle. This procedure was applied to X-ray data for 215 structures released by the Protein Data Bank in a recent six-month period. In 87% of cases our procedure yielded a model with at least 50% of Cα atoms matching those in the deposited models within 2 Å. Predictions from the iterative template-guided prediction procedure were more accurate than those obtained without templates. It is concluded that AlphaFold predictions obtained based on sequence information alone are usually accurate enough to solve the crystallographic phase problem with molecular replacement, and a general strategy for macromolecular structure determination that includes AI-based prediction both as a starting point and as a method of model optimization is suggested.
Trend in tropopause warming and its influence aircraft performance
Authors: Cizrelioğullari Mehmet Necati , Imanov Tapdig Veyran , Gunay Tugrul , Shaiq Amir Aliyev
Published: February 2023

Purpose

Temperature anomalies in the upper troposphere have become a reality as a result of global warming, which has a noticeable impact on aircraft performance. The purpose of this study is to investigate the total air temperature (TAT) anomaly observed during the cruise level and its impact on engine parameter variations.

Design/methodology/approach

Empirical methodology is used in this study, and it is based on measurements and observations of anomalous phenomena on the tropopause. The primary data were taken from the Boeing 747-8F's enhanced flight data recorder, which refers to the quantitative method, while the qualitative method is based on a literature review and interviews. The GEnx Integrated Vehicle Health Management system was used for the study's evaluation of engine performance to support the complete range of operational priorities throughout the entire engine lifecycle.

Findings

The study's findings indicate that TAT and SAT anomalies, which occur between 270- and 320-feet flight level, have a substantial impact on aircraft performance at cruise altitude and, as a result, on engine parameters, specifically an increase in fuel consumption and engine exhaust gas temperature values. The TAT and Ram Rise anomalies were the focus of the atmospheric deviations, which were assessed as major departures from the International Civil Aviation Organizations–defined International Standard Atmosphere, which is obvious on a positive tendency and so goes against the norms.

Research limitations/implications

Necessary fixed flight parameters gathered from the aircraft's enhanced airborne flight recorder (EAFR) via Aeronautical Radio Incorporated (ARINC) 664 Part 7 at a certain velocity and altitude interfacing with the diagnostic program direct parameter display (DPD), allow for analysis of aircraft performance in a real-time frame. Thus, processed data transmits to the ground maintenance infrastructure for future evaluation and for proper maintenance solutions.

Originality/value

A real-time analysis of aircraft performance is possible using the diagnostic program DPD in conjunction with necessary fixed flight parameters obtained from the aircraft's EAFR via ARINC 664 Part 7 at a specific speed and altitude. Thus, processed data is transmitted to the ground infrastructure for maintenance to be evaluated in the future and to find the best maintenance fixes.
Routine failure in Macedonia: a critique of the Global Financial Crisis from the periphery
Authors: Mattioli Fabio
Published: February 2023

In most Western analyses, the Global Financial Crisis (GFC) constituted a systemic failure that spread across the entire capitalist system from the United States. That was not, however, the discourse that circulated in (and about) Macedonia – a peripheral country that had been mired in economic disasters since its transition from socialism. Local experts and citizens believed that Macedonia hadnotbeen severely impacted by the GFC. This essay asks how economic crises and their aftermaths are experienced and evaluated when they are effectively routine or ‘normal’. Overall, it argues that, in a landscape punctuated by continual disruption, the GFC appeared not as a failure, but as a new reconfiguration of power that strengthened the position of new elites through increasingly oppressive relations of (inter)dependence.
Endocrine modulating chemicals in food packaging: A review of phthalates and bisphenols
Authors: Tumu Khairun , Vorst Keith , Curtzwiler Greg
Published: February 2023

Phthalates and bisphenol chemicals have been widely used globally in packaging materials and consumer products for several decades. These highly functional chemicals have become a concern due to their toxicity (i.e., endocrine/hormone modulators) and ability to migrate from food contact materials (FCMs) into food matrices and the environment resulting in human and environmental health risks. FCMs, composed of postconsumer materials, are particularly high risk for containing these compounds. The evaluation of postconsumer recycled feedstocks in FCMs is compulsory and selection of an appropriate detection method to comply with applicable regulations is necessary to evaluate human and environmental safety. Numerous regulations have been proposed and passed globally for both compound classes that are recognized as priority pollutants by the United States Environmental Protection Agency and the European Union. Several brand owners and retailers have also released their own “restricted substance lists” due to the mounting consumer and regulatory concerns. This review article has two goals: (1) discuss the utilization, toxicology, human exposure routes, and occurrence levels of phthalates and bisphenols in FCMs and associated legislation in various countries and (2) discuss critical understanding and updates for detection/quantification techniques. Current techniques discussed include extraction and sample preparation methods (solid‐phase microextraction [SPME], headspace SPME, Soxhlet procedure, ultrasound‐assisted extraction), chromatographic techniques (gas, liquid, detectors), and environmental/blank considerations for quantification. This review complements a previous review of phthalates in foods from 2009 by discussing phthalate and bisphenol characteristics, analytical methods of determining concentrations in packaging materials, and their influence on the migration potential into food.
Pharmacokinetics, withdrawal time, and dietary risk assessment of enrofloxacin and its metabolite ciprofloxacin, and sulfachloropyridazine‐trimethoprim in Taihe black‐boned silky fowls
Authors: Yuan Lijuan , Wu Huizhen , Wang Jianmei , Zhou Min , Zhang Li , Xiang Jianjun , Liao Qiegen , Luo Linguang , Qian Mingrong , Zhang Dawen
Published: February 2023

Enrofloxacin (ENR) and sulfachloropyridazine combined with trimethoprim (TMP) were commonly used in poultries to treat bacterial infections. In this study, the pharmacokinetics of these antibiotics in four tissues of Taihe black‐boned silky fowls was studied. The results showed that these drugs were absorbed and distributed rapidly, with the highest concentration showing in skin. Meanwhile, ENR and its metabolite ciprofloxacin (CIP) and TMP were depleted slowly, particularly in skin with the elimination half‐lives being 37.1, 36.9, and 72.7 days, respectively. It may be attributed to the abundance of melanin in skin. The dietary risk assessment suggested that the long‐term dietary intakes of ENR, CIP, and TMP showed a considerable threat to human health. Based on the experiment, the withdrawal times of 284 days for ENR + CIP and 159 days for TMP were acquired, which showed that these drugs are not appropriate for the application in Taihe black‐boned silky fowls.
The migration and loss of water in emulsified surimi gels prepared with different phase states of lipids: Effect of freeze‐thawing treatments
Authors: Liu Cikun , Feng Ruonan , Li Jun , Hu Zhongliang , Xu Yanshun , Xia Wenshui , Jiang Qixing
Published: February 2023

The freeze‐thawing (FT) stability generally correlates well with the economic value and acceptability of frozen surimi‐based products. However, quality changes of emulsified surimi gels under FT conditions are still unclear. Therefore, the gel properties of samples with different phase states of lipids (lard, lard + soybean oil, and soybean oil) were investigated at FT conditions. Results showed that the soybean oil evidently improved the rheological behaviors of sols/gels compared to the lard group. The moisture content of samples with different lipids decreased by 2.40%–2.71% after 4 FT cycles. With increasing FT cycles, the water‐holding capacity decreased accompanied by the increase of cooking loss. Spin–spin relaxation spectra and hydrogen proton density images proved the occurrence of water migration of gels during these processes. Better gel integrity was observed in samples consisting of soybean oil, where the proportion of pores was lower than those with lard regardless of FT treatments. Additionally, the intermolecular forces of gels also changed under FT treatments. There results suggested that the lipids with different phase states affected the migration and loss of water in emulsified surimi gels under FT cycles.

Practical Application

The quality changes of heating‐induced surimi gel products under frozen storage have been ignored, especially the emulsified surimi gels. This study discloses the changes of the gel properties in emulsified gel products with different phase states of lipids after FT treatments, which provides critical insights into the quality improvement of this novel emulsified surimi product during processing, storage, and transportation.
Chromosome‐level genome assembly of a triploid poplar Populus alba ‘Berolinensis’
Authors: Chen Song , Yu Yue , Wang Xinyu , Wang Sui , Zhang Tianjiao , Zhou Yan , He Ruihan , Meng Nan , Wang Yiran , Liu Wenxuan , Liu Zhijie , Liu Jinwen , Guo Qiwen , Huang Haijiao , Sederoff Ronald R. , Wang Guohua , Qu Guanzheng , Chen Su
Published: February 2023

Many recent studies have provided significant insights into polyploid breeding, but limited research has been carried out on trees. The genomic information needed to understand growth and response to abiotic stress in polyploidy trees is largely unknown, but has become critical due to the threats to forests imposed by climate change. Populus alba ‘Berolinensis,’ also known “Yinzhong poplar,” is a triploid poplar from northeast China. This hybrid triploid poplar is widely used as a landscape ornamental and in urban forestry owing to its adaptation to adverse environments and faster growth than its parental diploid. It is an artificially synthesized male allotriploid hybrid, with three haploid genomes of P. alba ‘Berolinensis’ originating from different poplar species, so it is attractive for studying polyploidy genomic mechanisms in heterosis. In this study, we focused on the allelic genomic interactions in P. alba ‘Berolinensis,’ and generated a high‐quality chromosome‐level genome assembly consisting of 19 allelic chromosomes. Its three haploid chromosome sets are polymorphic with an average of 25.73 nucleotide polymorphism sites per kilobase. We found that some stress‐related genes such as RD22 and LEA7 exhibited sequence differences between different haploid genomes. The genome assembly has been deposited in our polyploid genome online analysis website TreeGenomes (https://www.treegenomes.com). These polyploid genome‐related resources will provide a critical foundation for the molecular breeding of P. alba ‘Berolinensis’ and help us uncover the allopolyploidization effects of heterosis and abiotic stress resistance and traits of polyploidy species in the future.
Birthweight and gestational age in the Faroe Islands: A comparison between birthweight and gestational age in the Faroe Islands and other Nordic countries
Authors: Olsen Sunnvá Hanusardóttir , Reynstind Diana , Hallgrímsson Hlynur , Kesmodel Ulrik Schiøler
Published: February 2023

Introduction

This study aimed to examine Faroese infants' birthweight and gestational age in 2010–2019 and compare these findings with other Nordic countries. Risk factors for high birthweight among Faroese infants were also investigated in this study.

Material and methods

All singleton liveborn infants registered in the Faroese Birth Registry in 2010–2019 were included in the study (n = 6121). A comparison was made with data on birthweight and gestational age from Denmark, Iceland, Norway, and Sweden.

Results

The mean birthweight increased significantly from 3652 g (95% confidence interval [CI]: 3505–3699 g) in 2010 to 3745 g (95% CI: 3700–3790 g) in 2019, a mean increase in birthweight of 93 g (95% CI: 28–158 g) (p < 0.05). The birthweight increased 186 g (95% CI: 179–193 g) for each gestational week and 11 g (95% CI: 7–15 g) for each year. Changes in gestational age explained 31% of the change in birthweight. The proportion of infants weighing 4500 g or more increased significantly from 6.1% in 2010 to 9.6% in 2019 (p < 0.05). The risk of giving birth to an infant weighing 4000 g or more was consistently associated with previously giving birth (OR 1.98 (95% CI: 1.71–2.30)) and gestational age (OR 1.28 (95% CI: 1.23–1.33) per week increase in gestational age). Infants born in gestational weeks 40 and 42 in 2019 had a higher birthweight z‐score than infants born in gestational weeks 40 and 42 in 2010. Compared to other Nordic countries, Faroese infants' mean birthweight was high, the Faroe Islands had a higher number of infants born with a weight of 4000 g or more and a higher proportion of infants born in gestational week 41 or later (31.5%).

Conclusions

Our results showed that the mean birthweight and the proportion of infants with high birthweight significantly increased during 2010–2019 in the Faroe Islands. The mean birthweight, the proportion of infants with high birthweight and the gestational age at birth for Faroese infants was higher than all other Nordic countries. The reasons for this require further investigation.
Conspiracy theories and clinical decision‐making
Authors: Stout Nathan
Published: February 2023

When a patient's treatment decisions are the product of delusion, this is often taken as a paradigmatic case of undermined decisional capacity. That is to say, when a patient refuses treatment on the basis of beliefs that in no way reflect reality, clinicians and ethicists tend to agree that their refusal is not valid. During the COVID‐19 pandemic, however, we have witnessed many patients refuse potentially life‐saving interventions not based on delusion but on conspiracy beliefs. Importantly, many of the beliefs espoused by conspiracy theorists resemble delusions in a number of relevant ways. For instance, conspiracy beliefs often posit states of affairs that could not possibly exist in the world, they are recalcitrant in the face of disconfirming evidence, and they tend to put the believer in a state of paranoia. Given these similarities, how should we think about conspiracy theorists' capacity for making clinical decisions? In this paper, I attempt to answer this question by first offering an account of just what makes some set of beliefs count as a conspiracy theory. Second, I attempt to disambiguate conspiracy beliefs from delusions by exploring important conceptual and psychological features of both. Finally, I apply standard criteria for assessing a patient's decision‐making capacity to instances of conspiracy beliefs and argue that, although the picture is muddy, there may be cases in which conspiracy beliefs undermine capacity. I end by exploring the implications that this might have for surrogate decision‐making and addressing potential objections.
Workplace gender segregation in standard and non‐standard employment regimes in the US labour market
Authors: Makarevich Alex
Published: February 2023

This study provides a comprehensive analysis of workplace gender segregation in non‐standard employment in the United States. It compares segregation in standard and three non‐standard work arrangements paying special attention to independent contracting – a segment of contingent employment representing novel and consequential developments in work organization. In line with the prediction that inequality is lower in more marketized sectors of the labour market, my analyses based on a representative sample of the contemporary US workforce reveal that workplace gender segregation is lower in non‐standard employment. I further find that the degree of segregation corresponds to the degree of attachment to the employer and that segregation is lower in segments of the economy with higher market competition. Overall, my analyses indicate that a shift towards alternative work arrangements can reduce overall workplace segregation but does not lead to uniform desegregation across occupations, and that institutions of employment and market pressures faced by employers play significant roles in the effect of alternative work arrangements on workplace segregation.
Long‐term outcomes of total colectomy for severe constipation
Authors: Johnston Ben J. , Clark David A. , Warwick Andrea M.
Published: February 2023

Aim

Surgery for constipation is usually reserved for patients with severe and refractory symptoms because of concerns about perioperative morbidity and unpredictable functional outcomes. The aim of this paper is to identify the long‐term outcomes of patients who have undergone total colectomy and ileorectal anastomosis for severe constipation.

Method

Patients who had undergone a total colectomy and ileorectal anastomosis for severe constipation were identified from a prospectively maintained database and sent a postal survey assessing functional symptoms, patient satisfaction and the impact of symptoms on quality of life. Information regarding the surgery, perioperative complications and hospitalizations were also collected. Functional outcomes of the surgery were evaluated with the Gastrointestinal Quality of Life Index, St Marks incontinence score, Wexner continence score, obstructed defaecation syndrome score and Cleveland Clinic constipation score.

Results

Seventy‐one questionnaires were posted and 32 (45%) patients responded. The mean time since surgery was 15.3 years (range 2.9–30.4 years) Most patients were happy with the surgery. Ongoing symptoms were common, the most frequent of these were abdominal pain, experienced by 23 patients (71.9%), and faecal incontinence, experienced by 17 patients (53%). Fourteen patients (43.8%) required subsequent hospital admission due to bowel obstruction and eight patients (25%%) had subsequent surgery for adhesions. There was an association between patient quality of life and subsequent surgeries.

Conclusion

Most patients were happy and viewed their life as improved following total colectomy for severe constipation. This is despite a high rate of ongoing functional symptoms.
Deliberate delays in offering abortion to pregnant women with fetal anomalies after 24 weeks' gestation at a centre in South Africa
Authors: Kleinsmidt Anita , Malope Malebo , Urban Michael
Published: February 2023

South Africa has an abortion law which codifies the broad themes of reproductive rights set out in the Constitution of South Africa, other laws and national guidelines. Certain wording of the conditions in the Choice Act for abortion after 20 weeks' gestation, are open to interpretation, being ‘severe malformation of the fetus’ and ‘risk of injury to the fetus’. From 24 weeks onwards, abortion is carried out by feticide/induced fetal cardiac asystole (‘IFCA’) and subsequent induction of labour in South Africa. Some maternal‐fetal units have developed guidelines to assist clinicians and patients in decision‐making around eligibility for abortion after 20 weeks' gestation, given the broad terms in the law. We consider the guideline used by an institution in the Western Cape for abortion after 23 weeks and 6 days gestation, in terms of its alignment with the law on reproductive rights and its compliance with fair and transparent procedures. We also note its effect on respect for patients and on staff professionalism.
Once‐weekly semaglutide use in patients with type 2 diabetes: Real‐world data from the SURE Italy observational study
Authors: Napoli Raffaele , Berra Cesare , Catarig Andrei‐Mircea , Di Loreto Chiara , Donatiello Emily , Berentzen Tina Landsvig , Pitocco Dario , Giorgino Francesco
Published: February 2023

Aims

SURE Italy, a multicentre, prospective, open‐label, observational, real‐world study, investigated once‐weekly semaglutide in patients with type 2 diabetes (T2D) in routine clinical practice.

Materials and Methods

Adults with T2D and ≥1 documented glycated haemoglobin (HbA1c) level within 12 weeks of semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~30 weeks). Other endpoints included changes in body weight, waist circumference and patient‐reported outcomes, and the proportion of patients achieving HbA1c <7.0% or <6.5%, weight loss ≥5% and a post‐hoc composite endpoint (HbA1c reduction of ≥1%‐point and weight loss ≥5%). These endpoints were reported for patients on semaglutide at EOS [effectiveness analysis set (EAS)]. Safety data were reported in the full analysis set.

Results

Of 579 patients who initiated semaglutide (full analysis set), 491 completed the study on treatment (EAS). Mean baseline HbA1c was 8.0%, and 20.7% (120 of 579) of patients had HbA1c <7.0%. Mean semaglutide dose at EOS was 0.66 ± 0.28 mg. In the EAS, mean HbA1c and body weight decreased by 1.1%‐point (95% confidence interval 1.20, 1.05; P < .0001) and 4.2 kg (95% confidence interval 4.63, 3.67; P < .0001), respectively. At EOS, 61.7% and 40.8% of patients achieved HbA1c <7.0% and <6.5%, respectively, 40.5% achieved weight loss ≥5% and 25.3% achieved the post‐hoc composite endpoint. Patient‐reported outcomes improved from baseline to EOS. No new safety concerns were identified.

Conclusions

In routine clinical practice in Italy, patients with T2D treated with once‐weekly semaglutide for 30 weeks achieved clinically significant improvements in HbA1c, body weight and other outcomes.
Loss of ATP2C1 function promotes trafficking and degradation of NOTCH1: Implications for Hailey‐Hailey disease
Authors: Zonfrilli Azzurra , Truglio Federica , Simeone Alessandra , Pelullo Maria , De Turris Valeria , Benelli Dario , Checquolo Saula , Bellavia Diana , Palermo Rocco , Uccelletti Daniela , Screpanti Isabella , Cialfi Samantha , Talora Claudio
Published: February 2023

Hailey‐Hailey disease (HHD) is a rare autosomal dominantly inherited disorder caused by mutations in the ATP2C1 gene that encodes an adenosine triphosphate (ATP)‐powered calcium channel pump. HHD is characterized by impaired epidermal cell‐to‐cell adhesion and defective keratinocyte growth/differentiation. The mechanism by which mutant ATP2C1 causes HHD is unknown and current treatments for affected individuals do not address the underlying defects and are ineffective. Notch signalling is a direct determinant of keratinocyte growth and differentiation. We found that loss of ATP2C1 leads to impaired Notch1 signalling, thus deregulation of the Notch signalling response is therefore likely to contribute to HHD manifestation. NOTCH1 is a transmembrane receptor and upon ligand binding, the intracellular domain (NICD) translocates to the nucleus activating its target genes. In the context of HHD, we found that loss of ATP2C1 function promotes upregulation of the active NOTCH1 protein (NICD‐Val1744). Here, deeply exploring this aspect, we observed that NOTCH1 activation is not associated with the transcriptional enhancement of its targets. Moreover, in agreement with these results, we found a cytoplasmic localization of NICD‐Val1744. We have also observed that ATP2C1‐loss is associated with the degradation of NICD‐Val1744 through the lysosomal/proteasome pathway. These results show that ATP2C1‐loss could promote a mechanism by which NOTCH1 is endocytosed and degraded by the cell membrane. The deregulation of this phenomenon, finely regulated in physiological conditions, could in HHD lead to the deregulation of NOTCH1 with alteration of skin homeostasis and disease manifestation.
Analysis method of cellular stress caused by intermediate dose‐rate irradiation using a cell lysate array technique
Authors: Morishima Nobuhiro , Ogata Hiromitsu , Magae Junji , Ito Yoshihiro , Kobayashi Junya
Published: February 2023

Ionizing radiation damages DNA and may lead to the development of cancer. Irradiation also generates reactive oxygen species (ROS) which cause damage to various biological molecules. Relatively low dose‐rate irradiation causes less damage. However, the damage and its effects on cell fate are difficult to evaluate. To develop a method to analyze the damage and accompanying changes in physiology in cells irradiated by γ‐rays at a relatively low dose‐rate, we used the protein array technique to quantify marker proteins involved in the stress response and the regulation of cell growth and death. This method enabled efficient analyses of many replicates of experimental data on cell lysate samples. We detected relatively small changes in the levels of these proteins in the irradiated cells. Changes in protein levels suggested ROS production and DNA damage as well as cell cycle retardation and the progression of cellular senescence. Thus, our approach shows promise for analyzing the biological effects of relatively low dose‐rate irradiation.
Navigating digital transformation through an information quality strategy: Evidence from a military organisation
Authors: Struijk Mylène , Angelopoulos Spyros , Ou Carol X. J. , Davison Robert M.
Published: February 2023

The use of digital technologies for extracting information from various data sources can help organisations to reduce uncertainty and improve decision‐making. The increasing availability in volume, velocity, and variety of data, however, can give rise to significant risks and challenges in ensuring a high level of information quality (IQ). Pre‐digital organisations can be particularly susceptive to such challenges due to their limited experience with digital technologies and IQ governance. We adopt a theory‐infused interventionist research approach to assist a pre‐digital multinational military organisation in navigating its digital transformation (DT) by focusing on IQ. We design and implement an IQ strategy (IQS) by drawing upon organisational information processing theory and examining how the level of IQ can affect the balance between information processing requirements and capacity. We demonstrate that an IQS that incorporates both technological, as well as IQ governance solutions, can support organisations in setting the scope of their DT, decreasing employees' resistance to change, and increasing their satisfaction, while concurrently improving organisational efficiency. Our work stresses the importance of IQ in the digital era and delineates how pre‐digital organisations can navigate DT by strategically addressing IQ.