bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of SMAD3 effectively reduces ADAMTS-5 expression in the early stages of osteoarthritis
Authors: Xiang Wei , Wang Chao , Zhu Zhoujun , Wang Dui , Qiu Zhenyu , Wang Weishan 
Published: February 2023

Abstract
Objective
As one of the most important protein-degrading enzymes, ADAMTS-5 plays an important role in the regulation of cartilage homeostasis, while miRNA-140 is specifically expressed in cartilage, which can inhibit the expression of ADAMTS-5 and delay the progression of OA (osteoarthritis). SMAD3 is a key protein in the TGF-β signaling pathway, inhibiting the expression of miRNA-140 at the transcriptional and post-transcriptional levels, and studies have confirmed the high expression of SMAD3 in knee cartilage degeneration, but whether SMAD3 can mediate the expression of miRNA-140 to regulate ADAMTS-5 remains unknown.

Methods
Sprague–Dawley (SD) rat chondrocytes were extracted in vitro and treated with a SMAD3 inhibitor (SIS3) and miRNA-140 mimics after IL-1 induction. The expression of ADAMTS-5 was detected at the protein and gene levels at 24 h, 48 h, and 72 h after treatment. The OA model of SD rats was created using the traditional Hulth method in vivo, with SIS3 and lentivirus packaged miRNA-140 mimics injected intra-articularly at 2 weeks, 6 weeks and 12 weeks after surgery. The expression of miRNA-140 and ADAMTS-5 in the knee cartilage tissue was observed at the protein and gene levels. Concurrently, knee joint specimens were fixed, decalcified, and embedded in paraffin prior to immunohistochemical, Safranin O/Fast Green staining, and HE staining analyses for ADAMTS-5 and SMAD3.

Results
In vitro, the expression of ADAMTS-5 protein and mRNA in the SIS3 group decreased to different degrees at each time point. Meanwhile, the expression of miRNA-140 in the SIS3 group was significantly increased, and the expression of ADAMTS-5 in the miRNA-140 mimics group was also significantly downregulated (P < 0.05). In vivo, it was found that ADAMTS-5 protein and gene were downregulated to varying degrees in the SIS3 and miRNA-140 mimic groups at three time points, with the most significant decrease at the early stage (2 weeks) (P < 0.05), and the expression of miRNA-140 in the SIS3 group was significantly upregulated, similar to the changes detected in vitro. Immunohistochemical results showed that the expression of ADAMTS-5 protein in the SIS3 and miRNA-140 groups was significantly downregulated compared to that in the blank group. The results of hematoxylin and eosin staining showed that in the early stage, there was no obvious change in cartilage structure in the SIS3 and miRNA-140 mock groups. The same was observed in the results of Safranin O/Fast Green staining; the number of chondrocytes was not significantly reduced, and the tide line was complete.

Conclusion
The results of in vitro and in vivo experiments preliminarily showed that the inhibition of SMAD3 significantly reduced the expression of ADAMTS-5 in early OA cartilage, and this regulation might be accomplished indirectly through miRNA-140.
No bladder irrigation versus continuous bladder irrigation after HoLEP: a propensity score matching analysis
Authors: Hao Yunwu , Chen Degang , Shen Xudong , Chen Yang , Hao Zongyao 
Published: February 2023

Abstract
Purpose
In this study, the feasibility of a no bladder irrigation strategy after transurethral holmium laser enucleation of the prostate (HoLEP) for the treatment of benign prostatic hyperplasia (BPH) was studied.

Methods
From August 2021 to December 2021, the clinical data of 62 patients who received no bladder irrigation after HoLEP (Group A) were studied. The control group contained the clinical data of 150 patients in the same therapy group (from January 2021 to July 2021) who received continuous bladder irrigation after HoLEP (Group B). The baseline was consistent after using the propensity score matching (PSM) method, and the differences between groups were compared. The pre- and postoperative complications, international prostate symptom score (IPSS), quality of life (QOL), maximum urinary flow rate (Qmax), and postvoid residual urine (PVR) of the two groups were compared, accompanied by a follow-up evaluation of surgical effects.

Results
47 pairs of patients were successfully matched by PSM. There was no statistically significant difference in the intraoperative conditions and the incidence of early postoperative complications between the two groups (P > 0.05). Before and one month after the surgery, significant differences were also found in the IPSS, QOL, Qmax, and PVR of both groups (P < 0.05). Within one month after the surgery, no statistically significant difference was found in IPSS, QOL, Qmax, PVR, or the incidence of early postoperative complications between the two groups (P > 0.05).

Conclusion
For appropriately selected patients according to the exclusion criteria, the no bladder irrigation strategy after HoLEP for BPH is safe and effective.
Resilience in advanced cancer caregiving promoted by an intimate partner’s support network: insights through the lens of complexity science. A framework analysis
Authors: Opsomer Sophie , Joossens Sofie , Lauwerier Emelien , De Lepeleire Jan , Pype Peter 
Published: February 2023

Abstract
Background
The tremendous physical and mental burden that comes with caregiving puts the intimate partners of patients diagnosed with advanced cancer at risk for mental disorders. However, most partners seem to be protected by resilience. Such a resilience process is promoted by certain individual characteristics (e.g., flexibility, positive attitude, internal strength, capacity to balance incoming and outgoing information, and ability to ask for and accept support and advice) and by the availability of a support network, consisting of family, friends, and healthcare professionals. Such a heterogeneous group striving towards the same goals can be considered a complex adaptive system (CAS), a concept stemming from complexity science.

Aims
To study the behavior of the support network through the lens of complexity science and to provide insights to the means by which an available network may promote resilience.

Methods
Nineteen interviews with members from the support networks of eight intimate partners were analyzed deductively using the CAS principles as a coding framework. Subsequently, the quotes under each principle were coded inductively to concretize patterns in the behavior of the support networks. Eventually, the codes were charted into a matrix to identify intra- and inter-CAS similarities, differences, and patterns.

Findings
The network’s behavior adapts dynamically to the changing circumstances as the patient’s prognosis worsens. Furthermore, the behavior is based on internalized basic rules (such as reassuring availability and maintaining communication without being intrusive), attractors (e.g., feeling meaningful, appreciated, or connected), and the history of the support network. However, the interactions are non-linear and often unpredictable due to the context member’s own concerns, needs, or emotions.

Conclusions
Applying the lens of complexity science to the behavior of an intimate partner’s support network gives us insight into the network’s behavioral patterns. Indeed, a support network is a dynamic system that behaves according to the principles of a CAS and adapts resiliently to the changing circumstances as the patient’s prognosis worsens. Moreover, the behavior of the support network appears to promote the intimate partner’s resilience process throughout the patient’s care period.
Response to Tsuda et al. “demonstrating the undermining of science and health policy after the Fukushima nuclear accident by applying the toolkit for detecting misused epidemiological methods”
Authors: Cléro Enora , Demoury Claire , Grosche Bernd , Liutsko Liudmila , Motreff Yvon , Ohba Takashi , Oughton Deborah , Pirard Philippe , Rogel Agnès , Schneider Thierry , Van Nieuwenhuyse An , Laurier Dominique , Cardis Elisabeth 
Published: February 2023

Abstract
Background
The SHAMISEN (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) European project was conducted in 2015-2017 to review the lessons learned from the experience of past nuclear accidents and develop recommendations for preparedness and health surveillance of populations affected by a nuclear accident. Using a toolkit approach, Tsuda et al. recently published a critical review of the article by Cléro et al. derived from the SHAMISEN project on thyroid cancer screening after nuclear accident.

Main body
We address the main points of criticism of our publication on the SHAMISEN European project.

Conclusion
We disagree with some of the arguments and criticisms mentioned by Tsuda et al. We continue to support the conclusions and recommendations of the SHAMISEN consortium, including the recommendation not to launch a mass thyroid cancer screening after a nuclear accident, but rather to make it available (with appropriate information counselling) to those who request it.
Legal sourcing of ten cannabis products in the Canadian cannabis market, 2019–2021: a repeat cross-sectional study
Authors: Wadsworth Elle , Rynard Vicki , Driezen Pete , Freeman Tom P. , Rychert Marta , Wilkins Chris , Hall Wayne , Gabrys Robert , Hammond David 
Published: February 2023

AbstractBackgroundOne of the objectives of cannabis legalization in Canada is to transition consumers from the illegal to the legal market. Little is known about how legal sourcing varies across different cannabis product types, provinces, and frequency of cannabis use.MethodsData were analyzed from Canadian respondents in the International Cannabis Policy Study, a repeat cross-sectional survey conducted annually from 2019 to 2021. Respondents were 15,311 past 12-month cannabis consumers of legal age to purchase cannabis. Weighted logistic regression models estimated the association between legal sourcing (“all”/ “some”/ “none”) of ten cannabis product types, province, and frequency of cannabis use over time.ResultsThe percentage of consumers who sourced “all” their cannabis products from legal sources in the past 12 months varied by product type, ranging from 49% of solid concentrate consumers to 82% of cannabis drink consumers in 2021. The percentage of consumers sourcing “all” their respective products legally was greater in 2021 than 2020 across all products. Legal sourcing varied by frequency of use: weekly or more frequent consumers were more likely to source “some” (versus “none”) of their products legally versus less frequent consumers. Legal sourcing also varied by province, with a lower likelihood of legal sourcing in Québec of products whose legal sale was restricted (e.g., edibles).ConclusionLegal sourcing increased over time, demonstrating progress in the transition to the legal market for all products in the first three years of legalization in Canada. Legal sourcing was highest for drinks and oils and lowest for solid concentrates and hash.
WWP2 drives the progression of gastric cancer by facilitating the ubiquitination and degradation of LATS1 protein
Authors: Zou Jianping , Zhou Ling , Le Yi , Fang Zhi , Zhong Min , Nie Fengting , Wei Xianpin , Zhang Xiaomei , Chen Zhen , Cai Lingling , Wang Heng , Xiong Jianping , Fang Ziling , Xiang Xiaojun 
Published: February 2023

Abstract
Background
Large tumor suppressor kinase 1 (LATS1), one of the predominant components of the Hippo pathway, has been characterized as a key player controlling the proliferation and invasion of cancer cells, including gastric cancer (GC) cells. However, the mechanism by which the functional stability of LATS1 is modulated has yet to be elucidated.

Methods
Online prediction tools, immunohistochemistry and western blotting assays were used to explore the expression of WW domain-containing E3 ubiquitin ligase 2 (WWP2) in GC cells and tissues. Gain- and loss-of-function assays, as well as rescue experiments were performed to determine the role of the WWP2-LATS1 axis in cell proliferation and invasion. Additionally, the mechanisms involving WWP2 and LATS1 were assessed by coimmunoprecipitation (Co-IP), immunofluorescence, cycloheximide and in vivo ubiquitination assays.

Results
Our results demonstrate a specific interaction between LATS1 and WWP2. WWP2 was markedly upregulated and correlated with disease progression and a poor prognosis in GC patients. Moreover, ectopic WWP2 expression facilitated the proliferation, migration and invasion of GC cells. Mechanistically, WWP2 interacts with LATS1, resulting in its ubiquitination and subsequent degradation, leading to increased transcriptional activity of YAP1. Importantly, LATS1 depletion abolished the suppressive effects of WWP2 knockdown on GC cells. Furthermore, WWP2 silencing attenuated tumor growth by regulating the Hippo-YAP1 pathway in vivo.

Conclusions
Our results define the WWP2-LATS1 axis as a critical regulatory mechanism of the Hippo-YAP1 pathway that promotes GC development and progression.
Ultrasound-guided interlaminar approach for nusinersen administration in patients with spinal muscular atrophy with spinal fusion or severe scoliosis
Authors: Wei Cuijie , Liang Zhenwei , Wu Ying , Liu Shan , Qiu Jianxing , Meng Lingchao , Li Chunde , Li Shuang , Bao Xinhua , Wang Zhaoxia , Chen Luzeng , Xiong Hui 
Published: February 2023

Abstract
Background
Intrathecal injection of medications can be challenging in spinal muscular atrophy (SMA) patients with severe scoliosis or after spine surgery. Here we report our experience with real-time ultrasound (US)-guided intrathecal administration of nusinersen in patients with SMA.

Methods
Seven patients (six children and one adult) with either spinal fusion or severe scoliosis were enrolled. We performed intrathecal injections of nusinersen under US guidance. The efficacy and safety of US-guided injection were explored.

Results
Five patients had undergone spinal fusion, while the other two presented severe scoliosis. Success was achieved in 19/20 lumbar punctures (95%), 15 of which were performed through the near-spinous process approach. The intervertebral space with a designated channel was selected for the five postoperative patients, while the interspaces with the smallest rotation angle were chosen for the other two patients with severe scoliosis. In 89.5% (17/19) of the punctures, the number of insertions was no more than two. No major adverse events were observed.

Conclusion
Given its safety and efficacy, real-time US guidance is recommended for SMA patients with spine surgery or severe scoliosis, and the near-spinous process view can be used as a interlaminar puncture approach for US guidance.
Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-𝜅B-IL-6 axis of tumor-associated macrophages
Authors: Zhou Boxuan , Mo Zhaohong , Lai Guie , Chen Xiaohong , Li Ruixi , Wu Runxin , Zhu Jia , Zheng Fang 
Published: February 2023

Abstract
Background
Circular RNAs (circRNAs) have important regulatory functions in cancer, but the role of circRNAs in the tumor microenvironment (TME) remains unclear. Moreover, we also explore the effects of si-circRNAs loaded in nanoparticles as therapeutic agent for anti-tumor in vivo.

Methods
We conducted bioinformatics analysis, qRT-PCR, EdU assays, Transwell assays, co-culture system and multiple orthotopic xenograft models to investigate the expression and function of circRNAs. Additionally, PLGA-based nanoparticles loaded with si-circRNAs were used to evaluate the potential of nanotherapeutic strategy in anti-tumor response.

Results
We identified oncogene SERPINE2 derived circRNA, named as cSERPINE2, which was notably elevated in breast cancer and was closely related to poor clinical outcome. Functionally, tumor exosomal cSERPINE2 was shuttled to tumor associated macrophages (TAMs) and enhanced the secretion of Interleukin-6 (IL-6), leading to increased proliferation and invasion of breast cancer cells. Furthermore, IL-6 in turn increased the EIF4A3 and CCL2 levels within tumor cells in a positive feedback mechanism, further enhancing tumor cSERPINE2 biogenesis and promoting the recruitment of TAMs. More importantly, we developed a PLGA-based nanoparticle loaded with si-cSERPINE2, which effectively attenuated breast cancer progression in vivo.

Conclusions
Our study illustrates a novel mechanism that tumor exosomal cSERPINE2 mediates a positive feedback loop between tumor cells and TAMs to promote cancer progression, which may serve as a promising nanotherapeutic strategy for the treatment of breast cancer.
Recommendations from a Canadian Delphi consensus study on best practice for optimal referral and appropriate management of severe asthma
Authors: Godbout K. , Bhutani M. , Connors L. , Chan C. K. N. , Connors C. , Dorscheid D. , Dyck G. , Foran V. , Kaplan A. G. , Reynolds J. , Waserman S. 
Published: February 2023

Abstract
Background
In Canada, severe asthma affects an estimated 5–10% of people with asthma and is associated with frequent exacerbations, poor symptom control and significant morbidity from the disease itself, as well as the high dose inhaled, and systemic steroids used to treat it. Significant heterogeneity exists in service structure and patient access to severe asthma care, including access to biologic treatments. There appears to be over-reliance on short-acting beta agonists and frequent oral corticosteroid use, two indicators of uncontrolled asthma which can indicate undiagnosed or suboptimally treated severe asthma. The objective of this modified Delphi consensus project was to define standards of care for severe asthma in Canada, in areas where the evidence is lacking through patient and healthcare professional consensus, to complement forthcoming guidelines.

Methods
The steering group of asthma experts identified 43 statements formed from eight key themes. An online 4-point Likert scale questionnaire was sent to healthcare professionals working in asthma across Canada to assess agreement (consensus) with these statements. Consensus was defined as high if ≥ 75% and very high if ≥ 90% of respondents agreed with a statement.

Results
A total of 150 responses were received from HCPs including certified respiratory educators, respirologists, allergists, general practitioners/family physicians, nurses, pharmacists, and respiratory therapists. Consensus amongst respondents was very high in 37 (86%) statements, high in 4 (9%) statements and was not achieved in 2 (5%) statements. Based on the consensus scores, ten key recommendations were proposed. These focus on referrals from primary and secondary care, accessing specialist asthma services, homecare provision for severe asthma patients and outcome measures.

Conclusions
Implementation of these recommendations across the severe asthma care pathway in Canada has the potential to improve outcomes for patients through earlier detection of undiagnosed severe asthma, reduction in time to severe asthma diagnosis, and initiation of advanced phenotype specific therapies.
Maternal adverse childhood experiences impact fetal adrenal volume in a sex-specific manner
Authors: Duffy Korrina A. , Sammel Mary D. , Johnson Rachel L. , Kim Deborah R. , Wang Eileen Y. , Ewing Grace , Hantsoo Liisa , Kornfield Sara L. , Bale Tracy L. , Epperson C. Neill 
Published: February 2023

AbstractBackgroundThe mechanisms by which parental early life stress can be transmitted to the next generation, in some cases in a sex-specific manner, are unclear. Maternal preconception stress may increase susceptibility to suboptimal health outcomes via in utero programming of the fetal hypothalamic–pituitary–adrenal (HPA) axis.MethodsWe recruited healthy pregnant women (N = 147), dichotomized into low (0 or 1) and high (2+) adverse childhood experience (ACE) groups based on the ACE Questionnaire, to test the hypothesis that maternal ACE history influences fetal adrenal development in a sex-specific manner. At a mean (standard deviation) of 21.5 (1.4) and 29.5 (1.4) weeks gestation, participants underwent three-dimensional ultrasounds to measure fetal adrenal volume, adjusting for fetal body weight (waFAV).ResultsAt ultrasound 1,waFAV was smaller in high versus low ACE males (b = − 0.17;z = − 3.75;p < .001), but females did not differ significantly by maternal ACE group (b = 0.09; z = 1.72;p = .086). Compared to low ACE males,waFAV was smaller for low (b = − 0.20;z = − 4.10;p < .001) and high ACE females (b = − 0.11;z = 2.16;p = .031); however, high ACE males did not differ from low (b = 0.03;z = .57;p = .570) or high ACE females (b = − 0.06;z = − 1.29;p = .196). At ultrasound 2,waFAV did not differ significantly between any maternal ACE/offspring sex subgroups (ps ≥ .055). Perceived stress did not differ between maternal ACE groups at baseline, ultrasound 1, or ultrasound 2 (ps ≥ .148).ConclusionsWe observed a significant impact of high maternal ACE history onwaFAV, a proxy for fetal adrenal development, but only in males. Our observation that thewaFAV in males of mothers with a high ACE history did not differ from thewaFAV of females extends preclinical research demonstrating a dysmasculinizing effect of gestational stress on a range of offspring outcomes. Future studies investigating intergenerational transmission of stress should consider the influence of maternal preconception stress on offspring outcomes.
A latent rhythm complexity model for attribute-controlled drum pattern generation
Authors: Mezza Alessandro Ilic , Zanoni Massimiliano , Sarti Augusto 
Published: February 2023

AbstractMost music listeners have an intuitive understanding of the notion of rhythm complexity. Musicologists and scientists, however, have long sought objective ways to measure and model such a distinctively perceptual attribute of music. Whereas previous research has mainly focused on monophonic patterns, this article presents a novel perceptually-informed rhythm complexity measure specifically designed for polyphonic rhythms, i.e., patterns in which multiple simultaneous voices cooperate toward creating a coherent musical phrase. We focus on drum rhythms relating to the Western musical tradition and validate the proposed measure through a perceptual test where users were asked to rate the complexity of real-life drumming performances. Hence, we propose a latent vector model for rhythm complexity based on a recurrent variational autoencoder tasked with learning the complexity of input samples and embedding it along one latent dimension. Aided by an auxiliary adversarial loss term promoting disentanglement, this effectively regularizes the latent space, thus enabling explicit control over the complexity of newly generated patterns. Trained on a large corpus of MIDI files of polyphonic drum recordings, the proposed method proved capable of generating coherent and realistic samples at the desired complexity value. In our experiments, output and target complexities show a high correlation, and the latent space appears interpretable and continuously navigable. On the one hand, this model can readily contribute to a wide range of creative applications, including, for instance, assisted music composition and automatic music generation. On the other hand, it brings us one step closer toward achieving the ambitious goal of equipping machines with a human-like understanding of perceptual features of music.