bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-carbohydrate diet in the treatment of type 2 diabetes mellitus (LoCaT): study protocol for a multicenter, randomized controlled trial
Authors: Xia Xinyi , Xu Miao , Gu Yunjie , Li Yangxue , Li Li , Yin Jun
Published: June 2023

Background

Low-carbohydrate diet (LCD) is an emerging therapy for type 2 diabetes mellitus (T2DM). Although its effect on glucose control has been confirmed in previous clinical trials, most of those studies have focused on comparing calorie-restricted LCD to iso-caloric low-fat diets. In this study, we aim to compare the effects of LCD and canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with T2DM.

Methods

This is a multicenter, randomized controlled trial. We will recruit 120 patients with poor-controlled T2DM. Participants will be randomly divided into canagliflozin and LCD groups in a 1:1 ratio. The primary outcome is the change in hemoglobin A1C levels after the 3-month intervention. The secondary outcomes are the time in range and cost of antihyperglycemic agents. Exploratory outcomes include physical examination, body composition, glucose variability, appetite, glycolipid metabolism, liver lipid content, and urine glucose threshold.

Discussion

No previous study has compared an LCD with antihyperglycemic agents. In LoCaT, participants’ metabolism will be assessed from multiple perspectives. It is believed that the finding obtained from this trial will optimize the treatments for patients with T2DM.

Trial registration

Chinese Clinical Trial Registry ChiCTR1900027592. Registered on November 20, 2019.
Effect of xenon on brain injury, neurological outcome, and survival in patients after aneurysmal subarachnoid hemorrhage—study protocol for a randomized clinical trial
Authors: Laaksonen Mikael , Rinne Jaakko , Rahi Melissa , Posti Jussi P. , Laitio Ruut , Kivelev Juri , Saarenpää Ilkka , Laukka Dan , Frösen Juhana , Ronkainen Antti , Bendel Stepani , Långsjö Jaakko , Ala-Peijari Marika , Saunavaara Jani , Parkkola Riitta , Nyman Mikko , Martikainen Ilkka K. , Dickens Alex M. , Rinne Juha , Valtonen Mika , Saari Teijo I. , Koivisto Timo , Bendel Paula , Roine Timo , Saraste Antti , Vahlberg Tero , Tanttari Juha , Laitio Timo
Published: June 2023

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest.

Methods

The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain.

Discussion

Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality.

Trial registration

ClinicalTrials.gov NCT04696523. Registered on 6 January 2021.

EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.
Estimating malaria transmission risk through surveillance of human–vector interactions in northern Ghana
Authors: Coleman Sylvester , Yihdego Yemane , Gyamfi Frank , Kolyada Lena , Tongren Jon Eric , Zigirumugabe Sixte , Dery Dominic B. , Badu Kingsley , Obiri-Danso Kwasi , Boakye Daniel , Szumlas Daniel , Armistead Jennifer S. , Dadzie Samuel K.
Published: June 2023

Background

Vector bionomics are important aspects of vector-borne disease control programs. Mosquito-biting risks are affected by environmental, mosquito behavior and human factors, which are important for assessing exposure risk and intervention impacts. This study estimated malaria transmission risk based on vector–human interactions in northern Ghana, where indoor residual spraying (IRS) and insecticide-treated nets (ITNs) have been deployed.

Methods

Indoor and outdoor human biting rates (HBRs) were measured using monthly human landing catches (HLCs) from June 2017 to April 2019. Mosquitoes collected were identified to species level, and Anopheles gambiae sensu lato (An. gambiae s.l.) samples were examined for parity and infectivity. The HBRs were adjusted using mosquito parity and human behavioral observations.

Results

Anopheles gambiae was the main vector species in the IRS (81%) and control (83%) communities. Indoor and outdoor HBRs were similar in both the IRS intervention (10.6 vs. 11.3 bites per person per night [b/p/n]; z = −0.33, P = 0.745) and control communities (18.8 vs. 16.4 b/p/n; z = 1.57, P = 0.115). The mean proportion of parous An. gambiae s.l. was lower in IRS communities (44.6%) than in control communities (71.7%). After adjusting for human behavior observations and parity, the combined effect of IRS and ITN utilization (IRS: 37.8%; control: 57.3%) on reducing malaria transmission risk was 58% in IRS + ITN communities and 27% in control communities with ITNs alone (z = −4.07, P < 0.001). However, this also revealed that about 41% and 31% of outdoor adjusted bites in IRS and control communities respectively, occurred before bed time (10:00 pm). The mean directly measured annual entomologic inoculation rates (EIRs) during the study were 6.1 infective bites per person per year (ib/p/yr) for IRS communities and 16.3 ib/p/yr for control communities. After considering vector survival and observed human behavior, the estimated EIR for IRS communities was 1.8 ib/p/yr, which represents about a 70% overestimation of risk compared to the directly measured EIR; for control communities, it was 13.6 ib/p/yr (16% overestimation).

Conclusion

Indoor residual spraying significantly impacted entomological indicators of malaria transmission. The results of this study indicate that vector bionomics alone do not provide an accurate assessment of malaria transmission exposure risk. By accounting for human behavior parameters, we found that high coverage of ITNs alone had less impact on malaria transmission indices than combining ITNs with IRS, likely due to observed low net use. Reinforcing effective communication for behavioral change in net use and IRS could further reduce malaria transmission.

Graphical Abstract
Prevalence and resistance profile of bacteria isolated from wound infections among a group of patients in upper Egypt: a descriptive cross-sectional study
Authors: Ahmed Eman Farouk , Rasmi Asia Helmi , Darwish Abdou M. A. , Gad Gamal Fadl Mahmoud
Published: June 2023

Aim

This cross-sectional survey aimed to identify aerobic bacteria, antimicrobial resistance, and multi-drug resistance profiles of bacteria isolated from different wound infections among a group of Egyptian patients.

Results

Of 120 positive samples, 170 isolates were identified. Polymicrobial infections were determined in 55% of samples. The dominant Gram-positive isolated strains were Staphylococcus aureus, especially from wound infections because of accidents (71.8%). Piperacillin, methicillin, ampicillin/sulbactam, and amoxicillin/clavulanic acid were all highly resistant to S. aureus and Coagulase-negative Staphylococci. The prevalence of methicillin-resistant S. aureus in wound infections was 89.9%. S. aureus showed superior sensitivity to vancomycin (85.3%) and linezolid (81.3%). The highest prevalence of Gram-negative isolates was for Pseudomonas aeruginosa (40%), which was highly sensitive to ciprofloxacin (79.2%) and highly resistant to levofloxacin (83.3%). Several isolates revealed a multi-drug resistance profile (52.4%). The overall MDR rate of Gram-positive and Gram-negative isolates were 50% and 54.9%, respectively.

Conclusion

The prevalence of MRSA isolated from various wound infections and MDR is a warning issue in Upper Egypt. It should implement a health education strategy and hygiene measures to prevent the spread of wound infection-causing organisms in the community.
Circulating plasma NT-proBNP predicts subclinical coronary atherosclerosis on CT angiography among older adults in Uganda
Authors: Shakil Saate S , Temu Tecla M , Kityo Cissy , MMed Geoffrey Erem MBChB , Bittencourt Marcio S , Longenecker Chris T
Published: June 2023

Objective

Phenotypes and mechanisms of cardiovascular disease (CVD) may differ across global populations. In sub-Saharan Africa (SSA), distinct environmental determinants may influence development and progression of atherosclerotic coronary artery disease (CAD).

Methods

We investigated associations between 6 established markers of myocardial stress and subsequent subclinical CAD (sCAD), defined as presence of any atherosclerosis on coronary CT angiography (CCTA) in a 2-year prospective cohort of Ugandan adults enriched for cardiometabolic risk factors (RFs) and HIV. Six plasma biomarkers were measured baseline among 200 participants (50% with HIV) aged ≥ 45 years with ≥ 1 cardiovascular RF. At 2-year follow-up, 132 participants (52% with HIV) who returned underwent coronary CCTA.

Results

In logistic regression models adjusted for cardiovascular RFs (age, diabetes, hypertension, hyperlipidemia, smoking, obesity) and non-traditional RFs (HIV, chronic kidney disease), only NT-proBNP predicted subsequent subclinical CAD (p < 0.008, Bonferroni correction for multiple testing). In sensitivity analyses adjusted for ASCVD risk category (instead of individual RFs) in the baseline cohort with multiple imputation applied to missing year 2 CCTA data (n = 200), NT-proBNP remained significantly associated with subsequent CAD (p < 0.008).

Conclusions

NT-proBNP consistently predicted subclinical CAD in Uganda in the absence of such an association among other markers of myocardial stress, suggesting a role for NT-proBNP in atherosclerosis independently of coronary microvascular dysfunction.
An overview of meta-analyses on radiomics: more evidence is needed to support clinical translation
Authors: Zhong Jingyu , Lu Junjie , Zhang Guangcheng , Mao Shiqi , Chen Haoda , Yin Qian , Hu Yangfan , Xing Yue , Ding Defang , Ge Xiang , Zhang Huan , Yao Weiwu
Published: June 2023

Objective

To conduct an overview of meta-analyses of radiomics studies assessing their study quality and evidence level.

Methods

A systematical search was updated via peer-reviewed electronic databases, preprint servers, and systematic review protocol registers until 15 November 2022. Systematic reviews with meta-analysis of primary radiomics studies were included. Their reporting transparency, methodological quality, and risk of bias were assessed by PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 checklist, AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews, version 2) tool, and ROBIS (Risk Of Bias In Systematic reviews) tool, respectively. The evidence level supporting the radiomics for clinical use was rated.

Results

We identified 44 systematic reviews with meta-analyses on radiomics research. The mean ± standard deviation of PRISMA adherence rate was 65 ± 9%. The AMSTAR-2 tool rated 5 and 39 systematic reviews as low and critically low confidence, respectively. The ROBIS assessment resulted low, unclear and high risk in 5, 11, and 28 systematic reviews, respectively. We reperformed 53 meta-analyses in 38 included systematic reviews. There were 3, 7, and 43 meta-analyses rated as convincing, highly suggestive, and weak levels of evidence, respectively. The convincing level of evidence was rated in (1) T2-FLAIR radiomics for IDH-mutant vs IDH-wide type differentiation in low-grade glioma, (2) CT radiomics for COVID-19 vs other viral pneumonia differentiation, and (3) MRI radiomics for high-grade glioma vs brain metastasis differentiation.

Conclusions

The systematic reviews on radiomics were with suboptimal quality. A limited number of radiomics approaches were supported by convincing level of evidence.

Clinical relevance statement

The evidence supporting the clinical application of radiomics are insufficient, calling for researches translating radiomics from an academic tool to a practicable adjunct towards clinical deployment.

Graphical Abstract
Integrating host transcriptomic signatures for distinguishing autoimmune encephalitis in cerebrospinal fluid by metagenomic sequencing
Authors: Fan Siyuan , He Xiangyan , Zhu Zhongyi , Chen Lu , Zou Yijun , Chen Zhonglin , Yu Jialin , Chen Weijun , Guan Hongzhi , Ma Jinmin
Published: June 2023

Background

The early accurate diagnoses for autoimmune encephalitis (AE) and infectious encephalitis (IE) are essential since the treatments for them are different. This study aims to discover some specific and sensitive biomarkers to distinguish AE from IE at early stage to give specific treatments for good outcomes.

Results

We compared the host gene expression profiles and microbial diversities of cerebrospinal fluid (CSF) from 41 patients with IE and 18 patients with AE through meta-transcriptomic sequencing. Significant differences were found in host gene expression profiles and microbial diversities in CSF between patients with AE and patients with IE. The most significantly upregulated genes in patients with IE were enriched in pathways related with immune response such as neutrophil degranulation, antigen processing and presentation and adaptive immune system. In contrast, those upregulated genes in patients with AE were mainly involved in sensory organ development such as olfactory transduction, as well as synaptic transmission and signaling. Based on the differentially expressed genes, a classifier consisting of 5 host genes showed outstanding performance with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95.

Conclusions

This study provides a promising classifier and is the first to investigate transcriptomic signatures for differentiating AE from IE by using meta-transcriptomic next-generation sequencing technology.
How can ecosystem engineer plants boost productivity in east Mediterranean drylands
Authors: Constantinou Elena , Sarris Dimitrios , Psichoudaki Magda , Cabello Javier , Vogiatzakis Ioannis N.
Published: June 2023

Background

Water availability is the key limiting factor for plant productivity in drylands covering ca. 40% of Earth’s land surface. For such ecosystems to retain productivity and biodiversity under climatic change, it would be valuable to identify/promote keystone plant species that (i) have developed strategies to more efficiently utilize moisture resources not easily accessible and (ii) improve moisture conditions for neighboring plants. The very deep-rooted Ziziphus lotus, considered an ecosystem engineer, is one such example. However, it is not known which biotic traits: (a) canopy interception of moisture/rainfall, (b) hydraulic redistribution of deep ground moisture by roots, or non-biotic factors: (c) soil’s volume, and (d) organic matter content, Z. lotus activates/modulates to play such a role. We, thus, selected dryland ecosystems where the plant dominates and measured for potential effects on the less deep-rooted Thymbra capitata. For assessing impacts on ecosystem productivity, we measured the spatial aggregation of ca. 3600 T. capitata plants. As a proxy for soil moisture availability and its spatial variability, we conducted a 7-year-long study using thymes’ nighttime rehydration. Sampling extended up to 15 m away from Z. lotus.

Results

The density of T. capitata plants growing up to 5 m around Z. lotus vs. thymes growing 10–15 m away was found significantly increased (2.5–4.5 times), while their stem/leaf moisture was ca. 10% higher at predawn compared to nightfall during the dry season. This suggests that ecosystem productivity is driven by a greater soil moisture availability around Z. lotus permitting more thyme daytime transpiration, in contrast to thymes growing further away. The phenomenon appeared only under dry topsoil (during the dry season; becoming stronger during dry years). Morning dew/rainfall interception from the canopy or soil depth/organic matter did not show significant effects, leaving only the hydraulic lift properties of Z. lotus as the most likely driver for soil moisture availability.

Conclusions

The deep-rooting properties and hydraulic lift potential of Z. lotus may be the key in permitting it to boost ecosystem productivity. Such hydraulic plant traits require more attention as they may prove valuable in combating desertification and restoring ecosystems in arid/semiarid regions threatened by climate change.
Sanitary installations and wastewater plumbing as reservoir for the long-term circulation and transmission of carbapenemase producing Citrobacter freundii clones in a hospital setting
Authors: Hamerlinck Hannelore , Aerssens Annelies , Boelens Jerina , Dehaene Andrea , McMahon Michael , Messiaen Anne-Sophie , Vandendriessche Stien , Velghe Anja , Leroux-Roels Isabel , Verhasselt Bruno
Published: June 2023

Background

Accumulating evidence shows a role of the hospital wastewater system in the spread of multidrug-resistant organisms, such as carbapenemase producing Enterobacterales (CPE). Several sequential outbreaks of CPE on the geriatric ward of the Ghent University hospital have led to an outbreak investigation. Focusing on OXA-48 producing Citrobacter freundii, the most prevalent species, we aimed to track clonal relatedness using whole genome sequencing (WGS). By exploring transmission routes we wanted to improve understanding and (re)introduce targeted preventive measures.

Methods

Environmental screening (toilet water, sink and shower drains) was performed between 2017 and 2021. A retrospective selection was made of 53 Citrobacter freundii screening isolates (30 patients and 23 environmental samples). DNA from frozen bacterial isolates was extracted and prepped for shotgun WGS. Core genome multilocus sequence typing was performed with an in-house developed scheme using 3,004 loci.

Results

The CPE positivity rate of environmental screening samples was 19.0% (73/385). Highest percentages were found in the shower drain samples (38.2%) and the toilet water samples (25.0%). Sink drain samples showed least CPE positivity (3.3%). The WGS data revealed long-term co-existence of three patient sample derived C. freundii clusters. The biggest cluster (ST22) connects 12 patients and 8 environmental isolates taken between 2018 and 2021 spread across the ward. In an overlapping period, another cluster (ST170) links eight patients and four toilet water isolates connected to the same room. The third C. freundii cluster (ST421) connects two patients hospitalised in the same room but over a period of one and a half year. Additional sampling in 2022 revealed clonal isolates linked to the two largest clusters (ST22, ST170) in the wastewater collection pipes connecting the rooms.

Conclusions

Our findings suggest long-term circulation and transmission of carbapenemase producing C. freundii clones in hospital sanitary installations despite surveillance, daily cleaning and intermittent disinfection protocols. We propose a role for the wastewater drainage system in the spread within and between rooms and for the sanitary installations in the indirect transmission via bioaerosol plumes. To tackle this problem, a multidisciplinary approach is necessary including careful design and maintenance of the plumbing system.
Update on the pathological roles of prostaglandin E2 in neurodegeneration in amyotrophic lateral sclerosis
Authors: Nango Hiroshi , Tsuruta Komugi , Miyagishi Hiroko , Aono Yuri , Saigusa Tadashi , Kosuge Yasuhiro
Published: June 2023

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of upper and lower motor neurons. The pathogenesis of ALS remains largely unknown; however, inflammation of the spinal cord is a focus of ALS research and an important pathogenic process in ALS. Prostaglandin E2 (PGE2) is a major lipid mediator generated by the arachidonic-acid cascade and is abundant at inflammatory sites. PGE2 levels are increased in the postmortem spinal cords of ALS patients and in ALS model mice. Beneficial therapeutic effects have been obtained in ALS model mice using cyclooxygenase-2 inhibitors to inhibit the biosynthesis of PGE2, but the usefulness of this inhibitor has not yet been proven in clinical trials. In this review, we present current evidence on the involvement of PGE2 in the progression of ALS and discuss the potential of microsomal prostaglandin E synthase (mPGES) and the prostaglandin receptor E-prostanoid (EP) 2 as therapeutic targets for ALS. Signaling pathways involving prostaglandin receptors mediate toxic effects in the central nervous system. In some situations, however, the receptors mediate neuroprotective effects. Our recent studies demonstrated that levels of mPGES-1, which catalyzes the final step of PGE2 biosynthesis, are increased at the early-symptomatic stage in the spinal cords of transgenic ALS model mice carrying the G93A variant of superoxide dismutase-1. In addition, in an experimental motor-neuron model used in studies of ALS, PGE2 induces the production of reactive oxygen species and subsequent caspase-3-dependent cytotoxicity through activation of the EP2 receptor. Moreover, this PGE2-induced EP2 up-regulation in motor neurons plays a role in the death of motor neurons in ALS model mice. Further understanding of the pathophysiological role of PGE2 in neurodegeneration may provide new insights to guide the development of novel therapies for ALS.
Facing ostracism: micro-coding facial expressions in the Cyberball social exclusion paradigm
Authors: Mulder Rosa H. , Bakermans-Kranenburg Marian J. , Veenstra Johan , Tiemeier Henning , van IJzendoorn Marinus H.
Published: June 2023

Background

Social exclusion is often measured with the Cyberball paradigm, a computerized ball-tossing game. Most Cyberball studies, however, used self-report questionnaires, leaving the data vulnerable to reporter bias, and associations with individual characteristics have been inconsistent.

Methods

In this large-scale observational study, we video-recorded 4,813 10-year-old children during Cyberball and developed a real-time micro-coding method measuring facial expressions of anger, sadness and contempt, in a multi-ethnic population-based sample. We estimated associations between facial expressions and self-reported negative feelings, explored associations of child characteristics such as sex and parental national origin with observed and self-reported feelings during social exclusion, and tested associations of observed and self-reported feelings during social exclusion with behavior problems at age 14.

Results

Facial expressions of sadness and anger were associated with self-reported negative feelingsduringthe game, but not with such feelingsafterthe game. Further, girls reported to have had less negative feelings during the game than boys, but no such sex-differences were found in total observed emotions. Likewise, children with parents of Moroccan origin reported less negative feelings during the game than Dutch children, but their facial expressions did not indicate that they were differently affected. Last, observed emotions related negatively to later internalizing problems, whereas self-report on negative feelings during the game related positively to later internalizing and externalizing problems.

Conclusions

We show that facial expressions are associated with self-reported negative feelings during social exclusion, discuss that reporter-bias might be minimized using facial expressions, and find divergent associations of observed facial expressions and self-reported negative feelings with later internalizing problems.
Metal Trade and National Integration: bronze technology and metal resources of Yue Style Bronzes from Hunan (8 ~ 5 C. BCE)
Authors: Ma Jiangbo , Wu Xiaotong , Yan Xiansheng
Published: June 2023

A large number of Yue style bronzes with regional cultural characteristics were unearthed in Hunan, which is of great significance for studying the cross-regional circulation of bronze technology and metal resources in the south of the Yangtze River during the Late Bronze Age (8 ~ 5 C. BCE) in China. In this study, 30 Yue style bronzes and 3 Chu style bronzes unearthed from five regions in Hunan Province were analyzed for chemical composition, metallography and lead isotopes. The results show that the alloy materials of Hunan Yue style bronze ware are diverse. The containers are mainly leaded tin bronze, with both tin bronze and copper. The weapons or tools are mostly tin bronze, and the alloy composition is primarily tin. The lead isotope ratio analysis results showed three main ore sources: polymetallic deposits in the Nanling Mountains, the eastern Hubei-northern Jiangxi metallogenic belt and the western Henan Qinling-Dabie metallogenic belt. The extensive source of minerals reflects the frequent trade of metal resources between Yue people and the Chu state, which is not only the economic basis for the close relationship between Hunan Yue people and Chu State but also an important driving force for the southward expansion of the Chu state and national integration in Hunan.
A novel cysteine catalytic oxidation-based colorimetric approach for sensitive analysis of acute pancreatitis-related microRNA
Authors: Gong Mingwei , Jiang Guoyan , Rong Yuan , Yang Zeping , She Dong , Sun Chunhong
Published: June 2023

It is essential to establish simple, sensitive and accurate quantitative approaches for microRNAs (miRNAs) identification due to its crucial roles in a variety of physiological and pathological processes. Herein, we propose a novel RCA-based colorimetric method for sensitive and reliable miRNA analysis. In this approach, cyclization of the padlock sequence by miRNA-21 initiates the RCA to produce numerous G-rich sequences. The generated G-rich sequences fold to G-quadruplex DNAzyme that is capable of catalyzing cysteine to cystine which could mediate the gold nanoparticle-based color reaction, outputting results that can be observed directly by naked eyes. Based on this, the approach exhibits a wide detection range with a low limit of detection of 4 fM. In addition, the dual target recognition endows the method a greatly improved selectivity.
Comparison of machine learning models and CEUS LI-RADS in differentiation of hepatic carcinoma and liver metastases in patients at risk of both hepatitis and extrahepatic malignancy
Authors: Li Jianming , Li Huarong , Xiao Fan , Liu Ruiqi , Chen Yixu , Xue Menglong , Yu Jie , Liang Ping
Published: June 2023

Background

CEUS LI-RADS (Contrast Enhanced Ultrasound Liver Imaging Reporting and Data System) has good diagnostic efficacy for differentiating hepatic carcinoma (HCC) from solid malignant tumors. However, it can be problematic in patients with both chronic hepatitis B and extrahepatic primary malignancy. We explored the diagnostic performance of LI-RADS criteria and CEUS-based machine learning (ML) models in such patients.

Methods

Consecutive patients with hepatitis and HCC or liver metastasis (LM) who were included in a multicenter liver cancer database between July 2017 and January 2022 were enrolled in this study. LI-RADS and enhancement features were assessed in a training cohort, and ML models were constructed using gradient boosting, random forest, and generalized linear models. The diagnostic performance of the ML models was compared with LI-RADS in a validation cohort of patients with both chronic hepatitis and extrahepatic malignancy.

Results

The mild washout time was adjusted to 54 s from 60 s, increasing accuracy from 76.8 to 79.4%. Through feature screening, washout type II, rim enhancement and unclear border were identified as the top three predictor variables. Using LI-RADS to differentiate HCC from LM, the sensitivity, specificity, and AUC were 68.2%, 88.6%, and 0.784, respectively. In comparison, the random forest and generalized linear model both showed significantly higher sensitivity and accuracy than LI-RADS (0.83 vs. 0.784; all P < 0.001).

Conclusions

Compared with LI-RADS, the random forest and generalized linear model had higher accuracy for differentiating HCC from LM in patients with chronic hepatitis B and extrahepatic malignancy.
Single-cell transcriptome profiling of sepsis identifies HLA-DRlowS100Ahigh monocytes with immunosuppressive function
Authors: Yao Ren-Qi , Zhao Peng-Yue , Li Zhi-Xuan , Liu Yu-Yang , Zheng Li-Yu , Duan Yu , Wang Lu , Yang Rong-Li , Kang Hong-Jun , Hao Ji-Wei , Li Jing-Yan , Dong Ning , Wu Yao , Du Xiao-Hui , Zhu Feng , Ren Chao , Wu Guo-Sheng , Xia Zhao-Fan , Yao Yong-Ming
Published: June 2023

Background

Sustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.

Methods

We adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9−/− mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.

Results

ScRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DRlowS100Ahigh monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.

Conclusions

This study identifies HLA-DRlowS100Ahigh monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.
Unpacking the ‘process of sustaining’—identifying threats to sustainability and the strategies used to address them: a longitudinal multiple case study
Authors: Lennox Laura , Antonacci Grazia , Harris Matthew , Reed Julie
Published: June 2023

Background

Although sustainability remains a recognised challenge for Quality Improvement (QI) initiatives, most available research continues to investigate sustainability at the end of implementation. As a result, the learning and continuous adjustments that shape sustainability outcomes are lost. With little understanding of the actions and processes that influence sustainability within QI initiatives, there is limited practical guidance and direction on how to enhance the sustainability of QI initiatives. This study aims to unpack the ‘process of sustaining’, by exploring threats to sustainability encountered throughout the implementation of QI Initiatives and identifying strategies used by QI teams to address these threats over time.

Methods

A longitudinal multiple case study design was employed to follow 4 QI initiatives over a 3-year period. A standardised sustainability tool was used quarterly to collect perceptions of sustainability threats and actions throughout implementation. Interviews (n=38), observations (32.5 h), documentary analysis, and a focus group (n=10) were conducted to enable a greater understanding of how the process of sustaining is supported in practice. Data were analysed using the Consolidated Framework for Sustainability (CFS) to conduct thematic analysis.

Results

Analysis identified five common threats to sustainability: workforce stability, improvement timelines, organisational priorities, capacity for improvement, and stakeholder support. Each of these threats impacted multiple sustainability constructs demonstrating the complexity of the issues encountered. In response to threats, 12 strategies to support the process of sustaining were identified under three themes: engagement (five strategies that promoted the development of relationships), integration (three strategies that supported initiatives to become embedded within local systems), and adaptation (four strategies that enhanced understanding of, and response to, emergent conditions and contextual needs).

Conclusions

Sustaining improvements from QI initiatives requires continuous investment in relationships, resilience to integrate improvements in local systems, and flexibility to understand emergent conditions. Findings provide practitioners, funders, and researchers with a better understanding of, and preparation for, the threats associated with sustaining improvements from QI initiatives and offer insight into specific actions that can be taken to mitigate these risks. This learning can be used to inform future initiative design and support, to optimise the sustainability of healthcare improvements.

Trial registration

Not applicable
Risk-Adapted Neoadjuvant Chemoradiotherapy in Rectal Cancer: Final Report of the OCUM Study
Authors: Ruppert Reinhard , Junginger Theodor , Kube Rainer , Strassburg Joachim , Lewin Andreas , Baral Joerg , Maurer Christoph A. , Sauer Joerg , Lauscher Johannes , Winde Guenther , Thomasmeyer Rena , Stelzner Sigmar , Bambauer Cornelius , Scheunemann Soenke , Faedrich Axel , Wollschlaeger Daniel , Merkel Susanne
Published: June 2023

PURPOSE

We investigated whether neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer can be restricted to those at high risk of locoregional recurrence (LR) without compromising oncological outcomes.

PATIENTS AND METHODS

In a prospective multicenter interventional study, patients with rectal cancer (cT2-4, any cN, cM0) were classified according to the minimal distance between the tumor, suspicious lymph nodes or tumor deposits, and mesorectal fascia (mrMRF). Patients with a distance >1 mm underwent up-front total mesorectal excision (TME; low-risk group), whereas those with a distance ≤1 mm and/or cT4 and cT3 tumors in the lower rectal third received nCRT followed by TME surgery (high-risk group). The primary end point was 5-year LR rate.

RESULTS

Of the 1,099 patients included, 884 (80.4%) were treated according to the protocol. A total of 530 patients (60%) underwent up-front surgery, and 354 (40%) had nCRT followed by surgery. Kaplan-Meier analyses revealed 5-year LR rates of 4.1% (95% CI, 2.7 to 5.5) for patients treated per protocol, 2.9% (95% CI, 1.3 to 4.5) after up-front surgery, and 5.7% (95% CI, 3.2 to 8.2) after nCRT followed by surgery. The 5-year rate of distant metastases was 15.9% (95% CI, 12.6 to 19.2) and 30.5% (95% CI, 25.4 to 35.6), respectively. In a subgroup analysis of 570 patients with lower and middle rectal third cII and cIII tumors, 257 (45.1%) were at low-risk. The 5-year LR rate in this group was 3.8% (95% CI, 1.4 to 6.2) after up-front surgery. In 271 high-risk patients (involved mrMRF and/or cT4), the 5-year rate of LR was 5.9% (95% CI, 3.0 to 8.8) and of metastases 34.5% (95% CI, 28.6 to 40.4); disease-free survival and overall survival were the worst.

CONCLUSION

The findings support the avoidance of nCRT in low-risk patients and suggest that in high-risk patients, neoadjuvant therapy should be intensified to improve prognosis.
Pharmacist-Driven Precision Medicine: A Ferry to Cross the Chasm of Interpreting Biomarker Testing Reports
Authors: Knepper Todd C. , Boyle Theresa A. , Hicks J. Kevin , Walko Christine M.
Published: June 2023

Pharmacists as molecular oncology subspecialists can be integral to the multidisciplinary precision oncology team.
When Patient Expectations Are Not Met: A Case Report
Authors: Sadowsky Aaron , Porat Yoad , Faruki Adeel A. , Vitter Jillian S.
Published: June 2023

Successful anesthetics occur when safe, effective perioperative care is coupled with patient satisfaction. We present the case of a 63-year-old woman with advanced Parkinson’s disease who presented for a deep brain stimulation (DBS) device battery change under monitored anesthesia care (MAC). While MAC is commonly utilized for a DBS battery change, our patient reported previously experiencing intraoperative pain, anxiety, and the inability to communicate discomfort under MAC, leading to posttraumatic stress disorder. This case report highlights the importance of preoperative informed consent, discussion of patient expectations, and proactive planning for intraoperative communication strategies when MAC is the chosen method.
Emergency Cricothyrotomy in a Harsh Environment: A Case Report of Complete Airway Obstruction Following a Lightning Strike
Authors: Pizzi Barbara , Petrucci Emiliano , Marinangeli Franco
Published: June 2023

A lightning strike is an extreme event with the highest mortality rate among electrical injuries. Death from a lightning strike is caused by either cardiac arrest or respiratory arrest. It is rare for upper airway damage to occur, but in these cases, airway control is recommended. If transoral intubation is unsuccessful, an emergency cricothyrotomy should be considered. Our case report describes an emergency cricothyroidotomy performed in a harsh environment on a mountain 2300 m above sea level on a patient with extensive burns of his supraglottic structures, after being directly hit by a lightning strike.
Virtual Reality Treatment of Severe Neuropathic Pain in an Adolescent Child: A Case Report
Authors: Sørensen Jens Christian Hedemann , Vlachou Maria , Milidou Ioanna , Knudsen Anne Lene , Meier Kaare
Published: June 2023

We describe virtual reality (VR) used as an effective intervention to treat severe chronic neuropathic pain in an otherwise healthy adolescent boy. The patient presented with severe pain and allodynia in the right foot after calcaneus extension surgery. Multiple medical and psychological interventions were unsuccessful over 3 years, with the pain leading the patient to drop out of school. VR gaming intervention provided the patient with significant pain relief and substantial improvement in functionality.

This case report details the VR intervention and its effect on the patient’s severe, medically refractory pain syndrome.
Introducing the First Distal Pharyngeal Airway
Authors: McMurray Roxanne R. , McMurray Megan R.
Published: June 2023

Airway obstruction during anesthesia is a common occurrence with potentially serious outcomes. Increasingly, patients are older, heavier, and more likely to have obstructive sleep apnea—all heightened risk factors for airway complications. These patients undergo procedures where distal pharyngeal tissues can relax, obstructing the airway. As a result, there is a need for airway devices that can stent open distal pharyngeal tissues to maintain adequate ventilation. To physically address this problem, the new distal pharyngeal airway (DPA) prevents airway obstruction and enables providers to maintain ventilation.
Removal of an Epidural Catheter in a Patient Receiving Ticagrelor: A Case Report
Authors: Wagh Harshal D. , Nair Prashant K. , Bhushan Deepak B.
Published: June 2023

We report a case of a patient who had a coronary angioplasty and received heparin, clopidogrel, and ticagrelor on the evening of bilateral total knee arthroplasties performed under combined spinal epidural anesthesia. After a multidisciplinary meeting, the epidural catheter was removed 5 days after the dose of clopidogrel. With the catheter still in place, ticagrelor was continued to prevent stent thrombosis. Removing an epidural catheter in a patient on antiplatelet therapy must be done after a risk-benefit assessment, multidisciplinary collaboration, and stringent neurologic monitoring. The focus should be on prevention of a spinal hematoma, and rapid diagnosis and treatment to optimize the neurologic outcome.
Pulmonary Injury Causing a Massive Air Leak During Liver Transplantation: A Case Report and Discussion of Decision-Making
Authors: Mavrothalassitis Orestes , Marcus Sivan Goldenberg , Roll Garrett R. , Tallarico Roberta Teixeira , Bokoch Michael P.
Published: June 2023

Pulmonary injury can occur during liver transplantation in patients with prior liver surgery, infection, or hepatocellular carcinoma treatments. Compromise of gas exchange during liver transplantation mandates rapid, multidisciplinary decision-making. We present a case of lung parenchymal injury causing a massive air leak during the dissection phase of a liver transplant. An endobronchial blocker was used for emergency lung isolation. Since oxygenation and pH were stable, we proceeded with liver transplantation to minimize graft ischemic time, followed by thoracic repair. The postoperative course was notable for adequate early liver function and discharge after prolonged postoperative ventilation and tube thoracostomy drainage.
Disconnection Surgery in Pediatric Epilepsy: A Single Center's Experience With 185 Cases
Authors: Wang Yao , Wang Ruofan , Liu Qingzhu , Liu Tong , Yu Hao , Liu Chang , Sun Yu , Liu Xiaoyan , Cai Lixin
Published: June 2023

BACKGROUND AND OBJECTIVES:

Lobar and multilobar disconnections have gradually become common surgical methods in pediatric epilepsy surgery in recent years. However, the surgical procedures, postoperative epilepsy outcomes, and complications reported by each center are quite different. To review and analyze the clinical data from lobar disconnection in treating intractable pediatric epilepsy and study the characteristics, surgical outcomes, and safety of different disconnection surgeries.

METHODS:

This was a retrospective analysis of 185 children with intractable epilepsy who underwent various lobar disconnections at the Pediatric Epilepsy Center, Peking University First Hospital. Clinical information was grouped according to their characteristics. The differences in the abovementioned characteristics among the different lobar disconnections were summarized, and risk factors affecting the surgical outcome and postsurgical complications were explored.

RESULTS:

Among the 185 patients, 149 patients (80.5%) achieved seizure freedom with a follow-up of 2.1 years. There were 145 patients (78.4%) with malformations of cortical development (MCD). The seizure onset time (median 6 months, P = .001) and surgery time (median 34 months, P = .000) of the MCD group were smaller. Differences were found in etiology, resection of the insular lobe and epilepsy outcome among different disconnection approaches. Both parieto-occipital disconnection (P = .038, odds ratio = 8.126) and MRI abnormalities larger than the disconnection extent (P = .030, odds ratio = 2.670) affected the epilepsy outcome. Early postoperative complications were observed in 43 patients (23.3%), and long-term postoperative complications were observed in 5 patients (2.7%).

CONCLUSION:

The most common etiology of epilepsy in children undergoing lobar disconnection is MCD, whose onset and operative ages are the youngest. Disconnection surgery obtained good seizure outcomes in the treatment of pediatric epilepsy with a low incidence of long-term complications. With advances in presurgical evaluation, disconnection surgery will play a more important role in young children with intractable epilepsy.
An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal
Authors: Omelková Michaela , Fenger Christina Dühring , Murray Marta , Hammer Trine Bjørg , Pravata Veronica M. , Bartual Sergio Galan , Czajewski Ignacy , Bayat Allan , Ferenbach Andrew T. , Stavridis Marios P. , van Aalten Daan M. F.
Published: June 2023

O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. Inborn OGT genetic variants were recently shown to mediate a novel type of congenital disorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. Here, we report an OGTC921Y variant that co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity. Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. These data establish a link between OGT-CDG and embryonic stem cell self-renewal, providing a foundation for examining the developmental aetiology of this syndrome.
Case Report: an unusual orbital tumor
Authors: Mahmoud Anis , Touil Hager , Hann Fadima , Messaoud Riadh
Published: June 2023

Introduction: Orbital lipoma is an extremely rare tumor, representing less than 1% of all orbital tumors. We review the literature and describe the presentation, the differential diagnosis and the management of this tumor.

Case report: We report the case of a 63-year-old patient who was referred for a diplopia with recent hemi-cranial headache. Physical examination showed no exophthalmos nor decrease in visual acuity. The patient complained of diplopia on elevation and oculomotricity examination showed limited elevation of the right eye. The Hess Lancaster test was in favor of a limited course of the right inferior rectus muscle. Magnetic resonance imaging revealed a fusiform tissue process in the right inferior rectus muscle with a fatty signal.  A complete excision of the tumor was performed by a trasncunjonctival approach. Cytopathological examination was consistent with a pleomorphic lipoma. The postoperative period was uneventful. The definitive histopathologic diagnosis was a lipoma. The postoperative Magnetic resonance imaging showed the complete disappearance of the lesion. With 3 years of follow up, there is no sign of recurrence or ocular motility trouble.

Conclusion: Lipomas are rare tumors in the orbit. The clinic is variable depending on the size and the site. The clinical diagnosis is difficult to make. Only histology allows the final diagnosis.