bluuebunny/crossref_metadata_2025 huggingface dataset:
Restructuring in a Mesolect: A Case Study on the Basis of the Formal Variation of the Infinitive in Ukrainian–Russian Surzhyk
Authors: Hentschel Gerd , Palinska Olesya
Published: December 2022

In addition to Ukrainian and Russian, Ukraine is linguistically characterized by a Ukrainian–Russian mixed speech called Surzhyk. Given the background of Ukrainian–Russian relations and the emancipation of Ukrainian from the previously dominant Russian, Surzhyk has become the subject of an emotional discussion in independent Ukraine. The majority of Ukrainian scholars working with pre-Labovian and implicit theoretical sociolinguistic (and contact linguistic) models view the distribution of Ukrainian and Russian elements in Surzhyk as spontaneous and chaotic. Furthermore, Surzhyk – together with many who use it – has been widely stigmatized, even by linguists, as a post-colonial legacy from the times of Russian and Soviet dominance.
Taking as an example the forms of verb infinitives, a corpus-based quantitative analysis of about 10,000 instances evidences that Surzhyk shows a considerable degree of stabilization in the use of competing morphological forms. This stabilization can be interpreted best as an instance of structure building in a mesolect between Ukrainian dialects on the one hand and, on the other hand, Russian and (to a certain degree) Ukrainian standard languages in competing roles during the recent history of Ukraine.
PhenoExam: gene set analyses through integration of different phenotype databases
Authors: Cisterna Alejandro , González-Vidal Aurora , Ruiz Daniel , Ortiz Jordi , Gómez-Pascual Alicia , Chen Zhongbo , Nalls Mike , Faghri Faraz , Hardy John , Díez Irene , Maietta Paolo , Álvarez Sara , Ryten Mina , Botía Juan A.
Published: December 2022

Background

Gene set enrichment analysis (detecting phenotypic terms that emerge as significant in a set of genes) plays an important role in bioinformatics focused on diseases of genetic basis. To facilitate phenotype-oriented gene set analysis, we developed PhenoExam, a freely available R package for tool developers and a web interface for users, which performs: (1) phenotype and disease enrichment analysis on a gene set; (2) measures statistically significant phenotype similarities between gene sets and (3) detects significant differential phenotypes or disease terms across different databases.

Results

PhenoExam generates sensitive and accurate phenotype enrichment analyses. It is also effective in segregating gene sets or Mendelian diseases with very similar phenotypes. We tested the tool with two similar diseases (Parkinson and dystonia), to show phenotype-level similarities but also potentially interesting differences. Moreover, we used PhenoExam to validate computationally predicted new genes potentially associated with epilepsy.

Conclusions

We developed PhenoExam, a freely available R package and Web application, which performs phenotype enrichment and disease enrichment analysis on gene set G, measures statistically significant phenotype similarities between pairs of gene sets G and G′ and detects statistically significant exclusive phenotypes or disease terms, across different databases. We proved with simulations and real cases that it is useful to distinguish between gene sets or diseases with very similar phenotypes.

Github R package URL is https://github.com/alexcis95/PhenoExam.

Shiny App URL is https://alejandrocisterna.shinyapps.io/phenoexamweb/.
Association between basal septal hypertrophy and left ventricular geometry in a community population
Authors: Gao Lan , Ma Wei , Li Min , Yang Ying , Qi Litong , Zhang Baowei , Wang Chonghui , Zhang Yan , Huo Yong
Published: December 2022

Background

Left ventricular (LV) geometry is closely associated with cardiovascular disease; however, few studies have evaluated the relationship between basal septal hypertrophy (BSH) and LV geometry. In this study, we examined the relationship between BSH and LV geometry in a Beijing community population.

Methods

The clinical and echocardiographic data of 1032 participants from a community in Beijing were analyzed. BSH was defined as a basal interventricular septal thickness ≥ 14 mm and a basal septal thickness/mid-septal thickness ≥ 1.3. On the basis of their echocardiographic characteristics, patients were described as having a normal geometry, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy. Multivariable logistic regression was used to analyze the relationship between BSH, LV mass index (LVMI), and relative wall thickness (RWT).

Results

The prevalence of BSH was 7.4% (95% confidence interval [CI] 5.8–9.0%). Basal and middle interventricular septal thickness, LV posterior wall thickness, and RWT were greater, while LVMI and LV end-diastolic dimension were lower in the BSH group than in the non-BSH group (p < 0.05). The BSH group accounted for the highest proportion of patients with concentric remodeling. A multivariable regression analysis showed that BSH increased by 3.99-times (odds ratio [OR] 3.99, 95% CI 2.05–7.78, p < 0.01) when RWT was > 0.42, but not when LVMI increased (OR 0.16, 95% CI 0.02–1.19, p = 0.07). There were no interactions between BSH and age, body mass index, sex, diabetes mellitus, coronary heart disease, stroke, and smoking in relation to an RWT > 0.42.

Conclusion

BSH was independently associated with an RWT > 0.42.
Reserve and resilience in CKD: concept introduction and baseline results from the Physical REsilience Prediction in Advanced REnal Disease (PREPARED) study
Authors: Bowling C. Barrett , Olsen Maren K. , Berkowitz Theodore S. Z. , Smith Battista , Floyd Breana , Majette Nadya , Miles Amy L. , Crowley Steven D. , Wang Virginia , Maciejewski Matthew L. , Whitson Heather E.
Published: December 2022

Background

The purpose of this manuscript is to introduce reserve and resilience as novel concepts in chronic kidney disease (CKD) research and present baseline data from a unique prospective cohort study designed to characterize recovery from functional decline after a health event.

Methods

The Physical REsilience Prediction in Advanced REnal Disease (PREPARED) study recruited a national, prospective cohort of Veterans ≥70 years old with an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2, prior nephrology care, and at high risk for hospitalization. Electronic health record data were paired with telephone surveys. Self-reported measures of reserve included physical, psychological, and cognitive capacity and environmental resources. We calculated counts (frequencies) and medians (25th, 75th percentiles) for baseline measures of reserve. The study’s longitudinal follow-up of physical function every 8 weeks or following an acute care encounter, which will be used to define resilience, is ongoing.

Results

Participants had a median (25th, 75th percentile) age of 76.3 (72.8, 81.4) years and eGFR of 23.4 (18.2, 28.8) ml/min/1.73 m2; 23.3% were Black, and 97.4% were male, 91.6% had hypertension, 67.4% had diabetes mellitus, 46.0% had coronary heart disease, and 39.8% had heart failure. Baseline measures of physical, psychological, and cognitive domains showed low reserve on average, but with wide ranges.

Conclusions

Despite similar levels of kidney function, older adults participating in PREPARED had a wide range of measures of reserve in other health domains. Non-renal measures of reserve may be important indicators of capacity of CKD patients to recover after acute care encounters.
Association of periprocedural phentolamine infusion with favorable outcome in patients with chronic kidney disease and chronic coronary syndrome undergoing coronary catheterization: a prospective randomized controlled pilot study
Authors: Hamila Mohamed abo , El Ghawaby Helmy , Zaki Mohamed , Soliman Mohamed , Gabr Khaled
Published: December 2022

Background

Chronic kidney disease (CKD) is a major risk factor for contrast induced acute kidney injury (CI-AKI) in chronic coronary syndrome (CCS) patients undergoing coronary catheterization. We aimed to evaluate the efficacy of phentolamine in prevention of CI-AKI in CKD and CCS patients undergoing percutaneous coronary catheterization for diagnostic angiography ± stenting.

Methods

Participants with CKD and CCS planned for percutaneous coronary catheterization were included, while participants with normal kidney functions were excluded. A consecutive sample of 107 participants (mean age 58.62 ± 8.96 years, 64.5% males) was selected, underwent diagnostic coronary angiography or percutaneous coronary intervention, and received either conventional CI-AKI prevention strategy (group 1) or periprocedural phentolamine and conventional CI-AKI prevention strategy (group 2).

Results

The percentages of study participants who had CI-AKI were 82.9% for group 1 and 17.1% for group 2, respectively. The incidence rate of CI-AKI was significantly lower in group 2 versus group 1 (p <  0.001). The urine output (ml/kg) and the urine output (ml/hour) within 72 hours post procedure was significantly higher in group 2 versus group 1 (t(105) = − 0.69,p <  0.001, t(105) = − 52.46,p < 0.001, respectively), the peak change in serum creatinine and the percentage of change relative to the baseline serum creatinine at 72 hours post procedure was significantly lower in group 2 versus group 1 (t(102) = 0.2, p 0.018, t(102) = 23.54,p < 0.001, respectively), and the incidence rate of major adverse cardiac and cerebrovascular events within 90 days post procedure was significantly lower in group 2 versus group 1 (t(102) = 1.168,P < 0.001), respectively. There was a statistically significant association of periprocedural phentolamine infusion with prevention of CI-AKI (OR = 0.041, 95% CI 0.0149–0.1128,P < 0.0001).

Conclusion

Our study highlights the potential role of phentolamine for protection of the kidney in CKD patients planned for coronary catheterization.

Trial registration

Pan African Clinical Trial Registry Number: PACTR202209493847741.

Date of Trial Registration: 22/09/2022.
Usefulness of the skeletal muscle index in postoperative ileus of colorectal cancer patients: a retrospective cohort study
Authors: Sasaki Maho , Fukuoka Tatsunari , Shibutani Masatsune , Sugimoto Atsushi , Maeda Kiyoshi , Ohira Masaichi
Published: December 2022

Background

Postoperative complications of colorectal cancer mainly include infections (surgical site infection, remote infection, etc.), post-operative ileus (POI), and anastomosis leakage. POI reportedly prolongs the hospital stay and increases medical costs. Therefore, predicting POI is very important. There have been some reports on the relationships between sarcopenia and postoperative complications in colorectal cancer patients, but none have been limited to POI. We therefore conducted a retrospective clinical study with a logistic regression analysis to confirm the risk factors for ileus after colorectal cancer surgery.

Methods

We retrospectively analyzed 213 patients who underwent elective oncological colorectal surgery for colorectal cancer from November 2017 to July 2021. The skeletal muscle mass (SMM, kg) was estimated using a whole-body bioelectrical impedance analysis (BIA), and the skeletal muscle index (SMI) was calculated as the SMM/height2. We divided all patients into 2 groups based on a low SMI (male < 8.958 kg/m2, female < 8.443 kg/m2) or normal SMI. Preoperative and intraoperative factors as well as, postoperative outcomes were then compared between the two groups.

Results

The median (range) age of the 213 included patients was 72.0 (33–91) years old. Complications were noted in 96 patients (45.1%), including 21 (9.9%) with POI. There were 68 (31.9%) low SMI patients. POI occurred significantly more frequently in low SMI patients (19.1%) than in normal SMI patients (5.5%) (p = 0.005). In the multivariate analysis, bleeding (p = 0.039) and a low SMI (p = 0.031) were significantly associated with POI. In addition, a propensity score matching analysis was performed to further reduce the selection bias. As a result, a low SMI was the only independent POI predictor among the 78 matched cases.

Conclusion

A preoperative low SMI in colorectal cancer patients was considered a risk factor for POI.
Urinary incontinence and related quality of life among elderly women in Tabas, South Khorasan, Iran
Authors: Najafi Zahra , Morowatisharifabad Mohammad Ali , Jambarsang Sara , Rezaeipandari Hassan , Hemayati Roya
Published: December 2022

Background

Urinary incontinence (UI) is one of the most common problems in old age that is often seen in women, which causes not only physical problems but also psychological, social, economic problems and poor quality of life. The aim of the present study was to evaluate the UI and related quality of life (QoL) in elderly women.

Methods

This cross-sectional study enrolled 369 women over 60 years old and living in Tabas city, Iran who were selected by cluster random sampling method. The instruments included the International Consultation on Incontinence Questionnaire-Short Form, the International Consultation on Incontinence Questionnaire Urinary Incontinence Quality of Life Module, and a demographic questionnaire. Data analysis was carried out using independent t-test, chi-square, and logistic regression in SPSS software.

Results

The UI prevalence among participants was 24.9% and stress urinary incontinence was the most common type (40.2% of all elderly patients). The mean UI-related QoL score was 38.04 ± 11.67 from the score range of 22–76. There was a significant positive correlation between UI-related QoL score and UI score (r = 0.585,p < 0.001). Age, body mass index (BMI), constipation, history of cesarean section, hypertension, and the use of angiotensin receptor blockers are factors increasing the odds of having UI in this study population.

Conclusion

Aging, some chronic diseases, high BMI, and the use of some drugs are related to UI prevalence. Also, it is associated with lower QOL among elderly women. Designing appropriate intervention programs, controlling chronic diseases, training in the proper use of drugs, and also some physical exercises can be effective in controlling and improving this common syndrome of old age and promoting their QoL.
Primary adrenal insufficiency and myocarditis in COVID-19 disease: a case report
Authors: Eskandari Delaram , Ziaee Amir , Amirfarhangi Anbardan Abdollah , Zeinali Elahe , Tirkan Atefe
Published: December 2022

Background

COVID-19 has different manifestations from respiratory to GI problems, and some of them are more common, but some are rare. Reporting rare cases can significantly advance our understanding of the disease.

Case presentation

In this case, we report an 18-year-old teenage boy with chest pain and resistant hypotension following COVID-19 infection, finally diagnosed as primary adrenal insufficiency and COVID-19 myocarditis.

Conclusion

Adrenal insufficiency can be life-threatening due to its adverse effects on hemodynamic and electrolyte equilibrium. In addition, COVID-19 induced myocarditis can make the situation more complicated.
Health-related quality of life in inflammatory bowel disease: a comparison of patients receiving nurse-led versus conventional follow-up care
Authors: Alvestad Line , Jelsness-Jørgensen Lars-Petter , Goll Rasmus , Clancy Anne , Gressnes Thomas , Valle Per Christian , Broderstad Ann Ragnhild
Published: December 2022

Background

Inflammatory bowel disease (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder with a considerable negative impact on health-related quality of life (HRQoL). During the past decade, IBD nurse specialists have been increasingly involved in follow-up care of IBD outpatients, in a consultative and coordinating role, closely cooperating with gastroenterologists.

Whether patients’ HRQoL differs between nurses’ follow-up care (NF) and conventional follow-up care (CF) has not been widely researched and the aim of this study was to compare two different follow-up regimes with respect to patients’ HRQoL.

Methods

This cross-sectional, multicenter study involved seven centers; five organized as CF, two as NF.

Results

A total of 304 patients aged 18–80 years, 174 females and 130 males, were included, of whom 140 received care under the NF model and 164 under the CF model. Participants in the NF group had a statistically significant higher median total score on the Inflammatory Bowel Disease Questionnaire (IBDQ) (p-value < .001). This pattern could also be seen in the sub-scores of the different IBDQ domains. Despite a trend of higher IBDQ score in all domains in the NF model, the overall result in our study did not reach the limit of 16 points, defined as clinically significant. A higher proportion of NF patients had IBDQ scores defined as remission, as well as a statistically significant higher frequency of outpatient check-ups during a two-year follow-up period.

Conclusions

Nurse-led models are not inferior to conventional models with regards to patient reported HRQoL except in the social domain where the model showed to be clinically significant better. Further studies are needed to advance efforts to implement these models and increase access to IBD care.
Development of a yeast whole-cell biocatalyst for MHET conversion into terephthalic acid and ethylene glycol
Authors: Loll-Krippleber Raphael , Sajtovich Victoria A. , Ferguson Michael W. , Ho Brandon , Burns Andrew R. , Payliss Brandon J. , Bellissimo Joseph , Peters Sydney , Roy Peter J. , Wyatt Haley D. M. , Brown Grant W.
Published: December 2022

Background

Over the 70 years since the introduction of plastic into everyday items, plastic waste has become an increasing problem. With over 360 million tonnes of plastics produced every year, solutions for plastic recycling and plastic waste reduction are sorely needed. Recently, multiple enzymes capable of degrading PET (polyethylene terephthalate) plastic have been identified and engineered. In particular, the enzymes PETase and MHETase from Ideonella sakaiensis depolymerize PET into the two building blocks used for its synthesis, ethylene glycol (EG) and terephthalic acid (TPA). Importantly, EG and TPA can be re-used for PET synthesis allowing complete and sustainable PET recycling.

Results

In this study we used Saccharomyces cerevisiae, a species utilized widely in bioindustrial fermentation processes, as a platform to develop a whole-cell catalyst expressing the MHETase enzyme, which converts monohydroxyethyl terephthalate (MHET) into TPA and EG. We assessed six expression architectures and identified those resulting in efficient MHETase expression on the yeast cell surface. We show that the MHETase whole-cell catalyst has activity comparable to recombinant MHETase purified from Escherichia coli. Finally, we demonstrate that surface displayed MHETase is active across a range of pHs, temperatures, and for at least 12 days at room temperature.

Conclusions

We demonstrate the feasibility of using S. cerevisiae as a platform for the expression and surface display of PET degrading enzymes and predict that the whole-cell catalyst will be a viable alternative to protein purification-based approaches for plastic degradation.
Effectiveness of seasonal malaria chemoprevention in three regions of Togo: a population-based longitudinal study from 2013 to 2020
Authors: Bakai Tchaa A. , Thomas Anne , Iwaz Jean , Atcha-Oubou Tinah , Tchadjobo Tchassama , Khanafer Nagham , Rabilloud Muriel , Voirin Nicolas
Published: December 2022

Background

In 2012, the World Health Organization (WHO) recommended seasonal malaria chemoprevention (SMC) in areas of high seasonal transmission. Though implemented since 2013, the effectiveness of SMC in Togo was never evaluated.

Methods

This study concerned routine data from 2013 to 2020 mass SMC campaigns for children under five in all health facilities of three Regions of Togo. Treatment coverage, reasons for non-treatment, and SMC-attributable adverse reactions were analysed per year and treatment round. Random effect logistic models estimated SMC effectiveness per health district, year, and treatment round.

Results

The overall coverage was 98% (7,971,877 doses for 8,129,668 children). Contraindication was the main reason for non-administration. Over the study period, confirmed malaria cases decreased from 11,269 (1st round of 2016) to 1395 (4th round of 2020). Only 2,398 adverse reactions were reported (prevalence: 3/10,000), but no severe Lyell syndrome or Stevens-Johnson-type skin reaction. Compared to 2016, malaria prevalence decrease was estimated at 22.6% in 2017 (p < 0.001) and 75% in 2020 (p < 0.001). SMC effectiveness ranged from 76.6% (2nd round) to 96.2% (4th round) comparison with the 1st round.

Conclusions

SMC reduced significantly malaria cases among children under five. The results reassure all actors and call for effort intensification to reach the WHO goals for 2030.
Development and application of a novel model to predict the risk of non-alcoholic fatty liver disease among lean pre-diabetics with normal blood lipid levels
Authors: Zhu Wentao , Shi Pei , Fu Jiwei , Liang An , Zheng Ting , Wu Xiaoping , Yuan Songsong
Published: December 2022

Background

Non-alcoholic fatty liver disease (NAFLD) has been associated with type 2 diabetes, but its relationship with pre-diabetes is still unknown. This study aims to determine whether pre-diabetes is associated with NAFLD, followed by establishing a NAFLD predictive nomogram for lean Chinese pre-diabetics with normal blood lipids.

Methods

Datasets from 3 previous studies, 1 (2774 pre-diabetics with normal blood lipids for training, 925 for validation), 2 (546 for longitudinal internal validation, post-5-year follow-up), and 3 (501 from another institution for external validation), were used. Kaplan-Meier determined cumulative NAFLD hazard, and least absolute shrinkage and selection operator regression analysis uncovered its risk factors. Multivariate logistic regression analysis constructed the nomogram, followed by validation with receiver operating characteristic curve, calibration plot, and decision curve analyses.

Results

NAFLD incidence increased with diabetes progression, and pre-diabetics had higher cumulative risk versus non-diabetics, even for lean individuals with normal blood lipids. Six risk factors were identified: body mass index, total cholesterol, alanine aminotransferase:aspartate aminotransferase, triglyceride:high density lipoprotein cholesterol, fasting blood glucose and γ-glutamyl-transferase. The nomogram yielded areas under the curve of 0.808, 0.785, 0.796 and 0.832, for respectively, training, validation, longitudinal internal validation, and external validation, which, along with calibration curve values of p = 0.794, 0.875, 0.854 and 0.810 for those 4 datasets and decision curve analyses, validated its clinical utility.

Conclusions

Lean pre-diabetic Chinese with normal blood lipids have higher NAFLD risk versus non-diabetics. The nomogram is able to predict NAFLD among such individuals, with high discrimination, enabling its use for early detection and intervention.
Engineering magnetic nano-manipulators for boosting cancer immunotherapy
Authors: Yan Bin , Wang Siyao , Liu Chen , Wen Nana , Li Hugang , Zhang Yihan , Wang Hao , Xi Ziyi , Lv Yi , Fan Haiming , Liu Xiaoli
Published: December 2022

Cancer immunotherapy has shown promising therapeutic results in the clinic, albeit only in a limited number of cancer types, and its efficacy remains less than satisfactory. Nanoparticle-based approaches have been shown to increase the response to immunotherapies to address this limitation. In particular, magnetic nanoparticles (MNPs) as a powerful manipulator are an appealing option for comprehensively regulating the immune system in vivo due to their unique magnetically responsive properties and high biocompatibility. This review focuses on assessing the potential applications of MNPs in enhancing tumor accumulation of immunotherapeutic agents and immunogenicity, improving immune cell infiltration, and creating an immunotherapy-sensitive environment. We summarize recent progress in the application of MNP-based manipulators to augment the efficacy of immunotherapy, by MNPs and their multiple magnetically responsive effects under different types of external magnetic field. Furthermore, we highlight the mechanisms underlying the promotion of antitumor immunity, including magnetically actuated delivery and controlled release of immunotherapeutic agents, tracking and visualization of immune response in real time, and magnetic regulation of innate/adaptive immune cells. Finally, we consider perspectives and challenges in MNP-based immunotherapy.
High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma
Authors: Tang Yuting , Ge Shengdong , Zheng Xiao , Zheng Jiejiao
Published: December 2022

Clear cell renal cell carcinoma (ccRCC) is a growing public health challenge worldwide. Hepcidin antimicrobial peptide (HAMP) is differentially expressed in various tumors. However, the roles and functions of HAMP in ccRCC remain unclear. In the present study, we integrated systematic bioinformatics approaches to investigate the roles and functions of HAMP and its association with immune cell infiltration in ccRCC. Compared with paracancerous tissue, HAMP expression was significantly upregulated in ccRCC patients. Meanwhile, we found good diagnostic performance of HAMP for ccRCC patients and its close associations with the clinicopathological features of ccRCC patients. In addition, we found that HAMP is closely related to multiple immune pathways and positively correlated with various immune cells. HAMP was a significant independent predictor for ccRCC. High expression of HAMP was associated with worse clinical prognosis and more immune cell infiltration in ccRCC patients. HAMP may offer potential as a biomarker to predict prognosis and the clinical treatment outcome of ccRCC patients.
Barium Sulfate Deposition in the Gastrointestinal Tract: Review of the literature
Authors: Zaccarini Daniel J. , Lubin David , Sanyal Soma , Abraham Jerrold L.
Published: December 2022

Background

Barium sulfate is utilized for imaging of the gastrointestinal tract and is usually not deposited within the wall of the intestine. It is thought that mucosal injury may allow barium sulfate to traverse the mucosa, and allow deposition to occur uncommonly. Most pathology textbooks describe the typical barium sulfate deposition pattern as small granular accumulation in macrophages, and do not describe the presence of larger rhomboid crystals. This review will summarize the clinical background, radiographic, gross, and microscopic features of barium sulfate deposition in the gastrointestinal tract. A review of the PubMed database was performed to identify all published cases of barium sulfate deposition in the gastrointestinal tract that have been confirmed by pathologic examination.

Conclusions

A review of the literature shows that the most common barium sulfate deposition pattern in the gastrointestinal tract is finely granular deposition (30 previously described cases), and less commonly large rhomboid crystals are seen (19 cases) with or without finely granular deposition. The fine granules are typically located in macrophages, while rhomboid crystals are usually extracellular. There are various methods to support that the foreign material is indeed barium sulfate, however, only a minority of studies perform ancillary testing. Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDS) can be useful for definitive confirmation. This review emphasizes the importance of recognizing both patterns of barium sulfate deposition, and the histologic differential diagnosis.
Calibration and evaluation of the relative biological effectiveness for carbon-ion radiotherapy in a new relative to a clinically applied treatment planning system
Authors: Wang Weiwei , Huang Zhijie , Sun Wei , Wang Xufei , Zhao Jingfang , Shen Hao
Published: December 2022

Background

The study objective was to validate the relative biological effectiveness (RBE) in RayStation for carbon-ion radiotherapy (CIRT) using the Syngo treatment planning system as reference.

Methods

Local effect model I was established in RayStation (Ray-LEM) with the same parameters as in LEM I in Syngo (Syngo-LEM). Three cube plans covering most of the tumors treated at our center were generated with Syngo-LEM. Ray-LEM re-calculated the Syngo plans and compared the RBEs to the Syngo counterparts. The results showed that RayStation RBE was smaller than Syngo RBE. To ensure that Ray-LEM reproduced Syngo RBE, the observed deviations were used to scale the maximum RBE (RBEmax) in Ray-LEM. After this calibration, we further compared the RayStation RBE to Syngo RBE using additional plans in both homogeneous phantoms and patients, to ensure that the calibrated Ray-LEM reproduced Syngo RBE even with more complex planning features.

Results

The calibration increased the RBEmax by 2.3% to raise the Ray-LEM RBE. The target mean RBE deviations in the phantom evaluation plans were median: 0.0 (minimum: − 1.1 to maximum: 0.7) %, and the target mean RBE deviations of the clinical target volumes of 16 patient cases were − 0.4 (− 1.5 to 0.2) %.

Conclusions

The residual RBE difference between RayStation and Syngo was found to be ≤ 1.0%. Thus, we can propose to use RayStation for clinical CIRT treatment planning. However, the potential differences due to the absorbed beam model warrants further exploration.
The role of the sirtuin family in cartilage and osteoarthritis: molecular mechanisms and therapeutic targets
Authors: Sun Kaibo , Wu Yuangang , Zeng Yi , Xu Jiawen , Wu Limin , Li Mingyang , Shen Bin
Published: December 2022

Osteoarthritis (OA) is mainly characterized by the progressive destruction of articular cartilage. Mounting studies have revealed that disruption of extracellular matrix (ECM) homeostasis, aberrant chondrocyte metabolism, an increase in the number of senescent chondrocytes and abnormal activation of cell death such as chondrocyte apoptosis and autophagy, are the crucial steps in OA development. Additionally, mitochondrial dysfunction also participates in the abovementioned processes and is the key element of OA pathogenesis. Sirtuin (SIRT) is a family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that can actively participate and primarily regulate chondrocyte function in OA pathophysiological processes. Some members of the SIRT family located in mitochondria can regulate mitochondrial function and mediate mitochondrial homeostasis via deacetylation to protect chondrocytes. In addition, SIRT can maintain ECM homeostasis, regulate chondrocyte metabolism, inhibit chondrocyte apoptosis and autophagy, and prevent chondrocyte senescence in cartilage by exerting its deacetylation activity. However, the molecular mechanism of the SIRT family against the onset and development of OA remains poorly elucidated. In this review, we will discuss the potential protective role of SIRT in the progression of OA and summarize several sirtuin-activating molecules as well as their potential therapeutic applications for OA.
Alpha-synuclein: a pathological factor with Aβ and tau and biomarker in Alzheimer’s disease
Authors: Shim Kyu Hwan , Kang Min Ju , Youn Young Chul , An Seong Soo A. , Kim SangYun
Published: December 2022

Background

Alpha-synuclein (α-syn) is considered the main pathophysiological protein component of Lewy bodies in synucleinopathies. α-Syn is an intrinsically disordered protein (IDP), and several types of structural conformations have been reported, depending on environmental factors. Since IDPs may have distinctive functions depending on their structures, α-syn can play different roles and interact with several proteins, including amyloid-beta (Aβ) and tau, in Alzheimer’s disease (AD) and other neurodegenerative disorders.

Main body

In previous studies, α-syn aggregates in AD brains suggested a close relationship between AD and α-syn. In addition, α-syn directly interacts with Aβ and tau, promoting mutual aggregation and exacerbating the cognitive decline. The interaction of α-syn with Aβ and tau presented different consequences depending on the structural forms of the proteins. In AD, α-syn and tau levels in CSF were both elevated and revealed a high positive correlation. Especially, the CSF α-syn concentration was significantly elevated in the early stages of AD. Therefore, it could be a diagnostic marker of AD and help distinguish AD from other neurodegenerative disorders by incorporating other biomarkers.

Conclusion

The overall physiological and pathophysiological functions, structures, and genetics of α-syn in AD are reviewed and summarized. The numerous associations of α-syn with Aβ and tau suggested the significance of α-syn, as a partner of the pathophysiological roles in AD. Understanding the involvements of α-syn in the pathology of Aβ and tau could help address the unresolved issues of AD. In particular, the current status of the CSF α-syn in AD recommends it as an additional biomarker in the panel for AD diagnosis.
Effects of non-modifiable risk factors of Alzheimer’s disease on intracortical myelin content
Authors: Fernandez-Alvarez Marina , Atienza Mercedes , Cantero Jose L.
Published: December 2022

Background

Non-modifiable risk factors of Alzheimer’s disease (AD) have lifelong effects on cortical integrity that could be mitigated if identified at early stages. However, it remains unknown whether cortical microstructure is affected in older individuals with non-modifiable AD risk factors and whether altered cortical tissue integrity produces abnormalities in brain functional networks in this AD-risk population.

Methods

Using relative T1w/T2w (rT1w/T2w) ratio maps, we have compared tissue integrity of normal-appearing cortical GM between controls and cognitively normal older adults with either APOE4 (N= 50), with a first-degree family history (FH) of AD (N= 52), or with the co-occurrence of both AD risk factors (APOE4+FH) (N= 35). Additionally, individuals with only one risk factor (APOE4 or FH) were combined into one group (N= 102) and compared with controls. The same number of controls matched in age, sex, and years of education was employed for each of these comparisons. Group differences in resting state functional connectivity (rs-FC) patterns were also investigated, using as FC seeds those cortical regions showing significant changes in rT1w/T2w ratios.

Results

Overall, individuals with non-modifiable AD risk factors exhibited significant variations in rT1w/T2w ratios compared to controls, being APOE4 and APOE4+FH at opposite ends of a continuum. The co-occurrence of APOE4 and FH was further accompanied by altered patterns of rs-FC.

Conclusions

These findings may have practical implications for early detection of cortical abnormalities in older populations with APOE4 and/or FH of AD and open new avenues to monitor changes in cortical tissue integrity associated with non-modifiable AD risk factors.
Hemolysin function of Listeria is related to biofilm formation: transcriptomics analysis
Authors: Li Ruidan , Liang Qian , Tian Sicheng , Zhang Yunwen , Liu Sijing , Ou Qian , Chen Zhaobin , Wang Chuan
Published: December 2022

Listeriolysin O (LLO) is the main virulence protein of Listeria monocytogenes (LM), that helps LM escape lysosomes. We previously found that the cellular immune response elicited by L.ivanovii (LI) is weaker than that elicited by LM. We speculated that this may be related to the function of ivanolysin O (ILO). Here, we constructed hemolysin gene deletion strain, LIΔilo, and a modified strain, LIΔilo::hly, in which ilo was replaced by hly. Prokaryotic transcriptome sequencing was performed on LI, LIΔilo, and LIΔilo::hly. Transcriptome differences between the three strains were compared, and genes and pathways with significant differences between the three strains were analyzed. Prokaryotic transcriptome sequencing results revealed the relationship of ilo to the ribosome, quorum sensing, and phosphotransferase system (PTS) pathways, etc. LIΔilo exhibited attenuated biofilm formation ability compared to LI. Biofilm formation was significantly recovered or even increased after replenishing hly. After knocking out ilo, the relative expression levels of some virulence genes, including sigB, prfA, actA, smcL, and virR, were up-regulated compared to LI. After replenishing hly, these genes were down-regulated compared to LIΔilo. The trend and degree of such variation were not completely consistent when cultured in media containing only monosaccharides or disaccharides. The results confirmed that hemolysin is related to some important biological properties of Listeria, including biofilm formation and virulence gene expression levels. This is the first comprehensive study on ILO function at the transcriptomic level and the first evidence of a relationship between Listeria hemolysin and biofilm formation.
Dandelion (Taraxacum mongolicum Hand.-Mazz.) suppresses the decrease in physical strength and exercise capacity caused by insufficient liver function
Authors: Zhang Yinglong , Li Bo , Wu Guangliang
Published: December 2022

In this study, D-galactose was used to establish a model of liver dysfunction caused by oxidative stress in mice, and the effect of dandelion on improving the exercise capacity of mice with liver dysfunction was observed and its mechanism was expounded. This study examined the role and mechanism of dandelion in improving running ability, swimming endurance, blood biochemical indices, histopathological changes, and tissue mRNA expression changes. The animal results showed that dandelion extended the running and swimming time to exhaustion in liver dysfunctional mice, reduced the serum levels of blood urea nitrogen (BUN), blood lactic acid (BLA) and malondialdehyde (MDA) in the liver, and increased hepatic glycogen (HG) and muscle glycogen (MG) levels as well as uperoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Histopathological observations suggested that dandelion alleviated lesions in the liver. The quantitative polymerase chain reaction (qPCR) analysis results showed that dandelion downregulated inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) mRNA expression and neuronal nitric oxide synthase (nNOS), copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and catalase (CAT) expression in the liver and skeletal muscle of the liver-dysfunctional mice. In contrast, dandelion downregulated syncytin-1 mRNA expression in skeletal muscle of mice with a dysregulated liver. The positional analysis showed that the main components of dandelion were gallic acid, protocatechuic acid, chlorogenic acid, caffeic acid, p-coumaric acid, rutin, myricitrin, isoquercitrin, isochlorogenic acid A, and luteolin.
Digital PCR-based evaluation of nucleic acid extraction kit performance for the co-purification of cell-free DNA and RNA
Authors: Deleu Jill , Schoofs Kathleen , Decock Anneleen , Verniers Kimberly , Roelandt Sofie , Denolf Angie , Verreth Joke , De Wilde Bram , Van Maerken Tom , De Preter Katleen , Vandesompele Jo
Published: December 2022

Background

Blood plasma, one of the most studied liquid biopsies, contains various molecules that have biomarker potential for cancer detection, including cell-free DNA (cfDNA) and cell-free RNA (cfRNA). As the vast majority of cell-free nucleic acids in circulation are non-cancerous, a laboratory workflow with a high detection sensitivity of tumor-derived nucleic acids is a prerequisite for precision oncology. One way to meet this requirement is by the combined analysis of cfDNA and cfRNA from the same liquid biopsy sample. So far, no study has systematically compared the performance of cfDNA and cfRNA co-purification to increase sensitivity.

Results

First, we set up a framework using digital PCR (dPCR) technology to quantify cfDNA and cfRNA from human blood plasma in order to compare cfDNA/cfRNA co-purification kit performance. To that end, we optimized two dPCR duplex assays, designed to quantify both cfDNA and cfRNA with the same assays, by ensuring that primers and probes are located within a highly abundant exon. Next, we applied our optimized workflow to evaluate the co-purification performance of two manual and two semi-automated methods over a range of plasma input volumes (0.06–4 mL). Some kits result in higher nucleic acid concentrations in the eluate, while consuming only half of the plasma volume. The combined nucleic acid quantification systematically results in higher nucleic acid concentrations as compared to a parallel quantification of cfDNA and cfRNA in the eluate.

Conclusions

We provide a framework to evaluate the performance of cfDNA/cfRNA co-purification kits and have tested two manual and two semi-automated co-purification kits in function of the available plasma input amount and the intended use of the nucleic acid eluate. We demonstrate that the combined quantification of cfDNA and cfRNA has a benefit compared to separate quantification. We foresee that the results of this study are instrumental for clinical applications to help increase mutation detection sensitivity, allowing improved disease detection and monitoring.
Cultural experiences in the framework of “cultural cities”: measuring the socioeconomic impact of culture in urban performance
Authors: Rausell-Köster Pau , Ghirardi Sendy , Sanjuán Jordi , Molinari Francesco , Abril Borja
Published: December 2022

This article defines "cultural experience" and places it in a holistic conceptual model; “the cultural city” where it plays a relevant role in improving the performing of cities. The conceptual model combines the basic elements of the heritage city, the smart city and the creative city. The city is interpreted from a threefold perspective; as a repository of resources, as a connective interface, and as the setting for citizens' life and social and professional experiences. In this context, each of these perspectives incorporates culture in a different way, enabling different models of value creation and different processes of production and reproduction of this value. In each of the urban models described above, production processes that combine symbolic, physical, financial, social, human and cultural capital in different ways and urban strategies are implemented to provide cultural experiences that ignite transformative effects through several spillovers. That means that culture, in its different dimensions, regains the role of a raw material and becomes the point of origin to activate development processes and improve urban performance. The integration of the dimensions of the heritage city, the creative city and the smart city through an enabling context is the core proposal of the “cultural city”. In alignment with the New European Agenda for Culture, we deepen the analysis in the specific spillovers on wellbeing and quality of life, citizen engagement and urban renewal as the backbone of a set of external effects of cultural experiences. In the final part of this article, we test the plausibility of this speculative proposal through some empirical evidence. We develop an OLS model with proxy indicators, that could be considered transitional indicators, for the three different potential strategies (heritage, smart, creative). The findings support the assertion that it is conceivable that the supply of cultural experiences through a variety of tactics (heritage city, smart city and creative city) can account in part for the growth of European cities in the years after the 2008 financial crisis. These strategies have contributed to the good performance of the urban device in a way that is positive, not negligible (accounting for around 50% of the variance in productivity) and statistically significant. The provision of a context that increases the cultural experiences for citizens has clearly improved the performance of European cities, and we develop some conceptual and empirical mechanisms to explain and measure the socioeconomic impacts of these processes.
Knowledge and practices on childhood anaemia, thalassaemia and iron deficiency among mothers of children aged between 6 and 59 months in a suburban area of Sri Lanka
Authors: Samararathna Ruwan , Gunaratne A. V. C. , Mettananda Sachith
Published: December 2022

Background

Childhood anaemia is one of the most common public health problems worldwide. Here, we aim to describe the knowledge and practices on childhood anaemia, thalassaemia and iron deficiency among mothers of children aged between 6 and 59 months in a suburban district of Sri Lanka.

Methods

We performed a cross-sectional survey in the Gampaha District of Sri Lanka from December 2020 to February 2021. One well-baby clinic each from four Medical Officer of Health areas in the district was selected using stratified random sampling. Mothers of all children aged between 6 and 59 months attending well-baby clinics were recruited until the sample size was achieved. Data were collected using a self-administered questionnaire and analysed using logistic regression.

Results

A total of 392 mothers were recruited; 53% of their children were males. Only 33% of mothers had an accurate understanding of anaemia, while 71% and 28%, respectively, could name at least one symptom and two causes of anaemia; 12% could not name a single food rich in iron. Only 13% of mothers knew that thalassaemia is a cause of anaemia, and 14% had been screened for thalassaemia. Logistic regression analysis that examined for factors associated with higher knowledge of anaemia revealed that an accurate understanding of anaemia was associated with maternal age over 30 years (p < 0.05) and maternal education level beyond grade ten (p < 0.001). In contrast, higher knowledge of symptoms of anaemia was associated with maternal employment (p < 0.01).

Conclusions

The knowledge of anaemia and awareness of thalassaemia among mothers was poor. Very few mothers were aware of iron-rich food and feed it to their children. Despite being located in a thalassaemia-endemic region, very few knew that thalassaemia is a cause of anaemia and have got themselves screened for thalassaemia.
Body Fat Distribution, Fasting Insulin Levels, and Insulin Secretion: A Bidirectional Mendelian Randomization Study
Authors: Gagnon Eloi , Mitchell Patricia L , Arsenault Benoit J
Published: December 2022

Context

Hyperinsulinemia and adiposity are associated with one another, but the directionality of this relation is debated.

Objective

Here, we tested the direction of the causal effects of fasting insulin (FI) levels and body fat accumulation/distribution using 2-sample bidirectional Mendelian randomization (MR).

Methods

We included summary statistics from large-scale genome-wide association studies for body mass index (BMI, n = 806 834), waist to hip ratio adjusted for BMI (WHRadjBMI, n = 694 649), abdominal subcutaneous, visceral and gluteofemoral adipose tissue (n = 38 965), FI levels (n = 98 210), pancreatic islets gene expression (n = 420), and hypothalamus gene expression (n = 155). We used inverse variance-weighted and robust MR methods that relied on statistically and biologically driven genetic instruments.

Results

Both BMI and WHRadjBMI were positively associated with FI. Results were consistent across all robust MR methods and when variants mapped to the hypothalamus (presumably associated with food behavior) were included. In multivariable MR analyses, when waist circumference and BMI were mutually adjusted, the direct effect of waist circumference on FI was 2.43 times larger than the effect of BMI on FI. FI was not associated with adiposity. By contrast, using genetic instruments mapped to gene expression in pancreatic islets (presumably more specific to insulin secretion), insulin was positively associated with BMI and abdominal subcutaneous and gluteofemoral adipose tissue, but not with visceral adipose tissue.

Conclusion

Although these results will need to be supported by experimental investigations, results of this MR study suggest that abdominal adiposity may be a key determinant of circulating insulin levels. Alternatively, insulin secretion may promote peripheral adipose tissue accumulation.