bluuebunny/crossref_metadata_2025 huggingface dataset:
EXPERIMENTS AT MODANE UNDERGROUND LABORATORY OR THE SWAN SONG OF RADIOCARBON ß-COUNTING BY GAS PROPORTIONAL COUNTER
Authors: Fontugne Michel , Hatté Christine , Jaudon Michel
Published: October 2021

In 1991, a 14C ß-counting installation with four proportional CO2 gas counters was tested at the Modane underground laboratory, 1700 m below the summit of Pointe du Fréjus, reducing the muon flux to 4 muons per square meter and per day. With cosmic radiation attenuated by a factor of 2.106, the background level of the counters was reduced by 65 to 85% while its variability was reduced by a factor of 30–80 depending on the type of counter. The dating limit of these counters extends to well beyond 60,000 years.
Association of dietary inflammatory index and metabolic syndrome in the elderly over 55 years in Northern China
Authors: Li Ruiqiang , Zhan Wenqiang , Huang Xin , Zhang Zechen , Zhou Meiqi , Bao Wei , Li Qingxia , Ma Yuxia
Published: October 2021

We assessed the association between the dietary inflammatory index (DII) and the development of metabolic syndrome in the elderly over 55 years in Northern China. The data of 1936 Chinese adults aged 55 years and over from a community-based neurological disease cohort study from 2018 to 2019 were analysed. Multiple logistic regression and restricted cubic splines regression were used for analysis, and social demographics, lifestyle and health-related factors were adjusted. In the fully adjusted model, the risk of metabolic syndrome increased by 1·28-fold in people with a pro-inflammatory diet. When we divide the metabolic syndrome by its components, high pro-inflammatory diet and hyperglycaemia, TAG, hypertension and abdominal obesity, we failed to observe a significant association between a high pro-inflammatory diet and HDL-cholesterol. However, these associations are moving in the expected direction. At the same time, the results of BMI subgroup analysis showed that with the increase of DII, obese people are at increased risk of metabolic syndrome, hyperglycaemia, high TAG, hypertension and abdominal obesity. Also in overweight people, the increase in DII is accompanied by an increased risk of hyperglycaemia and abdominal obesity. Higher inflammatory diet is related to metabolic syndrome, hypertension, hyperglycaemia, abdominal obesity and hypertriglyceridaemia. Further research is needed to confirm the role of inflammation and diet in the development of metabolic syndrome; however, it is desirable to reduce the dietary components associated with inflammation.
Restrained eating behaviour, anorexia nervosa and food consumption between children and adolescents: a scoping review
Authors: Pereira Emile Miranda , da Silva Karine Brito Beck , Costa Priscila Ribas de Farias , da Silva Laís Eloy Machado , Nepomuceno Carina Márcia Magalhães , da Silva Helena Benes Matos , Santos Belfort Érika , Cunha Carla de Magalhães , de Santana Mônica Leila Portela
Published: October 2021

Anorexia nervosa (AN) and restrained eating behaviour (REB) are characterised by reduced food intake to achieve body weight loss. This scope review aimed to describe the existing evidence on the association between AN, restrictive eating behaviour and food consumption. Studies with children and adolescents of both sexes of all races and ethnicities were included. Experimental and observational studies, systematic reviews, meta-analysis, case reports or series, conference abstracts, dissertations and theses were also included. The search was conducted in ten electronic databases and grey literature without language restriction on 14 November 2020. Twenty-four studies met the inclusion criteria. Most studies included girls and identified lower intake of energy content, fat and certain micronutrients. There was also a higher intake of caffeine, fibre, vegetables, legumes and fruits and a lower intake of low-quality snack, fast food, sweets and foods with high carbohydrate and fat contents. The need to improve the quality of the diet among study participants was also identified. Thus, it is recommended that the evaluation of food consumption be careful to develop effective prevention strategies for the development of AN/REB and minimise nutritional deficiencies in these individuals.
Baseball, Modernity, and Science Discourse in British Popular Culture, 1871–1883
Authors: Beaver Daniel C.
Published: October 2021

Baseball in the United Kingdom has long been considered a contradiction in terms, especially during the nineteenth century, with both the 1874 National Association Tour and the 1888 Spalding Tour viewed as financial and cultural failures in a sophisticated consumer society already dominated by cricket. This article takes a fresh look at evidence from the 1870s and 1880s in order to challenge this perspective. It presents the 1874 Tour as a transnational success, articulating shared Anglo-American assumptions about modernity, science, and social progress. This discourse informed a broad process of technology transfer involving new sources of industrial power as well as the corporal techniques of modern sport. The article also places the tour in the context of a unique historical phenomenon: the transatlantic diffusion of an early modern English game to the United Kingdom as the New York Game, a modern American sport. Previous accounts of the tour focused on a few selected reports, confirming American views of its financial failings and British disinterest in its exhibitions. When considered in light of hundreds of British accounts from the 1870s, including unexamined evidence of the first British baseball clubs less than two years after the tour, this perspective becomes unsustainable.
Long-term mortality predictors of ICU fungaemia
Authors: Xie Peng , Wang Wenqiang , Dong Maolong
Published: October 2021

Bloodstream fungal infections have a high mortality rate. There is little data about the long-term mortality rate of fungaemia.This study aimed to explore the mortality of fungaemia and the influencing factors associated with death. In total, 204 intensive care unit (ICU) patients with fungaemia from Multi-parameter Intelligent Monitoring in Intensive Care-III (MIMIC-III) Database were studied. Age, gender, major underlying diseases, data about vital signs and blood test results were analysed to identify the predictors of the mortality and prognosis of fungaemia in ICU patients. Cox regression models were constructed, together with Kaplan−Meier survival curves. The 30-day, 1-year, 2-year, 3-year and 4-year mortality rates were 41.2%, 62.3%, 68.1%, 72.5% and 75%, respectively. Age (P ＜ 0.001, OR = 1.530; P ＜ 0.001, OR = 1.485)，serum bilirubin (P = 0.016, OR = 2.125；P = 0.001, OR = 1.748) and international normalised ratio (INR) (P = 0.001, OR = 2.642; P ＜ 0.001 OR = 2.065) were predictors of both the 30-day and 4-year mortality rates. Renal failure (P = 0.009, OR = 1.643) performed good in prediction of the 4-year mortality. The mortality of fungaemia is high. Age，the serum bilirubin and INR are good predictors of the 30-day and 4-year mortality rates of fungaemia. Renal failure has good performance in predicting the long-term mortality.
ABELIAN CYCLES IN THE HOMOLOGY OF THE TORELLI GROUP
Authors: Lindell Erik
Published: October 2021

In the early 1980s, Johnson defined a homomorphism
$\mathcal {I}_{g}^1\to \bigwedge ^3 H_1\left (S_{g},\mathbb {Z}\right )$
, where
$\mathcal {I}_{g}^1$
is the Torelli group of a closed, connected, and oriented surface of genus g with a boundary component and
$S_g$
is the corresponding surface without a boundary component. This is known as the Johnson homomorphism.

We study the map induced by the Johnson homomorphism on rational homology groups and apply it to abelian cycles determined by disjoint bounding-pair maps, in order to compute a large quotient of
$H_n\left (\mathcal {I}_{g}^1,\mathbb {Q}\right )$
in the stable range. This also implies an analogous result for the stable rational homology of the Torelli group
$\mathcal {I}_{g,1}$
of a surface with a marked point instead of a boundary component. Further, we investigate how much of the image of this map is generated by images of such cycles and use this to prove that in the pointed case, they generate a proper subrepresentation of
$H_n\left (\mathcal {I}_{g,1}\right )$
for
$n\ge 2$
and g large enough.
AN APERIODIC TILE WITH EDGE-TO-EDGE ORIENTATIONAL MATCHING RULES
Authors: Walton James J. , Whittaker Michael F.
Published: October 2021

We present a single, connected tile which can tile the plane but only nonperiodically. The tile is hexagonal with edge markings, which impose simple rules as to how adjacent tiles are allowed to meet across edges. The first of these rules is a standard matching rule, that certain decorations match across edges. The second condition is a new type of matching rule, which allows tiles to meet only when certain decorations in a particular orientation are given the opposite charge. This forces the tiles to form a hierarchy of triangles, following a central idea of the Socolar–Taylor tilings. However, the new edge-to-edge orientational matching rule forces this structure in a very different way, which allows for a surprisingly simple proof of aperiodicity. We show that the hull of all tilings satisfying our rules is uniquely ergodic and that almost all tilings in the hull belong to a minimal core of tilings generated by substitution. Identifying tilings which are charge-flips of each other, these tilings are shown to have pure point dynamical spectrum and a regular model set structure.
Hepatocyte organoids and cell transplantation: What the future holds
Authors: Peng Weng Chuan , Kraaier Lianne J. , Kluiver Thomas A.
Published: October 2021

Historically, primary hepatocytes have been difficult to expand or maintain in vitro. In this review, we will focus on recent advances in establishing hepatocyte organoids and their potential applications in regenerative medicine. First, we provide a background on the renewal of hepatocytes in the homeostatic as well as the injured liver. Next, we describe strategies for establishing primary hepatocyte organoids derived from either adult or fetal liver based on insights from signaling pathways regulating hepatocyte renewal in vivo. The characteristics of these organoids will be described herein. Notably, hepatocyte organoids can adopt either a proliferative or a metabolic state, depending on the culture conditions. Furthermore, the metabolic gene expression profile can be modulated based on the principles that govern liver zonation. Finally, we discuss the suitability of cell replacement therapy to treat different types of liver diseases and the current state of cell transplantation of in vitro-expanded hepatocytes in mouse models. In addition, we provide insights into how the regenerative microenvironment in the injured host liver may facilitate donor hepatocyte repopulation. In summary, transplantation of in vitro-expanded hepatocytes holds great potential for large-scale clinical application to treat liver diseases.
Biobanking of human gut organoids for translational research
Authors: Perrone Francesca , Zilbauer Matthias
Published: October 2021

The development of human organoid culture models has led to unprecedented opportunities to generate self-organizing, three-dimensional miniature organs that closely mimic in vivo conditions. The ability to expand, culture, and bank such organoids now provide researchers with the opportunity to generate next-generation living biobanks, which will substantially contribute to translational research in a wide range of areas, including drug discovery and testing, regenerative medicine as well as the development of a personalized treatment approach. However, compared to traditional tissue repositories, the generation of a living organoid biobank requires a much higher level of coordination, additional resources, and scientific expertise. In this short review, we discuss the opportunities and challenges associated with the generation of a living organoid biobank. Focusing on human intestinal organoids, we highlight some of the key aspects that need to be considered and provide an outlook for future development in this exciting field.
Strategies for genetic manipulation of adult stem cell-derived organoids
Authors: Menche Constantin , Farin Henner F.
Published: October 2021

Organoid technology allows the expansion of primary epithelial cells from normal and diseased tissues, providing a unique model for human (patho)biology. In a three-dimensional environment, adult stem cells self-organize and differentiate to gain tissue-specific features. Accessibility to genetic manipulation enables the investigation of the molecular mechanisms underlying cell fate regulation, cell differentiation and cell interactions. In recent years, powerful methodologies using lentiviral transgenesis, CRISPR/Cas9 gene editing, and single-cell readouts have been developed to study gene function and carry out genetic screens in organoids. However, the multicellularity and dynamic nature of stem cell-derived organoids also present challenges for genetic experimentation. In this review, we focus on adult gastrointestinal organoids and summarize the state-of-the-art protocols for successful transgenesis. We provide an outlook on emerging genetic techniques that could further increase the applicability of organoids and enhance the potential of organoid-based techniques to deepen our understanding of gene function in tissue biology.
Dissecting single-cell genomes through the clonal organoid technique
Authors: Youk Jeonghwan , Kwon Hyun Woo , Kim Ryul , Ju Young Seok
Published: October 2021

The revolution in genome sequencing technologies has enabled the comprehensive detection of genomic variations in human cells, including inherited germline polymorphisms, de novo mutations, and postzygotic mutations. When these technologies are combined with techniques for isolating and expanding single-cell DNA, the landscape of somatic mosaicism in an individual body can be systematically revealed at a single-cell resolution. Here, we summarize three strategies (whole-genome amplification, microdissection of clonal patches in the tissue, and in vitro clonal expansion of single cells) that are currently applied for single-cell mutational analyses. Among these approaches, in vitro clonal expansion, particularly via adult stem cell-derived organoid culture technologies, yields the most sensitive and precise catalog of somatic mutations in single cells. Moreover, because it produces living mutant cells, downstream validation experiments and multiomics profiling are possible. Through the synergistic combination of organoid culture and genome sequencing, researchers can track genome changes at a single-cell resolution, which will lead to new discoveries that were previously impossible.
Growth differentiation factor-15 and the association between type 2 diabetes and liver fibrosis in NAFLD
Authors: Bilson Josh , Scorletti Eleonora , Bindels Laure B. , Afolabi Paul R. , Targher Giovanni , Calder Philip C. , Sethi Jaswinder K. , Byrne Christopher D.
Published: October 2021

Background

Type 2 diabetes mellitus (T2DM) is a strong risk factor for liver fibrosis in non-alcoholic fatty liver disease (NAFLD). It remains uncertain why T2DM increases the risk of liver fibrosis. It has been suggested that growth differentiation factor-15 (GDF-15) concentrations increase the risk of liver fibrosis. We aimed to investigate (a) whether GDF-15 concentrations were associated with liver fibrosis and involved in the relationship between T2DM and liver fibrosis and (b) what factors linked with T2DM are associated with increased GDF-15 concentrations.

Methods

Ninety-nine patients with NAFLD (61% men, 42.4% T2DM) were studied. Serum GDF-15 concentrations were measured by electro-chemiluminescence immunoassay. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. Regression modelling, receiver operator characteristic curve analysis and Sobel test statistics were used to test associations, risk predictors and the involvement of GDF-15 in the relationship between T2DM and liver fibrosis, respectively.

Results

Patients with NAFLD and T2DM (n = 42) had higher serum GDF-15 concentrations [mean (SD): 1271.0 (902.1) vs. 640.3 (332.5) pg/ml, p < 0.0001], and a higher proportion had VCTE assessed ≥F2 fibrosis (48.8 vs. 23.2%, p = 0.01) than those without T2DM. GDF-15 was independently associated with liver fibrosis (p = 0.001), and GDF-15 was the most important single factor predicting ≥F2 or ≥F3 fibrosis (≥F2 fibrosis AUROC 0.75, (95% CI 0.63–0.86), p < 0.001, with sensitivity, specificity, positive predictive (PPV) and negative predictive (NPV) values of 56.3%, 86.9%, 69.2% and 79.1%, respectively). GDF-15 was involved in the association between T2DM and ≥F2 fibrosis (Sobel test statistic 2.90, p = 0.004). Other factors associated with T2DM explained 60% of the variance in GDF-15 concentrations (p < 0.0001). HbA1c concentrations alone explained 30% of the variance (p < 0.0001).

Conclusions

GDF-15 concentrations are a predictor of liver fibrosis and potentially involved in the association between T2DM and liver fibrosis in NAFLD. HbA1c concentrations explain a large proportion of the variance in GDF-15 concentrations.
Fatty acid dysregulation in the anterior cingulate cortex of depressed suicides with a history of child abuse
Authors: Perlman Kelly , Chouinard-Watkins Raphaël , Tanti Arnaud , Cisbani Giulia , Orri Massimiliano , Turecki Gustavo , Bazinet Richard P. , Mechawar Naguib
Published: October 2021

Child abuse (CA) strongly increases the lifetime risk of suffering from major depression and predicts an unfavorable course for the illness. Severe CA has been associated with a specific dysregulation of oligodendrocyte function and thinner myelin sheaths in the human anterior cingulate cortex (ACC) white matter. Given that myelin is extremely lipid-rich, it is plausible that these findings may be accompanied by a disruption of the lipid profile that composes the myelin sheath. This is important to explore since the composition of fatty acids (FA) in myelin phospholipids can influence its stability, permeability, and compactness. Therefore, the objective of this study was to quantify and compare FA concentrations in postmortem ACC white matter in the choline glycerophospholipid pool (ChoGpl), a key myelin phospholipid pool, between adult depressed suicides with a history of CA (DS-CA) matched depressed suicides without CA (DS) and healthy non-psychiatric controls (CTRL). Total lipids were extracted from 101 subjects according to the Folch method and separated into respective classes using thin-layer chromatography. FA methyl esters from the ChoGpl fraction were quantified using gas chromatography. Our analysis revealed specific effects of CA in FAs from the arachidonic acid synthesis pathway, which was further validated with RNA-sequencing data. Furthermore, the concentration of most FAs was found to decrease with age. By extending the previous molecular level findings linking CA with altered myelination in the ACC, these results provide further insights regarding white matter alterations associated with early-life adversity.
SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation
Authors: Xu Gang , Li Ying , Zhang Shengyuan , Peng Haoran , Wang Yunyun , Li Dekang , Jin Taijie , He Zhuohao , Tong Yilun , Qi Chunting , Wu Guowei , Dong Kangyun , Gou Jizhou , Liu Yang , Xiao Tongyang , Qu Jing , Li Liang , Liu Liang , Zhao Ping , Zhang Zheng , Yuan Junying
Published: October 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection. We found evidence of RIPK1 activation in human COVID-19 lung pathological samples, and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2. Inhibition of RIPK1 using multiple small-molecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids. Furthermore, therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load, and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice. Mechanistically, we found that the RNA-dependent RNA polymerase of SARS-CoV-2, NSP12, a highly conserved central component of coronaviral replication and transcription machinery, promoted the activation of RIPK1. Furthermore, NSP12 323L variant, encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy, Italy, that carries a Pro323Leu amino acid substitution in NSP12, showed increased ability to activate RIPK1. Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells. Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19.
A novel mathematical modeling with solution for movement of fluid through ciliary caused metachronal waves in a channel
Authors: Khan Wasim Ullah , Imran Ali , Raja Muhammad Asif Zahoor , Shoaib Muhammad , Awan Saeed Ehsan , Kausar Khadija , He Yigang
Published: October 2021

In the present research, a novel mathematical model for the motion of cilia using non-linear rheological fluid in a symmetric channel is developed. The strength of analytical perturbation technique is employed for the solution of proposed physical process using mectachoronal rhythm based on Cilia induced flow for pseudo plastic nano fluid model by considering the low Reynolds number and long wave length approximation phenomena. The role of ciliary motion for the fluid transport in various animals is explained. Analytical expressions are gathered for stream function, concentration, temperature profiles, axial velocity, and pressure gradient. Whereas, transverse velocity, pressure rise per wave length, and frictional force on the wall of the tubule are investigated with aid of numerical computations and their outcomes are demonstrated graphically. A comprehensive analysis for comparison of Perturb and numerical solution is done. This analysis validates the analytical solution.
Arabidopsis thaliana PrimPol is a primase and lesion bypass DNA polymerase with the biochemical characteristics to cope with DNA damage in the nucleus, mitochondria, and chloroplast
Authors: García-Medel Paola L. , Peralta-Castro Antolín , Baruch-Torres Noe , Fuentes-Pascacio Alma , Pedroza-García José A. , Cruz-Ramirez Alfredo , Brieba Luis G.
Published: October 2021

PrimPol is a novel Primase–Polymerase that synthesizes RNA and DNA primers de novo and extents from these primers as a DNA polymerase. Animal PrimPol is involved in nuclear and mitochondrial DNA replication by virtue of its translesion DNA synthesis (TLS) and repriming activities. Here we report that the plant model Arabidopsis thaliana encodes a functional PrimPol (AtPrimPol). AtPrimPol is a low fidelity and a TLS polymerase capable to bypass DNA lesions, like thymine glycol and abasic sites, by incorporating directly across these lesions or by skipping them. AtPrimPol is also an efficient primase that preferentially recognizes the single-stranded 3′-GTCG-5′ DNA sequence, where the 3′-G is cryptic. AtPrimPol is the first DNA polymerase that localizes in three cellular compartments: nucleus, mitochondria, and chloroplast. In vitro, AtPrimPol synthesizes primers that are extended by the plant organellar DNA polymerases and this reaction is regulated by organellar single-stranded binding proteins. Given the constant exposure of plants to endogenous and exogenous DNA-damaging agents and the enzymatic capabilities of lesion bypass and re-priming of AtPrimPol, we postulate a predominant role of this enzyme in avoiding replication fork collapse in all three plant genomes, both as a primase and as a TLS polymerase.
The dialysis facility levels and sizes are associated with outcomes of incident hemodialysis patients
Authors: Kuo George , Lee Tao-Han , Chen Jia-Jin , Yen Chieh-Li , Fan Pei-Chun , Lee Cheng-Chia , Chang Chih-Hsiang
Published: October 2021

The outcomes of patients with incident kidney failure who start hemodialysis are influenced by several factors. Whether hemodialysis facility characteristics are associated with patient outcomes is unclear. We included adults diagnosed as having kidney failure requiring hemodialysis during January 1, 2001 to December 31, 2013 from the Taiwan National Health Insurance Research Database to perform this retrospective cohort study. The exposures included different sizes and levels of hemodialysis facilities. The outcomes were all-cause mortality, cardiovascular death, infection-related death, hospitalization, and kidney transplantation. During 2001–2013, we identified 74,406 patients and divided them in to three groups according to the facilities where they receive hemodialysis: medical center (n = 8263), non-center hospital (n = 40,008), and clinic (n = 26,135). The multivariable Cox model demonstrated that a larger facility size was associated with a low mortality risk (hazard ratio [HR] 0.991, 95% confidence interval [95% CI] 0.984–0.998; every 20 beds per facility). Compared with medical centers, patients in non-center hospitals and clinics had higher mortality risks (HR 1.13, 95% CI 1.09–1.17 and HR 1.11, 95% CI 1.06–1.15, respectively). Patients in medical centers and non-center hospitals had higher risk of hospitalization (subdistribution HR [SHR] 1.11, 95% CI 1.10–1.12 and SHR 1.22, 95% CI 1.21–1.23, respectively). Patients in medical centers had the highest rate of kidney transplantation among the three groups. In patients with incident kidney failure, a larger hemodialysis facility size was associated with lower mortality. Overall, medical center patients had a lower mortality rate and higher transplantation rate, whereas clinic patients had a lower hospitalization risk.
Effect of formaldehyde exposure on bacterial communities in simulating indoor environments
Authors: Guo Jianguo , Xiong Yi , Kang Taisheng , Zhu Hua , Yang Qiwen , Qin Chuan
Published: October 2021

Indoor formaldehyde (CH2O) exceeding the recommended level is a severe threat to human health. Few studies have investigated its effect on indoor surface bacterial communities, affecting habitants' health. This study used 20-L glass containers to mimic the indoor environment with bacterial inputs from human oral respiration. The behavior of bacterial communities responding to CH2O varied among the different CH2O levels. The bacterial community structure significantly changed over time in the 0.054 mg·m−3 CH2O group, which varied from the 0.1 mg·m−3 and 0.25 mg·m−3 CH2O groups. The Chao1 and Shannon index significantly increased in the 0.054 mg·m−3 CH2O group at 6 week, while they remained unchanged in the 0.25 mg·m−3 CH2O group. At 12 week, the Chao1 significantly increased in the 0.25 mg·m−3 CH2O group, while it remained unchanged in the 0.054 mg·m−3 CH2O group. Only a few Operational Taxonomic Units (OTUs) significantly correlated with the CH2O concentration. CH2O-induced OTUs mainly belong to the Proteobacteria and Firmicutes. Furthermore, bacterial communities formed at 6 or 12 weeks differed significantly among different CH2O levels. Functional analysis of bacterial communities showed that inferred genes related to chemical degradation and diseases were the highest in the 0.25 mg·m−3 CH2O group at 12 weeks. The development of nematodes fed with bacteria collected at 12 weeks was applied to evaluate the bacterial community's hazards. This showed significantly impaired growth in the 0.1 mg·m−3 and 0.25 mg·m−3 CH2O groups. These findings confirmed that CH2O concentration and exposure time could affect the indoor bacterial community and formed bacterial communities with a possibly more significant hazard to human health after long-term exposure to high CH2O levels.
Profile of esophageal squamous cell carcinoma mutations in Brazilian patients
Authors: Munari Fernanda Franco , dos Santos Wellington , Evangelista Adriane Feijó , Carvalho Ana Carolina , Pastrez Paula Aguiar , Bugatti Diego , Wohnrath Durval R. , Scapulatempo-Neto Cristovam , Guimarães Denise Peixoto , Longatto-Filho Adhemar , Reis Rui Manuel
Published: October 2021

Esophageal cancer is an aggressive tumor that has a high rate of incidence and mortality worldwide. It is the 10th most frequent type in Brazil, being squamous cell carcinoma (ESCC) the predominant subtype. There is currently an incessant search to identify the frequently altered genes associated with esophageal squamous cell carcinoma biology that could be druggable. This study aimed to analyze the somatic mutation profile of a large panel of cancer-related genes in Brazilian ESCC. In a series of 46 ESCC diagnoses at Barretos Cancer Hospital, DNA isolated from paired fresh-frozen and blood tissue, a panel of 150 cancer-related genes was analyzed by next-generation sequencing. The genes with the highest frequency of mutations were TP53 (39/46, 84.8%), followed by NOTCH1 (7/46, 15.2%), NFE2L2 (5/46, 10.8%), RB1 (3/46, 6.5%), PTEN (3/46, 6.5%), CDKN2A (3/46, 6.5%), PTCH1 (2/46, 4.3%) and PIK3CA (2/46, 4.3%). There was no significant association between molecular and patients’ clinicopathological features. Applying an evolutionary action score of p53 (EAp53), we observed that 14 (35.9%) TP53 mutations were classified as high-risk, yet no association with overall survival was observed. Concluding, this the largest mutation profile of Brazilian ESCC patients, which helps in the elucidation of the major cancer-related genes in this population.
DNA barcoding allows identification of undescribed crab megalopas from the open sea
Authors: Marco-Herrero Elena , Cuesta Jose A. , González-Gordillo J. Ignacio
Published: October 2021

Megalopas of 15 brachyuran crab species collected in the open sea plankton, and unknown until now, were identified using DNA barcodes (COI and 16S rRNA). Specimens belonging to the families Portunidae, Pseudorhombilidae and Xanthidae (Crustacea, Decapoda, Brachyura), and corresponding to the species Achelous floridanus, Arenaeus mexicanus, Callinectes amnicola, C. arcuatus, C. ornatus, C. toxones, Charybdis (Charybdis) hellerii, Portunus hastatus, Thalamita admete, Scopolius nuttingi, Etisus odhneri, Liomera cinctimanus, Neoliomera cerasinus, Pseudoliomera variolosa, and Williamstimpsonia stimpsoni, are described and illustrated, and compared with other congeneric species previously described. We also provide a new geographical record for N. cerasinus and the most remarkable features for each species.
Deregulation of hsa_circ_0001971/miR-186 and hsa_circ_0001874/miR-296 signaling pathways promotes the proliferation of oral squamous carcinoma cells by synergistically activating SHP2/PLK1 signals
Authors: Jun Wang , Shaobo Ouyang , Xianhua Zhang , Siyu Zhao , Mingyang Cheng , Xin Fan , Ying Cai , Lan Liao
Published: October 2021

It has been demonstrated that circ_0001874 and circ_0001971 are potential biomarkers for the diagnosis of oral squamous carcinoma (OSCC). MiR-186 was reported to serve as a tumor suppressor in OSCC, and the down-regulation of miR-186 was reported to lead to higher expression of oncogenic factor SHP2 and the activation of growth promoting signaling. In this study, we aimed to explore the possible molecular role of circ_0001874 and circ_0001971 signaling in the pathogenesis of OSCC. RT-qPCR, Western blot, online bioinformatics tools and luciferase assay were utilized to study the molecular signaling pathways of circ_0001874 and circ_0001971. MTT assay and FCM assay were performed to investigate the synergistic effect of circ_0001971 and circ_0001874 on cell proliferation and apoptosis. By observing the effect of different miRNAs on the levels of circ_0001847 and circ_0001971, it was identified that circ_0001847 and circ_0001971 respectively sponged the expression of miR-296 and miR-186 via binding to these miRNAs. Also, SHP2 mRNA and PLK1 mRNA were respectively targeted by miR-186 and miR-296-5p. We also established two signaling pathways, i.e., circ_0001971/miR-186/SHP2 and circ_0001874/miR-296-5p/PLK1, and validated the synergistic effect of circ_0001971 and circ_0001874 via observing their positive effect on cell proliferation and negative effect on cell apoptosis. The expression of miR-186 and miR-296-5p was generally lower in saliva of OSCC patients compared with that in OLK patients, while the expression of miR-186 and miR-296-5p was specifically up-regulated in saliva of OSCC patients. In conclusion, the finding of this study demonstrated that the relative level of hsa_circ_0001971 and hsa_circ_0001874 were different in the saliva of OSCC patients and could be used as predictive biomarkers for the development of OSCC. Furthermore, oncogenic effects of hsa_circ_0001971 and hsa_circ_0001874 in the development of OSCC might be, at least partially, mediated by its downstream signaling pathways including hsa_circ_0001971/microRNA-186/SHP2 and hsa_circ_0001874/microRNA-297/PLK1.
Comparison of in silico strategies to prioritize rare genomic variants impacting RNA splicing for the diagnosis of genomic disorders
Authors: Rowlands Charlie , Thomas Huw B. , Lord Jenny , Wai Htoo A. , Arno Gavin , Beaman Glenda , Sergouniotis Panagiotis , Gomes-Silva Beatriz , Campbell Christopher , Gossan Nicole , Hardcastle Claire , Webb Kevin , O’Callaghan Christopher , Hirst Robert A. , Ramsden Simon , Jones Elizabeth , Clayton-Smith Jill , Webster Andrew R. ,   Genomics England Research Consortium, Ambrose J. C. , Arumugam P. , Bevers R. , Bleda M. , Boardman-Pretty F. , Boustred C. R. , Brittain H. , Caulfield M. J. , Chan G. C. , Fowler T. , Giess A. , Hamblin A. , Henderson S. , Hubbard T. J. P. , Jackson R. , Jones L. J. , Kasperaviciute D. , Kayikci M. , Kousathanas A. , Lahnstein L. , Leigh S. E. A. , Leong I. U. S. , Lopez F. J. , Maleady-Crowe F. , McEntagart M. , Minneci F. , Moutsianas L. , Mueller M. , Murugaesu N. , Need A. C. , O’Donovan P. , Odhams C. A. , Patch C. , Perez-Gil D. , Pereira M. B. , Pullinger J. , Rahim T. , Rendon A. , Rogers T. , Savage K. , Sawant K. , Scott R. H. , Siddiq A. , Sieghart A. , Smith S. C. , Sosinsky A. , Stuckey A. , Tanguy M. , Taylor Tavares A. L. , Thomas E. R. A. , Thompson S. R. , Tucci A. , Welland M. J. , Williams E. , Witkowsa K. , Wood S. M. , Douglas Andrew G. L. , O’Keefe Raymond T. , Newman William G. , Baralle Diana , Black Graeme C. M. , Ellingford Jamie M.
Published: October 2021

The development of computational methods to assess pathogenicity of pre-messenger RNA splicing variants is critical for diagnosis of human disease. We assessed the capability of eight algorithms, and a consensus approach, to prioritize 249 variants of uncertain significance (VUSs) that underwent splicing functional analyses. The capability of algorithms to differentiate VUSs away from the immediate splice site as being ‘pathogenic’ or ‘benign’ is likely to have substantial impact on diagnostic testing. We show that SpliceAI is the best single strategy in this regard, but that combined usage of tools using a weighted approach can increase accuracy further. We incorporated prioritization strategies alongside diagnostic testing for rare disorders. We show that 15% of 2783 referred individuals carry rare variants expected to impact splicing that were not initially identified as ‘pathogenic’ or ‘likely pathogenic’; one in five of these cases could lead to new or refined diagnoses.
Identification and analyses of the chemical composition of a naturally occurring albino mutant chanterelle
Authors: Thorn R. Greg , Banwell Alicia , Pham Thu Huong , Vidal Natalia P. , Manful Charles Felix , Nadeem Muhammad , Ivanov Alexander G. , Szyszka Mroz Beth , Bonneville Michael B. , Hüner Norman Peter Andrew , Piercey-Normore Michele D. , Thomas Raymond
Published: October 2021

White chanterelles (Basidiomycota), lacking the orange pigments and apricot-like odour of typical chanterelles, were found recently in the Canadian provinces of Québec (QC) and Newfoundland & Labrador (NL). Our phylogenetic analyses confirmed the identification of all white chanterelles from NL and QC asCantharellus enelensis; we name these formaacolodorus. We characterized carotenoid pigments, lipids, phenolics, and volatile compounds in these and related chanterelles. White mutants ofC. enelensislacked detectable β-carotene, confirmed to be the primary pigment of wild-type, golden-orange individuals, and could also be distinguished by their profiles of fatty acids and phenolic acids, and by the ketone and terpene composition of their volatiles. We detected single base substitutions in the phytoene desaturase (Al-1) and phytoene synthase (Al-2) genes of the white mutant, which are predicted to result in altered amino acids in their gene products and may be responsible for the loss of β-carotene synthesis in that form.
Dialyzer surface area is a significant predictor of mortality in patients on hemodialysis: a 3-year nationwide cohort study
Authors: Abe Masanori , Masakane Ikuto , Wada Atsushi , Nakai Shigeru , Nitta Kosaku , Nakamoto Hidetomo
Published: October 2021

A target Kt/V of > 1.4 and use of a high-flux dialyzer are recommended for patients on hemodialysis. However, there is little information on the relationship between the dialyzer surface area and mortality in these patients. In this nationwide cohort study, we aimed to clarify this relationship by analyzing data from the Japanese Society for Dialysis Therapy for 2010–2013. We enrolled 234,638 patients on hemodialysis who were divided according to quartile for dialyzer surface area into the S group (small, < 1.5 m2), M group (medium, 1.5 m2), L group (large, 1.6 to < 2.0 m2), or XL group (extra-large, ≥ 2.0 m2). We assessed the association of each group with 3-year mortality using Cox proportional hazards models and performed propensity score matching analysis. By the end of 2013, a total of 53,836 patients on dialysis (22.9%) had died. There was a significant decrease in mortality with larger dialyzer surface areas. The hazard ratio (95% confidence interval) was significantly higher in the S group (1.15 [1.12–1.19], P < 0.0001) and significantly lower in the L group (0.89 [0.87–0.92] P < 0.0001) and XL group (0.75 [0.72–0.78], P < 0.0001) than in the M group as a reference after adjustment for all confounders. Findings were robust in several sensitivity analyses. Furthermore, the findings remained significant after propensity score matching. Hemodialysis using dialyzers, especially super high-flux dialyzers with a larger surface area might reduce mortality rates, and a surface area of ≥ 2.0 m2 is superior, even with the same Kt/V.
The influence of the grass mixture composition on the quality and suitability for football pitches
Authors: Wolski Karol , Markowska Joanna , Radkowski Adam , Brennensthul Marek , Sobol Łukasz , Pęczkowski Grzegorz , Bujak Henryk , Grzebieniarz Wiktoria , Radkowska Iwona , Khachatryan Karen
Published: October 2021

The selection of grass mixtures with appropriate visual and functional parameters for sowing football fields is a key element in shaping the sports infrastructure, ensuring the spectacularity of a match and comfort for players. The aim of the research was to investigate the properties of lawn grass mixtures and their suitability for football pitches. The experiment was conducted at the Toya Golf & Country Club (51° 20′ E, 17° 07′ N), Wrocław, Poland, between 2007 and 2009. 12 grass mixtures were selected, mainly based on red fescue, Kentucky bluegrass, and perennial ryegrass. The assessment was carried out using a nine-point scale, according to the Plant Variety Office methodology for crops and turf grass. Six features of sports turf were studied: appearance, density, colour, leaf fineness, overwintering, and susceptibility to disease and they significantly varied, depending on the grass mixture and the year of research. Our study showed that mixtures based on the dominance of meadow grass were characterized by higher values of the general visual aspect, colour and slenderness of the leaf blade and these based on the dominance of perennial ryegrass and co-dominance of perennial ryegrass and meadow grass were the most useful in terms of wintering, resistance to diseases and sodding.
Interpretable machine learning for early neurological deterioration prediction in atrial fibrillation-related stroke
Authors: Kim Seong-Hwan , Jeon Eun-Tae , Yu Sungwook , Oh Kyungmi , Kim Chi Kyung , Song Tae-Jin , Kim Yong-Jae , Heo Sung Hyuk , Park Kwang-Yeol , Kim Jeong-Min , Park Jong-Ho , Choi Jay Chol , Park Man-Seok , Kim Joon-Tae , Choi Kang-Ho , Hwang Yang Ha , Kim Bum Joon , Chung Jong-Won , Bang Oh Young , Kim Gyeongmoon , Seo Woo-Keun , Jung Jin-Man
Published: October 2021

We aimed to develop a novel prediction model for early neurological deterioration (END) based on an interpretable machine learning (ML) algorithm for atrial fibrillation (AF)-related stroke and to evaluate the prediction accuracy and feature importance of ML models. Data from multicenter prospective stroke registries in South Korea were collected. After stepwise data preprocessing, we utilized logistic regression, support vector machine, extreme gradient boosting, light gradient boosting machine (LightGBM), and multilayer perceptron models. We used the Shapley additive explanation (SHAP) method to evaluate feature importance. Of the 3,213 stroke patients, the 2,363 who had arrived at the hospital within 24 h of symptom onset and had available information regarding END were included. Of these, 318 (13.5%) had END. The LightGBM model showed the highest area under the receiver operating characteristic curve (0.772; 95% confidence interval, 0.715–0.829). The feature importance analysis revealed that fasting glucose level and the National Institute of Health Stroke Scale score were the most influential factors. Among ML algorithms, the LightGBM model was particularly useful for predicting END, as it revealed new and diverse predictors. Additionally, the effects of the features on the predictive power of the model were individualized using the SHAP method.
Impairment of emotional expression detection after unilateral medial temporal structure resection
Authors: Sato Wataru , Usui Naotaka , Sawada Reiko , Kondo Akihiko , Toichi Motomi , Inoue Yushi
Published: October 2021

Detecting emotional facial expressions is an initial and indispensable component of face-to-face communication. Neuropsychological studies on the neural substrates of this process have shown that bilateral amygdala lesions impaired the detection of emotional facial expressions. However, the findings were inconsistent, possibly due to the limited number of patients examined. Furthermore, whether this processing is based on emotional or visual factors of facial expressions remains unknown. To investigate this issue, we tested a group of patients (n = 23) with unilateral resection of medial temporal lobe structures, including the amygdala, and compared their performance under resected- and intact-hemisphere stimulation conditions. The participants were asked to detect normal facial expressions of anger and happiness, and artificially created anti-expressions, among a crowd with neutral expressions. Reaction times for the detection of normal expressions versus anti-expressions were shorter when the target faces were presented to the visual field contralateral to the intact hemisphere (i.e., stimulation of the intact hemisphere; e.g., right visual field for patients with right hemispheric resection) compared with the visual field contralateral to the resected hemisphere (i.e., stimulation of the resected hemisphere). Our findings imply that the medial temporal lobe structures, including the amygdala, play an essential role in the detection of emotional facial expressions, according to the emotional significance of the expressions.
The presynaptic glycine transporter GlyT2 is regulated by the Hedgehog pathway in vitro and in vivo
Authors: de la Rocha-Muñoz Andrés , Núñez Enrique , Vishwanath Anjali Amrapali , Gómez-López Sergio , Dhanasobhon Dhanasak , Rebola Nelson , López-Corcuera Beatriz , de Juan-Sanz Jaime , Aragón Carmen
Published: October 2021

The identity of a glycinergic synapse is maintained presynaptically by the activity of a surface glycine transporter, GlyT2, which recaptures glycine back to presynaptic terminals to preserve vesicular glycine content. GlyT2 loss-of-function mutations cause Hyperekplexia, a rare neurological disease in which loss of glycinergic neurotransmission causes generalized stiffness and strong motor alterations. However, the molecular underpinnings controlling GlyT2 activity remain poorly understood. In this work, we identify the Hedgehog pathway as a robust controller of GlyT2 expression and transport activity. Modulating the activation state of the Hedgehog pathway in vitro in rodent primary spinal cord neurons or in vivo in zebrafish embryos induced a selective control in GlyT2 expression, regulating GlyT2 transport activity. Our results indicate that activation of Hedgehog reduces GlyT2 expression by increasing its ubiquitination and degradation. This work describes a new molecular link between the Hedgehog signaling pathway and presynaptic glycine availability.
Genetically modifying skin microbe to produce violacein and augmenting microbiome did not defend Panamanian golden frogs from disease
Authors: Becker Matthew H , Brophy Jennifer A N , Barrett Kevin , Bronikowski Ed , Evans Matthew , Glassey Emerson , Kaganer Alyssa W , Klocke Blake , Lassiter Elliot , Meyer Adam J , Muletz-Wolz Carly R , Fleischer Robert C , Voigt Christopher A , Gratwicke Brian
Published: October 2021

We designed two probiotic treatments to control chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) on infected Panamanian golden frogs (Atelopus zeteki), a species that is thought to be extinct in the wild due to Bd. The first approach disrupted the existing skin microbe community with antibiotics then exposed the frogs to a core golden frog skin microbe (Diaphorobacter sp.) that we genetically modified to produce high titers of violacein, a known antifungal compound. One day following probiotic treatment, the engineered Diaphorobacter and the violacein-producing pathway could be detected on the frogs but the treatment failed to improve frog survival when exposed to Bd. The second approach exposed frogs to the genetically modified bacterium mixed into a consortium with six other known anti-Bd bacteria isolated from captive A. zeteki, with no preliminary antibiotic treatment. The consortium treatment increased the frequency and abundance of three probiotic isolates (Janthinobacterium, Chryseobacterium, and Stenotrophomonas) and these persisted on the skin 4 weeks after probiotic treatment. There was a temporary increase in the frequency and abundance of three other probiotics isolates (Masillia, Serratia, and Pseudomonas) and the engineered Diaphorobacter isolate, but they subsequently disappeared from the skin. This treatment also failed to reduce frog mortality upon exposure.
Covalent organic framework based nanoagent for enhanced mild-temperature photothermal therapy
Authors: Sun Qiaoqiao , Tang Kun , Song Liqun , Li Yanhua , Pan Wei , Li Na , Tang Bo
Published: October 2021

A cancer therapy strategy based on nanoscale COFs and GA was developed to enhance photothermal therapy at mild-temperature by inhibiting HSP90.
Amphiphilic γ-cyclodextrin–fullerene complexes with photodynamic activity
Authors: Miki Koji , Dan Zhang Zi , Kaneko Kaho , Kakiuchi Yui , Kojima Kentaro , Enomoto Akane , Oe Masahiro , Nogita Kohei , Murata Yasujiro , Harada Hiroshi , Ohe Kouichi
Published: October 2021

High-speed vibration milling of a mixture of lipophilic γ-cyclodextrin (γ-CD), hydrophilic γ-CD and fullerene or functionalization of preformed γ-CD–fullerene complexes afforded amphiphilic γ-CD–fullerene complexes with high photodynamic activity.