bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV status and knowledge of cervical cancer among women in Ghana
Authors: Enyan Nancy Innocentia Ebu , Ken-Amoah Sebastian , Tuoyire Derek Anamaale , Akakpo Kafui Patrick , Agyare Elizabeth , Obiri-Yeboah Dorcas
Published: February 2024

Background

Cervical cancer remains a disease of significant concern to women’s health. The aim of this study was to identify predictors of knowledge of cervical cancer among women living with HIV and those with negative or unknown HIV status at the Cape Coast Teaching Hospital (CCTH).

Methods

This study was based on a larger hospital-based analytical cross-sectional study conducted at the antiretroviral therapy (ART) and gynaecology clinics of the Cape Coast Teaching Hospital in Ghana. Participants were women living with HIV (WLHIV) and women without HIV or whose status was unknown, aged 25 to 65 years, seeking healthcare. Data were collected with a questionnaire and analysed using frequencies, percentages, Chi-square test, binary logistic regression and multivariate analysis.

Results

The mean age was 39.5 years (± 9.8) and 47.2 years (± 10.7) for women without or unknown HIV and WLHIV, respectively. HIV-negative/unknown women were mostly nulligravida (76%) and nullipara (69%), while WLHIV mostly had pregnancies (76%) and children (84%) in excess of seven. Knowledge of cervical cancer was statistically significantly associated with HIV status (X2 = 75.65; P-value = 0.001). The odds of having knowledge of cervical cancer for women considered to be negative/unknown for HIV were about three times (AOR = 3.07; 95% CI = 1.47, 6.41) higher than their compatriots with HIV. Women with post-secondary/tertiary (AOR = 4.45; 95% CI = 2.11, 9.35) education had significantly higher odds of having knowledge of cervical cancer than those with no education or those with just primary education.

Conclusions

To improve knowledge of cervical cancer among women, an intentionally structured health education programme is needed, particularly for WLHIV, those with lower levels of education and the unemployed.
Teaching breaking bad news in a gyneco-oncological setting: a feasibility study implementing the SPIKES framework for undergraduate medical students
Authors: Zemlin Cosima , Nourkami-Tutdibi Nasenien , Schwarz Pascal , Wagenpfeil Gudrun , Goedicke-Fritz Sybelle
Published: February 2024

Background

It is a crucial task for physicians to deliver life threatening information to patients (breaking bad news; BBN). Many aspects influence these conversations on both sides, patients, and doctors. BBN affects the patient-physician relationship, patients’ outcome, and physicians’ health. Many physicians are still untrained for this multi-facetted task and feel unprepared and overburdened when facing situations of BBN. Therefore, any faculties should aim to integrate communication skills into their medical curricula as early as possible. The SPIKES protocol is an effective framework to deliver BBN. Aim of this study is to evaluate the feasibility and obstacles of a BBN seminar and its acceptance and learning curve among undergraduate medical students.

Methods

158 2nd year undergraduate medical students attended a compulsory BBN seminar. The task was to deliver a cancer diagnosis to the patient within a patient - physician role-play in a gyneco-oncological setting before and after a presentation of the SPIKES protocol by the lecturer. The students evaluated important communication skills during these role-plays respectively. Self-assessment questionnaires were obtained at the beginning and end of the seminar.

Results

Most students indicated that their confidence in BBN improved after the seminar (p < 0.001). They like the topic BBN to be part of lectures (76%) and electives (90%). Communication skills improved. Lecturer and seminar were positively evaluated (4.57/5).

Conclusion

The seminar significantly increased confidence and self-awareness in delivering life-threatening news to patients among undergraduate medical students. Important learning aspects of BBN and communication skills could be delivered successfully to the participants within a short time at low costs. The integration of communication skills should be implemented longitudinally into medical curricula starting before clinical education to increase the awareness of the importance of communication skills, to decrease anxiety, stress, and workload for future doctors and– most importantly– to the benefit of our patients.
Usability and feasibility analysis of an mHealth-tool for supporting physical activity in people with heart failure
Authors: Blomqvist Andreas , Bäck Maria , Klompstra Leonie , Strömberg Anna , Jaarsma Tiny
Published: February 2024

Background

Physical inactivity and a sedentary lifestyle are common among people with heart failure (HF), which may lead to worse prognosis. On an already existing mHealth platform, we developed a novel tool called the Activity coach, aimed at increasing physical activity. The aim of this study was to evaluate the usability of the Activity coach and assess feasibility of outcome measures for a future efficacy trial.

Methods

A mixed-methods design was used to collect data. People with a HF diagnosis were recruited to use the Activity coach for four weeks. The Activity coach educates the user about physical activity, provides means of registering daily physical activity and helps the user to set goals for the next week. The usability was assessed by analysing system user logs for adherence, reported technical issues and by interviews about user experiences. Outcome measures assessed for feasibility were objective physical activity as measured by an accelerometer, and subjective goal attainment. Progression criteria for the usability assessment and for the proposed outcomes, were described prospectively.

Results

Ten people with HF were recruited, aged 56 to 78 with median age 72. Data from nine of the ten study participants were included in the analyses. Usability: The Activity coach was used 61% of the time and during the first week two study participants called to seek technical support. The Activity coach was found to be intuitive and easy to use by all study participants. An increased motivation to be more physically active was reported by six of the nine study participants. However, in spite of feeling motivated, four reported that their habits or behaviours had not been affected by the Activity coach. Feasibility: Data was successfully stored in the deployed hardware as intended and the accelerometers were used enough, for the data to be analysable. One finding was that the subjective outcome goal attainment, was challenging to collect. A proposed mitigator for this is to use pre-defined goals in future studies, as opposed to having the study participants be completely free to formulate the goals themselves.

Conclusions

It was confirmed that the Activity coach was easy to use. Furthermore, it might stimulate increased physical activity in a population of people with HF, who are physically inactive. The outcomes investigated seem feasible to include in a future efficacy trial.

Trial registration

ClinicalTrials.gov identifier: NCT05235763. Date of first registration: 11/02/2022.
RNA sequencing reveals differential long noncoding RNA expression profiles in bacterial and viral meningitis in children
Authors: Li Xin , Sun Suzhen , Zhang Huifeng
Published: February 2024

Background

We aimed to investigate the involvement of long non-coding RNA (lncRNA) in bacterial and viral meningitis in children.

Methods

The peripheral blood of five bacterial meningitis patients, five viral meningitis samples, and five healthy individuals were collected for RNA sequencing. Then, the differentially expressed lncRNA and mRNA were detected in bacterial meningitis vs. controls, viral meningitis vs. healthy samples, and bacterial vs. viral meningitis patients. Besides, co-expression and the competing endogenous RNA (ceRNA) networks were constructed. Receiver operating characteristic curve (ROC) analysis was performed.

Results

Compared with the control group, 2 lncRNAs and 32 mRNAs were identified in bacterial meningitis patients, and 115 lncRNAs and 54 mRNAs were detected in viral meningitis. Compared with bacterial meningitis, 165 lncRNAs and 765 mRNAs were identified in viral meningitis. 2 lncRNAs and 31 mRNAs were specific to bacterial meningitis, and 115 lncRNAs and 53 mRNAs were specific to viral meningitis. The function enrichment results indicated that these mRNAs were involved in innate immune response, inflammatory response, and immune system process. A total of 8 and 1401 co-expression relationships were respectively found in bacterial and viral meningitis groups. The ceRNA networks contained 1 lncRNA-mRNA pair and 4 miRNA-mRNA pairs in viral meningitis group. GPR68 and KIF5C, identified in bacterial meningitis co-expression analysis, had an area under the curve (AUC) of 1.00, while the AUC of OR52K2 and CCR5 is 0.883 and 0.698, respectively.

Conclusions

Our research is the first to profile the lncRNAs in bacterial and viral meningitis in children and may provide new insight into understanding meningitis regulatory mechanisms.
Efficient production of 1,2,4-butanetriol from corn cob hydrolysate by metabolically engineered Escherichia coli
Authors: Li Ping , Wang Mengjiao , Di Haiyan , Du Qihang , Zhang Yipeng , Tan Xiaoxu , Xu Ping , Gao Chao , Jiang Tianyi , Lü Chuanjuan , Ma Cuiqing
Published: February 2024

Corn cob is a major waste mass-produced in corn agriculture. Corn cob hydrolysate containing xylose, arabinose, and glucose is the hydrolysis product of corn cob. Herein, a recombinant Escherichia coli strain BT-10 was constructed to transform corn cob hydrolysate into 1,2,4-butanetriol, a platform substance with diversified applications. To eliminate catabolite repression and enhance NADPH supply for alcohol dehydrogenase YqhD catalyzed 1,2,4-butanetriol generation, ptsG encoding glucose transporter EIICBGlc and pgi encoding phosphoglucose isomerase were deleted. With four heterologous enzymes including xylose dehydrogenase, xylonolactonase, xylonate dehydratase, α-ketoacid decarboxylase and endogenous YqhD, E. coli BT-10 can produce 36.63 g/L 1,2,4-butanetriol with a productivity of 1.14 g/[L·h] using xylose as substrate. When corn cob hydrolysate was used as the substrate, 43.4 g/L 1,2,4-butanetriol was generated with a productivity of 1.09 g/[L·h] and a yield of 0.9 mol/mol. With its desirable characteristics, E. coli BT-10 is a promising strain for commercial 1,2,4-butanetriol production.
Extracellular vesicles produced by irradiated endothelial or Glioblastoma stem cells promote tumor growth and vascularization modulating tumor microenvironment
Authors: Castellani Giorgia , Buccarelli Mariachiara , D’Alessandris Quintino Giorgio , Ilari Ramona , Cappannini Andrea , Pedini Francesca , Boe Alessandra , Lulli Valentina , Parolini Isabella , Giannetti Stefano , Biffoni Mauro , Zappavigna Vincenzo , Marziali Giovanna , Pallini Roberto , Ricci-Vitiani Lucia
Published: February 2024

Background

Glioblastoma (GBM) is the most lethal primary brain tumor in adult, characterized by highly aggressive and infiltrative growth. The current therapeutic management of GBM includes surgical resection followed by ionizing radiations and chemotherapy. Complex and dynamic interplay between tumor cells and tumor microenvironment drives the progression and contributes to therapeutic resistance. Extracellular vesicles (EVs) play a crucial role in the intercellular communication by delivering bioactive molecules in the surrounding milieu modulating tumor microenvironment.

Methods

In this study, we isolated by ultracentrifugation EVs from GBM stem-like cell (GSC) lines and human microvascular endothelial cells (HMVECs) exposed or not to ionizing irradiation. After counting and characterization, we evaluated the effects of exposure of GSCs to EVs isolated from endothelial cells and vice versa. The RNA content of EVs isolated from GSC lines and HMVECs exposed or not to ionizing irradiation, was analyzed by RNA-Seq. Periostin (POSTN) and Filamin-B (FLNB) emerged in gene set enrichment analysis as the most interesting transcripts enriched after irradiation in endothelial cell-derived EVs and GSC-derived EVs, respectively. POSTN and FLNB expression was modulated and the effects were analyzed by in vitro assays.

Results

We confirmed that ionizing radiations increased EV secretion by GSCs and normal endothelial cells, affected the contents of and response to cellular secreted EVs. Particularly, GSC-derived EVs decreased radiation-induced senescence and promoted migration in HMVECs whereas, endothelial cell-derived EVs promoted tumorigenic properties and endothelial differentiation of GSCs. RNA-Seq analysis of EV content, identified FLNB and POSTN as transcripts enriched in EVs isolated after irradiation from GSCs and HMVECs, respectively. Assays performed on POSTN overexpressing GSCs confirmed the ability of POSTN to mimic the effects of endothelial cell-derived EVs on GSC migration and clonogenic abilities and transdifferentiation potential. Functional assays performed on HMVECs after silencing of FLNB supported its role as mediator of the effects of GSC-derived EVs on senescence and migration.

Conclusion

In this study, we identified POSTN and FLNB as potential mediators of the effects of EVs on GSC and HMVEC behavior confirming that EVs play a crucial role in the intercellular communication by delivering bioactive molecules in the surrounding milieu modulating tumor microenvironment.
Screening ovarian cancer by using risk factors: machine learning assists
Authors: Nopour Raoof
Published: February 2024

Background and aim

Ovarian cancer (OC) is a prevalent and aggressive malignancy that poses a significant public health challenge. The lack of preventive strategies for OC increases morbidity, mortality, and other negative consequences. Screening OC through risk prediction could be leveraged as a powerful strategy for preventive purposes that have not received much attention. So, this study aimed to leverage machine learning approaches as predictive assistance solutions to screen high-risk groups of OC and achieve practical preventive purposes.

Materials and methods

As this study is data-driven and retrospective in nature, we leveraged 1516 suspicious OC women data from one concentrated database belonging to six clinical settings in Sari City from 2015 to 2019. Six machine learning (ML) algorithms, including XG-Boost, Random Forest (RF), J-48, support vector machine (SVM), K-nearest neighbor (KNN), and artificial neural network (ANN) were leveraged to construct prediction models for OC. To choose the best model for predicting OC, we compared various prediction models built using the area under the receiver characteristic operator curve (AU-ROC).

Results

Current experimental results revealed that the XG-Boost with AU-ROC = 0.93 (0.95 CI = [0.91–0.95]) was recognized as the best-performing model for predicting OC.

Conclusions

ML approaches possess significant predictive efficiency and interoperability to achieve powerful preventive strategies leveraging OC screening high-risk groups.
Covid-19 vaccination: a mixed methods analysis of health system resilience in Latin America
Authors: Hernandez-Pineda Estefania , Amaya Ciro-Alberto , González-Uribe Catalina , Herrera Andrea , Velasco Nubia
Published: February 2024

Background

This paper discusses the stages of health system resilience (HSR) and the factors underlying differences in HSR during the covid-19 pandemic, especially the vaccination challenge. We studied the relationship between vaccination strategies and macro-context backgrounds in 21 Latin American countries. Our objective was to capture the impact of those aspects in the SR and identify potential improvements for future crises and for vaccination programs in general.

Methods

The study uses mixed-methods research to provide insights into how the countries’ backgrounds and vaccination strategies impact the HSR. Particularly, we used explanatory sequential mixed methods, which entails a quantitative-qualitative two-phase sequence. The quantitative phase was conducted using cluster and variance analysis, in which the HSR was measured using as a proxy the covid-19 vaccination outcomes in three cut-offs of reaching 25%, 50%, and 75% of population coverage. This approach allows us to discriminate covid-19 vaccination progress by stages and contrast it to the qualitative stage, in which we performed a country-case analysis of the background conditions and the changes in vaccination strategies that occurred during the corresponding dates.

Results

The paper provides a rich comparative case analysis of countries, classifying them by early, prompt, and delayed performers. The results show that differences in vaccination performance are due to flexibility in adapting strategies, cooperation, and the ability to design multilevel solutions that consider the needs of various actors in the health ecosystem. These differences vary depending on the vaccination stage, which suggests the importance of acknowledging learning, diffusion, and feedback processes at the regional level.

Conclusions

We identified the importance of societal well-being as an ideal country antecedent for high and sustained levels of performance in covid-19 vaccination. Whereas in other countries where the set-up and beginning phases were rough, the value of the operational decisions and the learning on the move regarding their own and their peers’ trajectories were crucial and were reflected in performance improvement. A contribution of this study is that the above-mentioned analysis was done using vaccination coverage cut-off points that allow a performance view that takes into consideration the stages of the vaccination progress and the learning process that goes with it. As well as framing this into the HSR shock cycles that allow to differentiate the stages of resilience on which countries must act.
Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China
Authors: Li Jun , Tang Mengli , Liu Zhaojun , Wei Yuhan , Xia Fengjun , Xia Yubing , Hu Yongmei , Wang Haichen , Zou Mingxiang
Published: February 2024

Background

Recently, extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) isolates have been increasingly detected and posed great challenges to clinical anti-infection treatments. However, little is known about extensively resistant hypervirulent P. aeruginosa (XDR-hvPA). In this study, we investigate its epidemiological characteristics and provide important basis for preventing its dissemination.

Methods

Clinical XDR-PA isolates were collected from January 2018 to January 2023 and identified using matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry; antibiotic susceptibility testing was performed by broth microdilution method, and minimum inhibitory concentrations (MICs) were evaluated. Virulence was evaluated using the Galleria mellonella infection model; molecular characteristics, including resistance genes, virulence genes, and homology, were determined using whole-genome sequencing.

Results

A total of 77 XDR-PA strains were collected; 47/77 strains were XDR-hvPA. Patients aged > 60 years showed a significantly higher detection rate of XDR-hvPA than of XDR-non-hvPA. Among the 47 XDR-hvPA strains, 24 strains carried a carbapenemase gene, including blaGES−1 (10/47), blaVIM−2 (6/47), blaGES−14 (4/47), blaIMP−45 (2/47), blaKPC−2 (1/47), and blaNDM−14 (1/47). ExoU, exoT, exoY, and exoS, important virulence factors of PA, were found in 31/47, 47/47, 46/47, and 29/47 strains, respectively. Notably, two XDR-hvPA simultaneously co-carried exoU and exoS. Six serotypes (O1, O4–O7, and O11) were detected; O11 (19/47), O7 (13/47), and O4 (9/47) were the most prevalent. In 2018–2020, O4 and O7 were the most prevalent serotypes; 2021 onward, O11 (16/26) was the most prevalent serotype. Fourteen types of ST were detected, mainly ST235 (14/47), ST1158 (13/47), and ST1800 (7/47). Five global epidemic ST235 XDR-hvPA carried blaGES and showed the MIC value of ceftazidime/avibactam reached the susceptibility breakpoint (8/4 mg/L).

Conclusions

The clinical detection rate of XDR-hvPA is unexpectedly high, particularly in patients aged > 60 years, who are seemingly more susceptible to contracting this infection. Clonal transmission of XDR-hvPA carrying blaGES, which belongs to the global epidemic ST235, was noted. Therefore, the monitoring of XDR-hvPA should be strengthened, particularly for elderly hospitalized patients, to prevent its spread.
A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration
Authors: Yang Shi-Yuan , Zhou Yu-Ning , Yu Xing-Ge , Fu Ze-Yu , Zhao Can-Can , Hu Yue , Lin Kai-Li , Xu Yuan-Jin
Published: February 2024

Background

Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities.

Results

Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-β (TGF-β) signaling pathway.

Conclusion

Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.

Graphical Abstract
SERPINC1 c.1247dupC: a novel SERPINC1 gene mutation associated with familial thrombosis results in a secretion defect and quantitative antithrombin deficiency
Authors: Ruf Maximilian , Cunningham Sarah , Wandersee Alexandra , Brox Regine , Achenbach Susanne , Strobel Julian , Hackstein Holger , Schneider Sabine
Published: February 2024

Background

Antithrombin (AT) is an important anticoagulant in hemostasis. We describe here the characterization of a novel AT mutation associated with clinically relevant thrombosis. A pair of sisters with confirmed type I AT protein deficiency was genetically analyzed on suspicion of an inherited SERPINC1 mutation. A frameshift mutation, c.1247dupC, was identified and the effect of this mutation was examined on the cellular and molecular level.

Methods

Plasmids for the expression of wild-type (WT) and mutated SERPINC1 coding sequence (CDS) fused to green fluorescent protein (GFP) or hemagglutinin (HA) tag were transfected into HEK293T cells. Subcellular localization and secretion of the respective fusion proteins were analyzed by confocal laser scanning microscopy and Western blot.

Results

The c.1247dupC mutation results in a frameshift in the CDS of the SERPINC1 gene and a subsequently altered amino acid sequence (p.Ser417LysfsTer48). This alteration affects the C-terminus of the AT antigen and results in impaired secretion as confirmed by GFP- and HA-tagged mutant AT analyzed in HEK293T cells.

Conclusion

The p.Ser417LysfsTer48 mutation leads to impaired secretion, thus resulting in a quantitative AT deficiency. This is in line with the type I AT deficiency observed in the patients.
Role of ferroptosis in chronic kidney disease
Authors: Li Shiyang , Han Qiuxia , Liu Chang , Wang Yixue , Liu Fengxun , Pan Shaokang , Zuo Lihua , Gao Dan , Chen Kai , Feng Qi , Liu Zhangsuo , Liu Dongwei
Published: February 2024

Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment.
Connexin32 gap junction channels deliver miR155-3p to mediate pyroptosis in renal ischemia-reperfusion injury
Authors: Chen Liubing , Fang Hongyi , Li Xiaoyun , Yu Peiling , Guan Yu , Xiao Cuicui , Deng Zhizhao , Hei Ziqing , Chen Chaojin , Luo Chenfang
Published: February 2024

Objectives

To explore whether the gap junction (GJ) composed by connexin32(Cx32) mediated pyroptosis in renal ischemia-reperfusion(I/R) injury via transmitting miR155-3p, with aim to provide new strategies for the prevention and treatment of acute kidney injury (AKI) after renal I/R.

Methods

8–10 weeks of male C57BL/ 6 wild-type mice and Cx32 knockdown mice were divided into two groups respectively: control group and renal I/R group. MCC950 (50 mg/kg. ip.) was used to inhibit NLRP3 in vivo. Human kidney tubular epithelial cells (HK - 2) and rat kidney tubular epithelial cells (NRK-52E) were divided into high-density group and low-density group, and treated with hypoxia reoxygenation (H/R) to mimic I/R. The siRNA and plasmid of Cx32, mimic and inhibitor of miR155-3p were transfected into HK - 2 cells respectively. Kidney pathological and functional injuries were measured. Western Blot and immunofluorescent staining were used to observe the expression of NLRP3, GSDMD, GSDMD-N, IL - 18, and mature IL-18. The secretion of IL-18 and IL-1β in serum, kidney tissue and cells supernatant were detected by enzyme-linked immuno sorbent assay (ELISA) kit, and the expression of NLPR3 and miR155-3p were detected by RT-qPCR and fluorescence in situ hybridization (FISH).

Results

Tubular pyroptosis were found to promote AKI after I/R in vivo and Cx32-GJ regulated pyroptosis by affecting the expression of miR155-3p after renal I/R injury. In vitro, H/R could lead to pyroptosis in HK-2 and NRK-52E cells. When the GJ channels were not formed, and Cx32 was inhibited or knockdown, the expression of miR155-3p was significantly reduced and the pyroptosis was obviously inhibited, leading to the reduction of injury and the increase of survival rate. Moreover, regulating the level of miR155-3p could affect survival rate and pyroptosis in vitro after H/R.

Conclusions

The GJ channels composed of Cx32 regulated tubular pyroptosis in renal I/R injury by transmitting miR155-3p. Inhibition of Cx32 could reduce the level of miR155-3p further to inhibit pyroptosis, leading to alleviation of renal I/R injury which provided a new strategy for preventing the occurrence of AKI.
Revealing role of epigenetic modifiers and DNA oxidation in cell-autonomous regulation of Cancer stem cells
Authors: Ferrer-Diaz Alejandra I. , Sinha Garima , Petryna Andrew , Gonzalez-Bermejo Ruth , Kenfack Yannick , Adetayo Oluwadamilola , Patel Shyam A. , Hooda-Nehra Anupama , Rameshwar Pranela
Published: February 2024

Background

Breast cancer cells (BCCs) can remain undetected for decades in dormancy. These quiescent cells are similar to cancer stem cells (CSCs); hence their ability to initiate tertiary metastasis. Dormancy can be regulated by components of the tissue microenvironment such as bone marrow mesenchymal stem cells (MSCs) that release exosomes to dedifferentiate BCCs into CSCs. The exosomes cargo includes histone 3, lysine 4 (H3K4) methyltransferases - KMT2B and KMT2D. A less studied mechanism of CSC maintenance is the process of cell-autonomous regulation, leading us to examine the roles for KMT2B and KMT2D in sustaining CSCs, and their potential as drug targets.

Methods

Use of pharmacological inhibitor of H3K4 (WDR5–0103), knockdown (KD) of KMT2B or KMT2D in BCCs, real time PCR, western blot, response to chemotherapy, RNA-seq, and flow cytometry for circulating markers of CSCs and DNA hydroxylases in BC patients. In vivo studies using a dormancy model studied the effects of KMT2B/D to chemotherapy.

Results

H3K4 methyltransferases sustain cell autonomous regulation of CSCs, impart chemoresistance, maintain cycling quiescence, and reduce migration and proliferation of BCCs. In vivo studies validated KMT2’s role in dormancy and identified these genes as potential drug targets. DNA methylase (DNMT), predicted within a network with KMT2 to regulate CSCs, was determined to sustain circulating CSC-like in the blood of patients.

Conclusion

H3K4 methyltransferases and DNA methylation mediate cell autonomous regulation to sustain CSC. The findings provide crucial insights into epigenetic regulatory mechanisms underlying BC dormancy with KMT2B and KMT2D as potential therapeutic targets, along with standard care. Stem cell and epigenetic markers in circulating BCCs could monitor treatment response and this could be significant for long BC remission to partly address health disparity.
The clinical value of P-wave terminal force in lead V1 in evaluating pericardial thickness in tuberculous constrictive pericarditis
Authors: Ren Yanhong
Published: February 2024

Aim

To investigate the relationship between p wave terminal force (Ptfv1) and pericardial thickness in patients with tuberculous constrictive pericarditis.

Methods

From January 2018 to October 2022, 95 patients with tuberculous constrictive pericarditis who needed pericarditis dissection in a hospital were collected, and 3 patients who did not meet the criteria were excluded, a total of 92 cases. The absolute value of Ptfv1 in conventional electrocardiogram was tested before surgery, and pericardial thickness was measured by echocardiography and chest CT. Pericardial thickness was measured after pericardial dissection. Pearson correlation analysis was used, R software was used to make scatter plot, and non-parametric square test was used. The correlation of postoperative measurements with echocardiography, chest CT and absolute value of Ptfv1 was analyzed.

Results

Pearson correlation analysis was conducted with postoperative measurements and echocardiography measurements, postoperative measurements and chest CT measurements, and postoperative measurements and absolute value of Ptfv1. Pearson correlation analysis showed that the correlation coefficients between postoperative measurements and echocardiography, chest CT and Ptfv1 values were statistically significant. Scatter plot and nonparametric Chi-square test showed that postoperative measurements were consistent with absolute values of echocardiography, chest CT and Ptfv1 (p < 0.05). And this study found that the distribution of the value of Ptfv1 ≥ 5 was higher than the value of Ptfv1 < 5 after pericardiectomy (0.95:0.05) in the absolute value of Ptfv1 ≥ 0.04 which measured before pericardiectomy. The hypothesis was statistically significant (p < 0.05).

Conclusion

The absolute value of Ptfv1 in electrocardiogram can be used as an auxiliary diagnostic index to evaluate pericardial thickness in tuberculous constrictive pericarditis.
Knowledge graph construction based on granulosa cells transcriptome from polycystic ovary syndrome with normoandrogen and hyperandrogen
Authors: Liu Wensu , Tang Tianyu , Feng Jianwei , Wang Chunyu , Lin Lin , Wang Shengli , Zeng Kai , Zou Renlong , Yang Zeyu , Zhao Yue
Published: February 2024

PCOS is a widespread disease that primarily caused in-pregnancy in pregnant-age women. Normoandrogen (NA) and Hyperandrogen (HA) PCOS are distinct subtypes of PCOS, while bio-markers and expression patterns for NA PCOS and HA PCOS have not been disclosed. We performed microarray analysis on granusola cells from NA PCOS, HA PCOS and normal tissue from 12 individuals. Afterwards, microarray data were processed and specific genes for NA PCOS and HA PCOS were identified. Further functional analysis selected IL6R and CD274 as new NA PCOS functional markers, and meanwhile selected CASR as new HA PCOS functional marker. IL6R, CD274 and CASR were afterwards experimentally validated on mRNA and protein level. Subsequent causal relationship analysis based on Apriori Rules Algorithm and co-occurrence methods identified classification markers for NA PCOS and HA PCOS. According to classification markers, downloaded transcriptome datasets were merged with our microarray data. Based on merged data, causal knowledge graph was constructed for NA PCOS or HA PCOS and female infertility on NA PCOS and HA PCOS. Gene-drug interaction analysis was then performed and drugs for HA PCOS and NA PCOS were predicted. Our work was among the first to indicate the NA PCOS and HA PCOS functional and classification markers and using markers to construct knowledge graphs and afterwards predict drugs for NA PCOS and HA PCOS based on transcriptome data. Thus, our study possessed biological and clinical value on further understanding the inner mechanism on the difference between NA PCOS and HA PCOS.
Plasma campesterol and ABCG5/ABCG8 gene loci on the risk of cholelithiasis and cholecystitis: evidence from Mendelian randomization and colocalization analyses
Authors: Mi Jiarui , Jiang Qingwei , Qi Zhengwei , Liu Zhengye , Bai Xiaoyin , Zheng Xia , Wu Jiaguo , Fang Yanfei , Yang Aiming , Chen Haotian
Published: February 2024

The causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation.
Oncogenic alterations in advanced NSCLC: a molecular super-highway
Authors: Friedlaender Alex , Perol Maurice , Banna Giuseppe Luigi , Parikh Kaushal , Addeo Alfredo
Published: February 2024

Lung cancer ranks among the most common cancers world-wide and is the first cancer-related cause of death. The classification of lung cancer has evolved tremendously over the past two decades. Today, non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma, comprises a multitude of molecular oncogenic subsets that change both the prognosis and management of disease.

Since the first targeted oncogenic alteration identified in 2004, with the epidermal growth factor receptor (EGFR), there has been unprecedented progress in identifying and targeting new molecular alterations. Almost two decades of experience have allowed scientists to elucidate the biological function of oncogenic drivers and understand and often overcome the molecular basis of acquired resistance mechanisms. Today, targetable molecular alterations are identified in approximately 60% of lung adenocarcinoma patients in Western populations and 80% among Asian populations. Oncogenic drivers are largely enriched among non-smokers, east Asians, and younger patients, though each alteration has its own patient phenotype.

The current landscape of druggable molecular targets includes EGFR, anaplastic lymphoma kinase (ALK), v-raf murine sarcoma viral oncogene homolog B (BRAF), ROS proto-oncogene 1 (ROS1), Kirstin rat sarcoma virus (KRAS), human epidermal receptor 2 (HER2), c-MET proto-oncogene (MET), neurotrophic receptor tyrosine kinase (NTRK), rearranged during transfection (RET), neuregulin 1 (NRG1). In addition to these known targets, others including Phosphoinositide 3-kinases (PI3K) and fibroblast growth factor receptor (FGFR) have garnered significant attention and are the subject of numerous ongoing trials.

In this era of personalized, precision medicine, it is of paramount importance to identify known or potential oncogenic drivers in each patient. The development of targeted therapy is mirrored by diagnostic progress. Next generation sequencing offers high-throughput, speed and breadth to identify molecular alterations in entire genomes or targeted regions of DNA or RNA. It is the basis for the identification of the majority of current druggable alterations and offers a unique window into novel alterations, and de novo and acquired resistance mechanisms.

In this review, we discuss the diagnostic approach in advanced NSCLC, focusing on current oncogenic driver alterations, through their pathophysiology, management, and future perspectives. We also explore the shortcomings and hurdles encountered in this rapidly evolving field.
Plant-based diets and cardiovascular risk factors: a comparison of flexitarians, vegans and omnivores in a cross-sectional study
Authors: Bruns Anja , Greupner Theresa , Nebl Josefine , Hahn Andreas
Published: February 2024

Background

The growing trend towards conscious and sustainable dietary choices has led to increased adoption of flexitarian diets, characterised by plant-based eating habits with occasional consumption of meat and processed meat products. However, the cardiovascular disease (CVD) risk factors associated with flexitarian diets compared to both vegans and omnivores remain underexplored.

Methods

In this cross-sectional study, 94 healthy participants aged 25–45 years, categorized into long-term flexitarians (FXs ≤ 50 g/day of meat and meat products, n = 32), vegans (Vs, no animal products, n = 33), and omnivores (OMNs ≥ 170 g/day of meat and meat products, n = 29) were included. Various CVD risk factors were measured, including fasting blood samples for metabolic biomarkers, body composition analysis via bioimpedance, blood pressure measurements, arterial stiffness evaluated through pulse wave velocity (PWV) and metabolic syndrome (MetS) severity was determined using browser-based calculations (MetS-scores). Dietary intake was assessed using a Food Frequency Questionnaire (FFQ), diet quality was calculated with the Healthy Eating Index-flexible (HEI-Flex), while physical activity levels were recorded using the validated Freiburger questionnaire.

Results

The data showed that FXs and Vs had more beneficial levels of insulin, triglycerides, total cholesterol, and LDL cholesterol compared to OMNs. Notably, FXs revealed the most favorable MetS-score results based on both BMI and waistline, and better PWV values than Vs and OMNs. In addition, FXs and Vs reported higher intake rates of vegetables, fruit, nuts/seeds and plant-based milk alternatives.

Conclusion

The flexitarian diet appears to confer cardiovascular benefits. While Vs had the most favorable results overall, this study supports that reducing meat and processed meat products intake, as in flexitarianism, may contribute to CVD risk factor advantages.
What motivates public collaborators to become and stay involved in health research?
Authors: Røssvoll Toril Beate , Liabo Kristin , Hanssen Tove Aminda , Rosenvinge Jan H. , Sundkvist Elisabeth , Pettersen Gunn
Published: February 2024

Background

People with lived experience of health and illness are increasingly being involved in research. Knowing what creates interest in becoming involved in health research may help identify appropriate ways of facilitating meaningful involvement. The study aimed to investigate why people became public collaborators in health research and what helped sustain their commitment to staying involved.

Methods

Semistructured individual qualitative interviews were conducted with 11 Norwegian public collaborators recruited from patient organisations. To enhance the quality and relevance of this study, three public collaborators were involved in framing the study and in the data analysis. One of them is a coauthor of this paper. The interviews were analysed through reflexive thematic analysis, and two themes were generated.

Results

The first theme, ‘research as a vehicle to impact’ showed how interest in becoming involved in research was founded on the possibility of impacting healthcare through research. Other inspiring factors were how they appraised the relevance of the research, in addition to the public collaborators’ own sense of moral duty to advocate for research related to their own as well as others, illnesses or diseases. The second theme, ‘‘Acknowledgement and accessibility’, framed how the participants perceived appreciation of experiential knowledge as crucial for maintaining motivation in their role as public collaborators. Other promoters of sustained involvement presented were training for both public collaborators and researchers, adequate allowance as a means for visualising and valuing PPI, and accessible language.

Conclusions

This study contributes to the understanding of how to facilitate meaningful and sustainable PPI, which requires a safe space for collaboration and attention to accessibility. Facilitating meaningful involvement may, in turn, increase the potential impact and sustainability of PPI.
Emanuel syndrome due to unusual pattern
Authors: El-Bassyouni Hala T. , Ashaat Engy A. , Hamed Khaled , Rashed Maha , Abd-Elnaby Azza E. , Shehab Marwa
Published: February 2024

Background

The hallmarks of Emanuel syndrome are pre- and postnatal growth retardation, microcephaly, global developmental delay, ear anomalies, and in males, heart, kidney, and genital abnormalities.

Results

This study describes the atypical features of Emanuel syndrome, a rare chromosomal disorder. The patient had several physical features that are common in Emanuel syndrome, such as microcephaly, hypotonia, and ear anomalies. However, he exhibited certain unusual characteristics, including the lack of a prominent forehead, epicanthic folds, and a downward slanting palpebral fissure. There was infratentorial brain involution with a minor infarction in the left cerebral hemisphere and cerebellar hypoplasia on the magnetic resonance imaging (MRI) scan of the brain. Additionally, the patient had bilateral mild hearing loss and an aberrant epileptogenic pattern on the electroencephalogram (EEG). Orodental examination showed a long philtrum, everted fissured thick lower lip, highly attached labial frenum, and prominent median palatine raphe. The karyotype revealed 45XY t(11;22)(p15.5;q11.22), which is different from the typical karyotype of Emanuel syndrome.

Conclusions

This case sheds light on the possibility of alternative genetic mechanisms, beyond chromosomal abnormalities, in patients presenting with multiple congenital anomalies and facial dysmorphism.
The possible anti-inflammatory effect of extra virgin olive oil with colchicine in treatment of resistant cases of familial Mediterranean fever in a cohort of pediatric Egyptian patients
Authors: Osman Walla’a A. , Taher Heba , Darweesh Hanan , Abdel Samie Mai , Shaker Olfat G. , Labib Dina A. , Ateyya Hayam
Published: February 2024

Background

People of Mediterranean descent are primarily affected by the autoinflammatory genetic condition known as familial Mediterranean fever (FMF). The disease is resistant to colchicine therapy in 10–20% of patients. Numerous recent animal studies showed promising results of extra virgin olive oil (EVOO) to control inflammation. The objective of this study was to assess the effectiveness of combining EVOO with colchicine in the treatment of colchicine-resistant familial Mediterranean fever (CRFMF) patients.

Results

Both the frequency of episodes and inflammatory indicators significantly decreased after a three-month course of daily EVOO treatment with colchicine. The average erythrocyte sedimentation rate (ESR) of patients was 78.6 mm/h before the EVOO administration, and it dropped to 27.8 mm/h, after that. Additionally, after taking EVOO, the mean serum amyloid A (SAA) decreased from 123.82 mg/dl to 59.78 mg/L. Also, the average C-reactive protein (CRP) decreased from 34.22 to 7.84 mg/dl following its administration; the mean nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) level decreased from 134.92 to 64.23 pg/ml. The mean caspase-1 level decreased from 7.8 to 4.98 ng/ml; and the mean levels of cytokines, interleukin 6 (IL-6), interleukin 1 beta (IL-1 β), and tumor necrosis factor-alpha (TNF-α) decreased from 9.8, 18.14, and 52.7 pg/ml, respectively, to 5.95, 12.51, and 29.39 pg/ml. Finally following the administration of EVOO, there was a notable overall improvement in the quality of life of (CRFMF) patients.

Conclusion

EVOO demonstrated a significant positive impact when paired with the tolerated dosage of colchicine in the management of CRFMF. Improvements were observed in both clinical and laboratory settings, including a reduction in the attack frequency and serum levels of inflammatory markers, such as NLRP3, caspase-1, ESR, CRP, IL-1β, IL-6, and TNF-α without any negative side effects.