bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the correlation and interaction between urinary metals level and diabetes:A case-control study of community-dwelling elderly
Authors: Wang Rui , He Pei , Duan Siyu , Zhang Zhongyuan , Dai Yuqing , Li Meiyan , Shen Zhuoheng , Li Xiaoyu , Song Yanan , Sun Yiping , Zhang Rui , Sun Jian , Yang Huifang
Published: February 2023

Background
It has been reported that metal exposure is associated with the risk of diabetes, but the results are inconsistent.The relationship between diabetes and a single metal might be attenuated or strengthened due to the complex interactions of metals and the chronic diseases comorbidity (especially in the elderly). However, the evidence of multiple metal exposure effect in participants with diabetes only is limited, particularly in the elderly. The present case-control study of 188 diabetic and 376 healthy participants aimed to evaluate the potential relationships between the concentrations of 9 metals in urine and the risk of diabetes and to access the interactive effects of metals in Chinese community-dwelling elderly.
Methods
The urine levels of 9 metals (cobalt, zinc, copper, arsenic, molybdenum, cadmium, tellurium, thallium, lead) were detected by inductively coupled plasma mass spectrometry (ICP-MS) in 564 adults recruited from Yinchuan Community Health Service Center (Yinchuan, China).Logistic regression and restricted cubic spline (RCS) analysis were used to explore the associations and dose-response relationships of urine metals with diabetes. To analysis of multi-metal exposures and diabetes risk, weighted quantile sum regression Models (WQS) and the Bayesian Kernel Machine Regression (BKMR) model were applied.
Results
The concentrations of cobalt, zinc, copper, arsenic, molybdenum, cadmium, tellurium, thallium and lead were higher in the diabetes group (p < 0.05). In logistic regression analysis, we found that the OR values of urinary cobalt, zinc, copper, arsenic, molybdenum, cadmium, tellurium, thallium, and lead quartiles showed an increasing trend. In the single-metal model, the adjusted ORs(95%CI) in the highest quartiles were 2.94(1.72,5.05) for cobalt,5.05 (2.85,8.93) for zinc, 2.28(1.32,3.91) for copper, 1.99(1.15,3.43) for arsenic, 2.61(1.54,4.43) for molybdenum, 2.89(1.68,4.96) for cadmium, 2.52(1.44,4.41) for tellurium, 3.53(2.03,6.12) for thallium and 2.18(1.27,3.75) for lead compared with the lowest quartile. And in the RCS model, the concentrations of cobalt, zinc, copper, arsenic, molybdenum, cadmium, tellurium, thallium and lead showed a nonlinear dose-response relationship with diabetes risk (P-overall < 0.05,P-nonlinear < 0.05). The results from multi-pollutant models all indicated that metal mixture was positively associated with the risk of diabetes, and Zn and Tl were the major contributors to the combined effect.
Conclusion
Elevated levels of urine cobalt, zinc, copper, arsenic, molybdenum, cadmium, tellurium, thallium and lead were associated with increased risk of diabetes. There is a positive interaction between Zn and Tl on diabetes.
Is Food Insecurity a Predictor of Sustainable and Healthy Eating Behaviors?
Authors: SELÇUK Kevser TARI , Atan Ramazan Mert , ARSLAN Sedat , ŞAHİN Nursel
Published: February 2023

In this cross-sectional study, it was aimed to investigate the relationship between food insecurity and sustainable and healthy eating (SHE) behaviors in adults. The study included 410 adults who were reached through social media applications. Data were collected through an online questionnaire including the Descriptive Information Form, the Household Food Insecurity Access Scale (HFIAS), and the SHE Behaviors Scale. The proportion of participants determined as mildly food insecure, moderately food insecure and severely food insecure was 10.2%, 6.6%, and 7.6%, respectively. Household food insecurity is adversely correlated with the Healthy and Balanced Diet (β:-0.226, p < 0.001), Quality Labels (β:-0.230, p < 0.001), Seasonal Foods and Avoidance of Food Waste (β:-0.261, p < 0.001), Animal Welfare (β:-0.174, p < 0.001) and Fat Intake (β:-0.181, p < 0.001). Household food insecurity is the negative predictor of healthy and balanced diet, Quality Labels, Seasonal Foods and Avoidance of Food Waste, Animal Welfare and Fat Intake.
Creep and strength characteristics of cemented gangue backfill under coupling effect of load and acid corrosion
Authors: Guo Yuxia , Zhao Yonghui , Feng Guorui
Published: February 2023

Cemented gangue backfill technology is beneficial to the reuse of solid waste and sustainable economic development. However, Mine water has a great impact on the strength and deformation of cemented gangue backfill (CGB). In this study, the CGB specimens under load were placed in simulated acid mine water (H2SO4 solution). The changes of deformation, resistivity, and ultrasonic pulse velocity (UPV) of CGB were monitored. On the 360th day, the stress-strain curve and acoustic emission (AE) energy of the specimen during loading were recorded. the degradation mechanism of CGB was discussed by scanning electron microscope (SEM), and X-ray diffraction (XRD). The results showed that: the deformation of CGB increased with time. The effect of H2SO4 solution concentration on the deformation was different in early and late stages. Applying 80% stress-strength ratio (SSR) reduced the strength and increased the deformation. The UPV and resistivity had different characteristics at different corrosion ages, which could be used as long-term stability monitoring of CGB. The CGB showed the strongest AE energy characteristics near the peak stress. The AE energy decreased with the increase of pH value in the pore compaction stage, and the AE activity of the CGB under 80% SSR was much greater than that of the CGB under 40% SSR. The erosion of H2SO4 solution on the CGB was inhibited by applying a small load. Excessive load aggravated the erosion deterioration of CGB due to initial plastic damage. The research results can provide reference for durability design of CGB.
Optical coherence tomographic findings of glaucomatous
eyes with papillomacular retinoschisis
Authors: Ishida Tomoka , Kita Yoshiyuki , Mizuno Masaharu , Hirota Kazunari , Koto Takashi , Inoue Makoto , Hirakata Akito
Published: February 2023

Objectives
To investigate the topographic relationship between the shape of the optic nerve head (ONH) margin detected by optical coherence tomography (OCT) and the clinical characteristics of papillomacular retinoschisis (PMRS) in glaucomatous eyes.
Methods
The medical record of patients with a PMRS in a glaucomatous eye were reviewed. The eyes were placed into two groups determined by the shape of the ONH margin in the OCT images; eyes with an externally oblique ONH margin (Group 1) and the eyes with an internally oblique ONH margin (Group 2). We compared the clinical characteristics of the PMRS between these two groups.
Results
We studied 31 eyes of 29 patients with PMRS and glaucoma with 24 eyes in Group 1 and 7 eyes in Group 2. The optic nerve fiber layer schisis on the lamina cribosa (LC), beta zone, and gamma zone, and the LC defects were detected significantly more frequently in Group 1 than in Group 2 eyes (P < 0.05). A retinal nerve fiber schisis was observed around the ONH significantly more frequently in Group 2 than Group 1 eyes (P < 0.01).
Conclusion
These findings suggest that the PMRS in Group 1 eyes develops most likely around the LC defects while the PMRS in Group 2 eyes develops most likely from the optic nerve fiber layer around the ONH.
Single-cell profiling reveals the trajectory of FOLR2-expressing tumor-associated macrophages to regulatory T cells in the progression of lung adenocarcinoma
Authors: Yu Yang , Xiang Chan , Zhang Min , Shang Zhanxian , Chen Shengnan , Zhao Jikai , Ding Bowen , Jiang Dong , Zhu Qian , Teng Haohua , Zhu Lei , Shao Jinchen , Zhao Ruiying , Yu Yang
Published: February 2023

The authors have requested that this preprint be removed from Research Square.
Case Report: A Case Report and Literature Analysis on Intestinal Tuberculosis Intestinal Perforation Complicated by Umbilical Intestinal Fistula and Bladder Ileal Fistula
Authors: Chen Tianyan , Liu Guobin , Kang Quan , Song Xiaofeng , Chen Bolin
Published: February 2023

Objectives and design: This article is to make pediatric surgeons fully aware of the atypical manifestations caused by intestinal tuberculosis, as well as the principles and methods of diagnosis and treatment reported in this case and related literature.
Materials and methods: Description of a case report.
Results: We report a rare case of umbilical fistula and bladder ileal fistula caused by intestinal perforation secondary to intestinal tuberculosis，and analysis and summary the literature on the diagnosis and treatment of intestinal TB.
Conclusions: This is a rare case of umbilical fistula and bladder ileal fistula caused by intestinal perforation secondary to intestinal tuberculosis. The purpose of this article is to make the surgical community aware of this atypical presentation of intestinal tuberculosis so that they can be prepared if they encounter this condition in the future.
The association between fear of missing out and mobile phone addiction: A meta-analysis
Authors: Zhang Yali , Zhang Weina
Published: February 2023

Background
Numerous studies have explored the association between fear of missing out and mobile phone addiction, but the results were inconsistent. This study aims at exploring the relationship between fear of missing out and mobile phone addiction, as well as the reasons for the different results of previous studies.
Methods
In order to achieve our goals, a meta-analysis of 42 studies (43 effect sizes) was conducted with a random-effects model in this research.
Results
The main effect analysis revealed a high positive correlation between fear of missing out and mobile phone addiction (r = 0.47, 95%CI=[0.44, 0.50]). Furthermore, the measurements applied to quantify the variables moderated the strength of the association between fear of missing out and mobile phone addiction, whereas age, gender, year of publication and cultural background didn't.
Conclusions
The results indicated that fear of missing out was closely related to mobile phone addiction, which complied with the Theory of Compensatory Internet Use. In the future, experimental and longitudinal studies are needed to explore the dynamic relationship between fear of missing out and mobile phone addiction.
The belowground of the resurrection plant Myrothamnus flabellifolia: Exploring the desiccation-tolerant root-associated microbiome
Authors: Tebele Shandry M. , Marks Rose A. , Farrant Jill Margaret
Published: February 2023

Aims and Background
The resurrection plant Myrothamnus flabellifolia tolerates complete desiccation and is a great model for studying how plants cope with extreme drought. The response to desiccation in M. flabellifolia leaves has been studied extensively, but little is known about how the associated microbiome contributes to desiccation tolerance. Root-associated microbes play a major role in stress tolerance, and are an attractive target for enhancing drought tolerance in staple crops. However, how these dynamics play out under the most extreme water limitation remains underexplored.
Methods
The high-throughput amplicon metagenomic technique was used to investigated the bacterial and fungal communities in the bulk soil, rhizosphere, and endosphere of the M. flabellifolia.
Results
The bacterial phyla that were most abundant across all compartments were Acidobacteriota, Actinobacteria, Chloroflexi, Planctomycetes andProteobacteria, while fungal phyla were Ascomycotaand Basidiomycota. Although the bulk soil hosted multiple beneficial root-associated microbes, the rhizosphere compartment showed the highest functional diversity of bacteria and fungi. In contrast, the endosphere exhibited a low abundance and diversity of microbes. These findings suggest that M. flabellifolia recruits soil microbes from bulk to rhizosphere, many of which may confer extreme drought tolerance and promote plant growth.
Conclusion
The diverse rhizosphere microbiome is filtered to result in a highly selective endosphere microbiome. We find that compartment niches act as the major driver of microbial diversity, but that soil physicochemical factors also influence the microbial composition. These results suggest that the root-associated microbiome of M. flabellifolia is highly structured and may aid in plant function.
Predicting response and toxicity to immune checkpoint inhibitors in lung cancer using antibodies to frameshift neoantigens
Authors: Shen Luhui , Brown Justin R , Johnston Stephen Albert , Altan Mehmet , Sykes Kathryn Frances
Published: February 2023

Purpose:To evaluate a new class of blood-based biomarkers, anti-frameshift peptide antibodies, for predicting both tumor responses and adverse immune events to immune checkpoint inhibitor (ICI) therapies in advanced lung cancer patients.Experimental Design:Serum samples were obtained from 74 lung cancer patients prior to palliative PD-(L)1 therapies with subsequently recorded tumor responses and immune adverse events (irAEs). Pretreatment samples were assayed on microarrays of frameshift peptides (FSPs), representing ~375,000 variant peptides that tumor cells can be informatically predicted to produce from translated mRNA processing errors. Serum-antibodies recognizing these ligands were measured. Differential binding profiles of best-response and adverse-event contrasts were analyzed. Binding activities shared among an outcome group but distinct relative to the other were identified. Antibody bound FSPs were used in iterative resampling analyses to develop predictive models of clinical response and immune toxicity.Results:Lung cancer serum samples were classified based on predictive models of ICI treatment outcomes. Disease progression was predicted with 100% accuracy pretreatment in the full cohort of all response categories, although half of the samples did not show the minimum number of differential binding events to classify. This model included samples from patients that i) would show either responsive or stable outcomes, ii) would be administered either single or combination therapies and iii) were diagnosed with different lung cancer subtypes. Removing the stable disease group or those who would receive combination chemotherapy increased the proportion of samples classified. On the other hand, removing small cell lung cancer from the non-small cell cancer samples had little impact. Informatic analyses showed that several of the FSPs in the all-response model mapped to translations of variant mRNAs from the same genes. In the predictive model for treatment toxicities, binding to irAE-associated FSPs provided 88% prediction accuracy pretreatment, with no indeterminates. Several of the classifying FSPs displayed sequence similarity to self-proteins.Conclusions:Anti-FSP antibodies may serve as biomarkers for predicting ICI outcomes when tested against ligands corresponding to mRNA-error derived FSPs. Model performances suggest this approach might provide a single test to predict treatment response to ICI and identify patients at high risk for immunotherapy toxicities.
Dietary Exposure Risk Assessment of Pyrethroids in Fruits and Vegetables: A National Scale Investigation
Authors: Li Qianqian , Li Bei , Chen Dawei , Zhang Rong , Liu Shuyan , Yang Shupeng , Li Yi , Li Jianxun
Published: February 2023

The pyrethroids (PYRs) were extensively used to increase agriculture outputs. However, the cumulative exposures of PYRs would bring about potential risks through food intake. It is in urgent requirement to explore the cumulative exposures on the fruits and vegetables. In this study, a total of 1720 samples incorporating eight primary fruits and vegetables collected around China were investigated to assess the health risk for adults and children from eight PYRs. The relative potency factor (RPF) method was employed to reveal both chronic and acute cumulative exposure. As a result, the hazard index (HI) were 0.004%~0.200% and 11.85%~99.19% for chronic and acute cumulative dietary exposure, respectively. The national wide investigation indicated the cumulative assessments were not hazardous. Besides, the acute intake of pear, grape, and lettuce should be paid on more attention, particularly. This study provides compelling evidence to develop relative policy and regulation to improve the food quality and safety.
The mannitol-modified emodin nano drug restored the intestinal barrier function and alleviated inflammation in a mouse model of DSS-induced colitis
Authors: Xu Yinyue , Zhu Min , Wu Jiang , Luo Longbiao , Dong Sijing , Zhang Menggai , Liu Xue , Wang Ke , Wang Yitao , Jing Wanghui , Wang Lin , Wang Sicen
Published: February 2023

Background
Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to develop safe and effective drugs for treating UC. Emodin, a natural anthraquinone derivative presenting in various medicinal herbs, has demonstrated therapeutic effects against colitis. However, low bioavailability due to poor water solubility limits its clinical applications.
Methods
Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal cells expressing mannose receptors. Colitis was induced in a mouse model using dextran sulphate sodium (DSS), and the different drug formulations were administered to the mice via drinking water. The levels of inflammation-related factors in the colon tissues and fecal matter were measured by enzyme linked immunosorbent assay (ELISA). Intestinal permeability was evaluated using fluorescein isothiocyanate dextran. HE staining, in vivo imaging, real-time PCR and western blotting were performed to assess intestinal barrier dysfunction.
Results
Both EmB and EmB-MO markedly alleviated the symptoms of colitis, including body weight loss, stool inconsistency and bloody stools, and restored the levels of pro- and anti-inflammatory cytokines. However, the therapeutic effects of EmB-MO on the macroscopic and immunological indices were stronger compared to that of EmB, and similar to that of 5-aminosalicylicacid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium, and restored the levels of the gut barrier proteins ZO-1 and occludin.
Conclusions
Encapsulation of EmB-MO significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced colitis. Our findings provide novel insights into developing emodin-derived drugs for the management of UC.
RankDMG: a differentially methylated gene analysis method for three special scenarios
Authors: Fan Qi , Zheng Linyong , Chen Haifeng , He Jun , Yang Fenglong , Shen Xiaopei , Yan Haidan
Published: February 2023

Background
Common methods of identification of differentially methylated genes (DMGs) mainly detect differences between case and control groups, which cannot tell whether a gene is differentially methylated in a specific disease sample (first scenario), and are not applicable for the study with no normal control (one-phenotype, second scenario). Also, these methods have low detection capacity at the control-limited (third) scenario.
Results
we developed a method, termed RankDMG, to analyze DNA methylation data in the three special scenarios. For the individualized DMG analysis, RankDMG showed remarkable performances in simulated and real data, independent of measured platforms. Using DMGs detected by common methods as ‘gold standard’, the DMGs identified by RankDMG using only one-phenotype data were comparable to those detected by common methods using case-control samples. Moreover, even when the number of disease samples reduced to five, RankDMG could also identify disease-related DMGs for control-limited data.
Conclusion
RankDMG provides a novel tool to dissect the inter-individual heterogeneity of tumor at epigenetic level, and it could analyze the one-phenotype and control-limited methylation data. RankDMG is provided as an open source tool via https://github.com/FunMoy/RankDMG.
Screw fixation without fusion for low lumbar Chance fracture accompanied by spinal epidural hematoma in patient with ankylosing spondylitis
Authors: Kim Dae Kyun , Kim Seok Won
Published: February 2023

Ankylosing spondylitis (AS) is a chronic inflammatory disease involving the sacroiliac joint and axial spine. AS may render the ankylosed spine prone to trauma and cause an increased frequency of associated epidural hematomas in spine fractures. Herein, we report a rare case of L5 chance fracture and epidural hematoma in a 27-year-old female patient with AS. She was treated surgically but without bone fusion or decompressive laminectomy due to the neurologically intact status despite significant neural compression by the spinal epidural hematoma (SEH). We believe that conservative treatment with close observation of neurological status may be effective in SEH presenting with mild neurological symptoms despite significant neural compression. It was possible to preserve motion segments by minimally invasive percutaneous screw fixation instead of conventional long-level fixation and bone fusion in low lumbar chance fractures accompanying SEH in patients with AS.
A simple and available measurement of onco-exosome dsDNA to protein ratio as a potential tumor marker
Authors: Sun Yifan , Li Miao , Zhang Xiaoshan , Xu Dongjie , Wu Jie , Gu Xinrui , Khan Adeel , Shen Han , Li Zhiyang
Published: February 2023

Background: Exosomes have great potential as new biomarkers in liquid biopsy. However, due to the limitations of exosome extraction and component analysis procedures, further clinical applications of exosomes are hampered. Carcinoembryonic antigen (CEA) is a commonly used broad-spectrum tumor marker that is strongly expressed in a variety of malignancies.
Results: In this study, CEA+ exosomes were directly separated from serum using immunomagnetic beads, and the nucleic acid to protein ultraviolet absorption ratio (NPr) of CEA+ exosomes was determined. It was found that the NPr of CEA+ exosomes in tumor group was higher than that of healthy group. We further analyzed the exosome-derived nucleic acid components using fluorescent staining and found that the concentration ratio of double-stranded DNA to protein (dsDPr) in CEA+ exosomes was also significantly different between the two groups, with a sensitivity of 100% and a specificity of 41.67% for the diagnosis of pan-cancer. The AUC of dsDPr combined with NPr was 0.87 and the ACU of dsDPr combined with CA242 could reach 0.94, showing good diagnostic performance for pan-cancer.
Conclusions: This study demonstrates that the dsDPr of CEA+ exosomes can effectively distinguish exosomes derived from tumor patients and healthy individuals, which can be employed as a simple and cost-effective non-invasive screening technology to assist tumor diagnosis.
Fungi associated with stem collar necroses of Fraxinus excelsior affected by ash dieback
Authors: Peters Sandra , Fuchs Sebastian , Bien Steffen , Bußkamp Johanna , Langer Gitta Jutta , Langer Ewald Johannes
Published: February 2023

In recent decades the vitality and physical stability of European ash trees in Germany have been reduced by European ash dieback, especially when associated with stem collar necroses and rots. This study was carried out to investigate the composition of the fungal communities associated with stem collar necroses. Filamentous fungi were isolated from 58 ash trees out of nine forest stands in northern, eastern, and central Germany. Obtained isolates were identified to a genus or species level by means of morphological and molecular analyses. In total 162 morphotypes including endophytic, saprotrophic and pathogenic fungi were isolated. For 33 species found no prior reports from Fraxinus excelsior were recognised, including Cryptostroma corticale and Diplodia sapinea. None of the identified species were found at all studied sites, though Diplodia fraxini was the most common fungi with regard to frequency within all isolates, occurring at seven sample sites. This species is followed by Hymenoscyphus fraxineus, Armillaria spp., Neonectria punicea, Diaporthe cf. eres, Fusarium cf. lateritium, and Paracucurbitaria sp. in order of frequency within all isolates. The aforementioned species are characterised and analysed in respect to their occurrence in stem collar necroses and at sample sites. The influence of site conditions on the fungal composition was described for five intensively sampled sites with a minimum of five studied trees (Schwansee, Rhüden, Berggießhübel, Satrup, and Schlangen). The sampling site of Schlangen was further subdivided into four subplots with different positions in the terrain. In the remaining four extensive sample sites either one or two trees, respectively, were sampled and analysed (Oranienbaumer Heide, Woltershausen, Wolfenbüttel, and Neuhege). Over all sample sites fungal communities of symptomatic stem tissue are similar concerning the most frequent fungi, but vary greatly according to singularly isolated fungi.
Clinical characteristics and outcomes of women with adenomyosis pain during pregnancy: a retrospective study
Authors: SAYAMA Seisuke , IRIYAMA Takayuki , TAKEIRI Yotaro , HASHIMOTO Ayako , TOSHIMITSU Masatake , ICHINOSE Mari , SEYAMA Takahiro , SONE Kenbun , KUMASAWA Keiichi , NAGAMATSU Takeshi , KOGA Kaori , OSUGA Yutaka
Published: February 2023

Background
Adenomyosis is known to be associated with unfavorable perinatal outcomes, but the patient population among women with adenomyosis who is at high risk for adverse perinatal outcomes remains unclear. Recent case reports show that some women with adenomyosis experience pain at the adenomyosis lesion during pregnancy and have detrimental perinatal outcomes. However, the prevalence of pain onset in women with adenomyosis has not been studied, nor has its influence on perinatal outcomes. This study aimed to clarify the clinical characteristics of pain developing in adenomyosis lesions during pregnancy and the perinatal outcomes associated with this phenomenon.
Methods
This was a single-center retrospective analysis of a cohort of women with adenomyosis who delivered between 2011 and 2021. The incidence of pain onset at adenomyosis lesions among women with adenomyosis during pregnancy was analyzed retrospectively from medical records. Pain during pregnancy was defined as persistent pain at the adenomyosis site with administration of analgesics for pain relief, and its association with perinatal outcomes was analyzed.
Results
Among 91 singleton pregnancies with adenomyosis, 12 pregnancies (13.2%) presented with pain at the adenomyosis site during pregnancy. In total, 5 of the 12 pregnancies (41.7%) developed preeclampsia, which resulted in preterm delivery, and only 3 of the 12 pregnancies (25.0%) achieved term delivery. The incidence of preeclampsia and preterm delivery was higher in those who experienced pain than in those who did not (41.7% vs. 13.9%; p < 0.05, and 66.7% vs. 31.7%; p < 0.05, respectively). Among the women who had pain during pregnancy, the maximum C-reactive protein level was significantly higher in women who developed preeclampsia than in those who did not (5.45 vs. 0.12 mg/dL, p < 0.05).
Conclusion
Our study revealed that adenomyosis can cause pain in over one of eight pregnancies with adenomyosis, which may be associated with the increased incidence of preeclampsia resulting in preterm delivery. Women who present with pain at the adenomyosis lesion, especially those with high C-reactive protein levels, may be at a high risk for the future development of preeclampsia and consequent preterm delivery.
topr: an R package for viewing and annotating genetic association results
Authors: Juliusdottir Thorhildur
Published: February 2023

Background
The successful identification of genetic loci for complex traits in genome-wide association studies (GWAS) has resulted in thousands of GWAS summary statistics becoming publicly available for hundreds of complex traits from multiple cohorts and studies. Visualisation is an important aid for interpreting, comparing, validating, and obtaining an overview of large amounts of data. However, the current software is limited in its ability and flexibility to annotate and simultaneously display multiple GWAS results which is useful when interpreting and comparing association results. Therefore, I created the topr R package to facilitate visualisation, annotation, and comparisons of single or multiple GWAS results. It contains functions tailored for viewing and analysing GWAS results.
Results
topr provides a fast and elegant visual display of association results, along with the annotation of association peaks with their nearest gene. Association results from multiple analyses can be viewed simultaneously over the entire genome or in a more detailed regional view along with gene information. Users can perform the essential steps of visually exploring and annotating association results and generating elegant publication-ready plots.
Conclusions.
topr is developed as a package for the R statistical computing environment, released under the GNU General Public License, and is freely available on the Comprehensive R Archive Network (http://cran.r-project.org/package=topr). The source code is available at GitHub (https://github.com/GenuityScience/topr). topr provides several advantages and advances over the current alternatives, particularly in its gene annotation functionality and customisable display of single- or multiple-association results. With topr, I provide a flexible tool with multiple features to aid in the analysis and evaluation of GWAS association results.
Epithelial Hyperplasia as a Cause of Irregular Astigmatism: Successful Treatment by Mechanical Removal of the Epithelium Only
Authors: Victoria de Rojas Silva Mª , Juan Álvarez de Toledo , Adrián Tobío Ruibal
Published: February 2023

Background
The corneal epithelium remodeling in response to changes in the anterior corneal surface (keratoconus, corneal refractive surgery) is well-documented in the literature. However, several conditions may induce a different behavior of the epithelium, in which focal areas of epithelial thickening induce irregular astigmatism. This case report presents a very unusual case of irregular astigmatism induced by an epithelial hyperplasia of unknown etiology, which was treated by mechanical removal of only the epithelium.
Case presentation
A 29-year-old woman underwent implantable collamer lens implantation to correct myopia. The patient provided written informed consent. The procedure was uneventful in both eyes. Twenty months later, she complained of decreased visual acuity in the left eye (LE) (uncorrected distance visual acuity (UCDVA) was 20/30; corrected distance visual acuity was 20/20 with + 1.00 -2.25 x 170). Corneal topography revealed a nasal steepening in the LE. Although the corneal thickness map was normal, epithelial thickness mapping revealed a localized nasal area of epithelial hyperplasia in the LE, that matched with the area of steepest curvature. Slit lamp examination showed a total clear cornea with no signs of abnormality. Medical history was unremarkable and a case of epithelial hyperplasia without active inflammation of unknown etiology was considered. The decision was made to perform a mechanical removal of the corneal epithelium after application of diluted alcohol. One month after the procedure, the topography of the epithelized cornea showed a regular bow tie pattern and UCDVA improved to 20/20. No recurrence of the epithelial hyperplasia was detected after eight months.
Conclusions
Focal epithelial hyperplasia may induce irregular astigmatism. Epithelial thickness mapping is a very helpful technology to assess cases with irregular topography. De-epithelization as an isolated procedure may be useful to manage these cases successfully. Further investigations are required to understand the mechanism that may trigger the spontaneous development of a focal epithelial hyperplasia.
Association between Renal Function and the Treatment of Diabetic Macular Edema: Two-Year Long-Term Follow-Up
Authors: Chou Yu-Bai , Chang Jin-Yu , Chou Yiing-Jenq , Pu Christy
Published: February 2023

Background: To determine the correlation between the severity of chronic kidney disease (CKD) and treatment of diabetic macular edema (DME).
Methods: The retrospective 2-year cohort study included eyes with DME confirmed using spectral-domain optical coherence tomography in Taipei Veterans General Hospital, Taiwan, between 2010 and 2020. All the eyes were treated with an intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) during regular follow-up over 2 years. They were categorized into 3 different groups: an estimated glomerular filtration rate ≥ 60 (mL/min per 1.73 m2 ) (group A), <60 (group B), and patients undergoing hemodialysis (group C). The main outcome measures were (1) visual improvement, (2) structural improvement, and (3) the injection frequency of anti-VEGF in the different groups.
Results: In this study, 167 eyes from 120 patients were enrolled. Compared with groups B and C, the eyes in group A experienced the only significant visual improvement at month 3, month 6, and month 12 (P=.0001, .0002, .0013, respectively). The presence of subretinal fluid and intraretinal cysts was significantly decreased in groups A and B. In the treatment frequency analysis, the number of injections was the highest in group A and lowest in group C during the 2-year study period (P = .04).
Conclusions: The severity of CKD had an impact on the DME treatment. The less severe CKD was, the greater the visual improvement that could be achieved. In addition, relatively poor renal function required a lower anti-VEGF injection frequency. The active prevention of the progression of CKD may play a key role in DME treatment.
Identification, classification and characterization of the dermonecrotic toxins in venom glands of Hottentotta saulcyi, Androctonus crassicauda and Hemiscorpius lepturus using transcriptome analysis
Authors: Baradaran Masumeh , Salabi Fatemeh
Published: February 2023

Venom phospholipase D (PLDs), known as dermonecrotic toxins, are the major molecules in the crude venom of scorpions that are mainly responsible for lethality and dermonecrotic lesions during scorpion envenoming. The purpose of this study was fourfold: First to identify transcripts coding for venom dermonecrotic toxin by transcriptomic analysis of the venom from Androctonus crassicauda, Hottentotta saulcyi, and Hemiscorpius lepturus; second to classify them by sequence similarity to known PLDs and motif extraction method; third to characterize scorpion PLDs; and fourth to investigate phylogenetic relationships of the PLD proteins. This is the first report of the presence of dermonecrotic toxin sequence in A. crassicauda and H. saulcyi venom. We found that the venom gland of scorpions encodes two PLD isoforms; PLD1 ScoTox-beta and PLD2 ScoTox-alpha I. Two highly conserved regions shared by all PLDs beta are GAN and HPCDC (HX2PCDC), and the most important conserved regions shared by all PLDs alpha are two copies of the HKDG (HxKx4Dx6G) motif. We found that PLD1 is a 31–43 kDa acidic protein containing signal sequences and PLD2 is a 128 kDa basic protein without known signal sequences. The gene structures of PLD1 and PLD2 contain 6 and 21 exons respectively.
Improved YOLOv5 infrared tank target detection method under ground background
Authors: Liang Chao , Yan Zhengang , Ren Meng , Wu Jiangpeng , Tian Liping , Guo Xuan , Li Jie
Published: February 2023

To solve the problem of low target detection accuracy caused by the change of imaging scale, complex ground background and inconspicuous infrared target characteristics when infrared image seeker detects ground tank targets. In this paper, a You Only Look Once, Transform Head Squeeze-and-Excitation (YOLOv5s-THSE) model is proposed based on the YOLOv5s model, and a multihead attention mechanism is added to the backbone and neck of the network. The Cross Stage Partial, Squeeze-and-Exclusion (CSP_SE) module is added to the neck of the network, a small target detector is introduced into the head of the network, and the complete center section over union loss function is used in the model. Through various improvement measures, the background of the infrared target is suppressed, and the detection ability of the infrared tank target is improved. Experiments on infrared tank target data sets show that the model proposed in this paper can effectively improve the detection performance of infrared tank targets under ground background compared with several methods, such as YOLOv5s, YOLOv5s + SE, and YOLOV 5s + Convective Block Attention Module (CBAM).
Dog1 Expression in Neuroendocrine Neoplasms: Potential Applications and Diagnostic Pitfalls
Authors: Marando Alessandro , Tucci Francesco , Aquilano Maria Costanza , Blasi Elena Di , Bonoldi Emanuela
Published: February 2023

Neuroendocrine neoplasms (NENs) represent a heterogeneous group of rare tumors, more frequently arising from gastroenteropancreatic tract and lungs. At the time of diagnosis, 20% of cases are metastatic, and 10% of cases are considered as cancer of unknown primary origin. Several immunohistochemical markers are routinely used to confirm the neuroendocrine differentiation, first among all Synaptophysin and Chromogranin-A; on the other hand, different immunohistochemical markers are used to establish primary anatomical site, as TTF1, CDX2, Islet-1 and Calcitonin, but no marker is available in order to distinguish among different sites of the digestive tract. DOG1 (discovered on GIST-1) is a gene normally expressed in interstitial cells of Cajal and, in routine practice, DOG1 immunostaining is used in diagnosis of GIST (gastrointestinal stromal tumor). DOG1 expression has been described in several neoplasms other than GIST, both in mesenchymal and epithelial neoplasms. In the present study, DOG1 immunostaining has been performed in a large cohort of neuroendocrine neoplasms, including neuroendocrine tumors and neuroendocrine carcinomas, in order to evaluate frequency, intensity and pattern of expression in different anatomical site and in different tumor grade. DOG1 expression was detected in a large percentage of neuroendocrine tumors, with statistically significant association between DOG1 expression and gastrointestinal tract neuroendocrine tumors. As a consequence, DOG1 could be included in marker panel for the identification of primary site in neuroendocrine metastases of unknown primary origin; moreover, these results recommend careful evaluation of DOG1 expression in gastrointestinal neoplasms, in particular in differential diagnosis between epithelioid GIST and neuroendocrine tumors.
Histone acetyltransferase CSRP2BP promotes the epithelial–mesenchymal transition and metastasis of cervical cancer cells by activating N-cadherin
Authors: Yang xiaohui , Sun Fei , Gao Yueying , Liu Mian , Wei Yunjian , Jie Qiuling , Wang Yibing , Li Mengyongwei , Mei Jiaoqi , Mei Jingjing , Ma Linna , Shi Yuechuan , Chen Manling , Li Yongsheng , Li Qi , Liu Mingyao , Ma Yanlin
Published: February 2023

Background:Dysregulated epithelial–mesenchymal transition (EMT) is involved in cervical cancer metastasis and is associated with histone acetylation. However, the underlying molecular mechanisms of histone acetylation in cervical cancer EMT and metastasis are still elusive.Methods:Here, we systematically investigated the expression patterns of histone acetylation genes and their correlations with EMT pathway in cervical cancer. The expression ofhistone acetyltransferase CSRP2BP among cervical cancer tissues and cell lines was detected using Western blotting and immunohistochemistry analyses. The effect of CSRP2BP on cervical cancer cell proliferation and tumorigenicity were determined by cell growth curve, EdU assay, flow cytometryand xenotransplantation assays. Wound healing assays, transwell migration assays and pulmonary metastasis model were used to evaluate the effect of CSRP2BP on the cellinvasion, metastasis of cervical cancer cellsin vivoandin vitro. RNA-seq, Chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP) and luciferase reporter were further applied to research for the roles and molecular mechanisms of CSRP2BP in promoting cervical cancer EMT and matastasis.Results:We prioritized a top candidate histone acetyltransferase, CSRP2BP, as a key player in cervical cancer EMT and metastasis. The expression of CSRP2BP was significantly increased in cervical cancer tissues and high CSRP2BP expression was associated with poor prognosis. Overexpression of CSRP2BP promoted cervical cancer cell proliferation and metastasis bothin vitroandin vivo,while knockdown of CSRP2BP obtained the opposite effect. In addition, CSRP2BP-promoted resistant to cisplatin chemotherapy. Mechanistically, CSRP2BP mediated histone 4 acetylation at lysine sites 5 and 12, and cooperate with the transcription factor SMAD4, bound to the SEB2 domain of theN-cadheringene promotor region and upregulated N-cadherin transcription. Consequently, CSRP2BP involved cervical cancer cell EMT and matastasis dependent on activating N-cadherin.Conclusions:These findings reveal for the first time the involvement of histone acetyltransferase CSRP2BP in cervical cancer metastasis partially through promoting the EMT process and imply that CSRP2BP could be a prognostic marker and a potential therapeutic target for combating cervical cancer metastasis.
Pulcherrimin protects Bacillus subtilis against oxidative stress during biofilm development
Authors: Chai Yunrong , Angelini Leticia , Santos Renato Corrêa dos , Fox Gabriel , Paruthiyil Srinand , Gozzi Kevin , Shemesh Moshe
Published: February 2023

Pulcherrimin is an iron-binding reddish pigment produced by various bacterial and yeast species. In the soil bacterium Bacillus subtilis, this pigment is first synthesized intracellularly as the colorless pulcherriminic acid by using two molecules of tRNA-charged leucine as the substrate; pulcherriminic acid molecules are then secreted and bind to ferric iron extracellularly to form the red-colored pigment pulcherrimin. The biological importance of pulcherrimin is not well understood. A previous study showed that secretion of pulcherrimin caused iron depletion in the surroundings and growth arrest on cells located at the edge of a B. subtilis colony biofilm. In this study, we identified that pulcherrimin is primarily produced under biofilm conditions and provides protection to cells in the biofilm against oxidative stress. We presented molecular evidence on how pulcherrimin lowers the level of reactive oxygen species (ROS) and alleviates oxidative stress and DNA damage caused by ROS accumulation in a mature biofilm. We also performed global transcriptome profiling to identify differentially expressed genes in the pulcherrimin-deficient mutant compared to wild type, and further characterized the regulation of genes by pulcherrimin that are related to iron homeostasis, DNA damage response (DDR), and oxidative stress response. Based on our findings, we propose pulcherrimin as an important antioxidant as well as a signal modulating B. subtilis biofilm development.
Hydrogeophysical Investigation of Shallow Aquifers and Possible Pollution Interaction of Dumpsite, Douala Basin Cameroon
Authors: Ahmed Mbouemboue Nsangou Moussa , Lordon Anatole Eugene Djieto , Agyingi Christopher m. , Kevin Zebaze Mba
Published: February 2023

Landfill leachate contains thousands of complex components that become part of groundwater after infiltration. Landfills have serious environmental consequences for air, soil, surface water, and groundwater, particularly in sedimentary formations such as those found in the Douala sub basin. The present study investigated the possible dump sites pollution effects on shallow aquifer groundwater system in part of Maképé Missoké (Northern river N’gongué), Douala city, Cameroon. A total of 08 profiles were ran using the electrical resistivity tomography (ERT) to locate the aquifer and then afterward 10 points were selected for groundwater sampling in the study area and were analysed for selected major ions and bacteriological test. The ERT results show predominantly low to intermediate (0.03-1173ohmm) resistivity zones of leachate which extend down to a depth of > 30m below the surface. The physicochemical analyses results show that their elemental composition values for Ca2+(0.63–26.64 mg/l), K+ (0.52–19.41 mg/l), Cl−(2.21–52.51 mg/l), SO42−(0.71–83.27 mg/l), NO3−(8.38–51.44 mg/l), Na+(4.95–64.42 mg/l), Mg2+ (< 0.03–3.79 mg/l) tie with what was obtained in other areas worldwide for a typical dumpsite or landfill leachate and wells A4 and A6 and borehole A3 are not within the Cameroon drinking water standard based on their K and NO3 content respectively (14.35, 19.31 and 51.44). Results from bacteriological analyses show that 05 of the water samples (A4: >3000cfu, A6: 44cfu, A7: >3000cfu, A16: 32cfu, A17: 13cfu) which are especially from hand dug wells and streams are not drinkable as of the Cameroon drinking water standards and WHO. The multi-parameter and resistivity meter (multi-electrodes) were found to be good instruments that can be used to monitor the environment. The Douala aquifer at Makepé Missoké was characterized and observed to be polluted at the landfill site.
Influence of Multiple Water Uses on an Important Cross-border Watershed in South America
Authors: Boeira Lukas dos Santos , Collares Gilberto Loguercio , Santos Gabriel Borges dos , Possa Thais Magalhães , Terra Viviane Santos Silva
Published: February 2023

Knowing water behavior in a watershed is extremely important to manage its multiple uses adequately. One of the models that has been highlighted by several studies and strategies to diagnose and understand hydrological processes and, consequently, define multiple water uses, is the Large Basin Model (MGB). The Mirim-São Gonçalo watershed (MSGW), which is a cross-border basin that stretches over the extreme south of Brazil and northeastern Uruguay, has significant environmental, economic, political and social importance to the population that lives there. This study aims at applying the distributed MGB to the MSGW to describe hydrodynamic processes and fluctuation resulting from water levels by considering input and output in the system, natural and anthropic ones, based on the Water Exploitation Index (WEI) and the Water Commitment Index (WCI). Results show that the adapted MGB enabled to simulate hydrological-hydrodynamic characteristics in the MSGW when information on winds were inserted. Results of the Brazilian part of the basin were better due to the distribution of input data. Regarding multiple uses, both the WCI and the WEI clearly show that the Uruguayan part of the basin is in a comfortable situation, in contrast with the Brazilian part, which needs special and criterial care since its situation is more critical.