bluuebunny/crossref_metadata_2025 huggingface dataset:
A Developmentally Prometastatic Niche to Hepatoblastoma in Neonatal Liver mediated by the Cxcl1/Cxcr2 Axis
Authors: Fan Li , Pan Qingfei , Yang Wentao , Koo Selene C. , Tian Cheng , Li Liyuan , Lu Meifen , Brown Anthony , Ju Bensheng , Easton John , Ranganathan Sarangarajan , Shin Soona , Bondoc Alexander , Yang Jun J. , Yu Jiyang , Zhu Liqin
Published: October 2021

Background and Rationale

Hepatoblastoma (HB) is the most common pediatric liver cancer. Its predominant occurrence in very young children led us to investigating whether the neonatal liver provides a protumorigenic niche to HB development.

Methods

HB development was compared between orthotopic transplantation models established in postnatal day 5 and 60 mice (P5Tx and P60Tx models). Single-cell RNA-sequencing was performed using tumor and liver tissues from both models and the top candidate cell types and genes identified are investigated for their roles in HB cell growth, migration, and survival.

Results

We found that various HB cell lines including HepG2 cells were consistently and considerably more tumorigenic and metastatic in the P5Tx model than in the P60Tx models. Sc-RNAseq of the P5Tx and P60Tx HepG2 models revealed that the P5Tx tumor was more hypoxic and had a larger number of activated hepatic stellate cells (aHSCs) in the tumor-surrounding liver which express significantly higher levels of Cxcl1 than those from the P60Tx model. We found these differences were developmentally present in normal P5 and P60 liver. We showed that the Cxcl1/Cxcr2 axis mediated HB cell migration and was critical to HB cell survival under hypoxia. Treating HepG2 P60Tx model with recombinant CXCL1 protein induced intrahepatic and pulmonary metastasis and CXCR2 knockout in HepG2 cells abolished their metastatic potential in the P5Tx model. Lastly, we showed that in metastatic HB patient tumors there was a similar larger population of aHSCs in the tumor-surrounding liver than in localized tumors, and tumor hypoxia was uniquely associated with HB patient prognosis among pediatric cancers.

Conclusion

We demonstrated that the neonatal liver provides a prometastatic niche to HB development via the Cxcl1/Cxcr2 axis.
Environmental DNA analysis needs local reference data to inform taxonomy-based conservation policy – A case study from Aotearoa / New Zealand
Authors: Czechowski Paul , de Lange Michel , Heldsinger Michael , Rayment Will , Hepburn Christopher , Ladds Monique , Knapp Michael
Published: October 2021

Effective management of biodiversity requires regular surveillance of multiple species. Analysis of environmental DNA by metabarcoding (eDNA) holds promise to achieve this relatively easily. However, taxonomic inquiries into eDNA data need suitable molecular reference data, which are often lacking. We evaluate the impact of this reference data void in a case study of fish diversity in the remote fiords of New Zealand. We compared eDNA-derived species identifications against Baited Remote Underwater Video (BRUV) data collected at the same time and locations as the eDNA data. Furthermore, we cross referenced both eDNA and BRUV data against species lists for the same region obtained from literature surveys and the Ocean Biodiversity Information System (OBIS). From all four data sources, we obtained a total of 116 species records (106 ray-finned fishes, 10 cartilaginous fishes; 59 from literature, 44 from eDNA, 25 from BRUV, 25 from OBIS). Concordance of taxonomies between the data sources dissolved with lowering taxonomic levels, most decisively so for eDNA data. BRUV agreed with local biodiversity information much better and fared better in detecting regional biodiversity dissimilarities. We provide evidence that eDNA metabarcoding will remain a powerful but impaired tool for species-level biodiversity management without locally generated reference data.
Light-independent regulation of algal photoprotection by CO2availability
Authors: Ruiz-Sola M. Águila , Flori Serena , Yuan Yizhong , Villain Gaelle , Sanz-Luque Emanuel , Redekop Petra , Tokutsu Ryutaro , Kueken Anika , Tsichla Angeliki , Kepesidis Georgios , Allorent Guillaume , Arend Marius , Iacono Fabrizio , Finazzi Giovanni , Hippler Michael , Nikoloski Zoran , Minagawa Jun , Grossman Arthur R. , Petroutsos Dimitris
Published: October 2021

Photosynthetic algae have evolved mechanisms to cope with suboptimal light and CO2conditions. When light energy exceeds CO2fixation capacity,Chlamydomonas reinhardtiiactivates photoprotection, mediated by LHCSR1/3 and PSBS, and the CO2Concentrating Mechanism (CCM). How light and CO2signals converge to regulate these processes remains unclear. Here, we show that excess light activates photoprotection- and CCM-related genes by altering intracellular CO2concentrations and that depletion of CO2drives these responses, even in total darkness. High CO2levels, derived from respiration or impaired photosynthetic fixation, repressLHCSR3/CCM genes while stabilizing the LHCSR1 protein. Finally, we show that the CCM regulator CIA5 also regulates photoprotection, controllingLHCSR3andPSBStranscript accumulation while inhibiting LHCSR1 protein accumulation. This work has allowed us to dissect the effect of CO2and light on CCM and photoprotection, demonstrating that light often indirectly affects these processes by impacting intracellular CO2levels.
Piezo activity levels need to be tightly regulated to maintain normal morphology and function in pericardial nephrocytes
Authors: Schulz Kristina , Hazelton-Cavill Paris , Alornyo Karl K. , Edenhofer Ilka , Lindenmeyer Maja , Lohr Christian , Huber Tobias B. , Denholm Barry , Koehler Sybille
Published: October 2021

Due to their position on glomerular capillaries, podocytes are continuously counteracting biomechanical filtration forces. Most therapeutic interventions known to generally slow or prevent the progression of chronic kidney disease appear to lower these biomechanical forces on podocytes, highlighting the critical need to better understand podocyte mechano-signalling pathways. Here we investigated whether the mechanotransducer Piezo is involved in a mechanosensation pathway inDrosophilanephrocytes, the podocyte homologue in the fly.

Loss of function analysis in Piezo depleted nephrocytes reveal a severe morphological and functional phenotype. Further, pharmacological activation of endogenous Piezo with Yoda1 causes a significant increase of intracellular Ca++upon exposure to a mechanical stimulus in nephrocytes, as well as filtration disturbances. Elevated Piezo expression levels also result in a severe nephrocyte phenotype. Interestingly, expression of Piezo which lacks mechanosensitive channel activity, does not result in a severe nephrocyte phenotype, suggesting the observed changes in Piezo wildtype overexpressing cells are caused by the mechanosensitive channel activity. Moreover, blocking Piezo activity using the tarantula toxin GsMTx4 reverses the phenotypes observed in nephrocytes overexpressing Piezo.

Taken together, here we provide evidence that Piezo activity levels need to be tightly regulated to maintain normal pericardial nephrocyte morphology and function.
Molecular basis of ocean acidification sensitivity and adaptation in Mytilus galloprovincialis
Authors: Kapsenberg Lydia , Bitter Mark C. , Miglioli Angelica , Pelejero Carles , Gattuso Jean-Pierre , Dumollard Rémi
Published: October 2021

One challenge in global change biology is to identify the mechanisms underpinning physiological sensitivities to environmental change and to predict their potential to adapt to future conditions. Using ocean acidification as the representative stressor, molecular pathways associated with abnormal larval development of a globally distributed marine mussel are identified. The targeted developmental stage was the trochophore stage, which is, for a few hours, pH sensitive and is the main driver of developmental success. RNA sequencing and in situ RNA hybridization were used to identify processes associated with abnormal development, and DNA sequencing was used to identify which processes evolve when larvae are exposed to low pH for the full duration of their larval stage. Trochophores exposed to low pH exhibited 43 differentially expressed genes. Thirteen genes, none of which have previously been identified in mussel trochophores, including three unknown genes, were expressed in the shell field. Gene annotation and in situ hybridization point to two core processes associated with the response to low pH: development of the trochophore shell field and the cellular stress response. Encompassing both of these processes, five genes demonstrated changes in allele frequency that are indicative of rapid adaptation. Thus, genes underpinning the most pH-sensitive developmental processes also exhibit scope to adapt via genetic variation currently maintained in the mussel population. These results provide evidence that protecting species’ existing genetic diversity is a critical management action to maximize the potential for rapid adaptation under a changing environment.
Activity-dependent endoplasmic reticulum Ca2+ uptake depends on Kv2.1-mediated endoplasmic reticulum/plasma membrane junctions to promote synaptic transmission
Authors: Panzera Lauren C. , Johnson Ben , Cho In Ha , Tamkun Michael M. , Hoppa Michael B.
Published: October 2021

The endoplasmic reticulum (ER) forms a continuous and dynamic network throughout a neuron, extending from dendrites to axon terminals, and axonal ER dysfunction is implicated in several neurological disorders. In addition, tight junctions between the ER and plasma membrane (PM) are formed by several molecules including Kv2 channels, but the cellular functions of many ER-PM junctions remain unknown. Dynamic Ca2+ uptake into the ER during electrical activity plays an essential role in synaptic transmission as failure to allow rapid ER Ca2+ filling during stimulation activates stromal interaction molecule 1 (STIM1) and decreases both presynaptic Ca2+ influx and synaptic vesicle exocytosis. Our experiments demonstrate that Kv2.1 channels are necessary for enabling ER Ca2+ uptake during electrical activity as genetic depletion of Kv2.1 rendered both the somatic and axonal ER unable to accumulate Ca2+ during electrical stimulation. Moreover, our experiments show that the loss of Kv2.1 in the axon impairs synaptic vesicle fusion during stimulation via a mechanism unrelated to modulation of membrane voltage. Thus, our data demonstrate that the non-conducting role of Kv2.1 in forming stable junctions between the ER and PM via ER VAMP-associated protein (VAP) binding couples ER Ca2+ uptake with electrical activity. Our results further suggest that Kv2.1 has a critical function in neuronal cell biology for Ca2+-handling independent of voltage and reveals a novel and critical pathway for maintaining ER lumen Ca2+ levels and efficient neurotransmitter release. Taken together these findings reveal an essential non-classical role for both Kv2.1 and the ER-PM junctions in synaptic transmission.

Significance

The endoplasmic reticulum (ER) extends throughout the neuron as a continuous organelle, and its dysfunction is associated with several neurological disorders. During electrical activity, the ER takes up Ca2+ from the cytosol which has been shown to support synaptic transmission. This close choreography of ER Ca2+ uptake with electrical activity suggests functional coupling of the ER to sources of voltage-gated Ca2+ entry through an unknown mechanism. Here we report a non-conducting role for Kv2.1 through its ER binding domain that is necessary for ER Ca2+ uptake during neuronal activity. Loss of Kv2.1 profoundly disables neurotransmitter release without altering presynaptic voltage suggesting that Kv2.1-mediated signaling hubs play an important neurobiological role in Ca2+ handling and synaptic transmission independent of ion conduction.
DeePVP: Identification and classification of phage virion protein using deep learning
Authors: Fang Zhencheng , Feng Tao , Zhou Hongwei
Published: October 2021

The poor annotation of phage virion protein (PVP) is the bottleneck of many areas of viral research, such as viral phylogenetic analysis, viral host identification and antibacterial drug design. Because of the high diversity of the PVP sequences, the PVP annotation remains a great challenging bioinformatic task. Based on deep learning, we present DeePVP that contains a main module and an extended module. The main module aims to identify the PVPs from non-PVP over a phage genome, while the extended module can further classify the predicted PVP into one of the ten major classes of PVP. Compared with the state-of-the-art tools that can distinguish PVP from non-PVP, DeePVP’s main module performs much better, with an F1-score 9.05% higher in the PVP identification task. Compared with PhANNs, a tool that can further classify the predicted PVP into a specific class, the overall accuracy of DeePVP’s extended module is approximately 3.72% higher in the PVP classification task. Two application cases on the genome of mycobacteriophage PDRPxv and Escherichia phage HP3 show that the predictions of DeePVP are much more reliable and can better reveal the compact PVP-enriched region, which may be conserved during the viral evolution process, over the phage genome.
An Hfq-dependent post-transcriptional mechanism fine tunes RecB expression inEscherichia coli
Authors: Kalita Irina , Iosub Ira Alexandra , McLaren Lorna , Goossens Louise , Granneman Sander , El Karoui Meriem
Published: October 2021

All living organisms have developed strategies to respond to chromosomal damage and preserve genome integrity. One such response is the repair of DNA double-strand breaks (DSBs), one of the most toxic forms of DNA lesions. InEscherichia coli, DSBs are repaired via RecBCD-dependent homologous recombination. RecBCD is essential for accurate chromosome maintenance, but its over-expression can lead to reduced DNA repair ability. This apparent paradox suggests that RecBCD copy numbers may need to be tightly controlled within an optimal range. Using single-molecule fluorescence microscopy, we have established that RecB is present in very low abundance at mRNA and protein levels. RecB transcription shows high fluctuations, yet cell-to-cell protein variability remains remarkably low. Here, we show that the post-transcriptional regulator Hfq binds torecBmRNA and down-regulates RecB protein translationin vivo. Furthermore, specific disruption of the Hfq-binding site leads to more efficient translation ofrecBmRNAs. In addition, we observe a less effective reduction of RecB protein fluctuations in the absence of Hfq. This fine-tuning Hfq-mediated mechanism might have the underlying physiological function of maintaining RecB protein levels within an optimal range.
Breaking the Crosstalk of the Cellular Tumorigenic Network in NSCLC by a Highly Effective Drug Combination
Authors: Gürgen Dennis , Conrad Theresia , Becker Michael , Sebens Susanne , Röcken Christoph , Hoffmann Jens , Langhammer Stefan
Published: October 2021

Non-small cell lung cancer (NSCLC) is commonly diagnosed at advanced stages limiting treatment options. Although, targeted therapy has become integral part of NSCLC treatment therapies often fail to improve patient’s prognosis. Based on previously published criteria for selecting drug combinations for overcoming resistances, NSCLC patient-derived xenograft (PDX) tumors were treated with a low dose combination of cabozantinib, afatinib, plerixafor and etoricoxib.

All PDX tumors treated, including highly therapy-resistant adeno-and squamous cell carcinomas without identifiable driver mutations, were completely suppressed by this drug regimen, leading to an ORR of 81% and a CBR of 100%. The application and safety profile of this low dose therapy regimen was well manageable in the pre-clinical settings.

Overall, this study provides evidence of a relationship between active paracrine signaling pathways of the cellular tumorigenic network, which can be effectively targeted by a low-dose multimodal therapy to overcome therapy resistance and improve prognosis of NSCLC.
Habitat determines convergent evolution of cephalic horns in vipers
Authors: Busschau Theo , Boissinot Stephane
Published: October 2021

Phenotypic convergence of traits in similar environments can provide insights into the evolutionary processes shaping trait evolution. Among squamate reptiles, horn-like cephalic appendages have evolved under various selective pressures, including selection for defence, crypsis or sexual selection. Yet, among snakes, particularly vipers, the functional and evolutionary significance of horns are unknown. We used a comparative phylogenetic approach with habitat and diet data on 263 viper taxa to shed light on the selective pressures underlying horn evolution in vipers. We detected significant correlations with habitat but not diet. The relative positions of horns are ecologically divergent in that supranasal horns are positively correlated with terrestrial forest habitats while supraocular horns are negatively correlated with terrestrial forest habitats and associated with arboreal or sparsely vegetated habitats. Multiple independent origins of supranasal or supraocular horns in similar habitats provide evidence of adaptive convergence. Comparisons with other snake lineages suggest that cephalic appendages may have evolved under selection for crypsis in ambush foraging snakes.
Alternative Cdc20 translational isoforms bypass the spindle assembly checkpoint to control mitotic arrest duration
Authors: Tsang Mary Jane , Cheeseman Iain M.
Published: October 2021

Mitotic chromosome segregation defects activate the Spindle Assembly Checkpoint (SAC), which inhibits the APC/C co-activator Cdc20 to induce a prolonged cell cycle arrest. Once errors are corrected, the SAC is silenced thereby allowing anaphase onset and mitotic exit to proceed. However, in the presence of persistent, unresolvable errors, cells can undergo “mitotic slippage”, exiting mitosis into a tetraploid G1 state and escaping the cell death that results from a prolonged arrest. The molecular logic that allows cells to balance these dueling mitotic arrest and slippage behaviors remains unclear. Here we demonstrate that human cells modulate their mitotic arrest duration through the presence of conserved, alternative Cdc20 translational isoforms. Translation initiation at downstream start sites results in truncated Cdc20 isoforms that are resistant to SAC-mediated inhibition and promote mitotic exit even in the presence of mitotic perturbations. Targeted molecular changes or naturally-occurring mutations in cancer cells that alter the relative Cdc20 isoform levels or its translational regulatory control modulate both mitotic arrest duration and anti-mitotic drug sensitivity. Our work reveals a critical role for the differential translational regulation of Cdc20 in mitotic arrest timing, with important implications for the diagnosis and treatment of human cancers.
ZELDA: a 3D Image Segmentation and Parent-Child relation plugin for microscopy image analysis in napari
Authors: D’Antuono Rocco , Pisignano Giuseppina
Published: October 2021

Bioimage analysis workflows allow the measurement of sample properties such as fluorescence intensity and polarization, cell number, and vesicles distribution, but often require the integration of multiple software tools. Furthermore, it is increasingly appreciated that to overcome the limitations of the 2D-view-based image analysis approaches and to correctly understand and interpret biological processes, a 3D segmentation of microscopy data sets becomes imperative.

Despite the availability of numerous algorithms for the 2D and 3D segmentation, the latter still offers some challenges for the end-users, who often do not have either an extensive knowledge of the existing software or coding skills to link the output of multiple tools. While several commercial packages are available on the market, fewer are the open-source solutions able to execute a complete 3D analysis workflow.

Here we present ZELDA, a new napari plugin that easily integrates the cutting-edge solutions offered by python ecosystem, such as scikit-image for image segmentation, matplotlib for data visualization, and napari multi-dimensional image viewer for 3D rendering. This plugin aims to provide interactive and zero-scripting customizable workflows for cell segmentation, vesicles counting, parent-child relation between objects, signal quantification, and results presentation; all included in the same open-source napari viewer, and “few clicks away”.
Operators’ risk awareness towards operations’ risk assessment: a field study in the motor vehicle field
Authors: Demichela Micaela , Comberti Lorenzo , Baldissone Gabriele
Published: October 2021

Purpose

The purpose of the research was to verify if there was an alignment between the risk assessed and the risk perceived or if some inconsistencies arise that could affect the safety of the operators. In fact, eventual inconsistencies should be analysed, interpreted and managed to maximise the information and training process, if needed.

Design/methodology/approach

The adopted approach in this work relies on the collection of the perception of the operators about the level of risk in a work environment and its comparison with the level of risk assessed by the company. The collection of data was performed through a survey designed ad hoc, subministrated to all the workers in the area under study, being them involved in the production and in the maintenance. The survey’s structure and aim were described to the operator by the researchers and returned by the operators in a voluntary and anonymous way.

Findings

The information collected allowed identifying a gap between the risk assessed and the risk perceived by the plant operators. For example, for the use of personal protective equipments, the data highlighted a discrepancy between the knowledge about their need and the behaviour in using them, which resulted in the revision of both communication and training processes, with the adoption of a more participatory approach.

Originality/value

The originality of the work is in the data set, originally collected for this study, in the data collection form, also devised specifically for the case under study, despite it can be easily adapted for other work environment, and in the purpose itself, aimed at pushing risk assessment towards a personalised and adaptive approach.
Contrasting patterns of risk from human and non‐human predators shape temporal activity of prey
Authors: Gaynor Kaitlyn M. , McInturff Alex , Brashares Justin S.
Published: October 2021

Spatiotemporal variation in predation risk arises from interactions between landscape heterogeneity, predator densities and predator hunting mode, generating landscapes of fear for prey species that can have important effects on prey behaviour and ecosystem dynamics.

As widespread apex predators, humans present a significant source of risk for hunted animal populations. Spatiotemporal patterns of risk from hunters can overlap or contrast with patterns of risk from other predators. Human infrastructure can also reshape spatial patterns of risk by facilitating or impeding hunter or predator movement, or deterring predators that are themselves wary of humans.

We examined how anthropogenic and natural landscape features interact with hunting modes of rifle hunters and mountain lionsPuma concolorto generate spatiotemporal patterns of risk for their primary prey. We explored the implications of human‐modified landscapes of fear for Columbian black‐tailed deerOdocoileus hemionus columbianusin Mendocino County, California. We used historical harvest records, hunter GPS trackers and camera trap records of mountain lions to model patterns of risk for deer. We then used camera traps to examine deer spatial and temporal activity patterns in response to this variation in risk.

Hunters and mountain lions exhibited distinct, contrasting patterns of spatiotemporal activity. Risk from rifle hunters, who rely on long lines of sight, was highest in open grasslands and near roads and was confined to the daytime. Risk from mountain lions, an ambush predator, was highest in dense shrubland habitat, farther from developed areas, and during the night and crepuscular periods. Areas of human settlement provided a refuge from both hunters and mountain lions. We found no evidence that deer avoided risk in space at the scale of our observations, but deer adjusted their temporal activity patterns to reduce the risk of encounters with humans and mountain lions in areas of higher risk.

Our study demonstrates that interactions between human infrastructure, habitat cover and predator hunting mode can result in distinct spatial patterns of predation risk from hunters and other predators that may lead to trade‐offs for prey species. However, distinct diel activity patterns of predators may create vacant hunting domains that reduce costly trade‐offs for prey. Our study highlights the importance of temporal partitioning as a mechanism of predation risk avoidance.
Soil initial bacterial diversity and nutrient availability determine the rate of xenobiotic biodegradation
Authors: Jayaramaiah Ramesha H. , Egidi Eleonora , Macdonald Catriona A. , Wang Jun‐Tao , Jeffries Thomas C. , Megharaj Mallavarapu , Singh Brajesh K.
Published: October 2021

Understanding the relative importance of soil microbial diversity, plants and nutrient management is crucial to implement an effective bioremediation approach to xenobiotics‐contaminated soils. To date, knowledge on the interactive effects of soil microbiome, plant and nutrient supply on influencing biodegradation potential of soils remains limited. In this study, we evaluated the individual and interactive effects of soil initial bacterial diversity, nutrient amendments (organic and inorganic) and plant presence on the biodegradation rate of pyrene, a polycyclic aromatic hydrocarbon. Initial bacterial diversity had a strong positive impact on soil biodegradation potential, with soil harbouring higher bacterial diversity showing ~ 2 times higher degradation rates than soils with lower bacterial diversity. Both organic and inorganic nutrient amendments consistently improved the degradation rate in lower diversity soils and had negative (inorganic) to neutral (organic) effect in higher diversity soils. Interestingly, plant presence/type did not show any significant effect on the degradation rate in most of the treatments. Structural equation modelling demonstrated that initial bacterial diversity had a prominent role in driving pyrene biodegradation rates. We provide novel evidence that suggests that soil initial microbial diversity, and nutrient amendments should be explicitly considered in the design and employment of bioremediation management strategies for restoring natural habitats disturbed by organic pollutants.
Extracellular vesicle production in Gram‐positive bacteria
Authors: Dean Scott N. , Thakur Meghna , Spangler Joseph R.
Published: October 2021

This is a highlight on the article ‘Extracellular vesicle formation in Lactococcus lactis is stimulated by prophage‐encoded holin‐lysin system’ by Yue Liu, Eddy Smid and Tjakko Abee.
Breeding phenology of a terrestrial‐breeding frog is associated with soil water potential: Implications for conservation in a changing climate
Authors: Hoffmann Emily P. , Mitchell Nicola J.
Published: October 2021

Amphibian breeding is often linked to environmental cues. Given accelerating global climate change and habitat alteration, it is important to understand how environmental changes may affect male calling activity, the necessary precursor to mating. Here, we investigate the calling phenology and activity of Geocrinia alba, a critically endangered terrestrial‐breeding frog with a highly restricted distribution in southwestern Australia – a region undergoing significant warming and drying. We investigated whether calling periods differed across eight sites during a single breeding season, and the environmental conditions associated with calling activity at the start, peak and end of the calling period. We found consistent and prolonged calling activity over several months of the austral spring, but the length of the calling period varied two‐fold across sites, ranging from 3 to 6 months. Initiation of calling by G. alba was relatively similar across sites and was associated with warmer temperatures and higher soil water potential. However, the end of the calling period varied from October to January and was significantly associated with decreasing soil water potential. Calling only occurred when soils were close to saturation point, between −8 to −11 kPa, and therefore, breeding opportunities were likely also constrained by the length of time that soils were close to saturation. Changes in the regional climate, such as declining winter rainfall, could result in shorter breeding periods and consequently reduced breeding opportunities. More broadly, our study highlights the sensitivity of amphibians, particularly terrestrial‐breeding species, to changes in soil water potential and temperature, and the importance of maintaining suitable hydrological conditions during the breeding period.
Alcohol intake and stomach cancer risk in Japan: A pooled analysis of six cohort studies
Authors: Tamura Takashi , Wakai Kenji , Lin Yingsong , Tamakoshi Akiko , Utada Mai , Ozasa Kotaro , Sugawara Yumi , Tsuji Ichiro , Ono Ayami , Sawada Norie , Tsugane Shoichiro , Ito Hidemi , Nagata Chisato , Kitamura Tetsuhisa , Naito Mariko , Tanaka Keitaro , Shimazu Taichi , Mizoue Tetsuya , Matsuo Keitaro , Inoue Manami ,   for the Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan
Published: October 2021

The association between alcohol intake and stomach cancer risk remains controversial. We undertook a pooled analysis of data from six large‐scale Japanese cohort studies with 256 478 participants on this topic. Alcohol intake as ethanol was estimated using a validated questionnaire. The participants were followed for incidence of stomach cancer. We calculated study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) for stomach cancer according to alcohol intake using a Cox regression model. Summary HRs were estimated by pooling the study‐specific HRs using a random‐effects model. During 4 265 551 person‐years of follow‐up, 8586 stomach cancer cases were identified. In men, the multivariate‐adjusted HRs (95% CIs) of stomach cancer were 1.00 (0.87‐1.15) for occasional drinkers, and 1.00 (0.91‐1.11) for <23 g/d, 1.09 (1.01‐1.18) for 23 to <46 g/d, 1.18 (1.09‐1.29) for 46 to <69 g/d, 1.21 (1.05‐1.39) for 69 to <92 g/d, and 1.29 (1.11‐1.51) for ≥92 g/d ethanol in regular drinkers compared with nondrinkers. In women, the multivariate‐adjusted HRs were 0.93 (0.80‐1.08) for occasional drinkers, and 0.85 (0.74‐0.99) for <23 g/d, and 1.22 (0.98‐1.53) for ≥23 g/d in regular drinkers compared with nondrinkers. The HRs for proximal and distal cancer in drinkers vs nondrinkers were 1.69 (1.15‐2.47) and 1.24 (0.99‐1.55) for ≥92 g/d in men, and 1.60 (0.76‐3.37) and 1.18 (0.88‐1.57) for ≥23 g/d in women, respectively. Alcohol intake increased stomach cancer risk in men, and heavy drinkers showed a greater point estimate of risk for proximal cancer than for distal cancer.
Prediction of the differences in tumor mutation burden between primary and metastatic lesions by radiogenomics
Authors: Hoshino Isamu , Yokota Hajime , Iwatate Yosuke , Mori Yasukuni , Kuwayama Naoki , Ishige Fumitaka , Itami Makiko , Uno Takashi , Nakamura Yuki , Tatsumi Yasutoshi , Shimozato Osamu , Nagase Hiroki
Published: October 2021

Tumor mutational burden (TMB) is gaining attention as a biomarker for responses to immune checkpoint inhibitors in cancer patients. In this study, we evaluated the status of TMB in primary and liver metastatic lesions in patients with colorectal cancer (CRC). In addition, the status of TMB in primary and liver metastatic lesions was inferred by radiogenomics on the basis of computed tomography (CT) images. The study population included 24 CRC patients with liver metastases. DNA was extracted from primary and liver metastatic lesions obtained from the patients and TMB values were evaluated by next‐generation sequencing. The TMB value was considered high when it equaled to or exceeded 10/100 Mb. Radiogenomic analysis of TMB was performed by machine learning using CT images and the construction of prediction models. In 7 out of 24 patients (29.2%), the TMB status differed between the primary and liver metastatic lesions. Radiogenomic analysis was performed to predict whether TMB status was high or low. The maximum values for the area under the receiver operating characteristic curve were 0.732 and 0.812 for primary CRC and CRC with liver metastasis, respectively. The sensitivity, specificity, and accuracy of the constructed models for TMB status discordance were 0.857, 0.600, and 0.682, respectively. Our results suggested that accurate inference of the TMB status is possible using radiogenomics. Therefore, radiogenomics could facilitate the diagnosis, treatment, and prognosis of patients with CRC in the clinical setting.
Liver transplant after donation from controlled circulatory death versus brain death: A UNOS database analysis and publication bias adjusted meta‐analysis
Authors: Ziogas Ioannis A. , Kakos Christos D. , Esagian Stepan M. , Skarentzos Konstantinos , Alexopoulos Sophoclis P. , Shingina Alexandra , Montenovo Martin I.
Published: October 2021

Background

Donation after circulatory death (DCD) is an increasingly utilized alternative to donation after brain death (DBD) to expand the liver donor pool. We compared the outcomes of liver transplant (LT) after DCD versus DBD.

Methods

A PRISMA‐compliant systematic literature review was performed using the PubMed, Cochrane Library, and Embase databases (end‐of‐search‐date: July 2, 2020). US outcomes were analyzed using the UNOS database (February, 2002–September, 2020). Pooled hazard ratios (HR) for patient and graft survival were obtained through random effect meta‐analyses and adjusted for publication bias.

Results

Thirteen studies reporting on 1426 DCD and 5385 DBD LT recipients were included. 5620 DCD and 87561 DBD LT recipients were analyzed from the UNOS database. Meta‐analysis showed increased risk of patient mortality for DCD (HR = 1.36; 95%CI, 1.09–1.70; P = .01; I2 = 53.6%). When adjusted for publication bias, meta‐analysis showed no difference in patient survival between DCD and DBD (HR = 1.15; 95%CI, .91–1.45; P = .25; I2 = 61.5%). Meta‐analysis showed increased risk of graft loss for DCD (HR = 1.50; 95%CI, 1.20–1.88; P < .001; I2 = 67.8%). When adjusted for publication bias, meta‐analysis showed a reduction in effect size (HR = 1.36; 95%CI, 1.06–1.74; P = .02; I2 = 73.5%).

Conclusion

When adjusted for publication bias, no difference was identified between DCD and DBD regarding patient survival, while DCD was associated with an increased risk of graft loss.
The expression pattern of CD10 and CD31 identifies fine fibrovascular stroma of grade 1‐endometrial endometrioid carcinomas in cytology
Authors: Norimatsu Yoshiaki , Nishikawa Takeshi , Suzuki Hisae , Hosokawa Sho , Yano Hiroko , Maeda Yoshinobu , Kurokawa Tetsuji , Shinagawa Akiko , Kobayashi Tadao K. , Fulciniti Franco
Published: October 2021

Introduction

The objective of this study was to assess the diagnostic utility of CD10 in the differential diagnosis of grade 1‐endometrial endometrioid carcinoma (G1‐EEC) and the metaplastic changes associated with the endometrial glandular and stromal breakdown (EGBD) on liquid‐based cytological (LBC) samples.

Methods

(1) The type and distribution of CD10‐positive cells in EGBD and G1‐EEC patients were evaluated. (2) Based on the results from (1), histological and cytological specimens were double‐immunostained with CD31 and CD10 to confirm whether CD10‐positive tubular‐canalicular material found in (1) was represented by fine threads of endometrial‐type fibrovascular stroma. (3) Based on the results from (2), additional immunostaining of histological specimens was performed for CD146 and αSMA as markers of perivascular cells.

Results

(1) CD10 positive cells showed two main patterns of expression: cytoplasmic immunoreactivity in the form of dense brown granules in EGBD and tubular‐canalicular branching patterns in G1‐EEC. (2) The tubular‐canalicular material observed in cytological specimens of G1‐EEC samples co‐expressed CD10 and CD31, and was interpreted as representing fine threads of endometrial fibrovascular stroma in the corresponding histological samples. Conversely, metaplastic changes in EGBD cases, only a few CD31‐positive signals were found inside the condensed stromal clusters with CD10‐positive. (3) Cells surrounding the CD31‐positive vascular endothelial cells expressed CD146 and αSMA; moreover, some of the thin CD10‐positive fibrous stromal strands also co‐expressed αSMA.

Conclusions

CD10 is a very useful immunomarker for distinguishing between G1‐EEC and the metaplastic changes of EGBD in LBC samples.
Growing cotton to produce food: Unravelling interactions between value chains in southern Mali
Authors: Dissa Arouna , Bijman Jos , Slingerland Maja , Sanogo Ousmane Mama , Giller Ken E , Descheemaeker Katrien
Published: October 2021

Motivation

Most transaction cost economic frameworks, commonly used to examine and explain the co‐ordination of agricultural transactions, use a linear approach for a single product transaction. This ignores the concurrence of multiple transactions by smallholder farmers in developing countries.

Purpose

This study aims to understand co‐ordination among multiple product transactions by smallholder farmers and to identify ways to remove impediments to market participation. It develops an adapted transaction cost framework, considering contract types and forms of market participation as building blocks for co‐ordination structures.

The framework was applied to explain co‐ordination structures between smallholders and buyers of cotton and cereals in southern Mali.

Methods and approach

To make the framework operational, we did the following: (1) selected transaction characteristics; (2) elaborated benchmarks to describe the intensity of transactions; (3) identified co‐ordination structures; and (4) scored the intensity of transactions. Both quantitative and qualitative data were collected.

Findings

The majority of farmers grew cotton and sold it to a parastatal company, the sole buyer, that also supported the provision of inputs. Inputs were used to grow not only cotton, but also cereals. Most farmers sold cereals on spot markets to collectors and traders.

Using different structures allowed smallholders to obtain inputs and services, to pursue different income sources over the year, and to balance flexibility and security.

Policy implications

Collective organizations of smallholder farmers should be supported to improve their financial and managerial capacities to allow them to co‐ordinate better with buyers and input suppliers.

Institutional innovations to better balance risks for smallholders and buyers deserve consideration. These innovations include crop insurance, long‐term credit, and warehouse receipts.
Predictors of fever response in tuberculous meningitis: A clinical, MRI and biomarker study
Authors: Kalita Jayantee , Pandey Prakash C. , Shukla Ruchi , Haldar Rudrashish
Published: October 2021

Background

Central nervous system (CNS) has a different immune surveillance system; therefore, fever at admission and timeline of fever response after antitubercular treatment (ATT) may follow a different course in CNS infection. We report the predictors of fever response in tuberculous meningitis (TBM) including the effect of tumour necrosis factor‐α (TNF‐α) in cerebrospinal fluid (CSF) and its gene expression at mRNA of peripheral blood mononuclear cells (PBMCs).

Methods

Fifty‐seven patients with TBM were prospectively evaluated. Their clinical findings and severity of meningitis were recorded. The expression of TNF‐α gene in PBMCs was quantified by real‐time polymerase chain reaction and TNF‐α concentration in CSF by cytokine bead array both in the patients and 14 matched controls.

Results

All the patients had history of fever for a median duration of 75 days. The admission temperature ranged between 37.2°C and 40°C and correlated with CSF cell counts (p < 0.05). Cranial MRI was abnormal in 54 (94.7%) and revealed exudates in 33(57.9%), hydrocephalus in 27(47.4%), infarction in 27(47.4%) and tuberculoma in 33(57.9%) patients. Fever subsided after a median duration of 18 (2 60) days of treatment. Twelve (21.8%) patients only became afebrile within 10 days. The expression of TNF‐α gene correlated with CSF concentration of TNF‐α (p = 0.02) and independently predicted duration of defervescence [adjusted hazard ratio 1.02 (95% CI 1.00–1.04; p = 0.01).

Conclusion

In the patients with TBM, defervescence takes longer time, and TNF‐α gene expression predicts the duration of defervescence. Future studies are needed to evaluate the role of TNF‐α‐modifying drugs in TBM.
Surveillance and control of SARS‐CoV‐2 in mustelids: An evolutionary perspective
Authors: Díaz Adriana V. , Walker Martin , Webster Joanne P.
Published: October 2021

The relevance of mustelids in SARS‐CoV‐2 transmission has become increasingly evident. Alongside experimental demonstration of airborne transmission among ferrets, the major animal model for human respiratory diseases, transmission of SARS‐CoV‐2 within‐ and/or between‐commercial mink farms has occurred and continues to occur. The number of mink reared for the luxury fur trade is approximately 60.5 million, across 36 mustelid‐farming countries. By July 2021, SARS‐CoV‐2 outbreaks have been reported in 12 of these countries, at 412 European and 20 North American mink farms. Reverse zoonotic transmission events (from humans to mink) have introduced the virus to farms with subsequent extensive mink‐to‐mink transmission as well as further zoonotic (mink‐to‐human) transmission events generating cases among both farm workers and the broader community. Overcrowded housing conditions inherent within intensive mink farms, often combined with poor sanitation and welfare, both guarantee spread of SARS‐CoV‐2 and facilitate opportunities for viral variants, thereby effectively representing biotic hubs for viral transmission and evolution of virulence. Adequate preventative, surveillance and control measures within the mink industry are imperative both for the control of the current global pandemic and to mitigate against future outbreaks.
Predators mitigate the destabilising effects of heatwaves on multitrophic stream communities
Authors: Ross Samuel R. P.‐J. , García Molinos Jorge , Okuda Atsushi , Johnstone Jackson , Atsumi Keisuke , Futamura Ryo , Williams Maureen A. , Matsuoka Yuichi , Uchida Jiro , Kumikawa Shoji , Sugiyama Hiroshi , Kishida Osamu , Donohue Ian
Published: October 2021

Amidst the global extinction crisis, climate change will expose ecosystems to more frequent and intense extreme climatic events, such as heatwaves. Yet, whether predator species loss—a prevailing characteristic of the extinction crisis—will exacerbate the ecological consequences of extreme climatic events remains largely unknown. Here, we show that the loss of predator species can interact with heatwaves to moderate the compositional stability of ecosystems. We exposed multitrophic stream communities, with and without a dominant predator species, to realistic current and future heatwaves and found that heatwaves destabilised algal communities by homogenising them in space. However, this happened only when the predator was absent. Additional heatwave impacts on multiple aspects of stream communities, including changes to the structure of algal and macroinvertebrate communities, as well as total algal biomass and its temporal variability, were not apparent during heatwaves and emerged only after the heatwaves had passed. Taken together, our results suggest that the ecological consequences of heatwaves can amplify over time as their impacts propagate through biological interaction networks, but the presence of predators can help to buffer such impacts. These findings underscore the importance of conserving trophic structure, and highlight the potential for species extinctions to amplify the effects of climate change and extreme events.
Impact of oral health guidance on the tongue‐lip motor function of outpatients at a dental hospital
Authors: Hatanaka Yukiko , Furuya Junichi , Sato Yuji , Uchida Yoshiki , Osawa Tokiko , Shichita Toshiharu , Suzuki Hiroyuki , Minakuchi Shunsuke
Published: October 2021

Objective

To clarify the effect of oral health guidance on tongue‐lip motor function in the outpatients visiting the Showa University Dental Hospital (Tokyo, Japan).

Background

The management of the oral function of older people visiting a dental hospital is important. Previous studies have revealed that tongue‐lip motor function is easy to improve. However, the impact of oral health guidance on tongue‐lip motor function in the outpatients of dental hospital requires further elucidation.

Materials and Methods

The participants (n = 35) included patients who were diagnosed with low tongue‐lip motor function on evaluation by oral diadochokinesis (ODK) at the outpatient clinic. They underwent a second examination approximately 6‐12 months later. Their demographic characteristics were recorded. Oral health guidance was provided through an educational leaflet on oral hypofunction when the participants visited the clinic. It included content on tongue twisters, voice training and a range of movement and muscle training of the tongue and lip.

Results

Following oral health guidance on tongue‐lip motor function, the ODK values changed from 5.6 at the first examination to 6.0 at the second for /pa/, from 5.6 to 5.8 for /ta/ and from 5.2 to 5.4 for /ka/. This improvement was not significantly associated with age, sex, measurement period or number of visits.

Conclusion

The findings of this longitudinal study suggested that oral health guidance using an oral hypofunction educational leaflet may be effective in improving the tongue‐lip motor function of outpatients who had low tongue‐lip motor function, regardless of the measurement period or the number of visits to the dental hospital.
Influence of heat treatment temperature on the properties of the lithium disilicate‐fluorcanasite glass‐ceramics
Authors: Kraipok Arnon , Intawin Pratthana , Bintachitt Patamas , Leenakul Wilaiwan , Khamman Orawan , Eitssayeam Sukum , Tunkasiri Tawee , Pengpat Kamonpan
Published: October 2021

This study aims to investigate the influence of heat treatment temperatures on the mechanical properties and chemical solubility (CS) of lithium disilicate‐fluorcanasite glass‐ceramics and to develop new dental materials. The glasses and glass‐ceramics were prepared using CaF2‐SiO2‐CaO‐K2O‐Na2O‐Li2O‐Al2O3‐P2O5‐based glass system using a conventional melt quenching method followed by a two‐stage crystallization process. This two‐stage method involves two heating temperature steps: first at a constant temperature (TS1) of 600°C and second step at varying temperatures (TS2) of 650, 700, 750, and 800°C. The crystallization behavior, phase formation, microstructure, translucency characteristic, density, hardness, fracture strength, and CS were investigated. It was found that the lithium disilicate crystal acted as the main crystalline phase, and the crystalline phase of fluorcanasite occurred at the heat treatment temperatures of 750 and 800°C. In addition, it was found that density, hardness, fracture strength, and CS increased while the translucency values decreased with increasing heat treatment temperatures. Furthermore, the CS increased dramatically when the fluorcanasite phases occurred in the glass‐ceramic samples. The maximum density values, Vickers hardness, fracture toughness, and flexural strength are 2.56 g/cm3, 6.73 GPa, 3.38 MPa.m1/2, and 259 MPa, respectively. These results may offer a possibility to design a new material for dental applications based on lithium disilicate‐fluorcanasite glass‐ceramics.