bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer risk following surgical removal of tonsils and adenoids — a population-based, sibling-controlled cohort study in Sweden
Authors: Liang Jinfeng , Huang Yi , Yin Li , Sadeghi Fatemeh , Yang Yanping , Xiao Xue , Adami Hans-Olov , Ye Weimin , Zhang Zhe , Fang Fang
Published: May 2023

Background

Removal of tonsils and adenoids is among the most common surgical procedures worldwide. Evidence of increased risk of cancer following such surgery is, however, inconclusive.

Methods

We conducted a population-based, sibling-controlled cohort study of 4,953,583 individuals in Sweden with a follow-up during 1980–2016. History of tonsillectomy, adenotonsillectomy, and adenoidectomy was identified from the Swedish Patient Register whereas incident cases of cancer during follow-up were identified from the Swedish Cancer Register. We used Cox models to calculate hazard ratios (HR) with 95% confidence intervals (CI) of cancer in both a population and a sibling comparison. The sibling comparison was used to assess the potential impact of familial confounding, due to shared genetic or non-genetic factors within a family.

Results

We found a modestly increased risk for any cancer following tonsillectomy, adenoidectomy, or adenotonsillectomy in both the population (HR 1.10; 95%CI 1.07–1.12) and sibling (HR 1.15; 95%CI 1.10–1.20) comparisons. The association did not differ greatly by type of surgery, age at surgery, or potential indication for surgery, and persisted more than two decades after surgery. An excess risk was consistently observed for cancer of the breast, prostate, thyroid, and for lymphoma in both population and sibling comparisons. A positive association was observed for pancreatic cancer, kidney cancer, and leukemia in the population comparison whereas a positive association was observed for esophageal cancer in the sibling comparison.

Conclusions

Surgical removal of tonsils and adenoids is associated with a modestly increased risk of cancer during the decades following the surgery. The association is unlikely attributed to confounding due to shared genetic or non-genetic factors with a family.
Gender inequalities in violence victimization and depression in Brazil: results from the 2019 national health survey
Authors: Mrejen Matías , Rosa Leonardo , Rosa Dayana , Hone Thomas
Published: May 2023

Background

Violence is a worldwide public health challenge and has been linked to depression in many settings. Depression is higher in women and differential exposure to violence is a potential risk factor – especially in countries with high-levels of violence. This paper provides a comprehensive characterization of the association between violence victimization and depression in Brazil, focusing on sex/gender inequalities.

Methods

We used data from the 2019 wave of the National Health Survey (PNS) in Brazil to assess whether respondents had depression (using PHQ-9) and if they were victims of violence, differentiating by the type of violence, the frequency of victimization, and the primary aggressor. We used logit models to assess the association between victimization and the likelihood of having depression. We predicted probabilities of being depressed, considering the interaction between violence victimization and sex/gender, to analyze the differences between men and women.

Results

Rates of violence victimization and depression were higher among women than among men. The odds of being depressed were 3.8 (95%CI: 3.5–4.2) times higher among victims of violence than among non-victims, and 2.3 (95%CI: 2.1–2.6) times higher among women than among men, adjusting for socioeconomic factors. For any given income level, racial/ethnic or age group, victims of violence who were women had the highest predicted probabilities of being depressed – e.g., 29.4% (95%CI: 26.1–32.8) for lower-income women, 28.9% (95%CI: 24.4–33.2) for black women, and 30.4% (95%CI: 25.4–35.4) for younger women that suffered violence. Over one in three women that suffered multiple types of violence, experienced violence more frequently, or where the aggressor was an intimate partner or another family member were predicted to have depression.

Conclusions

Being a victim of violence was strongly associated with higher risk of depression in Brazil, with women more likely to be both victims of violence and develop depression. Frequent, sexual, physical or psychological violence, and intimate partners or family member perpetrators were major risk factors for depression and should be a public health priority.
A hybrid nanopharmaceutical for specific-amplifying oxidative stress to initiate a cascade of catalytic therapy for pancreatic cancer
Authors: Liu Fan , Xiang Qinyanqiu , Luo Yuanli , Luo Ying , Luo Wenpei , Xie Qirong , Fan Jingdong , Ran Haitao , Wang Zhigang , Sun Yang
Published: May 2023

Background

Oxidative stress (OS) induced by an imbalance of oxidants and antioxidants is an important aspect in anticancer therapy, however, as an adaptive response, excessive glutathione (GSH) in the tumor microenvironment (TME) acts as an antioxidant against high reactive oxygen species (ROS) levels and prevents OS damage to maintain redox homoeostasis, suppressing the clinical efficacy of OS-induced anticancer therapies.

Results

A naturally occurring ROS-activating drug, galangin (GAL), is introduced into a Fenton-like catalyst (SiO2@MnO2) to form a TME stimulus-responsive hybrid nanopharmaceutical (SiO2-GAL@MnO2, denoted SG@M) for enhancing oxidative stress. Once exposed to TME, as MnO2 responds and consumes GSH, the released Mn2+ converts endogenous hydrogen peroxide (H2O2) into hydroxyl radicals (·OH), which together with the subsequent release of GAL from SiO2 increases ROS. The “overwhelming” ROS cause OS-mediated mitochondrial malfunction with a decrease in mitochondrial membrane potential (MMP), which releases cytochrome c from mitochondria, activates the Caspase 9/Caspase 3 apoptotic cascade pathway. Downregulation of JAK2 and STAT3 phosphorylation levels blocks the JAK2/STAT3 cell proliferation pathway, whereas downregulation of Cyclin B1 protein levels arrest the cell cycle in the G2/M phase. During 18 days of in vivo treatment observation, tumor growth inhibition was found to be 62.7%, inhibiting the progression of pancreatic cancer. Additionally, the O2 and Mn2+ released during this cascade catalytic effect improve ultrasound imaging (USI) and magnetic resonance imaging (MRI), respectively.

Conclusion

This hybrid nanopharmaceutical based on oxidative stress amplification provides a strategy for multifunctional integrated therapy of malignant tumors and image-visualized pharmaceutical delivery.

Graphical Abstract
Estrogen-sensitive activation of SGK1 induces M2 macrophages with anti-inflammatory properties and a Th2 response at the maternal–fetal interface
Authors: Lou Yiyun , Fu Zhujing , Tian Ye , Hu Minhao , Wang Qijing , Zhou Yuanyuan , Wang Ning , Zhang Qin , Jin Fan
Published: May 2023

Background

Decidual macrophages participate in immune regulation at the maternal–fetal interface. Abnormal M1/M2 polarization of decidual macrophages might predispose immune maladaptation in recurrent pregnancy loss (RPL). However, the mechanism of decidual macrophage polarization is unclear. We explored the role of Estradiol (E2)-sensitive serum-glucocorticoid regulated kinase (SGK) 1 in promoting macrophage polarization and suppressing inflammation at the maternal–fetal interface.

Methods

We assessed serum levels of E2 and progesterone during first trimester of pregnancy in women with or without threatened miscarriages (ended in live birth, n = 448; or early miscarriages, n = 68). For detection of SGK1 in decidual macrophages, we performed immunofluorescence labeling and western blot analysis applying decidual samples from RPL (n = 93) and early normal pregnancy (n = 66). Human monocytic THP-1 cells were differentiated into macrophages and treated with Toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS), E2, inhibitors or siRNA for in vitro analysis. Flow cytometry analysis were conducted to detect macrophages polarization. We also applied ovariectomized (OVX) mice with hormones exploring the mechanisms underlying the regulation of SGK1 activation by E2 in the decidual macrophages in vivo.

Results

SGK1 expression down regulation in the decidual macrophages of RPL was consistent with the lower concentration and slower increment of serum E2 from 4 to 12 weeks of gestation seen in these compromised pregnancies. LPS reduced SGK1 activities, but induced the pro-inflammatory M1 phenotype of THP-1 monocyte-derived macrophages and T helper (Th) 1 cytokines that favored pregnancy loss. E2 pretreatment promoted SGK1 activation in the decidual macrophages of OVX mice in vivo. E2 pretreatment amplified SGK1 activation in TLR4-stimulated THP-1 macrophages in vitro through the estrogen receptor beta (ERβ) and PI3K pathway. E2-sensitive activation of SGK1 increased M2 macrophages and Th2 immune responses, which were beneficial to successful pregnancy, by inducing ARG1 and IRF4 transcription, which are implicated in normal pregnancy. The experiments on OVX mice have shown that pharmacological inhibition of E2 promoted nuclear translocation of NF-κB in the decidual macrophages. Further more, pharmacological inhibition or knockdown of SGK1 in TLR4-stimulated THP-1 macrophages activated NF-κB by promoting its nuclear translocation, leading to increased secretion of pro-inflammatory cytokines involved in pregnancy loss.

Conclusion

Our findings highlighted the immunomodulatory roles of E2-activated SGK1 in Th2 immune responses by priming anti-inflammatory M2 macrophages at the maternal–fetal interface, resulting in a balanced immune microenvironment during pregnancy. Our results suggest new perspectives on future preventative strategies for RPL.
Association between cancer history and second-generation drug-eluting stent thrombosis: insights from the REAL-ST registry
Authors: Hamana Tomoyo , Otake Hiromasa , Kuramitsu Shoichi , Shinozaki Tomohiro , Ohya Masanobu , Horie Kazunori , Kawamoto Hiroyoshi , Yamanaka Futoshi , Natsuaki Masahiro , Shiomi Hiroki , Nakazawa Gaku , Ando Kenji , Kadota Kazushige , Saito Shigeru , Kimura Takeshi ,   on behalf of the REAL-ST Registry Investigators
Published: May 2023

Background

Cancer-associated thrombosis is a frequent complication of cancer; however, little evidence is available regarding the association between cancer history and coronary artery stent thrombosis (ST). We aimed to investigate the relationship between cancer history and second-generation drug-eluting stent thrombosis (G2-ST).

Methods

From the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation Drug-Eluting Stent Implantation) registry, this study evaluated 1265 patients (G2- ST cases, n = 253; controls, n = 1012) with cancer-related information available.

Results

The prevalence of patients with cancer history was higher (12.3% vs. 8.5%, p = 0.065), and that of currently diagnosed and currently treated cancer was significantly higher in ST cases than controls (3.6% vs. 1.4%, p = 0.021; 3.2% vs. 1.3%, p = 0.037, respectively). Multivariable logistic regression analysis revealed that cancer history was associated with late ST (odds ratio [OR]: 2.80, 95% confidence intervals [CI]: 0.92–8.55, p = 0.071) and very late ST (OR: 2.40, 95% CI: 1.02-5.65, p = 0.046), but not with early ST (OR: 1.01, 95% CI: 0.51-2.00, p = 0.97). During the median follow-up period of 872 days after the index ST events, patients with cancer history showed a higher mortality than those without, among both ST cases (hazard ratio [HR]: 1.93, 95% CI: 1.06-3.51, p = 0.031) and controls (HR: 1.93, 95% CI: 1.09-3.40, p = 0.023).

Conclusion

A post hoc analysis of REAL-ST registry revealed that patients with G2-ST had a higher prevalence of currently diagnosed and currently treated cancer. Notably, cancer history was associated with the occurrence of late and very late ST, but not with early ST.
Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles
Authors: Hanelova Klara , Raudenska Martina , Kratochvilova Monika , Navratil Jiri , Vicar Tomas , Bugajova Maria , Gumulec Jaromir , Masarik Michal , Balvan Jan
Published: May 2023

Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. Many studies suggest that cancer cells release higher amounts of EVs exposing phosphatidylserine (PS) at the surface. There are lots of interconnections between EVs biogenesis and autophagy machinery. Modulation of autophagy can probably affect not only the quantity of EVs but also their content, which can deeply influence the resulting pro-tumourigenic or anticancer effect of autophagy modulators. In this study, we found that autophagy modulators autophinib, CPD18, EACC, bafilomycin A1 (BAFA1), 3-hydroxychloroquine (HCQ), rapamycin, NVP-BEZ235, Torin1, and starvation significantly alter the composition of the protein content of phosphatidylserine-positive EVs (PS-EVs) produced by cancer cells. The greatest impact had HCQ, BAFA1, CPD18, and starvation. The most abundant proteins in PS-EVs were proteins typical for extracellular exosomes, cytosol, cytoplasm, and cell surface involved in cell adhesion and angiogenesis. PS-EVs protein content involved mitochondrial proteins and signalling molecules such as SQSTM1 and TGFβ1 pro-protein. Interestingly, PS-EVs contained no commonly determined cytokines, such as IL-6, IL-8, GRO-α, MCP-1, RANTES, and GM-CSF, which indicates that secretion of these cytokines is not predominantly mediated through PS-EVs. Nevertheless, the altered protein content of PS-EVs can still participate in the modulation of the fibroblast metabolism and phenotype as p21 was accumulated in fibroblasts influenced by EVs derived from CPD18-treated FaDu cells. The altered protein content of PS-EVs (data are available via ProteomeXchange with identifier PXD037164) also provides information about the cellular compartments and processes that are affected by the applied autophagy modulators.
Identification of small molecules capable of enhancing viral membrane fusion
Authors: García-Murria Mª Jesús , Gadea-Salom Laura , Moreno Sandra , Rius-Salvador Marina , Zaragoza Oscar , Brun Alejandro , Mingarro Ismael , Martínez-Gil Luis
Published: May 2023

Several approaches have been developed to analyze the entry of highly pathogenic viruses. In this study, we report the implementation of a Bimolecular Multicellular Complementation (BiMuC) assay to safely and efficiently monitor SARS-CoV-2 S-mediated membrane fusion without the need for microscopy-based equipment. Using BiMuC, we screened a library of approved drugs and identified compounds that enhance S protein-mediated cell-cell membrane fusion. Among them, ethynylestradiol promotes the growth of SARS-CoV-2 and Influenza A virus in vitro. Our findings demonstrate the potential of BiMuC for identifying small molecules that modulate the life cycle of enveloped viruses, including SARS-CoV-2.
Effect of omega-3 polyunsaturated fatty acids supplementation for patients with osteoarthritis: a meta-analysis
Authors: Deng Wen , Yi Zhiqian , Yin Enzhi , Lu Rui , You Hongbo , Yuan Xuefeng
Published: May 2023

Background

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) confers anti-inflammatory efficacy, which has been suggested to be effective for patients with osteoarthritis (OA). However, previous studies evaluating the influence of n-3 PUFAs supplementation in patients with OA showed inconsistent results. We performed a systematic review and meta-analysis to comprehensively evaluate the influence of n-3 PUFAs on symptom and joint function of patients with OA.

Methods

Relevant randomized controlled trials (RCTs) were obtained by searching PubMed, Embase, and Cochrane Library databases. A random-effects model was employed to combine the results.

Results

Nine RCTs with 2070 patients with OA contributed to the meta-analysis. Pooled results showed that n-3 PUFAs supplementation could significantly relieve the arthritis pain as compared to placebo (standardized mean difference [SMD]: − 0.29, 95% confidence interval [CI] − 0.47 to − 0.11, p = 0.002, I2 = 60%). Besides, supplementation with n-3 PUFAs was also associated with improved joint function (SMD: − 0.21, 95% CI − 0.34 to − 0.07, p = 0.002, I2 = 27%). Subgroup analysis showed consistent results of studies with arthritis pain and joint function evaluated by the Western Ontario-McMaster University Osteoarthritis Index and other scales (p for subgroup difference = 0.33 and 0.34, respectively). No severe treatment-related adverse events (AEs) were observed in the included patients, and the incidence of overall AEs was similar between groups (odds ratio: 0.97, 95% CI 0.64–1.45, p = 0.86, I2 = 0%).

Conclusions

Supplementation of n-3 PUFAs is effective to relieve pain and improve joint function in patients with OA.
Quality of life of pediatric and adult individuals with osteogenesis imperfecta: a meta-analysis
Authors: Wehrli Susanne , Rohrbach Marianne , Landolt Markus Andreas
Published: May 2023

Background

Osteogenesis imperfecta (OI) is a group of rare inheritable disorders of connective tissue. The cardinal manifestations of OI are low bone mass and reduced bone mineral strength, leading to increased bone fragility and deformity that may lead to significant impairment in daily life. The phenotypic manifestations show a broad range of severity, ranging from mild or moderate to severe and lethal. The here presented meta-analysis aimed to analyze existing findings on quality of life (QoL) in children and adults with OI.

Methods

Nine databases were searched with predefined key words. The selection process was executed by two independent reviewers and was based on predetermined exclusion and inclusion criteria. The quality of each study was assessed using a risk of bias tool. Effect sizes were calculated as standardized mean differences. Between-study heterogeneity was calculated with the I2 statistic.

Results

Among the studies included two featured children and adolescents (N = 189), and four adults (N = 760). Children with OI had significantly lower QoL on the Pediatric quality of life inventory (PedsQL) with regards to the total score, emotional, school, and social functioning compared to controls and norms. The data was not sufficient to calculate differences regarding OI-subtypes. In the adult sample assessed with Short Form Health Survey Questionnaire, 12 (SF-12) and 36 items (SF-36), all OI types showed significantly lower QoL levels across all physical component subscales compared to norms. The same pattern was found for the mental component subscales namely vitality, social functioning, and emotional role functioning. The mental health subscale was significantly lower for OI type I, but not for type III and IV. All of the included studies exhibited a low risk of bias.

Conclusions

QoL was significantly lower in children and adults with OI compared to norms and controls. Studies in adults comparing OI subtypes showed that the clinical severity of the phenotype is not related to worse mental health QoL. Future research is needed to examine QoL in children and adolescents in more sophisticated ways and to better understand the association between clinical severity of an OI-phenotype/severity and mental health in adults.
Effective long-term sirolimus treatment in hypoxemia mainly due to intrapulmonary right-to-left shunt in a patient with multiple vascular anomalies
Authors: Liu Jinrong , Duan Xiaomin , Yin Jie , Yang Haiming , He Ruxuan , Zhao Shunying
Published: May 2023

Pulmonary arteriovenous malformations (PAVMs), particularly where feeding artery/arteries to PAVMs ≥ 3 mm can be treated with embolization. The treatment for hypoxemia resulting from multiple small or diffuse PAVMs remains unclear.

We report a girl aged 5 years and 10 months presented with cyanosis and decreased activity after exercise (83–85% of pulse oxygen saturation, SpO2). She had 1 skin lesion on her face and 1 suspected hemangioma on her left upper extremity at birth and that gradually disappeared spontaneously. Physical examination revealed clubbed fingers, and abundant vascular networks on her back. Contrast-enhanced lung CT (slice thickness:1.25 mm) with vascular three-dimensional reconstruction and abdominal CT revealed increased bronchovascular bundles, increased diameter of the pulmonary artery and ascending aorta, and intrahepatic portosystemic venous shunts due to patent ductus venosus. Echocardiography revealed increased diameter of aortic and pulmonary artery. Transthoracic contrast echocardiography was highly positive (bubble appearing in the left ventricle after 5 cardiac cycles). Abdominal doppler ultrasound revealed hepatic-portal venous shunt. Magnetic resonance imaging, artery and vein of the brain revealed multiple malformations of venous sinuses. The patient received sirolimus for 2 years and 4 months. Her condition improved significantly. SpO2gradually increased to 98%. Her finger clubbing gradually normalized.

Our report implicates sirolimus might be a potential treatment option in persistent hypoxemia mainly due to intrapulmonary right-to-left shunt even small multiple or diffusive PAVMs in pediatric patients with multiple cutaneous and visceral vascular anomalies.
Maturation of nucleus accumbens synaptic transmission signals a critical period for the rescue of social deficits in a mouse model of autism spectrum disorder
Authors: Matthiesen Melina , Khlaifia Abdessattar , Steininger Carl Frank David , Dadabhoy Maryam , Mumtaz Unza , Arruda-Carvalho Maithe
Published: May 2023

Social behavior emerges early in development, a time marked by the onset of neurodevelopmental disorders featuring social deficits, including autism spectrum disorder (ASD). Although social deficits are at the core of the clinical diagnosis of ASD, very little is known about their neural correlates at the time of clinical onset. The nucleus accumbens (NAc), a brain region extensively implicated in social behavior, undergoes synaptic, cellular and molecular alterations in early life, and is particularly affected in ASD mouse models. To explore a link between the maturation of the NAc and neurodevelopmental deficits in social behavior, we compared spontaneous synaptic transmission in NAc shell medium spiny neurons (MSNs) between the highly social C57BL/6J and the idiopathic ASD mouse model BTBRT+Itpr3tf/J at postnatal day (P) 4, P6, P8, P12, P15, P21 and P30. BTBR NAc MSNs display increased spontaneous excitatory transmission during the first postnatal week, and increased inhibition across the first, second and fourth postnatal weeks, suggesting accelerated maturation of excitatory and inhibitory synaptic inputs compared to C57BL/6J mice. BTBR mice also show increased optically evoked medial prefrontal cortex-NAc paired pulse ratios at P15 and P30. These early changes in synaptic transmission are consistent with a potential critical period, which could maximize the efficacy of rescue interventions. To test this, we treated BTBR mice in either early life (P4-P8) or adulthood (P60-P64) with the mTORC1 antagonist rapamycin, a well-established intervention for ASD-like behavior. Rapamycin treatment rescued social interaction deficits in BTBR mice when injected in infancy, but did not affect social interaction in adulthood.
LncRNA XIST facilitates hypertrophy of ligamentum flavum by activating VEGFA-mediated autophagy through sponging miR-302b-3p
Authors: Cao Yanlin , Li Jianjun , Qiu Sujun , Ni Songjia , Duan Yang
Published: May 2023

Background

Increasing evidences have shown that long non-coding RNAs (lncRNAs) display crucial regulatory roles in the occurrence and development of numerous diseases. However, the function and underlying mechanisms of lncRNAs in hypertrophy of ligamentum flavum (HLF) have not been report.

Methods

The integrated analysis of lncRNAs sequencing, bioinformatics analysis and real-time quantitative PCR were used to identify the key lncRNAs involved in HLF progression. Gain- and loss-function experiments were used to explore the functions of lncRNA X inactive specific transcript (XIST) in HLF. Mechanistically, bioinformatics binding site analysis, RNA pull-down, dual-luciferase reporter assay, and rescue experiments were utilized to investigate the mechanism by which XIST acts as a molecular sponge of miR-302b-3p to regulate VEGFA-mediated autophagy.

Results

We identified that XIST was outstandingly upregulated in HLF tissues and cells. Moreover, the up-regulation of XIST strongly correlated with the thinness and fibrosis degree of LF in LSCS patients. Functionally, knockdown of XIST drastically inhibited proliferation, anti-apoptosis, fibrosis and autophagy of HLF cells in vitro and suppressed hypertrophy and fibrosis of LF tissues in vivo. Intestinally, we uncovered that overexpression of XIST significantly promoted proliferation, anti-apoptosis and fibrosis ability of HLF cells by activating autophagy. Mechanistic studies illustrated that XIST directly medullated the VEGFA-mediated autophagy through sponging miR-302b-3p, thereby enhancing the development and progression of HLF.

Conclusion

Our findings highlighted that the XIST/miR-302b-3p/VEGFA-mediated autophagy axis is involved in development and progression of HLF. At the same time, this study will complement the blank of lncRNA expression profiles in HLF, which laid the foundation for further exploration of the relationship between lncRNAs and HLF in the future.
WONDER-01: immediate necrosectomy vs. drainage-oriented step-up approach after endoscopic ultrasound-guided drainage of walled-off necrosis—study protocol for a multicentre randomised controlled trial
Authors: Sato Tatsuya , Saito Tomotaka , Takenaka Mamoru , Iwashita Takuji , Shiomi Hideyuki , Fujisawa Toshio , Hayashi Nobuhiko , Iwata Keisuke , Maruta Akinori , Mukai Tsuyoshi , Masuda Atsuhiro , Matsubara Saburo , Hamada Tsuyoshi , Inoue Tadahisa , Ohyama Hiroshi , Kuwatani Masaki , Kamada Hideki , Hashimoto Shinichi , Shiratori Toshiyasu , Yamada Reiko , Kogure Hirofumi , Ogura Takeshi , Nakahara Kazunari , Doi Shinpei , Chinen Kenji , Isayama Hiroyuki , Yasuda Ichiro , Nakai Yousuke ,   for the WONDERFUL study group in Japan, collaborators
Published: May 2023

Background

With the increasing popularity of endoscopic ultrasound (EUS)-guided transmural interventions, walled-off necrosis (WON) of the pancreas is increasingly managed via non-surgical endoscopic interventions. However, there has been an ongoing debate over the appropriate treatment strategy following the initial EUS-guided drainage. Direct endoscopic necrosectomy (DEN) removes intracavity necrotic tissue, potentially facilitating early resolution of the WON, but may associate with a high rate of adverse events. Given the increasing safety of DEN, we hypothesised that immediate DEN following EUS-guided drainage of WON might shorten the time to WON resolution compared to the drainage-oriented step-up approach.

Methods

The WONDER-01 trial is a multicentre, open-label, superiority, randomised controlled trial, which will enrol WON patients aged ≥ 18 years requiring EUS-guided treatment in 23 centres in Japan. This trial plans to enrol 70 patients who will be randomised at a 1:1 ratio to receive either the immediate DEN or drainage-oriented step-up approach (35 patients per arm). In the immediate DEN group, DEN will be initiated during (or within 72 h of) the EUS-guided drainage session. In the step-up approach group, drainage-based step-up treatment with on-demand DEN will be considered after 72–96 h observation. The primary endpoint is time to clinical success, which is defined as a decrease in a WON size to ≤ 3 cm and an improvement of inflammatory markers (i.e. body temperature, white blood cell count, and C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, and recurrence of the WON.

Discussion

The WONDER-01 trial will investigate the efficacy and safety of immediate DEN compared to the step-up approach for WON patients receiving EUS-guided treatment. The findings will help us to establish new treatment standards for patients with symptomatic WON.

Trial registration

ClinicalTrials.gov NCT05451901, registered on 11 July 2022. UMIN000048310, registered on 7 July 2022. jRCT1032220055, registered on 1 May 2022.
Diagnostic performance of standardized typical CT findings for COVID-19: a systematic review and meta-analysis
Authors: Nam Bo Da , Hong Hyunsook , Yoon Soon Ho
Published: May 2023

Objective

To meta-analyze diagnostic performance measures of standardized typical CT findings for COVID-19 and examine these measures by region and national income.

Methods

MEDLINE and Embase were searched from January 2020 to April 2022 for diagnostic studies using the Radiological Society of North America (RSNA) classification or the COVID-19 Reporting and Data System (CO-RADS) for COVID-19. Patient and study characteristics were extracted. We pooled the diagnostic performance of typical CT findings in the RSNA and CO-RADS systems and interobserver agreement. Meta-regression was performed to examine the effect of potential explanatory factors on the diagnostic performance of the typical CT findings.

Results

We included 42 diagnostic performance studies with 6777 PCR-positive and 9955 PCR-negative patients from 18 developing and 24 developed countries covering the Americas, Europe, Asia, and Africa. The pooled sensitivity was 70% (95% confidence interval [CI]: 65%, 74%;I2 = 92%), and the pooled specificity was 90% (95% CI 86%, 93%;I2 = 94%) for the typical CT findings of COVID-19. The sensitivity and specificity of the typical CT findings did not differ significantly by national income and the region of the study (p > 0.1, respectively). The pooled interobserver agreement from 19 studies was 0.72 (95% CI 0.63, 0.81;I2 = 99%) for the typical CT findings and 0.67 (95% CI 0.61, 0.74;I2 = 99%) for the overall CT classifications.

Conclusion

The standardized typical CT findings for COVID-19 provided moderate sensitivity and high specificity globally, regardless of region and national income, and were highly reproducible between radiologists.

Critical relevance statement

Standardized typical CT findings for COVID-19 provided a reproducible high diagnostic accuracy globally.

Key points

Standardized typical CT findings for COVID-19 provide high sensitivity and specificity.

Typical CT findings show high diagnosability regardless of region or income.

The interobserver agreement for typical findings of COVID-19 is substantial.

Graphical abstract
Acute abdominal pain in women of reproductive age: keys to suggest a complication of endometriosis
Authors: Coutureau Juliette , Mandoul Caroline , Verheyden Cecile , Millet Ingrid , Taourel Patrice
Published: May 2023

Although endometriosis is a common gynecological condition in women of reproductive age, a complication of endometriosis is rarely considered as the differential diagnosis of acute abdominal pain in that context. However, acute events in women with endometriosis can represent life-threatening conditions, which require emergent treatment and often surgical management. Mass effect of endometriotic implants can give rise to obstructive complications, specifically occurring in the bowel or in the urinary tract, while inflammatory mediators released by ectopic endometrial tissue can lead to inflammation of the surrounding tissues or to superinfection of the endometriotic implants. Magnetic resonance imaging is the best imaging modality to reach the diagnosis of endometriosis, but an accurate diagnosis is possible on computed tomography, especially in the presence of stellar, mildly enhanced, infiltrative lesions in suggestive areas. The aim of this pictorial review is to provide an image-based overview of key findings for the diagnosis of acute abdominal complications of endometriosis.

Graphical Abstract
Short-term PET-derived kinetic estimation for the diagnosis of hepatocellular carcinoma: a combination of the maximum-slope method and dual-input three-compartment model
Authors: Wang Tao , Li Boqiao , Shi Hong , Li Pengfei , Deng Yinglei , Wang Siyu , Luo Qiao , Xv Dongdong , He Jianfeng , Wang Shaobo
Published: May 2023

Background

Kinetic estimation provides fitted parameters related to blood flow perfusion and fluorine-18-fluorodeoxyglucose (18F-FDG) transport and intracellular metabolism to characterize hepatocellular carcinoma (HCC) but usually requires 60 min or more for dynamic PET, which is time-consuming and impractical in a busy clinical setting and has poor patient tolerance.

Methods

This study preliminarily evaluated the equivalence of liver kinetic estimation between short-term (5-min dynamic data supplemented with 1-min static data at 60 min postinjection) and fully 60-min dynamic protocols and whether short-term 18F-FDG PET-derived kinetic parameters using a three-compartment model can be used to discriminate HCC from the background liver tissue. Then, we proposed a combined model, a combination of the maximum-slope method and a three-compartment model, to improve kinetic estimation.

Results

There is a strong correlation between the kinetic parameters K1 ~ k3, HPI and $${{\varvec{V}}}_{{\varvec{b}}}$$

V

b

in the short-term and fully dynamic protocols. With the three-compartment model, HCCs were found to have higher k2, HPI and k3 values than background liver tissues, while K1, k4 and $${{\varvec{V}}}_{{\varvec{b}}}$$

V

b

values were not significantly different between HCCs and background liver tissues. With the combined model, HCCs were found to have higher HPI, K1 and k2, k3 and $${{\varvec{V}}}_{{\varvec{b}}}$$

V

b

values than background liver tissues; however, the k4 value was not significantly different between HCCs and the background liver tissues.

Conclusions

Short-term PET is closely equivalent to fully dynamic PET for liver kinetic estimation. Short-term PET-derived kinetic parameters can be used to distinguish HCC from background liver tissue, and the combined model improves the kinetic estimation.

Clinical relevance statement

Short-term PET could be used for hepatic kinetic parameter estimation. The combined model could improve the estimation of liver kinetic parameters.

Graphical Abstract
Differentiation of placenta percreta through MRI features and diffusion-weighted magnetic resonance imaging
Authors: Li Hang , Lu Tao , Li Mou , Wang Yishuang , Zhang Feng , Yuan Yi , Zhu Meilin , Zhao Xinyi
Published: May 2023

Objectives

To identify whether parameters measured from diffusion kurtosis and intravoxel incoherent motion help diagnose placenta percreta.

Methods

We retrospectively enrolled 75 patients with PAS disorders including 13 patients with placenta percreta and 40 patients without PAS disorders. Each patients underwent diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI). The apparent diffusion coefficient (ADC), perfusion fraction (f), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), mean diffusion kurtosis (MK) and mean diffusion coefficient (MD) were measured by the volumetric analysis and compared. MRI features were also analyzed and compared. The receiver operating characteristic (ROC) curve and logistic regression analysis were used to evaluate the diagnostic efficiency of different diffusion parameters and MRI features for distinguishing placental percreta.

Results

D* was an independent risk factor from DWI for predicting placenta percreta with sensitivity of 73% and specificity of 76%. Focal exophytic mass remained as independent risk factor from MRI features for predicting placenta percreta with sensitivity of 72.7% and specificity of 88.1%. When the two risk factors were combined together, the AUC was the highest, 0.880 (95% CI 0.8–0.96).

Conclusion

D* and focal exophytic mass were associated with placenta percreta. A combination of the 2 risk factors can be used to predict placenta percreta.

Critical relevance statement

A combination of D* and focal exophytic mass can be used to differentiate placenta percreta.
Potential advantages of genetically modified mesenchymal stem cells in the treatment of acute and chronic liver diseases
Authors: Sani Farnaz , Sani Mahsa , Moayedfard Zahra , Darayee Maryam , Tayebi Lobat , Azarpira Negar
Published: May 2023

Liver damage caused by toxicity can lead to various severe conditions, such as acute liver failure (ALF), fibrogenesis, and cirrhosis. Among these, liver cirrhosis (LC) is recognized as the leading cause of liver-related deaths globally. Unfortunately, patients with progressive cirrhosis are often on a waiting list, with limited donor organs, postoperative complications, immune system side effects, and high financial costs being some of the factors restricting transplantation. Although the liver has some capacity for self-renewal due to the presence of stem cells, it is usually insufficient to prevent the progression of LC and ALF. One potential therapeutic approach to improving liver function is the transplantation of gene-engineered stem cells. Several types of mesenchymal stem cells from various sources have been suggested for stem cell therapy for liver disease. Genetic engineering is an effective strategy that enhances the regenerative potential of stem cells by releasing growth factors and cytokines. In this review, we primarily focus on the genetic engineering of stem cells to improve their ability to treat damaged liver function. We also recommend further research into accurate treatment methods that involve safe gene modification and long-term follow-up of patients to increase the effectiveness and reliability of these therapeutic strategies.
Mesenchymal stem/stromal cells-derived extracellular vesicles as a potentially more beneficial therapeutic strategy than MSC-based treatment in a mild metabolic osteoarthritis model
Authors: Warmink Kelly , Rios Jaqueline L. , Varderidou-Minasian Suzy , Torres-Torrillas Marta , van Valkengoed Devin R. , Versteeg Sabine , Eijkelkamp Niels , Weinans Harrie , Korthagen Nicoline M. , Lorenowicz Magdalena J.
Published: May 2023

Background

Mesenchymal stromal/stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) hold promise as a disease modifying treatment in osteoarthritis (OA). Obesity, and its associated inflammation, contribute to OA development and metabolic OA represents a specific and significant group of the OA patient population. Given their immunomodulatory properties, MSC and MSC-EVs are especially interesting for this group of patients as a therapeutic option. Here, we were the first to compare the therapeutic efficacy of MSCs and MSC-EVs in a mild OA model taking these metabolic aspects into consideration.

Methods

Male Wistar-Han rats (Crl:WI(Han) (n = 36) were fed a high fat diet for 24 weeks, with unilateral induction of OA by groove surgery after 12 weeks. Eight days after surgery rats were randomized in three treatment groups receiving MSCs, MSC-EVs or vehicle injection. Pain-associated behavior, joint degeneration, and local and systemic inflammation were measured.

Results

We demonstrated that despite not having a significant therapeutic effect, MSC-EV treatment results in lower cartilage degeneration, less pain behaviour, osteophytosis and joint inflammation, than MSC treatment. Suggesting that MSC-EVs could be a more promising therapeutic strategy than MSCs in this mild metabolic OA model.

Conclusion

In summary, we find that MSC treatment has negative effects on the joint in metabolic mild OA. This is an essential finding for the significant group of patients with metabolic OA phenotype, and might help to understand why clinical translation of MSC treatment shows varying therapeutic efficacy thus far. Our results also suggest that MSC-EV-based treatment might be a promising option for these patients, however MSC-EV therapeutic efficacy will need improvement.
Nile tilapia (Oreochromis niloticus) invasion impacts trophic position and resource use of commercially harvested piscivorous fishes in a large subtropical river
Authors: Shuai Fangmin , Li Jie , Lek Sovan
Published: May 2023

Background

Although freshwater ecosystems cover less than 1% of the earth's surface, they support extremely high levels of biodiversity and provide vital ecosystem services. However, due to the introduction of non-native fishes, aquatic ecosystem functioning has been altered, and in some cases, declined sharply. Quantifying the impacts of invasive species has proven problematic. In this study, we examined the relative trophic position of native piscivorous fishes to estimate the effects of invasive Nile tilapia on food webs in the downstream sections of an invaded large subtropical river, the Pearl River, China. Furthermore, we quantified how native piscivorous fish diets changed as the Nile tilapia invasion progressed.

Results

The trophic position of the widely distributed and locally important economically harvested piscivorous culter fish (Culterrecurviceps), mandarinfish (Sinipercakneri), and catfish (Pelteobagrusfulvidraco) lowered significantly in the invaded Dongjiang River compared to an uninvaded reference Beijiang River. The lower trophic position of these piscivorous fishes was reflected by a major reduction in the proportion of prey fish biomass in their diets following the Nile tilapia invasion. Small fishes in the diet of culter fish from the reference river (33% small fishes, 17% zooplankton) shifted to lower trophic level zooplankton prey in the invaded river (36% zooplankton, 25% small fish), possibly due to the presence of Nile tilapia. Additionally, small fishes in the diet of mandarinfish in the reference river (46% small fishes, 11% aquatic insects) declined in the invaded river (20% aquatic insects, 30% small fishes). Similarly, the diet of catfish from the reference river shifted from fish eggs (25% fish eggs, 25% aquatic insects) to aquatic insects in the invaded river (44% aquatic insects, 5% fish eggs).

Conclusions

The results of this study contributed to a growing body of evidence, suggesting that Nile tilapia can modify trophic interactions in invaded ecosystems. It is crucial to understand the processes outlined in this study in order to better assess non-native aquatic species, conserve the stability of freshwater ecosystems, and improve current conservation strategies in reaches of the Pearl River and other similar rivers that have experienced invasions of non-native species.
Better sleep quality and higher physical activity levels predict lower emotion dysregulation among persons with major depression disorder
Authors: Rezaie Leeba , Norouzi Ebrahim , Bratty Alexandra J. , Khazaie Habibolah
Published: May 2023

Background

People with Major Depression Disorders (MDD) often complain about sleep problems and experience emotion dysregulation. Prior research suggests physical activity can improve both sleep quality and emotional control. However, there is limited research on emotion regulation and the impact of physical activity and sleep in this population.

Objectives

The present study examined the relationships between sleep quality, emotion regulation, and physical activity levels among patients with MDD.

Methods

The sample consisted of 118 patients with MDD (mean age: 31.85 years) who completed questionnaires on sleep quality, physical activity, emotion regulation, and depression.

Results

Results showed that more sleep problems were associated with worse emotion dysregulation, and more physical activity was associated with fewer sleep problems and less emotion dysregulation. Furthermore, physical activity and sleep quality significantly predicted emotion dysregulation, with physical activity being the stronger predictor.

Conclusions

Results from this study suggest that individuals with MDD who are able to engage in physical activity and get better sleep could experience emotional regulation benefits.
De novo ADGRV1 variant in a patient with ictal asystole provides novel clues for increased risk of SUDEP
Authors: Ji Tuo , Downs Aaron W. , Dorris Luong , Zhong Ning
Published: May 2023

Background

Various cardiac and autonomic manifestations are frequently reported during seizures. Among the seizure-related arrhythmia, ictal tachycardia is the most common, followed by ictal bradycardia, with ictal asystole being the rarest. The occurrence of ictal asystole may obscure the clinical presentation and delay the diagnosis, representing a life-threatening presentation of epilepsy, with an elevated risk of sudden unexpected death in epilepsy patients (SUDEP). These cardiac abnormalities are being increasingly recognized as the key to elucidating the mechanisms of SUDEP.

Case presentation

We present a 35-year-old man with a history of focal-onset seizures with impaired consciousness since his mid-20 s. He developed different types of seizures for 2 years, described as tonic seizure and atonic seizure (drop attack). During such clinical events, he suffered from falls and cardiac arrest. However, thorough cardiac electrophysiology and imaging workup failed to reveal a cardiac etiology. Subsequent video electroencephalograph (EEG) monitoring was performed, and ictal bradycardia and ictal asystole were discovered. A cardiac pacemaker was implanted, and at 3-year follow-up, the patient did not suffer more atonic seizures, or falls. Genetic tests discovered a de novo variant of Adhesion G Protein-Coupled Receptor V1 (ADGRV1), which may provide a clue for the patient’s ictal asystole and the increased risk of SUDEP.

Conclusions

Considering the important impact of ictal bradycardia and asystole on the morbidity and potential mortality of epileptic patients, it is important to simultaneously utilize EEG and electrocardiogram to confirm the diagnosis. This case report highlights the link between the de novo variant of ADGRV1 and the ictal bradycardia/asystole phenotype and implicates the importance of genetic testing in adult epilepsy patients.
The usefulness of addition of breast-specific gamma imaging to mammography in women with dense breast
Authors: Kim Young Joong , Seo Jae Young , Kim Keum Won , Hwang Cheol Mog , Oh Dong Hyun
Published: May 2023

Background

Mammography (MG) has been adopted as a screening modality for breast cancer. However, the diagnostic yield was reported to decrease in women with dense breasts in MG. Several modalities have been introduced to improve the drawbacks. Breast-specific gamma imaging (BSGI) is a new technique in nuclear medicine imaging that could support breast cancer diagnosis. The aim of this study was to evaluate whether the addition of BSGI according to MG category could improve the accuracy of diagnosis and reduce unnecessary studies or biopsies.

Results

From February 2013 to December 2018, 548 patients with 628 breast lesions were enrolled in this retrospective study. The performances of BSGI and MG were evaluated for detecting breast cancer. We classified subgroups by adding the results of BSGI for BI-RADS category 0 and 4a lesions on MG. For each subgroup, diagnostic performance was calculated in overall and dense/non-dense. Factors associated with false-negative BSGI were evaluated. The sensitivity of BSGI (88.26%) was comparable to that of MG (87.95%) (P > 0.05). Specificity (81.44%) and AUC (0.85) of BSGI were significantly superior to those of MG (66.83% and 0.77, respectively). In the subgroup analysis of BSGI plus MG, the sensitivity of BSGI + MG0 and BSGI + MG4a were 95.98% and 94.64%, respectively. And specificities were 69.80% and 77.23%, respectively. Sensitivity and AUC of subgroups increased significantly compared to those of MG alone in overall and dense breasts. A nodule ≤ 10 mm and a low Ki-67 showed significant association with the false negativity of BSGI.

Conclusions

Applying BSGI to MG, notably for breast lesions with BI-RADS category 0 or 4a, could improve the diagnostic performance, even in dense breasts.