bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of uric acid with the risk of cardiovascular disease and all-cause mortality among individuals with chronic kidney disease: the Kailuan Study
Authors: Li Na , Cui Liufu , Shu Rong , Song Haicheng , Wang Jierui , Chen Shuohua , Han Yixuan , Yu Ping , Yuan Wei , Wang Jian , Gao Huanqing , Huang Tao , Gao Xiang , Wu Shouling , Geng Tingting
Published: July 2024

Aims

The relationship between uric acid (UA) concentrations and the risk of cardiovascular disease (CVD), especially for subtypes of CVD among individuals with chronic kidney disease (CKD), is not well understood. This study aimed to investigate whether UA concentration was associated with subtypes of CVD and all-cause mortality among individuals with CKD.

Methods and results

A total of 27 707 individuals with CKD, free of CVD at recruitment from the Kailuan Study, were included. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median follow-up of 11–12 years, we documented 674 myocardial infarctions, 1197 heart failures, 2406 strokes, and 5676 total deaths. Among participants with CKD, compared with those in the lowest tertile of UA, the HRs (95% CIs) of participants in the highest UA tertile were 1.38 (1.13–1.67) for myocardial infarction, 1.60 (1.38–1.85) for heart failure, 1.01 (0.91–1.12) for stroke, and 1.29 (1.21–1.38) for all-cause mortality. Subgroup analyses showed that the associations between UA and heart failure and all-cause mortality were stronger in individuals with estimated glomerular filtration rate <45 mL/min/1.73 m2 compared to their counterparts (Pinteraction < 0.05). Additionally, the association between UA and all-cause mortality was stronger among individuals without diabetes than those with diabetes (Pinteraction < 0.05).

Conclusion

In individuals with CKD, a higher concentration of UA was associated with a higher risk of myocardial infarction, heart failure, and all-cause mortality, following a dose–response relationship. Our data underscore the importance of UA screening among individuals with CKD for CVD and premature death prevention.
How to help countries improve resilience during a pandemic: an example of a Rapid Exchange Forum
Authors: Habl Claudia , Weiss Johannes , Gottlob Anita , Saso Miriam , Schutte Nienke , Bogaert Petronille , Paulo Marília Silva , Lapão Luís Velez
Published: July 2024

Background

The COVID-19 pandemic demanded quick exchanges between experts and institutions supporting governments to provide evidence-based information in response to the crisis. Initially, there was no regular cross-country forum in the field of population health. This paper describes the set-up and benefits of implementing such a forum.

Methods

A group of public health practitioners from academia, national public health institutes and ministries of health decided in April 2020 to meet bi-monthly to discuss a vast array of population health topics in a structured format called a Rapid Exchange Forum (REF). An ad-hoc mailing group was established to collect responses to questions brought forward in the forum from at least five countries within 24 h. This endeavour, which evolved as network of networks was awarded an EU grant in autumn 2020 and was called PHIRI (Population Health Information Research Infrastructure).

Results

Responses from up to 31 countries were compiled and shared immediately via the European Health Information Portal. This exchange was complemented by special REFs that focused on the advantages and disadvantages of vaccination, for example. By July 2023, 54 REFs had taken place with topics going beyond COVID-19.

Conclusion

The REF demonstrated its value for quick yet evidence-based cross-country exchange in times of crisis and was highly appreciated by countries and European Commission. It demonstrated its sustainability even after the acute crisis by expanding the topics covered and managing to continue exchange with the aim of capacity building and mutual learning, making it a true EU response and coordination mechanism.
PHIRI: lessons for an extensive reuse of sensitive data in federated health research
Authors: González-García Juan , González-Galindo Javier , Estupiñán-Romero Francisco , Thißen Martin , Lyons Ronan A , Telleria-Orriols Carlos , Bernal-Delgado Enrique ,   Population Health Information Research Infrastructure, Bogaert Petronille , Schutte Nienke , Derycke Pascal , Aldridge Sarah , Schmidt Andrea , Dolanski-Aghamanoukjan Lorenz , Zeitlin Jennifer , Philibert Marianne , Tolonen Hanna , Gissler Mikka , Rodríguez-Blázquez Carmen
Published: July 2024

Background

The extensive and continuous reuse of sensitive health data could enhance the role of population health research on public decisions. This paper describes the design principles and the different building blocks that have supported the implementation and deployment of Population Health Information Research Infrastructure (PHIRI), the strengths and challenges of the approach and some future developments.

Methods

The design and implementation of PHIRI have been developed upon: (i) the data visiting principle—data does not move but code moves; (ii) the orchestration of the research question throughout a workflow that ensured legal, organizational, semantic and technological interoperability and (iii) a ‘master–worker’ federated computational architecture that supported the development of four uses cases.

Results

Nine participants nodes and 28 Euro-Peristat members completed the deployment of the infrastructure according to the expected outputs. As a consequence, each use case produced and published their own common data model, the analytical pipeline and the corresponding research outputs. All the digital objects were developed and published according to Open Science and FAIR principles.

Conclusion

PHIRI has successfully supported the development of four use cases in a federated manner, overcoming limitations for the reuse of sensitive health data and providing a methodology to achieve interoperability in multiple research nodes.
Foresight in public health: a tutorial on application and insights on challenges from the PHIRI foresight exercise
Authors: Mutubuki Elizabeth N , Moye-Holz Daniela , Peyroteo Mariana , Lapão Luís Velez , Hilderink Henk B M
Published: July 2024

Background

The application of foresight to the field of public health is limited. There is growing need to anticipate uncertain future trends and to plan for them. Foresight provides tools to experts and policymakers to discuss and plan for possible futures. Hence, the aim of this study is to illustrate how the foresight six-step approach can be applied in public health, and to provide recommendations on dealing with challenges, drawn from the Population Health Information Research Infrastructure (PHIRI) foresight exercise.

Methods

In this tutorial, we describe the six-step approach as part of foresight methodology and give examples of possible challenges. Step 1 comprises the formulation of study objectives. Step 2 focuses on developing a conceptual model and applying the Demographic Economic Sociocultural Technological Ecological and Political-Institutional (DESTEP) framework to identify and prioritize driving forces for the topic of interest. In Step 3, a time horizon and spatial level are defined. Step 4 discusses scenario logics. Steps 5 and 6 discuss different types of scenarios and associated tools for analyses. Possible challenges encountered whilst applying the foresight methodology at each of the steps, were drawn from experiences during PHIRI foresight exercise.

Results

Challenges associated with applying the foresight six-step approach included: formulating concise objectives, developing a conceptual model, understanding driving forces and uncertainty and difficulties in building scenarios.

Conclusions

Understanding concepts used in the six-step approach and how they relate to each other remained difficult. Support from foresight experts, conducting more foresight exercises, tutorials and guidelines can enhance understanding and support building capacity.
COVID-19 health information system assessments in eight European countries: identified gaps, best practices and recommendations
Authors: Saso Miriam , Schutte Nienke , Borg Marika , Calleja Neville , Schmidt Andrea E , Peyroteo Mariana , Lapão Luís Velez , Fehr Angela , Thißen Martin , Courtney Michael , Bogaert Petronille
Published: July 2024

Background

Global threats, such as the coronavirus disease 2019 (COVID-19) pandemic, have highlighted the critical importance of robust and well-functioning health information systems (HIS) in effectively addressing public health emergencies. To enhance the understanding and the functioning of such systems, it is crucial to perform HIS assessments. This article explores key gaps and identifies best practices in the COVID-19 HIS of eight European countries. Furthermore, it provides recommendations to strengthen European systems for better pandemic preparedness.

Methods

Assessments were carried out in eight European countries using an adapted version of the WHO support tool to strengthen HIS and the Joint Action on Health Information assessment tool. The assessments took place between January 2022 and April 2023.

Results

Four main themes emerged regarding the gaps and best practices identified in the various HIS: organizational, technical, legal and resources. The results of these assessments show different approaches implemented by countries to improve their HIS and respond to the demands of the pandemic.

Conclusions

It is imperative for countries to draw valuable insights from the COVID-19 pandemic and strengthen their HIS. This involves the adaptation or development of pandemic preparedness plans, strengthening legislative framework for data sharing and privacy protection, promotion of data standards and international definitions and implementation of a unique person identifier. Additionally, countries will have to act in this post-pandemic era and integrate the newly developed systems and innovations into existing structures, maintain and develop trust by citizens through transparent communication and engage in infodemic management and address resource gaps in the workforce.
Identification of methodological issues regarding direct impact indicators of COVID-19: a rapid scoping review on morbidity, severity and mortality
Authors: Garriga Cesar , Valero-Gaspar Teresa , Rodriguez-Blazquez Carmen , Diaz Asuncion , Bezzegh Péter , Daňková Šárka , Unim Brigid , Palmieri Luigi , Thiβen Martin , Pentz Richard , Cilović-Lagarija Šeila , Jogunčić Anes , Feteira-Santos Rodrigo , Vuković Jakov , Idavain Jane , Curta Anda , Sandu Petru , Vinko Matej , Forjaz Maria João
Published: July 2024

Background

During the first epidemic wave, COVID-19 surveillance focused on quantifying the magnitude and the escalation of a growing global health crisis. The scientific community first assessed risk through basic indicators, such as the number of cases or rates of new cases and deaths, and later began using other direct impact indicators to conduct more detailed analyses. We aimed at synthesizing the scientific community’s contribution to assessing the direct impact of the COVID-19 pandemic on population health through indicators reported in research papers.

Methods

We conducted a rapid scoping review to identify and describe health indicators included in articles published between January 2020 and June 2021, using one strategy to search PubMed, EMBASE and WHO COVID-19 databases. Sixteen experts from European public health institutions screened papers and retrieved indicator characteristics. We also asked in an online survey how the health indicators were added to and used in policy documents in Europe.

Results

After reviewing 3891 records, we selected a final sample of 67 articles and 233 indicators. We identified 52 (22.3%) morbidity indicators from 33 articles, 105 severity indicators (45.1%, 27 articles) and 68 mortality indicators (29.2%, 51). Respondents from 22 countries completed 31 questionnaires, and the majority reported morbidity indicators (29, 93.5%), followed by mortality indicators (26, 83.9%).

Conclusions

The indicators collated here might be useful to assess the impact of future pandemics. Therefore, their measurement should be standardized to allow for comparisons between settings, countries and different populations.
Risk factors for mid- and long-term mortality in lung transplant recipients aged 70 years and older
Authors: Pan Yining , Shi Jiang , Li Xuan , Luo Xiaojing , Zhang Jiaqin , Luo Caikang , Lin Yanwei , Huang Fei , He Wei , Lan Xiaoqing , He Junjie , Xu Yu , He Jianxing , Xu Xin
Published: July 2024

OBJECTIVES

With increased lung transplantation in those aged 70 and older, limited literature addresses risk factors affecting their survival. Our study aims to identify independent factors impacting mid- and long-term mortality in this elderly population.

METHODS

This study analyzed lung transplant patients over 70 from May 2005 to December 2022 using United Network for Organ Sharing data. The 3- or 5-year cohort excluded multi-organ, secondary transplantation and loss to follow-up. Univariable Cox analysis was conducted to assess recipient, donor and transplant factors. Factors with a significance level of P < 0.2 were subsequently included in a multivariable Cox model to identify correlations with 3- and 5-year mortality in patients aged over 70.

RESULTS

Multivariable analysis has identified key factors affecting 3- and 5-year mortality in elderly lung transplant patients over 70. Common notable factors include recipient total bilirubin, intensive care unit status at the time of transplantation, donor diabetes, Cytomegalovirus (CMV) mismatch and single lung transplantation. Additionally, Hispanic/Latino patients and ischaemia time of the transplant significantly impact the 3-year mortality, while recipient age, diabetes, nitric oxide use before transplantation and creatinine were identified as unique independent risk factors affecting the 5-year morality.

CONCLUSIONS

The study identified several independent risk factors that impact the mid- and long-term survival of lung transplantation for individuals over 70 years. These findings can contribute to the optimization of lung transplant treatment strategies and perioperative management in elderly patients, thereby enhancing the survival rate of this age group.
Does Collectivism Make a Difference? A Comparative Test of Common Ingroup Strategies to Reduce Affective Polarization
Authors: Park Jihye , Warner Benjamin R
Published: July 2024

Common national identity appeals have been identified as one of the most promising strategies to reduce affective political polarization. However, research on this is concentrated in highly individualistic Western democracies. Because much of the global population lives in more collectivist societies, it is important to conduct comparative tests to see if common national identity appeals operate similarly when considering the increasingly global problem of polarization. In this study, we investigate how the individualism–collectivism dimension of culture interacts with national identity salience as a polarization reduction strategy. Survey experiments were conducted in South Korea and the US. We find that priming national identity increases national pride much more in collectivist societies, but that the depolarizing effect of our national identity prime was only indirect and limited.
Natural Carriage of Streptococcus pneumoniae Is Associated With Increased Experimental Pneumococcal Carriage but Reduced Conjugate Vaccine Efficacy in a Human Challenge Model
Authors: Galafa Bridgette , Chikaonda Tarsizio , Kudowa Evaristar , Sichone Simon , Sibale Lusako , Thole Faith , Mkandawire Christopher , Dula Dingase , Nsomba Edna , Tembo Godwin , Chaponda Mphatso , Chirwa Anthony E , Nkhoma Vitumbiko , Ngoliwa Clara , Kamng'ona Raphael , Toto Neema , Makhaza Lumbani , Muyaya Alfred , Howard Ashleigh , Nyazika Tinashe K , Ndaferankhande John , Chimgoneko Lorensio , Banda Ndaziona P K , Chiwala Gift , Rylance Jamie , Ferreira Daniela , Jambo Kondwani C , Morton Ben , Henrion Marc Y R , Gordon Stephen B
Published: July 2024

Background

In Malawi, the national 13-valent pneumococcal conjugate vaccine (PCV13) demonstrated less herd immunity than in the United States, likely due to higher natural pneumococcal carriage rates. We assessed PCV13 efficacy against experimental pneumococcal carriage in healthy Malawian adults. We explored how natural carriage (pneumococcal carriage of any serotype apart from 6B) influenced experimental carriage rates and vaccine efficacy.

Methods

Healthy adults aged 18 to 40 years were randomly assigned to PCV13 (n = 98) or saline (n = 106), followed by intranasal SPN 6B inoculation at 20 000 (n = 40), 80 000 (n = 74), or 160 000 (n = 90) colony-forming units/100 µL at 28 days postvaccination. We evaluated natural and experimental pneumococcal carriage before and after vaccination on days 2, 7, and 14 postinoculation using culture and multiplex quantitative polymerase chain reaction (qPCR) targeting the lytA/cpsA genes, and we compared carriage rates by vaccination status.

Results

Of 204 participants, 19.6% (n = 40) exhibited experimental carriage detected by culture and 25.5% (n = 52) by qPCR. Vaccinated individuals had lower experimental carriage rates (10.2%, n = 10/98) than the placebo group (28.3%, 30/106). This difference in vaccine efficacy was more pronounced in participants without natural carriage (PCV13, 8%, 6/75; placebo, 25.9%, 21/81) vs those with natural carriage (PCV13, 14.8%, 4/27; placebo, 26.5%, 9/34). According to a log-binomial model, vaccine effectiveness (VE) was 62%, whether assessed by culture or qPCR. Natural carriers had lower VE (52%) vs participants with no natural carriage (69%).

Conclusions

We have shown that the PCV13 VE estimate (62%) is robust whether carriage is assessed by culture or qPCR. PCV13 had lower VE in natural carriers when compared with those without natural carriage at the inoculation visit.
Reducing diagnostic delays in acute hepatic porphyria using health records data and machine learning
Authors: Bhasuran Balu , Schmolly Katharina , Kapoor Yuvraaj , Jayakumar Nanditha Lakshmi , Doan Raymond , Amin Jigar , Meninger Stephen , Cheng Nathan , Deering Robert , Anderson Karl , Beaven Simon W , Wang Bruce , Rudrapatna Vivek A
Published: July 2024

Background

Acute hepatic porphyria (AHP) is a group of rare but treatable conditions associated with diagnostic delays of 15 years on average. The advent of electronic health records (EHR) data and machine learning (ML) may improve the timely recognition of rare diseases like AHP. However, prediction models can be difficult to train given the limited case numbers, unstructured EHR data, and selection biases intrinsic to healthcare delivery. We sought to train and characterize models for identifying patients with AHP.

Methods

This diagnostic study used structured and notes-based EHR data from 2 centers at the University of California, UCSF (2012-2022) and UCLA (2019-2022). The data were split into 2 cohorts (referral and diagnosis) and used to develop models that predict (1) who will be referred for testing of acute porphyria, among those who presented with abdominal pain (a cardinal symptom of AHP), and (2) who will test positive, among those referred. The referral cohort consisted of 747 patients referred for testing and 99 849 contemporaneous patients who were not. The diagnosis cohort consisted of 72 confirmed AHP cases and 347 patients who tested negative. The case cohort was 81% female and 6-75 years old at the time of diagnosis. Candidate models used a range of architectures. Feature selection was semi-automated and incorporated publicly available data from knowledge graphs. Our primary outcome was the F-score on an outcome-stratified test set.

Results

The best center-specific referral models achieved an F-score of 86%-91%. The best diagnosis model achieved an F-score of 92%. To further test our model, we contacted 372 current patients who lack an AHP diagnosis but were predicted by our models as potentially having it (≥10% probability of referral, ≥50% of testing positive). However, we were only able to recruit 10 of these patients for biochemical testing, all of whom were negative. Nonetheless, post hoc evaluations suggested that these models could identify 71% of cases earlier than their diagnosis date, saving 1.2 years.

Conclusions

ML can reduce diagnostic delays in AHP and other rare diseases. Robust recruitment strategies and multicenter coordination will be needed to validate these models before they can be deployed.
Towards travel therapy: addressing the health benefits of international travel
Authors: Flaherty Gerard T , Steffen Robert , Leder Karin
Published: July 2024

This perspective article discusses the physical, mental and sociocultural benefits of international travel and considers the case for prescribing travel for therapeutic reasons. It also identifies priorities for further research in this neglected area.
Testing the evolutionary potential of an alpine plant: phenotypic plasticity in response to growth temperature outweighs parental environmental effects and other genetic causes of variation
Authors: Arnold Pieter A , Wang Shuo , Notarnicola Rocco F , Nicotra Adrienne B , Kruuk Loeske E B
Published: July 2024

Phenotypic plasticity and rapid evolution are fundamental processes by which organisms can maintain their function and fitness in the face of environmental changes. Here we quantified the plasticity and evolutionary potential of an alpine herb Wahlenbergia ceracea. Utilizing its mixed-mating system, we generated outcrossed and self-pollinated families that were grown in either cool or warm environments, and that had parents that had also been grown in either cool or warm environments. We then analysed the contribution of environmental and genetic factors to variation in a range of phenotypic traits including phenology, leaf mass per area, photosynthetic function, thermal tolerance, and reproductive fitness. The strongest effect was that of current growth temperature, indicating strong phenotypic plasticity. All traits except thermal tolerance were plastic, whereby warm-grown plants flowered earlier, grew larger, and produced more reproductive stems compared with cool-grown plants. Flowering onset and biomass were heritable and under selection, with early flowering and larger plants having higher relative fitness. There was little evidence for transgenerational plasticity, maternal effects, or genotype×environment interactions. Inbreeding delayed flowering and reduced reproductive fitness and biomass. Overall, we found that W. ceracea has the capacity to respond rapidly to climate warming via plasticity, and the potential for evolutionary change.
Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study)
Authors: Márquez-Rodas Iván , Álvarez Ana , Arance Ana , Valduvieco Izaskun , Berciano-Guerrero Miguel-Ángel , Delgado Raquel , Soria Ainara , Lopez Campos Fernándo , Sánchez Pedro , Romero Jose Luis , Martin-Liberal Juan , Lucas Anna , Díaz-Beveridge Roberto , Conde-Moreno Antonio-José , Álamo de la Gala Maria del Carmen , García-Castaño Almudena , Prada Pedro José , González Cao María , Puertas Enrique , Vidal Joana , Foro Palmira , Aguado de la Rosa Carlos , Corona Juan Antonio , Cerezuela-Fuentes Pablo , López Paco , Luna Pablo , Aymar Neus , Puértolas Teresa , Sanagustín Pilar , Berrocal Alfonso
Published: July 2024

Background

Encorafenib plus binimetinib (EB) is a standard-of-care treatment for advanced BRAFV600-mutant melanoma. We assessed the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response.

Methods

E-BRAIN/GEM1802 was a prospective, multicenter, single-arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved a partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression. Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%.

Results

The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After 2 months, icRR was 70.8% (95% CI: 55.9–83.1); 10.4% complete response. Median intracranial progression-free survival (PFS) and OS were 8.5 (95% CI: 6.4–11.8) and 15.9 (95% CI: 10.7–21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grades 3–4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%).

Conclusions

Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high-grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.
Corilagin functionalized decellularized extracellular matrix as artificial blood vessels with improved endothelialization and anti-inflammation by reactive oxygen species scavenging
Authors: Wang Xu , Fu Hanmei , Wu Huibin , Peng Xiaohua , Peng Xu , Yu Xixun , Liu Hui , Wu Junmei , Luo Ling , Yan Shan , Cheng Xinglin , Zhou Xiong , Yuan Xiangyang
Published: July 2024

The performance of biological-originated blood vessels in clinical remains disappointing due to fast occlusion caused by acute thrombosis or long-standing inflammation. How to prevent rapid degradation and inhibit acute inflammation but maintain their high bioactivity is still a significant challenge. As a bioactive polyphenol in various traditional Chinese medicine, Corilagin (Cor) exhibits excellent anticoagulant, anti-inflammatory and rapid ROS consumption properties. Inspired by abundant supramolecular interactions in organisms, we selected it to crosslink tissues via purely H-bonds to simulate these natural interactions without introducing potential toxic aldehyde or carboxyl groups. Results show that 2 mg/ml was selected as the optimal Cor concentration to form a stable crosslinking network (FI > 95%) and effectively delay their degradation. Cor modification not only enhances ECs adhesion and monolayer function via accelerating VEGF and TGF-β secretion but also promotes macrophage transformation from pro-inflammatory M1 phenotype to anti-inflammatory M2 ones. In vitro and ex-vivo studies implied that Cor-crosslinked samples exhibited low platelet accumulation and decreased thrombin generation. In vivo evaluation further confirmed that Cor-introducing could effectively consume ROS, thus exhibiting rapid endothelialization, suppressed inflammation and reduced mineral deposition. Overall, Cor crosslinking provided a bright future for blood vessels’ long-term patency and adapted to various blood-contacting surfaces.
Simulation study for design of long counter for standard neutron fields from 1 keV to 20 MeV at NMIJ/AIST
Authors: Matsumoto Tetsuro , Masuda Akihiko , Harano Hideki , Manabe Seiya
Published: July 2024

A De-Pangher-type long counter was designed for neutron measurements in standard neutron fields based on the results of simulations using the MCNP6 code at the National Metrology Institute of Japan, the National Institute of Advanced Industrial Science and Technology. The effects of six parameters in the design on the energy response of the long counter were investigated. The energy response was then quantitatively evaluated for eight design candidates selected from the investigation. The calculation results show that these candidates have a flatter energy response from 100 eV to 10 MeV compared to that of the current long counter. These candidates also reduce the difference between the average energy response from 10 eV to 1 MeV and that from 10 to 20 MeV.
Impact of cardiac rehabilitation on erectile dysfunction in cardiovascular patients: a systematic review and meta-analysis
Authors: Sadeghi Masoumeh , Askari Ali , Bostan Fatemeh , Heidari Afshin , Rafiee Hamed , Alavi Tabatabaei Ghazaal , Ghasemi Golsa , Roohafza Hamidreza
Published: July 2024

Background

Cardiovascular diseases (CVDs) and erectile dysfunction (ED) frequently co-occur, significantly affecting the quality of life of individuals.

Aim

To assess the impact of cardiac rehabilitation (CR) on ED in patients with CVD through a systematic review and meta-analysis.

Methods

This study analyzed randomized controlled trials and other studies comparing CR with usual care for adult males (≥18 years) with any cardiac disease. Literature searches were extensive, and the risk of bias was evaluated by the Cochrane Collaboration tool. Data from 6 studies involving 668 participants were included in the meta-analysis.

Outcomes

The primary outcome was the improvement in ED, as measured with the International Index of Erectile Function.

Results

A statistically significant improvement in erectile function was observed across 6 studies, with a Morris dppc2 effect size of 0.38 (95% CI, 0.17-0.59). Despite initial high heterogeneity (I2 = 95.7%), identification and correction for selective outcome reporting bias mitigated this issue.

Clinical Translation

CR has a modest but statistically significant impact on improving ED in patients with CVD, indicating its potential positive contribution to the quality of life of this group.

Strengths and Limitations

The study’s strengths include a comprehensive literature search and a rigorous methodological approach. Limitations involve high heterogeneity among studies and a low level of evidence due to small sample sizes and study quality; however, the source of heterogeneity was identified and mitigated following risk-of-bias assessment.

Conclusion

The results suggest that CR has a statistically significant but modest impact on improving ED in patients with CVD. Clinicians should consider the integration of CR into the clinical management of these individuals. This study underscores the potential for CR to contribute positively to the quality of life for patients with CVD by addressing associated ED (PROSPERO: CRD42022374625).
Feminizing Patriarchy: Christian Churches and Gender Inequality in Rural Africa
Authors: Agadjanian Victor
Published: July 2024

In dialogue with the cross-national scholarship on gender and religion, the study uses a unique combination of rich qualitative and quantitative data from a predominantly Christian rural sub-Saharan setting to examine how churches modify, yet also sustain and even reinforce, patriarchal norms. It shows how churches replace the traditional, extended family-based model of gender inequality with a pseudo-modern model of individualized conjugal dependency. Although men increasingly disengage from the religious space, the growing feminization of that space does not translate into a more gender-egalitarian narrative: the church nurtures women’s agency yet also channels it to rearrange and reassert their subservience. To acquire legitimacy, church women are pressured to act as collective articulators, promoters, and guarantors of neo-patriarchal values and orders, and in particular, as builders and saviors of matrimonial integrity and viability. These dynamics reflect and are an integral part of the broader gendered constraints and precarities of contemporary rural society.
Promotion of maturation of human pluripotent stem cell-derived cardiomyocytes via treatment with the peroxisome proliferator-activated receptor alpha agonist Fenofibrate
Authors: Lee Seul-Gi , Rhee Jooeon , Seok Jin , Kim Jin , Kim Min Woo , Song Gyeong-Eun , Park Shinhye , Jeong Kyu Sik , Lee Suemin , Lee Yun Hyeong , Jeong Youngin , Kim C-Yoon , Chung Hyung Min
Published: July 2024

As research on in vitro cardiotoxicity assessment and cardiac disease modeling becomes more important, the demand for human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is increasing. However, it has been reported that differentiated hPSC-CMs are in a physiologically immature state compared to in vivo adult CMs. Since immaturity of hPSC-CMs can lead to poor drug response and loss of acquired heart disease modeling, various approaches have been attempted to promote maturation of CMs. Here, we confirm that peroxisome proliferator-activated receptor alpha (PPARα), one of the representative mechanisms of CM metabolism and cardioprotective effect also affects maturation of CMs. To upregulate PPARα expression, we treated hPSC-CMs with fenofibrate (Feno), a PPARα agonist used in clinical hyperlipidemia treatment, and demonstrated that the structure, mitochondria-mediated metabolism, and electrophysiology-based functions of hPSC-CMs were all mature. Furthermore, as a result of multi electrode array (MEA)-based cardiotoxicity evaluation between control and Feno groups according to treatment with arrhythmia-inducing drugs, drug response was similar in a dose-dependent manner. However, main parameters such as field potential duration, beat period, and spike amplitude were different between the 2 groups. Overall, these results emphasize that applying matured hPSC-CMs to the field of preclinical cardiotoxicity evaluation, which has become an essential procedure for new drug development, is necessary.
Walnut oil: a promising nutraceutical in reducing oxidative stress and improving cholinergic activity in an in vitro Alzheimer’s disease model
Authors: Demirel Göksun , Sanajou Sonia , Yirün Anıl , Çakır Deniz Arca , Özyurt Aylin Balcı , Berkkan Aysel , Baydar Terken , Erkekoğlu Pınar
Published: July 2024

Improving the quality of life in elderly patients and finding new treatment options for neurological diseases such as Alzheimer’s has become one of the priorities in the scientific world. In recent years, the beneficial effects and therapeutic properties of natural foods on neurological health have become a very remarkable issue. Walnut oil (WO) is a promising nutraceutical, with many phytochemicals and polyunsaturated fatty acids and is thought to be promising in the treatment of many neurological diseases and cognitive deficits, such as Alzheimer’s disease (AD). Polyphenolic compounds found in WO enhance intraneuronal signaling and neurogenesis and improve the sequestration of insoluble toxic protein aggregates. The objective of this study was to investigate the potential protective and therapeutic effects of WO in a model of AD induced by retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). In order to achieve this, the experimental groups were formed as follows: Control group, WO group, Alzheimer’s disease (AD) group, AD + WO applied group (AD + WO). WO supplementation almost significantly reduced oxidative stress in the ad model, providing 2-fold protection against protein oxidation. Additionally, WO showed a significant reduction in tau protein levels (2-fold), increased acetylcholine (ACh) levels (12%), and decreased acetylcholine esterase (AChE) activity (~50%). Since it has been known for centuries that WO does show any adverse effects on human health and has neuroprotective properties, it may be used in the treatment of AD as an additional nutraceutical to drug treatments.
Tip-to-base conduit widening remains consistent across cambial age and climates in Fagus sylvatica L.
Authors: Rita Angelo , Pericolo Osvaldo , Tumajer Jan , Ripullone Francesco , Gentilesca Tiziana , Saracino Antonio , Borghetti Marco
Published: July 2024

Water transport, mechanical support and storage are the vital functions provided by the xylem. These functions are carried out by different cells, exhibiting significant anatomical variation not only within species but also within individual trees. In this study, we used a comprehensive dataset to investigate the consistency of predicted hydraulic vessel diameter widening values in relation to the distance from the tree apex, represented by the relationship Dh ∝ Lβ (where Dh is the hydraulic vessel diameter, L the distance from the stem apex and β the scaling exponent). Our analysis involved 10 Fagus sylvatica L. trees sampled at two distinct sites in the Italian Apennines. Our results strongly emphasize that vessel diameter follows a predictable pattern with the distance from the stem apex and β ~ 0.20 remains consistent across cambial age and climates. This finding supports the hypothesis that trees do not alter their axial configuration represented by scaling of vessel diameter to compensate for hydraulic limitations imposed by tree height during growth. The study further indicates that within-tree variability significantly contributes to the overall variance of the vessel diameter-stem length exponent. Understanding the factors that contribute to the intraindividual variability in the widening exponent is essential, particularly in relation to interspecific responses and adaptations to drought stress.
Infection of Alfalfa Cotyledons by an Incompatible but Not a Compatible Species of Colletotrichum Induces Formation of Paramural Bodies and Secretion of EVs
Authors: Ghosh Suchismita , Regmi Kamesh C. , Stein Barry , Chen Jun , O'Connell Richard J. , Innes Roger W.
Published: July 2024

Hemibiotrophic fungi in the genus Colletotrichum employ a biotrophic phase to invade host epidermal cells followed by a necrotrophic phase to spread through neighboring mesophyll and epidermal cells. We used serial block face-scanning electron microscopy (SBF-SEM) to compare subcellular changes that occur in Medicago sativa (alfalfa) cotyledons during infection by Colletotrichum destructivum (compatible on M. sativa) and C. higginsianum (incompatible on M. sativa). Three-dimensional reconstruction of serial images revealed that alfalfa epidermal cells infected with C. destructivum undergo massive cytological changes during the first 60 h following inoculation to accommodate extensive intracellular hyphal growth. Conversely, inoculation with the incompatible species C. higginsianum resulted in no successful penetration events and frequent formation of papilla-like structures and cytoplasmic aggregates beneath attempted fungal penetration sites. Further analysis of the incompatible interaction using focused ion beam-scanning electron microscopy (FIB-SEM) revealed the formation of large multivesicular body-like structures that appeared spherical and were not visible in compatible interactions. These structures often fused with the host plasma membrane, giving rise to paramural bodies that appeared to be releasing extracellular vesicles (EVs). Isolation of EVs from the apoplastic space of alfalfa leaves at 60 h postinoculation showed significantly more vesicles secreted from alfalfa infected with incompatible fungus compared with compatible fungus, which in turn was more than produced by noninfected plants. Thus, the increased frequency of paramural bodies during incompatible interactions correlated with an increase in EV quantity in apoplastic wash fluids. Together, these results suggest that EVs and paramural bodies contribute to immunity during pathogen attack in alfalfa.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Inspirational Story of Agriculture at Living with the Land Attraction at EPCOT
Authors: Huang Yong , Kleiss Laura , Roberson Samantha , Strzyzewski Iris , Egbert Whitney , Simms Michael , Lockwood Lindsay , Sperry Mark , McFarland Shannon , Petitt Fred
Published: July 2024

Since its debut in 1982, The Land has embodied Walt Disney’s vision, capturing the attention of millions of EPCOT guests with venues focusing on agriculture and environmental stewardship and sustainability. The Land pavilion spans more than 8 acres in the World Nature section of EPCOT at the Walt Disney World Resort in Lake Buena Vista, Florida. The pavilion houses three attractions, namely Soarin’ Around the World, Awesome Planet, and the Living with the Land boat ride, complemented by a greenhouse walking tour entitled Behind the Seeds and two restaurants. Each attraction derives inspiration from nature and challenges mankind to be responsible stewards of planet earth. This feature article focuses on the Living with the Land boat ride attraction, which traverses greenhouses showcasing agricultural technologies and crops from around the world. The sections below describe both how various show elements are designed to engage guests and how the show is made possible by applying relevant science and technology.
Effect of Preoperative Motor Weakness on Postoperative Clinical Outcomes in Patients Undergoing Cervical Disk Replacement
Authors: Roca Andrea M. , Anwar Fatima N. , Medakkar Srinath S. , Loya Alexandra C. , Kaul Aayush , Wolf Jacob C. , Federico Vincent P. , Sayari Arash J. , Lopez Gregory D. , Singh Kern
Published: July 2024

Study Design:

This is a retrospective review.

Objective:

To examine the effect of preoperative motor weakness on clinical outcomes in patients undergoing cervical disk replacement (CDR).

Summary of Background Data:

Studies examining the effect of preoperative motor weakness on postoperative clinical outcomes in CDR are limited.

Methods:

Patient cohorts were based on documented upper-extremity motor weakness on physical exam versus no motor weakness. Demographics, perioperative characteristics, and preoperative patient-reported outcome measures (PROMs) were compared using univariate inferential statistics. PROMs consisted of Visual Analog Pain Scale-Neck (VAS-N), Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), VAS-Arm (VAS-A), 12-Item Short Form (SF-12) Physical Component Score (PCS), Oswestry Neck Disability Index (NDI), and SF-12 Mental Component Score (MCS). Postoperative PROMs were collected at the 6-week, 12-week, 6-month, and final follow-up up to 1-yeartime points, and intercohort minimum clinically important difference (MCID) achievement was compared through multivariable linear logistic regression adjusting for significant differences in preoperative characteristics.

Results:

A total of 118 patients formed cohorts based on documented upper-extremity weakness (n=73) versus no weakness (n=45). The average time to postoperative follow-up was 9.7±7.0 mo. The differences in insurance type between the 2 cohorts were significant (P<0.042). Perioperative diagnosis of foraminal stenosis was significantly more common in the motor weakness cohort (P<0.013). There were no differences in reported PROMs between cohorts. Patients with motor weakness reported significant MCID achievement for PROMIS-PF at 6-/12-weeks (P<0.012, P<0.041 respectively), SF-12 PCS at 6-months (P<0.042), VAS-N at final follow-up (P<0.021), and NDI at final follow-up (P<0.013).

Conclusions:

CDR patients with preoperative muscle weakness achieved MCID across several PROMs compared with patients without muscle weakness. Patients with motor weakness reported greater improvement in mental health, pain, and disability as early as 6 weeks and up to 1 year after CDR. This information serves to inform physicians that motor weakness may not indicate a negative overall outcome.
Vagus nerve modulates acute-on-chronic liver failure progression via CXCL9
Authors: Wu Li , Li Jie , Zou Ju , Tang Daolin , Chen Ruochan
Published: July 2024

Background:

Hepatic inflammatory cell accumulation and the subsequent systematic inflammation drive acute-on-chronic liver failure (ACLF) development. Previous studies showed that the vagus nerve exerts anti-inflammatory activity in many inflammatory diseases. Here, we aimed to identify the key molecule mediating the inflammatory process in ACLF and reveal the neuroimmune communication arising from the vagus nerve and immunological disorders of ACLF.

Methods:

Proteomic analysis was performed and validated in ACLF model mice or patients, and intervention animal experiments were conducted using neutralizing antibodies. PNU-282987 (acetylcholine receptor agonist) and vagotomy were applied for perturbing vagus nerve activity. Single-cell RNA sequencing (scRNA-seq), flow cytometry, immunohistochemical and immunofluorescence staining, and CRISPR/Cas9 technology were used for in vivo or in vitro mechanistic studies.

Results:

The unbiased proteomics identified C-X-C motif chemokine ligand 9 (CXCL9) as the greatest differential protein in the livers of mice with ACLF and its relation to the systematic inflammation and mortality were confirmed in patients with ACLF. Interventions on CXCL9 and its receptor C-X-C chemokine receptor 3 (CXCR3) improved liver injury and decreased mortality of ACLF mice, which were related to the suppressing of hepatic immune cells’ accumulation and activation. Vagus nerve stimulation attenuated while vagotomy aggravated the expression of CXCL9 and the severity of ACLF. Blocking CXCL9 and CXCR3 ameliorated liver inflammation and increased ACLF-associated mortality in ACLF mice with vagotomy. scRNA-seq revealed that hepatic macrophages served as the major source of CXCL9 in ACLF and were validated by immunofluorescence staining and flow cytometry analysis. Notably, the expression of CXCL9 in macrophages was modulated by vagus nerve-mediated cholinergic signaling.

Conclusions:

Our novel findings highlighted that the neuroimmune communication of the vagus nerve–macrophage–CXCL9 axis contributed to ACLF development. These results provided evidence for neuromodulation as a promising approach for preventing and treating ACLF.
Interfering with aggregated α-synuclein in advanced melanoma leads to a major upregulation of MHC class II proteins
Authors: Fokken Claudia , Silbern Ivan , Shomroni Orr , Pan Kuan-Ting , Ryazanov Sergey , Leonov Andrei , Winkler Nadine , Urlaub Henning , Griesinger Christian , Becker Dorothea
Published: July 2024

Melanoma is the most serious and deadly form of skin cancer and with progression to advanced melanoma, the intrinsically disordered protein α-synuclein is upregulated to high levels. While toxic to dopaminergic neurons in Parkinson’s disease, α-synuclein is highly beneficial for primary and metastatic melanoma cells. To gain detailed insights into this exact opposite role of α-synuclein in advanced melanoma, we performed proteomic studies of high-level α-synuclein-expressing human melanoma cell lines that were treated with the diphenyl-pyrazole small-molecule compound anle138b, which binds to and interferes with the oligomeric structure of α-synuclein. We also performed proteomic and transcriptomic studies of human melanoma xenografts that were treated systemically with the anle138b compound. The results reveal that interfering with oligomerized α-synuclein in the melanoma cells in these tumor xenografts led to a substantial upregulation and expression of major histocompatibility complex proteins, which are pertinent to enhancing anti-melanoma immune responses.
Personalized Amoxicillin Therapy in a Critically Ill Patient Undergoing Renal Replacement Therapy: A Grand Round
Authors: Garrigue Philippine , Reber Margot , Perinel-Ragey Sophie , Launay Manon
Published: July 2024

Background:

The case study discusses a complex scenario involving the use of amoxicillin in a critically ill patient undergoing intermittent renal replacement therapy.

Severe infections are complicated by septic shock and organ failure, requiring urgent and effective antibiotic treatment.

Methods:

The patient's comorbidities, including obesity and acute kidney injury, required careful consideration of the amoxicillin dosing strategies.

Results:

Therapeutic drug monitoring is critical for dose adjustment during treatment.

Conclusions:

This case highlights the importance of a collaborative approach between clinicians and therapeutic drug monitoring consultants to optimize antibiotic therapy for critically ill patients with renal impairment.