bluuebunny/crossref_metadata_2025 huggingface dataset:
A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases
Authors: Zheng Rui-fang , Kader Kaderyea , Liu Di-wei , Su Wen-ling , Xu Lei , Jin Yuan-yuan , Xing Jian-guo
Published: January 2024

Aim of the study

Cardiovascular disease (CVD) seriously endangers human health and is characterized by high mortality and disability. The effectiveness of Dracocephalum moldavica L. in the treatment of CVD has been proven by clinical practice. However, the mechanism by which DML can treat CVD has not been systematically determined.

Materials and methods

The active compounds in DML were screened by literature mining and pharmacokinetic analysis. Cytoscape software was used to construct the target-disease interaction network of DML in the treatment of CVD. Gene ontology and signalling pathway enrichment analyses were performed. The key target pathway network of DML compounds was constructed and verified by pharmacological experiments in vitro. A hydrogen glucose deprivation/reoxygenation model was established in H9c2 cells using hypoxia and glucose deprivation for 9 h combined with reoxygenation for 2 h. The model simulated myocardial ischaemic reperfusion injury to investigate the effects of total flavonoids of Cymbidium on cell viability, myocardial injury markers, oxidative stress levels, and reactive oxygen radical levels. Western blot analysis was used to examine NOX-4, Bcl-2/Bax, and PGC-1α protein expression.

Results

Twenty-seven active components were screened, and 59 potential drug targets for the treatment of CVD were obtained. Through the compound-target interaction network and the target-disease interaction network, the key targets and key signalling pathways, such as NOX-4, Bcl-2/Bax and PGC-1α, were obtained. TFDM significantly decreased LDH and MDA levels and the production of ROS and increased SOD activity levels in the context of OGD/R injury. Further studies indicated that NOX-4 and Bax protein levels and the p-P38 MAPK/P38 MAPK andp-Erk1/2/Erk1/2 ratios were suppressed by TFDM. The protein expression of Bcl-2 and PGC-1α was increased by TFDM.

Conclusions

Our results showed that DML had multicomponent, multitarget and multichannel characteristics in the treatment of CVD. The mechanism may be associated with the following signalling pathways: 1) the NOX-4/ROS/p38 MAPK signalling pathway, which inhibits inflammation and reactive oxygen species (ROS) production, and 2) the Bcl-2/Bax and AMPK/SIRT1/PGC-1α signalling pathways, which inhibit apoptosis.
A validation of an entropy-based artificial intelligence for ultrasound data in breast tumors
Authors: Huang Zhibin , Yang Keen , Tian Hongtian , Wu Huaiyu , Tang Shuzhen , Cui Chen , Shi Siyuan , Jiang Yitao , Chen Jing , Xu Jinfeng , Dong Fajin
Published: January 2024

Background

The application of artificial intelligence (AI) in the ultrasound (US) diagnosis of breast cancer (BCa) is increasingly prevalent. However, the impact of US-probe frequencies on the diagnostic efficacy of AI models has not been clearly established.

Objectives

To explore the impact of using US-video of variable frequencies on the diagnostic efficacy of AI in breast US screening.

Methods

This study utilized different frequency US-probes (L14: frequency range: 3.0-14.0 MHz, central frequency 9 MHz, L9: frequency range: 2.5-9.0 MHz, central frequency 6.5 MHz and L13: frequency range: 3.6-13.5 MHz, central frequency 8 MHz, L7: frequency range: 3-7 MHz, central frequency 4.0 MHz, linear arrays) to collect breast-video and applied an entropy-based deep learning approach for evaluation. We analyzed the average two-dimensional image entropy (2-DIE) of these videos and the performance of AI models in processing videos from these different frequencies to assess how probe frequency affects AI diagnostic performance.

Results

The study found that in testing set 1, L9 was higher than L14 in average 2-DIE; in testing set 2, L13 was higher in average 2-DIE than L7. The diagnostic efficacy of US-data, utilized in AI model analysis, varied across different frequencies (AUC: L9 > L14: 0.849 vs. 0.784; L13 > L7: 0.920 vs. 0.887).

Conclusion

This study indicate that US-data acquired using probes with varying frequencies exhibit diverse average 2-DIE values, and datasets characterized by higher average 2-DIE demonstrate enhanced diagnostic outcomes in AI-driven BCa diagnosis. Unlike other studies, our research emphasizes the importance of US-probe frequency selection on AI model diagnostic performance, rather than focusing solely on the AI algorithms themselves. These insights offer a new perspective for early BCa screening and diagnosis and are of significant for future choices of US equipment and optimization of AI algorithms.
Adolescent, parent, and provider attitudes toward a machine learning based clinical decision support system for selecting treatment for youth depression
Authors: Gunlicks-Stoessel Meredith , Liu Yangchenchen , Parkhill Catherine , Morrell Nicole , Choy-Brown Mimi , Mehus Christopher , Hetler Joel , August Gerald
Published: January 2024

Background

Machine learning based clinical decision support systems (CDSSs) have been proposed as a means of advancing personalized treatment planning for disorders, such as depression, that have a multifaceted etiology, course, and symptom profile. However, machine learning based models for treatment selection are rare in the field of psychiatry. They have also not yet been translated for use in clinical practice. Understanding key stakeholder attitudes toward machine learning based CDSSs is critical for developing plans for their implementation that promote uptake by both providers and families.

Methods

In Study 1, a prototype machine learning based Clinical Decision Support System for Youth Depression (CDSS-YD) was demonstrated to focus groups of adolescents with a diagnosis of depression (n = 9), parents (n = 11), and behavioral health providers (n = 8). Qualitative analysis was used to assess their attitudes towards the CDSS-YD. In Study 2, behavioral health providers were trained in the use of the CDSS-YD and they utilized the CDSS-YD in a clinical encounter with 6 adolescents and their parents as part of their treatment planning discussion. Following the appointment, providers, parents, and adolescents completed a survey about their attitudes regarding the use of the CDSS-YD.

Results

All stakeholder groups viewed the CDSS-YD as an easy to understand and useful tool for making personalized treatment decisions, and families and providers were able to successfully use the CDSS-YD in clinical encounters. Parents and adolescents viewed their providers as having a critical role in the use the CDSS-YD, and this had implications for the perceived trustworthiness of the CDSS-YD. Providers reported that clinic productivity metrics would be the primary barrier to CDSS-YD implementation, with the creation of protected time for training, preparation, and use as a key facilitator.

Conclusions

Machine learning based CDSSs, if proven effective, have the potential to be widely accepted tools for personalized treatment planning. Successful implementation will require addressing the system-level barrier of having sufficient time and energy to integrate it into practice.
Malaria elimination in Ghana: recommendations for reactive case detection strategy implementation in a low endemic area of Asutsuare, Ghana
Authors: Aidoo Ebenezer Krampah , Aboagye Frank Twum , Agginie George Edem , Botchway Felix Abekah , Osei-Adjei George , Appiah Michael , Takyi Ruth Duku , Sakyi Samuel Asamoah , Amoah Linda , Arthur George , Lawson Bernard Walter , Asmah Richard Harry , Boateng Paul , Ansah Otubea , Krogfelt Karen Angeliki
Published: January 2024

Background

Progress toward malaria elimination is increasing as many countries near zero indigenous malaria cases. In settings nearing elimination, interventions will be most effective at interrupting transmission when targeted at the residual foci of transmission. These foci may be missed due to asymptomatic infections. To solve this problem, the World Health Organization recommends reactive case detection (RACD). This case study was conducted to identify individuals with asymptomatic malaria, their predisposing risk factors and recommend RACD in Asutsuare, Ghana based on literature review and a cross sectional study.

Methods

The study involved a search on PubMed and Google Scholar of literature published between 1st January, 2009–14th August, 2023 using the search terms “malaria” in “Asutsuare”. Furthermore, structured questionnaires were administered to one hundred individuals without symptoms of malaria and screened using rapid diagnostic test (RDT) kits, microscopy and real-time polymerase chain reaction (rt-PCR). Malaria prevalence based on the three diagnostic techniques as well as potential malaria risk factors were assessed through questionnaires in a cross-sectional study.

Results

Cumulatively, sixty-four (64) studies (Google Scholar, 57 and PubMed, 7) were reviewed and 22 studies included in the literature on malaria in Asutsuare, Ghana. Significant risk factors were occupation, distance from a house to a waterbody, age group and educational level. Out of the 100 samples, 3 (3%) were positive by RDT, 6 (6%) by microscopy and 9 (9%) by rt-PCR. Ages 5–14.9 years had the highest mean malaria parasite densities of 560 parasites/µl with Plasmodium falciparum as the dominant species in 4 participants. Moreover, in the age group ≥ 15, 2 participants (1 each) harboured P. falciparum and Plasmodium malariae parasites. RDT had a higher sensitivity (76.54%; CI95 66.82–85.54) than rt-PCR (33.33%; CI95 4.33–77.72), while both rt-PCR and RDT were observed to have a higher specificity (92.55; CI95 85.26–96.95) and (97.30; CI95 93.87–99.13), respectively in the diagnosis of malaria.

Conclusion

In Asutsuare, Ghana, a low endemic area, the elimination of malaria may require finding individuals with asymptomatic infections. Given the low prevalence of asymptomatic individuals identified in this study and as repleted in the literature review, which favours RACD, Asutsuare is a possible setting receptive for RACD implementation.
Factors influencing patients’ adherence to malaria artemisinin-based combination therapy in Kamuli District, Uganda
Authors: Bawate Charles , Callender-Carter Sylvia T. , Guyah Bernard , Ouma Collins
Published: January 2024

Background

Patients’ adherence to artemisinin-based combination therapy (ACT) is a malaria control strategy. Studies report varied experiences regarding patients’ adherence to ACT. The study aimed at determining factors influencing patients’ adherence to ACT for malaria in Kamuli, Uganda.

Methods

In a longitudinal study, 1266 participants at 8 public health facilities were enrolled. Equal numbers (422) were assigned to the three arms (no follow-up, day 2 and day 4). To establish the mean difference between groups, Student t-test was used and a chi-square test was used for proportionality. A multivariate logistic regression analysis was used to establish the influence of predictor variables on the dependent variable. Statistical significance was established at p < 0.05.

Results

A total of 844 patients were analysed. The median age was 20 years, majority (64.3%) were females. Overall patients’ adherence was 588/844 (69.7%). At bivariate level, age (t-test = 2.258, p = 0.024), household head (χ2 = 14.484, p = 0.002), employment status (χ2 = 35.886, p < 0.0001), patients’ preference of ACT to other anti-malarials (χ2 = 15.981, p < 0.0001), giving a patient/caregiver instructions on how to take the medication (χ2 = 7.134, p = 0.011), being satisfied with getting ACT at facility (χ2 = 48.261, p < 0.0001), patient/caregiver knowing the drug prescribed (χ2 = 5.483, p = 0.019), patient history of saving ACT medicines (χ2 = 39.242, p < 0.0001), and patient ever shared ACT medicines (χ2 = 30.893, p < 0.0001) were all associated with patients’ adherence to ACT. Multivariate analysis demonstrated that adhering to ACT is 3.063 times higher for someone satisfied with getting ACT at the facility (OR = 3.063; p < 0.0001), 4.088 times for someone with history of saving ACT medicines (OR = 4.088; p < 0.0001), 2.134 times for someone who shared ACT (OR = 2.134; p = 0.03), and 2.817 times for someone with a household head (OR = 2.817; p = 0.008).

Conclusion

Patients’ adherence to ACT is generally good in the studied population. However, patients’ tendencies to save ACT for future use and sharing among family members is a threat, amidst the benefits associated with adherence. There is a need to educate all about adherence to medicines as prescribed, and tighten government medicine supply chain to avoid stock-outs.
Available but inaccessible: patient experiences during the first 2 years of a primary care-based medical cannabis program at an academic medical center
Authors: Freitag Eloise W. , Zolotov Yuval , Annam Jayabhargav , Labins Jaqueline , Yamada Jaclyn M. , Jillani Syeda Masharab , Arnsten Julia H. , Slawek Deepika E.
Published: January 2024

Background

Medical cannabis use and public acceptance in the United States have increased over the past 25 years. However, access to medical cannabis remains limited, particularly for underserved populations. To understand how patients experience medical cannabis accessibility, we measured medical cannabis use and barriers to use after medical cannabis certification in an urban safety-net academic medical center.

Methods

We conducted a retrospective cohort study among patients seen in Montefiore’s Medical Cannabis Program (MMCP) from 2017 to 2019. Patient demographic and clinical characteristics, as well purchase history of medical cannabis, were extracted from electronic medical records. We also administered a phone questionnaire to a subset of patients to assess usage patterns, effectiveness, and barriers to medical cannabis use.

Results

Among 562 patients who were newly certified for medical cannabis between 2017 and 2019, 45% purchased medical cannabis, while 55% did not. Patients who purchased medical cannabis were more likely to be white and have private insurance or Medicare. Unregulated cannabis use and current tobacco use were less common among those who purchased medical cannabis. In multivariable logistic regression analysis, unregulated cannabis use remained negatively associated with purchasing medical cannabis. Patients reported that affordability and dispensary accessibility were their main barriers to purchasing medical cannabis.

Conclusion

Among patients certified for medical cannabis use, fewer than half purchased medical cannabis after certification. Improving access to medical cannabis is crucial for ensuring equitable access to regulated cannabis, and to reducing unregulated cannabis use.
Expression of NELL2/NICOL-ROS1 lumicrine signaling-related molecules in the human male reproductive tract
Authors: Kiyozumi Daiji
Published: January 2024

The maturation of spermatozoa is a regulated process, influenced by genes expressing essential secreted proteins in the proximal epididymis. Recent genetic studies in rodents have identified the non-sex steroidal molecular signals that regulate gene expression in the proximal epididymis. Germ cells in the testis secrete ligand proteins into the seminiferous tubule lumen The ligand proteins travel through the male reproductive tract lumen to the epididymis, where they bind to receptors, triggering the differentiation of the luminal epithelium for sperm maturation. It is, however, not fully unveiled if such a testis-epididymis trans-luminal signaling mechanism exists in other species, especially humans. In the present study, the rodent-type testis-epididymis trans-luminal signaling in the human male reproductive tract was evaluated in a step-by-step manner by analyzing testis and epididymis gene expression and signaling mediator protein function. There was a significant correlation between the epididymal expressions of mouse genes upregulated by the trans-luminal signaling and those of their human orthologs, as evaluated by the correlation coefficient of 0.604. The transcript expression of NELL2 and NICOL encoding putative ligand proteins was also observed in human testicular cells. In vitro experiments demonstrated that purified recombinant human NELL2 and NICOL formed a molecular complex with similar properties to rodent proteins, which was evaluated by a dissociation equilibrium constant of 110 nM. Recombinant human NELL2 also specifically bound to its putative receptor human ROS1 in vitro. Collectively, these findings suggest that the rodent-type testis-epididymis secreted signaling mechanism is also possible in the human male reproductive tract.
Assessing unConventional Evidence (ACE) tool: development and content of a tool to assess the strengths and limitations of ‘unconventional’ source materials
Authors: Lewin Simon , Langlois Etienne V. , Tunçalp Özge , Portela Anayda
Published: January 2024

Background

When deciding whether to implement an intervention, decision-makers typically have questions on feasibility and acceptability and on factors affecting implementation. Descriptions of programme implementation and of policies and systems are rich sources of information for these questions. However, this information is often not based on empirical data collected using explicit methods. To use the information in unconventional source materials in syntheses or other decision support products, we need methods of assessing their strengths and limitations. This paper describes the development and content of the Assessing unConventional Evidence (ACE) tool, a new tool to assess the strengths and limitations of these sources.

Methods

We developed the ACE tool in four stages: first, we examined existing tools to identify potentially relevant assessment criteria. Second, we drew on these criteria and team discussions to create a first draft of the tool. Third, we obtained feedback on the draft from potential users and methodologists, and through piloting the tool in evidence syntheses. Finally, we used this feedback to iteratively refine the assessment criteria and to improve our guidance for undertaking the assessment.

Results

The tool is made up of 11 criteria including the purpose and context of the source; the completeness of the information presented; and the extent to which evidence is provided to support the findings made. Users are asked to indicate whether each of the criteria have been addressed. On the basis of their judgements for each criterion, users then make an overall assessment of the limitations of the source, ranging from no or very minor concerns to serious concerns. These assessments can then facilitate appropriate use of the evidence in decision support products.

Conclusions

Through focussing on unconventional source materials, the ACE tool fills an important gap in the range of tools for assessing the strengths and limitations of policy-relevant evidence and supporting evidence-informed decision-making.
PIGT promotes cell growth, glycolysis, and metastasis in bladder cancer by modulating GLUT1 glycosylation and membrane trafficking
Authors: Tan Mingyue , Pan Qi , Yu Chao , Zhai Xinyu , Gu Jianyi , Tao Le , Xu Dongliang
Published: January 2024

Background

Bladder cancer is very common worldwide. PIGT is a subunit of the glycosylphosphatidylinositol transamidase which involves in tumorigenesis and invasiveness. m6A modification of mRNA has been linked to cell proliferation, tumor progression and other biological events. However, how PIGT is regulated and what is the function of PIGT in bladder cancer remains to be elucidated.

Methods

PIGT was silenced or overexpressed to study its role in regulating bladder cancer. Cell proliferation and invasion were examined with the Cell Counting Kit-8, colony formation and Transwell assay, respectively. Cellular oxygen consumption rates or extracellular acidification rates were detected by a XF24 Analyzer. Quantitative RT-PCR and immunoblots were performed to detect mRNA and protein levels.

Results

PIGT was overexpressed in bladder cancer. Silencing PIGT inhibited cell proliferation, oxidative phosphorylation, and glycolysis. Overexpressing PIGT promoted cell proliferation, oxidative phosphorylation, glycolysis in vitro and tumor metastasis in vivo by activating glucose transporter 1 (GLUT1). PIGT also promoted GLUT1 glycosylation and membrane trafficking. Wilms’ tumor 1-associated protein (WTAP) mediated PIGT m6A modification, and m6A reader, insulin-like growth factor 2 mRNA-binding protein (IGF2BP2), binds to the methylated PIGT to promote the stability of PIGT, leading to up-regulation of PIGT.

Conclusion

WTAP mediates PIGT m6A modification to increase the stability of PIGT via the IGF2BP2, which enhances cell proliferation, glycolysis, and metastasis in bladder cancer by modulating GLUT1 glycosylation and membrane trafficking.
NCAPG2 promotes prostate cancer malignancy and stemness via STAT3/c-MYC signaling
Authors: Zhang Enchong , Chen Zhengjie , Liu Wangmin , Lin Lin , Wu Lina , Guan Johnny , Wang Jianfeng , Kong Chuize , Bi Jianbin , Zhang Mo
Published: January 2024

Background

Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men worldwide, and its incidence has risen substantially in recent years. Therefore, there is an urgent need to identify novel biomarkers and precise therapeutic targets for managing PCa progression and recurrence.

Methods

We investigated the clinical significance of NCAPG2 in PCa by exploring public datasets and our tissue microarray. Receiver operating characteristic (ROC) curve and survival analyses were performed to evaluate the correlation between NCAPG2 and PCa progression. Cell proliferation, wound healing, transwell, flow cytometry, cell cycle, tumor sphere formation, immunofluorescence (IF), co-immunoprecipitation (co-IP), and chromatin immunoprecipitation (ChIP) assays were conducted to further elucidate the molecular mechanism of NCAPG2 in PCa. Subcutaneous and orthotopic xenograft models were applied to investigate the effects of NCAPG2 on PCa proliferation in vivo. Tandem mass tag (TMT) quantitative proteomics was utilized to detect proteomic changes under NCAPG2 overexpression.

Results

NCAPG2 was significantly upregulated in PCa, and its overexpression was associated with PCa progression and unfavorable prognosis. Knockdown of NCAPG2 inhibited the malignant behavior of PCa cells, whereas its overexpression promoted PCa aggressiveness. NCAPG2 depletion attenuated the development and growth of PCa in vivo. TMT quantitative proteomics analyses indicated that c-MYC activity was strongly correlated with NCAPG2 expression. The malignancy-promoting effect of NCAPG2 in PCa was mediated via c-MYC. NCAPG2 could directly bind to STAT3 and induce STAT3 occupancy on the MYC promoter, thus to transcriptionally activate c-MYC expression. Finally, we identified that NCAPG2 was positively correlated with cancer stem cell (CSC) markers and enhanced self-renewal capacity of PCa cells.

Conclusions

NCAPG2 is highly expressed in PCa, and its level is significantly associated with PCa prognosis. NCAPG2 promotes PCa malignancy and drives cancer stemness via the STAT3/c-MYC signaling axis, highlighting its potential as a therapeutic target for PCa.
Function and mechanism of GBP1 in the development and progression of cervical cancer
Authors: Wang Senyu , Zhang Yajing , Ma Xiumin , Feng Yangchun
Published: January 2024

Guanylate binding protein 1 (GBP1) is the most concerned member of the GBP family, which has a series of effects such as anti-infection and anti-angiogenesis. Its role in malignant tumors including cervical cancer is still controversial. We aim to explore the effects of GBP1 on cervical cancer through bioinformatics and related experiments. In this study, we first found that GBP1 was generally expressed in cervical cancer in various online databases and was closely related to immune invasion. Secondly, we used multicolor immunofluorescence technology to verify the expression of GBP1 in cervical cancer tissues and its relationship with immune invasion, and explored its relationship with the prognosis of patients with cervical cancer. Knockdown and overexpression assays of GBP1 in vitro were used to prove GBP1 as a potential oncogene of cervical cancer, and its carcinogenicity was verified by in vivo experiment. In order to explore the potential mechanism of GBP1 in promoting cancer, RNA-seq was performed on GBP1 overexpression and knockdown expression cell lines, and GBP1 knockdown and overexpression were found to be associated with many RNA alternative splicing events, suggesting that GBP1 maybe a RNA binding protein (RBP) which affect the biological characteristics of cervical cancer cells through the alternative splicing pathway. However, the later RNA binding protein immunoprecipitation (RIP) assay proved that GBP1 was not a direct alternative splicing factor, while the co-immunoprecipitation (CoIP)-mass spectroscopy (MS) assay combined with protein protein interaction (PPI) analysis proved that 8 alternative splicing factors including Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK) were interacting proteins of GBP1. Combined with the existing reports and the results of RNA-seq alternative splicing analysis, it is speculated that GBP1 may regulate the alternative splicing of CD44 protein by binding to interacting protein-HNRNPK, and thus play a role in promoting cancer in cervical cancer.
Deficiency of Trex1 leads to spontaneous development of type 1 diabetes
Authors: Zhao Jiang-Man , Su Zhi-Hui , Han Qiu-Ying , Wang Miao , Liu Xin , Li Jing , Huang Shao-Yi , Chen Jing , Li Xiao-Wei , Chen Xia-Ying , Guo Zeng-Lin , Jiang Shuai , Pan Jie , Li Tao , Xue Wen , Zhou Tao
Published: January 2024

Background

Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes.

Methods

Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-β were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining.

Results

In this study, we established aTrex1-deletion Sprague Dawley rat model, and unexpectedly, we found that theTrex1−/−rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-β, inTrex1null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic β cells.

Conclusions

Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.
Institutionalization for good governance to reach sustainable health development: a framework analysis
Authors: Haghighi Hajar , Takian Amirhossein
Published: January 2024

Background

This article explores the concept of institutionalization, which is the process of transforming ideas into programs and automating actions, in the context of health system governance and sustainable development. Institutionalization is a key mechanism for creating accountable and transparent institutions, which are essential for achieving health system resilience and sustainability. This study identifies the components and dimensions of institutionalization in the health system and its relationship with good governance and sustainable health development.

Main text

We applied a scoping review method in five steps. First, we formulated a question for our research. Then, we concluded a comprehensive literature search in five electronic databases for identifying relevant studies. This review has two phases: identifying the concept of institutional approach and its components in health system, and its relationship with good governance to reach Sustainable Health Development (SHD). The third step was study selection, and the 1st author performed data abstraction. The key issues which are identified in our review, related to the concepts of SDH, its goals, pillars and principles; positive peace; good governance; components of institutional approach components, and their relations. Finally, we summarized and organized our findings in a format of a proposed conceptual framework, to underpin the role of institutionalization in the health system to achieve sustainable development.

Conclusion

Institutionalization is a key concept for achieving positive peace and good governance, which requires meaningful involvement of leaders, politicians, civil society, and public participation. It also depends on the conditions of justice, human rights, transparency, accountability and rule of law. In the wake of COVID-19, institutionalization is more crucial than ever for advancing sustainable development, especially in the context of low and middle-income countries (LMICs).
Surgical aortic valve replacement etiologies, hemodynamics, and outcomes in 1346 patients from the Malaysian heart centre
Authors: Roslan Aslannif , Soon Chong Kee , Sin Tey Yee , Aktifanus Ahmad Tantawi Jauhari , Ling Soh Si , Boon Wong Kian , Rusani Beni I. , Hadi Hafidz Abd , Kolanthaivelu Jayakhanthan , Yahaya Shaiful Azmi , Dillon Jeswant , Yunus Alwi M.
Published: January 2024

Background

This study examined the characteristics and outcomes of surgical aortic valve replacement (SAVR) both isolated and in combination with other cardiac surgery in Malaysia from 2015 to 2021.

Methods

This was a retrospective study of 1346 patients analyzed on the basis of medical records, echocardiograms and surgical reports. The overall sample was both considered as a whole and divided into aortic stenosis (AS)/aortic regurgitation (AR)-predominant and similar-severity subgroups.

Results

The most common diagnosis was severe AS (34.6%), with the 3 most common etiologies being bicuspid valve degeneration (45.3%), trileaflet valve degeneration (36.3%) and rheumatic valve disease (12.2%). The second most common diagnosis was severe AR (25.5%), with the most common etiologies being root dilatation (21.0%), infective endocarditis (IE) (16.6%) and fused prolapse (12.2%). Rheumatic valve disease was the most common mixed disease. A total of 54.5% had AS-predominant pathology (3 most common etiologies: bicuspid valve degeneration valve, degenerative trileaflet valve and rheumatic valve disease), 36.9% had AR-predominant pathology (top etiologies: root dilatation, rheumatic valve disease and IE), and 8.6% had similar severity of AS and AR. Overall, 62.9% of patients had trileaflet valve morphology, 33.3% bicuspid, 0.6% unicuspid and 0.3% quadricuspid. For AS, the majority were high-gradient severe AS (49.9%), followed by normal-flow low-gradient (LG) severe AS (10.0%), paradoxical low-flow (LF)-LG severe AS (6.4%) and classical LF-LG severe AS (6.1%). The overall in-hospital and total 1-year mortality rates were 6.4% and 14.8%, respectively. Pure severe AS had the highest mortality. For AS-predominant pathology, the etiology with the highest mortality was trileaflet valve degeneration; for AR-predominant pathology, it was dissection. The overall survival probability at 5 years was 79.5% in all patients, 75.7% in the AS-predominant subgroup, 83.3% in the AR-predominant subgroup, and 87.3% in the similar-severity subgroup.

Conclusions

The 3 most common causes of AS- predominant patients undergoing SAVR is bicuspid valve degeneration, degenerative trileaflet valve and rheumatic and for AR-predominant is root dilatation, rheumatic and IE. Rheumatic valve disease is an important etiology in our SAVR patients especially in mixed aortic valve disease.

Study registration IJNREC/562/2022.
Pharmacological properties of Polygonatum and its active ingredients for the prevention and treatment of cardiovascular diseases
Authors: Lin Hongyuan , Wang Wenhui , Peng Mengqi , Kong Yifan , Zhang Xiaowei , Wei Xiaohong , Shang Hongcai
Published: January 2024

Despite continued advances in prevention and treatment strategies, cardiovascular diseases (CVDs) remain the leading cause of death worldwide, and more effective therapeutic methods are urgently needed. Polygonatum is a traditional Chinese herbal medicine with a variety of pharmacological applications and biological activities, such as antioxidant activity, anti-inflammation, antibacterial effect, immune-enhancing effect, glucose regulation, lipid-lowering and anti-atherosclerotic effects, treatment of diabetes and anticancer effect. There has also been more and more evidence to support the cardioprotective effect of Polygonatum in recent years. However, up to now, there has been a lack of comprehensive studies on the active ingredients and their pharmacotoxicological effects related to cardiovascular diseases. Therefore, the main active components of Polygonatum (including Polysaccharides, Flavonoids, Saponins) and their biological activities were firstly reviewed in this paper. Furthermore, we summarized the pharmacological effects of Polygonatum’s active components in preventing and treating CVDs, and its relevant toxicological investigations. Finally, we emphasize the potential of Polygonatum in the prevention and treatment of CVDs.
3D-printed PCL@BG scaffold integrated with SDF-1α-loaded hydrogel for enhancing local treatment of bone defects
Authors: Wang Chenglong , Dong Jinlei , Liu Fanxiao , Liu Nan , Li Lianxin
Published: January 2024

Background

The long-term nonunion of bone defects is always a difficult problem in orthopaedics treatment. Artificial bone implants made of polymeric materials are expected to solve this problem due to their suitable degradation rate and good biocompatibility. However, the lack of mechanical strength, low osteogenic induction ability and poor hydrophilicity of these synthetic polymeric materials limit their large-scale clinical application.

Results

In this study, we used bioactive glass (BG) (20%, W/W) and polycaprolactone (PCL, 80%, W/W) as raw materials to prepare a bone repair scaffold (PCL@BG20) using fused deposition modelling (FDM) three-dimensional (3D) printing technology. Subsequently, stromal cell-derived factor-1α (SDF-1α) chemokines were loaded into the PCL@BG20 scaffold pores with gelatine methacryloyl (GelMA) hydrogel. The experimental results showed that the prepared scaffold had a porous biomimetic structure mimicking that of cancellous bone, and the compressive strength (44.89 ± 3.45 MPa) of the scaffold was similar to that of cancellous bone. Transwell experiments showed that scaffolds loaded with SDF-1α could promote the recruitment of bone marrow stromal cells (BMSCs). In vivo data showed that treatment with scaffolds containing SDF-1α and BG (PCL@BG-GelMA/SDF-1α) had the best effect on bone defect repair compared to the other groups, with a large amount of new bone and mature collagen forming at the bone defect site. No significant organ toxicity or inflammatory reactions were observed in any of the experimental groups.

Conclusions

The results show that this kind of scaffold containing BG and SDF-1α serves the dual functions of recruiting stem cell migration in vivo and promoting bone repair in situ. We envision that this scaffold may become a new strategy for the clinical treatment of bone defects.
Clinical study protocol on electronic cigarettes and nicotine pouches for smoking cessation in Pakistan: a randomized controlled trial
Authors: Hameed Abdul , Malik Daud
Published: January 2024

Background

Pakistan is one of most vulnerable low- and middle-income countries with 29 million adult active tobacco users. Smoking cessation services are lacking as the tobacco control initiatives have largely failed to address the smoking endemic. Over the last 5 years, Pakistan has witnessed the use of innovative tobacco harm reduction (THR) products such as e-cigarettes and nicotine pouches. However, their use remains limited. THR products are imported legally as consumer goods and are taxable. The lack of sufficient data for THR and its application is a challenge in gauging their effectiveness in assisting smokers quit combustible smoking. Evidence-based studies can help in measuring the effectiveness of e-cigarettes and nicotine pouches as smoking cessation aids.

Method

Keeping in view the study objectives, a sample size of 600 participants will be sufficient to assess the effectiveness of e-cigarettes and nicotine pouches for smoking cessation in Pakistan. Of these, 200 participants each will receive e-cigarettes and nicotine pouches along with basic care counselling, while the remaining 200 participants will only receive basic care counselling for 48 weeks. The association of participants’ characteristics with smoking and health status will be based on the bivariate and multivariate analysis. The simple t-test and variance analysis will assess the differences in intervention indicators between the control and treatment groups. For the inferential analysis, the average treatment impact will be based on the quasi-experimental techniques such as difference in difference (DID) or propensity score matching (PMS).

Discussion

The study will evaluate the participants at the baseline as they decide the quit date. After every 12 weeks, a follow-up survey with the participants will be conducted. Results are anticipated to inform the public, decision-makers, and researchers about the effects of using e-cigarettes and nicotine pouches in the short- and medium-term periods. Critically, the potential of e-cigarettes and other alternative nicotine delivery systems as smoking cessation aid will be assessed.

Trial registration

ClinicalTrials.gov
NCT05715164. Registered on February 6, 2023. Protocol version. Protocol version 1.0, 14-12-2022

Trial in progress and not yet recruiting participants. Estimated primary data collection date—April 2024
Exosome-mediated delivery of super-repressor IκBα alleviates inflammation and joint damages in rheumatoid arthritis
Authors: Lee Hae-In , Ahn Min-Joo , Yoo Jae-Kwang , Ahn So-Hee , Park Seon Young , Seo Hyangmi , Kim Moon-Ju , Lee Yu Jeong , Jang Hyun Hee , Shim Seung Cheol , Won Eun Jeong , Park Cheolhyoung , Choi Chulhee , Kim Tae-Jong
Published: January 2024

Background

This study aims to investigate the potential anti-inflammatory effects of exosomes engineered to carry super-repressor IκB (Exo-srIκB), an exosome-based NF-κB inhibitor, in the context of RA.

Methods

Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were collected from patients diagnosed with RA and treated with Exo-srIκB to test the therapeutic potential. Flow cytometry analysis was performed to assess the production of inflammatory cytokines (IL-17A and GM-CSF) by the cells. ELISA was utilized to measure the levels of TNF-α, IL-17A, IL-6, and GM-CSF. Arthritis was induced in SKG mice by intraperitoneal injection of curdlan. DBA/1 J mice were used in collagen-induced arthritis (CIA) experiments. After the development of arthritis, mice were injected with either Exo-Naïve (control exosome) or Exo-srIκB. Arthritis scores were recorded biweekly, and histological observations of the ankle joint were conducted using H&E and safranin-O staining. Additionally, bone erosion was evaluated using micro-CT imaging.

Results

In the ex vivo study involving human PBMCs and SFMCs, treatment with Exo-srIκB demonstrated a notable reduction in inflammatory cytokines. Furthermore, in both the SKG and CIA models, Exo-srIκB treatment exhibited significant reductions in inflammation, cartilage destruction, and bone erosion within the joint tissues when compared to the Exo-Naive control group. Additionally, the radiographic score assessed through microCT showed a significant decrease compared to the Exo-Naive control group.

Conclusion

Overall, these findings suggest that Exo-srIκB possesses anti-inflammatory properties in human RA cells and animal models, making it a promising therapeutic candidate for the treatment of RA.
Causal relationship between systemic lupus erythematosus and primary liver cirrhosis based on two-sample bidirectional Mendelian randomization and transcriptome overlap analysis
Authors: Wu Linyong , Li Songhua , Wu Chaojun , Wu Shaofeng , Lin Yan , Wei Dayou
Published: January 2024

Background

Overlapping cases of systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) are rare and have not yet been fully proven to be accidental or have a common genetic basis.

Methods

Two-sample bidirectional Mendelian randomization (MR) analysis was applied to explore the potential causal relationship between SLE and PBC. The heterogeneity and reliability of MR analysis were evaluated through Cochran’s Q-test and sensitivity test, respectively. Next, transcriptome overlap analysis of SLE and PBC was performed using the Gene Expression Omnibus database to identify the potential mechanism of hub genes. Finally, based on MR analysis, the potential causal relationship between hub genes and SLE or PBC was validated again.

Results

The MR analysis results indicated that SLE and PBC were both high-risk factors for the occurrence and development of the other party. On the one hand, MR analysis had heterogeneity, and on the other hand, it also had robustness. Nine hub genes were identified through transcriptome overlap analysis, and machine learning algorithms were used to verify their high recognition efficiency for SLE patients. Finally, based on MR analysis, it was verified that there was no potential causal relationship between the central gene SOCS3 and SLE, but it was a high-risk factor for the potential risk of PBC.

Conclusion

The two-sample bidirectional MR analysis revealed that SLE and PBC were high-risk factors for each other, indicating that they had similar genetic bases, which could to some extent overcome the limitation of insufficient overlap in case samples of SLE and PBC. The analysis of transcriptome overlapping hub genes provided a theoretical basis for the potential mechanisms and therapeutic targets of SLE with PBC overlapping cases.
Causality between rheumatoid arthritis and the risk of cognitive impairment: a Mendelian randomization study
Authors: Duan Lincheng , Li Shiyin , Li Haoming , Shi Yue , Xie Xiaolong , Feng Yue
Published: January 2024

Background

There is mounting proof that rheumatoid arthritis (RA) and cognitive decline are related. These studies, however, have not all been uniform, and others have not discovered such a correlation. It is essential to investigate the link between RA and cognitive decline.

Method

We conducted a Mendelian randomization analysis utilizing three different publicly accessible RA GWAS summary datasets and a variety of meticulously verified instrumental variables. We mostly used inverse variance weighting (IVW), as well as MR-Egger, weighted median, MR-PRESSO, and several sensitivity analyses, to figure out the link between RA and cognitive impairment (CI).

Results

Our MR study identified the causality between RA and declining cognitive performance (β = − 0.010, 95% CI of − 0.017 to − 0.003, P = 4.33E−03) and cognitive function (β = − 0.029, 95% CI of − 0.053 to − 0.005, P = 1.93E−02). The consistent direction of the connection is revealed by sensitivity analysis utilizing the weighted median and the MR-Egger method. Furthermore, we reproduced our findings across two additional RA datasets and found identical outcomes, strengthening the validity of our findings.

Conclusion

This study offers proof of causality between RA and an increased risk of CI. Our findings highlight the importance of examining RA patients for cognitive ability, which may open up fresh ideas for the prevention of CI.
Effects of single and repeated bouts of flywheel exercise on jump performance and muscle damage in athletes and non athletes
Authors: Shimizu Takashi , Tsuchiya Yosuke , Ueda Hisashi , Izumi Shigeki , Ochi Eisuke
Published: January 2024

Background

Although recent studies have investigated the effects of flywheel (FW) training on muscle function, the effects of transient FW exercise on jump performance in athletes are unknown. This study examined the effects of single and repeated bouts of FW squat exercises on jump performance and muscle damage in male collegiate basketball players.

Methods

The participants were 10 healthy college-age men (nonathletes) and 11 male basketball players (athletes). The intervention involved 100 squat exercises (10 repetitions × 10 sets) using an FW device. To examine the repeated-bout effects, the protocol was conducted again after a 2-week interval. Squat jumps, countermovement jumps, drop jumps, and rebound jumps were evaluated as jump performance, while isometric maximal voluntary contraction (MVC) torque in knee extension, muscle soreness, range of motion, thigh circumference, muscle thickness, and echo intensity were evaluated as markers of muscle damage. Measurements were taken at baseline, immediately after exercise, 24 h later, and 72 h later.

Results

The jump performance of nonathletes decreased after exercise (p < 0.05), while that of the athletes did not. The results were similar for muscle soreness. MVC torque decreased significantly after the first exercise in both groups (p < 0.05) and was significantly lower in the nonathletes versus athletes. Significant repeated-bout effects were found for muscle soreness in nonathletes but not athletes.

Conclusions

These results suggest that a single bout of FW exercise reduces jump performance in male nonathletes but not basketball players.
Physical and autonomic functionality in women with breast cancer pre and post chemotherapy: a case control study
Authors: Sousa Bruna Lorena Soares Cavalcante , dos Santos Rosa Thiago , Silvino Valmir Oliveira , Barros Esmeralda Maria Lustosa , de Luca Corrêa Hugo , do Prado Danilo Marcelo Leite , Veras-Silva Acácio Salvador , de Souza Mariana Duarte , de Lima Carlos Eduardo Batista , de Oliveira Luciano Fonseca Lemos , dos Santos Marcos Antonio Pereira
Published: January 2024

Background

Breast cancer (BC) is one of the most incident types of cancer among women in the world. Although chemotherapy is an effective way to treat several types of cancer, it may also cause serious complications, including cardiotoxicity. This study aimed to identify the impact of chemotherapy on functional capacity, muscle strength and autonomic function.

Methods

Ten breast cancer patients in therapeutic follow-up (TG) and ten women without comorbidities (CG) participated in the study (46±8.87 years old). Both groups were evaluated at two time points, before and 20 weeks after the start of chemotherapy. Functional capacity and muscle strength were assessed by 6-minute walk test (6MWT) and handgrip test, respectively. Autonomic function was assessed by heart rate variability analysis.

Results

TG presented greater reductions in the handgrip test for the non-dominant hand (TG ↓15.2%; CG: ↑1.1%, p<0.05) compared to GC. However, no significant differences were found regarding VO2max (p>0.05) and 6MWT total distance (p>0.05). Regarding the heart rate variability variables before and after follow-up period, rMSSD (CG= 39.15±37.66; TG= 14.89±8.28, p= 0.01) and SDNN (CG= 55.77±40.03; TG= 26.30±10.37, p= 0.02) showed effect in the group and time interaction, whereas the LF/HF ratio presented significant difference only in the time analysis (CG= 2.24±2.30; TG= 2.84±1.82, p= 0.04).

Conclusion

Chemotherapy used in the treatment of breast cancer patients resulted in decreased muscle strength and autonomic imbalance. The data suggests that chemotherapy may carry the risk of developing cardiovascular disease.

Trial registration

Registration not required.