bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of implementing performance-based financing for improving maternal and child health in Ethiopia
Authors: Koricho Mideksa Adugna , Dinsa Girmaye Deye , Khuzwayo Nelisiwe
Published: July 2024

Introduction

Performance Based Financing (PBF) supports realization of universal health coverage by promoting bargaining between purchasers and health service providers through identifying priority services and monitoring indicators. In PBF, purchasers use health statistics and information to make decisions rather than merely reimbursing invoices. In this respect, PBF shares certain elements of strategic health purchasing. PBF implementation began in Ethiopia in 2015 as a pilot at one hospital and eight health centers. Prior to this the system predominantly followed input-based financing where providers were provided with a predetermined budget for inputs for service provision. The purpose of the study is to determine whether the implementation of PBF is cost-effective in improving maternal and child health in Ethiopia compared to the standard care.

Methods

The current study used cost-effectiveness analysis to assess the effects of PBF on maternal and child health. Two districts implementing PBF and two following standard care were selected for the study. Both groups of selected districts share common grounds before initiating PBF in the selected group. The provider perspective costing approach was used in the study. Data at the district level were gathered retrospectively for the period of July 2018 to June 2021. Data from health service statistics were transformed to population level coverages and the Lives Saved Tool method used to compute the number of lives saved. Additionally for purpose of comparison, lives saved were translated into discounted quality-adjusted life years.

Results

The number of lives saved under PBF was 261, whereas number of lives saved under standard care was 194. The identified incremental cost per capita due to PBF was $1.8 while total costs of delivering service at PBF district was 8,816,370 USD per million population per year while the standard care costs 9,780,920 USD per million population per year. QALYs obtained under PBF and standard care were 6,118 and 4,526 per million population per year, respectively.

Conclusions

The conclusion made from this analysis is that, implementing PBF is cost-saving in Ethiopia compared to the standard care.

Limitations of the study

Due to lack of district-level survey-based data, such as prevalence and effects on maternal and child health, national-level estimates were used into the LiST tool.

There may be some central-level PBF start-up costs that were not captured, which may have spillover effects on the existing health system performance that this study has not considered.

There may be health statistics data accuracy differences between the PBF and non-PBF districts. The researchers considered using data from records as reported by both groups of districts,
An optimised protocol for the detection of lipofuscin, a versatile and quantifiable marker of cellular senescence
Authors: Davan-Wetton Camilla S. A. , Montero-Melendez Trinidad
Published: July 2024

Lipofuscin is a yellow-brown pigment typically found in the lysosomes that contains a mixture of molecules including lipids, metals and misfolded proteins. The use of Sudan black B to detect lipofuscin accumulation, a well described marker of cellular senescence and ageing, was first described in 2013 by Georgakopoulou, et al. Here, we provide an optimisation of the original protocol. Firstly, we adjusted the staining methodology for increased ease of use on cultured cells. Secondly, we show that Sudan black B-stained lipofuscin emits strong fluorescence in the far-red channel making it suitable for fluorescence microscopy detection and quantification. Moreover, we also demonstrate that this optimised protocol can be utilised in conjunction with standard immunofluorescence staining techniques, making possible the simultaneous detection of lipofuscin and other cellular proteins of interest, like additional markers of senescence. This is a significant advantage over the most commonly used method for senescence detection, based on beta galactosidase enzymatic activity. We therefore believe that these findings and the provided optimised protocol will represent a useful tool for the scientific community in the field of cellular senescence.
Proximal and distant expression of growth differentiation factor 15 (GDF15) correlate with neurological deficit following experimental ischemic stroke
Authors: Méloux Alexandre , Dogon Geoffrey , Rigal Eve , Rochette Luc , Bejot Yannick , Vergely Catherine
Published: July 2024

Background and purpose

Growth differentiation factor 15 (GDF15) has emerged as a promising biomarker in cerebro-cardiovascular disease, particularly in acute and chronic inflammatory stress situations. However, understanding the origins, targets and functions of GDF15 in clinical situations, such as ischemic stroke, remains a complex challenge. This study aims to assess the sources of GDF15 production following an experimental ischemic stroke.

Methods

Adult male Wistar rats underwent cerebral embolization through microspheres injection into the left or right internal carotid artery. Two hours post-surgery, GDF15 expression was analyzed in the brain, blood, lungs, liver and heart using quantitative RT-PCR and Western blotting.

Results

Stroke model induced large cerebral infarcts accompanied by severe neurological deficits. GDF15 gene expression exhibited a substantial increase in the ipsilateral cortex and cerebellum, with a lesser extent in the contralateral cortex. Regarding GDF15 protein expression, proGDF15 levels were elevated in the 3 aforementioned organs mentioned and the heart. However, the mature form of GDF15 was exclusively present and increased in the heart. Finally, the expression of GDF15 expression was correlated with the neurological deficit score.

Conclusions

Our findings suggest that both the GDF15 gene and pro-protein are expressed in the ischemic brain after a stroke, while only its mature form is expressed remotely in in the heart. The impact of increased GDF15 in the heart following a stroke remains to be established. This is particularly relevant in understanding its relationships with poor neurological outcomes, determining whether it may contribute to stroke-induced cardiac dysfunction.
Mechanical rheological model on the assessment of elasticity and viscosity in tissue inflammation: A systematic review
Authors: Kimondo Jotham Josephat , Said Ramadhan Rashid , Wu Jun , Tian Chao , Wu Zhe
Published: July 2024

Understanding the extent of inflammation is crucial for early disease detection, monitoring disease progression, and evaluating treatment responses. Over the past decade, researchers have demonstrated the need to understand the extent of inflammation through qualitative or quantitative characterization of tissue viscoelasticity using different techniques. In this scientific review, an examination of research on the association between elasticity and Viscosity in diseases, particularly as tissue inflammation progresses, is conducted. A review of utilizing mechanical rheological models to characterize quantitative viscoelastic parameters of normal and inflamed tissues is also undertaken. Based on inclusion and exclusion criteria, we identified 14 full-text studies suitable for review out of 290 articles published from January 2000 to January 2024. We used PRISMA guidelines for the systematic review. In the review, three studies demonstrated the criterion used by the researchers in identifying the best rheological model. Eleven studies showed the clinical application of the rheological model in quantifying the viscoelastic properties of normal and pathological tissue. The review quantified viscoelastic parameters for normal and pathological tissue across various soft tissues. It evaluated the effectiveness of each viscoelastic property in distinguishing between normal and pathological tissue stiffness. Furthermore, the review outlined additional viscoelastic-related parameters for researchers to consider in future stiffness classification studies.
Integration of the PD-L1 inhibitor atezolizumab and WT1/DC vaccination into standard-of-care first-line treatment for patients with epithelioid malignant pleural mesothelioma—Protocol of the Immuno-MESODEC study
Authors: Van den Bossche Jolien , De Laere Maxime , Deschepper Koen , Germonpré Paul , Valcke Yvan , Lamont Jan , Stein Barbara , Van Camp Kirsten , Germonpré Charlotte , Nijs Griet , Roelant Ella , Anguille Sébastien , Lion Eva , Berneman Zwi
Published: July 2024

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a very poor prognosis. Recently, immune checkpoint inhibition (ICI) has taken center stage in the currently ongoing revolution that is changing standard-of-care treatment for several malignancies, including MPM. As multiple arguments and accumulating lines of evidence are in support of the existence of a therapeutic synergism between chemotherapy and immunotherapy, as well as between different classes of immunotherapeutics, we designed a multicenter, single-arm, phase I/II trial in which both programmed-death-ligand 1 (PD-L1) inhibition and dendritic cell (DC) vaccination are integrated in the first-line conventional platinum/pemetrexed-based treatment scheme for epithelioid MPM patients (Immuno-MESODEC, ClinicalTrials.gov identifier NCT05765084). Fifteen treatment-naïve patients with unresectable epithelioid subtype MPM will be treated with four 3-weekly (±3 days) chemo-immunotherapy cycles. Standard-of-care chemotherapy consisting of cisplatinum (75mg/m2) and pemetrexed (500mg/m2) will be supplemented with the anti-PD-L1 antibody atezolizumab (1200 mg) and autologous Wilms’ tumor 1 mRNA-electroporated dendritic cell (WT1/DC) vaccination (8–10 x 106 cells/vaccination). Additional atezolizumab (1680 mg) doses and/or WT1/DC vaccinations (8–10 x 106 cells/vaccination) can be administered optionally following completion of the chemo-immunotherapy scheme. Follow-up of patients will last for up to 90 days after final atezolizumab administration and/or WT1/DC vaccination or 24 months after diagnosis, whichever occurs later. The trial’s primary endpoints are safety and feasibility, secondary endpoints are clinical efficacy and immunogenicity. This phase I/II trial will evaluate whether addition of atezolizumab and WT1/DC vaccination to frontline standard-of-care chemotherapy for the treatment of epithelioid MPM is feasible and safe. If so, this novel combination strategy should be further investigated as a promising advanced treatment option for this hard-to-treat cancer.
Assessment of knowledge and practices regarding taeniasis and cysticercosis in Pak Chong, Nakhon Ratchasima, Thailand: A cross-sectional study
Authors: Phumrattanaprapin Wuttipong , Tatiya-apiradee Nitima , Jantaban Pattana , Mahikul Wiriya
Published: July 2024

Background

Taeniasis and cysticercosis are parasitic infections caused by Taenia spp., mainly transmitted through the consumption of undercooked pork. Prevention requires increasing knowledge and awareness, improving meat inspection and hygiene, and promoting safe food handling and sanitation. The aim of this study was to evaluate the knowledge and practice (KP) of residents in Pak Chong District, Nakhon Ratchasima, Thailand, regarding taeniasis and cysticercosis.

Methods

A cross-sectional study was conducted in Pak Chong District, Nakhon Ratchasima, Thailand, and its 11 subdistrict municipalities. Study participants were selected using a stratified random sampling design. A validated questionnaire (Cronbach’s alpha = 0.70) was used to collect socio-demographic information and assess knowledge and practices related to taeniasis and cysticercosis. Descriptive statistics and multiple linear regression were used for the analysis.

Results

Of the 360 survey respondents, 65.0% (n = 234) were women, 82.2% (n = 296) were aged under 60 years, 99.2% (n = 357) identified as Buddhist, 87.5% (n = 315) had less than a bachelor’s degree education level, 54.2% (n = 195) had monthly family income ≥10,000 Thai baht, 10.6% (n = 38) were unemployed, and 26.1% (n = 93) lived in a town municipality. The survey revealed that 98.3% (n = 354) of participants were categorized as having less accurate knowledge and 83.6% (n = 301) were classified as more frequently engaging in correct prevention practices. Our study revealed that pig farmers (1.7%) occasionally permitted the pigs to forage freely. The results of multiple linear regression analysis revealed that knowledge scores were positively associated with household income ≥10,000 Thai baht (βadj = 1.50, 95% confidence interval [CI] 0.65 to 2.36). Practice scores were negatively associated with age over 60 years (βadj = −1.77, 95% CI −3.14 to −0.40) and living in a subdistrict municipality (βadj = −2.58, 95% CI −3.77 to −1.39). There was no association between KP regarding taeniasis and cysticercosis in the population of Pak Chong.

Conclusions

Overall, participants’ knowledge was lacking. Public education interventions are recommended to improve knowledge among residents with low socioeconomic status. These findings can inform the development of targeted interventions and educational programs in Pak Chong District, especially among elderly people in subdistrict municipalities, to improve practices for the prevention and control of these parasitic infections.
Long-term outcomes after revascularization in chronic total and non-total occluded coronary arteries: A regionwide cohort study
Authors: Holck Emil Nielsen , Jakobsen Lars , Winther Naja Stausholm , Mogensen Lone Juul-Hune , Christiansen Evald Høj
Published: July 2024

Background

Understanding the prognostic impact of percutaneous coronary intervention (PCI) in chronic total occlusion (CTO) is crucial for patient management. Previous studies have primarily been studying prognostic impact of successful versus unsuccessful CTO PCI. This study investigated the prognostic impact of successful and unsuccessful percutaneous coronary intervention (PCI) of chronic total occluded coronary arteries (CTO) with non-CTO PCI as reference.

Methods

Patients treated with PCI from 2009 to 2019 in the Central Region of Denmark were included in a population-based cohort study. We compared successful and unsuccessful CTO PCI with non-CTO PCI. Exclusion criteria was myocardial infarction within 30 days. Primary outcome was difference in a composite major adverse cardio- and cerebrovascular events (MACCE) encompassing all-cause death, any myocardial infarction, stroke, hospitalization for heart failure or revascularization tracked via nationwide registries.

Results

Of 21,141 screened patients, 10,638 were enrolled: 9,065 underwent non-CTO PCI, 1,300 had successful CTO PCI, and 273 had unsuccessful CTO PCI. Median follow-up time was 5.9 [3.5;9.0] years and 4,750 MACCEs were recorded. Compared to non-CTO PCI, the adjusted MACCE rate for successful CTO PCI was equivalent (Hazard Ratio (HR): 0.98, 95% Confidence Interval (CI): 0.90–1.07, p = 0.71). In contrast, unsuccessful CTO PCI was associated with a higher MACCE rate (HR: 1.22, 95% CI: 1.04–1.43, p<0.01). HR was adjusted for age, body-mass index, previous revascularization, smoking, kidney disease, two or three-vessel disease, left ventricular ejection fraction, diabetes and comorbidities.

Conclusions

The pre-specified hypothesis was accepted. Successful CTO PCI was associated with equivalent long-term outcomes as non-CTO PCI, and unsuccessful CTO PCI was identified as a high-risk group associated to worse outcomes.
The astrovirus N-terminal nonstructural protein anchors replication complexes to the perinuclear ER membranes
Authors: Ali Hashim , Noyvert David , Hankinson Jacqueline , Lindsey Gemma , Lulla Aleksei , Lulla Valeria
Published: July 2024

An essential aspect of positive-sense RNA virus replication is anchoring the replication complex (RC) to cellular membranes. Positive-sense RNA viruses employ diverse strategies, including co-translational membrane targeting through signal peptides and co-opting cellular membrane trafficking components. Often, N-terminal nonstructural proteins play a crucial role in linking the RC to membranes, facilitating the early association of the replication machinery. Astroviruses utilize a polyprotein strategy to synthesize nonstructural proteins, relying on subsequent processing to form replication-competent complexes. This study provides evidence for the perinuclear ER membrane association of RCs in five distinct human astrovirus strains. Using tagged recombinant classical human astrovirus 1 and neurotropic MLB2 strains, we establish that the N-terminal domain guides the ER membrane association. We identified di-arginine motifs responsible for the perinuclear ER retention and formation of functional RCs through mutational analysis of the N-terminal domain in replicon and reverse genetics systems. In addition, we demonstrate the association of key components of the astrovirus replication complex: double-stranded RNA, RNA-dependent RNA polymerase, protease, and N-terminal protein. Our findings highlight the intricate virus-ER interaction mechanism employed by astroviruses, potentially leading to the development of novel antiviral intervention strategies.
Expression analysis of thg1l during Xenopus laevis development
Authors: Martini Davide , De Cesari Chiara , Digregorio Matteo , Muscò Alessia , Giudetti Guido , Giannaccini Martina , Andreazzoli Massimiliano
Published: July 2024

The tRNA-histidine guanylyltransferase 1-like (THG1L), also known as induced in high glucose-1 (IHG-1), encodes for an essential mitochondria-associated protein highly conserved throughout evolution, that catalyses the 3′–5′ addition of a guanine to the 5′-end of tRNA-histidine (tRNAHis). Previous data indicated that THG1L plays a crucial role in the regulation of mitochondrial biogenesis and dynamics, in ATP production, and is critically involved in the modulation of apoptosis, cell-cycle progression and survival, as well as in cellular stress responses and redox homeostasis. Dysregulations of THG1L expression play a central role in various pathologies, including nephropathies, and neurodevelopmental disorders often characterized by developmental delay and cerebellar ataxia. Despite the essential role of THG1L, little is known about its expression during vertebrate development. Herein, we examined the detailed spatio-temporal expression of this gene in the developing Xenopus laevis. Our results show that thg1l is maternally inherited and its temporal expression suggests a role during the earliest stages of embryogenesis. Spatially, thg1l mRNA localizes in the ectoderm and marginal zone mesoderm during early stages of development. Then, at tadpole stages, thg1l transcripts mostly localise in neural crests and their derivatives, somites, developing kidney and central nervous system, therefore largely coinciding with territories displaying intense energy metabolism during organogenesis in Xenopus.
HIV Infection Is Associated With a Less Aggressive Phenotype of Inflammatory Bowel Disease: A Multicenter Study of the ENEIDA Registry
Authors: Calafat Margalida , Suria Carles , Mesonero Francisco , de Francisco Ruth , Yagüe Caballero Carmen , de la Peña Luisa , Hernández-Camba Alejandro , Marcé Ainhoa , Gallego Beatriz , Martín-Vicente Noelia , Rivero Montserrat , Iborra Marisa , Guerra Iván , Carrillo-Palau Marta , Madero Lucía , Burgueño Beatriz , Monfort David , Torres Gisela , Teller Marta , Ferrer Rosique Juan Ángel , Vega Villaamil Pablo , Roig Cristina , Ponferrada-Diaz Angel , Betoré Glaría Elena , Zabana Yamile , Gisbert Javier P. , Busquets David , Alcaide Noelia , Camps Blau , Legido Jesús , González-Vivo Maria , Bosca-Watts Marta Maia , Pérez-Martínez Isabel , Casas Deza Diego , Guardiola Jordi , Arranz Hernández Laura , Navarro Mercè , Gargallo-Puyuelo Carla J. , Cañete Fiorella , Mañosa Míriam , Domènech Eugeni ,   on behalf of the ENEIDA Registry of GETECCU
Published: July 2024

INTRODUCTION:

The coexistence of HIV infection and inflammatory bowel disease (IBD) is uncommon. Data on the impact of HIV on IBD course and its management are scarce. The aim of this study was to describe the IBD phenotype, therapeutic requirements, and prevalence of opportunistic infections (OIs) in IBD patients with a coexistent HIV infection.

METHODS:

Case-control, retrospective study includes all HIV-positive patients diagnosed with IBD in the Nationwide study on genetic and environmental determinants of inflammatory bowel disease registry. Patients with positive HIV serology (HIV-IBD) were compared with controls (HIV seronegative), matched 1:3 by year of IBD diagnosis, age, sex, and type of IBD.

RESULTS:

A total of 364 patients (91 HIV-IBD and 273 IBD controls) were included. In the whole cohort, 58% had ulcerative colitis, 35% had Crohn's disease (CD), and 7% were IBD unclassified. The HIV-IBD group presented a significantly higher proportion of proctitis in ulcerative colitis and colonic location in CD but fewer extraintestinal manifestations than controls. Regarding treatments, nonbiological therapies (37.4% vs 57.9%; P = 0.001) and biologicals (26.4% vs 42.1%; P = 0.007), were used less frequently among patients in the HIV-IBD group. Conversely, patients with HIV-IBD developed more OI than controls, regardless of nonbiological therapy use. In the multivariate analysis, HIV infection (odds ratio 4.765, 95% confidence interval (CI) 2.48–9.14; P < 0.001) and having ≥1 comorbidity (OR 2.445, 95% CI 1.23–4.85; P = 0.010) were risk factors for developing OI, while CD was protective (OR 0.372, 95% CI 0.18–0.78; P = 0.009).

DISCUSSION:

HIV infection seems to be associated with a less aggressive phenotype of IBD and a lesser use of nonbiological therapies and biologicals but entails a greater risk of developing OI.
Racial, Ethnic, and Sex Differences in Incidence-Based Mortality of Aggregate Upper Gastrointestinal Cancers
Authors: Malick Alyyah , Ferris Jennifer S. , Hur Chin , Abrams Julian A. , Soroush Ali
Published: July 2024

INTRODUCTION:

Current strategies for upper gastrointestinal (UGI) cancer screening primarily target cancer-specific risk, with the strongest focus on esophageal adenocarcinoma (EAC). However, all UGI cancers are amendable to screening and early detection with an upper endoscopic examination. This study assesses and explores incidence-based mortality (IBM) for cumulative UGI cancers, aiming to identify race-based or sex-based disparities.

METHODS:

We used Surveillance, Epidemiology, and End Results Research data to analyze patients diagnosed with EAC, esophageal squamous cell carcinoma, cardia gastric cancer, noncardia gastric cancer, or colorectal adenocarcinoma from 2000 to 2019. Age-adjusted IBM was calculated as a rate per 100,000 population and stratified by sex and race/ethnicity. We also compared UGI cancer IBM with that of colorectal cancer, a cancer with established population-wide endoscopic screening guidelines.

RESULTS:

Cumulative IBM for UGI cancers was 8.40 (95% confidence interval [CI] 8.34–8.46). The highest cancer-specific IBM rates were for EAC (2.26, 95% CI 2.23–2.29), followed by noncardia gastric cancer (2.07, 95% CI 2.04–2.10), cardia gastric cancer (1.60, 95% CI 1.57–1.62), esophageal squamous cell carcinoma (1.21, 95% CI 1.19–1.23), and miscellaneous UGI cancer (1.27, 95% CI 1.13–1.40). UGI cancer IBM was highest among Black men (16.43, 95% CI 15.97–16.89), American Indian/Alaska Native men (15.23, 95% CI 13.75–16.82), and Hispanic men (13.76, 95% CI 13.42–14.11). These rates are significantly greater than among White men (12.81, 95% CI 12.68–12.95).

DISCUSSION:

UGI cancers impose a significantly higher mortality burden on non-White population subgroups that are not currently targeted by any systematic screening approach.
Molecular Analysis of Persistent and Recurrent Barrett's Esophagus in the Setting of Endoscopic Therapy
Authors: Kumar Aarti , Rara Marianne , Yu Ming , Wen Kwun Wah , Grady William M. , Chak Amitabh , Iyer Prasad G. , Rustgi Anil K. , Wang Timothy C. , Rubenstein Joel H. , Liu Yue , Kresty Laura , Westerhoff Maria , Kwon Richard S. , Wamsteker Erik , Wang Tom , Berry Lynne , Canto Marcia I. , Shaheen Nicholas J. , Wang Kenneth K. , Abrams Julian A. , Stachler Matthew D.
Published: July 2024

INTRODUCTION:

Early neoplastic progression of Barrett's esophagus (BE) is often treated with endoscopic therapy. Although effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease.

METHODS:

We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre-treatment and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups.

RESULTS:

The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway (P = 0.01), amplifications of oncogenes (P = 0.01), and deletions of tumor suppressor genes (P = 0.02). These associations were no longer significant after adjusting for patient age and BE length. More than half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre-treatment and post-treatment samples that shared at least 50% of their driver mutations.

DISCUSSION:

Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. Although it was expected to find shared driver mutations in pre-treatment and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.
Better conversations with Parkinson’s: co-production of a novel speech and language therapy intervention with people living with Parkinson’s
Authors: Clay Philippa , Walton Tony , Malin Eirwen , Hutchinson Mark , Levitt Katie , Williams Chris , Crouch Helen , Beeke Suzanne , Bloch Steven
Published: July 2024

Effective engagement with stakeholders is key in health-care research and intervention development. There is currently a lack of evidence relating to the involvement of co-producers with Parkinson’s-related communication difficulties. This article provides a critical reflection on co-producing a novel speech and language therapy intervention (Better Conversations with Parkinson’s) with people living with Parkinson’s who have an interest in, or lived experience of, communication difficulties. Evaluation is based on qualitative comments and survey responses from patient and public involvement group members, documentation and outputs from the patient and public involvement group, and reflection using the Public Involvement Impact Assessment Framework. The co-production group, research team and organisation highly valued the expertise and collaboration as equal partners gained through co-production. Key enablers included skilled facilitation and adequate time and funding. Consideration should be given to the format of participation (online or face-to-face), recruitment strategies and the role of patient and public involvement, in order to improve access to underserved groups and strengthen the voice of public and patient involvement members. Co-production with people living with Parkinson’s and communication difficulties allowed the creation of a more credible, relevant intervention which responds to the needs of key stakeholders, and it was a positive experience with personal benefits for those involved. We propose offering a flexible choice of co-production methods to accommodate the differing experiences of patient and public involvement members with Parkinson’s and communication difficulties.
Molecular genetic abnormalities in ACTH-secreting pituitary tumors (corticotropinomas): fundamental research and prospects for use in clinical practice
Authors: Lapshina A. M.
Published: July 2024

In recent years, a large number of studies have been carried out to research molecular genetic abnormalities in ACTH-­secreting pituitary tumors. This review presents a comprehensive analysis of exome studies results (germline and somatic mutations, chromosomal abnormalities in corticotropinomas which developed as part of hereditary syndromes MEN 1, 2, 4, DICER1, Carney complex etc., and isolated tumors, respectively) and transcriptome (specific genes expression profiles in hormonally active and inactive corticotropinomas, regulation of cell cycles and signal pathways). Modern technologies (next-generation sequencing — NGS) allow us to study the state of the microRNAome, DNA methylome and inactive chromatin sites, in particular using RNA sequencing. Thus, a wide range of fundamental studies is shown, the results of which allow us to identify and comprehend the key previously known and new pathogenesis mechanisms and biomarkers of corticotropinomas. The characteristics of the most promising molecular genetic factors that can be used in clinical practice for screening and earlier diagnosis of hereditary syndromes and isolated corticotropinomas, differential diagnosis of various forms of endogenous hypercorticism, sensitivity to existing and potential therapies and personalized outcome determination of Cushing`s disease.
The causes of obesity relapse after weight loss
Authors: Guseinova R. M. , Dorovskikh A. V. , Vasyukova O. V. , Shestakova E. A. , Okorokov P. L. , Mokrysheva N. G.
Published: July 2024

The main problem of obesity treatment is the difficulty of long-term weight maintenance. From one point of view, it can easily be explained by patients’ low compliance and absence of self-control. From another point of view, body weight is regulated not only by persons will, but also by multiple physiological mechanisms. Moreover, studies demonstrate that the attempts to reduce body weight stimulate the activation of adaptive biological process that block weight reduction.

Despite the variety of obesity treatment methods, only few patients are able to achieve significant (at least 5–7%) weight loss and maintain the result. In most cases people return to the initial weight in about 3–5 years. Therefore it is relevant to study weight regain mechanisms in order to identify new effective obesity treatment strategies.

The objective of this review is to summarize the information about the main issues of central, peripheral and behavioral pathogenic mechanisms which lead to disease relapse after obesity treatment and ideas for future strategies to resolve them.
Adrenal insufficiency as part of X-linked adrenoleukodystrophy
Authors: Enikeeva S. R. , Chugunov I. S. , Kareva M. A. , Kurkina M. V. , Zakharova E. Y. , Michailova S. V. , Bezlepkina O. B. , Peterkova V. A. , Mokrysheva N. G.
Published: July 2024

BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative metabolic disease with a frequency 1:17,000 in newborn boys. Being a major part of X-ALD with an incidence of 70–80% of patients, adrenal insufficiency (AI) is a life-threatening condition without timely treatment. The possibility of developing AI during the whole disease duration and the absence of any predictive factor for AI joining shows the necessity of studying AI in X-ALD patients to optimize current diagnostic and treatment algorithms.

AIM: To study diagnostic and therapeutic features of primary adrenal insufficiency due to X-ALD.

MATERIALS AND METHODS: A retrospective observational comparative study was conducted in 66 male patients, examined and treated in the Pediatric endocrinology department of Endocrinology Research Centre, Research Centre for Medical Genetics, Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University Detached Structural Unit Russian Children’s Clinical Hospital (Moscow, Russia) for 2014–2022. All of patients were diagnosed with primary AI and a genetically confirmed X-ALD.

RESULTS: The median age of X-ALD manifestation was 6.6 years [4.7; 11.1]. The earliest age of AI diagnosis was 1.5 years at the preclinical stage and 1 year 8 months with clinical symptoms. The renin level was studied in 22.7% at the manifestation of AI (15/66 patients), mineralocorticoid deficiency was found in 7 patients. Family history was positive in 39.4% of patients (n=66), only in 15.1% (10/66 patients) of patients the disease was established at the preclinical stage. In 59.1% (n=66) the cerebral form of the disease (cALD) was established, in 16.6% — adrenomyeloneuropathy (AMN), and in 24.2% — isolated adrenal insufficiency (PAI). Age of AI establishment in the group of patients with AMN (15.6 years) significantly differs from the establishment of AI in patients with cALD (7.4 years, p=0.001) and PAI (5.6 years, p = 0.000). Mineralocorticoid therapy was prescribed simultaneously with glucocorticoid therapy in patients with cALD, in AMN and PAI patients it was added after 11 and 7 months, respectively (the differences between AMN and PAI groups were insignificant). Combined hormonal therapy receive 41% of patients with cALD, 54.5% of patients with AMN and 60% of patients with PAI.

CONCLUSION: It is necessary to examine all male patients with AI regardless of the manifestation age to exclude adrenoleukodystrophy, and it is also important to examine patients for the presence of AI regardless of X-ALD manifestation age. The assessment of renin level in the manifestation of AI is also needed to prescribe mineralcorticoid therapy timely. Studying family history is the main method to detect X-ALD at the preclinical stage.
Fulminant hypercorticism due to ACTG producing pheochromocytoma
Authors: Useinova Z. T. , Pigarova E. A. , Bel’tsevich D. G. , Chevais A. , Dzeranova L. K. , Sitkin I. I. , Tarbaeva N. V. , Khairieva A. V. , Degtyarev M. V. , Platonova N. M. , Troshina E. A. , Bondarenko E. V.
Published: July 2024

Endogenous hypercorticism (EH) is a severe symptom complex caused by hypercortisolemia; according to the etiology, ACTH-dependent and ACTH-independent variants are distinguished, which, according to the literature, occur in 70–80% and 20–30% of cases, respectively. A rare cause of ACTH-dependent endogenous hypercorticism is ACTH-ectopic syndrome (ACTH-ES) (about 15-20% of cases). ACTH-ES is a syndrome of adrenocorticotropic hormone (ACTH) hyperproduction by neuroendocrine tumors of extrahypophyseal origin. Various tumors can secrete ACTH: bronchopulmonary carcinoid, small cell lung cancer, less frequently, thymus carcinoid, islet cell tumors and pancreatic carcinoid, medullary thyroid cancer, carcinoid tumors of the intestine, ovaries, as well as pheochromocytoma (PCC).

This publication presents a clinical case of rarely detected paraneoplastic ACTH production by pheochromocytoma. The patient had clinical manifestations of hypercorticism, therefore, she applied to the Russian National Research Center of Endocrinology of the Ministry of Health of Russia. During the examination Cushing’s syndrome (CS) was confirmed, multispiral computed tomography (MSCT) of the abdominal cavity revealed a voluminous formation of the left adrenal gland. Additional examination recorded a multiple increase in urinary catecholamine levels. Subsequently, the patient underwent left-sided adrenalectomy. The diagnosis of pheochromocytoma was confirmed morphologically, immunohistochemical study demonstrated intensive expression of chromogranin A and ACTH by tumor cells.
Evaluation of the effect of SARS-CoV-2 infection on Doppler ultrasound and placental findings of pregnant women: a systematic review and meta-analysis
Authors: Chen Lanying , Yin Tingting , Cai Danni , Chen Xiaomin
Published: July 2024

Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect the human placenta and has been shown to have an adverse effect on Doppler ultrasound parameters and placental features. However, the specific effects of the SAS-CoV-2 infection on the fetal-placental unit in pregnant women remain unclear. The aim of this systematic review and meta-analysis was to evaluate the impact of SARS-CoV-2 infection on Doppler ultrasound and placental findings in pregnant women.Methods: A systematic search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. Odds ratios (ORs) were calculated, along with their 95% confidence intervals (CIs). Heterogeneity was assessed using Cochrane Q and I2 statistics and the appropriate P-value. The analysis used RevMan 5.3.Results: This meta-analysis included 1,210 pregnant women from 10 case-control studies. SARS-CoV-2–infected pregnant women exhibited higher likelihoods of placental abnormalities (OR, 2.62; 95% CI, 1.66 to 4.13), aberrant Doppler values (OR, 1.95; 95% CI, 1.16 to 3.27), an abnormal cerebroplacental ratio (OR, 2.68; 95% CI, 1.52 to 4.75), altered fetoplacental circulation (OR, 1.56; 95% CI, 1.07 to 2.28), and increased placental thickness and placental venous lakes (OR, 1.85; 95% CI, 1.25 to 2.72).Conclusion: According to this meta-analysis, pregnant women infected with SARS-CoV-2 are more likely to experience altered Doppler ultrasonography parameters and placental abnormalities, including increased placental thickness, placental venous lakes, altered fetoplacental circulation, and cerebroplacental ratio. However, the limited number of case-control studies requires larger sample sizes to validate and enhance the evidence.
In vitro heat insulation efficacy of 5% dextrose versus 0.9% saline during radiofrequency ablation
Authors: Ma Yanping , Wang Jinfen , Wu Tao , Zheng Bowen , Yin Tinghui , Lian Yufan , Ren Jie
Published: July 2024

Purpose: This study compared the efficacy of heat insulation between 5% dextrose and 0.9% saline in radiofrequency ablation (RFA). Accordingly, temperature variations and maximum temperatures were assessed at identical distances and heat field distributions.Methods: Cubes of porcine liver tissue, measuring 10 mm across, were selected to precisely align the ablation boundary with the tissue boundary. An 18-gauge electrode with a 7-mm tip was inserted into each cube (10 per group) in a stainless-steel cup containing 40 mL of 5% dextrose or 0.9% saline. Fixed ablation was performed for 3 minutes using continuous mode at 30 W, simulating the typical thermal environment during thyroid RFA. Real-time temperature measurements were recorded by sensors positioned 0, 1, 3, and 5 mm from the cube’s edge. A comparative analysis was conducted to assess the maximum temperature, temperature variation, and duration of temperatures exceeding 42℃.Results: In both groups, the temperature curve declined with increasing distance from the edge of the ablated tissue. However, 0.9% saline exhibited higher maximum temperatures at 1, 3, and 5 mm compared to 5% dextrose (1 mm: 44.55°C±5.25°C vs. 34.68°C±3.07°C; 3 mm: 39.64°C±2.53°C vs. 29.22°C±2.21°C; 5 mm: 38.86°C±2.14°C vs. 28.74°C±2.51°C; all P<0.001). Considering a nerve injury threshold of 42°C, the 0.9% saline also displayed a greater proportion of samples reaching this temperature and a longer duration of temperatures exceeding it (P<0.05).Conclusion: The heat insulation efficacy of 5% dextrose at 1-5 mm exceeds that of 0.9% saline at identical distances and in a common thermal environment during thyroid RFA.
¿Quién paga los daños que causa la IA? De la ética a la responsabilidad por productos defectuosos
Authors: Navarro Mendizábal Íñigo
Published: July 2024

La IA ofrece grandes beneficios, pero también puede causar daños, lo que nos debe llevar a reflexionar ética y jurídicamente sobre ella. Desde la reflexión ética surge una conclusión evidente: la IA no debe causar daños y como reverso de lo anterior, si un sistema con IA causa daños habrá que fijar un responsable que indemnice a la víctima de los daños causados. La existencia de esta responsabilidad además fomentará la fabricación de unos sistemas de IA más seguros y confiables. Lamentablemente, la legislación vigente no basta para abordar estos problemas, por lo que hace falta la introducción de nuevas regulaciones. Desde la UE se están abordando estas cuestiones buscando mitigar la dificultad probatoria y estableciendo que el fabricante será el responsable de los productos que incorporan sistemas de IA y que no tienen la seguridad que cabría legítimamente esperar.
Inteligencia artificial emocional en el reverso del test de Turing. Al borde de la singularidad tecnológica son precisas cuatro nuevas leyes para la robótica
Authors: Echarte Alonso Luis Enrique
Published: July 2024

En este artículo defiendo que el creciente desarrollo de la inteligencia artificial específica (IAE) y, en particular, de la IAE para la interacción emocional (IAE-E), puede ir desdibujando las fronteras existentes entre los problemas éticos asociados a la IA débil (IAD), pequeños y presentes, ahora o a corto plazo, y los asociados a la IA fuerte (IAF), de gran calado y solo teóricos o potencialmente presentes a largo plazo. En mi argumentación muestro la importancia que adquiere el test de Turing, por su aproximación objetivo-subjetiva, al análisis y evaluación del segundo tipo de riesgos. Porque no se trata únicamente de cuánto la IAE-E es capaz de simular la inteligencia humana, sino también de cuánto más susceptibles somos los seres humanos de ser persuadidos por dichas simulaciones. La conclusión principal a la que llego es que para que el desarrollo tecnológico depare en progreso humano, necesitamos ser conscientes de los efectos que tiene para la IA-E, primero, el paroxismo social en las estrategias de autoengaño, segundo, la barbarie del especialismo y, tercero, el primitivismo tecnológico y docente.
Enfrentamento de problemas éticos por enfermeiros do Serviço de Atendimento Móvel de Urgência
Authors: Sales de Jesus Ione , Oliveira Antunes Ferraz Mariana , Teixeira Dantas Farias Mariane , Nunes Azevedo Gabriela , Oliveira Santa Rosa Darci de
Published: July 2024

O atendimento pré-hospitalar móvel proporciona aos enfermeiros, vivências em contextos múltiplos, no entanto singulares, pois executam procedimentos complexos, deparando-se com situações, em que a tomada de decisões se baseia em valores e crenças internas. A pesquisa descreveu o enfrentamento de conflitos éticos durante atendimentos dos enfermeiros de um Serviço de Atendimento Móvel de Urgência. Estudo qualitativo de caráter exploratório e descritivo, com seis enfermeiros entrevistados, entre outubro e novembro de 2022. Os dados foram analisados pela técnica descritiva- compreensiva de Vietta (2015). A dinâmica e a natureza do serviço pré-hospitalar móvel favoreceram o surgimento de conflitos éticos no atendimento de emergência, especialmente as relações interprofissionais. Entretanto, enfrentar tais questões exige assunção de responsabilidade, conhecimento e adesão aos princípios bioéticos. O trabalho em equipe foi apontado como estratégia relevante para reduzir conflitos éticos, enquanto a inadequação comportamental entre membros da equipe e a gestão constituíram barreiras no processo de tomada de decisão.
Domestic cat – the unspoken threat to wildlife in the sub-urban location of Maribor
Authors: Bedrač Larisa , Šajna Nina
Published: July 2024

The monitoring of domestic cats' prey brought home was conducted between the 13th of March and the 1st of May 2023 in two residential areas near Maribor, Slovenia. This study aimed to provide information about the amount, diversity, and frequency of prey that the cats captured to identify the predatory impact of domestic cats in peri-urban areas. We present the results of the prey captured, whether the prey was brought alive or not, and whether it was eaten or not. We further provide information about the predation frequency of domestic cats concerning circadian activity, according to weather conditions and air temperature. The frequencies of various taxonomic groups of prey captured were described concerning land use in a location and species' biology. Our results include a total of 50 records of 12 species (3 species of birds and 9 of mammals). Domestic cats were more active during the mornings, on days without rain and the frequency of bringing home prey increased with higher temperatures.
The impact of the light tube and the distance of the light trap from a stream on a caddisfly (Insecta: Trichoptera) catch
Authors: Urbanič Gorazd
Published: July 2024

The author studied the impact of the light tube and the distance of the light trap from the Poltarica stream on a caddisfly catch. Four light traps, containing blacklight and bluelight tubes, respectively, were placed at different distances from the stream bank. The most efficient was the light trap placed 10 m away, followed by the light trap at the stream bank and the light trap 50 m away. However, males of the most abundant species Potamophylax cingulatus, which belonged to two subspecies, showed different distributional pattern. Among the used light traps, the one containing bluelight tube was less efficient than those with blacklight tubes.
Decolonizing Cameroon’s language policies: a critical assessment
Authors: Kamdem Seraphin , Ojongnkpot Comfort , van Pinxteren Bert
Published: July 2024

Due to its colonial history and prevalent multilingualism, Cameroon is a country where language policies have profoundly impacted socioeconomic and political life. Cameroon has 273 local languages and two official languages, English and French. The two official languages have been a crystallization point for discontent and civil unrest, leading to secessionist sentiments and violence. In this paper, we assess Cameroon’s language policies, firstly by providing a brief historical and legal overview based in the literature. We then present a new decolonial analytical framework, building on but extending existing theoretical frameworks. Our new analysis shows that a transition to using indigenous languages in formal education and other domains is not necessary at present. However, we argue that such a transition will become unavoidable in future. We show that it will be practically possible to use a limited number of indigenous languages as mediums of instruction, building on existing bilingualisms in the country. We believe these languages should be chosen using rational criteria and we introduce an approximate assessment of which languages are easy to learn and teach, and for speakers of which other languages. The transition we foresee requires planning and preparation. A different approach to Cameroon’s languages may help in building national unity and healing national wounds in the areas of sociolinguistic power-sharing and interregional cohabitation. We expect that our approach also holds benefits for other African countries.
Study on Sino-Saudi Strategic Partnership 1998-2008
Authors: Mohammed Al-Aboodi Nadia Kadhum , Maher Adnan Rania
Published: July 2024

The Chinese-Saudi strategic partnership took an economic turn and was documented by the two sides signing a series of agreements initiated by the 1999 Oil Strategic Partnership Agreement. Energy represented the cornerstone of Chinese- Saudi relations. The rise of China and its increasing demand for oil led to the strengthening of interactive economic relations between the two countries. They began to view each other as an important strategic cooperative partner. Relations witnessed significant development during the first decade of the twenty-first century and entered their golden age, which reached a new peak when the Chinese- Saudi Strategic Friendship was established in 2008.