bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated segmentation and quantitative analysis of organelle morphology, localization and content using CellProfiler
Authors: Laan Sebastiaan N.J. , Dirven Richard J. , Eikenboom Jeroen , Bierings Ruben ,   for the SYMPHONY consortium
Published: November 2022

One of the most used and versatile methods to study number, dimensions, content and localization of secretory organelles is confocal microscopy analysis. However, considerable heterogeneity exists in the number, size and shape of secretory organelles that can be present in the cell. One thus needs to analyze large numbers of organelles for valid quantification. Properly evaluating these parameters requires an automated, unbiased method to process and quantitatively analyze microscopy data. Here, we describe two pipelines, run by CellProfiler software, called OrganelleProfiler and OrganelleContentProfiler. These pipelines were used on confocal images of endothelial colony forming cells (ECFC) which contain unique secretory organelles called Weibel-Palade bodies. Results show that the pipelines can quantify the cell count and size, and the organelle count, size, shape, relation to cells and nuclei, and distance to these objects. Furthermore, the pipeline is able to quantify secondary signals located in or on the organelle or in the cytoplasm. Cell profiler measurements were checked for validity using Fiji. To conclude, these pipelines provide a powerful, high-processing quantitative tool for analysis of cell and organelle characteristics. These pipelines are freely available and easily editable for use on different cell types or organelles.
Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation
Authors: Hilligan Kerry L. , Oyesola Oyebola O. , Namasivayam Sivaranjani , Howard Nina , Clancy Chad S. , Oland Sandra D. , Garza Nicole L. , Lafont Bernard A. P. , Johnson Reed F. , Mayer-Barber Katrin D. , Sher Alan , Loke P’ng
Published: November 2022

Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung migrating helminth,Nippostrongylus brasiliensis, enhances viral clearance and survival of human-ACE2 transgenic mice challenged with SARS-CoV-2 (SCV2). This protection is associated with a lymphocytic infiltrate including an increased accumulation of pulmonary SCV2-specific CD8+ T cells and anti-CD8 antibody depletion abrogated theN. brasiliensis-mediated reduction in viral loads. Pulmonary macrophages with a type-2 transcriptional signature persist in the lungs ofN. brasiliensisexposed mice after clearance of the parasite and establish a primed environment for increased antigen presentation. Accordingly, depletion of macrophages ablated the augmented viral clearance and accumulation of CD8+ T cells driven by priorN. brasiliensisinfection. Together, these findings support the concept that lung migrating helminths can limit disease severity during SCV2 infection through macrophage-dependent enhancement of anti-viral CD8+ T cell responses.

Abstract Figure
A comparative atlas of single-cell chromatin accessibility in the human brain
Authors: Li Yang Eric , Preissl Sebastian , Miller Michael , Johnson Nicholas D. , Wang Zihan , Jiao Henry , Zhu Chenxu , Wang Zhaoning , Xie Yang , Poirion Olivier , Kern Colin , Pinto-Duarte Antonio , Tian Wei , Siletti Kimberly , Emerson Nora , Osteen Julia , Lucero Jacinta , Lin Lin , Yang Qian , Zhu Quan , Espinoza Sarah , Yanny Anna Marie , Nyhus Julie , Dee Nick , Casper Tamara , Shapovalova Nadiya , Hirschstein Daniel , Hodge Rebecca D. , Linnarsson Sten , Bakken Trygve , Levi Boaz , Keene C. Dirk , Shang Jingbo , Lein Ed S. , Wang Allen , Behrens M. Margarita , Ecker Joseph R. , Ren Bing
Published: November 2022

The human brain contains an extraordinarily diverse set of neuronal and glial cell types. Recent advances in single cell transcriptomics have begun to delineate the cellular heterogeneity in different brain regions, but the transcriptional regulatory programs responsible for the identity and function of each brain cell type remain to be defined. Here, we carried out single nucleus ATAC-seq analysis to probe the open chromatin landscape from over 1.1 million cells in 42 brain regions of three neurotypical adult donors. Integrative analysis of the resulting data identified 107 distinct cell types and revealed the cell-type-specific usage of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly 1/3 of them displayed sequence conservation as well as chromatin accessibility in the mouse brain. On the other hand, nearly 40% cCREs were human specific, with chromatin accessibility associated with species-restricted gene expression. Interestingly, these human specific cCREs were enriched for distinct families of retrotransposable elements, which displayed cell-type-specific chromatin accessibility. We uncovered strong associations between specific brain cell types and neuropsychiatric disorders. We futher developed deep learning models to predict regulatory function of non-coding disease risk variants.
A Biologically Plausible Spiking Neural Network for Decoding Kinematics in the Hippocampus and Premotor Cortex
Authors: Taeckens Elijah , Dong Ryan , Shah Sahil
Published: November 2022

This work presents a spiking neural network for predicting kinematics from neural data towards accurate and energy-efficient brain machine interface. A brain machine interface is a technological system that interprets neural signals to allow motor impaired patients to control prosthetic devices. Spiking neural networks have the potential to improve brain machine interface technology due to their low power cost and close similarity to biological neural structures. The SNN in this study uses the leaky integrate-and-fire model to simulate the behavior of neurons, and learns using a local learning method that uses surrogate gradient to learn the parameters of the network. The network implements a novel continuous time output encoding scheme that allows for regression-based learning. The SNN is trained and tested offline on neural and kinematic data recorded from the premotor cortex of a primate and the hippocampus of a rat. The model is evaluated by finding the correlation between the predicted kinematic data and true kinematic data, and achieves peak Pearson Correlation Coefficients of 0.77 for the premotor cortex recordings and 0.80 for the hippocampus recordings. The accuracy of the model is benchmarked against a Kalman filter decoder and a LSTM network, as well as a spiking neural network trained with backpropagation to compare the effects of local learning.
Adjuvant effects of multifunctional transcription factor and BCG target YB-1: exogenous YB-1 enhances specific antibody productionin vivoand protects mice against lethalE. colichallenge
Authors: Shepelyakovskaya Anna O. , Alekseeva Ludmila , Meshcheryakova Elena A. , Boziev Khanafiy , Tsitrina Alexandra , Ivanov Vadim T. , Brovko Fedor , Kotelevtsev Yuri , Lathe Richard , Laman Alexander G.
Published: November 2022

There is growing interest in the beneficial effects of immune system boosting through the administration of adjuvants, not only in acute infections such as COVID but also in chronic degenerative disorders that are potentially associated with infection. The best-known immunopotentiators are Freund’s complete adjuvant (FCA) and its relative Bacille Calmete–Guérin (BCG), both based onMycobacteriumspecies. The key pathogen-associated molecular patterns (PAMPs) in both FCA and BCG are muramyl dipeptides (MDPs and glucosaminyl-MDP, GMDP). We previously identified the evolutionarily conserved protein Y-box factor YB-1/YBX1 as a primary target for MDP/GMDP. Unlike other host receptors for PAMPs, YB-1 is a diffusible molecule, and we therefore explored whetherin vivoadministration of YB-1, rather than its PAMP ligands, might enhance the immune response to a bacterial antigen and/or influence survival in the face of bacterial infection. We report that mice receiving YB-1 plus GMDPin vivomount a significantly increased B cell response versus GMDP alone against a test antigen (Yersinia pestisV antigen), and that YB-1 administration alone significantly promotes survival in the face of lethal bacterial (Escherichia coli) challengein vivo. Independent confirmation is warranted because recombinant YB-1 and its ligands could hold great promise both as adjuvants and as therapeutics.
Longitudinal map of transcriptome changes in the Lyme pathogenBorrelia burgdorferiduring tick-borne transmission
Authors: Sapiro Anne L. , Hayes Beth M. , Volk Regan F. , Zhang Jenny Y. , Brooks Diane M. , Martyn Calla , Radkov Atanas , Zhao Ziyi , Kinnersley Margie , Secor Patrick R. , Zaro Balyn W. , Chou Seemay
Published: November 2022

Borrelia burgdorferi(Bb), the causative agent of Lyme disease, adapts to vastly different environments as it cycles between tick vector and vertebrate host. During a tick bloodmeal,Bbalters its gene expression to prepare for vertebrate infection; however, the full range of transcriptional changes that occur over several days inside of the tick are technically challenging to capture. We developed an experimental approach to enrichBbcells to longitudinally define their global transcriptomic landscape inside nymphalIxodes scapularisticks during a transmitting bloodmeal. We identified 192Bbgenes that substantially change expression over the course of the bloodmeal from one to four days after host attachment. The majority of upregulated genes encode proteins found at the cell envelope or proteins of unknown function, including 45 outer surface lipoproteins embedded in the unusual protein-rich coat ofBb. As these proteins may facilitateBbinteractions with the host, we utilized mass spectrometry to identify candidate tick proteins that physically associate withBb. TheBbenrichment methodology along with theex vivo Bbtranscriptomes and candidate tick interacting proteins presented here provide a resource to facilitate investigations into key determinants ofBbpriming and transmission during the tick stage of its unique transmission cycle.
Modular, cement-free, customized headpost and connector-chamber implants for macaques
Authors: Psarou Eleni , Vezoli Julien , Schölvinck Marieke L. , Ferracci Pierre-Antoine , Zhang Yufeng , Grothe Iris , Roese Rasmus , Fries Pascal
Published: November 2022

Background

Neurophysiological studies with awake macaques typically require chronic cranial implants. Headpost and connector-chamber implants are used to allow head stabilization and to house connectors of chronically implanted electrodes, respectively.

New Method

We present long- lasting, modular, cement-free headpost implants made of titanium that consist of two pieces: a baseplate and a top part. The baseplate is implanted first, covered by muscle and skin and allowed to heal and osseointegrate for several weeks to months. The percutaneous part is added in a second, brief surgery. Using a punch tool, a perfectly round skin cut is achieved providing a tight fit around the implant without any sutures. We describe the design, planning and production of manually bent and CNC-milled baseplates. We also developed a remote headposting technique that increases handling safety. Finally, we present a modular, footless connector chamber that is implanted in a similar two- step approach and achieves a minimized footprint on the skull.

Results

Twelve adult male macaques were successfully implanted with a headpost and one with the connector chamber. To date, we report no implant failure, great headpost stability and implant condition, in four cases even more than 9 years post-implantation.

Comparison with Existing Methods

The methods presented here build on several related previous methods and provide additional refinements to further increase implant longevity and handling safety.

Conclusions

Optimized implants can remain stable and healthy for at least 9 years and thereby exceed the typical experiment durations. This minimizes implant-related complications and corrective surgeries and thereby significantly improves animal welfare.

Highlights

Long-lasting titanium implants for non-human primates

Refined implantation techniques that reduce post-operative complications

Minimized, footless connector chamber to house connectors of chronic arrays

Twelve adult male macaques were implanted with long-lasting headpost implants

Headpost implants so far without failure and with longevity up to > 9 years
Unsupervised Voxel-based Segmentation reveals a Landscape of Bacterial Ribosome Large Subunit Early Assembly
Authors: Sheng Kai , Li Ning , Rabuck-Gibbons Jessica N. , Dong Xiyu , Lyumkis Dmitry , Williamson James R.
Published: November 2022

Ribosome biogenesis is a complex but efficient process in rapidly growing bacteria, where assemble a functional 70S ribosome takes ~ 2 min, involving participation of 3 rRNAs, 50 r-proteins and dozens of assembly factors. In vitro reconstitution using different subsets of large subunit (50S, LSU) proteins with rRNAs, pioneered by Nierhaus lab, resulted in the Nierhaus assembly map, embodying the cooperativity and dependency for binding of LSU r-proteins to 23S rRNA. Critically absent from the Nierhaus map is the underlying folding of the rRNA that creates the binding sites for the r-proteins. In addition, the relationship of the observed cooperativity in vitro to the co-transcriptional assembly in cells remains to be determined.

Pre-50S intermediates accumulate at low temperature in ΔdeaD, a DEAD-box helicase implicated in 50S assembly. We solved 21 pre-50S density maps from intermediate-containing fractions using cryo-EM. In the newly solved maps, we discovered the earliest intermediate ever reported, consisting of domain I at the 5’-end of 23S rRNA. To probe the mechanism behind the maps during assembly, we developed a novel density map segmentation and dependency analysis method. Ten cooperative assembly blocks were identified from segmentation of the maps, and these were organized into a block dependency map. This is the first time the dependencies on folding of rRNA helices and ribosomal protein binding could be integrated into a complete assembly map. In addition, we showed how the exit tunnel is folded on the solvent side, serving as a scaffold for 50S maturation. Using this new segmentation analysis method, we revisited previously reported bL17-depletion and ΔsrmB datasets. Most remarkably, the other two datasets are also consistent with the block dependency, implying a unified early assembly pathway and flexible maturation landscape in early 50S biogenesis.
Heterozygous Inversion Breakpoints Suppress Meiotic Crossovers by Altering Recombination Repair Outcomes
Authors: Li Haosheng , Berent Erica , Hadjipanteli Savannah , Galey Miranda , Miller Danny E. , Crown Nicole
Published: November 2022

Heterozygous chromosome inversions suppress meiotic crossover (CO) formation within an inversion, potentially because they lead to gross chromosome rearrangements that produce inviable gametes. Interestingly, COs are also severely reduced in regions nearby but outside of inversion breakpoints even though COs in these regions do not result in rearrangements. Our mechanistic understanding of why COs are suppressed outside of inversion breakpoints is limited by a lack of data on the frequency of noncrossover gene conversions (NCOGCs) in these regions. To address this critical gap, we mapped the location and frequency of rare CO and NCOGC events that occurred outside of thedl-49 chrXinversion inD. melanogaster. We created full-sibling wildtype and inversion stocks and recovered COs and NCOGCs in the syntenic regions of both stocks, allowing us to directly compare rates and distributions of recombination events. We show that COs are completely suppressed within 500 kb of inversion breakpoints, are severely reduced within 2 Mb of an inversion breakpoint, and increase above wildtype levels 2-4 Mb from the breakpoint. We find that NCOGCs occur evenly throughout the chromosome and, importantly, occur at wildtype levels near inversion breakpoints. We propose a model in which COs are suppressed by inversion breakpoints in a distance-dependent manner through mechanisms that influence DNA double-strand break repair outcome but not double-strand break location or frequency. We suggest that subtle changes in the synaptonemal complex and chromosome pairing might lead to unstable interhomolog interactions during recombination that permits NCOGC formation but not CO formation.
A Dynamic Bayesian Actor Model explains Endpoint Variability in Homing Tasks
Authors: Kessler Fabian , Frankenstein Julia , Rothkopf Constantin A
Published: November 2022

Goal-directed navigation requires integrating information from a variety of internal and external spatial cues, representing them internally, planning, and executing motor actions sequentially. However, a comprehensive computational account of how these processes interact in an ambiguous, uncertain, and noisy environment giving rise to biases and variability observed in navigation behavior is currently unavailable. In this paper, we introduce an optimal control under uncertainty model, which provides a computational-level explanation of how landmarks and path integration interact and are combined to reduce variability in navigation. We apply our model to trajectory and end-point data from three previously published studies that employ a variant of the triangle completion task with landmarks. Contrary to observer models, which attribute human endpoint variability to perceptual cue combination processes only, this dynamic Bayesian actor model provides a unifying account of a wide range of phenomena found in this task by considering variability in perception, action, and internal representations jointly. Taken together, these findings have wide-ranging implications for the analysis and interpretation of human navigation behavior, including resolution of seemingly contradictory results on cue integration in navigation.
Reduced cholecystokinin-expressing interneuron input contributes to disinhibition of the hippocampal CA2 region in a mouse model of temporal lobe epilepsy
Authors: Whitebirch Alexander C. , Barnett Anastasia , Santoro Bina , Scharfman Helen E. , Siegelbaum Steven A.
Published: November 2022

A significant proportion of temporal lobe epilepsy (TLE) patients experience drug-resistant seizures associated with mesial temporal sclerosis, in which there is extensive cell loss in the hippocampal CA1 and CA3 subfields, with a relative sparing of dentate gyrus granule cells and the CA2 pyramidal neurons. A role for CA2 in seizure generation was suggested based on findings of a reduction in synaptic inhibition (Williamson & Spencer, 1994) and the presence of interictal- like spike activity in resected hippocampal tissue from TLE patients (Wittner et al., 2009). We recently found that in the pilocarpine-inducedstatus epilepticusmouse model of TLE there was an increase in CA2 intrinsic excitability associated with a loss of CA2 synaptic inhibition. Furthermore, chemogenetic silencing of CA2 significantly reduced seizure frequency, consistent with a role of CA2 in promoting seizure generation and/or propagation (Whitebirch et al., 2022). In the present study we explored the basis of this inhibitory deficit using immunohistochemical and electrophysiological approaches. We report a widespread decrease in the density of pro- cholecystokinin-immunopositive interneurons and a functional impairment of cholecystokinin- expressing interneuron-mediated inhibition of CA2 pyramidal neurons. We also found a decrease in the density of CA2 parvalbumin-immunopositive interneurons and disruption to the pyramidal neuron-associated perisomatic perineuronal net in the CA2 subfield. These data reveal a set of pathological alterations that may disrupt inhibition of CA2 pyramidal neurons and their downstream targets in epileptic mice.
Rickettsia parkeriHijacks Tick Hemocytes to Manipulate Cellular and Humoral Transcriptional Responses
Authors: Adegoke Abdulsalam , Ribeiro Jose M.C. , Brown Sidney , Smith Ryan C. , Karim Shahid
Published: November 2022

Blood-feeding arthropods rely on robust cellular and humoral immunity to control pathogen invasion and replication. Tick hemocytes produce factors that can facilitate or suppress microbial infection and pathogenesis. Despite the importance of hemocytes in regulating microbial infection, understanding of their basic biology and molecular mechanisms remains limited. Here we combined histomorphology and functional analysis to identify five distinct phagocytic and non-phagocytic hemocyte populations circulating within the Gulf Coast tickAmblyomma maculatum. Depletion of phagocytic hemocytes using clodronate liposomes revealed their function in eliminating bacterial infection. We provide the first direct evidence that an intracellular tick-borne pathogen,Rickettsia parkeri, infects phagocytic hemocytes inAm. maculatumto modify tick cellular immune responses. A massive RNA-seq dataset generated from hemocytes isolated from uninfected andR. parkeri-infected partially blood-fed ticks generated ∼40,000 differentially regulated transcripts, >11,000 of which were immune genes. Silencing two differentially regulated phagocytic immune marker genes (nimrod B2andeater) significantly reduced hemocyte phagocytosis. Together, these findings represent a significant step forward in understanding how hemocytes regulate microbial homeostasis and vector competence.
High-resolution small RNAs landscape provides insights into alkane adaptation in the marine alkane-degraderAlcanivorax dieseloleiB-5
Authors: Wei Guangshan , Li Sujie , Ye Sida , Wang Zining , Zarringhalam Kourosh , He Jianguo , Wang Wanpeng , Shao Zongze
Published: November 2022

Alkanes are widespread in the ocean, andAlcanivoraxis one of the most ubiquitous alkane-degrading bacteria in the marine ecosystem. Small RNAs (sRNAs) are usually at the heart of regulatory pathways, but sRNA-mediated alkane metabolic adaptability still remains largely unknown due to the difficulties of identification. Here, differential RNA sequencing (dRNA-seq) modified with a size selection (∼50-nt to 500-nt) strategy was used to generate high-resolution sRNAs profiling in the model speciesAlcanivorax dieseloleiB-5 under alkane (n-hexadecane) and non-alkane (acetate) conditions. As a result, we identified 549 sRNA candidates at single-nucleotide resolution of 5’-ends, with 63.4% of transcription start sites (TSSs) and 36.6% of processing sites (PSSs). These sRNAs originated from almost any locations in the genome, regardless of intragenic (65.8%), antisense (20.6%) and intergenic (6.2%) regions, and RNase E may function in the maturation of sRNAs. Most sRNAs locally distribute across the 15 reference genomes ofAlcanivorax, and only 7.5% of sRNAs are broadly conserved in this genus. Expression responses to alkane of several core conserved sRNAs, including 6S RNA, M1 RNA and tmRNA, indicate that they may participate in alkane metabolisms and result in more actively global transcription, RNA processing and stresses mitigation. Two novel CsrA-related sRNAs are identified, which may be involved in the translational activation of alkane metabolism-related genes by sequestering the global repressor CsrA. The relationships of sRNAs with characterized genes of the alkane sensing (ompS), chemotaxis (mcp, cheR, cheW2), transporting (ompT1, ompT2, ompT3) and hydroxylation (alkB1, alkB2, almA) were created based on the genome-wide targets prediction. Overall, the sRNAs landscape lays the ground for uncovering cryptic regulations in the critical marine bacterium, among which both core and species-specific sRNAs are implicated in the alkane adaptive metabolisms.
Retinoic acid signaling modulates smooth muscle cell phenotypic switching in atherosclerosis through epigenetic regulation of gene expression
Authors: Pan Huize , Ho Sebastian E. , Xue Chenyi , Cui Jian , Ross Leila S. , Reilly Muredach P.
Published: November 2022

BACKGROUND

Smooth muscle cells (SMCs) substantially contribute to the development of atherosclerosis through a process called “phenotypic switching.” Our previous work identified an SMC-derived intermediate cell type, termed “SEM” cells, which plays a crucial role in SMC transition to other cell types and in lesion development. Activation of retinoic acid (RA) signaling by all-trans retinoic acid (ATRA) attenuates atherosclerosis in mice coincident with suppression of SEM cell formation. However, the effect of RA signaling on advanced disease and the underlying molecular mechanisms by which RA modulates SMC transition to SEM cells are largely unknown.

METHODS

We applied SMC lineage tracing atheroprone mice and biochemistry and cell and molecular biology techniques (e.g., RNA sequencing, quantitative reverse transcription PCR, co-immunoprecipitation, and chromatin immunoprecipitation-quantitative PCR) to reveal the regulatory mechanisms of RA signaling in SMC transition to SEM cells.

RESULTS

Activation of RA signaling with ATRA in established atherosclerosis significantly reduced SEM cells and lesion size while increasing fibrous cap thickness. Mechanistically, retinoic acid receptor alpha (RARα) directly targets the promoters ofLy6aandLy6c1in mouse SMCs, and activation of RA signaling recruits EZH2 to the regulatory elements triggering local H3K27me3. Distinct from a molecular model that reported for RA recruitment of HDAC1 during embryogenesis, RARα/EZH2 complex recruits SIRT1 and SIRT6, rather than classical HDACs, to the regulatory regions of key SEM cell marker genes. This subsequently reduces multiple acetylated histone modifications (e.g., H3K27ac, H3K4ac, H3K9ac, H3K14ac, H3K56ac) with recruitment of the transcription corepressor, NCOR1, to repress downstream SEM cell marker genes.

CONCLUSIONS

Our findings provide novel mechanistic insights into RA modulating SMC phenotypic switching in atherosclerosis, suggesting molecular targets for preventive and therapeutic interventions for atherosclerosis and its clinical complications.
Correcting for volunteer bias in GWAS uncovers novel genetic variants and increases heritability estimates
Authors: van Alten Sjoerd , Domingue Benjamin W. , Faul Jessica , Galama Titus , Marees Andries T.
Published: November 2022

The implications of selection bias due to volunteering (volunteer bias) for genetic association studies are poorly understood. Because of its large sample size and extensive phenotyping, the UK Biobank (UKB) is included in almost all large genomewide association studies (GWAS) to date, as it is one of the largest cohorts. Yet, it is known to be highly selected. We develop inverse probability weighted GWAS (WGWAS) to estimate GWAS summary statistics in the UKB that are corrected for volunteer bias. WGWAS decreases the effective sample size substantially compared to GWAS by an average of 61% (from 337,543 to 130,684) depending on the phenotype. The extent to which volunteer bias affects GWAS associations and downstream results is phenotype-specific. Through WGWAS we find 11 novel genomewide significant loci for type 1 diabetes and 3 for breast cancer. These loci were not identified previously in any prior GWAS. Further, genetic variant’s effect sizes and heritability estimates become more predictive in WGWAS for certain phenotypes (e.g., educational attainment, drinks per week, breast cancer and type 1 diabetes). WGWAS also alters biological annotation relations in gene-set analyses. This suggests that not accounting for volunteer-based selection can result in GWASs that suffer from bias, which in turn may drive spurious associations. GWAS consortia may therefore wish to provide population weights for their data sets or rely more on population-representative samples.
The role of cholesterol metabolism in predicting clinical outcome of patients with severe COVID-19
Authors: Usenko T.S. , Miroshnikova V.V. , Bezrukova A.I. , Basharova K.S. , Landa S.B. , Korobova Z.R. , Liubimova N.E. , Vlasov I.N. , Nikolaev M.A. , Izyumchenko A.D. , Gavrilova E.G. , Shlyk I.V. , Chernitskaya E.L. , Kovalchuk Y.P. , Slominsky P.A. , Totolian A.A. , Polushin Yu.S. , Pchelina S.N.
Published: November 2022

Transcriptomic analysis conducted by us previously revealed upregulation of genes involved in low-density lipoprotein particle receptor (LDLR) activity pathway in lethal COVID-19. Last data suggested the possible role of extracellular vesicles and exomeres in COVID-19 pathogenesis. The aim of the present study was to retrospectively evaluate parameters of cholesterol metabolism as possible predictors of fatal outcome of COVID-19. Blood from 39 patients with severe COVID-19 (the main cohort) were collected at the time of admission to the intensive care unit (ICU) (T1) and 7 days after admission to the ICU (T2). After 30 days patients were divided into two subgroups according to outcome-21 non-survivors and 18 survivors. 28 patients (13 non-survivors and 15 survivors) with severe COVID-19 were included as the replication cohort. The study demonstrated that plasma low-and high-density lipoprotein cholesterol levels (LDL-C and HDL-C) were decreased and CCL20/MIP3ɑ, IL-10, IL-15, IL-27 concentrations were increased in non-survivors compared to controls in T1.STAB1gene expression was higher in non-survivors than in survivors (p=0.017) in T2. The conjoint fraction of exomeres and LDL particles measured by dynamic light scattering (DLS) was decreased in non-survivors com-pared to survivors in both the main and replication cohorts. We first showed that change of exomeres fraction may be critical in fatal outcome of COVID-19.
Experimental testing of a prototype cantilevered liquid-nitrogen-cooled silicon mirror
Authors: Cutler G. , Cocco D. , Bentley B. , Cervantes M. , Chavez P. , Chrzan J. , DiMaggio S. , Hussey R. , Ilmberger J. , Lindsay J. , Lizotte E. , McCombs K. , Morton S. , Paulovits G. , Pearson K. , Redding C. , Smith N. , Tokunaga K. , Zehm D. , DiMasi E. , Padmore H.
Published: November 2022

This report presents testing of a prototype cantilevered liquid-nitrogen-cooled silicon mirror. This mirror was designed to be the first mirror for the new soft X-ray beamlines to be built as part of the Advanced Light Source Upgrade. Test activities focused on fracture, heat transfer, modal response and distortion, and indicated that the mirror functions as intended.
[Li6(C2N2H8)11.5][Fe4Se8]: the first lithium-containing chalcogenidotetraferrate synthesized in solution
Authors: Fuss Friederike , Thiele Günther
Published: November 2022

The octaselenidotetraferrate(II/III) with six Li atoms as counter-ions chelated by ethylenediamine (en, C2H8N2), {[Li6(en)11.5][Fe4Se8]}
n
, was synthesized from Li, FeSe and Se in an ethylenediamine solution at room temperature. Its crystal structure was determined at 100 K and has triclinic (P\overline{1}) symmetry. The [Fe4Se8]6− anions show a connectivity comparable to a distorted tetrahedral cluster structure. Contact distances are given, and central structure features compared to literature known selenidoferrates with the same anion motif.
Crystal structure of racemic 2-[(β-arabinopyranosyl)sulfanyl]-4,6-diphenylpyridine-3-carbonitrile. Corrigendum
Authors: Hammad Sherif F. , Masoud Doaa M. , Elgemeie Galal H. , Jones Peter G.
Published: November 2022

An error in the interpretation of a reference in the paper by Hammad et al. [Acta Cryst. (2018), E74, 853–856] is corrected.
How detritivores, plant traits and time modulate coupling of leaf versus woody litter decomposition rates across species
Authors: Guo Chao , Tuo Bin , Ci Hang , Sai Bi‐Le , Zhang Yu , Yan En‐Rong , Cornelissen Johannes H. C.
Published: November 2022

Plant functional traits are increasingly used to understand ecological relationships and (changing) ecosystem functions. For understanding ecosystem‐level biogeochemistry, we need to understand how (much) traits co‐vary between different plant organs across species and its implications for litter decomposition. However, we do not know how the degree of synchronous variation in decomposition rates between organs across species could be influenced by different keystone invertebrates decomposing different senesced plant organs, especially in warm‐climate forests. Here we asked whether interspecific patterns in wood and leaf decomposition rates and in the spectra of resource economics traits underpinning them, co‐vary across woody species; and how (much) the keystone invertebrate decomposers of the litter of these organs enhance or lower such co‐variation of decomposition rates through time.

We addressed these questions through an 18‐month ‘common‐garden’ decomposition experiment using leaf, twig and branch litter of 41 woody species in two distant subtropical forest sites in east China. We quantified the effects of leaf, twig and branch functional traits and their respective key invertebrates (moth larvae, termites) on the decomposition rates of those organs.

Interspecific variation in wood traits was partly decoupled from that in leaf traits across species, while strong coupling was found between twigs and branches. The co‐variation between leaf and woody organ decomposition rates was altered dynamically through the shifting activities of the key decomposers, which created nonlinear relationships of invertebrate litter consumption as a function of species rankings along the resource economic trait spectra of leaves and branches.

The deviations from coupling of decomposition rates between organs were likely caused by combinations of three mechanisms: (1) (de‐)coupling between organs of other traits, not commonly considered in resource economics spectra (e.g. resins) (2) leaf and wood decomposers having specific diet requirements and (3) temporal patterns of the decomposers' activity.

Synthesis. Our study highlights the importance of considering the different ways by which invertebrate detritivores drive decomposition processes through time. Under the ongoing biodiversity decline, future research would benefit from a better understanding of the role of the dynamic interactions between detritivore activities and plant functional traits on the carbon turnover in ecosystems.
“Because we all love K‐Pop”: How young adults reshape symbolic boundaries in Paris, Manchester, and Philadelphia
Authors: Cicchelli Vincenzo , Octobre Sylvie , Katz‐Gerro Tally , Yodovich Neta , Handy Femida , Ruiz Stefanie
Published: November 2022

In this paper, we examine how young adults who are consumers of K‐Pop in three culturally diverse cities (Paris, Philadelphia, and Manchester) reshape their symbolic boundaries to face social challenges. Analyzing data from 132 interviews, we show how young adults mainly confront social exclusion in Paris, fight racism in Philadelphia and deal with xenophobia in Manchester. Although K‐Pop adds to the dynamics of exclusion due to being perceived as culturally foreign, our participants use K‐Pop as a resource to reshape social boundaries towards new forms of inclusion. They do this by relying on K‐Pop as a cultural product that promotes inclusion, and on their affiliation with the K‐Pop community on a local and global level.
Composition, formation mechanism, and removal method of off‐odor in soymilk products
Authors: Ji Guo‐Zhi , Li Xiao‐Min , Dong Yang , Shi Yu‐Dong
Published: November 2022

Soybean is a protein‐rich material for plant‐based products, and its application in soymilk products is limited due to its off‐odor such as beany. In order to explore a solution to address this issue, composition, formation mechanism, and removal methods of the off‐odor produced in the processing of soymilk products are comprehensively described in this paper. The main off‐odor compounds in soymilk products include hexanal, hexanol, 1‐octene‐3‐ol, (E,E)‐2, 4‐decadienal, 2‐pentylfuran, (E,E)‐2,4‐nonadienal, (E)‐2‐nonenal, (E) ‐2‐hexenal, and so on. These odor compounds are mainly produced by the enzymatic and nonenzymatic oxidation of unsaturated fatty acids. At present, physical methods are used to remove off‐odor in the industrial production of soymilk products, of which heat treatment is still the most effective. With the development of no beany soybean breeding technology, the combination of multiple methods will become a technical trend for removing off‐odor. Some new research directions are also explored about removal methods, which can provide a theoretical reference for the production and technical research of soymilk products.
Long‐term fasting glucose variability and risk of cancer in patients with type 2 diabetes mellitus: A retrospective population‐based cohort study in Shanghai
Authors: Cui Xiao‐rui , Li Jun , Yang Ya‐ting , Wu Jing‐yi , Xu Hui‐lin , Yu Yong‐fu , Qin Guo‐you
Published: November 2022

Backgrounds

Fasting blood glucose (FBG) variability may make an impact on adverse events in patients with diabetes mellitus. However, the association between long‐term changes in FBG and cancer remains unclear. We aimed to investigate this association in a large‐scale longitudinal study.

Methods

Data were collected from 46 761 patients with type 2 diabetes mellitus aged 20–80 years who participated in the Diabetes Standardized Management Program in Shanghai, China. We adopted four indicators, including standard deviation (SD), coefficient of variation (CV), variation independent of the mean (VIM), and average real variability (ARV) to describe FBG variability. Adjusted multivariable Cox regression analyses and restricted cubic splines were used to investigate the association between long‐term FBG variability and cancer risk. We also determined the interactive effect of FBG variability with hypertension and FBG‐mean with hypertension on cancer risk, respectively.

Results

In this study, we confirmed 2218 cancer cases (51.1% male) over a median follow‐up of 2.86 years. In the multivariable‐adjusted models, participants in the highest quartile of FBG variability had an increased risk of cancer compared with those in the lowest quartile. The nonlinear association was found when using FBG‐VIM, FBG‐ARV, and FBG‐SD in restricted cubic spline plots. There was a significant interaction effect of FBG variability with hypertension on cancer, whereas the effect of FBG‐mean with hypertension did not attain significance.

Conclusions

Our retrospective cohort study demonstrated a positive association between the long‐term changes in FBG and cancer risk in patients with type 2 diabetes mellitus. FBG variability may independently predict cancer incidence.
Combined modality therapy for patients with esophageal squamous cell carcinoma: Radiation dose and survival analyses
Authors: Shueng Pei‐Wei , Huang Chun‐Chieh , Liu Yu‐Ming , Wu Yuan‐Hong , Huang Pin‐I , Yen Sang‐Hue , Lin Kuan‐Heng , Hsu Chen‐Xiong
Published: November 2022

Background

We aimed to analyze the radiation dose and compare survival among combined modality therapy using modern radiation techniques for patients with esophageal squamous cell carcinoma (ESCC).

Methods

This retrospective study included patients with clinically staged T1‐4N0‐3M0 ESCC from 2014 to 2018. Patients who received combined modality therapies with curative intent were enrolled. The overall survival (OS) rates among combined modality therapy were compared. The clinical variables and impacts of radiation dose on survival were analyzed by the Kaplan–Meier method and Cox regression model.

Results

Of the 259 patients, 141 (54.4%) received definitive concurrent chemoradiotherapy (DCCRT); 67 (25.9%) underwent neoadjuvant chemoradiotherapy followed by surgery (NCRT+S); 51 (19.7%) obtained surgery followed by adjuvant chemoradiotherapy (S+ACRT). Two‐year OS rates of the DCCRT, NCRT+S and S+ACRT group were 48.9, 61.5 and 51.2%. In the subgroup analysis of DCCRT group, the 2‐year OS of patients receiving radiation dose 55–60 Gy was 57.1%. Multivariate analyses showed that clinical stage (p = 0.004), DCCRT with 55–60 Gy (p = 0.043) and NCRT+S with pathological complete response (pCR) (p = 0.014) were significant prognostic factors for better OS. The radiation dose–survival curve demonstrated a highly positive correlation between higher radiation dose and better survival.

Conclusion

Our results suggest that NCRT+S can provide a favorable survival for patients with ESCC, especially in patients who achieved pCR. The optimal radiation dose might be 55–60 Gy for patients receiving DCCRT via modern radiation techniques. Further randomized clinical studies are required to confirm the survival benefits between NCRT+S and DCCRT with escalated dose.
Peripheral nerve‐blocks and associations with length of stay and readmissions in fast‐track total hip and knee arthroplasty
Authors: Jørgensen Christoffer C. , Petersen Pelle B. , Daugberg Louise O. , Jakobsen Thomas , Gromov Kirill , Varnum Claus , Andersen Mikkel R. , Palm Henrik , Kehlet Henrik
Published: November 2022

Background

Peripheral nerve blocks (PNB) have recently been recommended in total hip (THA) and knee (TKA) arthroplasty as they may reduce pain, morphine consumption, length of stay (LOS) and complications. However, whether PNBs are associated with early discharge within an enhanced recovery protocol including multimodal analgesia is uncertain.

Methods

An observational multicenter study from January to August 2017 in six Danish Arthroplasty Centers with established fast‐track protocols. Prospective recording of preoperative characteristics and information on PNB, LOS and readmissions through the Danish National Patient Registry and medical records. Multiple logistic regression was used to investigate associations between PNB and a LOS >1 day, LOS >4 days, and 30‐days readmissions. We also reported on mobilization, pain, opioid and fall‐related complications leading to LOS >4 days or readmissions.

Results

A total of 2027 (58.6%) THA and 1432 (41.4%) TKAs with a median LOS of 1 day (IQR 1–2) and 5.3% (CI:4.6–6.1) 30‐days readmission rate were identified. PNB was used in 40.7% (CI:38.2–43.3) of TKA and 2.7% (CI:2.0–3.5) of THA, but with considerable interdepartmental variation (0.0–89.0% for TKA). There was no association between PNB and LOS >1 day (OR:1.19 CI:0.82–1.72; p = .354), LOS >4 days (OR:1.4 CI:0.68–2.89; p = .359) or 30‐days readmissions (OR:1.02 CI:0.63–1.65; p = .935) in TKA. Logistic regression in THA was not possible due to limited use of PNB. In TKA there were 12 (2.1% CI:1.2–3.6) with and 1 (0.1% CI:0.02–0.7) without a PNB, who had mobilization, pain or opioid‐related complications, and 5 (0.9% CI:0.4–2.0) versus 4 (0.5% CI:0.2–1.2) who fell. Correspondingly, 2 (3.7% CI:1.0–12.6) and 11 (0.6% CI:0.3–1.0) of THA patients had these complications, while 0 (0.0% CI:0.0–6.6) and 17 (0.8% CI:0.5–1.3) fell.

Conclusion

Routine use of peripheral nerve blocks was not associated with early discharge or 30‐days readmissions in fast‐track THA and TKA. Future studies should focus on benefits of PNB in high‐risk patients.
Outcome of intentional replantation of endodontically treated teeth with periapical pathosis: A systematic review and meta‐analysis
Authors: Javed Faizan , Zafar Kamil , Khan Farhan R.
Published: November 2022

The purpose of the present review was to examine success, survival and failure following intentional replantation of endodontically treated teeth with existing periapical pathosis and to determine the factors that might affect the outcome of replantation. Clinical trials, longitudinal studies, case series with >10 cases and at least 1‐year follow‐up were included. The average rate of success following intentional replantation was 77.23%. Meta‐analysis revealed the mean weighted survival to be 85.9% (95% CI: 79.6–91.2) Common complications include inflammatory root resorption (0%–27%) and ankylosis (0%–25%). Variables influencing successful outcome include extra alveolar dry time <15 min; root‐end resection (2–3 mm) and cavity preparation (3 mm); manipulation of the tooth using the crown only; and use of an appropriate storage media. The review concludes that intentional replantation is a viable treatment option with acceptable survival rates for endodontically treated teeth with periapical pathosis.
Preoperative serum CA125 level and age at diagnosis: An effective prognosis prediction tool for patients with early‐stage endometrial cancer
Authors: Sun Shuai , Wei Lichun , Zou Lijuan , Wang Tiejun , Liu Zi , He Jianli , Sun Xiaoge , Zhong Wei , Zhao Fengju , Li Xiaomei , Li Sha , Zhu Hong , Ma Zhanshu , Wang Wenhui , Zhang Fuquan , Hou Xiaorong , Hu Ke
Published: November 2022

Objective

To investigate the combined predictive value of the preoperative serum cancer antigen 125 (CA125) level and age at diagnosis among patients with early‐stage endometrial cancer (EC) after initial treatment.

Methods

We retrospectively analyzed data from patients with early‐stage EC from 1999 to 2015 in multiple institutions in China. All 447 patients received postoperative adjuvant radiotherapy for FIGO 2009 stage I and II EC with complete data on preoperative serum CA125 levels. All patients were divided into four groups according to the ESMO‐ESGO‐ESTRO risk classification. The predictive probability of 5‐year overall survival (OS) and the sensitivity and specificity of CA125 and age were calculated.

Results

The median follow‐up time was 59 months (3–201 months). The 5‐year OS and disease‐free survival rates were 94.4% and 89.1%. Multivariate analysis showed that the preoperative CA125 level and age at diagnosis were independent prognostic factors for 5‐year OS. The area under the curve for CA125 combined with age at diagnosis for 5‐year OS was .692, and the corresponding sensitivity and specificity were 68.2% and 68.2% (p < .002), which were significantly better than the corresponding values for CA125 or age alone. After all 447 patients were divided into four groups according to CA125 combined with age, the 5‐year OS of the elderly and higher CA125 group was only 73.7%.

Conclusions

Although preoperative CA125 had limited sensitivity in predicting the prognosis for early‐stage EC after initial treatment, it remains a useful serum marker for risk assessment of early‐stage EC. Combining CA125 with age may increase its predictive sensitivity.
Editorial: gluten‐free but not pain‐free in IBS
Authors: Fitzpatrick Jessica A. , Halmos Emma P.
Published: November 2022

LINKED CONTENT

This article is linked to Algera et al papers. To view these articles, visit https://doi.org/10.1111/apt.17239 and https://doi.org/10.1111/apt.17279
Editorial: gluten‐free but not pain‐free in IBS—authors' reply
Authors: Algera Joost P. , Magnusson Maria K. , Öhman Lena , Störsrud Stine , Simrén Magnus , Törnblom Hans
Published: November 2022

LINKED CONTENT

This article is linked to Algera et al papers. To view these articles, visit https://doi.org/10.1111/apt.17239 and https://doi.org/10.1111/apt.17253