bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring of Anthropogenic Sediment Plumes in the Clarion-Clipperton Zone, NE Equatorial Pacific Ocean
Authors: Haalboom Sabine , Schoening Timm , Urban Peter , Gazis Iason-Zois , de Stigter Henko , Gillard Benjamin , Baeye Matthias , Hollstein Martina , Purkiani Kaveh , Reichart Gert-Jan , Thomsen Laurenz , Haeckel Matthias , Vink Annemiek , Greinert Jens
Published: June 2022

The abyssal seafloor in the Clarion-Clipperton Zone (CCZ) in the NE Pacific hosts the largest abundance of polymetallic nodules in the deep sea and is being targeted as an area for potential deep-sea mining. During nodule mining, seafloor sediment will be brought into suspension by mining equipment, resulting in the formation of sediment plumes, which will affect benthic and pelagic life not naturally adapted to any major sediment transport and deposition events. To improve our understanding of sediment plume dispersion and to support the development of plume dispersion models in this specific deep-sea area, we conducted a small-scale, 12-hour disturbance experiment in the German exploration contract area in the CCZ using a chain dredge. Sediment plume dispersion and deposition was monitored using an array of optical and acoustic turbidity sensors and current meters placed on platforms on the seafloor, and by visual inspection of the seafloor before and after dredge deployment. We found that seafloor imagery could be used to qualitatively visualise the redeposited sediment up to a distance of 100 m from the source, and that sensors recording optical and acoustic backscatter are sensitive and adequate tools to monitor the horizontal and vertical dispersion of the generated sediment plume. Optical backscatter signals could be converted into absolute mass concentration of suspended sediment to provide quantitative data on sediment dispersion. Vertical profiles of acoustic backscatter recorded by current profilers provided qualitative insight into the vertical extent of the sediment plume. Our monitoring setup proved to be very useful for the monitoring of this small-scale experiment and can be seen as an exemplary strategy for monitoring studies of future, upscaled mining trials. We recommend that such larger trials include the use of AUVs for repeated seafloor imaging and water column plume mapping (optical and acoustical), as well as the use of in-situ particle size sensors and/or particle cameras to better constrain the effect of suspended particle aggregation on optical and acoustic backscatter signals.
Transcriptome Analysis of Turbot (Scophthalmus maximus) Infected With Aeromonas salmonicida Reveals a Direct Effect on Leptin Synthesis as a Neuroendocrine Mediator of Inflammation and Metabolism Regulation
Authors: Librán-Pérez Marta , Pereiro Patricia , Figueras Antonio , Novoa Beatriz
Published: June 2022

Aeromonas salmonicida subsp. salmonicida is the causative agent of furunculosis, a disease affecting numerous fish species worldwide. It is a highly pathogenic bacterium for turbot, whose farming production represents an important economic activity in several European countries and China. To better understand the response of this organism to A. salmonicida, we conducted RNA-Seq analysis of the head kidney from experimentally infected and uninfected turbot juveniles at 24 hours post-infection (hpi). As expected, among the differentially expressed genes (DEGs) between infected and uninfected fish, we observed the modulation of a multitude of immune-related genes but also a high representation of genes linked to metabolism. Interestingly, one of the most upregulated genes was that encoding the hormone leptin. Leptin is a multifunctional hormone/cytokine that has been shown to play roles in the immune system, stress response, food intake, metabolism and energy balance. We used recombinant human leptin to elucidate its role during infection with A. salmonicida in turbot (anorexigenic activity, ability to modulate metabolism and the immune response, and its effect on survival and bacterial load during infection). We found that the intraperitoneal administration of leptin was able to alter the response to the bacteria at the immune level, but especially at the metabolic level, which resulted in a higher survival rate without affecting the bacterial load. Based on this, we hypothesized that leptin could offer great potential as a therapeutic treatment during furunculosis outbreaks by reducing the impact of sepsis. Our results reveal the complex interplay between bacterial activity and the regulation of food intake, metabolism and inflammation.
Utility of Dendrochronology Crossdating Methods in the Development of Arctic Coralline Red Algae Clathromorphum compactum Growth Increment Chronology for Sea Ice Cover Reconstruction
Authors: Leclerc Natasha , Halfar Jochen , Porter Trevor J. , Black Bryan A. , Hetzinger Steffen , Zulian Meghan , Tsay Alexandra
Published: June 2022

Paleoclimate and paleoenvironmental reconstructions from increment-yielding archives strongly depend on precise age models. Like bivalves, corals, trees, and speleothems, the coralline alga Clathromorphum compactum produces annual growth increments and shows considerable promise as an environmental archive for arctic and subarctic regions. Though their growth increment widths correlate with temperature and sea ice cover in high Arctic regions, existing timeseries have not been crossdated. In fact, previous studies have shown a lack of inter-sample correlation in non-crossdated timeseries suggesting possible age model dating errors. Here, we use dendrochronology crossdating techniques and COFECHA software to ensure and validate synchrony between C. compactum timeseries (<141 years) from three specimens collected near Beechey Island, Nunavut, Canada. Results showed that non-crossdated timeseries constructed by four coralline red algae researchers using annual increments of the same C. compactum samples were highly variable and showcase the likelihood of dating errors in non-crossdated timeseries. Crossdating improved inter-series correlations, and correlations to sea ice-related records, suggesting that at least three crossdated timeseries are required to isolate paleoclimate signals. Our findings suggest that future reconstructions with C. compactum should employ crossdating techniques to reduce dating errors and allow for more precise climate reconstructions.

Lay Abstract

Long-term environmental records provide a critical baseline to examine how humans have impacted Earth’s natural climate. An important piece to consider is sea ice’s role in natural climate variability because its brightness limits warming by reflecting solar irradiation back to space. However, instrumental records of sea ice rarely extend beyond the early satellite era (late 1970s), limiting our understanding of how sea ice affects natural climate variability in the preindustrial era. A lack of historical baseline prompted the development of sea ice proxies, including the long-lived marine alga, Clathromorphum compactum. Similar to tree-rings, C. compactum produces a new mineralized layer each year, and layer thicknesses have been shown to respond to sea ice cover, making them useful to record long-term sea ice variability. However, a recent study showed that records had replicability problems, maybe due to dating mistakes. Our study applies tree-ring dating methods (dendrochronology) to match annual algal growth layers across algal specimens. Results showed that these new methods reduced dating errors, allowing for more precise past sea ice cover reconstructions.
Biomimetic Hierarchical Superstructures: Approaches Using Bicontinuous Microemulsions and Electrodeposition
Authors: Siller-Martínez Ana Sofia , Fuentes Keyla M. , Adesuji Elijah T. , Aceves Frida , Torres-Guerrero Verónica O. , Guardado-Villegas Esther , Basilio-Bernabé Karla , Ceballos Manuel , Navarro-Segura María , Rivera-Rangel Rubén Darío , Arizpe-Zapata J. Alejandro , Videa Marcelo , Sánchez-Domínguez Margarita
Published: June 2022

The current challenges in developing novel nanotechnological processes have led us to explore new methods for synthesizing nanomaterials whose functionalities rely on their structural complexity. In this respect, nature has always been a source of inspiration for proposing innovative technologies to improve the quality of life. Hierarchical superstructures (HSS) are of great interest because the self-assembly of low-dimensional nanostructures (up to the macroscale) allows the control and optimization of performance by coupling the properties of the individual blocks. Self-assembled surfactant structures are convenient for HSS synthesis because they provide a confined reaction medium which confers excellent control over the size of the building blocks. Furthermore, bicontinuous microemulsions offer a soft three-dimensional template due to their interconnected nature. Similarly, electrodeposition routes offer fast, robust, clean, and reproducible ways to synthesize metallic and multimetallic HSS. The combination of soft-templating and electrodeposition is a powerful tool for controlling the morphology and composition of the material. This work reviews polymeric, ceramic, and metallic hierarchical superstructures synthesized using bicontinuous microemulsions and electrodeposition techniques and compares them with matching natural patterns. The aim is to show how these synthetic routes can be exploited to obtain efficient biomimetic nanomaterials that improve their properties.
Comparison of Peripheral Blood Regulatory T Cells and Functional Subsets Between Ocular and Generalized Myasthenia Gravis
Authors: Rao Jie , Li Siyu , Wang Xinyu , Cheng Qi , Ji Yu , Fu Wenwen , Huang Hui , Shi Ling , Wu Xiaorong
Published: June 2022

Purpose

This study aims to discuss the function mechanism of regulatory T cells and its subsets in the pathogenic process of myasthenia gravis by contracting the activation levels of those cells in peripheral blood among healthy people, patients with ocular myasthenia gravis (oMG) and patients with generalized myasthenia gravis (gMG).

Method

Healthy people, newly diagnosed oMG patients, and gMG patients were enrolled in this study. The percentage of the CD3+CD4+CD25+ Treg cells, CD3+CD4+CD25+Foxp3+ Treg cells, CD3+CD4+CD25+Foxp3hi CD45RA–aTreg cells, CD3+CD4+CD25+Foxp3loCD45RA–n-sTreg cells, and CD3+CD4+CD25+ Foxp3loCD45RA+rTreg cells in the peripheral blood were examined by flow cytometry. And then analyzed the differences of Treg cells and its subsets among the study members.

Results

The percentage of the CD4+CD25+Treg cells in the peripheral blood of oMG patients and gMG patients were both lower than that of healthy people (p < 0.05), the percentage of patients with oMG had no distinct difference with that of patients with gMG (p = 0.475), however. Also, the percentage of CD3+CD4+CD25+Foxp3+Treg cells in the oMG and gMG patients’ group were both lower than that of healthy group. And the percentage of CD25+Foxp3+Treg cells in the peripheral blood of patients with oMG and healthy people were both higher than that of patients with gMG (p < 0.05). The percentage of rTreg in the CD3+CD4+CD25+Treg of the peripheral blood for both gMG and oMG patients’ group were lower than healthy group (p < 0.05), but there was no statistical significance between the oMG and gMG patients’ group (p = 0.232). The percentage of the aTreg cells in the CD3+CD4+CD25+Treg cells of the peripheral blood for the oMG patients was higher than that of gMG patients (p < 0.05), but both of them were lower than healthy group (p < 0.05). The percentage of n-sTreg cells in the peripheral blood descended among the gMG patients’ group, oMG patients’ group, and healthy group (p < 0.05).

Conclusion

The changes in the number and function of Treg cells and its subsets can cause the impairment of negative immune regulation, which may mediate the triggering of oMG and its progression to gMG.
Serological Immunoassay for Hansen’s Disease Diagnosis and Monitoring Treatment: Anti-Mce1A Antibody Response Among Hansen’s Disease Patients and Their Household Contacts in Northeastern Brazil
Authors: Lima Filipe Rocha , Filho Fred Bernardes , Antunes Vanderson Mayron Granemann , Santana Jaci Maria , de Almeida Regina Coeli Palma , Toro Diana Mota , Bragagnollo Vinicius Fozatti , Manso Gabriel Martins da Costa , de Paula Natália Aparecida , Alves Eliracema Silva , Riley Lee W. , Arruda Sérgio , Frade Marco Andrey Cipriani
Published: June 2022

Hansen’s disease (HD) is an ancient disease, but more than 200,000 new cases were reported worldwide in 2019. Currently, there are not many satisfactory immunoassay methods for its diagnosis. We evaluated antibodies against Mce1A as a promising new serological biomarker. We collected plasma from new cases, contacts, and endemic controls in the city of Parnaíba and treated patients at Carpina, a former HD colony in Piauí state, northeastern Brazil. Receiver operating characteristic (ROC) curves were used to assess the assay thresholds, specificity and sensitivity of the IgA, IgM, and IgG antibodies against α-Mce1A by indirect ELISA and compared it with IgM anti-PGL-I and molecular diagnosis by quantitative polymerase chain reaction (qPCR). Venn diagrams were generated to represent the overlap in the antibody positivity pattern. Multivariate analysis was performed to assess the potential predictor of antibodies for the outcome of having an HD diagnosis. IgA and IgG were positive in 92.3 and 84% of patients, respectively. IgM was negative for all treated patients. IgG had a sensitivity and specificity of 94.7 and 100%, respectively. IgM-positive individuals had a 3.6 chance of being diagnosed with HD [OR = 3.6 (95% CI = 1.1–11.6);p= 0.028], while IgA-positive individuals had a 2.3 chance [OR = 2.3 (95% CI = 1.2–4.3);p= 0.005] compared to endemic controls. We found that the Mce1A antibody profile can be an excellent diagnostic method of HD. IgA is an ideal biomarker for confirming contact with the bacillus. IgM has potential in the detection of active disease. IgG antibodies confirm the performance of these serological markers in diagnosis and therapeutic follow-up.
Blush in Lung Contusions Is Not Rare and Has a High Risk of Mortality in Patients With Blunt Chest Trauma
Authors: Tominaga Naoki , Hayakawa Mineji , Yokobori Shoji
Published: June 2022

Background

Patients with blunt chest trauma have a high mortality rate. The assessment of blush in hepatic and splenic trauma is important for determining the need for emergency hemostatic interventions. However, the frequency and importance of blush in lung contusions are unknown. Therefore, this study aimed to evaluate the frequency of blush in patients with lung contusions and elucidate the relationship between blush and the clinical outcomes of patients with blunt chest trauma.

Materials and Methods

In this retrospective observational study, we enrolled patients with an injury severity score of 16 or higher and a chest abbreviated injury scale (AIS) score of 3 or higher who were admitted to the emergency department of Hokkaido University Hospital from January 1, 2003, to December 31, 2016. Blush was defined as active extravasation of an intravascular contrast agent recognized on contrast-enhanced computed tomography. The date of trauma, trauma severity, treatments, and outcomes were obtained from the patients’ electronic medical records.

Results

During the study period, 83 patients had severe lung contusions and 13 had blush. In-hospital mortality of patients with blush was significantly higher than that of patients without blush (53 vs. 10%, P < 0.001). Patients with blush required thoracic drainage more frequently (100 vs. 71%, P < 0.001) and support through mechanical ventilation more often (100 vs. 64%, P < 0.001) and for a longer duration (median duration, 0 vs. 25 days, P = 0.001) than patients without blush.

Conclusions

Our study revealed that blush in lung contusions was not rare and was associated with a high risk of mortality in patients with severe blunt chest trauma. Clinicians should not hesitate to intervene if blush is detected in a lung contusion of a patient with blunt chest trauma.
Efficacy of Acupuncture and Moxibustion in Alopecia: A Narrative Review
Authors: Li Andraia R. , Andrews Laura , Hilts Alexis , Valdebran Manuel
Published: June 2022

Acupuncture is the practice of applying needles to target specific pressures points in the body. Since originating in China, acupuncture has been practiced for thousands of years to treat numerous conditions including chronic pain and mood disorders. Alopecia is a common dermatologic condition associated with psychological distress and decreased quality of life. Although it remains underexplored in western medicine, recent evidence suggests that acupuncture may be efficacious in the treatment of alopecia. In this review, we discuss the available evidence describing the efficacy of acupuncture or moxibustion alone (ACU) and in combination with other traditional and alternative interventions (ACU + TRAD) for hair loss. Additionally, the proposed physiologic mechanisms, targeted acupuncture points, and the benefits and barriers to treatment will be further described. An exploratory search using PubMed, EMBASE and Scopus databases was performed for studies that evaluated the effect of acupuncture and moxibustion on alopecia. In these studies, both ACU and ACU + TRAD were efficacious for numerous etiologies of hair loss including alopecia areata, androgenetic alopecia, and seborrheic alopecia. Given their ability to modulate the immune system, as well as neuronal networks associated with emotional cognition, the most frequently targeted acupoints were ST 36, GV 20, and LR 3. The proposed mechanistic effect is dependent upon disease etiology and is theorized to be twofold: reduction of inflammation and decrease in testosterone levels. The limited side effect profile of acupuncture makes it an advantageous treatment option, however, factors including cost, time, limited access, and aversion to needles may serve as barriers to treatment.
The Development of Predictive Nomogram of Recurrence for Patients With Endometrioma After Cystectomy Who Were Younger Than 45 Years Old and Received Postoperative Therapy
Authors: Gu Zhiyue , Li Xiaoyan , Shi Jinghua , Wu Yushi , Zhang Jing , Zhang Chenyu , Yan Hailan , Leng Jinhua
Published: June 2022

Objective:

This study aimed to establish an effective prognostic nomogram for the postoperative recurrence of endometrioma or endometriosis-related pain for patients with endometrioma after long-term follow-up, who were younger than 45 years old and received postoperative therapy.

Methods

The predictive nomogram was based on 323 patients who underwent cystectomy for endometrioma at Perking Union Medical College Hospital from January 2009 to April 2013, and the last follow-up occurred in September 2018. We collected information on all included patients, including preoperative data, intraoperative data, and long-term follow-up data after surgery. The Cox proportional hazards regression model was used to evaluate the prognostic effects of multiple clinical parameters on recurrence. The survival curve was depicted based on Kaplan-Meier method and compared by log-rank method. The Index of concordance (C-index) and calibration curves were used to access the discrimination ability and predictive accuracy of the nomogram respectively, and the results were further validated via bootstrap resampling. In addition, calculating the area under the curve (AUC) via risk scores of patients aimed to further access the prediction ability of the model.

Results

On multivariate analysis of derivation cohort, independent factors for recurrence such as dysmenorrhea degree, sum of both cyst diameters, presence of adenomyosis, and other essential factors for recurrence such as age at surgery, presence of uterine fibroids were all selected into the nomogram. The C-index of the nomogram for predicting recurrence was 0.683 (95% CI, 0.610- 0.755). The calibration curve for probability of recurrence for 7 years and 9 years showed great agreement between prediction by nomogram and actual observation. Furthermore, the AUCs of risk score for 7-year and 9-year were 0.680 and 0.790 respectively.

Conclusion

This research tried to develop the predictive nomogram of recurrence for patients with endometrioma after cystectomy. The C-index and calibration curve of nomogram, as well as the AUC of the nomogram was potential to predict the recurrence probability. In addition, this predictive nomogram needs external data sets to further validate its prognostic accuracy in the future.
Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases
Authors: Ujiie Hideyuki , Rosmarin David , Schön Michael P. , Ständer Sonja , Boch Katharina , Metz Martin , Maurer Marcus , Thaci Diamant , Schmidt Enno , Cole Connor , Amber Kyle T. , Didona Dario , Hertl Michael , Recke Andreas , Graßhoff Hanna , Hackel Alexander , Schumann Anja , Riemekasten Gabriela , Bieber Katja , Sprow Gant , Dan Joshua , Zillikens Detlef , Sezin Tanya , Christiano Angela M. , Wolk Kerstin , Sabat Robert , Kridin Khalaf , Werth Victoria P. , Ludwig Ralf J.
Published: June 2022

An estimated 20–25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors. Autoimmunity is another important cause of chronic skin inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, or B cell driven in chronic spontaneous urticaria, pemphigus and pemphigoid diseases. Rare causes of chronic skin inflammation are autoinflammatory diseases, or rheumatic diseases, such as cutaneous lupus erythematosus or dermatomyositis. Whilst we have seen a significant improvement in diagnosis and treatment, several challenges remain. Especially for rarer causes of chronic skin inflammation, early diagnosis is often missed because of low awareness and lack of diagnostics. Systemic immunosuppression is the treatment of choice for almost all of these diseases. Adverse events due to immunosuppression, insufficient therapeutic responses and relapses remain a challenge. For atopic dermatitis and psoriasis, a broad spectrum of innovative treatments has been developed. However, treatment responses cannot be predicted so far. Hence, development of (bio)markers allowing selection of specific medications for individual patients is needed. Given the encouraging developments during the past years, we envision that many of these challenges in the diagnosis and treatment of chronic inflammatory skin diseases will be thoroughly addressed in the future.
A Meta-Analysis on the Efficacy and Safety of Bacterial Lysates in Chronic Obstructive Pulmonary Disease
Authors: Huang Yongkang , Pei Yongjian , Qian Yajuan , Yao Zhen , Chen Chen , Du Juan , Shi Minhua , Zhou Tong
Published: June 2022

Background

Chronic obstructive pulmonary disease (COPD) is a common and frequently encountered disease of respiratory apparatus and is vulnerable to infection. Increasing studies reveal that bacterial lysates play an encouraging role in preventing exacerbations in these patients. We here investigated the efficacy and safety of bacterial lysates in COPD.

Methods

We performed systematic research on PubMed, EMBASE, the Cochrane Library (CENTRAL), and Web of Science by using the keywords and their synonyms for studies published before January 11, 2022. Two researchers screened the studies of literature independently according to the inclusion and exclusion criteria and extracted data from the included studies. Another two researchers assessed the risk of bias of each included using the Cochrane risk-of-bias tool. Meta-analysis was conducted using R (version 4.1.1, The R Foundation for Statistical Computing) and Review Manager (version 5.4.0, The Cochrane Collaboration).

Results

A total of 12 studies were included in this meta-analysis, and the pooled results showed that bacterial lysates were effective to reduce exacerbation rate (overall: relative risk [RR] = 0.83, 95% confidence interval [CI] 0.72–0.96; alkaline bacterial lysate subgroup [OM-85]: RR = 0.87, 95% CI 0.77–0.98; mechanical bacterial lysate subgroup [Ismigen]: RR = 0.70, 95% CI 0.41–1.20) and mean number of exacerbations (overall: MD = −0.42, 95% CI −0.75 to −0.08; alkaline bacterial lysate subgroup [OM-85]: MD = −0.72, 95% CI −1.35 to −0.09; mechanical bacterial lysate subgroup [Ismigen]: MD = −0.02, 95% CI −0.21 to 0.17). Bacterial lysates were also found beneficial in alleviating symptoms. The side effects were acceptable and slight.

Conclusion

Bacterial lysates can benefit patients with COPD by reducing exacerbations and alleviating symptoms. OM-85 is the preferable product based on the existing evidence. Further studies are needed to validate these findings.

Systematic Review Registration

[www.crd.york.ac.uk/prospero/], identifier [CRD42022299420].
Red Blood Cell Distribution Width Is Associated With Adverse Kidney Outcomes in Patients With Chronic Kidney Disease
Authors: Deng Xinwei , Gao Bixia , Wang Fang , Zhao Ming-hui , Wang Jinwei , Zhang Luxia
Published: June 2022

Background

Chronic kidney disease (CKD) is a global public health issue. Red blood cell distribution width (RDW) is a recently recognized potential inflammatory marker, which mirrors the variability in erythrocyte volume. Studies indicate that elevated RDW is associated with increased risk of mortality in CKD patients, while evidence regarding the impact of RDW on kidney outcome is limited.

Methods

Altogether 523 patients with CKD stage 1–4 from a single center were enrolled. We identified the cutoff point for RDW level using maximally selected log-rank statistics. The time-averaged estimated glomerular filtration rate (eGFR) slope was determined using linear mixed effects models. Rapid CKD progression was defined by an eGFR decline >5 ml/min/1.73 m2/year. The composite endpoints were defined as doubling of serum creatinine, a 30% decline in initial eGFR or incidence of eGFR < 15 ml/min/1.73 m2, whichever occurred first. Multivariable logistic regression or Cox proportional hazards regression was performed, as appropriate.

Results

During a median follow-up of 26 [interquartile range (IQR): 12, 36] months, 65 (12.43%) patients suffered a rapid CKD progression and 172 (32.89%) composite kidney events occurred at a rate of 32.3/100 patient-years in the high RDW group, compared with 14.7/100 patient-years of the remainder. The annual eGFR change was clearly steeper in high RDW group {−3.48 [95% confidence interval (CI): −4.84, −2.12] ml/min/1.73 m2/year vs. −1.86 [95% CI: −2.27, −1.45] ml/min/1.73 m2/year among those with RDW of >14.5% and ≤14.5%, respectively, P for between-group difference <0.05}. So was the risk of rapid renal function loss (odds ratio = 6.79, 95% CI: 3.08–14.97) and composite kidney outcomes (hazards ratio = 1.51, 95% CI: 1.02–2.23). The significant association remained consistent in the sensitivity analysis.

Conclusion

Increased RDW value is independently associated with accelerated CKD deterioration. Findings of this study suggest RDW be a potential indicator for risk of CKD progression.
Clinical Features of Urticaria: Results From a Hospital-Based Multicenter Study in China
Authors: Wang Xin , Liu Li-Juan , Li Lin-feng , Shi Xiao-Dong , Shen Yi-Wei
Published: June 2022

Background

The clinical features of urticaria have not been fully illustrated.

Objectives

To demonstrate clinical features of urticaria in different areas of southern and northern China.

Methods

In this hospital-based multicenter study, outpatients with urticaria filled in a questionnaire during the initial visit and follow-up (once per week, lasting for a month).

Results

Overall, 1,715 outpatients with urticaria with a mean age of 37.86 ± 16.08 years (range = 0.5–87 years) were recruited. The median disease duration was 1.94 ± 4.31 years (range = 0–58 years). More itching was observed in the northern areas higher than that in the southern areas (99.5 vs 94.1%, P < 0.001). The incidence of pain, arthralgia, and family history in southern areas was higher than that in northern areas (5.1 vs 1.1%, 9.6 vs 0, 10.6% vs 3.2%, P < 0.001). The leading subtypes of specified urticaria were chronic spontaneous urticaria (81.4%) and symptomatic dermographism (35.9%). The incidence of symptomatic dermographism and cold urticaria in the southern areas was lower than that in the northern areas (31.8 vs. 50.3%, 4 vs. 8.5%, P < 0.001). Allergic diseases were the most common concomitant disorders of urticaria. More than half of the patients had to avoid certain food, such as fish-prawn-crab (30.7%) and alcohol (20%). Ebastine (41.1%) was the most commonly prescribed drug. The disease duration negatively correlated with the severity of itching and number of wheals (>50/24H) (Spearman’s rank correlation test, p < 0.001).

Conclusion

This study provides a profile of clinical characteristics of urticaria in China and filled the gap in the field of regional comparative studies on urticaria.
Dose-Response Relationship of Uric Acid With Fasting Glucose, Insulin, and Insulin Resistance in a United States Cohort of 5,148 Non-diabetic People
Authors: Han Yingdong , Han Xinxin , Yin Yue , Cao Yu , Di Hong , Wu Juan , Zhang Yun , Zeng Xuejun
Published: June 2022

Background

There is a limited number of studies on the dose-response relationship between serum uric acid and impaired glucose metabolism in people without diabetes, and no large-scale research exploring the relationship in women without diabetes is based on menopausal status. Consequently, the present study aimed to investigate the above relationship in United States adults without diabetes.

Materials and Methods

Data from 2,498 men and 2,650 women aged ≥20 years were obtained from the National Health and Nutrition Examination Survey 2011–2016 conducted in the United States. Binary logistic regression analysis was applied to evaluate the association between uric acid and impaired glucose metabolism. Restricted cubic spline analysis, sensitivity analysis, and stratified analysis by menopausal status were performed to explore the above relationships.

Results

A positive correlation was found between uric acid and the risk of insulin resistance in all participants (P < 0.05). In binary logistic regression analysis, after adjusting for confounding factors, compared with the lowest quartile of uric acid, the odds ratio (95% confidence intervals) of insulin resistance in the highest quartile was 1.9 (1.1–3.1) and 2.2 (1.2–4.3) in men and women, respectively. A significant positive relationship was also observed between uric acid and impaired fasting glucose and hyperinsulinemia in women, while in men, uric acid was positively associated with the risk of hyperinsulinemia but not impaired fasting glucose. Restricted cubic spline showed that the odds ratios of insulin resistance and hyperinsulinemia increased with elevating uric acid levels in both men and women. When stratified by menopause, the association remained significant in pre-menopausal women aged ≥20, but insignificant in post-menopausal women.

Conclusion

Uric acid was positively associated with the risk of impaired glucose metabolism in a cohort of United States adults, and uric acid increased the risk of insulin resistance in pre-menopausal, but not in post-menopausal women.
Gut Microbiota Ecology and Inferred Functions in Children With ASD Compared to Neurotypical Subjects
Authors: Vernocchi Pamela , Ristori Maria Vittoria , Guerrera Silvia , Guarrasi Valerio , Conte Federica , Russo Alessandra , Lupi Elisabetta , Albitar-Nehme Sami , Gardini Simone , Paci Paola , Ianiro Gianluca , Vicari Stefano , Gasbarrini Antonio , Putignani Lorenza
Published: June 2022

Autism spectrum disorders (ASDs) is a multifactorial neurodevelopmental disorder. The communication between the gastrointestinal (GI) tract and the central nervous system seems driven by gut microbiota (GM). Herein, we provide GM profiling, considering GI functional symptoms, neurological impairment, and dietary habits. Forty-one and 35 fecal samples collected from ASD and neurotypical children (CTRLs), respectively, (age range, 3–15 years) were analyzed by 16S targeted-metagenomics (the V3–V4 region) and inflammation and permeability markers (i.e., sIgA, zonulin lysozyme), and then correlated with subjects’ metadata. Our ASD cohort was characterized as follows: 30/41 (73%) with GI functional symptoms; 24/41 (58%) picky eaters (PEs), with one or more dietary needs, including 10/41 (24%) with food selectivity (FS); 36/41 (88%) presenting high and medium autism severity symptoms (HMASSs). Among the cohort with GI symptoms, 28/30 (93%) showed HMASSs, 17/30 (57%) were picky eaters and only 8/30 (27%) with food selectivity. The remaining 11/41 (27%) ASDs without GI symptoms that were characterized by HMASS for 8/11 (72%) and 7/11 (63%) were picky eaters. GM ecology was investigated for the overall ASD cohort versus CTRLs; ASDs with GI and without GI, respectively, versus CTRLs; ASD with GI versus ASD without GI; ASDs with HMASS versus low ASSs; PEs versus no-PEs; and FS versus absence of FS. In particular, the GM of ASDs, compared to CTRLs, was characterized by the increase of Proteobacteria, Bacteroidetes, Rikenellaceae, Pasteurellaceae, Klebsiella, Bacteroides, Roseburia, Lactobacillus, Prevotella, Sutterella, Staphylococcus, and Haemophilus. Moreover, Sutterella, Roseburia and Fusobacterium were associated to ASD with GI symptoms compared to CTRLs. Interestingly, ASD with GI symptoms showed higher value of zonulin and lower levels of lysozyme, which were also characterized by differentially expressed predicted functional pathways. Multiple machine learning models classified correctly 80% overall ASDs, compared with CTRLs, based on Bacteroides, Lactobacillus, Prevotella, Staphylococcus, Sutterella, and Haemophilus features. In conclusion, in our patient cohort, regardless of the evaluation of many factors potentially modulating the GM profile, the major phenotypic determinant affecting the GM was represented by GI hallmarks and patients’ age.
Long-Term Humoral Response After a Second Dose of SARS-CoV-2 mRNA Vaccine in Japanese Kidney Transplant Recipients
Authors: Ohki Yutaro , Kawabe Mayuko , Yamamoto Izumi , Katsumata Haruki , Nakada Yasuyuki , Kobayashi Akimitsu , Urabe Fumihiko , Miki Jun , Yamada Hiroki , Kimura Takahiro , Matsuo Nanae , Tanno Yudo , Horino Tetsuya , Ohkido Ichiro , Yamamoto Hiroyasu , Yokoo Takashi
Published: June 2022

Background

The mortality rate due to COVID-19 in kidney transplant recipients (KTRs) is 16.8 to 32%. Vaccination against COVID-19 is expected to contribute to the prevention of infection, severe disease, and mortality; however, it has been reported that the humoral response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in KTRs is poor. Vaccination strategies against COVID-19 vary from country to country, and in Japan, the third dose is given 6 months after the second dose. Few studies have evaluated long-term humoral responses after the second dose of SARS-CoV-2 mRNA vaccine. In addition, the superiority of BNT162b2 vaccine and mRNA-1,273 vaccine in KTRs regarding humoral response is controversial.

Methods

Ninety-four KTRs were administered a second dose of the BNT162b2 or mRNA-1,273 vaccines, and anti-spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 antibody levels were measured 5 months (149.2 ± 45.5 days) later. The cutoff value of anti-S antibodies was defined ≥50 AU/ml and 1.4 Index for anti-N antibodies. The primary outcome was the rate of seropositivity, and factors associated with an appropriate humoral response were assessed by univariate and multivariate analysis.

Results

Of 94 KTRs, only 45 (47.9%) patients were positive for anti-S antibodies. The median anti-S SARS-CoV-2 IgG antibody titers was 35.3 (Interquartile range 3.8 to 159.7). Anti-N SARS-CoV-2 IgG antibodies in all patients were < 1.4 Index. Response to SARS-CoV-2 mRNA vaccines were 43.2 and 65% for BNT162b2 and mRNA-1,273, respectively (p = 0.152). In comparison with high-dose, low-dose of mycophenolic acid was a robust factor associated with an adequate humoral response.

Conclusion

The long-term humoral response after a second dose of SARS-CoV-2 mRNA vaccine in Japanese KTRs was poor. In comparison with high-dose, low-dose mycophenolic acid was related to an appropriate humoral response. Five months is too long to wait for a 3rd dose after 2nd dose of SARS-CoV-2 vaccine in KTRs. In this cohort, there was no statistical difference in humoral response to the BNT162b2 and mRNA-1,273 vaccines. Additional large observational studies and meta-analyses are needed to clarify the factors related to an appropriate humoral immune response to COVID-19 vaccination.
Association of Carbapenemase-Producing Enterobacterales Detected in Stream and Clinical Samples
Authors: Sung Gyung-Hye , Kim Si Hyun , Park Eun Hee , Hwang Suk Nam , Kim Jea-Dong , Kim Gyu Ri , Kim Eun-Young , Jeong Joseph , Kim Sunjoo , Shin Jeong Hwan
Published: June 2022

Background

The spread of carbapenem-resistant Enterobacterales (CRE) strains has caused treatment failure and is a worldwide threat to public health. However, there are limited reports on the prevalence of carbapenemase-producing Enterobacterales (CPE) in aquatic environments and its association with clinical isolates. This study aimed to investigate the prevalence of CPE in a stream environment and its genetic relationship with clinical isolates in Korea.

Methods

A total of 4,582 water samples were collected from 94 streams. Multiplex PCR and sequencing were used to detect and identify six carbapenemase genes. Multi-locus sequence typing (MLST) was performed to investigate the genetic relatedness between the environmental strains and clinical isolates.

Results

A total of 133 CRE strains were isolated from the streams. Klebsiella pneumoniae was the most common CRE (45.9%), followed by Enterobacter cloacae complex (29.3%), Escherichia coli (13.5%), Raoultella ornithinolytica (5.3%), and Citrobacter freundii (2.3%). Ninety (67.7%) isolates carried carbapenemase genes. K. pneumoniae carbapenemase-2 (36.7%) and New Delhi metallo-β-lactamase-5 (32.2%) were the common carbapenemases detected. Sequence type (ST)307 and ST11 K. pneumoniae strains harboring the blaKPC-2 gene were the most prevalent in stream and patient samples.

Conclusion

CPE was highly prevalent in streams and closely related to the isolates obtained from patients. Therefore, continuous monitoring of stream environments is required to control the spread of carbapenem resistance.
Chemical Genetic Validation of CSNK2 Substrates Using an Inhibitor-Resistant Mutant in Combination with Triple SILAC Quantitative Phosphoproteomics
Authors: Gyenis Laszlo , Menyhart Daniel , Cruise Edward S. , Jurcic Kristina , Roffey Scott E. , Chai Darren B. , Trifoi Flaviu , Fess Sam R. , Desormeaux Paul J. , Núñez de Villavicencio Díaz Teresa , Rabalski Adam J. , Zukowski Stephanie A. , Turowec Jacob P. , Pittock Paula , Lajoie Gilles , Litchfield David W.
Published: June 2022

Casein Kinase 2 (CSNK2) is an extremely pleiotropic, ubiquitously expressed protein kinase involved in the regulation of numerous key biological processes. Mapping the CSNK2-dependent phosphoproteome is necessary for better characterization of its fundamental role in cellular signalling. While ATP-competitive inhibitors have enabled the identification of many putative kinase substrates, compounds targeting the highly conserved ATP-binding pocket often exhibit off-target effects limiting their utility for definitive kinase-substrate assignment. To overcome this limitation, we devised a strategy combining chemical genetics and quantitative phosphoproteomics to identify and validate CSNK2 substrates. We engineered U2OS cells expressing exogenous wild type CSNK2A1 (WT) or a triple mutant (TM, V66A/H160D/I174A) with substitutions at residues important for inhibitor binding. These cells were treated with CX-4945, a clinical-stage inhibitor of CSNK2, and analyzed using large-scale triple SILAC (Stable Isotope Labelling of Amino Acids in Cell Culture) quantitative phosphoproteomics. In contrast to wild-type CSNK2A1, CSNK2A1-TM retained activity in the presence of CX-4945 enabling identification and validation of several CSNK2 substrates on the basis of their increased phosphorylation in cells expressing CSNK2A1-TM. Based on high conservation within the kinase family, we expect that this strategy can be broadly adapted for identification of other kinase-substrate relationships.
The Role of Microglia/Macrophages Activation and TLR4/NF-κB/MAPK Pathway in Distraction Spinal Cord Injury-Induced Inflammation
Authors: Liang Weishi , Han Bo , Hai Yong , Liu Yuzeng , Liu Xing , Yang Jincai , Sun Duan , Yin Peng
Published: June 2022

Distraction spinal cord injuries (DSCIs) often occur as the neurological complication of distraction forces following the implantation of internal fixation devices during scoliosis correction surgery. However, the underlying mechanism behind these injuries remains unclear. The present study aimed to explore the activation of microglia and macrophages, as well as changes in TLR4-mediated NF-κB and MAPK pathway activity after DSCIs in Bama miniature pigs. Prior to surgical intervention, the pigs were randomly divided into three groups: the sham group, the complete distraction spinal cord injury (CDSCI) group, and the incomplete distraction spinal cord injury (IDSCI) group. After surgery, the Tarlov scale and individual limb motor scale (ILMS) were used to evaluate changes in the pigs’ behavior. All pigs were euthanized 7 days after surgery, and histopathological examinations of the spinal cord tissues were performed. Immunohistochemistry was used to detect Caspase-3 expression in the anterior horn of spinal gray matter tissues. Immunofluorescence staining was utilized to assess the M1/M2 phenotype changes in microglia/macrophages and NF-κB P65 expression in central DSCI lesions, while western blotting was performed to determine the expression of TLR4/NF-κB/MAPK pathway-related proteins. The results of the present study showed that the Tarlov and ILMS scores decreased significantly in the two DSCI groups compared with the sham group. Hematoxylin and eosin (HE) and Nissl staining revealed that the tissue structure and nerve fiber tracts in the distracted spinal cord tissues were destroyed. Both DSCI groups showed the number of survived neurons decreased and the Caspase-3 expression increased. The results of the immunofluorescence staining indicated that the CD16 and CD206 expression in the microglia/macrophages increased. Between the two DSCI groups, the CDSCI group showed increased CD16 and decreased CD206 expression levels. The intensity of the fluorescence of NF-κB P65 was found to be significantly enhanced in pigs with DSCIs. Moreover, western blot results revealed that the expression of TLR4, p-IκBα, NF-κB P65, p-JNK, p-ERK, and p-P38 proteins increased in spinal cord tissues following DSCI. The present study was based on a porcine DSCI model that closely mimicked clinical DSCIs while clarifying DSCI-associated neuroinflammation mechanisms, in turn providing evidence for identifying potential anti-inflammatory targets.
The Mechanism of Bladder Injury in Fetal Rats With Myelomeningocele
Authors: Liu Ying , Chen Li , Bi Yunli , Shen Jian , Chen Hong , Ma Yujie
Published: June 2022

Background

Bladder dysfunction has been implicated as a major cause of progressive renal failure in children with neurogenic bladder. However, its pathogenesis remains unclear. This study aimed to compare the expression of proliferation, apoptosis, and neuromuscular-related proteins during the development of the bladder in myelomeningocele fetal rats, and to explore the characteristics of its abnormal development.

Methods

For the myelomeningocele group, Sprague Dawley pregnant rats were intragastrically injected with retinoic acid on the 10th day of gestation to induce myelomeningocele fetal rats. For the control group, the same amount of olive oil was injected to induce normal fetal rats. Bladders were harvested at embryonic days E16, E18, E20, and E22. Real-time quantitative polymerase chain reaction and western blotting were used to detect the protein levels of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, neuron-specific nuclear-binding protein (NeuN), α-smooth muscle actin (α-SMA), and mRNA at E16–E22; immunohistochemistry was used to detect the expression of cleaved caspase-3 at E22.

Results

The proliferation of bladder tissue cells was inhibited, with suppressed PCNA expression in myelomeningocele bladder tissue compared with that in control tissue at the early stage (E16). Myelomeningocele bladders showed increased tissue apoptosis in the late embryonic stage, with significantly higher cleaved caspase-3 protein expression than in the control bladders at E20 and E22. NeuN protein expression increased along with embryonic stage, although the expression at E20 and E22 was significantly lower in myelomeningocele bladders than in control bladders. α-SMA protein expression in myelomeningocele bladders increased gradually with the progression of pregnancy, although its expression was lower than that for control bladders at E22. Immunohistochemistry showed abundant positive staining for cleaved caspase-3 in the bladder mucosa and muscle layer of myelomeningocele bladders, and the expression of cleaved caspase-3 was significantly higher in myelomeningocele bladders than in control bladders.

Conclusions

Bladder dysfunction in myelomeningocele fetal rats is related to the inhibition of proliferation, promotion of apoptosis, and reduction of bladder nerve and smooth muscle-related protein synthesis.
MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4
Authors: Luo Qiancheng , Ma Hanning , Guo Enwei , Yu Lin , Jia Ling , Zhang Bingyu , Feng Gang , Liu Rui
Published: June 2022

Introduction

The objective of this study was to determine the NF-kappaB pathway, hub genes, and transcription factors (TFs) in monocytes implicated in the progression of neurovascular-related sepsis-induced cardiomyopathy (SIC) as well as potential miRNAs with regulatory functions.

Methods

: Sepsis-induced cardiomyopathy—and heart failure (HF)-related differentially expressed genes (DEGs) between SIC and HF groups were identified separately by differential analysis. In addition, DEGs and differentially expressed miRNAs (DEmiRNAs) in monocytes between sepsis and the HC group were identified. Then, common DEGs in SIC, HF, and monocyte groups were identified by intersection analysis. Based on the functional pathways enriched by these DEGs, genes related to the NF-kB-inducing kinase (NIK)/NF-kappaB signaling pathway were selected for further intersection analysis to obtain hub genes. These common DEGs, together with sepsis-related DEmiRNAs, were used to construct a molecular interplay network and to identify core TFs in the network.

Results

: A total of 153 upregulated genes and 25 downregulated genes were obtained from SIC-, HF-, and monocyte-related DEGs. Functional pathway analysis revealed that the upregulated genes were enriched in NF-κB signaling pathway. A total of eight genes associated with NF-κB signaling pathway were then further identified from the 178 DEGs. In combination with sepsis-related DEmiRNAs, HDAC7/ACTN4 was identified as a key transcriptional regulatory pair in the progression of SIC and in monocyte regulation. hsa-miR-23a-3p, hsa-miR-3175, and hsa-miR-23b-3p can regulate the progression of SIC through the regulation of HDAC7/ACTN4. Finally, gene set enrichment analysis (GSEA) suggested that HDAC7/ACTN4 may be associated with apoptosis in addition to the inflammatory response.

Conclusion

: hsa-miR-23a-3p, hsa-miR-3175, and hsa-miR-23b-3p are involved in SIC progression by regulating NF-κB signaling signaling pathway-related HDAC7/ACTN4 in monocytes and cardiac tissue cells. These mechanisms may contribute to sepsis-induced neurovascular damage.