bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in the diagnosis of the enigmatic primary adrenal leiomyosarcoma: two case reports and review of the literature
Authors: Suzuki Sawako , Takahashi Naoya , Sugo Masafumi , Ishiwata Kazuki , Ishida Akiko , Watanabe Suzuka , Igarashi Katsushi , Ruike Yutaro , Naito Kumiko , Fujimoto Masanori , Koide Hisashi , Imamura Yusuke , Sakamoto Shinichi , Ichikawa Tomohiko , Kubota Yoshihiro , Wada Takeshi , Yamazaki Yuto , Sasano Hironobu , Ikeda Jun-ichiro , Tatsuno Ichiro , Yokote Koutaro 
Published: December 2023

Abstract
Background
Primary adrenal leiomyosarcoma is a rare and aggressive mesenchymal tumor derived from the smooth muscle wall of a central adrenal vein or its tributaries; therefore, tumors tend to invade the inferior vena cava and cause thrombosis. The great majority of tumors grow rapidly, which makes the disease difficult to diagnose in its early clinical stages and needs differentiation from adrenocortical carcinomas for the selection of chemotherapy including mitotane which causes adrenal insufficiency.

Case presentation
We presented two patients with adrenal leiomyosarcoma who were referred to our hospital with abdominal pain and harboring large adrenal tumors and inferior vena cava thrombosis. The endocrine findings, including serum catecholamine levels, were unremarkable. These two patients were considered clinically inoperable, and CT-guided core needle biopsy was performed to obtain the definitive histopathological diagnosis and determine the modes of therapy. The masses were subsequently diagnosed as primary adrenal leiomyosarcoma based on the histological features and positive immunoreactivity for SMA (smooth muscle actin), desmin, and vimentin.

Conclusions
Adrenal leiomyosarcoma derived from the smooth muscle wall of a central adrenal vein or its tributaries is rare but should be considered a differential diagnosis in the case of nonfunctioning adrenal tumors extending directly to the inferior vena cava. CT-guided biopsy is considered useful for histopathological diagnosis and clinical management of patients with inoperable advanced adrenal tumors without any hormone excess.
MNCLCDA: predicting circRNA-drug sensitivity associations by using mixed neighbourhood information and contrastive learning
Authors: Li Guanghui , Zeng Feifan , Luo Jiawei , Liang Cheng , Xiao Qiu 
Published: December 2023

Abstract
Background
circRNAs play an important role in drug resistance and cancer development. Recently, many studies have shown that the expressions of circRNAs in human cells can affect the sensitivity of cells to therapeutic drugs, thus significantly influencing the therapeutic effects of these drugs. Traditional biomedical experiments required to verify this sensitivity relationship are not only time-consuming but also expensive. Hence, the development of an efficient computational approach that can accurately predict the novel associations between drug sensitivities and circRNAs is a crucial and pressing need.

Methods
In this research, we present a novel computational framework called MNCLCDA, which aims to predict the potential associations between drug sensitivities and circRNAs to assist with medical research. First, MNCLCDA quantifies the similarity between the given drug and circRNA using drug structure information, circRNA gene sequence information, and GIP kernel information. Due to the existence of noise in similarity information, we employ a preprocessing approach based on random walk with restart for similarity networks to efficiently capture the useful features of circRNAs and drugs. Second, we use a mixed neighbourhood graph convolutional network to obtain the neighbourhood information of nodes. Then, a graph-based contrastive learning method is used to enhance the robustness of the model, and finally, a double Laplace-regularized least-squares method is used to predict potential circRNA-drug associations through the kernel matrices in the circRNA and drug spaces.

Results
Numerous experimental results show that MNCLCDA outperforms six other advanced methods. In addition, the excellent performance of our proposed model in case studies illustrates that MNCLCDA also has the ability to predict the associations between drug sensitivity and circRNA in practical situations.

Conclusions
After a large number of experiments, it is illustrated that MNCLCDA is an efficient tool for predicting the potential associations between drug sensitivities and circRNAs, thereby can provide some guidance for clinical trials.
Mobilising context as complex and dynamic in evaluations of complex health interventions
Authors: Murdoch Jamie , Paparini Sara , Papoutsi Chrysanthi , James Hannah , Greenhalgh Trisha , Shaw Sara E. 
Published: December 2023

Abstract
Background
The relationship between healthcare interventions and context is widely conceived as involving complex and dynamic interactions over time. However, evaluations of complex health interventions frequently fail to mobilise such complexity, reporting context and interventions as reified and demarcated categories. This raises questions about practices shaping knowledge about context, with implications for who and what we make visible in our research. Viewed through the lens of case study research, we draw on data collected for the Triple C study (focused on Case study, Context and Complex interventions), to critique these practices, and call for system-wide changes in how notions of context are operationalised in evaluations of complex health interventions.

Methods
The Triple C study was funded by the Medical Research Council to develop case study guidance and reporting principles taking account of context and complexity. As part of this study, a one-day workshop with 58 participants and nine interviews were conducted with those involved in researching, evaluating, publishing, funding and developing policy and practice from case study research. Discussions focused on how to conceptualise and operationalise context within case study evaluations of complex health interventions. Analysis focused on different constructions and connections of context in relation to complex interventions and the wider social forces structuring participant’s accounts.

Results
We found knowledge-making practices about context shaped by epistemic and political forces, manifesting as: tensions between articulating complexity and clarity of description; ontological (in)coherence between conceptualisations of context and methods used; and reified versions of context being privileged when communicating with funders, journals, policymakers and publics.

Conclusion
We argue that evaluations of complex health interventions urgently requires wide-scale critical reflection on how context is mobilised - by funders, health services researchers, journal editors and policymakers. Connecting with how scholars approach complexity and context across disciplines provides opportunities for creatively expanding the field in which health evaluations are conducted, enabling a critical standpoint to long-established traditions and opening up possibilities for innovating the design of evaluations of complex health interventions.
A secreted form of chorismate mutase (Rv1885c) in Mycobacterium bovis BCG contributes to pathogenesis by inhibiting mitochondria-mediated apoptotic cell death of macrophages
Authors: Lee Mi-Hyun , Kim Hye Lin , Seo Hyejun , Jung Sangkwon , Kim Bum-Joon 
Published: December 2023

Abstract
Background
Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), and its pathogenicity is associated with its ability to evade the host defense system. The secretory form of the chorismate mutase of M. tuberculosis (TBCM, encoded by Rv1885c) is assumed to play a key role in the pathogenesis of TB; however, the mechanism remains unknown.

Methods
A tbcm deletion mutant (B∆tbcm) was generated by targeted gene knockout in BCG to investigate the pathogenic role of TBCM in mice or macrophages. We compared the pathogenesis of B∆tbcm and wild-type BCG in vivo by measuring the bacterial clearance rate and the degree of apoptosis. Promotion of the intrinsic apoptotic pathway was evaluated in infected bone marrow-derived macrophages (BMDMs) by measuring apoptotic cell death, loss of mitochondrial membrane potential and translocation of pore-forming proteins. Immunocytochemistry, western blotting and real-time PCR were also performed to assess the related protein expression levels after infection. Furthermore, these findings were validated by complementation of tbcm in BCG.

Results
Deletion of the tbcm gene in BCG leads to reduced pathogenesis in a mouse model, compared to wild type BCG, by promoting apoptotic cell death and bacterial clearance. Based on these findings, we found that intrinsic apoptosis and mitochondrial impairment were promoted in B∆tbcm-infected BMDMs. B∆tbcm down-regulates the expression of Bcl-2, which leads to mitochondrial outer membrane permeabilization (MOMP), culminating in cytochrome c release from mitochondria. Consistent with this, transcriptome profiling also indicated that B∆tbcm infection is more closely related to altered mitochondrial-related gene expression than wild-type BCG infection, suggesting an inhibitory role of TBCM in mitochondrial dysfunction. Moreover, genetic complementation of B∆tbcm (C∆tbcm) restored its capacity to inhibit mitochondria-mediated apoptotic cell death.

Conclusions
Our findings demonstrate the contribution of TBCM to bacterial survival, inhibiting intrinsic apoptotic cell death of macrophages as a virulence factor of M. tuberculosis complex (MTBC) strains, which could be a potential target for the development of TB therapy.
Human super antibody to viral RNA-dependent RNA polymerase produced by a modified Sortase self-cleave-bacteria surface display system
Authors: Glab-ampai Kantaphon , Mahasongkram Kodchakorn , Chulanetra Monrat , Saenlom Thanatsaran , Thueng-in Kanyarat , Sookrung Nitat , Chaicumpa Wanpen 
Published: December 2023

Abstract
Background
RNA-dependent RNA polymerase (RdRp) is a good target of anti-RNA virus agents; not only it is pivotal for the RNA virus replication cycle and highly conserved among RNA viruses across different families, but also lacks human homolog. Recently, human single-chain antibody (HuscFv) that bound to thumb domain of hepatitis C virus (HCV) RNA-dependent RNA polymerase (functionalized NS5B protein) was produced and engineered into cell-penetrating antibody (super antibody) in the form of cell-penetrating peptide (penetratin, PEN)-linked HuscFv (PEN-HuscFv34). The super antibody was produced and purified from inclusion body (IB) of a pen-huscfv34-vector-transformed Escherichia coli. The super antibody inhibited replication of alpha- and beta- coronaviruses, flaviviruses, and picornaviruses that were tested (broadly effective); thus, it has high potential for developing further towards a pan-anti-RNA virus agent. However, production, purification, and refolding of the super antibody molecules from the bacterial IB are laborious and hurdles to large-scale production. Therefore, in this study, Sortase-self-cleave method and bacteria surface display system were combined and modified for the super antibody production.

Methods and results
BL21 (DE3) ΔA E. coli, a strain lacking predominant outer membrane protein (OmpA) and ion and OmpT proteases, that displayed a membrane-anchored fusion protein, i.e., chimeric lipoprotein (Lpp′)-OmpA′, SUMO, Sortase protease, Sortase cleavage site (LPET↓G) and PEN-HuscFv34-6× His was generated. The soluble PEN-HuscFv34-6× His with glycine at the N-terminus could be released from the E. coli surface, simply by incubating the bacterial cells in a Sortase-cleavage buffer. After centrifugation, the G-PEN-HuscFv34-6× His could be purified from the supernatant. The purified G-PEN-HuscFv34-6× retained original cell-penetrating ability (being super antibody) and the broadly effective anti-RNA virus activity of the original IB-derived-PEN-HuscFv34.

Conclusion
The functionalized super antibody to RNA virus RdRp was successfully produced by using combined Sortase self-cleave and bacterial surface display systems with modification. The display system is suitable for downstream processing in a large-scale production of the super antibody. It is applicable also for production of other recombinant proteins in soluble free-folding form.
Clinical applications and utility of ctDNA in cervical cancer and its precursor lesions: from screening to predictive biomarker
Authors: Li Li , Tong Yixin , Wu Jianhong , Xu Xiangshang 
Published: December 2023

AbstractCervical cancer is a leading cause of gynecological cancer death in the world. Human papillomavirus (HPV) is the most causative factor of cervical cancer. In addition, many genetic factors are involved in cervical cancer development. Most studies focus on cervical samples to do research work about cervical cancer and precancerous lesions, but no sensitive or specific biomarkers were found. High-throughput genomic technologies are able to capture information from tumors and precancerous lesions in blood, thus providing a new way for the early diagnosis of cervical precancer and cervical cancer. Blood is an ideal specimen for detecting cancer biomarkers because it contains a lot of information, such as circulating tumor cells and circulating tumor DNA (ctDNA). This article reviews the clinical use and challenges of blood ctDNA testing in patients with cervical precancer and cervical cancer.
Utilising quantitative methods to study the intersectionality of multiple social disadvantages in women with common mental disorders: a systematic review
Authors: Alghamdi Nadia Alhamd , Dunn Kirsty , Cairns Deborah , Melville Craig 
Published: December 2023

AbstractWomen are at greater risk of common mental disorders. The intersectionality concept provides a framework to examine the effects of multiple social disadvantages on women’s mental health. We conducted a systematic review to collect and analyse information to identify the quantitative methodologies and study designs used in intersectional research to examine women’s mental health and multiple social disadvantages. Included studies used accepted statistical methods to explore the intersectional effects of gender and one or more types of social disadvantage from the PROGRESS-Plus inequity framework: a place of residence, race/ethnicity, occupation, gender/ sex, religion, education, socioeconomic status, social capital (O’Neill et al. J Clin Epidemiol 67:56–64, 2014). The scope of this systematic review was limited to studies that analysed common mental disorders in women and men comparatively. Studies focusing on only one gender were excluded, ensuring a comprehensive comparative analysis of the intersection of social disadvantages in mental health.Twelve papers were included in the narrative synthesis (Table 1). Eight of the included papers (67%) reported an intersectional effect of gender and one or more additional types of social disadvantage. The multiplicative effect of gender and socioeconomic status on the risk of common mental disorders was the most commonly reported interaction. This systematic review shows that multiplicative and simultaneous interactions of multiple social disadvantage increase the risk of common mental disorders experienced by women. Moreover, it underlines the potential for quantitative research methods to complement qualitative intersectionality research on gender and mental health. The findings of this systematic review highlight the importance of multiple social disadvantage in understanding the increased risk of mental health experienced by women.
Biodegradable nano black phosphorus based SDF1-α delivery system ameliorates Erectile Dysfunction in a cavernous nerve injury rat model by recruiting endogenous stem/progenitor cells
Authors: Fu Qingfeng , Song Lujie , Li Jitao , Yi Bocun , Huang Yue , Zhang Zhihong , Xin Zhongcheng , Zhu Jianqiang 
Published: December 2023

AbstractStem cell (SC) therapy has been shown high prospects in erectile dysfunction (ED) treatment. Without ethical issues and risks of immune rejection and tumorigenesis of exogenous SC therapy, endogenous stem/progenitor cells (S/PCs) have a better potential for ED management, and their homing and redistribution are controlled by SDF1-α/CXCR4 axis. Considering black phosphorus nanosheet (BPNS) has emerged as an efficient and safe drug vehicle due to its large surface area, biodegradability, and the ability to retain and slowly release its loaded drugs, BPNS is utilized to load SDF1-α, a chemokine for S/PCs, to construct the BP@SDF1-α complex to efficiently recruit stem cells (SCs) by injury-site injection and thus ameliorate ED within the bilateral cavernous nerve injury (BCNI) rat models. We find that BP@SDF1-α can efficiently recruit exogenous SCs and endogenous S/PCs to corpus cavernosum and main pelvic ganglion (MPG) by local administration. Of note, ascribing to endogenous S/PCs recruitment, it also successfully alleviates ED in BCNI rat models by enhancing the protein expression levels of α-SMA, CD31, and nNOs, and eliciting less collagen deposition in the penis after its combined injection at corpus cavernosum and MPG. Thus, this study provides a new insight into the treatment of ED with endogenous S/PCs.
Biodegradable Nano Black Phosphorus based SDF1-α delivery system ameliorates Erectile Dysfunction in a cavernous nerve Injury Rat Model by recruiting endogenous Stem/Progenitor cells
Living evidence and adaptive policy: perfect partners?
Authors: Turner Tari , Lavis John N. , Grimshaw Jeremy M. , Green Sally , Elliott Julian 
Published: December 2023

Abstract
Background
While there has been widespread global acceptance of the importance of evidence-informed policy, many opportunities to inform health policy with research are missed, often because of a mismatch between when and where reliable evidence is needed, and when and where it is available. ‘Living evidence’ is an approach where systematic evidence syntheses (e.g. living reviews, living guidelines, living policy briefs, etc.) are continually updated to incorporate new relevant evidence as it becomes available. Living evidence approaches have the potential to overcome a major barrier to evidence-informed policy, making up-to-date systematic summaries of policy-relevant research available at any time that policy-makers need them. These approaches are likely to be particularly beneficial given increasing calls for policy that is responsive, and rapidly adaptive to changes in the policy context.
We describe the opportunities presented by living evidence for evidence-informed policy-making and highlight areas for further exploration.

Discussion
There are several elements of living approaches to evidence synthesis that might support increased and improved use of evidence to inform policy. Reviews are explicitly prioritised to be ‘living’ by partnerships between policy-makers and researchers based on relevance to decision-making, as well as uncertainty of existing evidence, and likelihood that new evidence will arise. The ongoing nature of the work means evidence synthesis teams can be dynamic and engage with policy-makers in a variety of ways over time; and synthesis topics, questions and methods can be adapted as policy interests or contextual factors shift. Policy-makers can sign-up to be notified when relevant new evidence is found, and can be confident that living syntheses are up-to-date and contain all research whenever they access them. The always up-to-date nature of living evidence syntheses means producers can rapidly demonstrate availability of relevant, reliable evidence when it is needed, addressing a frequently cited barrier to evidence-informed policymaking.

Conclusions
While there are challenges to be overcome, living evidence provides opportunities to enable policy-makers to access up-to-date evidence whenever they need it and also enable researchers to respond to the issues of the day with up-to-date research; and update policy-makers on changes in the evidence base as they arise. It also provides an opportunity to build flexible partnerships between researchers and policy-makers to ensure that evidence syntheses reflect the changing needs of policy-makers.
Integrated plasma metabolomics and lipidomics profiling highlights distinctive signature of hepatocellular carcinoma in HCV patients
Authors: Caponigro Vicky , Tornesello Anna L. , Merciai Fabrizio , La Gioia Danila , Salviati Emanuela , Basilicata Manuela G. , Musella Simona , Izzo Francesco , Megna Angelo S. , Buonaguro Luigi , Sommella Eduardo , Buonaguro Franco M. , Tornesello Maria L. , Campiglia Pietro 
Published: December 2023

Abstract
Background
Early diagnosis of hepatocellular carcinoma (HCC) is essential towards the improvement of prognosis and patient survival. Circulating markers such as α-fetoprotein (AFP) and micro-RNAs represent useful tools but still have limitations. Identifying new markers can be fundamental to improve both diagnosis and prognosis. In this approach, we harness the potential of metabolomics and lipidomics to uncover potential signatures of HCC.

Methods
A combined untargeted metabolomics and lipidomics plasma profiling of 102 HCV-positive patients was performed by HILIC and RP-UHPLC coupled to Mass Spectrometry. Biochemical parameters of liver function (AST, ALT, GGT) and liver cancer biomarkers (AFP, CA19.9 e CEA) were evaluated by standard assays.

Results
HCC was characterized by an elevation of short and long-chain acylcarnitines, asymmetric dimethylarginine, methylguanine, isoleucylproline and a global reduction of lysophosphatidylcholines. A supervised PLS-DA model showed that the predictive accuracy for HCC class of metabolomics and lipidomics was superior to AFP for the test set (100.00% and 94.40% vs 55.00%). Additionally, the model was applied to HCC patients with AFP values < 20 ng/mL, and, by using only the top 20 variables selected by VIP scores achieved an Area Under Curve (AUC) performance of 0.94.

Conclusion
These exploratory findings highlight how metabo-lipidomics enables the distinction of HCC from chronic HCV conditions. The identified biomarkers have high diagnostic potential and could represent a viable tool to support and assist in HCC diagnosis, including AFP-negative patients.

Graphical abstract
Outcomes of carbon ion radiotherapy compared with segmentectomy for ground glass opacity-dominant early-stage lung cancer
Authors: Mizobuchi Teruaki , Nomoto Akihiro , Wada Hironobu , Yamamoto Naoyoshi , Nakajima Mio , Fujisawa Takehiko , Suzuki Hidemi , Yoshino Ichiro 
Published: December 2023

Abstract
Purpose
This study aimed to compare the outcomes of patients with ground-grass opacity (GGO)-dominant non-small cell lung cancer (NSCLC) who were treated with carbon ion radiotherapy (CIRT) versus segmentectomy.

Methods
A retrospective review of medical records was conducted. The study included 123 cases of clinical stage 0/IA peripheral NSCLC treated with single-fraction CIRT from 2003 to 2012, 14 of which were determined to be GGO-dominant and were assigned to CIRT group. As a control, 48 consecutive patients who underwent segmentectomy for peripheral GGO-dominant clinical stage IA NSCLC were assigned to segmentectomy group.

Results
The patients in CIRT group, compared with segmentectomy group, were significantly older (75 ± 7.2 vs. 65 ± 8.2 years, P = 0.000660), more likely to be male (13/14 vs. 22/48, P = 0.00179), and had a lower forced vital capacity (91 ± 19% vs. 110 ± 13%, P = 0.0173). There was a significant difference in the 5-years overall survival rate (86% vs. 96%, P = 0.000860), but not in the 5-years disease-specific survival rate (93% vs. 98%, P = 0.368).

Discussion
Compared with segmentectomy, CIRT may be an alternative option for patients with early GGO-dominant NSCLC who are poor candidates for, or who refuse, surgery.