bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yangmo decoction versus hyaluronic acid gel in women with intrauterine re-adhesion after hysteroscopic adhesiolysis: a retrospective efficacy and safety analysis
Authors: Dan Jiaxin , Cao Yi 
Published: September 2023

Abstract
Background
Hysteroscopic adhesiolysis is the preferred primary method for intrauterine adhesion. However, there is about a 60% of chance of re-adhesion after surgery. The objectives of the study were to evaluate the efficacy and safety of Yangmo decoction as a secondary treatment in preventing intrauterine re-adhesion against those of hyaluronic acid gel.

Methods
Women received oral Yangmo decoction (YD cohort, n = 105) or intrauterine hyaluronic acid gel (HA cohort, n = 125) or did not receive secondary re-adhesion prevention treatments (EP cohort, n = 165) after hysteroscopic adhesiolysis for 6 months. In addition, all women have received 3 mg of oral estrogen and 20 mg oral progesterone combination after hysteroscopic adhesiolysis for 3 months. Intrauterine re-adhesion after hysteroscopic adhesiolysis after 6 months with or without secondary treatment(s) was detected using hysteroscopy. The extent of the cavity, type of adhesion, and the menstrual pattern were included to define the American Fertility Society classification of intrauterine re-adhesions (AFS) score.

Results
Fewer numbers of women suffered from intrauterine re-adhesion after hysteroscopic adhesiolysis in the YD cohort than those of the HA (15(14%) vs. 40(32%), p = 0.0019) and the EP (15(14%) vs. 58(35%). p = 0.0001) cohorts. Among women who developed intrauterine re-adhesion, AFS score was fewer for women of the YD cohort than those of HA (2(2–1) vs. 4(4–3), p < 0.001) and the EP (2(2–1) vs. 4(4–4), p < 0.001) cohorts. AFS score after surgery was fewer for women of the HA cohort than those of the EP cohort (p < 0.05). Higher numbers of women of the YD cohort retained pregnancies after 6-months of treatment than those of the HA (55(52%) vs. 45(36%), p = 0.0161) and EP (55(52%) vs. 35(21%), p < 0.0001) cohorts. Among women who develop re-adhesion, 10(10%) women of the YD cohort only had successful pregnancies.

Conclusions
Yangmo decoction for 6 months after hysteroscopic adhesiolysis can reduce AFS score, prevent intrauterine re-adhesion, and increases the chances of successful pregnancies of women.

Level of evidence
IV.

Technical Efficacy
Stage 5.
In vitro cytotoxic effect of stigmasterol derivatives against breast cancer cells
Authors: Dube Nondumiso Premilla , Tembu Vuyelwa Jacqueline , Nyemba Getrude R , Davison Candace , Rakodi Goitsemodimo Herckious , Kemboi Douglas , de la Mare Jo-Anne , Siwe-Noundou Xavier , Manicum Amanda-Lee Ezra 
Published: September 2023

Abstract
Background
Stigmasterol is an unsaturated phytosterol that belong to the class of tetracyclic steroids abundant in Rhoicissus tridentata. Stigmasterol is an important constituent since it has shown impressive pharmacological effects such as anti-osteoarthritis, anticancer, anti-diabetic, anti-inflammatory, antiparasitic, immunomodulatory, antifungal, antioxidant, antibacterial, and neuroprotective activities. Furthermore, due to the presence of π system and hydroxyl group, stigmasterol is readily derivatized through substitution and addition reactions, allowing for the synthesis of a wide variety of stigmasterol derivatives.

Methods
Stigmasterol (1) isolated from Rhoicissus tridentata was used as starting material to yield eight bio-active derivatives (2–9) through acetylation, epoxidation, epoxide ring opening, oxidation, and dihydroxylation reactions. The structures of all the compounds were established using spectroscopic techniques, NMR, IR, MS, and melting points. The synthesized stigmasterol derivatives were screened for cytotoxicity against the hormone receptor-positive breast cancer (MCF-7), triple-negative breast cancer (HCC70), and non-tumorigenic mammary epithelial (MCF-12 A) cell lines using the resazurin assay.

Results
Eight stigmasterol derivatives were successfully synthesized namely; Stigmasterol acetate (2), Stigmasta-5,22-dien-3,7-dione (3), 5,6-Epoxystigmast-22-en-3β-ol (4), 5,6-Epoxystigmasta-3β,22,23-triol (5), Stigmastane-3β,5,6,22,23-pentol (6), Stigmasta-5-en-3,7-dion-22,23-diol (7), Stigmasta-3,7-dion-5,6,22,23-ol (8) and Stigmast-5-ene-3β,22,23-triol (9). This is the first report of Stigmasta-5-en-3,7-dion-22,23-diol (7) and Stigmasta-3,7-dion-5,6,22,23-ol (8). The synthesized stigmasterol analogues showed improved cytotoxic activity overall compared to the stigmasterol (1), which was not toxic to the three cell lines tested (EC50 ˃ 250 µM). In particular, 5,6-Epoxystigmast-22-en-3β-ol (4) and stigmast-5-ene-3β,22,23-triol (9) displayed improved cytotoxicity and selectivity against MCF-7 breast cancer cells (EC50 values of 21.92 and 22.94 µM, respectively), while stigmastane-3β,5,6,22,23-pentol (6) showed improved cytotoxic activity against the HCC70 cell line (EC50: 16.82 µM).

Conclusion
Natural products from Rhoicissus tridentata and their derivatives exhibit a wide range of pharmacological activities, including anticancer activity. The results obtained from this study indicate that molecular modification of stigmasterol functional groups can generate structural analogues with improved anticancer activity. Stigmasterol derivatives have potential as candidates for novel anticancer drugs.
Planning ahead for research participation: survey of public and professional stakeholders’ views about the acceptability and feasibility of advance research planning
Authors: Shepherd Victoria , Hood Kerenza , Wood Fiona 
Published: September 2023

Abstract
Background
Anticipatory planning in the UK focuses on supporting people who anticipate periods of impaired capacity to express their wishes about future care through processes such as advance care planning. Other countries have extended anticipatory planning to include processes for people to prospectively express their preferences about research participation. Advance research planning (ARP) is thought to extend autonomy and ensure that ‘proxy’ decisions about research are based on their wishes and preferences.

Methods
A cross-sectional survey was conducted with two stakeholder groups (members of the public including people living with capacity-affecting conditions and family members; researchers and other professionals) who were recruited via research registries and other routes. Online questionnaires were used to capture the perspectives of the two groups. Responses were analysed using descriptive statistics and content analysis.

Results
A total of 327 participants (members of the public n = 277, professionals n = 50) completed the survey (November 2022 - March 2023). ARP was supported by 97% of public contributors and 94% of professionals. Participants thought that ARP should include the person’s general wishes about research, specific types of studies, and who should make decisions on their behalf. They identified a number of challenges, including how ARP could take account of changes in individuals’ preferences or circumstances whilst protecting their rights and interests. Implementation barriers included the potential time, complexity, and cost involved. These could be addressed by embedding ARP in existing anticipatory planning pathways and aligning it with other research enrolment activities. Relationships and trust played a key role, including underpinning who should support the delivery of ARP, how they are trained, and when it is undertaken.

Conclusions
There were high levels of support for introducing ARP in the UK. Further research should explore practical barriers and stakeholder concerns and identify any unintended consequences. Future activities should include developing ARP interventions alongside training and other resources, and also focus on public awareness campaigns, and engaging policymakers and other stakeholders.
Substantially more children receiving antidepressants see a specialist than reported by Jack et al.
Authors: Taxiarchi Vicky P. , Chew-Graham Carolyn A. , Pierce Matthias 
Published: September 2023

AbstractWe would like to draw attention to evidence of substantial bias in the article published in this journal by Jack et al. (BMC Med 18:1-12, 2020). They provide an analysis of antidepressant prescribing to children and young people (CYP; ages 5 to 17) in primary care in England and reported that only 24.7% of CYP prescribed SSRIs for the first time were seen by a child and adolescent psychiatrist—contrary to national guidelines. We believe that their analysis is based on incomplete data that misses a large proportion of specialist mental health contacts. This is because the dataset Jack et al. used to capture specialist mental health contact—The Hospital Episode Statistics (HES) dataset—has poor coverage, as most CYP mental health services do not submit data. We demonstrate the level of underreporting with an analysis of events in a large primary care dataset where there has been a record of definite contact with CYP mental health services. We report that as many as three quarters of specialist CYP contacts with mental health specialists are missed in the HES dataset, indicating that the figure presented by Jack et al. is substantially wrong.
Diagnostic yield of targeted next-generation sequencing for pediatric hereditary hemolytic anemia
Authors: Choi Yu Jeong , Kim Hongkyung , Ahn Won Kee , Lee Seung-Tae , Han Jung Woo , Choi Jong Rak , Lyu Chuhl Joo , Hahn Seungmin , Shin Saeam 
Published: September 2023

Abstract
Background
Hereditary hemolytic anemia (HHA) refers to a heterogeneous group of genetic disorders that share one common feature: destruction of circulating red blood cells (RBCs). The destruction of RBCs may be due to membranopathies, enzymopathies, or hemoglobinopathies. Because these are genetic disorders, incorporation of next-generation sequencing (NGS) has facilitated the diagnostic process of HHA.

Method
Genetic data from 29 patients with suspected hereditary anemia in a tertiary hospital were retrospectively reviewed to evaluate the efficacy of NGS on hereditary anemia diagnosis. Targeted NGS was performed with custom probes for 497 genes associated with hematologic disorders. After genomic DNA was extracted from peripheral blood, prepared libraries were hybridized with capture probes and sequenced using NextSeq 550Dx (Illumina, San Diego, CA, USA).

Result
Among the 29 patients, ANK1 variants were detected in five, four of which were pathogenic or likely pathogenic variants. SPTB variants were detected in six patients, five of which were classified as pathogenic or likely pathogenic variants. We detected g6pd pathogenic and spta1 likely pathogenic variants in two patients and one patient, respectively. Whole-gene deletions in both HBA1 and HBA2 were detected in two patients, while only HBA2 deletion was detected in one patient. One likely pathogenic variant in PLKR was detected in one patient, and one likely pathogenic variant in ALAS2 was detected in another.

Conclusion
Here, NGS played a critical role in definitive diagnosis in 18 out of 29 patients (62.07%) with suspected HHA. Thus, its incorporation into the diagnostic workflow is crucial.
Platelet-derived biomaterial with hyaluronic acid alleviates temporal-mandibular joint osteoarthritis: clinical trial from dish to human
Authors: Peng Bou-Yue , Singh Abhinay Kumar , Tsai Ching-Yu , Chan Chun-Hao , Deng Yue-Hua , Wu Chi-Ming , Chou Yen-Ru , Tsao Wen , Wu Chia-Yu , Deng Win-Ping 
Published: September 2023

Abstract
Background
Bioactive materials have now raised considerable attention for the treatment of osteoarthritis (OA), such as knee OA, rheumatoid OA, and temporomandibular joint (TMJ) OA. TMJ-OA is a common disease associated with an imbalance of cartilage regeneration, tissue inflammation, and disability in mouth movement. Recently, biological materials or molecules have been developed for TMJ-OA therapy; however, ideal treatment is still lacking. In this study, we used the combination of a human platelet rich plasma with hyaluronic acid (hPRP/HA) for TMJ-OA therapy to perform a clinical trial in dish to humans.

Method
Herein, hPRP was prepared, and the hPRP/HA combined concentration was optimized by MTT assay. For the clinical trial in dish, pro-inflammatory-induced in-vitro and in-vivo mimic 3D TMJ-OA models were created, and proliferation, gene expression, alcian blue staining, and IHC were used to evaluate chondrocyte regeneration. For the animal studies, complete Freund’s adjuvant (CFA) was used to induce the TMJ-OA rat model, and condyle and disc regeneration were investigated through MRI. For the clinical trial in humans, 12 patients with TMJ-OA who had disc displacement and pain were enrolled. The disc displacement and pain at baseline and six months were measured by MRI, and clinical assessment, respectively.

Results
Combined hPRP/HA treatment ameliorated the proinflammatory-induced TMJ-OA model and promoted chondrocyte proliferation by activating SOX9, collagen type I/II, and aggrecan. TMJ-OA pathology–related inflammatory factors were efficiently downregulated with hPRP/HA treatment. Moreover, condylar cartilage was regenerated by hPRP/HA treatment in a proinflammatory-induced 3D neocartilage TMJ-OA-like model. During the animal studies, hPRP/HA treatment strongly repaired the condyle and disc in a CFA-induced TMJ-OA rat model. Furthermore, we performed a clinical trial in humans, and the MRI data demonstrated that after 6 months of treatment, hPRP/HA regenerated the condylar cartilage, reduced disc displacement, alleviated pain, and increased the maximum mouth opening (MMO). Overall, clinical trials in dish to human results revealed that hPRP/HA promoted cartilage regeneration, inhibited inflammation, reduced pain, and increased joint function in TMJ-OA.

Conclusion
Conclusively, this study highlighted the therapeutic potential of the hPRP and HA combination for TMJ-OA therapy, with detailed evidence from bench to bedside.
Trial registration Taipei Medical University Hospital (TMU-JIRB No. N201711041). Registered 24 November 2017. https://tmujcrc.tmu.edu.tw/inquiry_general.php.
Anti-malarial activity of the alkaloid, heptaphylline, and the furanocoumarin, imperatorin, from Clausena anisata against human Plasmodium falciparum malaria parasites: ex vivo trophozoitocidal, schizonticidal and gametocytocidal approach
Authors: Kumatia Emmanuel Kofi , Zoiku Felix Kwame , Asase Alex , Tung Nguyen Huu 
Published: September 2023

Abstract
Background
The erythrocytic stage of the life cycle of the malaria parasite, Plasmodium falciparum, consists of trophozoite, schizont and gametocyte stages in humans. Various anti-malarial agents target different stages of the parasite to produce treatment outcomes. This study reports on the stage-specific anti-malarial activity of heptaphylline and imperatorin against human P. falciparum in addition to their cytotoxicity and selectivity indices (SI).

Methods
The compounds were isolated from Clausena anisata using column chromatography and their structures elucidated using NMR spectroscopy. The anti-malarial activity was determined by measuring the trophozoitocidal, schizonticidal and gametocytocidal activities of the compounds using the SYBR green assay. Cytotoxicity was evaluated using the tetrazolium-based colorimetric assay.

Results
Heptaphylline and imperatorin produced trophozoitocidal, schizonticidal and gametocytocidal activities with IC50s of 1.57 (0.2317)–26.92 (0.3144) µM with those of artesunate (the standard drug) being 0.00024 (0.0036)–0.0070 (0.0013) µM. In the cytotoxicity assay, the compounds produced CC50S greater than 350 µM and SI of 13.76–235.90. Also, the trophozoitocidal and schizonticidal activities of the compounds were more pronounced than their gametocytocidal activity. Imperatorin was 42.04% more trophozoitocidal than hepthaphyline. However, hepthaphyline has more schizonticidal and gametocytocidal properties than imperatorin.

Conclusion
Heptaphylline and imperatorin are promising anti-malarial agents, since they possess potent anti-malarial activity with weak cytotoxicity on RBCs. However, imperatorin is a better anti-malarial prophylactic agent whereas heptaphylline is a better malaria treatment agent.
Mediators of parental educational differences in the intake of carbonated sugar-sweetened soft drinks among adolescents, and the moderating role of neighbourhood income
Authors: Mekonnen Teferi , Papadopoulou Eleni , Lien Nanna , Andersen Lene F. , Pinho Maria Gabriela Matias , Havdal Hanne Hennig , Andersen Oddbjørn Klomsten , Gebremariam Mekdes K. 
Published: September 2023

Abstract
Background
Existing evidence suggests that the intake of sugar-sweetened beverages (SSB) among adolescents remains a public health concern and that socioeconomic differences in intake exist. Tackling these challenges requires identifying the factors associated with SSB intake and the mediators of socioeconomic differences in SSB intake among adolescents. Thus, this study aimed to explore (i) factors at different levels of the ecological model associated with the intake of carbonated soft drinks with added sugar (hereafter called soft drinks), (ii) mediators of the association between parental education and the intake of soft drinks(iii) whether neighbourhood income moderates the indirect effect of parental education on adolescents’ soft drink intake through potential mediators.

Methods
Data from 826 7th graders in Oslo, Norway, who participated in the TACKLE cross-sectional study conducted in 2020 were used. The association between factors at the individual, interpersonal and neighbourhood food environment levels and the intake of soft drinks among adolescents was assessed, as well as the mediating roles of these factors for the differences in intake by parental education, using multiple logistic regression and mediation analysis, respectively. Moderated mediation analyses were used to explore whether an indirect effect of parental education on adolescents' soft drink intake through potential mediators varies across neighbourhood income areas.

Results
Higher perceived accessibility of SSB at home, increased parental modelling for SSB intake, and increased frequency of food/drink purchased from the neighbourhood store were associated with a higher intake of soft drinks among adolescents and mediated the differences in intake by parental education. Neighbourhood food environment factors were neither statistically significantly associated with adolescents’ higher intake of soft drinks nor explained the differences in intake by parental education. Moderated mediation analysis showed that the mediating effect of perceived accessibility of SSB at home on the association between parental education and adolescent soft drink intake was stronger among those living in low neighbourhood income.

Conclusions
Our study identified modifiable factors at the intrapersonal level (perceived accessibility of SSB at home and frequency of food/drink purchased from neighbourhood shops) and interpersonal levels (parental modelling for SSB intake) associated with a higher intake of soft drinks among adolescents and mediated the differences in the intake by parental education. The modifiable factors identified in this study could be targeted in public health initiatives among adolescents aimed at reducing the intake of soft drinks and the related differences by parental education.
Meta analysis of the diagnostic value of circulating miRNA in benign and malignant pulmonary nodules
Authors: Hong Ziqiang , Cui Baiqiang , Bai Xiangdou , Li Hongchao , Cheng Tao , Sheng Yannan , Lu Yingjie , Wu Xusheng , Jin Dacheng , Zhao Jing , Gou Yunjiu 
Published: September 2023

Abstract
Objective
A meta-analysis was conducted to assess the impact of miRNAs in circulation on diagnosing benign and malignant pulmonary nodules (BPNs and MPNs).

Methods
Electronic databases such as Embase, PubMed, Web of Science, and The Cochrane Library were utilized for diagnostic tests of circulating miRNAs to diagnose BPNs and MPNs from the library creation to February 2023. Meta-analysis of the included literature was performed using Stata 16, Meta-Disc 1.4, and Review Manager 5.4 software. This study determined the combined sensitivity, specificity, diagnostic ratio (DOR), positive/negative likelihood ratios (PLR/NLR), as well as value of area under the receiver operating characteristic (ROC) curve.

Results
This meta-analysis included 14 publications and 17 studies. According to our findings, the pooled sensitivity for miRNA in diagnosing benign and malignant pulmonary nodules was 0.82 [95% CI (0.74, 0.88)], specificity was 0.84 [95% CI (0.79, 0.88)], whereas the DOR was 22.69 [95% CI (13.87, 37.13)], PLR was 5.00 [95% CI (3.87, 6.46)], NLR was 0.22 [95% CI (0.15, 0.32)], and the area under the working characteristic curve (AUC) of the subject was 0.89 [95% CI (0.86, 0.91)].

Conclusion
Circulating miRNAs could be used with sensitivity, specificity, DOR, PLR, NLR, and AUC as biomarkers to diagnose pulmonary nodules (PNs). However, more research is needed to determine the optimum miRNA combinations for diagnosing PNs due to the significant heterogeneity on previous studies.
Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer
Authors: Wang Zhen Zhen , Wen Xiao Ling , Wang Na , Li Xu Hua , Guo Yu , Zhu Xu , Fu Shu Heng , Xiong Fei Fan , Li Jin , Wang Limei , Gao Xiao Ling , Wang Hong Jiu 
Published: September 2023

Abstract
Background
IFN-λ has been shown to have a dual function in cancer, with its tumor-suppressive roles being well-established. However, the potential existence of a negative ‘‘tumor-promoting’’ effect of endogenous IFN-λ is still not fully understood.

Methods
We conducted a comprehensive review and analysis of the perturbation of IFN-λ genes across various cancer types. Correlation coefficients were utilized to examine the relationship between endogenous IFN-λ expression and clinical factors, immune cell infiltration, tumor microenvironment, and response to immunotherapy. Genes working together with IFN-λ were obtained by constructing the correlation-based network related to IFN-λ and the gene interaction network in the KEGG pathway and IFN-λ-related genes obtained from the networks were integrated as candidate markers for the prognosis model. We then applied univariate and multivariate COX regression models to select cancer-specific independent prognostic markers associated with IFN-λ and to investigate risk factors for these genes by survival analysis. Additionally, computational methods were used to analyze the transcriptome, copy number variations, genetic mutations, and methylation of IFN-λ-related patient groups.

Result
Endogenous expression of IFN-λ has been linked to poor prognosis in cancer patients, with the genes IFN-λ2 and IFN-λ3 serving as independent prognostic markers. IFN-λ acts in conjunction with related genes such as STAT1, STAT2, and STAT3 to affect the JAK-STAT signaling pathway, which promotes tumor progression. Abnormalities in IFN-λ genes are associated with changes in immune checkpoints and immune cell infiltration, which in turn affects cancer- and immune-related pathways. While there is increased immune cell infiltration in patients with IFN-λ expression, this does not improve survival prognosis, as T-cell dysfunction and an inflammatory environment are also present. The amplification of IFNL2 and IFNL3 copy number variants drives specific endogenous expression of IFN-λ in patients, and those with this specific expression have been found to have more mutations in the TP53 gene and lower levels of DNA methylation.

Conclusion
Our study integrated multi-omics data to provide a comprehensive insight into the dark side of endogenous IFN-λ, providing a fundamental resource for further discovery and therapeutic exploration in cancer.