bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a quantitative method to evaluate pedicle screw loosening after spinal instrumentation using digital tomosynthesis
Authors: Mataki Kentaro , Hara Yuki , Okano Eriko , Nagashima Katsuya , Noguchi Hiroshi , Shibao Yosuke , Miura Kousei , Takahashi Hiroshi , Funayama Toru , Koda Masao , Yamazaki Masashi
Published: April 2022

Background

In general, the diagnosis of pedicle screw (PS) loosening is evaluated qualitatively based on the presence of a radiolucent area around the implant wider than 1 mm on plain radiographs and computed tomography (CT). Digital tomosynthesis is a novel imaging technology that can acquire reconstructed tomographic images of patients in different postures with relatively low radiation. In this study, PS loosening is evaluated quantitatively by measuring the PS displacement angle in the vertebrae using digital tomosynthesis.

Methods

We evaluated 41 patients who underwent posterior spinal fusion surgery using PS. The 72 pedicle screws at the cranial end of the fused segments were evaluated. The patients were divided in two groups, one with PS loosening (7 patients, 12 screws) and the other without PS loosening (34 patients, 60 screws), based on conventional CT findings. All patients underwent tomosynthesis in two different postures during a single CT session.

Results

The displacement angles of the PS in patients in a lying position and in a standing position were measured using selected slices of the same cross-sectional view from digital tomosynthesis. The displacement angle was significantly greater in the PS loosening group (5.7°) than in the group without PS loosening (0.6°) (p<0.01). Based on the ROC analysis, the optimal cut-off value of the PS displacement angle for identification of loosened screws was 1.7° with a sensitivity of 100% and specificity of 93% (AUC = 0.98).

Conclusions

This new method using digital tomosynthesis has the potential to aid diagnosis of PS loosening quantitatively and more accurately than conventional evaluations.
Aerosol exposure of staff during dental treatments: a model study
Authors: Melzow Florentina , Mertens Sarah , Todorov Hristo , Groneberg David A. , Paris Sebastian , Gerber Alexander
Published: April 2022

Background

Due to exposure to potentially infectious aerosols during treatments, the dental personnel is considered being at high risk for aerosol transmitted diseases like COVID-19. The aim of this study was to evaluate aerosol exposure during different dental treatments as well as the efficacy of dental suction to reduce aerosol spreading.

Methods

Dental powder-jet (PJ; Air-Flow®), a water-cooled dental handpiece with a diamond bur (HP) and water-cooled ultrasonic scaling (US) were used in a simulation head, mounted on a dental unit in various treatment settings. The influence of the use of a small saliva ejector (SE) and high-volume suction (HVS) was evaluated. As a proxy of aerosols, air-born particles (PM10) were detected using a Laser Spectrometer in 30 cm distance from the mouth. As control, background particle counts (BC) were measured before and after experiments.

Results

With only SE, integrated aerosol levels [median (Q25/Q75) µg/m3 s] for PJ [91,246 (58,213/118,386) µg/m3 s, p < 0.001, ANOVA] were significantly increased compared to BC [7243 (6501/8407) µg/m3 s], whilst HP [11,119 (7190/17,234) µg/m3 s, p > 0.05] and US [6558 (6002/7066) µg/m3 s; p > 0.05] did not increase aerosol levels significantly. The use of HVS significantly decreased aerosol exposure for PJ [37,170 (29,634/51,719) µg/m3 s; p < 0.01] and HP [5476 (5066/5638) µg/m3 s; p < 0.001] compared to SE only, even reaching lower particle counts than BC levels for HP usage (p < 0.001).

Conclusions

To reduce the exposure to potentially infectious aerosols, HVS should be used during aerosol-forming dental treatments.
Association between mass media exposure and endorsement of HIV-infected female teachers' teaching: insight from 2014 Ghana Demographic and Health Survey
Authors: Appiah Francis , Fenteng Justice Ofosu Darko , Darteh Andrews Ohene , Dare Felix , Saah Joel Afram , Takyi Matthew , Ayerakwah Patience Ansomah , Boakye Kingsley , Ameyaw Edward Kwabena
Published: April 2022

Introduction

Ghana recorded 19,931 new annual HIV infections in 2018 translating to 14,181 AIDS-related deaths. Mass media is capable of ensuring the sustainability of initiatives aimed at curbing HIV/AIDS epidemic by reducing HIV/AIDS stigma and discrimination. The study aimed at exploring if mass media plays a role in whether HIV-infected female teachers should be allowed to teach in Ghana.

Materials and methods

The study used women’s file of the 2014 Ghana Demographic and Health Survey (GDHS). The current study was restricted to 6025 women who had complete information on the variables analysed. Binary Logistic regression was conducted between mass media and the dependent variable whilst controlling for the effect of the significant covariates. The results were presented in odds ratio (OR) and adjusted odds ratio (AOR) at 95% confidence interval (CI). All analyses were carried out using STATA version 14.0.

Results

Generally, 51% of the women mentioned that HIV-infected female teachers should be allowed to teach in Ghana. Women who accessed mass media had higher odds of endorsing that HIV-infected female teachersshould be allowed to teach compared to those without access to mass media [AOR = 1.37, CI 1.200–1.555], just as among those  with secondary or higher education compared to those with no formal education [AOR = 1.30, CI 1.102–1.529]. Rural inhabitants had decreased odds of proclaiming that HIV-infected female teachers should be allowed to continue teaching compared with urban residents [AOR = 0.83, CI 0.717–0.957].

Conclusions

Endorsement of HIV-positive female teachers’ continued teaching was associated with access to mass media. This is suggestive that various mass media platforms could help to reach the public with HIV/AIDS-related information, particularly those that touch on stigma and discrimination, which will potentially increase women’s knowledge and shape their perceptions about persons living with HIV.
Socioeconomic status of practice location and Australian GP registrars’ training: a cross-sectional analysis
Authors: Moad Dominica , Tapley Amanda , Fielding Alison , van Driel Mieke L. , Holliday Elizabeth G. , Ball Jean I. , Davey Andrew R. , FitzGerald Kristen , Spike Neil A. , Magin Parker
Published: April 2022

Background

Socioeconomic status (SES) is a major determinant of health. In Australia, areas of socioeconomic disadvantage are characterised by complex health needs and inequity in primary health care provision. General Practice (GP) registrars play an important role in addressing workforce needs, including equitable health care provision in areas of greater socioeconomic disadvantage.

We aimed to characterize GP registrars’ practice location by level of socioeconomic disadvantage, and establish associations (of registrar, practice, patient characteristics, and registrars’ clinical behaviours) with GP registrars training being undertaken in areas of greater socioeconomic disadvantage.

Methods

A cross-sectional analysis from the Registrars’ Clinical Encounters in Training (ReCEnT) study. ReCEnT is an ongoing, multi-centre, cohort study that documents 60 consecutive consultations by each GP registrar once in each of their three six-monthly training terms. The outcome factor was the practice location’s level of socioeconomic disadvantage, defined using the Index of Relative Socio-economic Disadvantage (SEIFA-IRSD). The odds of being in the lowest quintile was compared to the other four quintiles. Independent variables related to the registrar, patient, practice, and consultation.

Results

A total of 1,736 registrars contributed 241,945 consultations. Significant associations of training being in areas of most disadvantage included: the registrar being full-time, being in training term 1, being in the rural training pathway; patients being Aboriginal or Torres Strait Islander, or from a non-English-speaking background; and measures of continuity of care.

Conclusions

Training in areas of greater social disadvantage, as well as addressing community need, may provide GP registrars with richer learning opportunities.
Linking resilience and regulation across system levels in healthcare – a multilevel study
Authors: Øyri Sina Furnes , Wiig Siri
Published: April 2022

Background

TheQuality Improvement Regulationwas introduced to the Norwegian healthcare system in 2017 as a new national regulatory framework to support local quality and safety efforts in hospitals. A research-based response to this, was to develop a study with the overall research question: How does a new healthcare regulation implemented across three system levels contribute to adaptive capacity in hospital management of quality and safety? Based on development and implementation of the Quality Improvement Regulation, this study aims to synthesize findings across macro, meso, and micro-levels in the Norwegian healthcare system.

Methods

The multilevel embedded case study collected data by documents and interviews. A synthesizing approach to findings across subunits was applied in legal dogmatic and qualitative content analysis. Setting: three governmental macro-level bodies, three meso-level County Governors and three micro-level hospitals. Participants: seven macro-level regulators, 12 meso-level chief county medical officers/inspectors and 20 micro-level hospital managers/quality advisers.

Results

Based on a multilevel investigation,three themes were discovered. All system levels considered theQuality Improvement Regulationto facilitate adaptive capacity and recognized contextual flexibility as an important regulatory feature. Participants agreed on uncertainty and variation to hamper the ability to plan and anticipate risk. However, findings identified conflicting views amongst inspectors and hospital managers about their collaboration, with different perceptions of the impact of external inspection. The study found no changes in management- or clinical practices, nor substantial change in the external inspection approach due to the new regulatory framework.

Conclusions

TheQuality Improvement Regulationfacilitates adaptive capacity, contradicting the assumption that regulation and resilience are “hopeless opposites”. However, governmental expectations to implementation and external inspection were not fully linked with changes in hospital management. Thus, the study identified a missing link in the current regime. We suggest that macro, meso and micro-levels should be considered collaborative partners in obtaining system-wide adaptive capacity, to ensure efficient risk regulation in quality improvement and patient safety processes. Further studies on regulatory processes could explore how hospital management and implementation are influenced by regulators’, inspectors’, and managers’ professional backgrounds, positions, and daily trade-offs to adapt to changes and maintain high quality care.
Opening up safely: public health system requirements for ongoing COVID-19 management based on evaluation of Australia’s surveillance system performance
Authors: Lokuge Kamalini , D’Onise Katina , Banks Emily , Street Tatum , Jantos Sydney , Baptista Mohana , Glass Kathryn
Published: April 2022

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) community transmission was eliminated in Australia from 1/11/2020 to 30/6/2021, allowing evaluation of surveillance system performance in detecting novel outbreaks, including against variants of concern (VoCs). This paper aims to define system requirements for coronavirus disease 2019 (COVID-19) surveillance under future transmission and response scenarios, based on surveillance system performance to date.

Methods

This study described and evaluated surveillance systems and epidemiological characteristics of novel outbreaks based on publicly available data, and assessed surveillance system sensitivity and timeliness in outbreak detection. These findings were integrated with analysis of other critical COVID-19 public health measures to establish future COVID-19 management requirements.

Results

Twenty-five epidemiologically distinct outbreaks and five distinct clusters were identified in the study period, all linked through genomic sequencing to novel introductions from international travellers. Seventy percent (21/30) were detected through community testing of people with acute respiratory illness, and 30% (9/30) through quarantine screening. On average, 2.07% of the State population was tested in the week preceding detection for those identified through community surveillance. From 17/30 with publicly available data, the average time from seeding to detection was 4.9 days. One outbreak was preceded by unexpected positive wastewater results. Twenty of the 24 outbreaks in 2021 had publicly available sequencing data, all of which identified VoCs. A surveillance strategy for future VoCs similar to that used for detecting SARS-CoV-2 would require a 100–1000-fold increase in genomic sequencing capacity compared to the study period. Other essential requirements are maintaining outbreak response capacity and developing capacity to rapidly engineer, manufacture, and distribute variant vaccines at scale.

Conclusions

Australia’s surveillance systems performed well in detecting novel introduction of SARS-CoV-2 while community transmission was eliminated; introductions were infrequent and case numbers were low. Detection relied on quarantine screening and community surveillance in symptomatic members of the general population, supported by comprehensive genomic sequencing. Once vaccine coverage is maximised, future COVID-19 control should shift to detection of SARS-CoV-2 VoCs, requiring maintenance of surveillance systems and testing all international arrivals, alongside greatly increased genomic sequencing capacity. Effective government support of localised public health response mechanisms and engagement of all sectors of the community is crucial to current and future COVID-19 management.
Ketone body β-hydroxybutyrate ameliorates colitis by promoting M2 macrophage polarization through the STAT6-dependent signaling pathway
Authors: Huang Chongyang , Wang Jun , Liu Hongbin , Huang Ruo , Yan Xinwen , Song Mengyao , Tan Gao , Zhi Fachao
Published: April 2022

Background

Ketone body β-hydroxybutyrate (BHB) has received more and more attentions, because it possesses a lot of beneficial, life-preserving effects in the fields of clinical science and medicine. However, the role of BHB in intestinal inflammation has not yet been investigated.

Methods

Colonic mucosa of inflammatory bowel disease (IBD) patients and healthy controls were collected for evaluation of BHB level. Besides, the therapeutic effect of exogenous BHB in a murine model of acute dextran sulfate sodium (DSS)-induced colitis were assessed by body weight change, colon length, disease activity index, and histopathological sections. The regulatory effectors of BHB were analyzed by RT-qPCR, immunofluorescence, and microbe analysis in vivo. Moreover, the molecular mechanism of BHB was further verified in bone marrow-derived macrophages (BMDMs).

Results

In this study, significantly reduced BHB levels were found in the colonic mucosa from IBD patients and correlated with IBD activity index. In addition, we demonstrated that the administration of exogenous BHB alleviated the severity of acute experimental colitis, which was characterized by less weight loss, disease activity index, colon shortening, and histology scores, as well as decreased crypt loss and epithelium damage. Furthermore, BHB resulted in significantly increased colonic expression of M2 macrophage-associated genes, including IL-4Ra, IL-10, arginase 1 (Arg-1), and chitinase-like protein 3, following DSS exposure, suggesting an increased M2 macrophage skewing in vivo. Moreover, an in vitro experiment revealed that the addition of BHB directly promoted STAT6 phosphorylation and M2 macrophage-specific gene expression in IL-4-stimulated macrophages. Besides, we found that BHB obviously increased M2 macrophage-induced mucosal repair through promoting intestinal epithelial proliferation. However, the enhancement effect of BHB on M2 macrophage-induced mucosal repair and anti-inflammation was completely inhibited by the STAT6 inhibitor AS1517499.

Conclusions

In summary, we show that BHB promotes M2 macrophage polarization through the STAT6-dependent signaling pathway, which contributes to the resolution of intestinal inflammation and the repair of damaged intestinal tissues. Our finding suggests that exogenous BHB supplement may be a useful therapeutic approach for IBD treatment.
Measurement of procalcitonin in saliva of pigs: a pilot study
Authors: López-Martínez María José , Escribano Damián , Martínez-Miró Silvia , Ramis Guillermo , Manzanilla Edgar G. , Tecles Fernando , Martínez-Subiela Silvia , Cerón José J.
Published: April 2022

Background

Procalcitonin (PCT) is a widely used biomarker of sepsis in human medicine and can have potential applications in the veterinary field. This study aimed to explore whether PCT could be measured in the saliva of pigs and whether its concentration changes in sepsis. Therefore, a specific assay was developed and analytically validated, and changes in PCT concentration were evaluated in two conditions: a) in an experimental model of sepsis produced by the administration of lipopolysaccharide (LPS) to pigs (n = 5), that was compared with a model of non-septic inflammation induced by turpentine oil (n = 4), and b) in healthy piglets (n = 11) compared to piglets with meningitis (n = 20), a disease that usually involves sepsis and whose treatment often requires large amounts of antibiotics in farms.

Results

The assay showed coefficients of variation within the recommended limits and adequate linearity after serial sample dilutions. The method's detection limit was set at 68 μg/L, and the lower limit of quantification was 414 μg/L. In the LPS experiment, higher concentrations of PCT were found after 24 h in the animals injected with LPS (mean = 5790 μg/L) compared to those treated with turpentine oil (mean = 2127 μg/L,P = 0.045). Also, animals with meningitis had higher concentrations of PCT (mean = 21515 μg/L) than healthy pigs (mean = 6096 μg/L, P value < 0.0001).

Conclusions

According to these results, this assay could be potentially used as a tool for the non-invasive detection of sepsis in pigs, which is currently a topic of high importance due to antibiotic use restriction.
Comment on Balsamo et al.: Birt-Hogg-Dubé syndrome with simultaneous hyperplastic polyposis of the gastrointestinal tract: case report and review of the literature
Authors: van de Beek Irma , van Steensel Maurice A. M. , Houweling Arjan C.
Published: April 2022

The publication by Balsamo and colleagues describes a patient with Birt-Hogg-Dubé syndrome and hyperplastic polyposis throughout the gastro-intestinal tract. We question whether the diagnosis of BHD in this patient was justified. Using the previously proposed diagnostic criteria for establishing the diagnosis of BHD as a guideline, we systematically describe our concerns. In our opinion, the patient described by Balsamo and colleagues does not meet any of the proposed major and minor criteria for the diagnosis of Birt-Hogg-Dubé syndrome. Therefore, we believe that it is not justified to suggest a possible association between hyperplastic polyposis and Birt-Hogg-Dubé syndrome based on this patient, even though a higher risk for colorectal polyposis in Birt-Hogg-Dubé syndrome has not been excluded so far.
Inter-assay variability of next-generation sequencing-based gene panels
Authors: Quy Pham Nguyen , Fukuyama Keita , Kanai Masashi , Kou Tadayuki , Kondo Tomohiro , Yoshioka Masahiro , Matsubara Junichi , Sakuma Tomohiro , Minamiguchi Sachiko , Matsumoto Shigemi , Muto Manabu
Published: April 2022

Background

Tumor heterogeneity has been known to cause inter-assay discordance among next-generation sequencing (NGS) results. However, whether preclinical factors such as sample type, sample quality and analytical features of gene panel can affect the concordance between two different assays remains largely unexplored.

Methods

Replicate sets of DNA samples extracted from formalin-fixed paraffin-embedded tissues (FFPE) (n = 20) and fresh frozen (FF) tissues (n = 10) were herein analyzed using a tumor-only (TO) and paired tumor–normal (TN) gene panel in laboratories certified by the Clinical Laboratory Improvement Amendment. Reported variants from the TO and TN panels were then compared. Furthermore, additional FFPE samples were sequentially sliced from the same FFPE block and submitted to another TN panel assay.

Results

Substantial discordance (71.8%) was observed between the results of the two panels despite using identical DNA samples, with the discordance rate being significantly higher for FFPE samples (p < 0.05). Among the 99 variants reported only in the TO panel, 32.3% were consistent with germline variants, which were excluded in the TN panel, while 30.3% had an allele frequency of less than 5%, some of which were highly likely to be artificial calls. The comparison of two independent TN panel assay results from the same FFPE block also showed substantial discordance rate (55.3%).

Conclusions

In the context of clinical settings, our comparative analysis revealed that inter-NGS assay discordance commonly occurred due to sample types and the different analytical features of each panel.
Distinct lipid membrane interaction and uptake of differentially charged nanoplastics in bacteria
Authors: Dai Shang , Ye Rui , Huang Jianxiang , Wang Binqiang , Xie Zhenming , Ou Xinwen , Yu Ning , Huang Cheng , Hua Yuejin , Zhou Ruhong , Tian Bing
Published: April 2022

Background

Nanoplastics have been recently found widely distributed in our natural environment where ubiquitously bacteria are major participants in various material cycles. Understanding how nanoplastics interact with bacterial cell membrane is critical to grasp their uptake processes as well as to analyze their associated risks in ecosystems and human microflora. However, little is known about the detailed interaction of differentially charged nanoplastics with bacteria. The present work experimentally and theoretically demonstrated that nanoplastics enter into bacteria depending on the surface charges and cell envelope structural features, and proved the shielding role of membrane lipids against nanoplastics.

Results

Positively charged polystyrene nanoplastics (PS-NH2, 80 nm) can efficiently translocate across cell membranes, while negatively charged PS (PS-COOH) and neutral PS show almost no or much less efficacy in translocation. Molecular dynamics simulations revealed that the PS-NH2 displayed more favourable electrostatic interactions with bacterial membranes and was subjected to internalisation through membrane penetration. The positively charged nanoplastics destroy cell envelope of Gram-positive B. subtilis by forming membrane pore, while enter into the Gram-negative E. coli with a relatively intact envelope. The accumulated positively charged nanoplastics conveyed more cell stress by inducing a higher level of reactive oxygen species (ROS). However, the subsequently released membrane lipid-coated nanoplastics were nearly nontoxic to cells, and like wise, stealthy bacteria wrapped up with artifical lipid layers became less sensitive to the positively charged nanoplastics, thereby illustrating that the membrane lipid can shield the strong interaction between the positively charged nanoplastics and cells.

Conclusions

Our findings elucidated the molecular mechanism of nanoplastics’ interaction and accumulation within bacteria, and implied the shielding and internalization effect of membrane lipid on toxic nanoplastics could promote bacteria for potential plastic bioremediation.

Graphical Abstract
Early and strong antibody responses to SARS-CoV-2 predict disease severity in COVID-19 patients
Authors: Plūme Jānis , Galvanovskis Artis , Šmite Sindija , Romanchikova Nadezhda , Zayakin Pawel , Linē Aija
Published: April 2022

Background

Antibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent data suggest that antibody levels also may have a prognostic significance in COVID-19. Most of the serological studies so far rely on testing antibodies against spike (S) or nucleocapsid (N) protein, however antibodies can be directed against other structural and nonstructural proteins of the virus, whereas their frequency, biological and clinical significance is unknown.

Methods

A novel antigen array comprising 30 SARS-CoV-2 antigens or their fragments was developed and used to examine IgG, IgA, IgE and IgM responses to SARS-CoV-2 in sera from 103 patients with COVID-19 including 34 patients for whom sequential samples were available, and 20 pre-pandemic healthy controls.

Results

Antibody responses to various antigens are highly correlated and the frequencies and peak levels of antibodies are higher in patients with severe/moderate disease than in those with mild disease. This finding supports the idea that antibodies against SARS-CoV-2 may exacerbate the severity of the disease via antibody-dependent enhancement. Moreover, early IgG and IgA responses to full length S protein may be used as an additional biomarker for the identification of patients who are at risk of developing severe disease. Importantly, this is the first study reporting that SARS-CoV-2 elicits IgE responses and their serum levels positively correlate with the severity of the disease thus suggesting a link between high levels of antibodies and mast cell activation.

Conclusions

This is the first study assessing the prevalence and dynamics IgG, IgA, IgE and IgM responses to multiple SARS-CoV-2 antigens simultaneously. Results provide important insights into the pathogenesis of COVID-19 and have implications in planning and interpreting antibody-based epidemiological studies.
Comparison of the effects of different calorie amounts of enteral nutrition in hypercatabolism associated with ghrelin-POMC in endotoxemic rats
Authors: Duan Jianfeng , Cheng Minhua , Xu Yali , Tang Shaoqiu , Li Xiaoyao , Chen Yan , Lu Huimin , Gao Tao , Yu Wenkui
Published: April 2022

Background

Hypercatabolism often occurs in critically ill patients, and it increases infection rates and mortality in these patients. Enteral nutrition (EN) is commonly used in case of hypercatabolism. However, the effect of amount of calories in EN on hypercatabolism remains unexplored.

Objective

Here, we compared the effect of low-calorie, medium-calorie and high-calorie EN on hypercatabolism in the acute phase of endotoxemia, which is associated with gastrointestinal hormones and hypothalamic neuropeptide proopiomelanocortin (POMC).

Methods

Overall 84 adult male Sprague–Dawley rats were used for research. A set of rats were divided into 5 groups, Control (NS) and lipopolysaccharide (LPS) groups were fed a standard chow diet; LPS + L (LPS + 40 kcal/kg/day EN), LPS + M (LPS + 80 kcal/kg/day EN) and LPS + H (LPS + 120 kcal/kg/day EN) groups received EN through a gastric tube for 3 days. Another set of rats were used for parallel control experiment and divided into 5 groups: NS + F (saline + fasting) and LPS + F (LPS + fasting) groups were given no food, NS + L (saline + 40 kcal/kg/day EN), NS + M (saline + 80 kcal/kg/day EN) and NS + H (saline + 120 kcal/kg/day EN) groups received EN through a gastric tube for 3 days. Hypercatabolism was evaluated by assessing skeletal muscle protein synthesis and atrophy, insulin resistance, and corticosterone levels. Moreover, serum inflammatory factors, gastrointestinal hormones, hypothalamic ghrelin, growth hormone secretagogue receptor-1α, hypothalamic neuropeptide, and intestinal injury indicators were detected.

Results

Low-calorie EN effectively increased serum and hypothalamic ghrelin possibly due to slight intestinal barrier damage, thereby decreasing hypothalamic POMC expression; consequently, it alleviated rat insulin resistance, reduced blood cortisol levels and muscle atrophy, and improved the survival rate of rats in the acute phase of endotoxemia. Interestingly, with an increase in calories in enteral nutrition, the aforementioned effects did not increase.

Conclusions

Low-calorie EN could effectively increase gastrointestinal hormone ghrelin by reducing intestinal damage and suppressing POMC expression to ameliorate hypercatabolism when compared with medium-calorie and high-calorie EN. Therefore Low-calorie EN may be preferred for providing EN in the acute stage of endotoxemia.
L-theanine prevents progression of nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway
Authors: Liang Juanjuan , Gu Lili , Liu Xianli , Yan Xintong , Bi Xiaowen , Fan Xirui , Zhou Jinyi , Lu Shuai , Luo Lan , Yin Zhimin
Published: April 2022

Background

L-theanine, a non-protein amino acid was found principally in the green tea, has been previously shown to exhibit potent anti-obesity property and hepatoprotective effect. Herein, we investigated the effects of L-theanine on alleviating nonalcoholic hepatic steatosis in vitro and in vivo, and explored the underlying molecular mechanism.

Methods

In vitro, HepG2 and AML12 cells were treated with 500 μM oleic acid (OA) or treated with OA accompanied by L-theanine. In vivo, C57BL/6J mice were fed with normal control diet (NCD), high‐fat diet (HFD), or HFD along with L-theanine for 16 weeks. The levels of triglycerides (TG), accumulation of lipid droplets and the expression of genes related to hepatocyte lipid metabolic pathways were detected in vitro and in vivo.

Results

Our data indicated that, in vivo, L-theanine significantly reduced body weight, hepatic steatosis, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), TG and LDL cholesterol (LDL-C) in HFD-induced nonalcoholic fatty liver disease (NAFLD) mice. In vitro, L-theanine also significantly alleviated OA induced hepatocytes steatosis. Mechanic studies showed that L-theanine significantly inhibited the nucleus translocation of sterol regulatory element binding protein 1c (SREBP-1c) through AMPK-mTOR signaling pathway, thereby contributing to the reduction of fatty acid synthesis. We also identified that L-theanine enhanced fatty acid β-oxidation by increasing the expression of peroxisome proliferator–activated receptor α (PPARα) and carnitine palmitoyltransferase-1 A (CPT1A) through AMP-activated protein kinase (AMPK). Furthermore, our study indicated that L-theanine can active AMPK through its upstream kinase Calmodulin-dependent protein kinase kinase-β (CaMKKβ).

Conclusions

Taken together, our findings suggested that L-theanine alleviates nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway.
Rice bacterial blight resistant cultivar selection based on visible/near-infrared spectrum and deep learning
Authors: Zhang Jinnuo , Feng Xuping , Wu Qingguan , Yang Guofeng , Tao Mingzhu , Yang Yong , He Yong
Published: April 2022

Background

Rice bacterial blight (BB) has caused serious damage in rice yield and quality leading to huge economic loss and food safety problems. Breeding disease resistant cultivar becomes the eco-friendliest and most effective alternative to regulate its outburst, since the propagation of pathogenic bacteria is restrained. However, the BB resistance cultivar selection suffers tremendous labor cost, low efficiency, and subjective human error. And dynamic rice BB phenotyping study is absent from exploring the pattern of BB growth with different genotypes.

Results

In this paper, with the aim of alleviating the labor burden of plant breeding experts in the resistant cultivar screening processing and exploring the disease resistance phenotyping variation pattern, visible/near-infrared (VIS–NIR) hyperspectral images of rice leaves from three varieties after inoculation were collected and sent into a self-built deep learning model LPnet for disease severity assessment. The growth status of BB lesion at the time scale was fully revealed. On the strength of the attention mechanism inside LPnet, the most informative spectral features related to lesion proportion were further extracted and combined into a novel and refined leaf spectral index. The effectiveness and feasibility of the proposed wavelength combination were verified by identifying the resistant cultivar, assessing the resistant ability, and spectral image visualization.

Conclusions

This study illustrated that informative VIS–NIR spectrums coupled with attention deep learning had great potential to not only directly assess disease severity but also excavate spectral characteristics for rapid screening disease resistant cultivars in high-throughput phenotyping.
Retrospective evaluation of a robust hybrid planning technique established for irradiation of breast cancer patients with included mammary internal lymph nodes
Authors: Hennet Marina , Radonic Stephan , Schneider Uwe , Hartmann Matthias
Published: April 2022

Background

The irradiation of breast cancer patients with included internal mammary lymph nodes challenges radiation planning with regard to robustness and protection of OARs. In this publication, a feasible hybrid radiation technique is presented with a retrospective dosimetric and radiobiological analysis of patient data of our institute from 2016 to 2020 and robustness analysis.

Methods

The proposed hybrid irradiation technique consists of two IMRT tangents and two partial VMAT fields. The retrospective dosimetric and radiobiological evaluation are made for 217 patient treatments (right- and left-sided). The robustness is evaluated regarding an artificial swelling from 0.4 to 1.5 cm for a random example patient and compared to a pure VMAT planning technique with use of a virtual bolus. The out of field stray dose is calculated for a selected patient plan and compared to alternative radiation techniques.

Results

The coverage D95% of the PTVEval (with breast swelling of 1.5 cm) changes for the hybrid plan from 96.1 to 92.1% of prescribed dose and for the pure VMAT plan from 94.3 to 87%. The retrospective dosimetric evaluation of patient irradiations reveals a Dmean for total lung 6.5 ± 0.9 Gy (NTCP[Semenenko 2008] 2.8 ± 0.5%), ipsilateral lung 10.9 ± 1.5 Gy, contralateral lung 2.2 ± 0.6 Gy, heart 2.1 ± 1.1 Gy (ERR[Schneider 2017] 0.02 ± 0.17%) and contralateral breast 1.7 ± 0.6 Gy. The scatter dose of the hybrid irradiation technique is higher than for pure VMAT and lower than for pure IMRT irradiation.

Conclusions

The feasibility of the proposed planning technique is shown by treating many patients with this technique at our radiotherapy department. The hybrid radiation technique shows a good sparing of the OARs in the retrospective analysis and is robust with regards to a breast swelling of up to 1.5 cm. The slightly higher stray dose of the hybrid technique compared to a pure VMAT technique originates from higher number of MUs and lower conformity.
Applicability of a pathological complete response magnetic resonance-based radiomics model for locally advanced rectal cancer in intercontinental cohort
Authors: Boldrini Luca , Lenkowicz Jacopo , Orlandini Lucia Clara , Yin Gang , Cusumano Davide , Chiloiro Giuditta , Dinapoli Nicola , Peng Qian , Casà Calogero , Gambacorta Maria Antonietta , Valentini Vincenzo , Lang Jinyi
Published: April 2022

Background

Predicting pathological complete response (pCR) in patients affected by locally advanced rectal cancer (LARC) who undergo neoadjuvant chemoradiotherapy (nCRT) is a challenging field of investigation, but many of the published models are burdened by a lack of reliable external validation. Aim of this study was to evaluate the applicability of a magnetic resonance imaging (MRI) radiomic-based pCR model developed and validated in Europe, to a different cohort of patients from an intercontinental cancer center.

Methods

The original model was based on two clinical and two radiomics features extracted from T2-weighted 1.5 T MRI of 161 LARC patients acquired before nCRT, considered as training set. Such model is here validated using the T2-w 1.5 and 3 T staging MRI of 59 LARC patients with different clinical characteristics consecutively treated in mainland Chinese cancer center from March 2017 to January 2018. Model performance were evaluated in terms of area under the receiver operator characteristics curve (AUC) and relative parameters, such as accuracy, specificity, negative and positive predictive value (NPV and PPV).

Results

An AUC of 0.83 (CI 95%, 0.71–0.96) was achieved for the intercontinental cohort versus a value of 0.75 (CI 95%, 0.61–0.88) at the external validation step reported in the original experience. Considering the best cut-off threshold identified in the first experience (0.26), the following predictive performance were obtained: 0.65 as accuracy, 0.64 as specificity, 0.70 as sensitivity, 0.91 as NPV and 0.28 as PPV.

Conclusions

Despite the introduction of significant different factors, the proposed model appeared to be replicable on a real-world data extra-European patients’ cohort, achieving a TRIPOD 4 level.
Translating, contextually adapting, and pilot testing of psychosocial and mental health assessment instruments for Congolese refugees in Rwanda and Uganda
Authors: Kasujja Rosco , Bangirana Paul , Chiumento Anna , Hasan Tasdik , Jansen Stefan , Kagabo Daniel M. , Popa Maria , Ventevogel Peter , White Ross G.
Published: April 2022

Background

Forcibly displaced people are at elevated risk of experiencing circumstances that can adversely impact on mental health. Culturally and contextually relevant tools to assess their mental health and psychosocial needs are essential to inform the development of appropriate interventions and investigate the effectiveness of such interventions.

Methods

We conducted two related studies: (1) to translate and contextually adapt the Patient Health Questionnaire (PHQ-9), a measure of depressive symptomatology, along with assessment instruments measuring levels of daily stress (Checklist for Daily & Environmental Stressors; CDES), social capital (Shortened and Adapted Social Capital Assessment Tool; SASCAT) and perceived social support (Multidimensional Scale of Perceived Social Support; MSPSS) for use with Congolese refugees; (2) to conduct pilot testing of the assessment instruments (including cognitive interviewing about participants’ views of completing them) and a validation of the adapted PHQ-9 using a ‘known group’ approach by recruiting Congolese refugees from refugee settings in Rwanda (n = 100) and Uganda (n = 100).

Results

Study 1 resulted in the translation and adaptation of the assessment instruments. No substantive adaptations were made to the SASCAT or MSPSS, while notable linguistic and contextual adaptations were made in both sites to the CDES and the PHQ-9. The cognitive interviewing conducted in Study 2 indicated that the adapted assessment instruments were generally well received by members of the refugee communities. Participants recruited on the basis that local informants adjudged them to have high levels of depressive symptoms had significantly higher PHQ-9 scores (M = 11.02; SD = 5.84) compared to those in the group adjudged to have low levels of depressive symptoms (M = 5.66; SD = 5.04). In both sites, the adapted versions of the PHQ-9 demonstrated concurrent validity via significant positive correlations with levels of daily stressors. Each of the four adapted assessment instruments demonstrated at least adequate levels of internal consistency in both sites.

Conclusions

The adapted versions of the PHQ-9, CDES, SASCAT and MSPSS are appropriate for use amongst Congolese refugees in Rwanda and Uganda. We recommend further application of the approaches used in the current studies for contextually adapting other assessment instruments in humanitarian settings.
Oncometabolites drive tumorigenesis by enhancing protein acylation: from chromosomal remodelling to nonhistone modification
Authors: Fu Yidian , Yu Jie , Li Fang , Ge Shengfang
Published: April 2022

Metabolites are intermediate products of cellular metabolism catalysed by various enzymes. Metabolic remodelling, as a biochemical fingerprint of cancer cells, causes abnormal metabolite accumulation. These metabolites mainly generate energy or serve as signal transduction mediators via noncovalent interactions. After the development of highly sensitive mass spectrometry technology, various metabolites were shown to covalently modify proteins via forms of lysine acylation, including lysine acetylation, crotonylation, lactylation, succinylation, propionylation, butyrylation, malonylation, glutarylation, 2-hydroxyisobutyrylation and β-hydroxybutyrylation. These modifications can regulate gene expression and intracellular signalling pathways, highlighting the extensive roles of metabolites. Lysine acetylation is not discussed in detail in this review since it has been broadly investigated. We focus on the nine aforementioned novel lysine acylations beyond acetylation, which can be classified into two categories: histone acylations and nonhistone acylations. We summarize the characteristics and common functions of these acylation types and, most importantly, provide a glimpse into their fine-tuned control of tumorigenesis and potential value in tumour diagnosis, monitoring and therapy.
Extracellular vesicle IL-32 promotes the M2 macrophage polarization and metastasis of esophageal squamous cell carcinoma via FAK/STAT3 pathway
Authors: Sun Yixuan , Qian Yuzhen , Chen Chunxia , Wang Hongfei , Zhou Xiuman , Zhai Wenjie , Qiu Lu , Zhou Xiaowen , Ning Haoming , Zhao Yumiao , Shi Chao , Han Lu , Qi Yuanming , Wu Yahong , Gao Yanfeng
Published: April 2022

Background

Metastasis is the leading cause of mortality in human cancers, including esophageal squamous cell carcinoma (ESCC). As a pro-inflammatory cytokine, IL-32 was reported to be a poor prognostic factor in many cancers. However, the role of IL-32 in ESCC metastasis remains unknown.

Methods

ESCC cells with ectopic expression or knockdown of IL-32 were established and their effects on cell motility were detected. Ultracentrifugation, Transmission electron microscopy and Western blot were used to verify the existence of extracellular vesicle IL-32 (EV-IL-32). Coculture assay, immunofluorescence, flow cytometry, and in vivo lung metastasis model were performed to identify how EV-IL-32 regulated the crosstalk between ESCC cells and macrophages.

Results

Here, we found that IL-32 was overexpressed and positively correlated to lymph node metastasis of ESCC. IL-32 was significantly higher in the tumor nest compared with the non-cancerous tissue. We found that IL-32β was the main isoform and loaded in EV derived from ESCC cells. The shuttling of EV-IL-32 derived from ESCC cells into macrophages could promote the polarization of M2 macrophages via FAK-STAT3 pathway. IL-32 overexpression facilitated lung metastasis and was positively correlated with the proportion of M2 macrophages in tumor microenvironment.

Conclusions

Taken together, our results indicated that EV-IL-32 derived from ESCC cell line could be internalized by macrophages and lead to M2 macrophage polarization via FAK-STAT3 pathway, thus promoting the metastasis of ESCC. These findings indicated that IL-32 could serve as a potential therapeutic target in patients with ESCC.
Emerging therapies for glioblastoma: current state and future directions
Authors: Rong Liang , Li Ni , Zhang Zhenzhen
Published: April 2022

Glioblastoma (GBM) is the most common high-grade primary malignant brain tumor with an extremely poor prognosis. Given the poor survival with currently approved treatments for GBM, new therapeutic strategies are urgently needed. Advances in decades of investment in basic science of glioblastoma are rapidly translated into innovative clinical trials, utilizing improved genetic and epigenetic profiling of glioblastoma as well as the brain microenvironment and immune system interactions. Following these encouraging findings, immunotherapy including immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have offered new hope for improving GBM outcomes; ongoing studies are using combinatorial therapies with the aim of minimizing adverse side-effects and augmenting antitumor immune responses. In addition, techniques to overcome the blood-brain barrier (BBB) for targeted delivery are being tested in clinical trials in patients with recurrent GBM. Here, we set forth the rationales for these promising therapies in treating GBM, review the potential novel agents, the current status of preclinical and clinical trials, and discuss the challenges and future perspectives in glioblastoma immuno-oncology.
A longitudinal, retrospective registry-based validation study of RETTS©, the Swedish adult ED context version
Authors: Wireklint Sara C. , Elmqvist Carina , Fridlund Bengt , Göransson Katarina E.
Published: April 2022

Background

Triage and triage related work has been performed in Swedish Emergency Departments (EDs) since the mid-1990s. The Rapid Emergency Triage and Treatment System (RETTS©), with annual updates, is the most applied triage system. However, the national implementation has been performed despite low scientific foundation for triage as a method, mainly related to the absence of adjustment to age and gender. Furthermore, there is a lack of studies of RETTS© in Swedish ED context, especially of RETTS© validity. Hence, the aim the study was to determine the validity of RETTS©.

Methods

A longitudinal retrospective register study based on cohort data from a healthcare region comprising two EDs in southern Sweden. Two editions of RETTS© was selected; year 2013 and 2016, enabling comparison of crude data, and adjusted for age-combined Charlson comorbidity index (ACCI) and gender. All patients ≥ 18 years visiting either of the two EDs seeing a physician, was included. Primary outcome was ten-day mortality, secondary outcome was admission to Intensive Care Unit (ICU). The data was analysed with descriptive, and inferential statistics.

Results

Totally 74,845 patients were included. There was an increase in patients allocated red or orange triage levels (unstable) between the years, but a decrease of admission, both to general ward and ICU. Of all patients, 1031 (1.4%) died within ten-days. Both cohorts demonstrated a statistically significant difference between the triage levels, i.e. a higher risk for ten-day mortality and ICU admission for patients in all triage levels compared to those in green triage level. Furthermore, significant statistically differences were demonstrated for ICU admission, crude as well as adjusted, and for adjusted data ten-day mortality, indicating that ACCI explained ten-day mortality, but not ICU admission. However, no statistically significant difference was found for the two annual editions of RETTS© considering ten-day mortality, crude data.

Conclusion

The annual upgrade of RETTS© had no statistically significant impact on the validity of the triage system, considering the risk for ten-day mortality. However, the inclusion of ACCI, or at least age, can improve the validity of the triage system.

Graphical Abstract