bluuebunny/crossref_metadata_2025_split 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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractExtracellular 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

AbstractSeveral 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

Abstract
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

Abstract
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

AbstractPulmonary 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

AbstractSocial 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.