bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilineage-differentiating stress-enduring cells alleviate atopic dermatitis-associated behaviors in mice
Authors: Fei WenDi , Wu JunLin , Gao MengDie , Wang Qian , Zhao Ya Yu , Shan ChunLi , Shen Yu , Chen Gang
Published: December 2021

Background

Pruritus is a recurring, long-lasting skin disease with few effective treatments. Many patients have unsatisfactory responses to currently available antipruritic treatments, and effective therapeutics are urgently needed to relieve symptoms. A previous study reported that mesenchymal stem cell (MSC)-mediated immune regulation could be used to treat skin inflammatory diseases. Multilineage-differentiating stress-enduring (Muse) cells are a new type of pluripotent stem cell that may also have the potential to treat inflammatory skin diseases.

Methods

Muse cells were isolated from human bone marrow-derived MSCs (BMSCs) via the 8-h longterm trypsin incubation (LTT) method. Repeated use of 2,4-dinitrofluorobenzene (DNFB) induced atopic dermatitis (AD) in a mouse model. Immunofluorescence, behavior recording, and image analysis were used to evaluate the therapeutic effect of subcutaneous Muse cell injection. Real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of inflammatory factors. In vitro, wound healing and cell proliferation experiments were used to examine the effect of Muse cell supernatant on keratinocytes.

Results

Our results showed that subcutaneous injection of Muse cells after AD model induction significantly alleviated scratching behavior in mice. The evaluation of dermatitis and photos of damaged skin on the back of the neck revealed that Muse cells reduced dermatitis, playing an active role in healing the damaged skin. The activation of spinal glial cells and scratching behavior were also reduced by Muse cell injection. In addition, we also showed that the expression levels of the inflammatory factors interleukin (IL)-6, IL-17α, and IL-33 in both the spinal cord and skin were suppressed by Muse cells. Furthermore, Muse cells not only exerted anti-inflammatory effects on lipopolysaccharide (LPS)-induced human HaCat cells but also promoted wound healing and keratinocyte proliferation.

Conclusions

In vivo, Muse cells could alleviate scratching symptoms, reduce epidermal inflammation, and promote wound healing. In vitro, Muse cells could also promote the migration and proliferation of keratinocytes. In summary, Muse cells may become a new therapeutic agent for the treatment of AD.
Induction of meiosis by embryonic gonadal somatic cells differentiated from pluripotent stem cells
Authors: Wang Haiying , Liu Linlin , Liu Chang , Wang Lingling , Chen Jiyu , Wang Huasong , Heng Dai , Zeng Ming , Liu Chun , Zhou Zhongcheng , Ye Xiaoying , Wan Yajuan , Li Huiyu , Liu Lin
Published: December 2021

Background

Depletion of oocytes leads to ovarian aging-associated infertility, endocrine disruption and related diseases. Excitingly, unlimited oocytes can be generated by differentiation of primordial germ cell like cells (PGCLCs) from pluripotent stem cells. Nevertheless, development of oocytes and follicles from PGCLCs relies on developmentally matched gonadal somatic cells, only available from E12.5 embryos in mice. It is therefore imperative to achieve an in vitro source of E12.5 gonadal somatic cells.

Methods

We explored to identify small molecules, which can induce female embryonic stem cells (ESCs) into gonadal somatic cell like cells.

Results

Using RNA-sequencing, we identified signaling pathways highly upregulated in E12.5_gonadal somatic cells (E12.5_GSCs). Through searching for the activators of these pathways, we identified small-molecule compounds Vitamin C (Vc) and AM580 in combination (V580) for inducing differentiation of female embryonic stem cells (ESCs) into E12.5_GSC-like cells (E12.5_GSCLCs). After V580 treatment for 6 days and sorted by a surface marker CD63, the cell population yielded a transcriptome profile similar to that of E12.5_GSCs, which promoted meiosis progression and folliculogenesis of primordial germ cells. This approach will contribute to the study of germ cell and follicle development and oocyte production and have implications in potentially treating female infertility.

Conclusion

ESCs can be induced into embryonic gonadal somatic cell like cells by small molecules.
Sex differences in the immune response to acute COVID-19 respiratory tract infection
Authors: Qi Shaohua , Ngwa Conelius , Morales Scheihing Diego A. , Al Mamun Abdullah , Ahnstedt Hilda W. , Finger Carson E. , Colpo Gabriela Delevati , Sharmeen Romana , Kim Youngran , Choi HuiMahn A. , McCullough Louise D. , Liu Fudong
Published: December 2021

Background

Sex differences in COVID-19 are increasingly recognized globally. Although infection rates are similar between the sexes, men have more severe illness. The mechanism underlying these sex differences is unknown, but a differential immune response to COVID-19 has been implicated in several recent studies. However, how sex differences shape the immune response to COVID-19 remains understudied.

Methods

We collected demographics and blood samples from over 600 hospitalized patients diagnosed with COVID-19 from May 24th 2020 to April 28th, 2021. These patients were divided into two cohorts: Cohort 1 was further classified into three groups based on the severity of the disease (mild, moderate and severe); Cohort 2 patients were longitudinally followed at three time points from hospital admission (1 day, 7 days, and 14 days). MultiPlex and conventional ELISA were used to examine inflammatory mediator levels in the plasma in both cohorts. Flow cytometry was conducted to examine leukocyte responses in Cohort 2.

Results

There were more COVID+ males in the total cohort, and the mortality rate was higher in males vs. females. More male patients were seen in most age groups (in 10-year increments), and in most ethnic groups. Males with severe disease had significantly higher levels of pro-inflammatory cytokines (IL-6, IL-8, MCP-1) than females; levels of IL-8, GRO, sCD40L, MIP-1β, MCP-1 were also significantly higher in severe vs. mild or control patients in males but not in females. Females had significantly higher anti-inflammatory cytokine IL-10 levels at 14 days compared to males, and the level of IL-10 significantly increased in moderate vs. the control group in females but not in males. At 7 days and 14 days, males had significantly more circulating neutrophils and monocytes than females; however, B cell numbers were significantly higher in females vs. males.

Conclusion

Sex differences exist in hospitalized patients with acute COVID-19 respiratory tract infection. Exacerbated inflammatory responses were seen in male vs. female patients, even when matched for disease severity. Males appear to have a more robust innate immune response, and females mount a stronger adaptive immune response to COVID-19 respiratory tract infection.
GADD34-mediated dephosphorylation of eIF2α facilitates pseudorabies virus replication by maintaining de novo protein synthesis
Authors: Zhu Ting , Jiang Xueli , Xin Hangkuo , Zheng Xiaohui , Xue Xiaonuan , Chen Ji-Long , Qi Baomin
Published: December 2021

Viruses have evolved multiple strategies to manipulate their host’s translational machinery for the synthesis of viral proteins. A common viral target is the alpha subunit of eukaryotic initiation factor 2 (eIF2α). In this study, we show that global protein synthesis was increased but the eIF2α phosphorylation level was markedly decreased in porcine kidney 15 (PK15) cells infected with pseudorabies virus (PRV), a swine herpesvirus. An increase in the eIF2α phosphorylation level by salubrinal treatment or transfection of constructs expressing wild-type eIF2α or an eIF2α phosphomimetic [eIF2α(S51D)] attenuated global protein synthesis and suppressed PRV replication. To explore the mechanism involved in the inhibition of eIF2α phosphorylation during PRV infection, we examined the phosphorylation status of protein kinase R-like endoplasmic reticulum kinase (PERK) and double-stranded RNA-dependent protein kinase R (PKR), two kinases that regulate eIF2α phosphorylation during infection with numerous viruses. We found that the level of neither phosphorylated (p)-PERK nor p-PKR was altered in PRV-infected cells or the lungs of infected mice. However, the expression of growth arrest and DNA damage-inducible protein 34 (GADD34), which promotes eIF2α dephosphorylation by recruiting protein phosphatase 1 (PP1), was significantly induced both in vivo and in vitro. Knockdown of GADD34 and inhibition of PP1 activity by okadaic acid treatment led to increased eIF2α phosphorylation but significantly suppressed global protein synthesis and inhibited PRV replication. Collectively, these results demonstrated that PRV induces GADD34 expression to promote eIF2α dephosphorylation, thereby maintaining de novo protein synthesis and facilitating viral replication.
Identification of a new amino acid mutation in the HN protein of NDV involved in pathogenicity
Authors: Chen Xi , Jia Yanqing , Wei Ning , Ye Chao , Hao Huafang , Xiao Sa , Wang Xinglong , Liu Haijin , Yang Zengqi
Published: December 2021

The fusion (F) and haemagglutinin-neuraminidase (HN) proteins of Newcastle disease virus (NDV) are viral entry proteins and are recognized as the major virulence determinants. Previously, a lentogenic NDV virus (CE16) was derived from a mesogenic strain (CI10) through sequential passages in chick embryos. Whole-genome sequence analysis revealed that the two homologous strains shared the same F protein but differed in HN with two amino acid (aa) substitutions (A215G and T430A). To elucidate the molecular reasons for virulence attenuation, two original plasmids (HN-CI10 and HN-CE16) and two single-point mutants (G215A and A430T) reverse-mutated from HN-CE16 were constructed to analyse the known biological functions of HN. The results showed that the A430T substitution significantly weakened the haemadsorption (HAd) activity, increased the neuraminidase (NA) activity, improved the fusion-promoting activity, and enhanced the cleavage-promoting activity of HN-CE16. However, G215A failed to induce obvious functional changes. Therefore, the aa residue HN430 may play a key role in determining virulence. To test this hypothesis, further studies on A430T were conducted through reverse genetics using an infectious cDNA clone. At the viral level, the A430T-mutated virus showed dramatic promotion of viral plaque formation, propagation, and pathogenicity in vitro and in vivo. This study demonstrates a new virulence site associated with HN protein functions, viral propagation, and pathogenicity. All these findings could lay a foundation for illuminating the molecular mechanism of NDV virulence.
An integrative model of patients’ perceived value of healthcare service quality in North Cyprus
Authors: Sanıl Mert , Eminer Fehiman
Published: December 2021

Background

Improving healthcare quality has become an essential objective for all health institutions worldwide to address the need to improve services, manage costs and satisfy patient expectations about the quality of care. As health is one of the leading service sectors of the North Cyprus economy, analysing patients’ perceived value of healthcare service quality is crucial. In this research, a comparative analysis of existing models revealed affordability, acceptability and accessibility as the leading modern service quality indicators affecting patients’ perceived value of healthcare service quality. The quality of services is a leading factor impacting business competition and retention dictated by the current market. This study aimed to investigate the factors that influence patient perceptions of healthcare service quality in North Cyprus.

Methods

A self-administered questionnaire was carried out among 388 patients of public and private hospitals in North Cyprus, and the data were analysed using partial least squares-structural equation modelling.

Results

Empirical results highlight that the acceptability of healthcare services is a prerequisite for perceiving a high value of service quality. The affordability and accessibility of services, respectively, were less effective. Results concerning mediating effects confirm that acceptability could fully mediate the relationship between affordability and perceived value and could partially mediate the impact of accessibility on the perceived quality of healthcare services.

Conclusion

This study contributes to healthcare theory and practice by developing a conceptual framework to provide policymakers and managers with a practical understanding of factors that affect healthcare service quality.
The need for nutritional assessment and interventions based on the prognostic nutritional index for patients with femoral fractures: a retrospective study
Authors: He Miao , Fan Qinghong , Zhu Yuhang , Liu Dexing , Liu Xingxing , Xu Shan , Peng Jiachen , Zhu Zhaoqiong
Published: December 2021

Background

The incidence of adverse perioperative outcomes in surgery for femoral fractures is high and associated with malnutrition. Here, we identified independent factors and assessed the predictive value of the prognostic nutritional index (PNI) for perioperative adverse outcomes in patients with femoral fractures.

Methods

This retrospective study included 343 patients who underwent surgery for a single femur fracture. Demographic characteristics, surgery and anaesthesia records and blood test results at admission, 1 day postoperatively and before discharge were evaluated using logistic regression analysis. The discriminatory ability of the independent factors was assessed using the receiver operating characteristic curve analysis, and DeLong’s test was used to compare the area under the curve (AUC).

Results

Overall, 159 patients (46.4%) experienced adverse perioperative outcomes. Amongst these, 123 (35.9%) had lower limb vein thrombus, 68 (19.8%) had hospital-acquired pneumonia, 6 (1.7%) were transferred to the postoperative intensive care unit, 4 (1.2%) had pulmonary embolism, 3 (0.9%) died during hospitalisation and 9 (2.6%) had other adverse outcomes, including incision disunion, renal and liver function impairment, acute heart failure, acute cerebral infarction and stress gastroenteritis. The PNI at admission, age, postoperative hospital stay, time to admission, hypertension, combined injures and surgery type were independent factors for adverse perioperative outcomes. Based on the AUC (PNI at admission: 0.772 [0.723–0.821], P < 0.001; age: 0.678 [0.622–0.734], P < 0.001; postoperative hospital stay: 0.608 [0.548–0.668], P = 0.001; time to admission: 0.585 [0.525–0.646], P = 0.006), the PNI at admission had optimal discrimination ability, indicating its superiority over other independent factors (age vs. PNI at admission, P = 0.002; postoperative hospital stay vs. PNI at admission, P < 0.001; time to admission vs. PNI at admission, P < 0.001).

Conclusions

Patients with femoral fractures require a nutritional assessment and appropriate nutritional intervention at admission, and that the PNI value at admission may be a good nutritional assessment indicator.
Effect of plant growth-promoting rhizobacterial treatment on growth and physiological characteristics of Triticum aestivum L. under salt stress
Authors: Lee Dong Gun , Lee Ji Min , Choi Chang Geun , Lee Hojoung , Moon Jun Cheol , Chung Namhyun
Published: December 2021

Salinity stress is a serious abiotic stress that affects crop quality and production. Rhizospheric microbes have immense potential in synthesizing and releasing various compounds that regulate plant growth and soil physicochemical properties. The aim of the present study was to evaluate the efficacy of indole-3-acetic acid (IAA)-producing rhizobacteria as biofertilizers under salt stress. Among the isolated strains from various soil samples, Bacillus megaterium strain PN89 with multifarious plant growth-promoting traits was selected and used as a monoculture and co-culture with two other standard strains. The plant promoting activity was evaluated using the paper towel method and pot test to observe the effects on the early stage and vegetative growth of wheat (Triticum aestivum L.). The treatment using PGPR strain presented noticeable but varying effects on plant growth under salt stress, that is, PGPR treatment often displayed a significant increase in germination percentage, root and shoot length, and other growth parameters of wheat compared to those in the non-inoculated control. Thus, these results suggest that B. megaterium PN89 can be applied as a bio-fertilizer to alleviate salt stress in T. aestivum.
Mass Concrete Placement of the Offshore Wind Turbine Foundation: A Statistical Approach to Optimize the Use of Fly Ash and Silica Fume
Authors: Van Tran Mien , Chau Vinh Ngoc
Published: December 2021

The experimental program investigated concrete with a large amount of fly ash (FA) with silica fume (SF) to replace Portland cement on the results of semi-adiabatic test, compressive strength test, and the rapid chloride permeability test (RCPT). The replacement ratios of cement by a combination of FA and SF were 30%, 35%, and 40% by mass. The percentages of SF to replace cement were 0%, 4%, and 8% by mass. Three different water-to-binder ratios (W/B) of 0.34, 0.36, and 0.38 were also investigated. Multiple linear regression was applied to construct the predicted equations (models) for the semi-adiabatic temperature rise test and the compressive strength test. Models were assessed statistically and were used to solve the concrete mixture design optimization problems. The mixture with W/B of 0.36, 31% FA, and 5% SF was found to optimally satisfy the multi-objective problem: 28-day compressive strength of 50 MPa, low heat of hydration, and very low chloride penetrability classification. Field test on the actual wind turbine foundation of the optimal mixture revealed the maximum temperature rise was 74.8 °C and the maximum temperature differential was 21.9 °C.
Investigating the utility of a high-temperature Thellier-style paleointensity experimental protocol
Authors: Grappone J. Michael , Russell James M. , Biggin Andrew J.
Published: December 2021

High-quality data are vital to the research field of paleointensity, which has long suffered from poor-quality and/or sparse data. Previous paleointensity work has established that repeatedly heating specimens increases the opportunity for thermochemical alteration to decrease the reliability of paleointensity data. In addition, recent work has shown that repeatedly heating specimens in paleointensity experiments can also exaggerate the effects of non-ideal, non-single domain grains. Arai plots resulting from paleointensity experiments containing such grains are often curvilinear (two-slope) across most of the specimen’s unblocking temperature spectrum, except in the temperature range nearest to the grains’ Curie temperature. This study tests the following strategy to mitigate these effects: that of performing a Thellier paleointensity experiment using fewer temperature steps that are also concentrated at higher temperatures. For this purpose, we use natural specimens with well-constrained rock magnetic data from the Hawaiian Scientific Observation Hole 1 (SOH1) drill core in paleointensity experiments with starting temperatures ranging from 200 °C to 500+ °C. Those experiments that focused in on the portion of the unblocking temperature spectrum nearest the Curie temperature of the specimen (HiTeCT) had an exceptionally low success rate, whereas those with initial temperatures at comparatively moderate temperatures (200–400 °C) had high success rates (~ 70%). Thermochemical alteration was minimized with a start temperature of 400 °C, but the curvature of the Arai plots had no clear dependance on start temperature. We conclude herein that increasing the start temperature can help avoid the effects of low-temperature alterations. Additionally, we found that the approach of focusing in on the highest temperature range is not a feasible one to apply in paleointensity experiments, in general, and consider this likely to be a result of a lack of intermediate-temperature checks for alteration and insufficient independence of temperature steps.

Graphical abstract
Application of an improved clustering approach on GPS height time series at CMONOC stations in Southwestern China
Authors: Wu Shuguang , Li Zhao , Li Houpu , Nie Guigen , Liu Jingnan , He Yuefan
Published: December 2021

The hydrological, geological and meteorological conditions in southwestern China are relatively complex, so that the land surface deformation presents various features. Using 58 Crustal Movement Observation Network of China (CMONOC) stations across four provinces in Southwestern China, we adopt an improved clustering algorithm to classify 49 stations into 12 clusters with different similarity levels. Our results show that the average annual signals of GPS stations within each cluster have strong consistency, while obvious differences exist among the 12 clusters, indicating that clustering algorithm helps to describe surface deformation features more accurately in regions with complex conditions. We then combine other earth observation techniques, such as the Gravity Recovery and Climate Experiment (GRACE) satellite datasets and surface loading models (SLM), and observe that GPS, GRACE and SLM have strong correlation in their monthly displacement series at GPS stations. After excluding non-clustered stations according to our previous clustering results, the correlation coefficients of GPS/GRACE and GPS/SLM are enhanced. Also, the RMS reduction rates of GPS coordinate time series have been improved after deducting displacements obtained from GRACE and SLM, thus the clustering algorithm proves to be effective in improving the consistency of three techniques in joint detection of surface deformation. Moreover, the vertical displacements of four riverside GPS stations in the Three Gorges Reservoir (TGR) area show significant negative correlation with water level of TGR, hence we conclude that the Three Gorges Dam (TGD) may directly affect the consistency of GPS annual signals of its upstream and downstream GPS stations.

Graphical Abstract
Hysteretic device characteristics indicate cardiac contractile state for guiding mechanical circulatory support device use
Authors: Chang Brian Y. , Zhang Zhengyang , Feng Kimberly , Josephy Noam , Keller Steven P. , Edelman Elazer R.
Published: December 2021

Background

Acute heart failure and cardiogenic shock remain highly morbid conditions despite prompt medical therapy in critical care settings. Mechanical circulatory support (MCS) is a promising therapy for these patients, yet remains managed with open-loop control. Continuous measure of cardiac function would support and optimize MCS deployment and weaning. The nature of indwelling MCS provides a platform for attaining this information. This study investigates how hysteresis modeling derived from MCS device signals can be used to assess contractility changes to provide continuous indication of changing cardiac state. Load-dependent MCS devices vary their operation with cardiac state to yield a device–heart hysteretic interaction. Predicting and examining this hysteric relation provides insight into cardiac state and can be separated by cardiac cycle phases. Here, we demonstrate this by predicting hysteresis and using the systolic portion of the hysteresis loop to estimate changes in native contractility. This study quantified this measurement as the enclosed area of the systolic portion of the hysteresis loop and correlated it with other widely accepted contractility metrics in animal studies (n = 4) using acute interventions that alter inotropy, including a heart failure model. Clinical validation was performed in patients (n = 8) undergoing Impella support.

Results

Hysteresis is well estimated from device signals alone (r = 0.92, limits of agreement: − 0.18 to 0.18). Quantified systolic area was well correlated in animal studies with end-systolic pressure–volume relationship (r = 0.84), preload recruitable stroke work index (r = 0.77), and maximum slope of left ventricular pressure (dP/dtmax) (r = 0.95) across a range of inotropic conditions. Comparable results were seen in patients with dP/dtmax (r = 0.88). Diagnostic capability from ROC analysis yielded AUC measurements of 0.92 and 0.90 in animal and patients, respectively.

Conclusions

Mechanical circulatory support hysteretic behavior can be well modeled using device signals and used to estimate contractility changes. Contractility estimate is correlated with other accepted metrics, captures temporal trends that elucidate changing cardiac state, and is able to accurately indicate changes in inotropy. Inherently available during MCS deployment, this measure will guide titration and inform need for further intervention.
Seasonality, shelf life and storage atmosphere are main drivers of the microbiome and E. coli O157:H7 colonization of post-harvest lettuce cultivated in a major production area in California
Authors: Leonard Susan R. , Simko Ivan , Mammel Mark K. , Richter Taylor K. S. , Brandl Maria T.
Published: December 2021

Background

Lettuce is linked to recurrent outbreaks of Shiga toxin-producing Escherichia coli (STEC) infections, the seasonality of which remains unresolved. Infections have occurred largely from processed lettuce, which undergoes substantial physiological changes during storage. We investigated the microbiome and STEC O157:H7 (EcO157) colonization of fresh-cut lettuce of two cultivars with long and short shelf life harvested in the spring and fall in California and stored in modified atmosphere packaging (MAP) at cold and warm temperatures.

Results

Inoculated EcO157 declined significantly less on the cold-stored cultivar with short shelf life, while multiplying rapidly at 24 °C independently of cultivar. Metagenomic sequencing of the lettuce microbiome revealed that the pre-storage bacterial community was variable but dominated by species in the Erwiniaceae and Pseudomonadaceae. After cold storage, the microbiome composition differed between cultivars, with a greater relative abundance (RA) of Erwiniaceae and Yersiniaceae on the cultivar with short shelf life. Storage at 24 °C shifted the microbiome to higher RAs of Erwiniaceae and Enterobacteriaceae and lower RA of Pseudomonadaceae compared with 6 °C. Fall harvest followed by lettuce deterioration were identified by recursive partitioning as important factors associated with high EcO157 survival at 6 °C, whereas elevated package CO2 levels correlated with high EcO157 multiplication at 24 °C. EcO157 population change correlated with the lettuce microbiome during 6 °C storage, with fall microbiomes supporting the greatest EcO157 survival on both cultivars. Fall and spring microbiomes differed before and during storage at both temperatures. High representation of Pantoea agglomerans was a predictor of fall microbiomes, lettuce deterioration, and enhanced EcO157 survival at 6 °C. In contrast, higher RAs of Erwinia persicina, Rahnella aquatilis, and Serratia liquefaciens were biomarkers of spring microbiomes and lower EcO157 survival.

Conclusions

The microbiome of processed MAP lettuce evolves extensively during storage. Under temperature abuse, high CO2 promotes a lettuce microbiome enriched in taxa with anaerobic capability and EcO157 multiplication. In cold storage, our results strongly support a role for season and lettuce deterioration in EcO157 survival and microbiome composition, suggesting that the physiology and microbiomes of fall- and spring-harvested lettuce may contribute to the seasonality of STEC outbreaks associated with lettuce grown in coastal California.
Post-SARS-CoV-2 vaccination venous sinus thrombosis: a literature review of 308 cases
Authors: Finsterer Josef , Zarrouk Sinda
Published: December 2021

There is accumulating evidence that SARS-CoV-2 vaccinations can be complicated by venous sinus thrombosis (VST). This review aimed at summarising and discussing previous and recent advances regarding the diagnosis, pathogenesis, treatment, and outcome of post-SARS-CoV-2 vaccination VST. At least 308 patients with post-SARS-CoV-2 vaccination VST have been reported as per the end of July 2021. Ages among these 308 patients ranged between 22 and 81 years, 69 were male and 197 were female. Post-SARS-CoV-2 vaccination VST most commonly occurred with the ChAdOx1-S vaccine followed by the BNT126b2 vaccine. In the vast majority of cases, VST occurred after the first dose. Only in six patients did VST occur after the second dose. Latency between vaccination and onset of VST ranged between 0 and 24 days. Regarding treatment, most patients received heparin followed by oral anticoagulants. Seven patients received IVIGs and six patients received steroids because of concomitant vaccine-induced immune thrombotic thrombocytopenia. Complete recovery was reported in 5 patients. Partial recovery was reported in 9 patients. Eight patients were alive or discharged. Sixty-two patients died. The outcome was not specified in the remainder. In conclusion, SARS-CoV-2 vaccinations can be complicated by VST. There is female preponderance and the outcome is frequently poor.
Effect of experimental moringa and propolis toothpastes on surface microhardness of simulated hypersensitive dentin
Authors: Riad Hoda R. , Mosallam Osama S. , Salama Alaa H. , Moharam Lamiaa M. , Zaazou Mohamed H , Niazi Hanan A. , Ibrahim Mokhtar N.
Published: December 2021

Objective

Objective was to investigate the effect of NovaMin toothpaste and two experimental toothpastes on surface microhardness of hypersensitive dentin.

Methods

Eighty specimens were prepared and divided randomly into eight groups (n = 10/group) according to the tested toothpastes (NovaMin, moringa and propolis toothpastes) and the acidic challenge (with or without 6% citric acid challenge). Enamel surfaces were removed, and the dentin surfaces were exposed on which the three tested toothpastes were brushed twice a day for 1 week using an electric toothbrush, then a 4-d citric acid cycling model with pH 5 was performed. The prepared specimens were stored in artificial saliva until the microhardness test was performed. Statistical analysis was done using One-way ANOVA followed by Tukey post hoc test.

Results

NovaMin-containing toothpaste showed an increased dentin surface microhardness following a week of twice daily brushing compared to other groups. However, NovaMin-containing toothpaste showed the highest microhardness values following pH cycling with citric acid of pH 5 compared to other tested groups.

Conclusions

NovaMin-containing toothpaste showed a partial recovery of dentin microhardness at pH 5 during the acidic challenge. Moreover, propolis- and moringa-containing toothpastes had an insignificant effect on dentin surface microhardness with and without citric acid challenge.
Influence of parental anxiety on children’s behaviour during their visits to dental clinic: a short clinical study
Authors: Thribhuvanan Lakshmi , Saravanakumar M. S. , Anjana G.
Published: December 2021

Background

Anxiety and fear of dental treatment in children have been recognized as sources of serious health problems. Parents are known to subtly transmit feelings of fear and anxiety to their children Commonly which has influence on children’s dental anxiety are maintenance of general health of the child, past dental history, oral hygiene practices and attitudes in the family towards oral health and high dental anxiety of parents, all of these contributed to sustained and elevated levels of children’s dental anxiety.

Aim

This study was undertaken to evaluate the influence of parental anxiety on their children during their visit to dental clinics.

Objective

To determine the relationship between parental anxiety level and that of a child.

Methods

A short clinical study was performed to assess the influence of parental anxiety on their children during their visit to dental clinics. Twenty subjects were randomly selected and their parents were given the Modified Dental Anxiety Scale Questionnaire (MDAS) and their physiologic parameters were measured during each visit. Similarly, the children’s responses were analyzed using the Facial Image Scale (FIS) and their physiologic parameters were measured.

Results

The values show a positive correlation (P < 0.05) between the scores (MDAS and FIS) and physiologic parameters (blood pressure and heart rate) of parents and their children.

Conclusion

The dental anxiety levels in parents influence the anxiety levels in children.
DIPS (Dystonia Image-based Programming of Stimulation: a prospective, randomized, double-blind crossover trial)
Authors: Lange Florian , Roothans Jonas , Wichmann Tim , Gelbrich Götz , Röser Christoph , Volkmann Jens , Reich Martin
Published: December 2021

Introduction

Deep brain stimulation of the internal globus pallidus is an effective treatment for dystonia. However, there is a large variability in clinical outcome with up to 25% non-responders even in highly selected primary dystonia patients. In a large cohort of patients we recently demonstrated that the variable clinical outcomes of pallidal DBS for dystonia may result to a large degree by the exact location and stimulation volume within the pallidal region. Here we test a novel approach of programing based on these insights: we first defined probabilistic maps of anti-dystonic effects by aggregating individual electrode locations and volumes of tissue activated of > 80 patients collected in a multicentre effort. We subsequently modified the algorithms to be able to test all possible stimulation settings of de novo patients in silico based on the expected clinical outcome and thus potentially predict the best possible stimulation parameters for the individual patients.

Methods

Within the framework of a BMBF-funded study, this concept of a computer-based prediction of optimal stimulation parameters for patients with dystonia will be tested in a randomized, controlled crossover study. The main parameter for clinical efficacy and primary endpoint is based on the blinded physician rating of dystonia severity reflected by Clinical Dystonia Rating Scales for both interventions (best clinical settings and model predicted settings) after 4 weeks of continuous stimulation. The primary endpoint is defined as “successful treatment with model predicted settings” (yes or no). The value is “yes” if the motor symptoms with model predicted settings are equal or better (tolerance 5% of absolute difference in percentages) to clinical settings. Secondary endpoints will include measures of quality of life, calculated energy consumption of the neurostimulation system and physician time for programming.

Perspective

We envision, that computer-guided deep brain stimulation programming in silico might provide optimal stimulation settings for patients with dystonia without the burden of months of programming sessions. The study protocol is designed to evaluate which programming method is more effective in controlling motor symptom severity and improving quality of life in dystonia (best clinical settings and model predicted settings).

Trial registration Registered with ClinicalTrials.gov on Oct 27, 2021 (NCT05097001).
Genetic structure and evolutionary diversity of mating-type (MAT) loci in Hypsizygus marmoreus
Authors: Wang Gang , Wang Yuanyuan , Chen Lianfu , Wang Hongbo , Guo Lin , Zhou Xuan , Dou Meijie , Wang Baiyu , Lin Jingxian , Liu Lei , Wang Zhengchao , Deng Youjin , Zhang Jisen
Published: December 2021

The mating compatibility in fungi is generally governed by genes located within a single or two unlinked mating type (MAT) loci. Hypsizygus marmoreus is an edible mushroom in the order Agaricales with a tetrapolar system, which contains two unlinked MAT loci-homeodomain (HD) transcription factor genes and pheromone/pheromone receptor genes (P/R). In this study, we analyzed the genetic structure and diversity of MAT loci in tetrapolar system of H. marmoreus through sequencing of 54 heterokaryon and 8 homokaryon strains. Although within the HD loci, the gene order was conserved, the gene contents were variable, and the HD loci haplotypes were further classified into four types. By analyzing the structure, phylogeny, and the HD transmissibility based on the progeny of these four HD mating-type loci types, we found that they were heritable and tightly linked at the HD loci. The P/R loci genes were found to comprise three pheromone receptors, three pheromones, and two pheromone receptor-like genes. Intra- and inter-specific phylogenetic analyses of pheromone receptors revealed that the STE3 genes were divided into three groups, and we thus theorize that they diverged before speciation. Comparative analysis of the MAT regions among 73 Basidiomycete species indicated that the diversity of HD and P/R loci in Agaricales and Boletales may contribute to mating compatibility. The number of HD genes were not correlated with the tetrapolar or bipolar systems. In H. marmoreus, the expression levels of these genes at HD and P/R loci of compatible strains were found higher than in those of homonuclear/homokaryotic strains, indicating that these mating genes acted as switches for mating processes. Further collinear analysis of HD loci in interspecific species found that HD loci contains conserved recombination hotspots showing major rearrangements in Coprinopsis cinerea and Schizophyllum commune, suggesting different mechanisms for evolution of physically linked MAT loci in these groups. It seems likely that gene rearrangements are common in Agaricales fungi around HD loci. Together, our study provides insights into the genomic basis of mating compatibility in H. marmoreus.
Bilirubin levels as an independent predictor of myocarditis in patients with COVID-19
Authors: Cosgun Muharrem Said
Published: December 2021

Background

Myocardial damage worsens the clinical course and prognosis of coronavirus disease 2019 (COVID-19) patients. High total bilirubin levels have been associated with a poor prognosis in COVID-19. This study aimed to investigate the predictive value of the total bilirubin level, a marker of heme oxygenase-1 enzyme activity, in determining myocarditis in patients with COVID-19.

Results

A total of 190 patients diagnosed with COVID-19 were enrolled in the study. The patients were divided into two groups based on their troponin positivity. The study group (n = 95) consisted of patients with high troponin, and the control group (n = 95) consisted of patients without high troponin levels. The D-dimer (727 [572–995] vs. 591 [440–790],p = 0.001), C-reactive protein (CRP) (30.0 [10–48] vs. 10.3 [5.8–15.9],p < 0.001), and total bilirubin (9.5 [8.2–12.1] vs. 7.0 [5.3–8.0],p < 0.001) levels were significantly higher in the study group. In multivariate analysis, CRP (odds ratio [OR]: 1.103; 95% confidence interval [CI]: 1.060–1.148;p < 0.001) and total bilirubin (OR: 1.612; 95% CI: 1.330–1.954;p < 0.001) levels were independent predictors of myocarditis in COVID-19.

Conclusions

Total bilirubin levels can be used as an early predictor of myocarditis in COVID-19 and can contribute to therapy management.
Patterns of recurrence after low-dose postoperative radiotherapy for head and neck squamous cell carcinoma
Authors: Makino Wataru , Heianna Joichi , Ishikawa Kazuki , Kusada Takeaki , Maemoto Hitoshi , Ariga Takuro , Matayoshi Akira , Nakasone Toshiyuki , Hirakawa Hitoshi , Agena Shinya , Yamashita Yukashi , Maeda Hiroyuki , Murayama Sadayuki
Published: December 2021

Background

Postoperative chemoradiotherapy is recommended for patients with head and neck squamous cell carcinoma with positive margins or extracapsular extension at high risk of recurrence. However, high-dose radiotherapy in the head and neck region often causes severe acute and late radiation-related adversities. In our institution, the radiation dose has been relatively lower than that used in Western countries to reduce radiation-related toxicities. Therefore, in this study, we examined the treatment outcomes of low-dose postoperative chemoradiotherapy.

Methods

The outcomes of 90 consecutive head and neck squamous cell carcinoma patients who received postoperative radiotherapy between June 2009 and December 2016 were retrospectively analyzed. All patients received postoperative three-dimensional conformal radiotherapy with or without concurrent systemic chemotherapy. The median patient age was 65 years. Concurrent chemoradiotherapy was administered at a total dose of 50.4 Gy in 28 fractions (daily fraction, 1.8 Gy). High-risk patients received 10.8 Gy of boost irradiation in six fractions. For radiotherapy alone, the irradiation dose was up to 54 Gy in 30 fractions and 64.8 Gy in 36 fractions for high-risk patients to increase the treatment intensity.

Results

The median follow-up period was 40.5 months. The 3-year locoregional control and overall survival rates were 67.5% and 82.7%, respectively. A significantly higher proportion of patients with oral cavity carcinoma experienced locoregional failure (p = 0.004). The acute adverse events were mild, and the only late adverse event was grade 3 dysphagia (n = 3).

Conclusion

This study suggests that de-escalation of the postoperative radiation dose can potentially reduce the severe adverse events of irradiation in patients while ensuring its effectiveness. In patients with oral cavity carcinoma, it might be necessary to increase the radiation dose.
Lumbar nerve root blocks using MRI – the effectiveness and safety of ultrasound/MRI fusion image guidance
Authors: Wilson David John , Allen Gina , Bullock Stuart , Denton Jon
Published: December 2021

Objective:

To compare the outcome of nerve root injection guided by ultrasound/MRI fusion with radiofrequency needle tracking (eTRAX©) and the same procedure undertaken by fluoroscopic guidance.

Methods:

This is a retrospective audit of anonymised clinical records from before and after a change in the imaging technique used to perform nerve root blocks. We studied 181 consecutive patients who had undergone a nerve root block, the first 124 guided by fluoroscopic technique and the next 57 guided by ultrasound/MRI fusion with radiofrequency needle guidance. Using pain diaries, we reviewed the outcome scores at 24 h and 2 weeks. We recorded the use of analgesia, the patient’s satisfaction, complications and the duration of the procedures.

Results:

Completed pain diaries were returned by 61% in the fluoroscopy group and 67% in the fusion imaging group. The visual analogue pain score was reduced at 24 h by 3.29 [standard deviation (SD) 2.35] for the fluoroscopy group and by 3.69 (SD 2.58) in the fusion group (p 0.399). At two weeks the pain reduction was 3.27 (SD 2.57) for the fluoroscopic group and 4.21 (SD 2.95) for the fusion group (p 0.083). There was no statistically significant difference between the groups. The patient’s satisfaction scores were similar for both groups. The procedure by the two guidance methods took a similar time to perform. There were no serious complications in either group. One patient in the fusion-guided nerve root block group experienced paraesthesia in the nerve distribution for 2 h.

Conclusion:

Ultrasound/MRI fusion imaging with needle tracking is an effective alternative to fluoroscopic image-guided injection.

Advances in knowledge:

Fusion imaging guidance provides the same outcome as fluoroscopic guidance. Fusion imaging guidance avoids the need for ionising radiation.
Mathematical evaluation of post-radiotherapy salivary gland function using salivary gland scintigraphy
Authors: Itonaga Tomohiro , Tokuuye Koichi , Mikami Ryuji , Shimizu Akira , Sato Hiroki , Yoshimura Mana , Tsukahara Kiyoaki , Saito Kazuhiro
Published: December 2021

Objective:

Xerostomia is the most common treatment-related toxicity after radiotherapy (RT) for head and neck carcinoma, reducing the quality of life of patients due to a decrease in salivary gland function.

Methods:

Salivary gland scintigraphy was performed to quantitatively evaluate the salivary gland functions in patients undergoing RT. It was done chronologically for 62 salivary glands of 31 patients before RT and retested 12 months later.

Results:

The salivary gland functions of most patients deteriorated post-RT and recovered when the radiation dose to the salivary gland was not high. The mean dose to the salivary gland was found to be the most reliable factor in deteriorating salivary gland function, and the tolerance dose was determined to be 46 Gy. The recovery rate of salivary gland function after 1 year of RT was 72% in the RT alone group (n = 10), 56% in the conformal radiotherapy group (n = 15), and 44% in the bioradiotherapy group (n = 6).

Conclusion:

Scintigraphy revealed that the salivary glands recovered from post-RT hypofunction when decreased doses were administered. The determined tolerance dose of 46 Gy may guide the approach to minimizing associated xerostomia in RT.

Advances in knowledge:

In this study, the average tolerated dose to the salivary glands was 46 Gy.
The effect of a siamese pumpkin and tuna-based powder (CHAGURO) diet in improving HbA1c, HDL-C, and chol/HDL ratios in prediabetes individuals with dyslipidemia: a randomised trial
Authors: Sudargo Toto , Prameswari Atika Anif , Aulia Bianda , Aristasari Tira , Ratri Fitria Aninda , Muslichah Rahadyana , Putri Sheila Rosmala
Published: December 2021

Background: The study aimed to examine the effect of administering CHAGURO (a product of the combination of siamese pumpkin and tuna-based powder) on the lipid profile in prediabetes individuals with dyslipidemia.

Methods: The experimental trial was conducted with two intervention groups, with each group receiving a dose of 7.5g/70kg body weight (BW)/day (low dose) and 15g/70kg BW/day (high dose) for 60 days. Respondents were randomized into intervention groups using simple randomization. Before and after the intervention, pre-test and post-test examinations were performed, factors examined included hemoglobin A1c (HbA1c), lipid profile, blood pressure, eating intake with the SQ-FFQ (Semi Quantitative-Food Frequency Questionnaire) interview, body mass index (BMI), and physical activity using InternationalPhysical Activity Questionnaires-Short Form (IPAQ-SF). During the intervention, blood pressure and BMI data were taken before and after the study. Statistical analysis included descriptive tests, independent and paired T-tests, and analysis of variance (ANOVA).

Results: Compared to the baseline, HbA1c, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides in the two groups did not improve significantly by 60 days. For lipid variables, a significant improvement in the cholesterol/high-density lipoprotein (chol/HDL) ratios were observed when compared against the baseline for the two groups. When comparing the changes between groups, 7.5 g of CHAGURO showed a larger improvement in HDL-C (mean differences: 1.86 mg/dL; 95% CI: -0.86-4.59), compared to 15 g of CHAGURO (mean differences: -3.62 mg/dL; 95% CI: -7.53-0.28). A significant (p<0.05) decrease in the chol/HDL ratio was observed in the 7.5 g CHAGURO group (mean differences: -0.20 mg/dL; 95% CI: -0.39-(-0.01)).

Conclusions: CHAGURO can be a functional food alternative to improve the condition of prediabetes people with dyslipidemia.

Trial registration: Dr. Sardjito General Hospital (KE/FK/0951/EC/2020), 27/08/2020