bluuebunny/crossref_metadata_2025 huggingface dataset:
A cross-sectional study on resilience, anxiety, depression, and psychoactive substance use among heterosexual and sexual minority adolescents in Nigeria
Authors: Ibigbami Olanrewaju Ibikunle , Oginni Olakunle Ayokunmi , Bradley Cory , Lusher Joanne , Sam-Agudu Nadia Adjoa , Folayan Morenike Oluwatoyin
Published: September 2023

Background

Mental health-related problems predispose alcohol and other psychoactive substances use as coping strategies. We assessed associations between resilience and anxiety symptoms, depressive symptoms, problematic alcohol, and multiple psychoactive substance use among sexual minority and heterosexual adolescents in Nigeria.

Methods

This was a secondary analysis of a subset of data generated through an online cross-sectional study conducted between 16thand 31stof October 2020. Data extracted for adolescents in Nigeria age 13–19 years were: dependent variables (alcohol use using the CAGE test, multiple psychoactive substance use, depressive symptoms using the Patient Health Questionnaire-9, and anxiety symptoms using the Generalized Anxiety Disorder-7 measure); independent variables (resilience using the Connor-Davidson resilience scale and sexual identity), and confounding factors (age and sex). Associations between dependent and independent variables were determined using multivariable logistic regression analyses after controlling for confounders.

Results

Of the 1419 adolescent participants, 593 (42%) were sexual minority individuals, 533 (37.6%) had high depressive symptoms, 381 (26.8%) had high anxiety symptoms, 177 (12.5%) had problematic alcohol use and 389 (27.4%) used multiple psychoactive substances. Resilience was significantly associated with lower odds of anxiety (AOR:0.96, 95% CI: 0.94–0.97,p < 0.001) and depressive (AOR:0.94, 95% CI: 0.92–0.96,p < 0.001) symptoms, problematic alcohol use (AOR:0.97, 95% CI: 0.95–0.99,p = 0.002), and multiple psychoactive substance use (AOR:0.95, 95% CI: 0.93–0.96,p < 0.001). Sexual minority adolescents had significantly higher odds of anxiety (AOR:4.14, 95% CI: 3.16–5.40,p < 0.001) and depressive symptoms (AOR:4.79; 95% CI: 3.73–6.15,p < 0.001), problematic alcohol use (AOR:2.48, 95% CI: 1.76–3.49,p < 0.001), and multiple psychoactive substance use (AOR:5.69, 95% CI: 4.34–7.47,p < 0.001).

Conclusion

Sexual minority adolescents and adolescents with low resilience have a higher need for interventions to reduce the risk of anxiety, depression, and the use of alcohol and other psychoactive substances.
The causal relationship between thyroid function, autoimune thyroid dysfunction and lung cancer: a mendelian randomization study
Authors: Wang Xinhui , Liu Xue , Li Yuchen , Tang Mulin , Meng Xue , Chai Yuwei , Zhang Li , Zhang Haiqing
Published: September 2023

Background

The role of thyroid hormones in cancers has been discussed in observational studies; however, the causal relationship between them remains controversial.

Methods

The SNPs associated with hypothyroidism and hyperthyroidism were selected from a FinnGen biobank of 342,499 (190,879 females and 151,620 males) Finnish adult subjects. Data from the Thyroidomics Consortium on 72,167 individuals were used to assess genetically determined thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Lung cancer, lung adenocarcinoma and squamous cell lung cancer GWAS data from the International Lung Cancer Consortium(ILCCO). Six different Mendelian randomization (MR) Methods, including Inverse variance weighted (IVW), MR-Egger, Simple mode, MR-Pleiotropy Residual Sum and Outlier methods (MR-PRESSO), Weighted mode and Weighted median were used to Two-Sample MR analysis. IVW was used as the primary estimate. Sensitivity analyses were examined via four aspects (Cochran’s Q-test, MR Egger intercept analysis, Funnel plot and Leave-one-out sensitivity test).

Results

The OR of hypothyroidism on lung cancer was 0.918 (95% CI, 0.859–0.982; p = 0.013) in MR analysis with IVW method. No evidence for effects of hyperthyroidism, TSH and FT4 on lung cancer risk was found via six MR methods. Meanwhile, there was no evidence for effects of lung cancer on hypothyroidism through six MR methods. Lung adenocarcinoma and squamous cell lung carcinoma were further analyzed on the basis of lung cancer. The OR of hypothyroidism on lung adenocarcinoma was 0.893(95% CI, 0.813–0.981; p = 0.019), the OR of hypothyroidism on squamous cell lung cancer was 0.888(95%CI,0.797–0.990, p = 0.032) in MR analysis with IVW method.

Conclusion

In summary, hypothyroidism genetically had a protective causal association with lung cancer. Furthermore, hypothyroidism had protective effects both on lung adenocarcinoma and squamous cell lung cancer. Further work is needed to elucidate the potential mechanisms.
Neoadjuvant chemotherapy weakens the prognostic value of the pathological tumor burden score for colorectal cancer liver metastases
Authors: Liao Leen , Sun Hui , He Jiahua , Liu Yujun , Pan Zhizhong , Wu Xiaojun , Fan Wenhua , Peng Jianhong , Li Cong
Published: September 2023

Background

The pathological tumor burden score (TBS) has been proven to be a better risk stratification tool for liver metastasis of colorectal cancer than the traditional clinical risk score (CRS). The aim of this study was to evaluate the prognostic value of the pathological tumor burden score in patients with or without neoadjuvant chemotherapy (NAC).

Methods

A total of 348 patients with colorectal liver metastases (CRLM) who underwent curative hepatic resection were retrospectively enrolled from September 1999 to December 2016. Univariable and multivariable Cox regression analyses were conducted to identify the independent predictors of prognosis. Kaplan–Meier curves and log-rank tests were used to determine whether TBS has enough discriminatory ability under certain grouping.

Results

Patients who received NAC had a higher median TBS than patients who did not receive NAC (4.07 vs. 2.69, P < 0.001). Among patients who did not receive NAC, those with TBS > 3 showed a significantly worse 3-year RFS (41.1% vs. 63.6%, P < 0.001) and 3-year OS rate (73.3% vs. 84.1%, P = 0.003) than those with TBS ≤ 3. Among the patients who received NAC, those with TBS ≤ 3 or TBS > 3 showed comparable 3-year RFS (33.3% vs. 26.4%, P = 0.400) and 3-year OS rates (76.5% vs. 58.2%, P = 0.064) to those who did not. Regardless of the regimen and response to NAC, there was no significant difference about 3-year RFS and 3-year OS rates between the TBS ≤ 3 and TBS > 3 groups.

Conclusion

Pathological TBS can be applied to predict the RFS and OS of patients suffering from CRLM who did not receive NAC. However, pathological TBS might not be regard as prognosis in patients who did receive NAC.
“I didn’t know it was going to be like this.”: unprepared for end-of-Life care, the experiences of care aides care in long-term care
Authors: Booi Laura , Sixsmith Judith , Chaudhury Habib , O’connor Deborah , Surr Claire , Young Melanie , Sixsmith Andrew
Published: September 2023

Background

Care aides provide up to 70–90% of the direct care for residents in long-term care (LTC) and thus hold great potential in improving residents’ quality of life and end-of-life (EoL) care experiences. Although the scope and necessity of the care aide role is predicted to increase in the future, there is a lack of understanding around their perceptions and experiences of delivering EoL care in LTC settings. The aim of this study was to gain an understanding of the perspectives, experiences, and working conditions of care aides delivering end-of-life care in LTC in a rural setting, within a high-income country.

Methods

Data were collected over ten months of fieldwork at one long-term care home in western Canada; semi-structured interviews (70 h) with 31 care aides; and observation (170 h). Data were analysed using Reflexive Thematic Analysis.

Results

Two themes were identified: (i) the emotional toll that delivering this care takes on the care aids and; (ii) the need for healing and support among this workforce. Findings show that the vast majority of care aides reported feeling unprepared for the delivery of the complex care work required for good EoL care. Findings indicate that there are no adequate resources available for care aides’ to support the mental and emotional aspects of their role in the delivery of EoL care in LTC. Participants shared unique stories of their own self-care traditions to support their grief, processing and emotional healing.

Conclusions

To facilitate the health and well-being of this essential workforce internationally, care aides need to have appropriate training and preparation for the complex care work required for good EoL care. It is essential that mechanisms in LTC become mandatory to support care aides’ mental health and emotional well-being in this role. Implications for practice highlight the need for greater care and attention played on the part of the educational settings during their selection and acceptance process to train care aides to ensure they have previous experience and societal awareness of what care in LTC settings entails, especially regarding EoL experiences.
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

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

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

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

We 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

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

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

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

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

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

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.
Metastasis organotropism in colorectal cancer: advancing toward innovative therapies
Authors: He Kai , Wang Zhihan , Luo Maochao , Li Bowen , Ding Ning , Li Lei , He Bo , Wang Han , Cao Jiangjun , Huang Canhua , Yang Jun , Chen Hai-Ning
Published: September 2023

Distant metastasis remains a leading cause of mortality among patients with colorectal cancer (CRC). Organotropism, referring to the propensity of metastasis to target specific organs, is a well-documented phenomenon in CRC, with the liver, lungs, and peritoneum being preferred sites. Prior to establishing premetastatic niches within host organs, CRC cells secrete substances that promote metastatic organotropism. Given the pivotal role of organotropism in CRC metastasis, a comprehensive understanding of its molecular underpinnings is crucial for biomarker-based diagnosis, innovative treatment development, and ultimately, improved patient outcomes. In this review, we focus on metabolic reprogramming, tumor-derived exosomes, the immune system, and cancer cell-organ interactions to outline the molecular mechanisms of CRC organotropic metastasis. Furthermore, we consider the prospect of targeting metastatic organotropism for CRC therapy.
Vibrational spectroscopy identifies myocardial chemical modifications in heart failure with preserved ejection fraction
Authors: Pioppi Leonardo , Parvan Reza , Samrend Alan , Silva Gustavo Jose Justo , Paolantoni Marco , Sassi Paola , Cataliotti Alessandro
Published: September 2023

Background

Vibrational spectroscopy can be a valuable tool to monitor the markers of cardiovascular diseases. In the present work, we explored the vibrational spectroscopy characteristics of the cardiac tissue in an experimental model of heart failure with preserved ejection fraction (HFpEF). The goal was to detect early cardiac chemical modifications associated with the development of HFpEF.

Methods

We used the Fourier-transform infrared (FTIR) and Raman micro-spectroscopic techniques to provide complementary and objective tools for the histological assessment of heart tissues from an animal model of HFpEF. A new sampling technique was adopted (tissue print on a CaF2 disk) to characterize the extracellular matrix.

Results

Several spectroscopic markers (lipids, carbohydrates, and glutamate bands) were recognized in the cardiac ventricles due to the comorbidities associated with the pathology, such as obesity and diabetes. Besides, abnormal collagen cross-linking and a decrease in tryptophan content were observed and related to the stiffening of ventricles and to the inflammatory state which is a favourable condition for HFpEF.

Conclusions

By the analyses of tissues and tissue prints, FTIR and Raman techniques were shown to be highly sensitive and selective in detecting changes in the chemistry of the heart in experimental HFpEF and its related comorbidities. Vibrational spectroscopy is a new approach that can identify novel biomarkers for early detection of HFpEF.
Mitochondrial dysfunction in neurodegenerative disorders: Potential therapeutic application of mitochondrial transfer to central nervous system-residing cells
Authors: Bustamante-Barrientos Felipe A. , Luque-Campos Noymar , Araya María Jesús , Lara-Barba Eliana , de Solminihac Javiera , Pradenas Carolina , Molina Luis , Herrera-Luna Yeimi , Utreras-Mendoza Yildy , Elizondo-Vega Roberto , Vega-Letter Ana María , Luz-Crawford Patricia
Published: September 2023

Mitochondrial dysfunction is reiteratively involved in the pathogenesis of diverse neurodegenerative diseases. Current in vitro and in vivo approaches support that mitochondrial dysfunction is branded by several molecular and cellular defects, whose impact at different levels including the calcium and iron homeostasis, energetic balance and/or oxidative stress, makes it difficult to resolve them collectively given their multifactorial nature. Mitochondrial transfer offers an overall solution since it contains the replacement of damage mitochondria by healthy units. Therefore, this review provides an introducing view on the structure and energy-related functions of mitochondria as well as their dynamics. In turn, we summarize current knowledge on how these features are deregulated in different neurodegenerative diseases, including frontotemporal dementia, multiple sclerosis, amyotrophic lateral sclerosis, Friedreich ataxia, Alzheimer´s disease, Parkinson´s disease, and Huntington’s disease. Finally, we analyzed current advances in mitochondrial transfer between diverse cell types that actively participate in neurodegenerative processes, and how they might be projected toward developing novel therapeutic strategies.
Online prediction for respiratory movement compensation: a patient-specific gating control for MRI-guided radiotherapy
Authors: Li Yang , Li Zhenjiang , Zhu Jian , Li Baosheng , Shu Huazhong , Ge Di
Published: September 2023

Background

This study aims to validate the effectiveness of linear regression for motion prediction of internal organs or tumors on 2D cine-MR and to present an online gating signal prediction scheme that can improve the accuracy of MR-guided radiotherapy for liver and lung cancer.

Materials and methods

We collected 2D cine-MR sequences of 21 liver cancer patients and 10 lung cancer patients to develop a binary gating signal prediction algorithm that forecasts the crossing-time of tumor motion traces relative to the target threshold. Both 0.4 s and 0.6 s prediction windows were tested using three linear predictors and three recurrent neural networks (RNNs), given the system delay of 0.5 s. Furthermore, an adaptive linear regression model was evaluated using only the first 30 s as the burn-in period, during which the model parameters were adapted during the online prediction process. The accuracy of the predicted traces was measured using amplitude metrics (MAE, RMSE, and R2), and in addition, we proposed three temporal metrics, namely crossing error, gating error, and gating accuracy, which are more relevant to the nature of the gating signals.

Results

In both 0.6 s and 0.4 s prediction cases, linear regression outperformed other methods, demonstrating significantly smaller amplitude errors compared to the RNNs (P < 0.05). The proposed algorithm with adaptive linear regression had the best performance with an average gating accuracy of 98.3% and 98.0%, a gating error of 44 ms and 45 ms, for liver cancer and lung cancer patients, respectively.

Conclusion

A functional online gating control scheme was developed with an adaptive linear regression that is both more cost-efficient and accurate than sophisticated RNN based methods in all studied metrics.
Database-aided UHPLC-Q-orbitrap MS/MS strategy putatively identifies 52 compounds from Wushicha Granule to propose anti-counterfeiting quality-markers for pharmacopoeia
Authors: Li Xican , Chen Shaoman , Zeng Jingyuan , Cai Rongxin , Liang Yilan , Chen Chuanbin , Chen Ban , Li Chunhou
Published: September 2023

Wushicha Granule, an over-the-counter-drug (OTC) prescription, consists of 19 traditional Chinese herbals medicines (CHMs), such as Chaihu, Hongcha, Chuanxiong, Houpo, and Gancao. The five however have not been effectively characterized by the quality-markers (Q-markers) system in current Pharmacopoeia. The study therefore established a novel database-aided ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry (UHPLC-Q-orbitrap MS/MS) strategy. The strategy has putatively identified 52 compounds from Wushicha Granule, mainly including flavonoids, saponins, alkaloid, lignins, and lactones. Especially, saponin “glycyrrhetinic acid” in the Granule was specifically identified as 18β-configuration (rather than 18α-configuration). Meanwhile, two pairs of isomers were fully discriminated, including vitexin vs isovitexin and daidzein vs 7,4'-dihydroxyflavone. 8β-Glycyrrhetinic acid, together with saponin saikosaponin A, alkaloid caffeine, lactone S-senkyunolide A, and lignin magnolol, were further studied using quantum chemical calculation, UV–vis spectra, and anti-counterfeiting validation experiment. In the validation experiment, they have successfully recognized 6 counterfeit Wushicha Granules, by means of a LC–MS equipped extraction software. Based on these results, 8β-glycyrrhetinic acid is recommended to replace the old Q-marker “glycyrrhetinic acid”; while saikosaponin A, caffeine, S-senkyunolide A, and magnolol are recommended as new Q-markers. These recommendations can not only recognize the counterfeits regarding Chaihu, Hongcha, Chuanxiong, Houpo, and Gancao, but also prevent the possible safety-incident. All these will greatly improve the efficiency and specificity of current Pharmacopoeia.
Lycium barbarum polysaccharide inhibits ischemia-induced autophagy by promoting the biogenesis of neural stem cells-derived extracellular vesicles to enhance the delivery of miR-133a-3p
Authors: Li Rong , Duan Wenjie , Feng Tingle , Gu Chenyang , Zhang Qiankun , Long Jun , Huang Shiying , Chen Lukui
Published: September 2023

Background

Neural stem cell-derived extracellular vesicles (NSC-EVs) mediated endogenous neurogenesis determines a crucial impact on spontaneous recovery after stroke. Here, we checked the influence of Lycium barbarum polysaccharide (LBP) on the biogenesis of NSC-EVs and then focused on studying mechanisms of LBP in ameliorating ischemic stroke outcome.

Methods

LBP was prepared to precondition NSCs and isolate EVs. MCAO models and primary NSCs were administrated to evaluate the therapeutic effect. RT-PCR, western blot, flow cytometry, and immunofluorescence techniques were performed to explore the mechanism.

Results

LBP pretreatment increased the production of NSC-EVs and improved the neuroprotective and recovery effects of NSC-EV in ischemic stroke mice. LBP-pretreated NSC-EV in a dose-dependent manner substantially reduced neuronal death compared with NSC-EV. Screening of the signaling cascade involved in the interaction between NSC-EV and neurons revealed that AMPK/mTOR signaling pathway inhibited autophagic activity in neurons receiving either treatment paradigm. NSC-EVs but not EVs collected from NSCs pretreated with the anti-miR-133a-3p oligonucleotide reduced cell death, whereas the anti-oligonucleotide promoted autophagy activity and cell death by modulating AMPK/mTOR signaling in OGD-induced primary neurons.

Conclusion

LBP activated AMPK/mTOR signaling pathway by increasing the enrichment and transfer of miR-133a-3p in NSC-EVs to inhibit stroke-induced autophagy activity.
The fusion of multiple scale data indicates that the carbon sink function of the Qinghai-Tibet Plateau is substantial
Authors: Zeng Jingyu , Zhou Tao , Xu Yixin , Lin Qiaoyu , Tan E. , Zhang Yajie , Wu Xuemei , Zhang Jingzhou , Liu Xia
Published: September 2023

Background

The Qinghai-Tibet Plateau is the “sensitive area” of climate change, and also the “driver” and “amplifier” of global change. The response and feedback of its carbon dynamics to climate change will significantly affect the content of greenhouse gases in the atmosphere. However, due to the unique geographical environment characteristics of the Qinghai-Tibet Plateau, there is still much controversy about its carbon source and sink estimation results. This study designed a new algorithm based on machine learning to improve the accuracy of carbon source and sink estimation by integrating multiple scale carbon input (net primary productivity, NPP) and output (soil heterotrophic respiration, Rh) information from remote sensing and ground observations. Then, we compared spatial patterns of NPP and Rh derived from the fusion of multiple scale data with other widely used products and tried to quantify the differences and uncertainties of carbon sink simulation at a regional scale.

Results

Our results indicate that although global warming has potentially increased the Rh of the Qinghai-Tibet Plateau, it will also increase its NPP, and its current performance is a net carbon sink area (carbon sink amount is 22.3 Tg C/year). Comparative analysis with other data products shows that CASA, GLOPEM, and MODIS products based on remote sensing underestimate the carbon input of the Qinghai-Tibet Plateau (30–70%), which is the main reason for the severe underestimation of the carbon sink level of the Qinghai-Tibet Plateau (even considered as a carbon source).

Conclusions

The estimation of the carbon sink in the Qinghai-Tibet Plateau is of great significance for ensuring its ecological barrier function. It can deepen the community’s understanding of the response to climate change in sensitive areas of the plateau. This study can provide an essential basis for assessing the uncertainty of carbon sources and sinks in the Qinghai-Tibet Plateau, and also provide a scientific reference for helping China achieve “carbon neutrality” by 2060.
Myocardial native T1 mapping and extracellular volume quantification in asymptomatic female carriers of Duchenne muscular dystrophy gene mutations
Authors: Masárová Lucia , Panovský Roman , Pešl Martin , Mojica-Pisciotti Mary Luz , Holeček Tomáš , Kincl Vladimír , Juříková Lenka , Máchal Jan , Opatřil Lukáš , Feitová Věra
Published: September 2023

Background

Female carriers of dystrophin gene mutations (DMD-FC) were previously considered non-manifesting, but in recent decades, cardiomyopathy associated with muscular dystrophy and myocardial fibrosis has been described. Our study aimed to assess prospectively myocardial fibrosis in asymptomatic DMD-FC compared to a sex-matched control group (CG) with similar age distribution using native T1 mapping and extracellular volume (ECV) quantification by cardiovascular magnetic resonance (CMR) imaging.

Materials and methods

38 DMD-FC with verified genetic mutation and 22 healthy volunteers were included. Using CMR, native T1 relaxation time and ECV quantification were determined in each group. Late gadolinium enhancement (LGE) was assessed in all cases.

Results

There were 38 DMD-FC (mean age 39.1 ± 8.8 years) and 22 healthy volunteers (mean age 39.9 ± 12.6 years) imagined by CMR. The mean global native T1 relaxation time was similar for DMD-FC and CG (1005.1 ± 26.3 ms vs. 1003.5 ± 25.0 ms; p-value = 0.81). Likewise, the mean global ECV value was also similar between the groups (27.92 ± 2.02% vs. 27.10 ± 2.89%; p-value = 0.20). The segmental analysis of mean ECV values according to the American Heart Association classification did not show any differences between DMD-FC and CG. There was a non-significant trend towards higher mean ECV values of DMD-FC in the inferior and inferolateral segments of the myocardium (p-value = 0.075 and 0.070 respectively).

Conclusion

There were no statistically significant differences in the mean global and segmental native T1 relaxation times and the mean global or segmental ECV values. There was a trend towards higher segmental mean ECV values of DMD-FC in the inferior and inferolateral walls of the myocardium.