bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of brain cancer atlas maps with multimodal imaging features
Authors: Capobianco Enrico , Dominietto Marco
Published: June 2023

Background

Glioblastoma Multiforme (GBM) is a fast-growing and highly aggressive brain tumor that invades the nearby brain tissue and presents secondary nodular lesions across the whole brain but generally does not spread to distant organs. Without treatment, GBM can result in death in about 6 months. The challenges are known to depend on multiple factors: brain localization, resistance to conventional therapy, disrupted tumor blood supply inhibiting effective drug delivery, complications from peritumoral edema, intracranial hypertension, seizures, and neurotoxicity.

Main text

Imaging techniques are routinely used to obtain accurate detections of lesions that localize brain tumors. Especially magnetic resonance imaging (MRI) delivers multimodal images both before and after the administration of contrast, which results in displaying enhancement and describing physiological features as hemodynamic processes. This review considers one possible extension of the use of radiomics in GBM studies, one that recalibrates the analysis of targeted segmentations to the whole organ scale. After identifying critical areas of research, the focus is on illustrating the potential utility of an integrated approach with multimodal imaging, radiomic data processing and brain atlases as the main components. The templates associated with the outcome of straightforward analyses represent promising inference tools able to spatio-temporally inform on the GBM evolution while being generalizable also to other cancers.

Conclusions

The focus on novel inference strategies applicable to complex cancer systems and based on building radiomic models from multimodal imaging data can be well supported by machine learning and other computational tools potentially able to translate suitably processed information into more accurate patient stratifications and evaluations of treatment efficacy.

Graphical Abstract
Attenuation of OX40 signaling suppression by age disrupts peripheral deletion of CD4+ T cells specific for the epidermal autoantigen desmoglein 3
Authors: Iriki Hisato , Mukai Miho , Asahina Yasuhiko , Kubo Yoko , Ito Hiromi , Amagai Masayuki , Takahashi Hayato
Published: June 2023

Various autoimmune responses increase with age, but the underlying mechanism is not clear. In this study, we used CD4+ T cells expressing a transgenic T cell receptor specific for desmoglein 3 (Dsg3), which is the target antigen of the autoimmune bullous disease pemphigus vulgaris, to examine how peripheral immunological tolerance against pathogenic autoreactive CD4+ T cells changes with age. Dsg3-specific T cells were deleted within 14 days after adoptive transfer into young mice (8 weeks old), while they escaped deletion when transferred into older mice over 42 weeks old. Dsg3-specific T cells produced higher levels of the proinflammatory cytokine IFN-γ in aged mice than in young mice. In addition, the expression levels of both OX40 and Birc5, which are important for cell survival in T cell clonal proliferation, were higher in aged than in young mice. The dysfunction in suppressing proinflammatory cytokine secretion and Birc5 upregulation in Dsg3-specific autoreactive T cells may reflect an aspect of the preliminary steps in autoimmune disease development in the aged population. Understanding this mechanism may lead to better risk evaluation of autoimmune disease development and to onset prevention.
Early postnatal microglial ablation in the Ccdc39 mouse model reveals adverse effects on brain development and in neonatal hydrocephalus
Authors: Brown Farrah N. , Iwasawa Eri , Shula Crystal , Fugate Elizabeth M. , Lindquist Diana M. , Mangano Francesco T. , Goto June
Published: June 2023

Background

Neonatal hydrocephalus is a congenital abnormality resulting in an inflammatory response and microglial cell activation both clinically and in animal models. Previously, we reported a mutation in a motile cilia gene, Ccdc39 that develops neonatal progressive hydrocephalus (prh) with inflammatory microglia. We discovered significantly increased amoeboid-shaped activated microglia in periventricular white matter edema, reduced mature homeostatic microglia in grey matter, and reduced myelination in the prh model. Recently, the role of microglia in animal models of adult brain disorders was examined using cell type-specific ablation by colony-stimulating factor-1 receptor (CSF1R) inhibitor, however, little information exists regarding the role of microglia in neonatal brain disorders such as hydrocephalus. Therefore, we aim to see if ablating pro-inflammatory microglia, and thus suppressing the inflammatory response, in a neonatal hydrocephalic mouse line could have beneficial effects.

Methods

In this study, Plexxikon 5622 (PLX5622), a CSF1R inhibitor, was subcutaneously administered to wild-type (WT) and prh mutant mice daily from postnatal day (P) 3 to P7. MRI-estimated brain volume was compared with untreated WT and prh mutants P7-9 and immunohistochemistry of the brain sections was performed at P8 and P18-21.

Results

PLX5622 injections successfully ablated IBA1-positive microglia in both the WT and prh mutants at P8. Of the microglia that are resistant to PLX5622 treatment, there was a higher percentage of amoeboid-shaped microglia, identified by morphology with retracted processes. In PLX-treated prh mutants, there was increased ventriculomegaly and no change in the total brain volume was observed. Also, the PLX5622 treatment significantly reduced myelination in WT mice at P8, although this was recovered after full microglia repopulation by P20. Microglia repopulation in the mutants worsened hypomyelination at P20.

Conclusions

Microglia ablation in the neonatal hydrocephalic brain does not improve white matter edema, and actually worsens ventricular enlargement and hypomyelination, suggesting critical functions of homeostatic ramified microglia to better improve brain development with neonatal hydrocephalus. Future studies with detailed examination of microglial development and status may provide a clarification of the need for microglia in neonatal brain development.
A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations
Authors: Stružinská Ivana , Hájková Nikola , Hojný Jan , Krkavcová Eva , Michálková Romana , Dvořák Jiří , Němejcová Kristýna , Matěj Radoslav , Laco Jan , Drozenová Jana , Fabian Pavel , Hausnerová Jitka , Méhes Gábor , Škapa Petr , Švajdler Marián , Cibula David , Frühauf Filip , Bártů Michaela Kendall , Dundr Pavel
Published: June 2023

Background

Molecular aberrations occurring in primary ovarian clear cell carcinoma (OCCC) can be of diagnostic, predictive, and prognostic significance. However, a complex molecular study including genomic and transcriptomic analysis of large number of OCCC has been lacking.

Methods

113 pathologically confirmed primary OCCCs were analyzed using capture DNA NGS (100 cases; 727 solid cancer related genes) and RNA-Seq (105 cases; 147 genes) in order to describe spectra and frequency of genomic and transcriptomic alterations, as well as their prognostic and predictive significance.

Results

The most frequent mutations were detected in genes ARID1A, PIK3CA, TERTp, KRAS, TP53, ATM, PPP2R1A, NF1, PTEN, and POLE (51,47,27,18,13,10,7,6,6, and 4%, respectively). TMB-High cases were detected in 9% of cases. Cases with POLEmut and/or MSI-High had better relapse-free survival. RNA-Seq revealed gene fusions in 14/105 (13%) cases, and heterogeneous expression pattern. The majority of gene fusions affected tyrosine kinase receptors (6/14; four of those were MET fusions) or DNA repair genes (2/14). Based on the mRNA expression pattern, a cluster of 12 OCCCs characterized by overexpression of tyrosine kinase receptors (TKRs) AKT3, CTNNB1, DDR2, JAK2, KIT, or PDGFRA (p < 0.00001) was identified.

Conclusions

The current work has elucidated the complex genomic and transcriptomic molecular hallmarks of primary OCCCs. Our results confirmed the favorable outcomes of POLEmut and MSI-High OCCC. Moreover, the molecular landscape of OCCC revealed several potential therapeutical targets. Molecular testing can provide the potential for targeted therapy in patients with recurrent or metastatic tumors.
Bioecological representations and social characteristics of students influence their attitudes toward wild vertebrates
Authors: da Silva Amanda Rozendo , Braga-Pereira Franciany , Borges Anna Karolina Martins , de Oliveira José Valberto , da Silva Moacyr Xavier Gomes , Alves Rômulo Romeu Nóbrega
Published: June 2023

Background

The origin of different human emotions directed towards animals (whether in the utilitarian, affective, conflictual, or cosmological context) is strongly influenced by sociocultural factors, although our genetic predispositions also play an important role in the origin of these emotions. Such emotions guide people’s representations of different species, which in turn affect their attitudes toward them. For this reason, understanding the factors that guide such attitudes becomes a key element in making conservationist decisions. In this sense, the main objective of this study was to analyze how sociocultural characteristics and bioecological representations can influence students’ attitudes of empathy or antipathy towards vertebrate species; as well as which classes and species are related to greater and lesser support in people for their conservation.

Methods

To do so, 667 interviews were conducted with students from urban (n = 1) and rural (n = 2) schools in the Brazilian semi-arid region. We used mixed generalized linear models (GLMM) to examine the effect of social factors and bioecological representations on empathy and antipathy attitudes and multiple factor analysis (MFA) to examine the relationship between the biological characteristics of the animals (positive or negative) and the attitudes toward them (antipathetic or empathetic).

Results

Through GLMM, we found that students from the urban area and from lower school levels are more extreme in their responses, more frequently expressing both empathy and antipathy towards wild animals. Regarding gender, women had a higher frequency of responses associated with aversion than men for species perceived as dangerous and poisonous (p < 0.001). Through the MFA, we found greater support (empathy) for the conservation of fish species (31.56%), birds (29.37%) and mammals (25.94%), with emphasis on the Red-cowled cardinal (Paroaria dominicana) and clownfish (Amphiprion ocellaris) species, and less support (antipathy) for reptile and amphibian species such as rattlesnakes (Crotalus durissus) and horned frogs (Ceratophrys joazeirensis).

Conclusions

The attitudinal ambivalence reflected by varying empathy for certain species and antipathy to others has important implications for wildlife conservation. Understanding the socioeconomic factors and emotions that influence attitudes towards animals can enable integrating educational strategies for the conservation of species, especially those which are culturally important.
Expansion of India’s national child healthcare programme, Rashtriya Bal Swasthya Karyakram (RBSK), for rare disease management : a health policy perspective
Authors: Chaube Pragya , Singh Arun K. , Choudhury Mohua Chakraborty
Published: June 2023

Rare diseases (RD) are severe and debilitating conditions. They are one of the leading causes of childhood mortality globally. In India, RDs have not been considered in most healthcare programs which usually cater to more common diseases. We believe, that for efficient utilization of resources in a resource-constrained healthcare system, existing programs must integrate RD management strategies. In this study, we explore the utility, expandability, and limitation of one of the important national child healthcare programs, Rashtriya Bal Swasthya Karyakram (RBSK) which translates to National Child Healthcare Program. We found that RBSK has immense potential to cater to RDs through some of its unique features, such as comprehensive screening, wide target age group, and efficient utilization of resources. We provide recommendations that can help to strengthen the present program. This study will inspire other low-resource countries to identify and expand existing public healthcare programs for RD management. Moreover, RBSK can serve as a model program to integrate RD management globally.
XENERA-1: a randomised double-blind Phase II trial of xentuzumab in combination with everolimus and exemestane versus everolimus and exemestane in patients with hormone receptor-positive/HER2-negative metastatic breast cancer and non-visceral disease
Authors: Schmid Peter , Cortes Javier , Joaquim Ana , Jañez Noelia Martínez , Morales Serafín , Díaz-Redondo Tamara , Blau Sibel , Neven Patrick , Lemieux Julie , García-Sáenz José Ángel , Hart Lowell , Biyukov Tsvetan , Baktash Navid , Massey Dan , Burris Howard A. , Rugo Hope S.
Published: June 2023

Background

Xentuzumab is a humanised monoclonal antibody that binds to IGF-1 and IGF-2, neutralising their proliferative activity and restoring inhibition of AKT by everolimus. This study evaluated the addition of xentuzumab to everolimus and exemestane in patients with advanced breast cancer with non-visceral disease.

Methods

This double-blind, randomised, Phase II study was undertaken in female patients with hormone-receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative advanced breast cancer with non-visceral disease who had received prior endocrine therapy with or without CDK4/6 inhibitors. Patients received a weekly intravenous infusion of xentuzumab (1000 mg) or placebo in combination with everolimus (10 mg/day orally) and exemestane (25 mg/day orally). The primary endpoint was progression-free survival (PFS) per independent review.

Results

A total of 103 patients were randomised and 101 were treated (n = 50 in the xentuzumab arm and n = 51 in the placebo arm). The trial was unblinded early due to high rates of discordance between independent and investigator assessment of PFS. Per independent assessment, median PFS was 12.7 (95% CI 6.8–29.3) months with xentuzumab and 11.0 (7.7–19.5) months with placebo (hazard ratio 1.19; 95% CI 0.55–2.59; p = 0.6534). Per investigator assessment, median PFS was 7.4 (6.8–9.7) months with xentuzumab and 9.2 (5.6–14.4) months with placebo (hazard ratio 1.23; 95% CI 0.69–2.20; p = 0.4800). Tolerability was similar between the arms, with diarrhoea (33.3–56.0%), fatigue (33.3–44.0%) and headache (21.6–40.0%) being the most common treatment-emergent adverse events. The incidence of grade ≥ 3 hyperglycaemia was similar between the xentuzumab (2.0%) and placebo (5.9%) arms.

Conclusions

While this study demonstrated that xentuzumab could be safely combined with everolimus and exemestane in patients with HR-positive/HER2-negative advanced breast cancer with non-visceral disease, there was no PFS benefit with the addition of xentuzumab.

Trial registration ClinicalTrials.gov, NCT03659136. Prospectively registered, September 6, 2018.
Effect of interscalene brachial plexus block with dexmedetomidine and ropivacaine on postoperative analgesia in patients undergoing arthroscopic shoulder surgery: a randomized controlled clinical trial
Authors: Luan Hengfei , Hao Conghui , Li Han , Zhang Xiaobao , Zhao Zhibin , Zhu Pin
Published: June 2023

Background

Dexmedetomidine, a potent and highly selective α2-adrenoreceptor agonist has become a popular adjuvant to local anesthetics. The study was designed to explore the effect of dexmedetomidine added to ropivacaine for interscalene brachial plexus block (IBPB) on postoperative analgesia in patients undergoing arthroscopic shoulder surgery.

Methods

Forty-four adult patients undergoing arthroscopic shoulder surgery were randomly divided into 2 groups. Group R received 0.25% ropivacaine alone, whereas group RD received 0.25% ropivacaine and 0.5 μg/kg dexmedetomidine. A total volume of 15 ml was administered for ultrasound-guided IBPB in both groups. Duration of analgesia, visual analog scale (VAS) pain score, frequency of PCA pressed, first time of PCA pressed, sufentanil consumption, and patient satisfaction with analgesia quality were recorded.

Results

Compared with group R, the duration of analgesia was prolonged (8.25±1.76 vs. 11.55±2.41 h; P<0.05), the VAS pain scores were decreased at 8 and 10 h postoperatively (3 (2–3) vs. 0 (0–0) and 2 (2–3) vs. 0 (0–2.25), respectively; P<0.05), the frequencies of PCA pressed were decreased at 4–8 and 8–12 h time intervals (0 (0–0.25) vs. 0 (0–0) and 5 (1.75–6) vs. 0 (0–2), respectively; P<0.05), the time of first PCA pressed was prolonged (9.27±1.85 vs. 12.98±2.35 h; P<0.05), the total 24h sufentanil consumption was reduced (108.72±15.92 vs. 94.65±12.47 μg; P<0.05 ) and patient satisfaction score was also improved (3 (3–4) vs. 4 (4–5); P<0.05) in group RD.

Conclusion

We concluded that adding 0.5 μg/kg dexmedetomidine to 0.25% ropivacaine for IBPB provided better postoperative analgesia, decreased the sufentanil consumption and improved the patient’s satisfaction in patients undergoing arthroscopic shoulder surgery.
Improved genetic prediction of the risk of knee osteoarthritis using the risk factor-based polygenic score
Authors: Morita Yugo , Kamatani Yoichiro , Ito Hiromu , Ikegawa Shiro , Kawaguchi Takahisa , Kawaguchi Shuji , Takahashi Meiko , Terao Chikashi , Ito Shuji , Nishitani Kohei , Nakamura Shinichiro , Kuriyama Shinichi , Tabara Yasuharu , Matsuda Fumihiko , Matsuda Shuichi ,   on behalf of the Nagahama study group
Published: June 2023

Background

Polygenic risk score (PRS) analysis is used to predict disease risk. Although PRS has been shown to have great potential in improving clinical care, PRS accuracy assessment has been mainly focused on European ancestry. This study aimed to develop an accurate genetic risk score for knee osteoarthritis (OA) using a multi-population PRS and leveraging a multi-trait PRS in the Japanese population.

Methods

We calculated PRS using PRS-CS-auto, derived from genome-wide association study (GWAS) summary statistics for knee OA in the Japanese population (same ancestry) and multi-population. We further identified risk factor traits for which PRS could predict knee OA and subsequently developed an integrated PRS based on multi-trait analysis of GWAS (MTAG), including genetically correlated risk traits. PRS performance was evaluated in participants of the Nagahama cohort study who underwent radiographic evaluation of the knees (n = 3,279). PRSs were incorporated into knee OA integrated risk models along with clinical risk factors.

Results

A total of 2,852 genotyped individuals were included in the PRS analysis. The PRS based on Japanese knee OA GWAS was not associated with knee OA (p = 0.228). In contrast, PRS based on multi-population knee OA GWAS showed a significant association with knee OA (p = 6.7 × 10−5, odds ratio (OR) per standard deviation = 1.19), whereas PRS based on MTAG of multi-population knee OA, along with risk factor traits such as body mass index GWAS, displayed an even stronger association with knee OA (p = 5.4 × 10−7, OR = 1.24). Incorporating this PRS into traditional risk factors improved the predictive ability of knee OA (area under the curve, 74.4% to 74.7%; p = 0.029).

Conclusions

This study showed that multi-trait PRS based on MTAG, combined with traditional risk factors, and using large sample size multi-population GWAS, significantly improved predictive accuracy for knee OA in the Japanese population, even when the sample size of GWAS of the same ancestry was small. To the best of our knowledge, this is the first study to show a statistically significant association between the PRS and knee OA in a non-European population.

Trial registration

No. C278.
Comprehensive DNA methylation profiling of COVID-19 and hepatocellular carcinoma to identify common pathogenesis and potential therapeutic targets
Authors: Luo Huiyan , Chen Jixin , Jiang Qiyin , Yu Yifan , Yang Miaolun , Luo Yuehua , Wang Xiongwen
Published: June 2023

Background & aims

The effects of SARS-CoV-2 infection can be more complex and severe in patients with hepatocellular carcinoma (HCC) as compared to other cancers. This is due to several factors, including pre-existing conditions such as viral hepatitis and cirrhosis, which are commonly associated with HCC.

Methods

We conducted an analysis of epigenomics in SARS-CoV-2 infection and HCC patients, and identified common pathogenic mechanisms using weighted gene co-expression network analysis (WGCNA) and other analyses. Hub genes were identified and analyzed using LASSO regression. Additionally, drug candidates and their binding modes to key macromolecular targets of COVID-19 were identified using molecular docking.

Results

The epigenomic analysis of the relationship between SARS-CoV-2 infection and HCC patients revealed that the co-pathogenesis was closely linked to immune response, particularly T cell differentiation, regulation of T cell activation and monocyte differentiation. Further analysis indicated that CD4+ T cells and monocytes play essential roles in the immunoreaction triggered by both conditions. The expression levels of hub genes MYLK2, FAM83D, STC2, CCDC112, EPHX4 and MMP1 were strongly correlated with SARS-CoV-2 infection and the prognosis of HCC patients. In our study, mefloquine and thioridazine were identified as potential therapeutic agents for COVID-19 in combined with HCC.

Conclusions

In this research, we conducted an epigenomics analysis to identify common pathogenetic processes between SARS-CoV-2 infection and HCC patients, providing new insights into the pathogenesis and treatment of HCC patients infected with SARS-CoV-2.
Learning through clinical extramural studies: an observational study
Authors: Cashman Diane , Rackard Sue
Published: June 2023

Background

Veterinary medicine programmes require students to learn in formal educational settings and through workplace experiences. Previous studies have indicated that learning in the clinical workplace can be informal as students participate in daily activities of service provision by veterinary teams. It can be complex however for students to transition from a traditional formal educational setting to learning in the workplace and students must be able to self-regulate their learning. This requires students to set their own learning goals, consider available learning opportunities and to evaluate if intended learning outcomes have been attained. There is a need to identify strategies students undertake to self-regulate their learning in the workplace to design supports to enhance their learning. The aim of this study was to provide a detailed description of how final year veterinary medicine students plan, learn and reflect on their learning in the workplace context of clinical extramural studies (CEMS) prior to the COVID-19 pandemic.

Methods

An observational repeated cross-sectional design study was conducted with two groups of final year veterinary medicine students in University College Dublin. Data was collected in two stages by analysing student activity records and surveying students in 2017 and 2018. Participants were asked to describe how they planned their CEMS, to describe the types of learning activities they participated in, and describe their reflections of CEMS.

Results

The results are interpreted through the lens of self-regulated learning theory. Analyses of student CEMS activity records indicate that students from both groups primarily participated in small animal / production animal or mixed practice work placements. The majority of respondents of the survey indicated that CEMS was a valuable learning opportunity and they were motivated by placements that would support their future career goals. Financing CEMS placements was a key obstacle to their planning. The majority of respondents indicated varying frequencies of engaging in different types of learning activities and noted that finding suitable placements that facilitated practical skill development and active student learning was a challenge. Implications for veterinary education are discussed.

Conclusions

Student perspectives on planning and learning in the CEMS workplace context yielded important insights into the factors that influence their self-regulatory activities which can help inform future educational interventions to support student learning.
Encapsulated peracetic acid as a valid broad-spectrum antimicrobial alternative, leading to beneficial microbiota compositional changes and enhanced performance in broiler chickens
Authors: Galgano Salvatore , Conway Leah , Dalby Nikki , Fellows Adrian , Houdijk Jos G. M.
Published: June 2023

Background

Antimicrobial alternatives are urgently needed, including for poultry production systems. In this study, we tested the potential broad-range antimicrobial alternative peracetic acid, delivered in feed via the hydrolysis of encapsulated precursors through a 28-day study using 375 Ross 308 broiler chickens. We tested two peracetic acid concentrations, 30 and 80 mg/kg on birds housed on re-used litter, and we evaluated the impact of both levels on gut microbial communities, bacterial concentration, antimicrobial resistance genes relative abundance and growth performance when compared to control birds housed on either clean or re-used litter.

Results

Body weight gain and feed conversion ratio improved in peracetic acid fed birds. At d 28, birds given 30 mg/kg of peracetic acid had a decreased Firmicutes and an increased Proteobacteria abundance in the jejunum, accompanied by an increase inBacillus,FlavonifractorandRombustiain the caeca, and a decreased abundance of tetracycline resistance genes. Chicken given 80 mg/kg of peracetic acid had greater caecal abundance of macrolides lincosamides and streptogramins resistance genes. Growth performance on clean litter was reduced compared to re-used litter, which concurred with increased caecal abundance ofBlautia, decreased caecal abundance ofEscherichia/Shigella, AnaerostipesandJeotgalicoccus, and greater gene abundance of vancomycin, tetracycline, and macrolides resistance genes.

Conclusions

Peracetic acid could be used as a safe broad-spectrum antimicrobial alternative in broilers. Encapsulated precursors were able to reduce the bacterial concentration in the jejunum whilst promoting the proliferation of probiotic genera in the caeca, especially at the low peracetic acid concentrations tested, and improve growth performance. Moreover, our findings offer further insights on potential benefits of rearing birds on re-used litter, suggesting that the latter could be associated with better performance and reduced antimicrobial resistance risk compared to clean litter rearing.
Structural characterization of water-soluble polysaccharides isolated from leaves of Hedera nepalensis
Authors: Ho ChungHyok , Wang Yuwen , Liu Xianbin , Zhou Yifa , Pak UnHak , Sun Lin
Published: June 2023

Background

Hedera nepalensis is a traditional medicinal plants, and the dried leaves of it are generally used for the cure and treatment of many diseases, also widely known as Chang-Chun-Teng in Chinese. Until now, structural characterization of water-soluble polysaccharides isolated from leaves of Hedera nepalensis have been scarcely studied, even though the chemical compounds derived from it and their biological activities have been widely studied.

Methods

Water-soluble polysaccharides (WHNP) were isolated from the dried leaves of Hedera nepalensis, and their structural features were investigated. One neutral polysaccharide fraction (WHNP-N) and three major pectin fractions (WHNP-A2b, WHNP-A2c and WHNP-A3b) were obtained from WHNP, respectively. There was no analysis of the neutral fraction (WHNP-N), while the structural characterization of three major pectin fractions (WHNP-A2b, WHNP-A2c and WHNP-A3b) were further studied by monosaccharide composition, HPGPC, NMR and methylation analyses.

Results

The results indicated that two fractions WHNP-A2b (Mw = 45.8 kDa) and WHNP-A3b (Mw = 58.6 kDa) were mainly composed of rhamnogalacturonan I (RG-I). In WHNP-A2b, RG-I domains primarily substituted with α-L-1,5/1,3,5-arabinan, type II arabinogalactan (AG-II), β-D-1,4-galactan and/or type I arabinogalactan (AG-I) as side chains, while RG-I-type pectin of WHNP-A3b mainly branched with α-L-1,5/1,3,5-arabinan, β-D-1,4-galactan and AG-II side chains. WHNP-A2c (Mw = 12.4 kDa) was primarily comprised of galacturonic acid (GalA, 60.8%), and enzymatic analysis indicated that this fraction mainly consisted of rhamnogalacturonan I (RG-I), rhamnogalacturonan II (RG-II) and homogalacturonan (HG) domains with mass ratios of 1.8:1.0:0.6. On the other hand, WHNP-A2c was found to be rich in RG-I domains, which contained α-L-1,5/1,3,5-arabinan, AG-II, β-D-1,4-galactan and/or AG-I as side chains. The HG domains of WHNP-A2c was released in the form of un-esterified and partly methyl-esterified and/or acetyl-esterified oligogalacturonides with a 1 to 7 degree of polymerization after endo-polygalacturonase degradation.

Conclusion

Our results reveal the structural characteristics of these polysaccharide fractions, which will contribute to elucidating their structure–activity relationships.

Graphical Abstract
Ultra-high b-Value DWI in predicting progression risk of locally advanced rectal cancer: a comparative study with routine DWI
Authors: Zhang Guangwen , Xu Ziliang , Zheng Jianyong , Wang Mian , Ren Jialiang , Wei Xiaocheng , huan Yi , Zhang Jinsong
Published: June 2023

Background

The prognosis prediction of locally advanced rectal cancer (LARC) was important to individualized treatment, we aimed to investigate the performance of ultra-high b-value DWI (UHBV-DWI) in progression risk prediction of LARC and compare with routine DWI.

Methods

This retrospective study collected patients with rectal cancer from 2016 to 2019. Routine DWI (b = 0, 1000 s/mm2) and UHBV-DWI (b = 0, 1700 ~ 3500 s/mm2) were processed with mono-exponential model to generate ADC and ADCuh, respectively. The performance of the ADCuh was compared with ADC in 3-year progression free survival (PFS) assessment using time-dependent ROC and Kaplan-Meier curve. Prognosis model was constructed with ADCuh, ADC and clinicopathologic factors using multivariate COX proportional hazard regression analysis. The prognosis model was assessed with time-dependent ROC, decision curve analysis (DCA) and calibration curve.

Results

A total of 112 patients with LARC (TNM-stage II-III) were evaluated. ADCuh performed better than ADC for 3-year PFS assessment (AUC = 0.754 and 0.586, respectively). Multivariate COX analysis showed that ADCuh and ADC were independent factors for 3-year PFS (P < 0.05). Prognostic model 3 (TNM-stage + extramural venous invasion (EMVI) + ADCuh) was superior than model 2 (TNM-stage + EMVI + ADC) and model 1 (TNM-stage + EMVI) for 3-year PFS prediction (AUC = 0.805, 0.719 and 0.688, respectively). DCA showed that model 3 had higher net benefit than model 2 and model 1. Calibration curve demonstrated better agreement of model 1 than model 2 and model 1.

Conclusions

ADCuh from UHBV-DWI performed better than ADC from routine DWI in predicting prognosis of LARC. The model based on combination of ADCuh, TNM-stage and EMVI could help to indicate progression risk before treatment.
Biocatalysis of triglycerides transesterification using fungal biomass: a biorefinery approach
Authors: Elhussiny Nadeem I. , Mohamed Ahmed M. A. , El-Refai Heba A. , Mohamed Sayeda S. , Shetaia Yousseria M. , Amin Hala A. , Klöck Gerd
Published: June 2023

Background

The use of microbial biomasses, such as fungal biomass, to catalyze the transesterification of triglycerides (TG) for biodiesel production provides a sustainable, economical alternative while still having the main advantages of expensive immobilized enzymes.

Results

Biomasses of Aspergillus flavus and Rhizopus stolonifera were used to catalyze the transesterification of TG in waste frying oil (WFO). Isopropanol as an acyl-acceptor reduced the catalytic capability of the biomasses, while methanol was the most potent acyl-acceptor with a final fatty acid methyl ester (FAME) concentration of 85.5 and 89.7%, w/w, for R. stolonifer and A. flavus, respectively. Different mixtures of the fungal biomasses were tested, and higher proportions of A. flavus biomass improved the mixture's catalytic capability. C. sorokiniana cultivated in synthetic wastewater was used as feedstock to cultivate A. flavus. The biomass produced had the same catalytic capability as the biomass produced in the control culture medium. Response surface methodology (RSM) was adopted using central composite design (CCD) to optimize the A. flavus biomass catalytic transesterification reaction, where temperature, methanol concentration, and biomass concentration were selected for optimization. The significance of the model was verified, and the suggested optimum reaction conditions were 25.5 °C, 250 RPM agitation with 14%, w/w, biomass, 3 mol/L methanol, and a reaction duration of 24 h. The suggested optimum conditions were tested to validate the model and a final FAME concentration of 95.53%. w/w was detected.

Conclusion

Biomasses cocktails might be a legitimate possibility to provide a cheaper technical solution for industrial applications than immobilized enzymes. The use of fungal biomass cultivated on the microalgae recovered from wastewater treatment for the catalysis of transesterification reaction provides an additional piece of the puzzle of biorefinery. Optimizing the transesterification reaction led to a valid prediction model with a final FAME concentration of 95.53%, w/w.
Mixed neuroendocrine–non-neuroendocrine neoplasm of the ampulla of Vater: a case report
Authors: Date Kenjiro , Tatsuguchi Takaaki , Shimokawa Yuzo , Niina Yusuke , Kitahara Daichi , Kuga Hirotaka , Tamiya Sadafumi , Nishihara Kazuyoshi , Nakano Toru
Published: June 2023

Background

Mixed neuroendocrine–non-neuroendocrine neoplasms of the ampulla of Vater are rare and heterogenous, making it difficult to achieve a definitive preoperative diagnosis. Herein, we describe a patient in whom a provisional diagnosis of mixed neuroendocrine–non-neuroendocrine neoplasm of the ampulla of Vater was made preoperatively.

Case presentation

Computed tomography revealed an enhancing periampullary tumor in a 69-year-old man with obstructive jaundice. Subsequent duodenoscopy revealed an ulcerated lesion in the swollen ampulla of Vater, from which six biopsies were collected. Pathological examination revealed adenocarcinoma in five of them. The remaining one was a neuroendocrine neoplasm according to immunohistochemical analysis. With a provisional diagnosis of mixed neuroendocrine–non-neuroendocrine neoplasm of the ampulla of Vater, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy with modified Child’s reconstruction and was discharged without complications. Pathological examination revealed both adenocarcinoma and neuroendocrine carcinomas, each accounting for ≥ 30% of the tumor, resulting in a definitive diagnosis of mixed neuroendocrine–non-neuroendocrine neoplasm of the ampulla of Vater. Lymph node metastases with neuroendocrine components were also observed. Adjuvant chemotherapy was not administered because of the patient’s renal dysfunction. Liver and lymph node metastases were detected 2 months after surgery, the neuroendocrine component being considered responsible for that relapse. The patient underwent platinum-based chemotherapy at 50% dosage, which initially resulted in significant tumor shrinkage; however, he died 6 months after surgery.

Conclusions

While these tumors’ heterogeneity make definitive preoperative diagnosis of mixed neuroendocrine–non-neuroendocrine neoplasm of the ampulla of Vater difficult, the possibility of this disease can be considered by careful examination. Further study is needed to establish the optimal diagnostic criteria and treatment strategy.
A case of safe airway management by fiber-optic nasotracheal intubation in general anesthesia in a pediatric patient with Hajdu-Cheney syndrome: a case report
Authors: Kokita Atsushi , Chaki Tomohiro , Yamakage Michiaki
Published: June 2023

Background

Hajdu-Cheney syndrome (HCS) is an extremely rare disorder characterized by progressive acro-osteolysis. A unique facial structure and deformity of the cervical spine are associated with a difficult airway. Although several reports describe general anesthesia with orotracheal intubation for patients with HCS, there have been no reports of nasotracheal intubation with a risk of skull base fracture. We describe nasotracheal intubation for oral surgery in a patient with HCS.

Case presentation

A 13-year-old girl with HCS was scheduled for dental surgery. Preoperative computed tomography revealed no abnormalities including fractures in the skull base or cervical spine. After confirming a lack of vocal cord paralysis by bronchofiberscopic inspection from the nose, general anesthesia was induced with sevoflurane, remifentanil, and rocuronium. Fiber-optic nasotracheal intubation was successfully performed without complications such as depletion of oxygen saturation and massive epistaxis, and the surgery was completed uneventfully. She was discharged the day after surgery with no anesthesia-related complications.

Conclusions

We were able to safely manage the airway of a patient with HCS by nasotracheal intubation under general anesthesia.
The understanding of medical undergraduates and interns towards basic life support: a cross-sectional study
Authors: Sharma Ankur , Goyal Shilpa , Singh Nehal C. , Kothari Nikhil , Bhatia Pradeep
Published: June 2023

Background

The aim of this study is to understand the attitude and knowledge of medical undergraduates and interns for basic life support (BLS) measures. We also correlated the need for frequent orientation courses beginning at an earlier stage of the medical curriculum. This cross-sectional study was done based on the questionnaire relating to attitude and knowledge for BLS. The participants were 7th and 9th-semester medical undergraduates and the interns of a tertiary care center.

Results

A total of 213 participants completed the questionnaire. The majority of them were interns (40.37%). Maximum (94.1%) of the participants opined that the entire medical and nursing fraternity should be exposed to simulation-based training on BLS. Most (80.3%) of them were aware of recent American Heart Association guidelines 2020, and 96.7% knew the correct meaning of cardiopulmonary resuscitation, but they did not know the subsequent steps in BLS according to the guidelines.

Conclusions

We conclude that awareness of BLS lacked in students of medical school despite regular orientation programs. We recommend the need for frequent orientation courses for BLS and initiate them at the elementary level of education.
Intensive care unit length of stay and mortality comparison between on-pump and off-pump coronary artery bypass graft: a retrospective study
Authors: Ibrahim Rita Zahara , Joyo Ericko Ongko
Published: June 2023

Background

Recently, coronary artery bypass graft (CABG) techniques, both on-pump (ONCABG) and off-pump (OPCABG), were compared to seek the most effective approach to reduce the cost of prolonged intensive care unit length of stay (ICU LOS) and mortality. This study aims to compare ICU LOS and mortality in ONCABG and OPCABG.

Results

Demographic data of 1569 patients show the variance of characteristics. The analysis shows significant and longer ICU LOS in OPCABG than ONCABG (2.151 ± 0.100 vs. 1.573 ± 0.246 days; p = 0.028). Similar results were demonstrated after adjustment of covariates effects (3.146 ± 0.281 vs. 2.548 ± 0.245 days; p = 0,022). Logistic regression shows no significant difference in mortality in OPCABG and ONCABG, both in the unadjusted (OR [CI 95%] 1.133 [0.485–2.800]; p = 0.733) and the adjusted models (OR [CI 95%] 1.133 [0.482–2.817]; p = 0,735).

Conclusion

ICU LOS was significantly longer in OPCABG patients than in ONCABG patients in the author's centre. There was no significant difference in mortality between the two groups. This finding highlights a discrepancy between recently published theories and the practices observed in the author's centre.
First-Line, Fixed-Duration Nivolumab Plus Ipilimumab Followed by Nivolumab in Clinically Diverse Patient Populations With Unresectable Stage III or IV Melanoma: CheckMate 401
Authors: Dummer Reinhard , Corrie Pippa , Gutzmer Ralf , Meniawy Tarek M. , Del Vecchio Michele , Lebbé Céleste , Guida Michele , Dutriaux Caroline , Dreno Brigitte , Meyer Nicolas , Ferrucci Pier Francesco , Dalle Stéphane , Khattak Muhammad Adnan , Grob Jean-Jacques , Briscoe Karen , Larkin James , Mansard Sandrine , Lesimple Thierry , Guidoboni Massimo , Sabatini Silvia , Richtig Erika , Herbst Rudolf , Lobo Maurice , Askelson Margarita , Ascierto Paolo A. , Maio Michele
Published: June 2023

PURPOSE

To address the paucity of data in patients with historically poor outcomes, we conducted the single-arm phase IIIb CheckMate 401 study to evaluate the safety and efficacy of nivolumab plus ipilimumab followed by nivolumab monotherapy in clinically diverse patient populations with advanced melanoma.

METHODS

Treatment-naive patients with unresectable stage III-IV melanoma received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg (240 mg following a protocol amendment) once every 2 weeks for ≤24 months. The primary end point was the incidence of grade 3-5 select treatment-related adverse events (TRAEs). Overall survival (OS) was a secondary end point. Outcomes were evaluated in subgroups defined by Eastern Cooperative Oncology Group performance status (ECOG PS), brain metastasis status, and melanoma subtype.

RESULTS

In total, 533 patients received at least one dose of study drug. Grade 3-5 select TRAEs affecting the GI (16%), hepatic (15%), endocrine (11%), skin (7%), renal (2%), and pulmonary (1%) systems occurred in the all-treated population; similar incidence rates were observed across all subgroups. At 21.6 months' median follow-up, 24-month OS rates were 63% in the all-treated population, 44% in the ECOG PS 2 subgroup (including patients with cutaneous melanoma only), 71% in the brain metastasis subgroup, 36% in the ocular/uveal melanoma subgroup, and 38% in the mucosal melanoma subgroup.

CONCLUSION

Nivolumab plus ipilimumab followed by nivolumab monotherapy was tolerable in patients with advanced melanoma and poor prognostic characteristics. Efficacy was similar between the all-treated population and patients with brain metastases. Reduced efficacy was observed in patients with ECOG PS 2, ocular/uveal melanoma, and/or mucosal melanoma, highlighting the continued need for novel treatment options for these difficult-to-treat patients.
Intimate Foreign Relations
Authors: Litvin Margaret
Published: June 2023

Visualizing Soviet internationalism as a student dormitory, this essay identifies a new transnational subgenre, the Soviet dormitory novel, and analyzes four examples: Nazim Hikmet’s Life’s Good, Brother (Turkish, 1964); Ismail Kadare’s Twilight of the Eastern Gods (Albanian, 1978); Sonallah Ibrahim’s Ice (Arabic, 2011); and Yurii Andrukhovych’s Moscoviad (Ukrainian, 2000). These works each depict a different decade and come from different locations on the concentric map of Soviet influence: the Afro-Asian world, Eastern Europe, and the non-Russian USSR. Together, they reveal some shared formal features of the dormitory novel and some unintended consequences of Soviet internationalism, including the various racisms it rejected but helped perpetuate.
The Rise of Dutch Neo-Calvinist Political Economy, 1830–1905
Authors: Hengstmengel Joost
Published: June 2023

The years 1904–5 seemed to mark the birth of neo-Calvinist political economy in the Netherlands. It was then that three jurists affiliated with the Free University of Amsterdam, an institution founded by the theologian Abraham Kuyper, published their first economic writings. This article deals with the rise of neo-Calvinist political economy, which mirrored the emergence of Catholic economic thought that took place in precisely the same period, and seeks to explain where the ideal of this religious approach to economics came from. It describes the awakening of a socioeconomic commitment in Dutch Réveil circles, the influence of Thomas Chalmers's Christian political economy on the antirevolutionary statesman Guillaume Groen van Prinsterer, and the place of economics in Kuyper's neo-Calvinist worldview. It is shown that Groen van Prinsterer's desire to infuse economic science with biblical views was eventually replaced by Kuyper's vision of formulating a full-fledged Calvinist alternative to mainstream economics. Despite some attempts at Calvinist political economy at the dawn of the nineteenth century, this project never really got off the ground.
Aesthetic Historicism Now
Authors: Sussman Matthew
Published: June 2023

This essay traces the concept of “aesthetic historicism” in literary studies, from its first appearance in the writing of Erich Auerbach to its influence on an array of contemporary currents loosely associated with “new formalism,” such as historical formalism, historical poetics, and historical stylistics. It argues that while Auerbachian aesthetic historicism played a key role in relativizing standards of aesthetic judgment—and thus arguing against aesthetic universals—a newly invigorated version would conceive the history of criticism as a chronicle of different formalisms, each contributing to the construction of “the aesthetic” across time and space.
George Gissing Goes Out in Style: The Syntax of Class after 1890
Authors: Millen Alexander
Published: June 2023

Literary historians often cite George Gissing’s New Grub Street (1891) as a chronicle of a waning literary scene, but his sentences offer altogether stranger demonstrations of how a threatened form of realism attempts to grasp a radically transformed and transforming social situation. Drawing on recent work on the politics of style, this essay argues that Gissing’s narrative style is best understood in terms of two motivating forces powerfully at work in late nineteenth-century Britain: an ascendant popular culture and the massive expansion of the imperial regime. By focusing less on the rumble and verve of an incipient modernism than on the creaky cadences of a realism not long for the world, we begin to discern tectonic shifts at the level of the sentence within and beyond Gissing’s late novels (and the triple-decker). Such shifts allow us to understand how the residual realism of nineteenth-century social-problem fiction attempts to map the world-system. A discussion of Gissing’s style is thus an opportunity to specify the motivating forces at work in his writing and to speculate more broadly about how novelistic prose registers working-class massification and the internationalization of British economic and social worlds in the late nineteenth century.