bluuebunny/crossref_metadata_2025 huggingface dataset:
Native amphibian toxin reduces invasive crayfish feeding with potential benefits to stream biodiversity
Authors: Bucciarelli Gary M. , Smith Sierra J. , Choe Justin J. , Shin Phoebe D. , Fisher Robert N. , Kats Lee B.
Published: September 2023

Background

Biodiversity is generally reduced when non-native species invade an ecosystem. Invasive crayfish, Procambarus clarkii, populate California freshwater streams, and in the Santa Monica Mountains (Los Angeles, USA), their introduction has led to trophic cascades due to omnivorous feeding behavior and a rapid rate of population growth. The native California newt, Taricha torosa, possesses a neurotoxin, tetrodotoxin (TTX), that affects freshwater animal behavior. Given P. clarkii has a limited evolutionary history with TTX, we hypothesized that TTX may affect crayfish feeding behaviors. To determine if TTX affects P. clarkii behavior, we measured cumulative movement and various feeding behaviors of P. clarkii exposed to (i) waterborne, ecologically realistic concentrations of TTX (~ 3.0 × 10− 8 moles/L), (ii) an anuran chemical cue to account for intraguild cues, or (iii) a T. torosa chemical cue with quantitated TTX in it (~ 6.2 × 10− 8 moles/L).

Results

We found that the presence of TTX in any form significantly reduced crayfish movement and decreased the amount of food consumed over time. Crayfish responses to the anuran treatment did not significantly differ from controls.

Conclusion

Our laboratory results show that naturally occurring neurotoxin from native California newts limits invasive crayfish foraging and feeding rates, which may play a role in preserving local stream ecosystems by limiting invasive crayfish behaviors that are detrimental to biodiversity.
Characterization and in silico analysis of the domain unknown function DUF568-containing gene family in rice (Oryza sativa L.)
Authors: Chen Kai , Wang Yilin , Nong Xiaoyan , Zhang Yichi , Tang Tang , Chen Yun , Shen Qikun , Yan Changjie , Lü Bing
Published: September 2023

Background

Domains of unknown function (DUF) proteins are a number of uncharacterized and highly conserved protein families in eukaryotes. In plants, some DUFs have been predicted to play important roles in development and response to abiotic stress. Among them, DUF568-containing protein family is plant-specific and has not been described previously. A basic analysis and expression profiling was performed, and the co-expression and interaction networks were constructed to explore the functions of DUF568 family in rice.

Results

The phylogenetic tree showed that the 8, 9 and 11 DUF568 family members from rice, Arabidopsis and maize were divided into three groups. The evolutionary relationship between DUF568 members in rice and maize was close, while the genes in Arabidopsis were more distantly related. The cis-elements prediction showed that over 82% of the elements upstream of OsDUF568 genes were responsive to light and phytohormones. Gene expression profile prediction and RT-qPCR experiments revealed that OsDUF568 genes were highly expressed in leaves, stems and roots of rice seedling. The expression of some OsDUF568 genes varied in response to plant hormones (abscisic acid, 6-benzylaminopurine) and abiotic stress (drought and chilling). Further analysis of the co-expression and protein–protein interaction networks using gene ontology showed that OsDUF568 − related genes were enriched in cellular transports, metabolism and processes.

Conclusions

In summary, our findings suggest that the OsDUF568 family may be a vital gene family for the development of rice roots, leaves and stems. In addition, the OsDUF568 family may participate in abscisic acid and cytokinin signaling pathways, and may be related to abiotic stress resistance in these vegetative tissues of rice.
Genomic classification and antimicrobial resistance profiling of Streptococcus pneumoniae and Haemophilus influenzae isolates associated with paediatric otitis media and upper respiratory infection
Authors: Lobb Briallen , Lee Matthew C. , McElheny Christi L. , Doi Yohei , Yahner Kristin , Hoberman Alejandro , Martin Judith M. , Hirota Jeremy A. , Doxey Andrew C. , Shaikh Nader
Published: September 2023

Acute otitis media (AOM) is the most common childhood bacterial infectious disease requiring antimicrobial therapy. Most cases of AOM are caused by translocation of Streptococcus pneumoniae or Haemophilus influenzae from the nasopharynx to the middle ear during an upper respiratory tract infection (URI). Ongoing genomic surveillance of these pathogens is important for vaccine design and tracking of emerging variants, as well as for monitoring patterns of antibiotic resistance to inform treatment strategies and stewardship.

In this work, we examined the ability of a genomics-based workflow to determine microbiological and clinically relevant information from cultured bacterial isolates obtained from patients with AOM or an URI. We performed whole genome sequencing (WGS) and analysis of 148 bacterial isolates cultured from the nasopharynx (N = 124, 94 AOM and 30 URI) and ear (N = 24, all AOM) of 101 children aged 6–35 months presenting with AOM or an URI. We then performed WGS-based sequence typing and antimicrobial resistance profiling of each strain and compared results to those obtained from traditional microbiological phenotyping.

WGS of clinical isolates resulted in 71 S. pneumoniae genomes and 76 H. influenzae genomes. Multilocus sequencing typing (MSLT) identified 33 sequence types for S. pneumoniae and 19 predicted serotypes including the most frequent serotypes 35B and 3. Genome analysis predicted 30% of S. pneumoniae isolates to have complete or intermediate penicillin resistance. AMR predictions for S. pneumoniae isolates had strong agreement with clinical susceptibility testing results for beta-lactam and non beta-lactam antibiotics, with a mean sensitivity of 93% (86–100%) and a mean specificity of 98% (94–100%). MLST identified 29 H. influenzae sequence types. Genome analysis identified beta-lactamase genes in 30% of H. influenzae strains, which was 100% in agreement with clinical beta-lactamase testing. We also identified a divergent highly antibiotic-resistant strain of S. pneumoniae, and found its closest sequenced strains, also isolated from nasopharyngeal samples from over 15 years ago.

Ultimately, our work provides the groundwork for clinical WGS-based workflows to aid in detection and analysis of H. influenzae and S. pneumoniae isolates.
Risk factors and longitudinal changes of dyslipidemia among Chinese people living with HIV receiving antiretroviral therapy
Authors: Li Xiuxia , Song Xiaojing , Han Yang , Qiu Zhifeng , Cao Wei , Li Taisheng
Published: September 2023

Background

Antiretroviral therapy (ART) improved the prognosis of people living with human immunodeficiency virus (HIV) (PLWH). Life-long treatment is required in PLWH and is accompanied by various metabolic abnormalities in the disease course. Data about the epidemiology and the dynamic changes of dyslipidemia in PLWH receiving antiretroviral therapy were scarce in Asian countries. This study aimed to explore the risk factors of dyslipidemia and analyze the longitudinal changes of dyslipidemia among Chinese PLWH receiving HAART.

Methods

We conducted a longitudinal analysis of PLWH enrolled in two large multicenter clinical trials across China, and outpatients followed at the clinic of Peking Union Medical College Hospital. Demographic data and clinical parameters were collected. The risk factors and longitudinal changes in lipid profiles associated with HIV-1 infection were analyzed. The definition of dyslipidemia was made based on the National Cholesterol Education Program, Adult Treatment Panel (NCEP-ATP) III guidelines.

Results

A total of 1542 PLWH were included. The median follow-up was 6 years. At baseline, the concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 4.1 ± 0.91 mmol/L, 1.2 (interquartile ranges [IQR] 0.85–1.75) mmol/L, 1.1 ± 0.37 and 2.4 ± 0.76 mmol/L, respectively. The rate of hypercholesterolemia, hyperglyceridemia, high LDL-C, and low HDL-C were 10.18%, 26.39%, 9.08%, and 44.94%, respectively. The overall prevalence of dyslipidemia was 69.3%, which raised to 84.3% after antiretroviral therapy, substantially higher. CD4/CD8 ratio < 0.3 and viral load > 105 copies/mL were risk factors associated with any subtype of dyslipidemia. A negative correlation between CD8+CD38+ percentage and HDL-C concentration was found. The regimens including efavirenz (EFV) and tenofovir (TDF) showed better lipid profiles. Longitudinal analysis revealed that both the level and the percentage of abnormal TG and HDL-C occurred drastic change in the first 6 months after ART initiation (from 4.07 to 4.41, from 1.11 to 1.28mmol/L, from 26.39 to 31.1% and from 44.94 to 29.5%, respectively).

Conclusions

The prevalence of dyslipidemia is high in PLWH and increases after ART, mainly represented as high TG and low HDL-C and associated with advanced stage of HIV-1 infection. The greatest changes in lipids occurred in the early stage after initiating ART therapy. The results suggest that dyslipidemia should be monitored and managed when starting ART.
eGFRcystatinC/eGFRcreatinine ratio < 0.6 in patients with SARS-CoV-2 pneumonia: a prospective cohort study
Authors: Avotins Lauris , Kroica Juta , Petersons Aivars , Zentina Dace , Kravale Zaiga , Saulite Anna , Racenis Karlis
Published: September 2023

Background

Shrunken Pore Syndrome (SPS), defined as a reduced ratio between two estimated filtration rates (based on cystatin C and creatinine) is an increasingly recognized risk factor for long-term mortality. Although some patients with other conditions might be erroneously identified as SPS. Our aim was to bring the focus on possible pathophysiologic mechanisms influencing the ratio in the setting of SARS-CoV-2 pneumonia and acute kidney injury.

Methods

A single-centered prospective cohort study was conducted to investigate biomarkers in symptomatic COVID-19 pneumonia patients admitted to a hospital in Latvia. Nineteen biomarkers were measured in blood and three in urine samples. Associations were sought between these biomarkers, chronic diseases and the estimated GFRcystatinC/eGFRcreatinine ratio < 0.6, mortality rates, and acute kidney injury development. Data analysis was performed using SPSS Statistics, with significance set at p < 0.05.

Results

We included 59 patients (average age 65.5 years, 45.8% female) admitted with COVID-19. Acute kidney injury occurred in 27.1%, and 25.4% died. Ratio < 0.6 was seen in 38.6%, associated with female sex, diabetes, hypothyroidism, and higher age. Ratio < 0.6 group had mortality notably higher − 40.9% vs. 16.2% and more cases of acute kidney injury (40.9% vs. 18.9%). Cystatin C showed strong associations with the ratio < 0.6 compared to creatinine. Urea levels and urea/creatinine ratio were higher in the ratio < 0.6 group. After excluding acute kidney injury patients, ratio < 0.6 remained associated with higher cystatin C and urea levels. Other biomarkers linked to a kidney injury as NGAL, and proteinuria did not differ.

Conclusion

We prove that reduced ratio is common in hospitalized patients with SARS-CoV-2 pneumonia and is associated with increased mortality during hospitalization. Factors that influence this ratio are complex and, in addition to the possible shrinkage of pores, other conditions such as thickening of glomerular basal membrane, comorbidities, prerenal kidney failure and others may play an important role and should be addressed when diagnosing SPS. We highlight the need for additional diagnostic criteria for SPS and larger studies to better understand its implications in acute COVID-19 settings.
Association between food environments and fetal growth in pregnant Brazilian women
Authors: Victor Audêncio , Gotine Ana Raquel Manuel , Falcão Ila R. , Ferreira Andrêa J. F. , Flores-Ortiz Renzo , Xavier Sancho Pedro , Vasco Melsequisete Daniel , de Jesus Silva Natanael , Mahoche Manuel , Rodrigues Osiyallê Akanni Silva , de Cássia Ribeiro Rita , Rondó Patrícia H. , Barreto Maurício L.
Published: September 2023

Introduction

Birth weight is described as one of the main determinants of newborns’ chances of survival. Among the associated causes, or risk factors, the mother’s nutritional status strongly influences fetal growth and birth weight outcomes of the concept. This study evaluates the association between food deserts, small for gestational age (SGA), large for gestational age (LGA) and low birth weight (LBW) newborns.

Design

This is a cross-sectional population study, resulting from individual data from the Live Birth Information System (SINASC), and commune data from mapping food deserts (CAISAN) in Brazil. The newborn’s size was defined as follows: appropriate for gestational age (between 10 and 90th percentile), SGA (< 10th percentile), LGA (> 90th percentile), and low birth weight < 2,500 g. To characterize food environments, we used tertiles of the density of establishments which sell in natura and ultra-processed foods. Logistic regression modeling was conducted to investigate the associations of interest.

Results

We analyzed 2,632,314 live births in Brazil in 2016, after appropriate adjustments, women living in municipalities with limited availability of fresh foods had a higher chance of having newborns with SGA [OR2nd tertile: 1.06 (1.05–1.07)] and LBW [OR2nd tertile: 1.11 (1.09–1.12)]. Conversely, municipalities with greater availability of ultra-processed foods had a higher chance of having newborns with SGA [OR3rd tertile: 1.04 (1.02–1.06)] and LBW [OR2nd tertile: 1.13 (1.11–1.16)]. Stratification by race showed that Black and Mixed/Brown women had a higher chance of having newborns with SGA [OR3rd tertile: 1.09 (1.01–1.18)] and [OR3rd tertile: 1.06 (1.04–1.09)], respectively, while Mixed-race women also had a higher chance of having newborns with LBW [OR3rd tertile: 1.17 (1.14–1.20)]. Indigenous women were associated with LGA [OR3rd tertile: 1.20 (1.01–1.45)].

Conclusion

The study found that living in areas with limited access to healthy foods was associated with an increased risk of SGA and low birth weight among newborns, particularly among Black and Mixed/Brown women. Therefore, urgent initiatives aimed at reducing social inequalities and mitigating the impact of poor food environments are needed in Brazil.
Central retinal artery occlusion in a young child affected by COVID-19: a first case report
Authors: Abbati Giulia , Fazi Camilla , Fortunato Pina , Trapani Sandra
Published: September 2023

Background

Central retinal artery occlusion (CRAO) is an ophthalmic emergency, and its etiology is generally ascribed to vessel occlusion by a thrombus or embolus, eventually due to a hypercoagulable state. CRAO occurrence is described even in the pediatric population, but its incidence is very rare. SARS-CoV-2 infection has a multitude of presentations, and almost any organ may be involved including the ocular district. Cases of CRAO in patients affected by COVID-19 are reported in the literature in the adult population, but not in the pediatric one.

Case presentation

We describe the case of a six-year-old otherwise healthy girl, who presented a sudden and complete bilateral vision loss after a one-day fever. All the clinical, ophthalmological, laboratory and instrumental investigations led to the diagnosis of a right CRAO and the suspicion of a contralateral posterior optic nerve affection. These manifestations could not be ascribed to any etiological condition apart from the documented ongoing mild SARS-CoV-2 infection. Treatment with anticoagulants and steroids was tried but the visual outcome was poor during the one-month hospitalization and at the last follow-up.

Conclusions

To the best of our knowledge, this is the first report of CRAO in the course of SARS-CoV-2 infection in the pediatric age. In our review of the literature, we found few cases of CRAO in adults with COVID-19; we highlighted differences in anamnestic, clinical, and interventional aspects and therefore we tried to summarize the state of the art on this topic to facilitate further studies. Even if rare, the prognosis of CRAO is poor and the thrombolytic treatment could be effective only if rapidly administered, so the disease suspicion should be high in a patient with sudden vision loss, also in pediatric age.
Factors associated with the attraction and retention of family and community medicine and nursing residents in rural settings: a qualitative study
Authors: Tort-Nasarre G. , Vidal-Alaball Josep , Pedrosa M. J. Fígols , Abanades L. Vazquez , Arcarons A. Forcada , Rosanas J. Deniel
Published: September 2023

Background

The current shortage of primary care doctors and nurses is causing difficulties in replacement, and this shortage is expected to increase. This situation is more pronounced in rural environments than in urban ones. Family and community care specialty training is a key component of both the transition to clinical practice and the retention of new professionals. The aim of this study is to explore the attitudes and perceptions of internal medicine residents and internal nurse residents trained in a rural teaching unit on factors associated with recruitment and retention, including the role of the specialty training programme.

Methods

A qualitative study was conducted. Purposive sampling was used, and thirteen residents from the central Catalonia teaching unit who were in their final year of training participated in semistructured interviews. The data were collected during 2022 and were subsequently analysed with thematic analysis. The study is reported using the COREQ checklist.

Results

Six themes emerged from data related to perceptions and attitudes about the factors associated with recruitment and retention: training programme, characteristics of the family and community specialty, concept of rural life, family and relational factors, economic and resource factors, and recruitment and job opportunities.

Conclusions

Family and community medicine and nursing residents trained in rural settings expressed satisfaction with the specialty programme and most features of primary care, but they experienced a wide range of uncertainties in deciding on their professional future in terms of living in rural areas, family support, financial support and recruitment. This study identifies individual and structural factors that could be of great use to retain doctors and nurses in rural areas.
Cost comparisons and factors related to cost per stay in intensive care units in Belgium
Authors: Bruyneel Arnaud , Larcin Lionel , Martins Dimitri , Van Den Bulcke Julie , Leclercq Pol , Pirson Magali
Published: September 2023

Background

Given the variability of intensive care unit (ICU) costs in different countries and the importance of this information for guiding clinicians to effective treatment and to the organisation of ICUs at the national level, it is of value to gather data on this topic for analysis at the national level in Belgium. The objectives of the study were to assess the total cost of ICUs and the factors that influence the cost of ICUs in hospitals in Belgium.

Methods

This was a retrospective cohort study using data collected from the ICUs of 17 Belgian hospitals from January 01 to December 31, 2018. A total of 18,235 adult ICU stays were included in the study. The data set was a compilation of inpatient information from analytical cost accounting of hospitals, medical discharge summaries, and length of stay data. The costs were evaluated as the expenses related to the management of hospital stays from the hospital’s point of view. The cost from the hospital perspective was calculated using a cost accounting analytical methodology in full costing. We used multivariate linear regression to evaluate factors associated with total ICU cost per stay. The ICU cost was log-transformed before regression and geometric mean ratios (GMRs) were estimated for each factor.

Results

The proportion of ICU beds to ward beds was a median [p25-p75] of 4.7% [4.4–5.9]. The proportion of indirect costs to total costs in the ICU was 12.1% [11.4–13.3]. The cost of nurses represented 57.2% [55.4–62.2] of direct costs and this was 15.9% [12.0-18.2] of the cost of nurses in the whole hospital. The median cost per stay was €4,267 [2,050–9,658] and was €2,160 [1,545–3,221] per ICU day. The main factors associated with higher cost per stay in ICU were Charlson score, mechanical ventilation, ECMO, continuous hemofiltration, length of stay, readmission, ICU mortality, hospitalisation in an academic hospital, and diagnosis of coma/convulsions or intoxication.

Conclusions

This study demonstrated that, despite the small proportion of ICU beds in relation to all services, the ICU represented a significant cost to the hospital. In addition, this study confirms that nursing staff represent a significant proportion of the direct costs of the ICU. Finally, the total cost per stay was also important but highly variable depending on the medical factors identified in our results.
Impact of gallstone disease on the risk of stroke and coronary artery disease: evidence from prospective observational studies and genetic analyses
Authors: Zhang Li , Zhang Wenqiang , He Lin , Cui Huijie , Wang Yutong , Wu Xueyao , Zhao Xunying , Yan Peijing , Yang Chao , Xiao Changfeng , Tang Mingshuang , Chen Lin , Xiao Chenghan , Zou Yanqiu , Liu Yunjie , Yang Yanfang , Zhang Ling , Yao Yuqin , Li Jiayuan , Liu Zhenmi , Yang Chunxia , Jiang Xia , Zhang Ben
Published: September 2023

Background

Despite epidemiological evidence associating gallstone disease (GSD) with cardiovascular disease (CVD), a dilemma remains on the role of cholecystectomy in modifying the risk of CVD. We aimed to characterize the phenotypic and genetic relationships between GSD and two CVD events – stroke and coronary artery disease (CAD).

Methods

We first performed a meta-analysis of cohort studies to quantify an overall phenotypic association between GSD and CVD. We then investigated the genetic relationship leveraging the largest genome-wide genetic summary statistics. We finally examined the phenotypic association using the comprehensive data from UK Biobank (UKB).

Results

An overall significant effect of GSD on CVD was found in meta-analysis (relative risk [RR] = 1.26, 95% confidence interval [CI] = 1.19–1.34). Genetically, a positive shared genetic basis was observed for GSD with stroke ($${r}_{g}$$

r
g

=0.16, P = 6.00 × 10–4) and CAD ($${r}_{g}$$

r
g

=0.27, P = 2.27 × 10–15), corroborated by local signals. The shared genetic architecture was largely explained by the multiple pleiotropic loci identified in cross-phenotype association study and the shared gene-tissue pairs detected by transcriptome-wide association study, but not a causal relationship (GSD to CVD) examined through Mendelian randomization (MR) (GSD-stroke: odds ratio [OR] = 1.00, 95%CI = 0.97–1.03; GSD-CAD: OR = 1.01, 95%CI = 0.98–1.04). After a careful adjustment of confounders or considering lag time using UKB data, no significant phenotypic effect of GSD on CVD was detected (GSD-stroke: hazard ratio [HR] = 0.95, 95%CI = 0.83–1.09; GSD-CAD: HR = 0.98, 95%CI = 0.91–1.06), further supporting MR findings.

Conclusions

Our work demonstrates a phenotypic and genetic relationship between GSD and CVD, highlighting a shared biological mechanism rather than a direct causal effect. These findings may provide insight into clinical and public health applications.
Analysis of acid-tolerance mechanism based on membrane microdomains in Saccharomyces cerevisiae
Authors: Lv Xueqin , Jin Ke , Yi Yu , Song Lingang , Xiu Xiang , Liu Yanfeng , Li Jianghua , Du Guocheng , Chen Jian , Liu Long
Published: September 2023

Background

Saccharomyces cerevisiae has been used in the biosynthesis of acid products such as organic acids owing to its acid tolerance. Improving the acid tolerance of S. cerevisiae is beneficial for expanding its application range. Our previous study isolated the TAMC strain that was tolerant to a pH 2.3 through adaptive laboratory evolution; however, its mechanism underlying tolerance to low pH environment remains unclear.

Results

In this study, through visual observation and order analysis of plasma membrane and membrane microdomains, we revealed that the membrane microdomains of TAMC strain play an indispensable role in acid tolerance. Transcriptomic analysis showed an increase in the expression of genes related to key components of membrane microdomains in TAMC strain. Furthermore, an obvious reduction was observed in the acid tolerance of the strain with sterol C-24 methyltransferase encoding gene ERG6 knockout for inhibiting membrane microdomain formation. Finally, colocalization analysis of H+-ATPase PMA1 and plasma membrane protein PMP1 showed that disruption of membrane microdomains could inhibit the formation of the H+-ATPase complex.

Conclusions

Membrane microdomains could provide a platform for forming H+-ATPase complexes to facilitate intracellular H+ homeostasis, and thereby improve cell acid resistance. This study proposed a novel acid tolerance mechanism, providing a new direction for the rational engineering of acid-tolerant strains.
Cost-effectiveness analysis of COVID-19 tests in the unified health system
Authors: Cedro Vinicius Queiroz Miranda , de Lima Gomes Stéfany , Simões Ana Clara Correa Duarte , Sverzut Tatiana do Valle Lovato , Bertti Keila Cristina Xavier , Tristão Marcelo Tadeu , Cavalcanti Yuri Wanderley , Câmara João Victor Frazão , Pereira Antonio Carlos
Published: September 2023

Background

To evaluate the cost-effectiveness ratio and economic impact of the Rapid Antigen Test (TR-Ag) to replace RT-PCR for the detection of the new Coronavirus in the Unified Health System (SUS).

Methods

This is a cost-effectiveness analysis. Clinical protocols were used for the diagnosis of COVID-19 at the São José Municipal Hospital, located in the city of Itaberá-SP. The Incremental Cost-Effectiveness Ratio (ICER) was divided into two scenarios. In the first, the accuracy reported by the test manufacturers was included, and in the second, the cost resulting from a systematic review. Both were compared with the performance of the RT-PCR test. The increase in diagnoses was chosen as a health outcome and absenteeism was used as a criterion for assessing the economic impact.

Results

The analysis resulted in incremental cost-effectiveness ratios of R$ 42,136.67 and R$ 68,329.73 for every thousand tests, according to the accuracy of the manufacturers’ TR-Ag tests and what is reported in the literature in relation to RT-PCR, respectively. The average value found for the RT-PCR test (R$ 202.87) represents an increase of 165.32% in cost in relation to the value found for the TR-Ag. 4,305 tests were performed between April 2020 and December 2021 at the referral hospital. Also, maintaining the use of RT-PCR as the first choice for diagnosing COVID-19 and regulating absenteeism in the economically active population could have an impact of up to R$ 1,022,779.68 on municipal management.

Conclusion

It is concluded that the TR-Ag are configured as a cost-effective alternative for the SUS in the detection of the new Coronavirus. The strategy becomes economically favorable for the expansion of testing, combating the COVID-19 pandemic and reducing the impact on the local economy. However, studies are needed to validate the accuracy of the tests so that economic evaluations on the subject are more assertive.
Framework for determining the optimal course of action when efficiency and affordability measures differ by perspective in cost-effectiveness analysis—with an illustrative case of HIV treatment in Mozambique
Authors: Corlis Joseph , Zhu Jinyi , Macul Hélder , Tiberi Orrin , Boothe Makini A. S. , Resch Stephen C.
Published: September 2023

Background

Cost-effectiveness analysis (CEA) is a standard tool for evaluating health programs and informing decisions about resource allocation and prioritization. Most CEAs evaluating health interventions in low- and middle-income countries adopt a health sector perspective, accounting for resources funded by international donors and country governments, while often excluding out-of-pocket expenditures and time costs borne by program beneficiaries. Even when patients’ costs are included, a companion analysis focused on the patient perspective is rarely performed. We view this as a missed opportunity.

Methods

We developed methods for assessing intervention affordability and evaluating whether optimal interventions from the health sector perspective also represent efficient and affordable options for patients. We mapped the five different patterns that a comparison of the perspective results can yield into a practical framework, and we provided guidance for researchers and decision-makers on how to use results from multiple perspectives. To illustrate the methodology, we conducted a CEA of six HIV treatment delivery models in Mozambique. We conducted a Monte Carlo microsimulation with probabilistic sensitivity analysis from both patient and health sector perspectives, generating incremental cost-effectiveness ratios for the treatment approaches. We also calculated annualized patient costs for the treatment approaches, comparing the costs with an affordability threshold. We then compared the cost-effectiveness and affordability results from the two perspectives using the framework we developed.

Results

In this case, the two perspectives did not produce a shared optimal approach for HIV treatment at the willingness-to-pay threshold of 0.3 × Mozambique’s annual GDP per capita per DALY averted. However, the clinical 6-month antiretroviral drug distribution strategy, which is optimal from the health sector perspective, is efficient and affordable from the patient perspective. All treatment approaches, except clinical 1-month distributions of antiretroviral drugs which were standard before Covid-19, had an annual cost to patients less than the country’s annual average for out-of-pocket health expenditures.

Conclusion

Including a patient perspective in CEAs and explicitly considering affordability offers decision-makers additional insights either by confirming that the optimal strategy from the health sector perspective is also efficient and affordable from the patient perspective or by identifying incongruencies in value or affordability that could affect patient participation.
Flexible parametric methods for calculating life expectancy in small populations
Authors: Tyrer Freya , Chudasama Yogini V. , Lambert Paul C. , Rutherford Mark J.
Published: September 2023

Background

Life expectancy is a simple measure of assessing health differences between two or more populations but current life expectancy calculations are not reliable for small populations. A potential solution to this is to borrow strength from larger populations from the same source, but this has not formally been investigated.

Methods

Using data on 451,222 individuals from the Clinical Practice Research Datalink on the presence/absence of intellectual disability and type 2 diabetes mellitus, we compared stratified and combined flexible parametric models, and Chiang’s methods, for calculating life expectancy. Confidence intervals were calculated using the Delta method, Chiang’s adjusted life table approach and bootstrapping.

Results

The flexible parametric models allowed calculation of life expectancy by exact age and beyond traditional life expectancy age thresholds. The combined model that fit age interaction effects as a spline term provided less bias and greater statistical precision for small covariate subgroups by borrowing strength from the larger subgroups. However, careful consideration of the distribution of events in the smallest group was needed.

Conclusions

Life expectancy is a simple measure to compare health differences between populations. The use of combined flexible parametric methods to calculate life expectancy in small samples has shown promising results by allowing life expectancy to be modelled by exact age, greater statistical precision, less bias and prediction of different covariate patterns without stratification. We recommend further investigation of their application for both policymakers and researchers.
Non-coding RNAs/DNMT3B axis in human cancers: from pathogenesis to clinical significance
Authors: Huang Chunjie , Azizi Paniz , Vazirzadeh Masoud , Aghaei-Zarch Seyed Mohsen , Aghaei-Zarch Fatemehsadat , Ghanavi Jalaledin , Farnia Poopak
Published: September 2023

Cancer is a complex disease with many contributing factors, and researchers have gained extensive knowledge that has helped them understand the diverse and varied nature of cancer. The altered patterns of DNA methylation found in numerous types of cancer imply that they may play a part in the disease’s progression. The human cancer condition involves dysregulation of the DNA methyltransferase 3 beta (DNMT3B) gene, a prominent de novo DNA methyltransferase, and its abnormal behavior serves as an indicator for tumor prognosis and staging. The expression of non-coding RNAs (ncRNAs), which include microRNAs (miRNA), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), is critical in controlling targeted gene expression and protein translation and their dysregulation correlates with the onset of tumors. NcRNAs dysregulation of is a critical factor that influences the modulation of several cellular characteristics in cancerous cells. These characteristics include but are not limited to, drug responsiveness, angiogenesis, metastasis, apoptosis, proliferation, and properties of tumor stem cell. The reciprocal regulation of ncRNAs and DNMT3B can act in synergy to influence the destiny of tumor cells. Thus, a critical avenue for advancing cancer prevention and treatment is an inquiry into the interplay between DNMT3B and ncRNAs. In this review, we present a comprehensive overview of the ncRNAs/DNMT3B axis in cancer pathogenesis. This brings about valuable insights into the intricate mechanisms of tumorigenesis and provides a foundation for developing effective therapeutic interventions.
Vitamin D status in hospitalized COVID‑19 patients is associated with disease severity and IL-5 production
Authors: Qiu Yali , Bao Wuping , Tian Xue , Zhang Yingying , Pan Yilin , Xie Guogang , Bao Aihua , Yin Dongning , Zhang Min , Zhou Yan
Published: September 2023

Background

There are many studies on the relationship between vitamin D and coronavirus disease 2019 (COVID-19), while the results are matters of debate and the mechanisms remain unknown. The present study was performed to assess the impact of serum 25-hydroxyvitamin D [25(OH)D] levels on the severity of disease in hospitalized COVID-19 patients and identify potential mechanisms of 25(OH)D alterations.

Methods

A total of 399 hospitalized COVID-19 patients were recruited from three centers between December 19, 2022, and February 1, 2023. Medical history, laboratory examination, and radiologic data were retrospectively collected. The patients were divided into four groups based on disease severity. Serum 25(OH)D levels in the patients were determined by the electrochemiluminescence method and cytokines were detected by flow cytometry. The relationship between serum 25(OH)D status and the severity of COVID-19, and the correlation between 25(OH)D levels and cytokines in COVID-19 patients were assessed.

Results

Levels of 25(OH)D were significantly lower in the deceased group than in the other three groups (P < 0.05), and lower in the critical group than in the general group (P < 0.05). There were no significant differences in the 25(OH)D levels between the general and severe groups (P > 0.05). The levels of 25(OH)D (odds ratio = 0.986, 95% confidence interval: 0.973–0.998, P = 0.024) and IL-5 (odds ratio = 1.239, 95% confidence interval: 1.104–1.391, P = 0.04) were independent risk factors for the severity of COVID-19 disease upon admission. Serum 25(OH)D levels were able to predict the mortality of patients with COVID-19, and the predictive value was even higher when combined with IL-5 levels and eosinophil (Eos) count. Circulating 25(OH)D status correlated negatively with the expression of IL-5 (r=-0.262, P < 0.001) and was positively linked with CD8+ T cell counts (r=-0.121, P < 0.05) in patients with COVID-19.

Conclusions

This study found that the serum 25(OH)D status combined with IL-5 levels and Eos counts could be identified as a predictive factor for recognizing the risk of COVID-19 mortality. The serum 25(OH)D status in COVID-19 patients correlated negatively with the expression of IL-5. The potential mechanism for this relationship is worth further exploration.
Proteomic alterations in the brain and blood–brain barrier during brain Aβ accumulation in an APP knock-in mouse model of Alzheimer’s disease
Authors: Ito Shingo , Yagi Ryotaro , Ogata Seiryo , Masuda Takeshi , Saito Takashi , Saido Takaomi , Ohtsuki Sumio
Published: September 2023

Background

Blood–brain barrier (BBB) dysfunction is supposed to be an early event in the development of Alzheimer’s disease (AD). This study aimed to investigate the relationship between BBB alterations and AD progression in terms of amyloid-β peptide (Aβ) accumulation in the brains of humanized amyloid precursor protein knock-in (APP-KI) mice.

Methods

Brain Aβ accumulation was examined using immunohistochemical analysis. Alterations in differentially expressed proteins were determined using sequential window acquisition of all theoretical fragment ion mass spectroscopy (SWATH-MS)-based quantitative proteomics, and Metascape, STRING, Gene Ontology, and KEGG were used for network analyses of altered biological pathways and processes. Statistical significance was determined using the unpaired two-tailed Student’s t-test and Welch’s t-test for two groups and one-way analysis of variance followed by Tukey’s test for more than two groups. Correlations between two groups were determined using Pearson’s correlation analysis.

Results

Brain Aβ accumulation in APP-KI mice was detectable at 2 months, increased significantly at 5 months, and remained elevated at 12 months of age. The levels of differentially expressed proteins in isolated brain capillaries were higher in younger mice, whereas those in the brain were higher in older mice. Network analyses indicated changes in basement membrane-associated and ribosomal proteins in the brain capillaries. There were no significant changes in key proteins involved in drug or Aβ transport at the BBB. In contrast, solute carrier transporter levels in astrocytes, microglia, and neurons were altered in the brain of older mice. Moreover, the levels of the lipid transporters Apoe and Apoj were upregulated in both the brain and isolated brain capillaries after Aβ accumulation.

Conclusions

Our results suggest that changes in the brain occurred after advanced Aβ accumulation, whereas initial Aβ accumulation was sufficient to cause alterations in the BBB. These findings may help elucidate the role of BBB alterations in AD progression and predict the distribution of drugs across the BBB in the brain of patients with AD.
Implementing contingency management for stimulant use in opioid treatment programs: protocol of a type III hybrid effectiveness-stepped-wedge trial
Authors: Becker Sara J. , DiClemente-Bosco Kira , Scott Kelli , Janssen Tim , Salino Sarah M. , Hasan Fariha N. , Yap Kimberly R. , Garner Bryan R.
Published: September 2023

Background

Contingency management (CM) is an evidence-based intervention for stimulant use and is highly effective in combination with medication for opioid use disorder. Yet, uptake of CM in opioid treatment programs that provide medication for opioid use disorder remains low. This paradox in which CM is one of the most effective interventions, yet one of the least available, represents one of the greatest research-to-practice gaps in the addiction health services field. Multi-level implementation strategies are needed to address barriers to CM implementation at both the provider- and organization-level. This type III hybrid effectiveness-implementation trial was funded by the National Institute on Drug Abuse to evaluate whether a multi-level implementation strategy, the Science of Service Laboratory (SSL), can effectively promote CM implementation in opioid treatment programs. Specific aims will test the effectiveness of the SSL on implementation outcomes (primary aim) and patient outcomes (secondary aim), as well as test putative mediators of implementation outcomes (exploratory aim).

Methods

Utilizing a fully powered type III hybrid effectiveness-implementation trial with a stepped wedge design, we propose to randomize a cohort of 10 opioid treatment programs to receive the SSL across four steps. Each step, an additional 2–3 opioid treatment programs will receive the SSL implementation strategy, which has three core components: didactic training, performance feedback, and external facilitation. At six intervals, each of the 10 opioid treatment programs will provide de-identified electronic medical record data from all available patient charts on CM delivery and patient outcomes. Staff from each opioid treatment program will provide feedback on contextual determinants influencing implementation at three timepoints.

Discussion

Between planning of this protocol and receipt of funding, the landscape for CM in the USA changed dramatically, with multiple Departments of Health launching state-wide CM initiatives. We therefore accelerated the protocol timeline and offered some cursory training resources to all sites as a preparation activity. We also began partnering with multiple Departments of Health to evaluate their rollout of CM using the measures outlined in this protocol.

Trial registration

This study protocol is registered via ClinicalTrials.gov Identifier: NCT05702021. Date of registration: January 27, 2023.
Is punctate palmoplantar keratoderma type 1 associated with malignancy? A systematic review of the literature
Authors: Gram S. B. , Bjerrelund J. , Jelsig A. M. , Bygum A. , Leboeuf-Yde C. , Ousager L. B.
Published: September 2023

Background

An association between punctate palmoplantar keratoderma type 1 (PPPK1) and malignancy has been proposed for decades. Some authors suggest that individuals with PPPK1 should undergo screening for various types of malignancies while others caution that an association is not well-established. In this systematic review, we summarized and evaluated the current evidence for a possible association between PPPK1 and malignancy.

Methods

The review was conducted along PRISMA guidelines. The search used Embase, MEDLINE, Scopus, and the Human Gene Mutation Database up to March 2022. All studies reporting on individuals with the diagnosis of PPPK1 with or without history of malignancy were included. Two authors screened for eligible studies, extracted predefined data, and performed a quality assessment.

Results

Of 773 studies identified, 45 were included. Most studies were reports on single families (24 of 45 studies) or multiple families (10 of 45 studies). The number of index cases with PPPK1 across all included studies was 280, and when family members reported with PPPK1 were added, a total of 817 individuals were identified. Overall, 23 studies reported on individuals with PPPK1 with a history of malignancy, whereas 22 studies reported on individuals with PPPK1 without a history of malignancy. Although the extracted data were not considered to be of sufficient quality to synthesize and answer our research question, the review did not confirm an association between PPPK1 and malignancy.

Conclusion

This review shows that there is a lack of well-designed studies on this topic to conclude whether individuals with PPPK1 have an increased risk of malignancy. Based on the present literature, however, we could not confirm an association between PPPK1 and malignancy and find it highly questionable if patients with PPPK1 should be offered surveillance for malignancies.
Circ-RAPGEF5 promotes intrahepatic cholangiocarcinoma progression by stabilizing SAE1 to facilitate SUMOylation
Authors: Zheng Junhao , Wang Yali , Tao Liye , Cai Jingwei , Shen Zefeng , Liu Yang , Pan Haoyu , Li Shihao , Ruan Yeling , Chen Tianyi , Ye Zhengtao , Lin Kainan , Sun Yin , Xu Junjie , Liang Xiao
Published: September 2023

Background

Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with a poor prognosis. The underlying functions and mechanisms of circular RNA and SUMOylation in the development of ICC remain poorly understood.

Methods

Circular RNA hsa_circ_0001681 (termed Circ-RAPGEF5 hereafter) was identified by circular RNA sequencing from 19 pairs of ICC and adjacent tissue samples. The biological function of Circ-RAPGEF5 in tumor proliferation and metastasis was examined by a series of in vitro assays. A preclinical model was used to validate the therapeutic effect of targeting Circ-RAPGEF5. RNA pull-down and dual-luciferase reporter assays were used to access the RNA interactions. Western blot and Co-IP assays were used to detect SUMOylation levels.

Results

Circ-RAPGEF5, which is generated from exons 2 to 6 of the host gene RAPGEF5, was upregulated in ICC. In vitro and in vivo assays showed that Circ-RAPGEF5 promoted ICC tumor proliferation and metastasis, and inhibited apoptosis. Additionally, high Circ-RAPGEF5 expression was significantly correlated with a poor prognosis. Further investigation showed that SAE1, a potential target of Circ-RAPGEF5, was also associated with poor oncological outcomes. RNA pull-down and dual-luciferase reporter assays showed an interaction of miR-3185 with Circ-RAPGEF5 and SAE1. Co-IP and western blot assays showed that Circ-RAPGEF5 is capable of regulating SUMOylation.

Conclusion

Circ-RAPGEF5 promotes ICC tumor progression and SUMOylation by acting as a sponge for miR-3185 to stabilize SAE1. Targeting Circ-RAPGEF5 or SAE1 might be a novel diagnostic and therapeutic strategy in ICC.
Influenza viruses circulation in a tertiary care children hospital in Rome: a comparison between 2022 and the previous 5 years
Authors: Ranno Stefania , Coltella Luana , Linardos Giulia , Di Maio Velia Chiara , Colagrossi Luna , Gentile Leonarda , Galeno Eugenia , Ciofi degli Atti Marta Luisa , Cristaldi Sebastian , Villani Alberto , Raponi Massimiliano , Perno Carlo Federico , Russo Cristina
Published: September 2023

Background

Influenza surveillance aims to determine onset, duration and intensity of the seasonal Influence-like Illness (ILI); data collection begins in the week 42 of a year and ends in the week 17 of the following year. In this observational study, we report the experience of a tertiary care children hospital in Rome about Influenza viruses circulation during the calendar year 2022 (January-December) in comparison with the previous five years (2017–2021), with a special focus on the weeks 18–41, usually not under surveillance.

Methods

This retrospective study involved 36782 respiratory samples referred to 21354 patients (pts), median age 2.63 years, admitted with respiratory symptoms at Bambino Gesù Children’s Hospital in the years 2017–2022. Respiratory viruses were detected by molecular Allplex™ Respiratory Panel Assays (Seegene, Korea).

Results

Regarding the pre pandemic years, 2017–2019, distribution of Flu positive patients focused in the first weeks of the year (weeks 1–17). During the pandemic period, Flu was not detected. In 2022, 239 Flu viruses were identified: 37 FluA (weeks 1–17), 29 FluA (weeks 18–41) and 168 FluA and 5 FluB (weeks 42–52). For the year 2022, during the non-epidemic period, the number of Flu viruses detected corresponded to 12.1% of total Flu detected, respect to 0-1.7% for the previous five years (p < 0.001).

Conclusions

When compared with pre SARS-CoV-2 pandemic years, our data show a significant increase in Influenza cases during weeks 18–41/2022 and reveal an unexpected summer circulation of these viruses: just weeks 26–30 showed to be influenza virus free. A national year-round Flu surveillance could be useful to understand if changing in influenza epidemiology is transitional or likely to persist in the following years.