bluuebunny/crossref_metadata_2025 huggingface dataset:
Label‐free Electrochemical Aptasensor for the Determination of Serotonin
Authors: Li Rong , Li Xiaoxia , Su Liu , Qi Hetong , Yue Xuanfeng , Qi Honglan
Published: September 2021

A label‐free electrochemical aptasensor was fabricated for the determination of serotonin (5‐HT) by the employment of specific binding between 5‐HT and aptamer and directly electrochemical measurement of 5‐HT oxidation. The comparison between two aptasensors and two strategies was studied. An electrochemical aptasensor fabricated using 57‐mer aptamer was facilely used to determine 5‐HT in the range from 1 μM to 100 μM with detection limit of 0.3 μM via one step recognition and detection. This work demonstrates that electrochemical method combing aptamer recognition and 5‐HT oxidation provides an alternative and promising method for the determination of 5‐HT with good selectivity and simplicity.
Performance evaluation, Optimization and exergy analysis of a high temperature co‐electrolysis power to gas process using Aspen Plus®‐a model based study
Authors: Khesa Neo , Mulopo Jean
Published: September 2021

In this paper, a high temperature coelectrolysis power to gas (LTE PtG) setup was developed that was fed a stereotypical feed in CO2 one could acquire from carbon capture and sequestration (CCS) retrofit. The electrolyzer was fed an equimolar 10 kmol/s feed in water and CO2 and the electrolyzer product was composed of 38.80 mole% CO2, 30.96 mole% CO, and 30.24 mole% H2 for a syngas conversion of 43.8%. The product from the methanation unit was only composed of 21.38 mole% CH4, with the rest (76.53 mole%) being predominantly CO2. The methanation unit was composed of only one Sabatier reactor operating at 313°C, which had 90% of its product recycled back to the front end of the unit. The electrolyzer was found to have a LHV efficiency of 31.49%, and the entire HTCE PtG process was found to have an efficiency of 74.31% with methane storage and 76.49% without methane storage. A novel adaptation was developed on previous work on the exergy analysis for flow‐sheet simulators which can be used for cyclic and noncyclic processes. The procedure was determined to be accurate, with irreversibilities determined across all the major subunits found to equal the irreversibility around the processes a whole. The electrolyzer was found to be responsible for the majority of the irreversibility within the setup, and this was attributed to the fact that water electrolysis is a very energy intensive process. The exergy efficiency of the electrolyzer was found to be 87.07% and that of the entire LTE PtG processes was found to be 84% with methane storage, and 87% without methane storage. In the end, it was determined that HTCE is unsuitable for the production of methane via retrofit with a methanation unit, and that it would be better suited for the production of liquid hydrocarbon fuels with much higher molecular carbon to hydrogen ratios.
Food neophobia and intervention of university students in China
Authors: Tian Hua , Chen Jie
Published: September 2021

Background

Food neophobia was defined as the unwillingness or avoidance to eat new foods. There are many studies on food neophobia in children, but few in university students. This study was to examine the level of food neophobia of Chinese university students. The aim is to find a way to help them relieve food neophobia.

Methods

A total of 2,366 university students (16–22 years old) from Xinyang normal university were recruited to conduct a questionnaire survey on food neophobia scale (FNS) of Chinese version, which contained 10 questions. Significant difference analysis and principal component analysis were conducted.

Results

For Chinese university students, willingness to try new food, trust in new food, eating disorder, and food pickiness were the characteristic indexes to evaluate the food neophobia. Gender had no significant effect, but long‐term nutrition courses had a great impact on food neophobia of university students.

Conclusions

The level of food neophobia of Chinese university students is relatively high. To formulate and implement a continuous diet and nutrition education plan is good and necessary to relieve the food neophobia.

Implications for Practice

These data complement the limited literature on food neophobia of university students, which will help to develop intervention plans to reduce eating disorders and support the need for further research to reveal the potential mechanism.
N‐3 PUFA deficiency disrupts oligodendrocyte maturation and myelin integrity during brain development
Authors: Leyrolle Quentin , Decoeur Fanny , Dejean Cyril , Brière Galadriel , Leon Stephane , Bakoyiannis Ioannis , Baroux Emilie , Sterley Tony‐Lee , Bosch‐Bouju Clémentine , Morel Lydie , Amadieu Camille , Lecours Cynthia , St‐Pierre Marie‐Kim , Bordeleau Maude , Roumes Helene , De Smedt‐Peyrusse Véronique , Séré Alexandran , Schwendimann Leslie , Grégoire Stephane , Bretillon Lionel , Acar Niyazi , Joffre Corinne , Ferreira Guillaume , Uricaru Raluca , Thebault Patricia , Gressens Pierre , Tremblay Marie‐Eve , Layé Sophie , Nadjar Agnes
Published: September 2021

Westernization of dietary habits has led to a progressive reduction in dietary intake of n‐3 polyunsaturated fatty acids (n‐3 PUFAs). Low maternal intake of n‐3 PUFAs has been linked to neurodevelopmental disorders, conditions in which myelination processes are abnormal, leading to defects in brain functional connectivity. Only little is known about the role of n‐3 PUFAs in oligodendrocyte physiology and white matter development. Here, we show that lifelong n‐3 PUFA deficiency disrupts oligodendrocytes maturation and myelination processes during the postnatal period in mice. This has long‐term deleterious consequences on white matter organization and hippocampus‐prefrontal functional connectivity in adults, associated with cognitive and emotional disorders. Promoting developmental myelination with clemastine, a first‐generation histamine antagonist and enhancer of oligodendrocyte precursor cell differentiation, rescues memory deficits in n‐3 PUFA deficient animals. Our findings identify a novel mechanism through which n‐3 PUFA deficiency alters brain functions by disrupting oligodendrocyte maturation and brain myelination during the neurodevelopmental period.
Predicting brain age during typical and atypical development based on structural and functional neuroimaging
Authors: Wang Qi , Hu Ke , Wang Meng , Zhao Yuxin , Liu Yong , Fan Lingzhong , Liu Bing
Published: September 2021

Exploring typical and atypical brain developmental trajectories is very important for understanding the normal pace of brain development and the mechanisms by which mental disorders deviate from normal development. A precise and sex‐specific brain age prediction model is desirable for investigating the systematic deviation and individual heterogeneity of disorders associated with atypical brain development, such as autism spectrum disorders. In this study, we used partial least squares regression and the stacking algorithm to establish a sex‐specific brain age prediction model based on T1‐weighted structural magnetic resonance imaging and resting‐state functional magnetic resonance imaging. The model showed good generalization and high robustness on four independent datasets with different ethnic information and age ranges. A predictor weights analysis showed the differences and similarities in changes in structure and function during brain development. At the group level, the brain age gap estimation for autistic patients was significantly smaller than that for healthy controls in both the ABIDE dataset and the healthy brain network dataset, which suggested that autistic patients as a whole exhibited the characteristics of delayed development. However, within the ABIDE dataset, the premature development group had significantly higher Autism Diagnostic Observation Schedule (ADOS) scores than those of the delayed development group, implying that individuals with premature development had greater severity. Using these findings, we built an accurate typical brain development trajectory and developed a method of atypical trajectory analysis that considers sex differences and individual heterogeneity. This strategy may provide valuable clues for understanding the relationship between brain development and mental disorders.
Differential diagnoses of solitary and multiple pigmented lesions of the oral mucosa: Evaluation of 905 specimens submitted to histopathological examination
Authors: Tavares Thalita Soares , Da Costa Adriana Aparecida Silva , Aguiar Maria Cássia Ferreira , Loyola Adriano Mota , Barcelos Natália Santos , Abreu Mauro Henrique Nogueira Guimarães , Mesquita Ricardo Alves , Tarquínio Sandra Beatriz Chaves , De Moraes Êmile , Vasconcelos Ana Carolina Uchôa , Costa Nádia Lago , Mendonça Elismauro Francisco , Cardoso Sérgio Vitorino , Nonaka Cassiano Franscisco Weege , Andrade Allany de Oliveira , Johann Aline Cristina Batista Rodrigues , Michels Arieli Carini , Libório‐Kimura Tatiana Nayara , Neto Gerson Oliveira Paiva , Caldeira Patrícia Carlos
Published: September 2021

Background

The aim was to analyze the frequency, clinical and demographic features of solitary and multiple/diffuse oral pigmented lesions submitted to histopathological examination, and to summarize the features that guide the clinical differential diagnosis.

Methods

Clinical and demographic data were retrieved from biopsy records and descriptive statistics were performed.

Results

Nine hundred and five (0.51%) oral pigmented lesions were retrieved among 177 356 specimens, being 95.9% solitary and 4.1% multiple/diffuse lesions. Regardless the overlapping clinical presentation, age, site, association with amalgam restoration, and a nodular appearance may help in the clinical differential diagnosis of solitary oral pigmentations. Patient's habits, site, and systemic signs and symptoms are helpful in the clinical differential diagnosis of multiple/diffuse lesions.

Conclusions

Oral pigmented lesions are a rare diagnosis in oral pathology and solitary lesions are more commonly submitted to biopsy. Some key features help in the differential diagnosis, though biopsy can be warranted in doubtful cases.
The RNA binding protein human antigen R is a gatekeeper of liver homeostasis
Authors: Subramanian Pallavi , Gargani Sofia , Palladini Alessandra , Chatzimike Margarita , Grzybek Michal , Peitzsch Mirko , Papanastasiou Anastasios D. , Pyrina Iryna , Ntafis Vasileios , Gercken Bettina , Lesche Mathias , Petzold Andreas , Sinha Anupam , Nati Marina , Thangapandi Veera Raghavan , Kourtzelis Ioannis , Andreadou Margarita , Witt Anke , Dahl Andreas , Burkhardt Ralph , Haase Robert , Domingues António Miguel de Jesus , Henry Ian , Zamboni Nicola , Mirtschink Peter , Chung Kyoung‐Jin , Hampe Jochen , Coskun Ünal , Kontoyiannis Dimitris L. , Chavakis Triantafyllos
Published: September 2021

Background and Aims

NAFLD is initiated by steatosis and can progress through fibrosis and cirrhosis to HCC. The RNA binding protein human antigen R (HuR) controls RNAs at the posttranscriptional level; hepatocyte HuR has been implicated in the regulation of diet‐induced hepatic steatosis. The present study aimed to understand the role of hepatocyte HuR in NAFLD development and progression to fibrosis and HCC.

Approach and Results

Hepatocyte‐specific, HuR‐deficient mice and control HuR‐sufficient mice were fed either a normal diet or an NAFLD‐inducing diet. Hepatic lipid accumulation, inflammation, fibrosis, and HCC development were studied by histology, flow cytometry, quantitative PCR, and RNA sequencing. The liver lipidome was characterized by lipidomics analysis, and the HuR–RNA interactions in the liver were mapped by RNA immunoprecipitation sequencing. Hepatocyte‐specific, HuR‐deficient mice displayed spontaneous hepatic steatosis and fibrosis predisposition compared to control HuR‐sufficient mice. On an NAFLD‐inducing diet, hepatocyte‐specific HuR deficiency resulted in exacerbated inflammation, fibrosis, and HCC‐like tumor development. A multi‐omic approach, including lipidomics, transcriptomics, and RNA immunoprecipitation sequencing revealed that HuR orchestrates a protective network of hepatic‐metabolic and lipid homeostasis–maintaining pathways. Consistently, HuR‐deficient livers accumulated, already at steady state, a triglyceride signature resembling that of NAFLD livers. Moreover, up‐regulation of secreted phosphoprotein 1 expression mediated, at least partially, fibrosis development in hepatocyte‐specific HuR deficiency on an NAFLD‐inducing diet, as shown by experiments using antibody blockade of osteopontin.

Conclusions

HuR is a gatekeeper of liver homeostasis, preventing NAFLD‐related fibrosis and HCC, suggesting that the HuR‐dependent network could be exploited therapeutically.
Regioselective Short Synthesis of Epiisoborneol Neopentyl Ether as Chiral Auxiliary: An Absolute Configuration Reset
Authors: Piątek Anna , Chapuis Christian
Published: September 2021

The regio‐selective four step synthesis of (1S,2R,3S,4R)‐4,7,7‐trimethyl‐3‐(neopentyloxy)bicyclo[2.2.1]heptan‐2‐ol, as recognized efficient chiral auxiliary, is presented. The strategy based on opening of the key acetal 15 (=(2S,3aR,4S,7R,7aS)‐2‐tert‐butyl‐4,8,8‐trimethylhexahydro‐2H‐4,7‐methano‐1,3‐benzodioxole) thus circumvents the poor reactivity of the neopentyl electrophile under alkylation conditions. Following the same strategy, but using the unreported acetal 22 (=(2R,3aS,4S,7R,7aR)‐2‐tert‐butyl‐4,8,8‐trimethylhexahydro‐2H‐4,7‐methano‐1,3‐benzodioxole), the corresponding unreported bis‐endo alcohol 23 (=(1R,2R,3S,4S)‐3‐(2,2‐dimethylpropoxy)‐4,7,7‐trimethylbicyclo[2.2.1]heptan‐2‐ol) could be isolated only in poor yield. An alternative regioselective synthesis, including an ultimate endo‐reduction remains to be found. Several erroneous chiroptical properties from the literature are corrected.
The influence of dietary patterns on outcomes in a Bayesian choice task
Authors: Dickinson David L , Garbuio Caleb
Published: September 2021

Background and Aims

Previous research has investigated the impact of diet on cognition, but the focus has often been on general cognition. This paper reports on a preregistered cross‐sectional study aimed at testing for specific executive function differences across individuals who self‐reported one of four distinct dietary patterns: No Diet, No Sugar, Vegetarian, or Mediterranean Diet pattern. Our hypotheses were aimed at testing whether adherence to a specialty diet improved decision making relative to those who reported following No Diet.

Methods

We administered an incentivized Bayesian choice task to all participants. The task involved multiple components of information—existing information (base rate odds) as well as new information (sample draw evidence)—to allow a test of how these information components were used in making probability assessments, and how this may differ by self‐reported dietary pattern. Sample size, hypotheses, and analysis plans were all determined ex ante and registered on the Open Science Framework. Multi‐variate linear and non‐linear estimation methods were used to analyze the data.

Results

Our data failed to support our pre‐registered hypotheses. In fact, we found some evidence that self‐reported adherence to a specialty No Sugar Diet was associated with a reduced decision accuracy and was connected to an increased imbalance in how the participant weighted the two available sources of information when making choices.

Conclusion

Our results suggest that decision making is nuanced among dietary groups, but that short‐term incentivized decisions in an ecologically valid field setting are likely not improved solely by following promoted dietary patterns such as the Mediterranean or Vegetarian diets.
The onset of Darcy–Brinkman–Rayleigh–Benard convection in a composite system with thermal diffusion
Authors: Sumithra Ramakrishna , Komala Basavarajappa , Manjunatha Narayanappa
Published: September 2021

The effect of thermal diffusion on the onset of double‐diffusive convection is analyzed by considering a composite system of the fluid‐saturated porous layer. The porous layer of the composite system is modeled employing the Darcy–Brinkman–Rayleigh–Benard model. The boundaries of the composite system are assumed to be rigid‐rigid under normal gravitational force. The governing equations satisfying the Darcy–Brinkman–Rayleigh–Benard model are solved using the regular perturbation method. A mathematical expression is derived for the critical thermal Rayleigh number by solving the coupled equation. The impact of various physical parameters on the onset of convection is graphically represented under the influence of the Soret effect and the stability of the system is analyzed.
Childhood head trauma and the risk of childhood brain tumours: A case‐control study in Ontario, Canada
Authors: Cheng Sierra , McLaughlin John R. , Brown M. Catherine , Al‐Sawaihey Hamad , Rutka James , Bouffet Eric , Hawkins Cynthia , Cairney A. Elizabeth , Ranger Adrianna , Fleming Adam J. , Johnston Donna , Greenberg Mark , Malkin David , Hung Rayjean J.
Published: September 2021

Head trauma in early childhood has been hypothesized as a potential risk factor for childhood brain tumours (CBTs). However, head trauma has not been extensively studied in the context of CBTs and existing studies have yielded conflicting results. A population‐based and hospital‐based case‐control study of children 0 to 15 years with newly diagnosed CBTs from 1997 to 2003 recruited across Ontario through paediatric oncology centres was conducted. Controls were frequency‐matched with cases by age, sex and geographical region. The association was assessed based on multivariable logistic regressions, accounting for child's age, sex, ethnicity, highest level of maternal education and maternal pack‐years of smoking during the pregnancy. Analyses were conducted separately based on age of first head trauma, sex and histology. A latency period analysis was conducted. Overall, based on 280 cases and 919 controls, CBTs were not significantly associated with previous history of head trauma (OR 1.34, 95% CI 0.96, 1.86), head trauma severity, number of head injuries, or head or neck X‐rays or computed tomography (CT) examinations. Results were consistent across sexes and histological subtypes. However, head trauma within the first year of life was significantly associated with CBTs (OR 2.00, 95% CI 1.01, 3.98), but the association diminished when adjusted for X‐ray or CT occurring during the same time period (OR 1.62, 95% CI 0.75, 3.49), albeit limited sample size. Overall, no association was observed between head trauma and CBTs among all children, while head trauma occurring within first year of life may warrant further investigation in future research.
Survival outcomes associated with completion of adjuvant oxaliplatin‐based chemotherapy for stage III colon cancer: A national population‐based study
Authors: Boyle Jemma M. , Kuryba Angela , Cowling Thomas E. , van der Meulen Jan , Fearnhead Nicola S. , Walker Kate , Braun Michael S. , Aggarwal Ajay
Published: September 2021

The impact of cycle completion rates of oxaliplatin‐based adjuvant chemotherapy for stage III colon cancer in real‐world practice is unknown. We assessed its impact, and that of treatment modification, on 3‐year cancer‐specific mortality. Four thousand one hundred and forty‐seven patients with pathological stage III colon cancer undergoing major resection from 2014 to 2017 in the English National Health Service were included. Chemotherapy data came from linked national administrative datasets. Competing risk regression analysis for 3‐year cancer‐specific mortality was performed according to completion of <6, 6‐11, or 12 5‐fluoropyrimidine and oxaliplatin (FOLFOX) cycles, or <4, 4‐7, or 8 capecitabine and oxaliplatin (CAPOX) cycles, adjusted for patient, tumour and hospital‐level characteristics. Median age was 64 years. Thirty‐two per cent of patients had at least one comorbidity. Forty‐two per cent of patients had T4 disease, and 40% had N2 disease. Compared to completion of 12 FOLFOX cycles, cancer‐specific mortality was higher in patients completing <6 cycles [subdistribution hazard ratios (sHR) 2.17; 95% CI 1.56‐3.03] or 6‐11 cycles (sHR 1.40; 95% CI 1.09‐1.78) (P < .001). Compared to completion of 8 CAPOX cycles, cancer‐specific mortality was higher in patients completing <4 cycles (sHR 2.02; 95% CI 1.53‐2.67) or 4‐7 cycles (sHR 1.63; 95% CI 1.27‐2.10) (P < .001). Dose reduction and early oxaliplatin discontinuation did not impact mortality in patients completing all cycles. Completion of all cycles of chemotherapy was associated with improved cancer‐specific survival in real‐world practice. Poor prognostic factors may have affected findings, however, patients completing <50% of cycles had poor outcomes. Clinicians may wish to facilitate completion with treatment modification in those able to tolerate it.
A transcriptome‐wide association study identifies novel candidate susceptibility genes for prostate cancer risk
Authors: Liu Duo , Zhu Jingjing , Zhou Dan , Nikas Emily G. , Mitanis Nikos T. , Sun Yanfa , Wu Chong , Mancuso Nicholas , Cox Nancy J. , Wang Liang , Freedland Stephen J. , Haiman Christopher A. , Gamazon Eric R. , Nikas Jason B. , Wu Lang
Published: September 2021

A large proportion of heritability for prostate cancer risk remains unknown. Transcriptome‐wide association study combined with validation comparing overall levels will help to identify candidate genes potentially playing a role in prostate cancer development. Using data from the Genotype‐Tissue Expression Project, we built genetic models to predict normal prostate tissue gene expression using the statistical framework PrediXcan, a modified version of the unified test for molecular signatures and Joint‐Tissue Imputation. We applied these prediction models to the genetic data of 79 194 prostate cancer cases and 61 112 controls to investigate the associations of genetically determined gene expression with prostate cancer risk. Focusing on associated genes, we compared their expression in prostate tumor vs normal prostate tissue, compared methylation of CpG sites located at these loci in prostate tumor vs normal tissue, and assessed the correlations between the differentiated genes' expression and the methylation of corresponding CpG sites, by analyzing The Cancer Genome Atlas (TCGA) data. We identified 573 genes showing an association with prostate cancer risk at a false discovery rate (FDR) ≤ 0.05, including 451 novel genes and 122 previously reported genes. Of the 573 genes, 152 showed differential expression in prostate tumor vs normal tissue samples. At loci of 57 genes, 151 CpG sites showed differential methylation in prostate tumor vs normal tissue samples. Of these, 20 CpG sites were correlated with expression of 11 corresponding genes. In this TWAS, we identified novel candidate susceptibility genes for prostate cancer risk, providing new insights into prostate cancer genetics and biology.
FIGO good practice recommendations on cervical cerclage for prevention of preterm birth
Authors: Shennan Andrew , Story Lisa , Jacobsson Bo , Grobman William A. ,   the FIGO Working Group for Preterm Birth
Published: September 2021

Cervical cerclage is an intervention which when given to the right women can prevent preterm birth and second‐trimester fetal losses. A history‐indicated cerclage should be offered to women who have had three or more preterm deliveries and/or mid‐trimester losses. An ultrasound‐indicated cerclage should be offered to women with a cervical length <25 mm if they have had one or more spontaneous preterm birth and/or mid‐trimester loss. In high‐risk women who have not had a previous mid‐trimester loss or preterm birth, an ultrasound‐indicated cerclage does not have a clear benefit in women with a short cervix. However, for twins, the advantage seems more likely at shorter cervical lengths (<15 mm). In women who present with exposed membranes prolapsing through the cervical os, a rescue cerclage can be considered on an individual case basis, taking into account the high risk of infective morbidity to mother and baby. An abdominal cerclage can be offered in women who have had a failed cerclage (delivery before 28 weeks after a history or ultrasound‐indicated [but not rescue] cerclage). If preterm birth has not occurred, removal is considered at 36–37 weeks in women anticipating a vaginal delivery.
FIGO good practice recommendations on the use of prenatal corticosteroids to improve outcomes and minimize harm in babies born preterm
Authors: Norman Jane , Shennan Andrew , Jacobsson Bo , Stock Sarah J. ,   the FIGO Working Group for Preterm Birth
Published: September 2021

For women with a singleton or a multiple pregnancy in situations where active neonatal care is appropriate, and for whom preterm birth is anticipated between 24 and 34 weeks of gestation, one course of prenatal corticosteroids should ideally be offered 18 to 72 h before preterm birth is expected to improve outcomes for the baby. However, if preterm birth is expected within 18 h, prenatal corticosteroids should still be administered. One course of corticosteroids includes two doses of betamethasone acetate/phosphate 12 mg IM 24 h apart, or two doses of dexamethasone phosphate 12 mg IM 24 h apart. In women in whom preterm birth is expected within 72 h and who have had one course of corticosteroids more than a week previously, one single additional course of prenatal corticosteroids could be given at risk of imminent delivery. Prenatal corticosteroids should not be offered routinely to women in whom late preterm birth between 34 and 36 weeks is anticipated. In addition, prenatal corticosteroids should not be given routinely before cesarean delivery at term. Neither should prenatal corticosteroids be given “just in case”. Instead, prenatal steroid administration should be reserved for women for whom preterm birth is expected within no more than 7 days, based on the woman's symptoms or an accurate predictive test.
FIGO good practice recommendations on delayed umbilical cord clamping
Authors: Bianchi Ana , Jacobsson Bo , Mol Ben W. ,   the FIGO Working Group for Preterm Birth
Published: September 2021

Delayed cord clamping in the first minute in preterm infants born before 34 weeks of gestation improves neonatal hematologic measures and may reduce mortality without increasing any other morbidity. In term‐born babies, it also seems to improve both the short‐ and long‐term outcomes and shows favorable scores in fine motor and social domains. However, there is insufficient evidence to show what duration of delay is best. The current evidence supports not clamping the cord before 30 seconds for preterm births. Future trials could compare different lengths of delay. Until then, a period of 30 seconds to 3 minutes seems justified for term‐born babies.
FIGO staging for carcinoma of the vulva: 2021 revision
Authors: Olawaiye Alexander B. , Cotler Joseph , Cuello Mauricio A. , Bhatla Neerja , Okamoto Aikou , Wilailak Sarikapan , Purandare Chittaranjan N. , Lindeque Gerhard , Berek Jonathan S. , Kehoe Sean
Published: September 2021

To revise the FIGO staging for carcinoma of the vulva using a new approach that involves analyses of prospectively collected data. The FIGO Committee for Gynecologic Oncology reviewed the recent literature to gain an insight into the impact of the 2009 vulvar cancer staging revision. The Committee resolved to revise the staging with a goal of simplification and actively collaborated with the United States National Cancer Database to analyze prospectively collected data on carcinoma of the vulva. Many tumor characteristics were collected for all stages of vulvar cancer treated between 2010 and 2017. Statistical analysis was performed with SAS software. Overall survival was estimated based on tumor characteristics. Log‐rank and Wilcoxon tests were used to analyze overall survival similarities between and within groups of tumor characteristics. Characteristics with similar survivals were then grouped into the same stages and substages. Kaplan–Meier overall survival curves were generated for the resulting stages and substages. There were 12 063 cases with available data. The resulting new staging for carcinoma of the vulva has two substages in Stage I, no substage in Stage II, three substages in Stage III, and two substages in Stage IV. The Kaplan–Meier overall survival curves showed clear separation between stages and substages. The 2021 vulvar cancer staging is the first from the FIGO Committee for Gynecologic Oncology to be derived from data analyses. This revision has a new definition for depth of invasion, uses the same definition for lymph node metastases utilized in cervical cancer, and allows findings from cross‐sectional imaging to be incorporated into vulvar cancer staging. The 2021 FIGO staging for carcinoma of the vulva is data‐derived, validated, and much simpler than earlier revisions.
Successful treatment with immunoadsorption therapy in four patients with severe and refractory anti‐N‐methyl‐D‐aspartate receptor encephalitis
Authors: Yang Yu , Zhang Bingjun , Li Min , Li Jing
Published: September 2021

There is still no optimal treatment for patients with severe anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis refractory to first‐line therapy (including intravenous methylprednisolone [IVMP] and intravenous immunoglobulin [IVIG]). A small study has shown that immunoadsorption (IA) is effective in treating anti‐NMDAR encephalitis. However, the effectiveness and safety of IA in the treatment of patients with refractory and severe anti‐NMDAR encephalitis is not fully known. Four patients with severe anti‐NMDAR encephalitis are reported, which were refractory to the first‐line immunotherapy including IVMP and IVIG. Immunoadsorption is performed during the fulminant stage of disease, and the effectiveness and safety of IA are assessed. The modified Rankin Scale (mRS) is used to assess neurological conditions before and after IA. Four patients with the most severe form of anti‐NMDAR encephalitis (two with teratoma and two with unknown origin) did not respond to one or more rounds of IVMP plus IVIG. They all required intensive care unit (ICU) support including long‐term mechanical ventilation, and thus developed ICU‐related complications. Gradual and steady improvement was observed after IA treatment. Except for mild hypotension in patient 1, no other adverse events were observed during IA. Two patients had good early overall recovery on discharge. The other two patients had a good outcome with mRS of 2 at the 12‐month follow‐up. This small case series suggests that IA may be an effective treatment option to accelerate the recovery of patients with severe and refractory anti‐NMDAR encephalitis.
Biochemical strategies of E3 ubiquitin ligases target viruses in critical diseases
Authors: Dubey Ankur R. , Jagtap Yuvraj A. , Kumar Prashant , Patwa Som M. , Kinger Sumit , Kumar Amit , Singh Sarika , Prasad Amit , Jana Nihar R. , Mishra Amit
Published: September 2021

Viruses are known to cause various diseases in human and also infect other species such as animal plants, fungi, and bacteria. Replication of viruses depends upon their interaction with hosts. Human cells are prone to such unwanted viral infections. Disintegration and reconstitution require host machinery and various macromolecules like DNA, RNA, and proteins are invaded by viral particles. E3 ubiquitin ligases are known for their specific function, that is, recognition of their respective substrates for intracellular degradation. Still, we do not understand how ubiquitin proteasome system‐based enzymes E3 ubiquitin ligases do their functional interaction with different viruses. Whether E3 ubiquitin ligases help in the elimination of viral components or viruses utilize their molecular capabilities in their intracellular propagation is not clear. The first time our current article comprehends fundamental concepts and new insights on the different viruses and their interaction with various E3 Ubiquitin Ligases. In this review, we highlight the molecular pathomechanism of viruses linked with E3 Ubiquitin Ligases dependent mechanisms. An enhanced understanding of E3 Ubiquitin Ligase‐mediated removal of viral proteins may open new therapeutic strategies against viral infections.
Association of serum adiponectin and leptin levels with renal function in kidney transplant recipients with or without new‐onset diabetes after transplantation
Authors: Pham Vu Thuy , Can Van Mao , Dang Thanh Chung , Nguyen Minh Tuan , Nguyen Trung Kien , Nguyen Duy Toan , Do Quyet , Tran Viet Tien , Le Viet Thang
Published: September 2021

Purpose

To evaluate serum adiponectin and leptin concentration in new‐onset diabetes after transplantation (NODAT) and non‐NODAT patients and association with renal function in kidney transplant recipients (KTRs).

Patients and methods

A study of 314 consecutive adults KTRs divided into four groups: 236 individuals without NODAT who had renal insufficiency (RI; n = 56) or normal renal function (n = 180) and 78 patients with NODAT who had RI (n = 17) or normal renal function (n = 61). NODAT was diagnosed based on venous fasting blood glucose or HbA1c with the criteria of the American Diabetes Association. Renal insufficiency was defined according to KDOQI 2002 guidelines.

Results

In the NODAT group, the median level of serum adiponectin was lower than that of non‐NODAT one (30 µg/ml vs 37.15 µg/ml, p < 0.001); in contrast, the median leptin concentration was higher (4.27 ng/ml vs 4.05 ng/ml, p = 0.024). In the RI group, both median serum adiponectin and leptin levels were higher than those of non‐RI one (Adiponectin: 40.01 µg/ml vs 33.7 µg/ml; Leptin: 4.51 ng/ml vs 3.91 ng/ml, p < 0.001 both). We found that BMI was related to both adiponectin and leptin levels in both NODAT, non‐NODAT, and all subject groups, based on univariate and multivariate linear regression analysis.

Conclusion

New‐onset diabetes after transplantation, BMI, and renal insufficiency were affected to the serum level of adiponectin and leptin in KTRs.
Formation of a protein corona on the surface of extracellular vesicles in blood plasma
Authors: Tóth Eszter Á. , Turiák Lilla , Visnovitz Tamás , Cserép Csaba , Mázló Anett , Sódar Barbara W. , Försönits András I. , Petővári Gábor , Sebestyén Anna , Komlósi Zsolt , Drahos László , Kittel Ágnes , Nagy György , Bácsi Attila , Dénes Ádám , Gho Yong Song , Szabó‐Taylor Katalin É. , Buzás Edit I.
Published: September 2021

In this study we tested whether a protein corona is formed around extracellular vesicles (EVs) in blood plasma. We isolated medium‐sized nascent EVs of THP1 cells as well as of Optiprep‐purified platelets, and incubated them in EV‐depleted blood plasma from healthy subjects and from patients with rheumatoid arthritis. EVs were subjected to differential centrifugation, size exclusion chromatography, or density gradient ultracentrifugation followed by mass spectrometry. Plasma protein‐coated EVs had a higher density compared to the nascent ones and carried numerous newly associated proteins. Interactions between plasma proteins and EVs were confirmed by confocal microscopy, capillary Western immunoassay, immune electron microscopy and flow cytometry. We identified nine shared EV corona proteins (ApoA1, ApoB, ApoC3, ApoE, complement factors 3 and 4B, fibrinogen α‐chain, immunoglobulin heavy constant γ2 and γ4 chains), which appear to be common corona proteins among EVs, viruses and artificial nanoparticles in blood plasma. An unexpected finding of this study was the high overlap of the composition of the protein corona with blood plasma protein aggregates. This is explained by our finding that besides a diffuse, patchy protein corona, large protein aggregates also associate with the surface of EVs. However, while EVs with an external plasma protein cargo induced an increased expression of TNF‐α, IL‐6, CD83, CD86 and HLA‐DR of human monocyte‐derived dendritic cells, EV‐free protein aggregates had no effect. In conclusion, our data may shed new light on the origin of the commonly reported plasma protein ‘contamination’ of EV preparations and may add a new perspective to EV research.
Effect of modulating glutamate signaling on myelinating oligodendrocytes and their development—A study in the zebrafish model
Authors: Turan Funda , Yilmaz Öznur , Schünemann Lena , Lindenberg Tobias T. , Kalanithy Jeshurun C. , Harder Alexander , Ahmadi Shiva , Duman Türker , MacDonald Ryan B. , Winter Dominic , Liu Changsheng , Odermatt Benjamin
Published: September 2021

Myelination is crucial for the development and maintenance of axonal integrity, especially fast axonal action potential conduction. There is increasing evidence that glutamate signaling and release through neuronal activity modulates the myelination process. In this study, we examine the effect of manipulating glutamate signaling on myelination of oligodendrocyte (OL) lineage cells and their development in zebrafish (zf). We use the “intensity‐based glutamate‐sensing fluorescent reporter” (iGluSnFR) in the zf model (both sexes) to address the hypothesis that glutamate is implicated in regulation of myelinating OLs. Our results show that glial iGluSnFR expression significantly reduces OL lineage cell number and the expression of myelin markers in larvae (zfl) and adult brains. The specific glutamate receptor agonist, L‐AP4, rescues this iGluSnFR effect by significantly increasing the expression of the myelin‐related genes, plp1b and mbpa, and enhances myelination in L‐AP4‐injected zfl compared to controls. Furthermore, we demonstrate that degrading glutamate using Glutamat‐Pyruvate Transaminase (GPT) or the blockade of glutamate reuptake by L‐trans‐pyrrolidine‐2,4‐dicarboxylate (PDC) significantly decreases myelin‐related genes and drastically declines myelination in brain ventricle‐injected zfl. Moreover, we found that myelin‐specific ClaudinK (CldnK) and 36K protein expression is significantly decreased in iGluSnFR‐expressing zfl and adult brains compared to controls. Taken together, this study confirms that glutamate signaling is directly required for the preservation of myelinating OLs and for the myelination process itself. These findings further suggest that glutamate signaling may provide novel targets to therapeutically boost remyelination in several demyelinating diseases of the CNS.
Subanalgesic morphine doses augment fentanyl analgesia by interacting with delta opioid receptors in male rats
Authors: Barker Katherine E. , Lecznar Alynn J. , Schumacher Jill M. , Morris Jeffrey S. , Gutstein Howard B.
Published: September 2021

Opioids are commonly used for the treatment of postoperative and post‐traumatic pain; however, their therapeutic effectiveness is limited by undesirable and life‐threatening side effects. Researchers have long attempted to develop opioid co‐administration therapies that enhance analgesia, but the complexity of opioid analgesia and our incomplete mechanistic understanding has made this a daunting task. We discovered that subanalgesic morphine doses (100 ng/kg–10 µg/kg) augmented the acute analgesic effect of fentanyl (20 µg/kg) following subcutaneous drug co‐administration to male rats. In addition, administration of equivalent drug ratios to naïve rat spinal cord membranes induced a twofold increase in G protein activation. The rate of GTP hydrolysis remained unchanged. We demonstrated that these behavioral and biochemical effects were mediated by the delta opioid receptor (DOP). Subanalgesic doses of the DOP‐selective agonist SNC80 also augmented the acute analgesic effect of fentanyl. Furthermore, co‐administration of the DOP antagonist naltrindole with both fentanyl‐morphine and fentanyl‐SNC80 combinations prevented augmentation of both analgesia and G protein activation. The mu opioid receptor (MOP) antagonist cyprodime did not block augmentation. Confocal microscopy of the substantia gelatinosa of rats treated with fentanyl, subanalgesic morphine, or this combination showed that changes in MOP internalization did not account for augmentation effects. Together, these findings suggest that augmentation of fentanyl analgesia by subanalgesic morphine is mediated by increased G protein activation resulting from a synergistic interaction between or heterodimerization of MOPs and DOPs. This finding is of great therapeutic significance because it suggests a strategy for the development of DOP‐selective ligands that can enhance the therapeutic index of clinically used MOP drugs.
Field‐flow fractionation for nanoparticle characterization
Authors: Lespes Gaëtane , De Carsalade Du Pont Valentin
Published: September 2021

This review presents field‐flow fractionation: The elements of theory enable the link between the retention and the characteristics of the nanometer‐sized analytes to be highlighted. In particular, the nature of force and its way of being applied are discussed. Four types of forces which determine four types of techniques were considered: hydrodynamic, sedimentation, thermal, and electrical; this is to show the importance of the choice of technique in relation to the characterization objectives. Then the separation performance is presented and compared with other separation techniques: field‐flow fractionation has the greatest intrinsic separation capability. The characterization strategies are presented and discussed; on the one hand with respect to the characteristics needed for the description of nanoparticles; on the other hand in connection with the choice of the nature of the force, and also of the detectors used, online or offline. The discussion is based on a selection of published study examples. Finally, current needs and challenges are addressed, and as response, trends and possible characterization solutions.
Sequential Post‐Polymerization Modification of Aldehyde Polymers to Ketone and Oxime Polymers
Authors: Lee Hyo Won , Lee Nam Joo , Kim Jeung Gon
Published: September 2021

A new sequential post‐polymerization modification route has been developed for the synthesis of multifunctional polymers from a simple aldehyde polymer. In the first modification step, a template polymer derived from the radical polymerization of 4‐vinyl benzaldehyde undergoes Rh‐catalyzed hydroacylation with alkenes to furnish a group of ketone polymers. In the second modification step, Schiff base formation with alkoxy ammonium salts introduces a second group—an oxime functionality. Both the steps are highly efficient, introducing evenly distributed dual functionalities at the same position.
Blood Neurofilament Light Chain in Genetic Ataxia: A Meta‐Analysis
Authors: Peng Linliu , Wang Shang , Chen Zhao , Peng Yun , Wang Chunrong , Long Zhe , Peng Huirong , Shi Yuting , Hou Xuan , Lei Lijing , Wan Linlin , Liu Mingjie , Zou Guangdong , Shen Lu , Xia Kun , Qiu Rong , Tang Beisha , Ashizawa Tetsuo , Klockgether Thomas , Jiang Hong
Published: September 2021

Background

No comprehensive meta‐analysis has ever been performed to assess the value of neurofilament light chain (NfL) as a biomarker in genetic ataxia.

Objective

We conducted a meta‐analysis to summarize NfL concentration and evaluate its utility as a biomarker in genetic ataxia.

Methods

Studies were included if they reported NfL concentration of genetic ataxia. We used log (mean ± SD) NfL to describe mean raw value of NfL. The effect size of NfL between genetic ataxia and healthy controls (HC) was expressed by mean difference. Correlation between NfL and disease severity was calculated.

Results

We identified 11 studies of 624 HC and 1006 patients, here referred to as spinocerebellar ataxia (SCA1, 2, 3, 6, and 7), Friedreich ataxia (FRDA), and ataxia telangiectasia (A‐T). The concentration of blood NfL (bNfL) elevated with proximity to expected onset, and progressively increased from asymptomatic to preclinical to clinical stage in SCA3. Compared with HC, bNfL levels were significantly higher in SCA1, 2, 3, and 7, FRDA, as well as A‐T, and the difference increased with the advancing disease in SCA3. bNfL levels correlated with disease severity in SCA3. There was a significant correlation between bNfL and longitudinal progression in SCA3. Additionally, bNfL increased with age in HC, yet this is probably masked by higher disease‐related effects on bNfL in genetic ataxia.

Conclusions

bNfL can be used as a potential biomarker to predict disease onset, severity, and progression of genetic ataxia. Reference‐value setting of bNfL should be divided according to age. © 2021 International Parkinson and Movement Disorder Society
The use of variable delay multipulse chemical exchange saturation transfer for separately assessing different CEST pools in the human brain at 7T
Authors: Schmitz‐Abecassis Bárbara , Vinogradov Elena , Wijnen Jannie P. , van Harten Thijs , Wiegers Evita C. , Hoogduin Hans , van Osch Matthias J. P. , Ercan Ece
Published: September 2021

Purpose

Current challenges of in vivo CEST imaging include overlapping signals from different pools. The overlap arises from closely resonating pools and/or the broad magnetization transfer contrast (MTC) from macromolecules. This study aimed to evaluate the feasibility of variable delay multipulse (VDMP) CEST to separately assess solute pools with different chemical exchange rates in the human brain in vivo, while mitigating the MTC.

Methods

VDMP saturation buildup curves were simulated for amines, amides, and relayed nuclear Overhauser effect. VDMP data were acquired from glutamate and bovine serum albumin phantoms, and from six healthy volunteers at 7T. For the in vivo data, MTC removal was performed via a three‐pool Lorentzian fitting. Different B1 amplitudes and mixing times were used to evaluate CEST pools with different exchange rates.

Results

The results show the importance of removing MTC when applying VDMP in vivo and the influence of B1 for distinguishing different pools. Finally, the optimal B1 and mixing times to effectively saturate slow‐ and fast‐exchanging components are also reported. Slow‐exchanging amides and rNOE components could be distinguished when using B1 = 1 μT and tmix = 10 ms and 40 ms, respectively. Fast‐exchanging components reached the highest saturation when using a B1 = 2.8 μT and tmix = 0 ms.

Conclusion

VDMP is a powerful CEST‐editing tool, exploiting chemical exchange‐rate differences. After MTC removal, it allows separate assessment of slow‐ and fast‐exchanging solute pools in in vivo human brain.
Influence of editing pulse flip angle on J‐difference MR spectroscopy
Authors: Tapper Sofie , Hui Steve C. N. , Saleh Muhammad G. , Zöllner Helge J. , Oeltzschner Georg , Near Jamie , Soher Brian J. , Edden Richard A. E.
Published: September 2021

Purpose

To investigate the editing‐pulse flip angle (FA) dependence of editing efficiency and ultimately to maximize the edited signal of commonly edited MR spectroscopy (MRS) signals, such as gamma‐aminobutyric acid (GABA) and lactate.

Methods

Density‐matrix simulations were performed for a range of spin systems to find the editing‐pulse FA for maximal editing efficiency. Simulations were confirmed by phantom experiments and in vivo measurements in 10 healthy participants using a 3T Philips scanner. Four MEGA‐PRESS in vivo measurements targeting GABA+ and lactate were performed, comparing the conventional editing‐pulse FA (FA = 180°) to the optimal one suggested by simulations (FA = 210°).

Results

Simulations and phantom experiments show that edited GABA and lactate signals are maximal at FA = 210°. Compared to conventional editing (FA = 180°), in vivo signals from GABA+ and lactate signals increase on average by 8.5% and 9.3%, respectively.

Conclusion

Increasing the FA of editing‐pulses in the MEGA‐PRESS experiment from 180° to 210° increases the edited signals from GABA+ and lactate by about 9% in vivo.