bluuebunny/crossref_metadata_2025 huggingface dataset:
IGF2BP3 prevent HMGB1 mRNA decay in bladder cancer and development
Authors: Lv Lei , Wei Qinqin , Zhang Jianxiao , Dong Yitong , Shan Zhenglei , Chang Na , Zhao Ye , Bian Po , Yi Qiyi
Published: March 2024

Background

IGF2BP3 functions as an RNA-binding protein (RBP) and plays a role in the posttranscriptional control of mRNA localization, stability, and translation. Its dysregulation is frequently associated with tumorigenesis across various cancer types. Nonetheless, our understanding of how the expression of the IGF2BP3 gene is regulated remains limited. The specific functions and underlying mechanisms of IGF2BP3, as well as the potential benefits of targeting it for therapeutic purposes in bladder cancer, are not yet well comprehended.

Methods

The mRNA and protein expression were examined by RT-qPCR and western blotting, respectively. The methylation level of CpG sites was detected by Bisulfite sequencing PCR (BSP). The regulation of IGF2BP3 expression by miR-320a-3p was analyzed by luciferase reporter assay. The functional role of IGF2BP3 was determined through proliferation, colony formation, wound healing, invasion assays, and xenograft mouse model. The regulation of HMGB1 by IGF2BP3 was investigated by RNA immunoprecipitation (RIP) and mRNA stability assays.

Results

We observed a significant elevation in IGF2BP3 levels within bladder cancer samples, correlating with more advanced stages and grades, as well as an unfavorable prognosis. Subsequent investigations revealed that the upregulation of IGF2BP3 expression is triggered by copy number gain/amplification and promoter hypomethylation in various tumor types, including bladder cancer. Furthermore, miR-320a-3p was identified as another negative regulator in bladder cancer. Functionally, the upregulation of IGF2BP3 expression exacerbated bladder cancer progression, including the proliferation, migration, and invasion of bladder cancer. Conversely, IGF2BP3 silencing produced the opposite effects. Moreover, IGF2BP3 expression positively correlated with inflammation and immune infiltration in bladder cancer. Mechanistically, IGF2BP3 enhanced mRNA stability and promoted the expression of HMGB1 by binding to its mRNA, which is a factor that promotes inflammation and orchestrates tumorigenesis in many cancers. Importantly, pharmacological inhibition of HMGB1 with glycyrrhizin, a specific HMGB1 inhibitor, effectively reversed the cancer-promoting effects of IGF2BP3 overexpression in bladder cancer. Furthermore, the relationship between HMGB1 mRNA and IGF2PB3 is also observed in mammalian embryonic development, with the expression of both genes gradually decreasing as embryonic development progresses.

Conclusions

Our present study sheds light on the genetic and epigenetic mechanisms governing IGF2BP3 expression, underscoring the critical involvement of the IGF2BP3-HMGB1 axis in driving bladder cancer progression. Additionally, it advocates for the investigation of inhibiting IGF2BP3-HMGB1 as a viable therapeutic approach for treating bladder cancer.

Graphical Abstract
Identification and expression analyses of B3 genes reveal lineage-specific evolution and potential roles of REM genes in pepper
Authors: Park Young-Soo , Cho Hye Jeong , Kim Seungill
Published: March 2024

Background

The B3 gene family, one of the largest plant-specific transcription factors, plays important roles in plant growth, seed development, and hormones. However, the B3 gene family, especially the REM subfamily, has not been systematically and functionally studied.

Results

In this study, we performed genome-wide re-annotation of B3 genes in five Solanaceae plants, Arabidopsis thaliana, and Oryza sativa, and finally predicted 1,039 B3 genes, including 231 (22.2%) newly annotated genes. We found a striking abundance of REM genes in pepper species (Capsicum annuum, Capsicum baccatum, and Capsicum chinense). Comparative motif analysis revealed that REM and other subfamilies (ABI3/VP1, ARF, RAV, and HSI) consist of different amino acids. We verified that the large number of REM genes in pepper were included in the specific subgroup (G8) through the phylogenetic analysis. Chromosome location and evolutionary analyses suggested that the G8 subgroup genes evolved mainly via a pepper-specific recent tandem duplication on chromosomes 1 and 3 after speciation between pepper and other Solanaceae. RNA-seq analyses suggested the potential functions of REM genes under salt, heat, cold, and mannitol stress conditions in pepper (C. annuum).

Conclusions

Our study provides evolutionary and functional insights into the REM gene family in pepper.
Whole genome identification, molecular docking and expression analysis of enzymes involved in the selenomethionine cycle in Cardamine hupingshanensis
Authors: Zeng Xixi , Luo Guoqiang , Fan Zhucheng , Xiao Zhijing , Lu Yanke , Xiao Qiang , Hou Zhi , Tang Qiaoyu , Zhou Yifeng
Published: March 2024

Background

The selenomethionine cycle (SeMTC) is a crucial pathway for the metabolism of selenium. The basic bioinformatics and functions of four enzymes involved in the cycle including S-adenosyl-methionine synthase (MAT), SAM-dependent methyltransferase (MTase), S-adenosyl-homocysteine hydrolase (SAHH) and methionine synthase (MTR), have been extensively reported in many eukaryotes. The identification and functional analyses of SeMTC genes/proteins in Cardamine hupingshanensis and their response to selenium stress have not yet been reported.

Results

In this study, 45 genes involved in SeMTC were identified in the C. hupingshanensis genome. Phylogenetic analysis showed that seven genes from ChMAT were clustered into four branches, twenty-seven genes from ChCOMT were clustered into two branches, four genes from ChSAHH were clustered into two branches, and seven genes from ChMTR were clustered into three branches. These genes were resided on 16 chromosomes. Gene structure and homologous protein modeling analysis illustrated that proteins in the same family are relatively conserved and have similar functions. Molecular docking showed that the affinity of SeMTC enzymes for selenium metabolites was higher than that for sulfur metabolites. The key active site residues identified for ChMAT were Ala269 and Lys273, while Leu221/231 and Gly207/249 were determined as the crucial residues for ChCOMT. For ChSAHH, the essential active site residues were found to be Asn87, Asp139 and Thr206/207/208/325. Ile204, Ser111/329/377, Asp70/206/254, and His329/332/380 were identified as the critical active site residues for ChMTR. In addition, the results of the expression levels of four enzymes under selenium stress revealed that ChMAT3-1 genes were upregulated approximately 18-fold, ChCOMT9-1 was upregulated approximately 38.7-fold, ChSAHH1-2 was upregulated approximately 11.6-fold, and ChMTR3-2 genes were upregulated approximately 28-fold. These verified that SeMTC enzymes were involved in response to selenium stress to varying degrees.

Conclusions

The results of this research are instrumental for further functional investigation of SeMTC in C. hupingshanensis. This also lays a solid foundation for deeper investigations into the physiological and biochemical mechanisms underlying selenium metabolism in plants.
Effect of residual myocardial ischemia on recovery of left ventricular function after primary percutaneous coronary intervention
Authors: Abdelhafez Mohamed Aly , Aly Karim M. E. , Youssef Amr A. A.
Published: March 2024

Background

It is unknown whether the existence of severe bystander damage will affect left ventricular (LV) healing following primary percutaneous coronary intervention (PPCI).

The aim of the present analysis was to follow LV recovery using 2D speckle tracking echocardiography (2-D STE) in cases with single versus multiple vessel disease with acute myocardial infarction (AMI) who underwent PPCI and to assess major adverse cardiovascular events (MACEs) within 3 months.

Patients and methods

This work was conducted at Assiut University Heart Hospital. Of 1026 screened subjects with AMI needing PPCI and assessed for eligibility, only 89 cases fulfilled the inclusion criteria. They were classified into Group A: single vessel and Group B: multiple vessel (≥ 2 vessels) disease. Their data were obtained on admittance and after 90 days.

Results

In group A compared to group B, there was a statistically preferable value at baseline in the global longitudinal strain- Apical 2 chamber (GLS-A2C) (-12.05 ± 3.57 vs. -10.38 ± 3.92, P = 0.039). At follow-up, the improvement was in all 2-D STE variables, including GLS-long axis (GLS-LAX) (-13.09 ± 3.84 vs.-10.75 ± 3.96, P = 0.006), GLS- apical 4 chamber (GLS-A4C) (-13.23 ± 3.51 vs.-10.62 ± 4.08, P = 0.002), GLS-A2C (-13.85 ± 3.41 vs-10.93 ± 3.97, P < 0.001) and GLS- average (GLS-AVG, P = 0.001). There was a considerable negative correlation between the recovery of LV performance and the existence of multi-vessel lesions (P = 0.009). There was no variance between the groups regarding MACEs.

Conclusions

Patients with single vessel lesions who underwent PPCI to the culprit lesion had better recovery of LV function than those with multi-vessel (≥ 2 vessels) lesions who underwent PPCI to the culprit lesion only. The presence of multivessel involvement was an independent risk factor for deterioration in GLS.

Trial Registration

Registered in clinical trial, clinicalTrial.gov ID NCT04103008 (25/09/2019). IRB registration: 17,100,834 (05/11/2019).
Paclitaxel-induced acute myocardial infarction: a case report and literature review
Authors: Kim Gi Eun , Ibrahim Ayman R. , Shalatouni Duha , Abouzeid Nadin H. , Othman Fahmi
Published: March 2024

Background

Paclitaxel is a chemotherapeutic agent commonly used for ovarian, lung, breast carcinoma, and Kaposi’s sarcoma. Its common side effects include hypersensitivity reaction, bone marrow suppression, and peripheral neuropathy. However, a rare and life-threatening side effect is paclitaxel-induced myocardial infarction.

Case presentation

A 71-year-old man with type 2 diabetes mellitus, hypertension, heavy smoking history, previous coronary artery disease with percutaneous coronary intervention (PCI) in left anterior descending artery (LAD), and non-small lung cancer presented with non-ST elevation myocardial infarction during infusion of paclitaxel infusion. Coronary angiogram showed de novo three vessel disease with 70% stenosis in ostial to distal left main artery (LM) and 80% in-stent re-stenosis in proximal to mid left anterior descending artery.

Conclusions

Physicians should be keeping this in mind when dealing with patients on paclitaxel, especially if they have previous risk factors for coronary artery disease.
Long-term effects and predictors of change of internet-delivered cognitive behavioural therapy on cardiac anxiety in patients with non-cardiac chest pain: a randomized controlled trial
Authors: Eriksson-Liebon Magda , Westas Mats , Johansson Peter , Mourad Ghassan
Published: March 2024

Background

Approximately half of patients who seek care at Emergency Departments due to chest pain are diagnosed with Non-Cardiac Chest Pain (NCCP). Concerns for heart disease and misinterpretation of the symptoms increase cardiac anxiety and have a negative impact on patients' lives. Psychological interventions such as internet-delivered cognitive behavioral therapy (iCBT) are effective in treating psychological conditions such as anxiety, by helping patients to learn how to manage chest pain.

Aims

To evaluate the effects of a nurse-led iCBT program on cardiac anxiety and secondary outcomes, as bodily sensations, depressive symptoms, health-related quality of life and chest pain frequency in patients with NCCP at 6- and 12-month follow-up, and to explore predictors that can have impact on the effects of the iCBT program on psychological distress.

Methods

A longitudinal study of a Randomized Controlled Trial (RCT) evaluating the long-term effects of an iCBT program (n = 54) in patients with NCCP, compared to psychoeducation (n = 55). The primary outcome, cardiac anxiety was measured using the Cardiac Anxiety Questionnaire (CAQ), and the secondary outcomes were measured with The Body Sensations Questionnaire (BSQ), Patient Health Questionnaire-9 (PHQ-9), The EuroQol Visual Analog Scale (EQ-VAS) and a self-developed question to measure chest pain frequency. All measurements were performed before and after the intervention, and 3, 6 and 12 months after the intervention. Linear mixed model was used to test between-group differences in primary and secondary outcomes and multiple regression analysis was used to explore factors that may have an impact on the treatment effect of iCBT on cardiac anxiety.

Results

A total of 85% (n = 93/109) participants completed the 12-month follow-up. Mixed model analysis showed no statistically significant interaction effect of time and group between the iCBT and psychoeducation groups regarding cardiac anxiety over the 12-month follow-up. However, there was a statistically significant interaction effect of time and group (p = .009) regarding chest pain frequency favouring the iCBT group. In addition, we found a group effect in health-related quality of life (p = .03) favouring the iCBT group. The regression analysis showed that higher avoidance scores at baseline were associated with improvement in cardiac anxiety at 12-month follow-up.

Conclusions

Cardiac anxiety was reduced in patients with NCCP, but iCBT was not more effective than psychoeducation. Patients with a high tendency to avoid activities or situations that they believe could trigger cardiac symptoms may benefit more from psychological interventions targeting cardiac anxiety.

Trial Registration

The trial was registered at ClinicalTrials.gov NCT03336112 on 08/11/2017.
Common predictors of cervical cancer related mortality in Ethiopia. A systematic review and meta-analysis
Authors: Hambisa Hunduma Dina , Asfaha Berhane Teklay , Ambisa Biniam , Gudeta Beyisho Abebech
Published: March 2024

Background

Cervical cancer accounts for 7.5% of all female cancer related deaths worldwide; peaking between the ages of 35 and 65, and not only kills young women but also destroys families with young children.

Objective

This review was intended to measure national level magnitude and the most common predictors of cervical cancer related mortality in Ethiopia.

Methods

Common Public databases like Science Direct, Embase, the Cochrane Library, and PubMed were thoroughly searched. The STATA 14 and Rev-Manager 5.3 statistical software packages were used for analysis, as well as a standardized data abstraction tool created in Microsoft Excel. The Cochrane Q-test statistics and the I2 test were used to assess non-uniformity. The pooled magnitude and predictors of cervical cancer related mortality were estimated using fixed-effect and random-effect models, respectively.

Result

The pooled mortality among cervical cancer patients was estimated that 16.39% at 95% confidence level fall in 13.89–18.88% in Ethiopia. The most common predictors of cervical cancer related mortality were late diagnosed, radiation therapy alone, and Being anemic were identified by this review. Among cervical cancer treatment modalities effectiveness of surgery with adjuvant therapy was also approved in this meta-analysis.

Conclusion and recommendation

In this study high cervical cancer-related mortality was reported as compared to national strategies to alleviate cervical cancer related mortality. Advanced implementation of cervical cancer screening at the national level for early diagnosis, anaemia detection, and combination anticancer therapy during initiation, as well as combination therapy, is critical to improve cervical cancer patient survival and decreasing mortality rates.
Identifying latent classes of physical activity profiles over time among adolescents in Ontario, Canada
Authors: Buchan M. Claire , Richmond Sarah A. , Skinner Kelly , Leatherdale Scott T.
Published: March 2024

Background

Physical activity behaviours are known to be highly correlated. Adolescents who participate in one type of physical activity (e.g., physical education) have a greater likelihood of participating in other physical activities (e.g., organized sports); however, little research has examined participation rates in various physical activity behaviours concurrently. This study identified longitudinal physical activity profiles among secondary school aged youth in Ontario, Canada.

Methods

We used data from the COMPASS Study, a school-based prospective cohort study of adolescents in Canada. Using a repeated measures latent class analysis, Ontario students who participated in grade 9 PE in 2015-16 were analysed through to 2018-19 (n = 1,917). Latent classes were defined by: PE participation, guideline adherence (≥ 60 min/day of moderate to vigorous activity over the last 7 days), and sport participation (varsity, community, and/or intramural). Multinomial logistic regression models were used to examine associations between latent class membership and student characteristics.

Results

Three distinct latent classes were identified for females and four were identified for males. These classes were: (1) Guidelines (high probability of guideline adherence; females: 44%; males: 16%), (2) PE & Sports (high probability of PE and sport participation; females: 33%; males: 43%), (3) Guidelines & Sports (high probability of guideline adherence and sport participation; females: 23%; males: 23%;), and (4) Inactive (low probability of all physical activity indicators; males: 18%). Strength training, sleep, and English grade were associated with class membership among females. Ethno-racial identity, weekly spending money, strength training, and English and math grades were associated with class membership among males.

Conclusions

Findings suggest that latent physical activity profiles differ by sex. Guideline adherence was the most common class among females, indicating high levels of independent physical activity, whereas PE & Sport participation was the most common class among males, indicating greater tendency towards organized activities. Additionally, a substantial number of male students were not engaging in any physical activity. Participation in both PE and sports did not necessarily lead to meeting physical activity guidelines, highlighting that these activities alone may not be providing sufficient levels of physical activity that align with current recommendations for Canadian youth.
Lifestyle factors and subacromial impingement syndrome of the shoulder: potential associations in finnish participants
Authors: Lv Zhengtao , Cui Jiarui , Zhang Jiaming , He Li
Published: March 2024

Background

Emerging evidence has indicated the associations between subacromial impingement syndrome (SIS) of shoulder and lifestyle factors. However, whether unhealthy lifestyle factors causally increase SIS risk is not determined. This study aims to evaluate whether lifestyle factors are the risk factors of SIS.

Methods

A two-sample Mendelian randomization (MR) study was designed to evaluate the effect of 11 lifestyle factors on SIS risk. Causality was determined using the inverse-variance weighted method to calculate the odds ratio (OR) and establish a 95% confidence interval (CI). Weighted median method, MR-Egger method and MR-PRESSO method were conducted as sensitivity analysis.

Results

Four lifestyle factors were identified causally associated with an increased risk of SIS using the IVW method: insomnia (OR: 1.66 95% CI 1.38, 2.00; P = 8.86 × 10− 8), short sleep duration (OR: 1.53 95% CI 1.14, 2.05: P = 0.0043), mobile phone usage (OR: 4.65, 95% CI 1.59, 13.64; P = 0.0051), and heavy manual or physical work (OR: 4.24, 95% CI 2.17, 8.26; P = 2.20 × 10− 5). Another causal but weak association was found between smoking initiation on SIS (OR: 1.17, 95% CI 1.01, 1.35; P = 3.50 × 10− 2). Alcohol, coffee consumption, physical activity, sedentary behavior, sleep duration and computer usage were not found to be causally associated with an increased risk of SIS. Sensitivity analyses indicated that the MR estimates were robust and no heterogeneity and pleiotropy were identified in these MR analyses.

Conclusion

Sleep habits and shoulder usage were identified as causal factors for SIS. This evidence supports the development of strategies aimed at improving sleep behaviors and optimizing shoulder usage patterns as effective measures to prevent SIS.
Team players and helpers – describing professional identity among finnish physicians in a cross-sectional study
Authors: Mattila Pyry , Hyppölä Harri , Heikkilä Teppo , Heistaro Sami , Kaila Minna , Kulmala Petri , Sumanen Markku , Mäntyselkä Pekka
Published: March 2024

Background

Every physician has a unique professional identity. However, little is known about the diversity of identities among physicians. This study aimed to quantitatively assess the professional identity of physicians in Finland using descriptions of professional identity.

Methods

This study was part of a larger cross-sectional Finnish Physician 2018 Study. The target population consisted of all Finnish physicians under the age of 70 (N = 24,827) in 2018. The sample was drawn from physicians born on even numbered days (N = 11,336) using the Finnish Medical Association register. A total of 5,187 (46%) physicians responded. Professional identity was examined by 27 given characterisations using a five-point Likert scale. Multivariate logistic regression was used in assessing how place of work, graduation year and gender were associated with identity descriptions.

Results

The descriptions which most physicians identified with were “member of a working group/team” (82%), “helper” (82%), and “health expert” (79%); the majority reported these as describing them very or quite well. Identity descriptions such as “prescriber of medications” (68% vs. 45%), “prioritiser” (57% vs. 35%) and “someone issuing certificates” (52% vs. 32%) were more popular among junior than senior physicians. The biggest differences between the genders were found in the descriptions “provider of comfort” (62% vs. 40%) and “someone engaged in social work” (45% vs. 25%), with which women identified more frequently than men.

Conclusions

Strong identification as a member of a team is an important finding in the increasingly multiprofessional world of health care. Importantly, most physicians shared several core professional identity descriptions (i.e., helper, health expert) that reflect the traditional image of an exemplary doctor.
Objective structured clinical examination to teach competency in planetary health care and management – a prospective observational study
Authors: Teichgräber Ulf , Ingwersen Maja , Sturm Max-Johann , Giesecke Jan , Allwang Manuel , Herzog Ida , von Gierke Frederike , Schellong Paul , Kolleg Matthias , Lange Kathleen , Wünsch Daniel , Gugel Katrin , Wünsch Anne , Zöllkau Janine , Petruschke Inga , Häseler-Ouart Kristin , Besteher Bianca , Philipp Swetlana , Mille Urte , Ouart Dominique , Jünger Jana ,   Jena Planetary Health Collaboration Group, Kamradt Thomas , Pletz Mathias , Stallmach Andreas , Coldewey Sina M. , Schleußner Ekkehard , Wedding Ulrich , Walter Martin
Published: March 2024

Background

Health professionals are increasingly called upon and willing to engage in planetary health care and management. However, so far, this topic is rarely covered in medical curricula. As the need for professional communication is particularly high in this subject area, this study aimed to evaluate whether the objective structured clinical examination (OSCE) could be used as an accompanying teaching tool.

Methods

During the winter semester 2022/2023, 20 third- and fifth-year medical students voluntarily participated in a self-directed online course, three workshops, and a formal eight-station OSCE on planetary health care and management. Each examinee was also charged alternatingly as a shadower with the role of providing feedback. Experienced examiners rated students’ performance using a scoring system supported by tablet computers. Examiners and shadowers provided timely feedback on candidates` performance in the OSCE. Immediately after the OSCE, students were asked about their experience using a nine-point Likert-scale survey and a videotaped group interview. Quantitative analysis included the presentation of the proportional distribution of student responses to the survey and of box plots showing percentages of maximum scores for the OSCE performance. The student group interview was analyzed qualitatively.

Results

Depending on the sub-theme, 60% -100% of students rated the subject of planetary health as likely to be useful in their professional lives. Similar proportions (57%-100%) were in favour of integrating planetary health into required courses. Students perceived learning success from OSCE experience and feedback as higher compared to that from online courses and workshops. Even shadowers learned from observation and feedback discussions. Examiners assessed students’ OSCE performance at a median of 80% (interquartile range: 83%-77%) of the maximum score.

Conclusions

OSCE can be used as an accompanying teaching tool for advanced students on the topic of planetary health care and management. It supports learning outcomes, particularly in terms of communication skills to sensitise and empower dialogue partners, and to initiate adaptation steps at the level of individual patients and local communities.
Evolution of compound eye morphology underlies differences in vision between closely related Drosophila species
Authors: Buffry Alexandra D. , Currea John P. , Franke-Gerth Franziska A. , Palavalli-Nettimi Ravindra , Bodey Andrew J. , Rau Christoph , Samadi Nazanin , Gstöhl Stefan J. , Schlepütz Christian M. , McGregor Alistair P. , Sumner-Rooney Lauren , Theobald Jamie , Kittelmann Maike
Published: March 2024

Background

Insects have evolved complex visual systems and display an astonishing range of adaptations for diverse ecological niches. Species of Drosophila melanogaster subgroup exhibit extensive intra- and interspecific differences in compound eye size. These differences provide an excellent opportunity to better understand variation in insect eye structure and the impact on vision. Here we further explored the difference in eye size between D. mauritiana and its sibling species D. simulans.

Results

We confirmed that D. mauritiana have rapidly evolved larger eyes as a result of more and wider ommatidia than D. simulans since they recently diverged approximately 240,000 years ago. The functional impact of eye size, and specifically ommatidia size, is often only estimated based on the rigid surface morphology of the compound eye. Therefore, we used 3D synchrotron radiation tomography to measure optical parameters in 3D, predict optical capacity, and compare the modelled vision to in vivo optomotor responses. Our optical models predicted higher contrast sensitivity for D. mauritiana, which we verified by presenting sinusoidal gratings to tethered flies in a flight arena. Similarly, we confirmed the higher spatial acuity predicted for Drosophila simulans with smaller ommatidia and found evidence for higher temporal resolution.

Conclusions

Our study demonstrates that even subtle differences in ommatidia size between closely related Drosophila species can impact the vision of these insects. Therefore, further comparative studies of intra- and interspecific variation in eye morphology and the consequences for vision among other Drosophila species, other dipterans and other insects are needed to better understand compound eye structure–function and how the diversification of eye size, shape, and function has helped insects to adapt to the vast range of ecological niches.
Incidence of new-onset hypertension before, during, and after the COVID-19 pandemic: a 7-year longitudinal cohort study in a large population
Authors: Trimarco Valentina , Izzo Raffaele , Pacella Daniela , Trama Ugo , Manzi Maria Virginia , Lombardi Angela , Piccinocchi Roberto , Gallo Paola , Esposito Giovanni , Piccinocchi Gaetano , Lembo Maria , Morisco Carmine , Rozza Francesco , Santulli Gaetano , Trimarco Bruno
Published: March 2024

Background

While the augmented incidence of diabetes after COVID-19 has been widely confirmed, controversial results are available on the risk of developing hypertension during the COVID-19 pandemic.

Methods

We designed a longitudinal cohort study to analyze a closed cohort followed up over a 7-year period, i.e., 3 years before and 3 years during the COVID-19 pandemic, and during 2023, when the pandemic was declared to be over. We analyzed medical records of more than 200,000 adults obtained from a cooperative of primary physicians from January 1, 2017, to December 31, 2023. The main outcome was the new diagnosis of hypertension.

Results

We evaluated 202,163 individuals in the pre-pandemic years and 190,743 in the pandemic years, totaling 206,857 when including 2023 data. The incidence rate of new hypertension was 2.11 (95% C.I. 2.08–2.15) per 100 person-years in the years 2017–2019, increasing to 5.20 (95% C.I. 5.14–5.26) in the period 2020–2022 (RR = 2.46), and to 6.76 (95% C.I. 6.64–6.88) in 2023. The marked difference in trends between the first and the two successive observation periods was substantiated by the fitted regression lines of two Poisson models conducted on the monthly log-incidence of hypertension.

Conclusions

We detected a significant increase in new-onset hypertension during the COVID-19 pandemic, which at the end of the observation period affected ~ 20% of the studied cohort, a percentage higher than the diagnosis of COVID-19 infection within the same time frame. This observation suggests that increased attention to hypertension screening should not be limited to individuals who are aware of having contracted the infection but should be extended to the entire population.
CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes
Authors: Schnell Oliver , Barnard-Kelly Katharine , Battelino Tadej , Ceriello Antonio , Larsson Helena Elding , Fernández-Fernández Beatriz , Forst Thomas , Frias Juan-Pablo , Gavin James R. , Giorgino Francesco , Groop Per-Henrik , Heerspink Hiddo J. L. , Herzig Stephan , Hummel Michael , Huntley George , Ibrahim Mahmoud , Itzhak Baruch , Jacob Stephan , Ji Linong , Kosiborod Mikhail , Lalic Nebosja , Macieira Sofia , Malik Rayaz A. , Mankovsky Boris , Marx Nikolaus , Mathieu Chantal , Müller Timo D. , Ray Kausik , Rodbard Helena W. , Rossing Peter , Rydén Lars , Schumm-Draeger Petra-Maria , Schwarz Peter , Škrha Jan , Snoek Frank , Tacke Frank , Taylor Bruce , Jeppesen Britta Tendal , Tesfaye Solomon , Topsever Pinar , Vilsbøll Tina , Yu Xuefeng , Standl Eberhard
Published: March 2024

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5–6, 2024 (http://www.cvot.org).
Protective effects of imeglimin on the development of atherosclerosis in ApoE KO mice treated with STZ
Authors: Sanada Junpei , Kimura Tomohiko , Shimoda Masashi , Iwamoto Yuichiro , Iwamoto Hideyuki , Dan Kazunori , Fushimi Yoshiro , Katakura Yukino , Nogami Yuka , Shirakiya Yoshiko , Yamasaki Yuki , Ikeda Tomoko , Nakanishi Shuhei , Mune Tomoatsu , Kaku Kohei , Kaneto Hideaki
Published: March 2024

Background

Imeglimin is a new anti-diabetic drug which promotes insulin secretion from pancreatic β-cells and reduces insulin resistance in insulin target tissues. However, there have been no reports examining the possible anti-atherosclerotic effects of imeglimin. In this study, we investigated the possible anti-atherosclerotic effects of imeglimin using atherosclerosis model ApoE KO mice treated with streptozotocin (STZ).

Methods

ApoE KO mice were divided into three groups: the first group was a normoglycemic group without injecting STZ (non-DM group, n = 10). In the second group, mice were injected with STZ and treated with 0.5% carboxymethyl cellulose (CMC) (control group, n = 12). In the third group, mice were injected with STZ and treated with imeglimin (200 mg/kg, twice daily oral gavage, n = 12). We observed the mice in the three groups from 10 to 18 weeks of age. Plaque formation in aortic arch and expression levels of various vascular factors in abdominal aorta were evaluated for each group.

Results

Imeglimin showed favorable effects on the development of plaque formation in the aortic arch in STZ-induced hyperglycemic ApoE KO mice which was independent of glycemic and lipid control. Migration and proliferation of vascular smooth muscle cells and infiltration of macrophage were observed in atherosclerotic lesions in STZ-induced hyperglycemic ApoE KO mice, however, which were markedly reduced by imeglimin treatment. In addition, imeglimin reduced oxidative stress, inflammation and inflammasome in hyperglycemic ApoE KO mice. Expression levels of macrophage makers were also significantly reduced by imeglimin treatment.

Conclusions

Imeglimin exerts favorable effects on the development of plaque formation and progression of atherosclerosis.
Effects of immediate loading directionality on the mechanical sensing protein PIEZO1 expression and early-stage healing process of peri-implant bone
Authors: Mao Chuanyuan , Yu Weijun , Li Guanglong , Xu Ziyuan , Gong Yuhua , Jin Min , Lu Eryi
Published: March 2024

Background

The reduced treatment time of dental implants with immediate loading protocol is an appealing solution for dentists and patients. However, there remains a significant risk of early peri-implant bone response following the placement of immediately loaded implants, and limited information is available regarding loading directions and the associated in vivo characteristics of peri-implant bone during the early stages. This study aimed to investigate the effects of immediate loading directionality on the expression of mechanical sensing protein PIEZO1 and the healing process of peri-implant bone in the early stage.

Methods

Thirty-two implants were inserted into the goat iliac crest models with 10 N static lateral immediate loading applied, followed by histological, histomorphological, immunohistochemical, X-ray microscopy and energy dispersive X-ray spectroscopy evaluations conducted after 10 days.

Results

From evaluations at the cellular, tissue, and organ levels, it was observed that the expression of mechanical sensing protein PIEZO1 in peri-implant bone was significantly higher in the compressive side compared to the tensile side. This finding coincided with trends observed in interfacial bone extracellular matrix (ECM) contact percentage, bone mass, and new bone formation.

Conclusions

This study provides a novel insight into the immediate loading directionality as a potential influence factor for dental implant treatments by demonstrating differential effects on the mechanical sensing protein PIEZO1 expression and related early-stage healing processes of peri-implant bone. Immediate loading directions serve as potential therapeutic influence factors for peri-implant bone during its early healing stage.
Economic evaluations in medical technological innovations a mapping review of methodologies
Authors: van Lieshout C. , Frederix G. W. J. , Schoonhoven L.
Published: March 2024

Rationale

Economic evaluations play an important role in the development and implementation of healthcare innovations. For pharmaceutical products, the methodologies used are laid down in guidelines, whereas for medical technologies the guidelines are not as strenuous. The aim of this review was therefore to analyze what types of methodologies are used in economic evaluations of medical technologies.

Methods

We performed a mapping review to identify economic evaluations for medical technologies. We decided to limit our search to one year (2022) and included cost utility and cost effectiveness analyses in which health technologies were evaluated. For each included study we identified the main methodological characteristics.

Results

A total of 364 papers were included in the analysis, 268 (74%) contained cost-utility analyses and 91 (25%) cost-effectiveness analyses. A model was used in 236 (64%) analyses, 117 analyses were trial based evaluations. Probabilistic sensitivity analyses and/or bootstrapping was performed in 266 (73%) analyses. Deterministic sensitivity analyses were used in 306 (84%). Time horizon and perspective were underreported in 15–25% of the included studies.

Conclusions

This review shows the wide range of methodologies used in economic evaluations as well as the extent and rigor in which these methodologies are used. Many of the included papers did no use or did not sufficiently report the use of appropriate standard methods. This may lead to research waste, a delay in successful implementation of valuable innovations and in the end may delay improvement patient outcomes.
Drivers of consumer food choices of multinational corporations’ products over local foods in Ghana: a maximum difference scaling study
Authors: Nyarko Eric , Bartelmeß Tina
Published: March 2024

Introduction

The fundamental transformation of food systems and retail environments in low-income countries is influencing consumers' food choices and dietary habits in unfavourable directions through the consumption of highly processed, energy-dense foods, predominantly manufactured by multinational food corporations. This study aims to identify the principal factors driving consumers' preference for multinational foods over local foods in the urban Accra region of Ghana.

Method

This cross-sectional survey involving a random sample of 200 consumers conducted in March/April 2023 using interviewer-administered questionnaires employed a maximum difference scaling approach to investigate the drivers of urban Ghanaian consumer food choices for multinational food corporations' products over local foods. The maximum difference scaling modelling analysis utilized in this study identifies the primary drivers of multinational food corporations' product preferences and the associated trade-offs.

Result

The study discovered that food quality and safe packaging, perceived healthiness, taste and flavour, and nutritional value were the most significant factors driving consumer preference for multinational food corporations' products over local foods in Ghana. The criterion food quality and safe packaging had the significantly highest utility than all other attributes in terms of consumer preference for products/meals from multinational food corporations over local foods.

Conclusion

The results of this study provide significant contributions to the existing body of research, as previous studies have not identified these factors as primary drivers of multinational food products. Public health authorities and nutritionists can use the study's findings to implement targeted quality assurance measures in local markets and to address the drivers in health education campaigns.
Successful surgical treatment of impending paradoxical embolism with pulmonary embolism and myocardial infarction
Authors: Liu Yong , Yang Zhiyun , Sun Xinxin , Yang Mei , Zhang Tao , Li Ruilin , Wei Ying , Cao Hao
Published: March 2024

Background

Paradoxical embolism is a rare cause of acute arterial occlusion. This phenomenon arises when embolic material travels from the venous system crosses an abnormal shunt such as patent foramen ovale, atrial septal defects, ventricular septal defects, or pulmonary arteriovenous malformations, into the arterial system. Impending paradoxical embolism refers to the presence of an entrapped thrombus in the patent foramen ovale.

Case presentation

We report a case of a 68-year-old female patient who presented with an impending paradoxical embolism, alongside both concomitant pulmonary embolism and myocardial infarction with ST-segment elevation. Swiftly addressed through emergency cardiac surgery and systemic anticoagulation, the patient’s condition was effectively treated.

Conclusions

While the ideal treatment strategy for impending paradoxical embolism remains a topic of debate due to limited and inconclusive evidence, emergent open surgery should be contemplated in patients as it signifies a critical clinical emergency.
Unveiling CXCR2 as a promising therapeutic target in renal cell carcinoma: exploring the immunotherapeutic paradigm shift through its inhibition by RCT001
Authors: Montemagno Christopher , Jacquel Arnaud , Pandiani Charlotte , Rastoin Olivia , Dawaliby Rosie , Schmitt Thomas , Bourgoin Maxence , Palenzuela Héliciane , Rossi Anne-Laure , Ambrosetti Damien , Durivault Jerome , Luciano Frederic , Borchiellini Delphine , Le Du Julie , Gonçalves Leticia Christina Pires , Auberger Patrick , Benhida Rachid , Kinget Lisa , Beuselinck Benoit , Ronco Cyril , Pagès Gilles , Dufies Maeva
Published: March 2024

Background

In clear cell renal cell carcinoma (ccRCC), first-line treatment combines nivolumab (anti-PD-1) and ipilimumab (anti-CTLA4), yielding long-term remissions but with only a 40% success rate. Our study explored the potential of enhancing ccRCC treatment by concurrently using CXCR2 inhibitors alongside immunotherapies.

Methods

We analyzed ELR + CXCL levels and their correlation with patient survival during immunotherapy. RCT001, a unique CXCR2 inhibitor, was examined for its mechanism of action, particularly its effects on human primary macrophages. We tested the synergistic impact of RCT001 in combination with immunotherapies in both mouse models of ccRCC and human ccRCC in the presence of human PBMC.

Resuts

Elevated ELR + CXCL cytokine levels were found to correlate with reduced overall survival during immunotherapy. RCT001, our optimized compound, acted as an inverse agonist, effectively inhibiting angiogenesis and reducing viability of primary ccRCC cells. It redirected M2-like macrophages without affecting M1-like macrophage polarization directed against the tumor. In mouse models, RCT001 enhanced the efficacy of anti-CTLA4 + anti-PD1 by inhibiting tumor-associated M2 macrophages and tumor-associated neutrophils. It also impacted the activation of CD4 T lymphocytes, reducing immune-tolerant lymphocytes while increasing activated natural killer and dendritic cells. Similar effectiveness was observed in human RCC tumors when RCT001 was combined with anti-PD-1 treatment.

Conclusions

RCT001, by inhibiting CXCR2 through its unique mechanism, effectively suppresses ccRCC cell proliferation, angiogenesis, and M2 macrophage polarization. This optimization potentiates the efficacy of immunotherapy and holds promise for significantly improving the survival prospects of metastatic ccRCC patients.
miR-430 regulates zygotic mRNA during zebrafish embryogenesis
Authors: Baia Amaral Danielson , Egidy Rhonda , Perera Anoja , Bazzini Ariel A
Published: March 2024

Background

Early embryonic developmental programs are guided by the coordinated interplay between maternally inherited and zygotically manufactured RNAs and proteins. Although these processes happen concomitantly and affecting gene function during this period is bound to affect both pools of mRNAs, it has been challenging to study their expression dynamics separately.

Results

By employing SLAM-seq, a nascent mRNA labeling transcriptomic approach, in a developmental time series we observe that over half of the early zebrafish embryo transcriptome consists of maternal-zygotic genes, emphasizing their pivotal role in early embryogenesis. We provide an hourly resolution of de novo transcriptional activation events and follow nascent mRNA trajectories, finding that most de novo transcriptional events are stable throughout this period. Additionally, by blocking microRNA-430 function, a key post transcriptional regulator during zebrafish embryogenesis, we directly show that it destabilizes hundreds of de novo transcribed mRNAs from pure zygotic as well as maternal-zygotic genes. This unveils a novel miR-430 function during embryogenesis, fine-tuning zygotic gene expression.

Conclusion

These insights into zebrafish early embryo transcriptome dynamics emphasize the significance of post-transcriptional regulators in zygotic genome activation. The findings pave the way for future investigations into the coordinated interplay between transcriptional and post-transcriptional landscapes required for the establishment of animal cell identities and functions.