bluuebunny/crossref_metadata_2025 huggingface dataset:
An in vitro study on the effects of serum proteins on Enterococcus faecalis adhesion to three types of root sealers and gutta-percha
Authors: Lin Xinwei , Chi Danlu , Gong Qimei , Tong Zhongchun
Published: December 2021

Background

The extrusion of overfilled materials that extend beyond the apical foramina into the periradicular tissue may serve as a reservoir for bacterial adhesion and further affect recovery from periapical diseases. The aim of this study was to evaluate the effects of serum proteins on Enterococcus faecalis adhesion and survival on the surface of a calcium hydroxide-based root canal sealer (Apexit Plus), an epoxy resin sealer (AH-Plus) and a bioceramic sealer (iRoot SP).

Methods

Apexit Plus, AH-Plus and iRoot SP were evenly coated on gutta-percha, using gutta-percha alone as the control. After root canal sealer setting, the number of E. faecalis adhering to the root canal sealers and gutta-percha was counted in fetal bovine serum (FBS) or tryptic soy broth supplemented with 1% glucose (TSBG) by viable cell plate counts. The morphology of 7-day-old E. faecalis biofilms in FSB and TSBG was observed by scanning electron microscopy (SEM). Furthermore, E. faecalis biofilms on the three root canal sealers were labeled with a LIVE/DEAD BacLight™ Bacterial Viability Kit, and the ratios of viable to dead cells were analyzed using laser scanning microscopy operative software (Zen software).

Results

In the assays, after 1 and 7 days, the number of E. faecalis adhering to the root canal sealers or gutta-percha in FBS were significantly lower than those in TSBG (P < 0.05). In FBS, E. faecalis adhesion to iRoot SP and gutta-percha was reduced to a greater extent than that adhered to Apexit Plus and AH-Plus. Few E. faecalis accumulated on iRoot SP in FBS, whereas many bacteria assembled on iRoot SP and formed biofilms in TSBG. The ratio of viable cells in the E. faecalis biofilm on iRoot SP was the lowest.

Conclusions

Calcium hydroxide-based root canal sealers, epoxy resin sealers and bioceramic sealers may provide a substrate for E. faecalis adhesion, and the bioceramic sealer in this study showed the least E. faecalis adhesion in the presence of serum proteins compared to the other two sealers.
Effects of prolonged incubation period and centralized quarantine on the COVID-19 outbreak in Shijiazhuang, China: a modeling study
Authors: Zhu Wenlong , Zhang Mengxi , Pan Jinhua , Yao Ye , Wang Weibing
Published: December 2021

Background

From 2 January to 14 February 2021, a local outbreak of COVID-19 occurred in Shijiazhuang, the capital city of Hebei Province, with a population of 10 million. We analyzed the characteristics of the local outbreak of COVID-19 in Shijiazhuang and evaluated the effects of serial interventions.

Methods

Publicly available data, which included age, sex, date of diagnosis, and other patient information, were used to analyze the epidemiological characteristics of the COVID-19 outbreak in Shijiazhuang. The maximum likelihood method and Hamiltonian Monte Carlo method were used to estimate the serial interval and incubation period, respectively. The impact of incubation period and different interventions were simulated using a well-fitted SEIR+q model.

Results

From 2 January to 14 February 2021, there were 869 patients with symptomatic COVID-19 in Shijiazhuang, and most cases (89.6%) were confirmed before 20 January. Overall, 40.2% of the cases were male, 16.3% were aged 0 to 19 years, and 21.9% were initially diagnosed as asymptomatic but then became symptomatic. The estimated incubation period was 11.6 days (95% CI 10.6, 12.7 days) and the estimated serial interval was 6.6 days (0.025th, 0.975th: 0.6, 20.0 days). The results of the SEIR+q model indicated that a longer incubation period led to a longer epidemic period. If the comprehensive quarantine measures were reduced by 10%, then the nucleic acid testing would need to increase by 20% or more to minimize the cumulative number of cases.

Conclusions

Incubation period was longer than serial interval suggested that more secondary transmission may occur before symptoms onset. The long incubation period made it necessary to extend the isolation period to control the outbreak. Timely contact tracing and implementation of a centralized quarantine quickly contained this epidemic in Shijiazhuang. Large-scale nucleic acid testing also helped to identify cases and reduce virus transmission.
Identification of new candidate biomarkers to support doxorubicin treatments in canine cancer patients
Authors: Walters Kristine , Stornetta Alessia , Jacobs Foster , Villalta Peter W. , Razzoli Maria , Grant Marianne , Zordoky Beshay , Bartolomucci Alessandro , Borgatti Antonella , Balbo Silvia
Published: December 2021

Background

Both human and veterinary cancer chemotherapy are undergoing a paradigm shift from a “one size fits all” approach to more personalized, patient-oriented treatment strategies. Personalized chemotherapy is dependent on the identification and validation of biomarkers that can predict treatment outcome and/or risk of toxicity. Many cytotoxic chemotherapy agents, including doxorubicin, base their mechanism of action by interaction with DNA and disruption of normal cellular processes. We developed a high-resolution/accurate-mass liquid chromatography-mass spectrometry DNA screening approach for monitoring doxorubicin-induced DNA modifications (adducts) in vitro and in vivo. We used, for the first time, a new strategy involving the use of isotope-labeled DNA, which greatly facilitates adduct discovery. The overall goal of this work was to identify doxorubicin-DNA adducts to be used as biomarkers to predict drug efficacy for use in veterinary oncology.

Results

We used our novel mass spectrometry approach to screen for adducts in purified DNA exposed to doxorubicin. This initial in vitro screening identified nine potential doxorubicin-DNA adduct masses, as well as an intense signal corresponding to DNA-intercalated doxorubicin. Two of the adduct masses, together with doxorubicin and its metabolite doxorubicinol, were subsequently detected in vivo in liver DNA extracted from mice exposed to doxorubicin. Finally, the presence of these adducts and analytes was explored in the DNA isolated from dogs undergoing treatment with doxorubicin. The previously identified nine DOX-DNA adducts were not detected in these preliminary three samples collected seven days post-treatment, however intercalated doxorubicin and doxorubicinol were detected.

Conclusions

This work sets the stage for future evaluation of doxorubicin-DNA adducts and doxorubicin-related molecules as candidate biomarkers to personalize chemotherapy protocols for canine cancer patients. It demonstrates our ability to combine in one method the analysis of DNA adducts and DNA-intercalated doxorubicin and doxorubicinol. The last two analytes interestingly, were persistent in samples from canine patients undergoing doxorubicin chemotherapy seven days after treatment. The presence of doxorubicin in all samples suggests a role for it as a promising biomarker for use in veterinary chemotherapy. Future studies will involve the analysis of more samples from canine cancer patients to elucidate optimal timepoints for monitoring intercalated doxorubicin and doxorubicin-DNA adducts and the correlation of these markers with therapy outcome.
Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study
Authors: Chevli Parag Anilkumar , Freedman Barry I. , Hsu Fang-Chi , Xu Jianzhao , Rudock Megan E. , Ma Lijun , Parks John S. , Palmer Nicholette D. , Shapiro Michael D.
Published: December 2021

Background

Incidence rates of cardiovascular disease (CVD) are increasing, partly driven by the diabetes epidemic. Novel prediction tools and modifiable treatment targets are needed to enhance risk assessment and management. Plasma metabolite associations with subclinical atherosclerosis were investigated in the Diabetes Heart Study (DHS), a cohort enriched for type 2 diabetes (T2D).

Methods

The analysis included 700 DHS participants, 438 African Americans (AAs), and 262 European Americans (EAs), in whom coronary artery calcium (CAC) was assessed using ECG-gated computed tomography. Plasma metabolomics using liquid chromatography-mass spectrometry identified 853 known metabolites. An ancestry-specific marginal model incorporating generalized estimating equations examined associations between metabolites and CAC (log-transformed (CAC + 1) as outcome measure). Models were adjusted for age, sex, BMI, diabetes duration, date of plasma collection, time between plasma collection and CT exam, low-density lipoprotein cholesterol (LDL-C), and statin use.

Results

At an FDR-corrected p-value < 0.05, 33 metabolites were associated with CAC in AAs and 36 in EAs. The androgenic steroids, fatty acid, phosphatidylcholine, and bile acid metabolism subpathways were associated with CAC in AAs, whereas fatty acid, lysoplasmalogen, and branched-chain amino acid (BCAA) subpathways were associated with CAC in EAs.

Conclusions

Strikingly different metabolic signatures were associated with subclinical coronary atherosclerosis in AA and EA DHS participants.
Rapid detection of a novel B1-β-lactamase gene, blaAFM-1 using a loop-mediated isothermal amplification (LAMP) assay
Authors: Qin Yingcheng , Duan Xiaonv , Peng Yuan , Rui Yongyu
Published: December 2021

Background

BlaAFM-1 (GenBank Accession No. 143105.1) is a new B1 subclass metallo-β-lactamase gene discovered by our group, and isolated from an Alcaligenes faecalis plasmid that renders carbapenem antibiotics ineffective. In this study, we generated a fast and reliable assay for blaAFM-1 detection.

Methods

We designed optimum loop-mediated isothermal amplification (LAMP) primers and constructed a recombinant plasmid AFM-1 to specifically detect blaAFM-1. Optimal LAMP primers were used to assess sensitivity of the recombinant plasmid AFM-1 and blaAFM-1-supplemented samples (simulated sputum and simulated feces). Fifty two samples, without blaAFM-1, were used to assess LAMP real-time assay specificity; these samples were verified by conventional PCR and sequencing for the absence of blaAFM-1. Three hundred clinical Gram-negative carbapenem-resistant strains were tested by LAMP assay for strains carrying blaAFM-1, which were confirmed by conventional PCR and Sanger sequencing. We calculated the sensitivity and its 95% confidence interval (95% CI), specificity and its 95% CI, and predictive values of the LAMP assay and conventional PCR/sequencing by investigating positive and negative clinical strains.

Results

The lowest limit of detection for the recombinant plasmid AFM-1 and blaAFM-1-supplemented samples (in both simulated sputum and simulated feces) was 101 copies/reaction. All amplification curves of the 52 blaAFM-1-free bacteria strains were negative, suggesting the LAMP assay had excellent specificity for detecting blaAFM-1. Among the 300 clinical strains, eight were positive for blaAFM-1 using LAMP. These LAMP results were consistent with conventional PCR and Sanger sequencing data. As with conventional PCR/sequencing, the LAMP method exhibits 100% sensitivity (95% CI 59.8–100%) and 100% specificity (95% CI 98.4–100%) for blaAFM-1 detection. The LAMP assay is also time-efficient (1 h) for blaAFM-1 detection.

Conclusions

We established a new LAMP assay with high sensitivity and specificity to detect the novel B1-β-lactamase gene, blaAFM-1.
The hazardous (mis)perception of Self-estimated Alcohol intoxication and Fitness to drivE—an avoidable health risk: the SAFE randomised trial
Authors: Köchling Jöran , Geis Berit , Chao Cho-Ming , Dieks Jana-K. , Wirth Stefan , Hensel Kai O.
Published: December 2021

Background

Worldwide, alcohol-related road traffic accidents represent a major avoidable health risk. The aim of this study was to evaluate the accuracy of self-estimating the degree of acute alcohol intoxication regarding the legal driving limit, and to identify risk factors for misjudgement.

Methods

In this prospective randomised controlled crossover trial, 90 social drinkers (mean age 23.9 ± 3.5 years, 50% female) consumed either beer or wine. Study group subjects were made aware when exceeding the legal driving limit (BrAC = 0.05%). Controls received no information about their BrAC. For crossover, beer or wine were consumed in the opposite order.

Results

39–53% of all participants exceeded the legal driving limit whilst under the impression to be still permitted to drive. Self-estimation was significantly more accurate on study day 2 (p = 0.009). Increasing BrAC positively correlated with self-estimation inaccuracy, which was reproducible during crossover. Multiple regression analysis revealed fast drinking and higher alcohol levels as independent risk factors for inaccurate self-estimation.

Conclusions

Social drinkers are commonly unaware of exceeding the legal driving limit when consuming alcohol. Self-estimating alcohol intoxication can be improved through awareness. Dedicated awareness programs, social media campaigns and government advice communications should be utilised to address this avoidable hazard.

Trial registration The trial was registered prospectively at the Witten/Herdecke University Ethics Committee (trial registration number 140/2016 on 04/11/2016) and at the DRKS—German Clinical Trials Register (trial registration number DRKS00015285 on 08/22/2018—Retrospectively registered). Trial protocol can be accessed online.
LINC00491 promotes cell growth and metastasis through miR-324-5p/ROCK1 in liver cancer
Authors: Wang Wei , Yang Tao , Li Dongsheng , Huang Yinpeng , Bai Guang , Li Qing
Published: December 2021

Background

LINC00491 was involved in some tumors development, but its function in liver cancer has not been reported. This study aimed to investigate LINC00491 expression and function in liver cancer progression.

Methods

Sixty liver cancer cases were enrolled. LINC00491, miR-324-5p and rho-associated kinase 1 (ROCK1) expression in liver cancer patients and cells were detected by quantitative reverse transcription-polymerase chain reaction and Western blot. HUH-7 and SK-Hep-1 cells were transfected to modulate LINC00491, miR-324-5p and ROCK1 expression. Cell counting kit-8 assay, colony formation assay, wound healing assay, Transwell experiment, Tunel assay and flow cytometry were performed to detected HUH-7 and SK-Hep-1 cells proliferation, migration, invasion, apoptosis and cell cycle. Biotin-RNA pull-down assay and Dual-Luciferase Reporter Assay was performed to detect the binding among LINC00491, miR-324-5p and ROCK1. Xenograft tumor and lung metastasis was performed using nude mice. Xenograft tumor and lung tissues of mice were experienced immunohistochemistry and hematoxylin–eosin staining.

Results

LINC00491 was highly expressed in liver cancer cases, associating with poor prognosis. si-LINC00491 inhibited proliferation, colony formation, invasion, migration, and induced cell cycle G1 arrest and apoptosis in HUH-7 and SK-Hep-1 cells. LINC00491 overexpression showed opposite effects. LINC00491 promoted ROCK1 expression by reducing miR-324-5p. miR-324-5p up-regulation or ROCK1 knockdown reversed LINC00491 promotion on liver SK-Hep-1 cells malignant phenotype. LINC00491 facilitated xenograft tumor growth and lung metastasis in mice.

Conclusion

LINC00491 was highly expressed in liver cancer patients, associating with poor prognosis. LINC00491 facilitated liver cancer progression by sponging miR-324-5p/ROCK1. LINC00491 might be a potential treatment target of liver cancer.
Hepatitis B virus polymerase-specific T cell epitopes shift in a mouse model of chronic infection
Authors: Hasanpourghadi Mohadeseh , Novikov Mikhail , Newman Dakota , Xiang ZhiQuan , Zhou Xiang Yang , Magowan Colin , Ertl Hildegund C. J.
Published: December 2021

Background

Chronic hepatitis B virus (HBV) infection (CHB) is a significant public health problem that could benefit from treatment with immunomodulators. Here we describe a set of therapeutic HBV vaccines that target the internal viral proteins.

Methods

Vaccines are delivered by chimpanzee adenovirus vectors (AdC) of serotype 6 (AdC6) and 7 (AdC7) used in prime only or prime-boost regimens. The HBV antigens are fused into an early T cell checkpoint inhibitor, herpes simplex virus (HSV) glycoprotein D (gD), which enhances and broadens vaccine-induced cluster of differentiation (CD8)+T cell responses.

Results

Our results show that the vaccines are immunogenic in mice. They induce potent CD8+T cell responses that recognize multiple epitopes. CD8+T cell responses increase after a boost, although the breadth remains similar. In mice, which carry high sustained loads of HBV particles due to a hepatic infection with an adeno-associated virus (AAV)8 vector expressing the 1.3HBV genome, CD8+T cell responses to the vaccines are attenuated with a marked shift in the CD8+T cells’ epitope recognition profile.

Conclusions

Our data show that in different stains of mice including those that carry a human major histocompatibility complex (MHC) class I antigen HBV vaccines adjuvanted with a checkpoint inhibitor induce potent and broad HBV-specific CD8+T cell responses and lower but still detectable CD4+T cell responses. CD8+T cell responses are reduced and their epitope specificity changes in mice that are chronically exposed to HBV antigens. Implications for the design of therapeutic HBV vaccines are discussed.
Effectiveness of a fortified drink in improving B vitamin biomarkers in older adults: a controlled intervention trial
Authors: Heffernan Maria , Doherty Leanne C. , Hack Mendes Roberta , Clarke Michelle , Hodge Stephanie , Clements Michelle , McAnena Liadhan , Rivelsrud Mari , Ward Mary , Strain J. J. , McNulty Helene , Brennan Lorraine
Published: December 2021

Background

Older adults are reported to have sub-optimal B vitamin status; targeted food-based solutions may help to address this. The objectives of the OptiAge food intervention study were to develop and investigate the effectiveness of a B vitamin-fortified drink in improving B vitamin biomarkers in older Irish adults with a primary outcome of change in the B vitamin biomarker status.

Methods

A double-blinded randomised controlled trial was performed in parallel at University College Dublin and Ulster University. Participants aged > 50 years were recruited following screening for exclusion criteria (i.e. taking medications known to interfere with B vitamin metabolism, supplements containing B vitamins, consuming > 4 portions of B vitamin-fortified foods per week or diagnosed with gastrointestinal, liver or pulmonary disease). Recruited participants meeting the inclusion criteria were randomised (by sex and study centre) to receive daily for 16 weeks either B vitamin-fortified or placebo drinks as developed by Smartfish, Norway. Each B vitamin-fortified drink (200 ml) contained 200 µg folic acid, 10 µg vitamin B12, 10 mg vitamin B6 and 5 mg riboflavin, while the placebo was an identical, isocaloric formulation without added B vitamins. Fasting blood samples were collected pre- and post-intervention which were used to measure the primary outcome of change in B vitamin biomarker levels.

Results

A total of 95 participants were randomised, of which 81 commenced the trial. Of these, 70 completed (37 in the active and 33 in the placebo groups). Intention to treat (ITT) analysis of the B vitamins demonstrated a significant improvement in all B vitamin biomarkers in the active compared to placebo groups: p < 0.01 for each of serum folate, serum vitamin B12 and plasma pyridoxal 5′-phosphate (vitamin B6) and the functional riboflavin biomarker, erythrocyte glutathione reductase activation coefficient (EGRac). Correspondingly, a significant lowering of serum homocysteine from 11.9 (10.3–15.1) µmol/L to 10.6 (9.4–13.0) µmol/L was observed in response to the active treatment (P < 0.001). Similar results were seen in a per-protocol analysis.

Conclusions

The results demonstrate that a B vitamin-fortified drink was effective in optimising B vitamin status, making this a useful intervention option to improve B vitamin status in older adults.

Trial registration ISRCTN, ISRCTN61709781—Retrospectively registered, https://www.isrctn.com/ISRCTN61709781
Quantitative analysis of macroscopic solute transport in the murine brain
Authors: Ray Lori A. , Pike Martin , Simon Matthew , Iliff Jeffrey J. , Heys Jeffrey J.
Published: December 2021

Background

Understanding molecular transport in the brain is critical to care and prevention of neurological disease and injury. A key question is whether transport occurs primarily by diffusion, or also by convection or dispersion. Dynamic contrast-enhanced (DCE-MRI) experiments have long reported solute transport in the brain that appears to be faster than diffusion alone, but this transport rate has not been quantified to a physically relevant value that can be compared to known diffusive rates of tracers.

Methods

In this work, DCE-MRI experimental data is analyzed using subject-specific finite-element models to quantify transport in different anatomical regions across the whole mouse brain. The set of regional effective diffusivities ($$D_{eff}$$

D

eff

), a transport parameter combining all mechanisms of transport, that best represent the experimental data are determined and compared to apparent diffusivity ($$D_{app}$$

D

app

), the known rate of diffusion through brain tissue, to draw conclusions about dominant transport mechanisms in each region.

Results

In the perivascular regions of major arteries, $$D_{eff}$$

D

eff

for gadoteridol (550 Da) was over 10,000 times greater than $$D_{app}$$

D

app

. In the brain tissue, constituting interstitial space and the perivascular space of smaller blood vessels, $$D_{eff}$$

D

eff

was 10–25 times greater than $$D_{app}$$

D

app

.

Conclusions

The analysis concludes that convection is present throughout the brain. Convection is dominant in the perivascular space of major surface and branching arteries (Pe > 1000) and significant to large molecules (> 1 kDa) in the combined interstitial space and perivascular space of smaller vessels (not resolved by DCE-MRI). Importantly, this work supports perivascular convection along penetrating blood vessels.
Phenotyping seedlings for selection of root system architecture in alfalfa (Medicago sativa L.)
Authors: Bucciarelli Bruna , Xu Zhanyou , Ao Samadangla , Cao Yuanyuan , Monteros Maria J. , Topp Christopher N. , Samac Deborah A.
Published: December 2021

Background

The root system architecture (RSA) of alfalfa (Medicago sativa L.) affects biomass production by influencing water and nutrient uptake, including nitrogen fixation. Further, roots are important for storing carbohydrates that are needed for regrowth in spring and after each harvest. Previous selection for a greater number of branched and fibrous roots significantly increased alfalfa biomass yield. However, phenotyping root systems of mature alfalfa plant is labor-intensive, time-consuming, and subject to environmental variability and human error. High-throughput and detailed phenotyping methods are needed to accelerate the development of alfalfa germplasm with distinct RSAs adapted to specific environmental conditions and for enhancing productivity in elite germplasm. In this study methods were developed for phenotyping 14-day-old alfalfa seedlings to identify measurable root traits that are highly heritable and can differentiate plants with either a branched or a tap rooted phenotype. Plants were grown in a soil-free mixture under controlled conditions, then the root systems were imaged with a flatbed scanner and measured using WinRhizo software.

Results

The branched root plants had a significantly greater number of tertiary roots and significantly longer tertiary roots relative to the tap rooted plants. Additionally, the branch rooted population had significantly more secondary roots > 2.5 cm relative to the tap rooted population. These two parameters distinguishing phenotypes were confirmed using two machine learning algorithms, Random Forest and Gradient Boosting Machines. Plants selected as seedlings for the branch rooted or tap rooted phenotypes were used in crossing blocks that resulted in a genetic gain of 10%, consistent with the previous selection strategy that utilized manual root scoring to phenotype 22-week-old-plants. Heritability analysis of various root architecture parameters from selected seedlings showed tertiary root length and number are highly heritable with values of 0.74 and 0.79, respectively.

Conclusions

The results show that seedling root phenotyping is a reliable tool that can be used for alfalfa germplasm selection and breeding. Phenotypic selection of RSA in seedlings reduced time for selection by 20 weeks, significantly accelerating the breeding cycle.
Clinical characteristics and risk factors associated with mortality in patients with severe community-acquired pneumonia and type 2 diabetes mellitus
Authors: Huang Dong , He Dingxiu , Gong Linjing , Wang Wen , Yang Lei , Zhang Zhongwei , Shi Yujun , Liang Zongan
Published: December 2021

Background

The present study was performed to investigate the impacts of type 2 diabetes mellitus (T2DM) on severe community-acquired pneumonia (SCAP) and to develop a novel prediction model for mortality in SCAP patients with T2DM.

Methods

This was a retrospective observational study conducted in consecutive adult patients with SCAP admitted to the intensive care unit (ICU) of West China Hospital, Sichuan University, China, between September 2011 and September 2019. The primary outcome was hospital mortality. A propensity score matching (PSM) analysis model with a 1:2 ratio was used for the comparisons of clinical characteristics and outcomes between T2DM and nondiabetic patients. The independent risk factors were identified via univariate and then multivariable logistic regression analysis and were then used to establish a nomogram.

Results

In total, 1262 SCAP patients with T2DM and 2524 matched patients without T2DM were included after PSM. Patients with T2DM had longer ICU length of stay (LOS) (13 vs. 12 days, P = 0.016) and higher 14-day mortality (15% vs. 10.8%, P < 0.001), 30-day mortality (25.7% vs. 22.7%, P = 0.046), ICU mortality (30.8% vs. 26.5%, P = 0.005), and hospital mortality (35.2% vs. 31.0%, P = 0.009) than those without T2DM. In SCAP patients with T2DM, the independent risk factors for hospital mortality were increased numbers of comorbidities and diabetes-related complications; elevated C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), brain natriuretic peptide (BNP) and blood lactate; as well as decreased blood pressure on admission. The nomogram had a C index of 0.907 (95% CI: 0.888, 0.927) in the training set and 0.873 (95% CI: 0.836, 0.911) in the testing set, which was superior to the pneumonia severity index (PSI, AUC: 0.809, 95% CI: 0.785, 0.833). The calibration curve and decision curve analysis (DCA) also demonstrated its accuracy and applicability.

Conclusions

SCAP patients with T2DM had worse clinical outcomes than nondiabetic patients. The nomogram has good predictive performance for hospital mortality and might be generally applied after more external validations.
Autologous full-thickness skin graft as reinforcement in parastomal hernia repair: a randomised controlled trial
Authors: Holmdahl Viktor , Gunnarsson Ulf , Strigård Karin
Published: December 2021

Background

Parastomal hernia is a common complication of an enterostomy and can have a significant impact on health-related quality of life. Currently used methods of repair have high recurrence rates and considerable risk for complications. We have developed a new technique for parastomal hernia repair that uses full-thickness skin graft as reinforcement.

Methods

This study protocol describes a multicentre randomised controlled trial on parastomal hernia repair comparing a new full-thickness skin graft technique with conventional synthetic composite mesh as reinforcement of the abdominal wall. Patients with a symptomatic parastomal hernia will be included and followed up at 3, 12 and 36 months, with surgical complication as the primary outcome. Secondary outcomes will be recurrence rate and health-related quality of life assessed with VHPQ, EORTC C30 and CR29. Tissue biology and collagen metabolism will be investigated pre- and postoperatively using biopsies of the abdominal wall fascia and blood samples.

Discussion

Parastomal hernia constitutes a major clinical problem where the prospects of a good result after hernia repair are presently poor. This new method of repair with full-thickness skin grafting could be a new alternative in our surgical toolbox, but before then, it must be evaluated properly.

Trial registration

ClinicalTrials.gov NCT03667287. Registered on September 12, 2018
Catalase deficiency facilitates the shuttling of free fatty acid to brown adipose tissue through lipolysis mediated by ROS during sustained fasting
Authors: Dutta Raghbendra Kumar , Lee Joon No , Maharjan Yunash , Park Channy , Choe Seong-Kyu , Ho Ye-Shih , Park Raekil
Published: December 2021

Background

Fatty acids (FA) derived from adipose tissue and liver serve as the main fuel in thermogenesis of brown adipose tissue (BAT). Catalase, a peroxisomal enzyme, plays an important role in maintaining intracellular redox homeostasis by decomposing hydrogen peroxide to either water or oxygen that oxidize and provide fuel for cellular metabolism. Although the antioxidant enzymatic activity of catalase is well known, its role in the metabolism and maintenance of energy homeostasis has not yet been revealed. The present study investigated the role of catalase in lipid metabolism and thermogenesis during nutrient deprivation in catalase-knockout (KO) mice.

Results

We found that hepatic triglyceride accumulation in KO mice decreased during sustained fasting due to lipolysis through reactive oxygen species (ROS) generation in adipocytes. Furthermore, the free FA released from lipolysis were shuttled to BAT through the activation of CD36 and catabolized by lipoprotein lipase in KO mice during sustained fasting. Although the exact mechanism for the activation of the FA receptor enzyme, CD36 in BAT is still unclear, we found that ROS generation in adipocytes mediated the shuttling of FA to BAT.

Conclusions

Taken together, our findings uncover the novel role of catalase in lipid metabolism and thermogenesis in BAT, which may be useful in understanding metabolic dysfunction.

Graphical Abstract
Finite-time stabilization of switched nonlinear singular systems with asynchronous switching
Authors: Wang Jing , Wang Xingtao
Published: December 2021

This paper is concerned with the finite-time stabilization of a class of switched nonlinear singular systems under asynchronous control. Asynchronism here refers to the delays in switching between the controller and the subsystem. First, the dynamic decomposition technique is used to prove that such a switched singular system is regular and impulse-free. Secondly, based on the state solutions of the closed-loop system in the matched time period and the mismatched time period of the system instead of constructing a Lyapunov function, the sufficient conditions for the finite-time stability of the asynchronous switched singular system are given, there is no limit to the stability of subsystems. Then, the mode-dependent state feedback controller that makes the original system stable is derived in the form of strict linear matrix inequalities. Finally, numerical examples are given to verify the feasibility and validity of the results.
Sustainable energy transition in Central Asia: status and challenges
Authors: Radovanović Mirjana , Filipović Sanja , Andrejević Panić Andrea
Published: December 2021

Background

The paper aims at gaining insight into the implementation of the process of sustainable energy transition in the countries of Central Asia: Kazakhstan, Kyrgyz Republic, Tajikistan, Turkmenistan, and Uzbekistan. Information and scientific studies on the situation in these countries is scarce. On the other hand, these are resource-rich countries, some are exporters, and all are energy transit countries. The main aim of the paper was realized by applying the energy policies and regulatory framework analysis, defining priorities and monitoring selected indicators prescribed by the International Energy Agency.

Methods

The following methods were used in the quantitative analysis: measurement of data intercorrelation; Pearson test of correlation; principal component analysis (with rotation method: Oblimin with Kaiser normalization); Kaiser–Meyer–Olkin measure of sampling adequacy, Bartlett’s test of sphericity and t-test. The period covered by the quantitative analysis: 1990–2018, provided that the available data for 2019 or 2020 were used in certain cases.

Results

Sustainable energy transition is, at the analysis of policies and data, at a low level. There is no adequate regulatory framework in these countries. The energy transition takes place exclusively within the framework of providing enough energy, without regard to sustainability, while even energy exporting countries are not making efforts to achieve a sustainable energy transition.

Conclusions

There are no indications that the energy transition in the countries of Central Asia will take place according to the standards of the European Union or global bodies. On the other hand, having in mind the natural resources of the mentioned countries and the specific geopolitical position, monitoring the changes is of special importance. The impact of changes on sustainability can be determined mainly ex post.
Phenylpropanoid metabolism enzyme activities and gene expression in postharvest melons inoculated with Alternaria alternata
Authors: Bai Yujia , Feng Zuoshan , Paerhati Maerhaba , Wang Jin
Published: December 2021

This study explored the mechanism of melon resistance toAlternaria alternata(A.alternata) infection in Jiashi and 86-1 melons. Melons were inoculated withA.alternataand the change in lesion diameter was measured. The changes in cinnamic acid-4-hydroxylase (C4H), phenylalanine ammonia lyase (PAL), and 4-coumaric acid coenzyme A ligase (4CL) activity and gene expression were studied in the pericarp tissues of Jiashi and 86-1 melons. The lesion diameter was smaller in Jiashi melon than in 86-1 melon, and the pericarp lesions were smaller than pulp lesions, indicating that Jiashi melon can resistA.alternatainfection better than 86-1 melon. After inoculation withA.alternata, the C4H, PAL, and 4CL activities of Jiashi and 86-1 melons peaked in the middle and late storage period, and the peak was higher in Jiashi melons. The gene expression changes were consistent with the enzyme activity. TheC4H,PAL, and4CLgene expression was significantly higher in Jiashi melon pericarp than in 86-1 melon, and the C4H, PAL, and 4CL activities in Jiashi melon were positively correlated with their gene expression, confirming the role of phenylpropanoid metabolism enzymes in resistance toA.alternata.
Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice
Authors: Park Mincheol , Hoang Gia Minh , Nguyen Thien , Lee Eunkyung , Jung Hyun Jin , Choe Youngshik , Lee Moon Hwan , Hwang Jae Youn , Kim Jae Gwan , Kim Tae
Published: December 2021

Background

Alzheimer’s disease (AD) is the most common cause of dementia, and is characterized by amyloid-β (Aβ) plaques and tauopathy. Reducing Aβ has been considered a major AD treatment strategy in pharmacological and non-pharmacological approaches. Impairment of gamma oscillations, which play an important role in perception and cognitive function, has been shown in mouse AD models and human patients. Recently, the therapeutic effect of gamma entrainment in AD mouse models has been reported. Given that ultrasound is an emerging neuromodulation modality, we investigated the effect of ultrasound stimulation pulsed at gamma frequency (40 Hz) in an AD mouse model.

Methods

We implanted electroencephalogram (EEG) electrodes and a piezo-ceramic disc ultrasound transducer on the skull surface of 6-month-old 5×FAD and wild-type control mice (n = 12 and 6, respectively). Six 5×FAD mice were treated with two-hour ultrasound stimulation at 40 Hz daily for two weeks, and the other six mice received sham treatment. Soluble and insoluble Aβ levels in the brain were measured by enzyme-linked immunosorbent assay. Spontaneous EEG gamma power was computed by wavelet analysis, and the brain connectivity was examined with phase-locking value and cross-frequency phase-amplitude coupling.

Results

We found that the total Aβ42 levels, especially insoluble Aβ42, in the treatment group decreased in pre- and infra-limbic cortex (PIL) compared to that of the sham treatment group. A reduction in the number of Aβ plaques was also observed in the hippocampus. There was no increase in microbleeding in the transcranial ultrasound stimulation (tUS) group. In addition, the length and number of microglial processes decreased in PIL and hippocampus. Encelphalographic spontaneous gamma power was increased, and cross-frequency coupling was normalized, implying functional improvement after tUS stimulation.

Conclusion

These results suggest that the transcranial ultrasound-based gamma-band entrainment technique can be an effective therapy for AD by reducing the Aβ load and improving brain connectivity.
Single-cell RNA-sequencing reveals the dynamic process and novel markers in porcine spermatogenesis
Authors: Zhang Lingkai , Li Fuyuan , Lei Peipei , Guo Ming , Liu Ruifang , Wang Ling , Yu Taiyong , Lv Yinghua , Zhang Tao , Zeng Wenxian , Lu Hongzhao , Zheng Yi
Published: December 2021

Background

Spermatogenesis is the process by which male gametes are formed from spermatogonial stem cells and it is essential for the reliable transmission of genetic information between generations. To date, the dynamic transcriptional changes of defined populations of male germ cells in pigs have not been reported.

Results

To characterize the atlas of porcine spermatogenesis, we profiled the transcriptomes of ~ 16,966 testicular cells from a 150-day-old pig testis through single-cell RNA-sequencing (scRNA-seq). The scRNA-seq analysis identified spermatogonia, spermatocytes, spermatids and three somatic cell types in porcine testes. The functional enrichment analysis demonstrated that these cell types played diverse roles in porcine spermatogenesis. The accuracy of the defined porcine germ cell types was further validated by comparing the data from scRNA-seq with those from bulk RNA-seq. Since we delineated four distinct spermatogonial subsets, we further identified CD99 and PODXL2 as novel cell surface markers for undifferentiated and differentiating spermatogonia, respectively.

Conclusions

The present study has for the first time analyzed the transcriptome of male germ cells and somatic cells in porcine testes through scRNA-seq. Four subsets of spermatogonia were identified and two novel cell surface markers were discovered, which would be helpful for studies on spermatogonial differentiation in pigs. The datasets offer valuable information on porcine spermatogenesis, and pave the way for identification of key molecular markers involved in development of male germ cells.
Imaging of peripheral vascular malformations — current concepts and future perspectives
Authors: Schmidt Vanessa F. , Masthoff Max , Czihal Michael , Cucuruz Beatrix , Häberle Beate , Brill Richard , Wohlgemuth Walter A. , Wildgruber Moritz
Published: December 2021

Vascular Malformations belong to the spectrum of orphan diseases and can involve all segments of the vascular tree: arteries, capillaries, and veins, and similarly the lymphatic vasculature. The classification according to the International Society for the Study of Vascular Anomalies (ISSVA) is of major importance to guide proper treatment. Imaging plays a crucial role to classify vascular malformations according to their dominant vessel type, anatomical extension, and flow pattern. Several imaging concepts including color-coded Duplex ultrasound/contrast-enhanced ultrasound (CDUS/CEUS), 4D computed tomography angiography (CTA), magnetic resonance imaging (MRI) including dynamic contrast-enhanced MR-angiography (DCE-MRA), and conventional arterial and venous angiography are established in the current clinical routine. Besides the very heterogenous phenotypes of vascular malformations, molecular and genetic profiling has recently offered an advanced understanding of the pathogenesis and progression of these lesions. As distinct molecular subtypes may be suitable for targeted therapies, capturing certain patterns by means of molecular imaging could enhance non-invasive diagnostics of vascular malformations. This review provides an overview of subtype-specific imaging and established imaging modalities, as well as future perspectives of novel functional and molecular imaging approaches. We highlight recent pioneering imaging studies including thermography, positron emission tomography (PET), and multispectral optoacoustic tomography (MSOT), which have successfully targeted specific biomarkers of vascular malformations.
Physical modelling techniques for the dynamical characterization and sound synthesis of historical bells
Authors: Carvalho Miguel , Debut Vincent , Antunes Jose
Published: December 2021

Capable of maintaining characteristics practically intact over the centuries, bells are musical instruments able to provide important and unique data for the study of musicology and archaeology essential to understand past manufacturing and tuning techniques. In this research we present a multidisciplinary approach based on both direct and reverse engineering processes for the dynamical characterization and sound synthesis of historical bells which proven particularly useful to extract and preserve important information for Cultural Heritage. It allows the assessment of the bell’s 3D morphology, sound properties and casting and tuning techniques over time. The accuracy and usefulness of the developed techniques are illustrated for three historical bells, including the oldest recognized bell in Portugal, dated 1287, and two eighteenth century bells from the Mafra National Palace carillons (Portugal). The proposed approach combines non-invasive up-to-date imaging technology with modelling and computational techniques from vibration analysis, and can be summarized in the following steps: (1) For the diagnosis of existing bells, a precise assessment of the bell geometry is achieved through 3D scanning technologies, used for the field measurement and reconstruction of a 3D geometry model of each bell; (2) To access the modal properties of the bells, for any given (at the design stage) or measured geometry, a finite element model is built to compute the significant frequencies of the bell partials, and the corresponding modal masses and modeshapes. In the case of existing bells, comparison of the computed modes with those obtained from vibrational data, through experimental modal identification, enables the validation (or otherwise correction) of the finite element model; (3) Using the computed or experimentally identified modes, time-domain dynamical responses can be synthesized for any conceivable bell, providing realistic sounds for any given clapper and impact location. Although this study primarily aimed to better understand the morphology and sounds of historical bells to inform their conservation/preservation, this technique can be also applied to modern instruments, either existing or at design stages. To a larger extent, it presents strong potential for applications in the bell industry, namely for restoration and re-tuning, as well as in virtual museology.
Attributes and references to honey bees (Insecta; Hymenoptera; Apidae) and their products in some Asian and Australian societies’ folkloristic domains
Authors: Meyer-Rochow V. B.
Published: December 2021

Background

References to insects in myths, stories, and idioms can be found in almost any culture, but with regard to references involving honey bee species in the Asia-Australian region, little information is available. Such references to bees can be highly informative by revealing attitudes of admiration, fear, ignorance, or even revulsion towards these insects.

Results

The subject is briefly reviewed and examples of references to bees of selected cultural communities are given. Although folkloristic references to honey bees were found to be mostly positive highlighting fearlessness, cleverness, and industriousness of the bees, some also touch upon their ability to cause pain.

Conclusions

Owing to the decreasing contacts and increasing alienization regarding insects generally, a plea is made to collect whatever information is still available about references to bees in songs, myths, stories, proverbs, and idioms and to compare such uses from different regions, e.g., North and South Korea. This would support other fields of research aiming to discover and to describe cultural relationships, migrations, and contacts between different peoples of the Asian/Australian region.
Interictal autonomic dysfunction in patients with epilepsy
Authors: Shaker Kanar K. , Al Mahdawi Akram M. , Hamdan Farqad B.
Published: December 2021

Background

Autonomic nervous system (ANS) symptoms are frequently present in people with epilepsy (PwE). They are generally more prominent when they originate from the temporal lobe. We aim to investigate the alterations of autonomic functions during the interictal period in patient with temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) using heart-based tests, blood pressure (BP)-based tests and sympathetic skin response (SSR). Forty-eight PwE with disease duration ranging from 2 to 15 years and 51 healthy individuals were studied. Long-term electroencephalography (EEG) monitoring, the heart rate variability (HRV) during normal breathing, deep breathing, Valsalva maneuver and standing, BP responses during standing, to isometric hand grip and to mental arithmetic, and the SSR was recorded for all participants.

Results

31 patients with TLE and 17 with IGE showed lower RR-IV values during deep breathing, Valsalva maneuver and standing, but not during rest, impaired BP responses during standing, isometric hand grip, and mental arithmetic. Also, prolonged SSR latencies. Within PwE group, no difference was noticed between males and females, nor between the left and right temporal lobes.

Conclusion

Abnormal autonomic (sympathetic and parasympathetic) regulatory functions suggest that epilepsy may alter the autonomic function and this is not only in TLE but rather in IGE too. These autonomic changes are irrespective of the localization of epilepsy between the two hemispheres. The ANS changes in epileptic patients, particularly those with autonomic symptoms, confirm that electrophysiologic measures of autonomic function may be of value in preventing sudden unexpected death in epilepsy.