bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of deprivation, age, and regional differences in COVID-19 mortality from 2020 to 2022: a retrospective analysis of public provincial data
Authors: Chen Anqi A. , Renouf Elizabeth M. , Dean Charmaine B. , Hu X. Joan
Published: January 2025

Background

Coronavirus disease (COVID-19) quickly spread around the world after its initial identification in Wuhan, China in 2019 and became a global public health crisis. COVID-19 related hospitalizations and deaths as important disease outcomes have been investigated by many studies while less attention has been given to the relationship between these two outcomes at a public health unit level. In this study, we aim to establish the relationship of counts of deaths and hospitalizations caused by COVID-19 over time across 34 public health units in Ontario, Canada, taking demographic, geographic, socio-economic, and vaccination variables into account.

Methods

We analyzed daily data of the 34 health units in Ontario between March 1, 2020 and June 30, 2022. Associations between numbers of COVID-19 related deaths and hospitalizations were explored over three subperiods according to the availability of vaccines and the dominance of the Omicron variant in Ontario. A generalized additive model (GAM) was fit in each subperiod. Heterogeneity across public health units was formulated via a random intercept in each of the models.

Results

Mean daily COVID-19 deaths increased quickly as daily hospitalizations increased, particularly when daily hospitalizations were less than 20. In all the subperiods, mean daily deaths of a public health unit was significantly associated with its population size and the proportion of confirmed cases in subjects over 60 years old. The proportion of fully vaccinated (2 doses of primary series) people in the 60 + age group was a significant factor after the availability of the COVID-19 vaccines. The deprivation index, a measure of poverty, had a significantly positive effect on COVID-19 mortality after the dominance of the Omicron variant in Ontario. Quantification of these effects was provided, including effects related to public health units.

Conclusions

The differences in COVID-19 mortality across health units decreased over time, after adjustment for other covariates. In the last subperiod when most public health protections were released and the Omicron variant dominated, the least advantaged group might suffer higher COVID-19 mortality. Interventions such as paid sick days and cleaner indoor air should be made available to counter lifting of health protections.
An introduction to MyBFF@school, a school-based childhood obesity intervention program: a cluster randomized controlled trial
Authors: Mokhtar Abdul Halim , Ishak Zahari , Zain Fuziah Md. , Selamat Rusidah , Yahya Abqariyah , Jalaludin Muhammad Yazid
Published: January 2025

Obesity trend among Malaysian children is on the rise. Noting that the tendency for them to grow into obese adults and the relationship of obesity to many non-communicable diseases, the My Body is Fit and Fabulous at School (MyBFF@school program) was designed to combat obesity among the schoolchildren. The program was piloted in 2014 in Putrajaya, Malaysia. There were several challenges during the pilot study which included strain in manpower, limited variation of physical activity, nutrition, and psychology modules, time-constraint after school hours, co-curriculum marks, contamination effect, and school selection. The main MyBFF@school in 2016 addressed the challenges and improvised the design which were elaborated in subsequent articles in this supplement. This cluster randomized controlled trial was conducted in three states; Federal Territory of Kuala Lumpur, Selangor and Negeri Sembilan in 23 primary and 15 secondary schools were selected through proportionate random sampling. The MyBFF@school intervention package consisted of physical activity, nutrition and psychology components were carried out for six months. Data were collected at baseline, mid (month-3) and end (month-6) of the study period. The effects of the program on body composition, clinical, physical fitness, nutrition, and psychology were assessed in primary schoolchildren aged 9 to 11 years old (children age group) and secondary schoolchildren (adolescent) aged 13 to 16 years old. The prevalence of overweight and obesity at screening (N=22,816) were 29.4% in primary and 26.8% in secondary schoolchildren. Outcomes of the trial is presented in this supplement. In summary, the MyBFF@school program is a school-based intervention for overweight and obese children and adolescent. It is a combination of physical activity, nutrition and psychology components. We present in this supplement, the rationale, methodology and the outcomes of this randomized control trial of the MyBFF@school program.
Exploring the contribution of integrated healthcare practices to malaria control in Ghana: perspectives of medical herbalists
Authors: Ampomah Irene G. , Devine Susan , Ampomah Genevieve A. , Emeto Theophilus I.
Published: January 2025

Background

The integration of herbal and orthodox medicines has gained momentum in global health, ensuring improved management of infectious diseases like malaria. This study explored the experiences of medical herbalists working in Ghana’s diverse ecological zones to understand the contributions of integrated healthcare to malaria control.

Methods

A phenomenological design was employed to conduct in-depth interviews with 19 purposively sampled medical herbalists. Framework analytical approach and Donabedian’s conceptual framework for quality of care were utilised in analysing the data.

Results

Findings revealed high awareness of integrated healthcare practices among participants. Medical herbalists perceived integrated care as instrumental in enhancing malaria management through factors such as improved quality assurance, increased accessibility to integrated health facilities, patient-centred care, follow-up practices, and opportunities for continuous professional development. However, structural and process-related challenges were identified, including inadequate healthcare personnel, medicines, and equipment. Additionally, limited promotional activities, non-comprehensive National Health Insurance Scheme (NHIS), and ineffective referral systems were recognised as barriers hindering the effectiveness of the integrated system and its potential contribution to malaria control.

Conclusion

Although national and health system-based challenges have thwarted the importance of integration on malaria control, medical herbalists feel optimistic about the intervention. To optimise the effectiveness of integrated healthcare in controlling malaria in Ghana would require policy modification and implementation. Future research could focus on developing healthcare frameworks, particularly for malaria, that prioritise quality service delivery within an integrated system.
The SIRT5-JIP4 interaction promotes osteoclastogenesis by modulating RANKL-induced signaling transduction
Authors: Zhu Kecheng , Sheng Chunxiang , Zhang Linlin , Yang Yuying , Chen Xiaojing , Jiang Tao , Song Jiaxi , Zhang Deng , Wang Xiao , Zhao Hongyan , Sun Lihao , Zhou Libin , Tao Bei , Liu Jianmin
Published: January 2025

Receptor activator of nuclear factor kappa-B ligand (RANKL) initiates a complex signaling cascade that is crucial for inducing osteoclast differentiation and activation. RANKL-induced signaling has been analyzed in detail, and the involvement of TNF receptor-associated factor 6 (TRAF6), calmodulin-dependent protein kinase (CaMK), NF-κB, mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1), and molecules that contain an immunoreceptor tyrosine-based activation motif (ITAM) has been reported. However, the precise molecular steps that regulate RANKL signaling remain largely unknown. Here, we revealed the indispensable role of a class III histone deacetylase (SIRT5) in the processes of RANKL-induced osteoclast differentiation and activation. SIRT5 expression in osteoclasts was increased during osteoclastogenesis upon stimulation with RANKL. The RANKL-induced signaling activation was suppressed in SIRT5-deficient osteoclasts but enhanced by SIRT5 overexpression. Mice with global or conditional monocytic lineage knockout of SIRT5 had increased bone mass and reduced osteoclast numbers. In the cytoplasm, SIRT5 interacted with the scaffold protein JNK-interacting protein 4 (JIP4) to finely regulate MAPK signaling, which was critical for osteoclast differentiation and activation. Pharmacological inhibition of the catalytic activity of SIRT5 effectively reversed bone loss in ovariectomized mice. Taken together, the results of this study reveal that the SIRT5-JIP4 axis is a novel positive regulator that finely regulates RANKL-induced osteoclast differentiation and suggest that targeting this axis is a therapeutic strategy for preventing osteoporotic bone loss.

Graphical Abstract
Machine learning and multi-omics in precision medicine for ME/CFS
Authors: Huang Katherine , Lidbury Brett A. , Thomas Natalie , Gooley Paul R. , Armstrong Christopher W.
Published: January 2025

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and multifaceted disorder that defies simplistic characterisation. Traditional approaches to diagnosing and treating ME/CFS have often fallen short due to the condition’s heterogeneity and the lack of validated biomarkers. The growing field of precision medicine offers a promising approach which focuses on the genetic and molecular underpinnings of individual patients. In this review, we explore how machine learning and multi-omics (genomics, transcriptomics, proteomics, and metabolomics) can transform precision medicine in ME/CFS research and healthcare. We provide an overview on machine learning concepts for analysing large-scale biological data, highlight key advancements in multi-omics biomarker discovery, data quality and integration strategies, while reflecting on ME/CFS case study examples. We also highlight several priorities, including the critical need for applying robust computational tools and collaborative data-sharing initiatives in the endeavour to unravel the biological intricacies of ME/CFS.
The interaction of tPA with NMDAR1 drives neuroinflammation and neurodegeneration in α-synuclein-mediated neurotoxicity
Authors: Torrente Daniel , Su Enming J. , Citalán-Madrid Alí Francisco , Schielke Gerald P. , Magaoay Daniel , Warnock Mark , Stevenson Tamara , Mann Kris , Lesept Flavie , Delétage Nathalie , Blanc Manuel , Norris Erin H. , Vivien Denis , Lawrence Daniel A.
Published: January 2025

The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice. We further investigate tPA’s potential role in SN pathology in an α-synuclein mouse model of Parkinson’s disease (PD). To characterize the mechanism of tPA action in α-synuclein-mediated pathology in the SN and to identify possible therapeutic pathways, we performed RNA-seq analysis of the SN and used multiple transgenic mouse models. These included tPA deficient mice and two newly developed transgenic mice, a knock-in model expressing endogenous levels of proteolytically inactive tPA (tPA Ala-KI) and a second model overexpressing proteolytically inactive tPA (tPA Ala-BAC). Our findings show that striatal GABAergic neurons send tPA+ projections to dopaminergic (DA)-neurons in the SN and that tPA is released from SN-derived synaptosomes upon stimulation. We also found that tPA levels in the SN increased following α-synuclein overexpression. Importantly, tPA deficiency protects DA-neurons from degeneration, prevents behavioral deficits, and reduces microglia activation and T-cell infiltration induced by α-synuclein overexpression. RNA-seq analysis indicates that tPA in the SN is required for the upregulation of genes involved in the innate and adaptive immune responses induced by α-synuclein overexpression. Overexpression of α-synuclein in tPA Ala-KI mice, expressing only proteolytically inactive tPA, confirms that tPA-mediated neuroinflammation and neurodegeneration is independent of its proteolytic activity. Moreover, overexpression of proteolytically inactive tPA in tPA Ala-BAC mice leads to increased neuroinflammation and neurodegeneration compared to mice expressing normal levels of tPA, suggesting a tPA dose response. Finally, treatment of mice with glunomab, a neutralizing antibody that selectively blocks tPA binding to the N-methyl-D-aspartate receptor-1 (NMDAR1) without affecting NMDAR1 ion channel function, identifies the tPA interaction with NMDAR1 as necessary for tPA-mediated neuroinflammation and neurodegeneration in response to α-synuclein-mediated neurotoxicity. Thus, our data identifies a novel pathway that promotes DA-neuron degeneration and suggests a potential therapeutic intervention for PD targeting the tPA-NMDAR1 interaction.
'Which treatment do you believe you received?' A randomised blinding feasibility trial of spinal manual therapy
Authors: Muñoz Laguna Javier , Kurmann Astrid , Hofstetter Léonie , Nyantakyi Emanuela , Braun Julia , Clack Lauren , Bang Heejung , Farshad Mazda , Foster Nadine E. , Puhan Milo A. , Hincapié Cesar A. ,   the SALuBRITY Blinding Clinician Group, Mühlemann Malin , Caviezel Curdin , Ehrler Marco , Häusler Melanie , Höltschi Céline , Kroismayr Daniela , Leemann Serafin , Mühlemann Daniel , Nyirö Luana , Rabold Lorene , Schmid Christof , Yilmaz Bedran , Granelli Fredrik , Sem Christophe
Published: January 2025

Background

Blinding is essential for mitigating biases in trials of low back pain (LBP). Our main objectives were to assess the feasibility of blinding: (1) participants randomly allocated to active or placebo spinal manual therapy (SMT), and (2) outcome assessors. We also explored blinding by levels of SMT lifetime experience and recent LBP, and factors contributing to beliefs about the assigned intervention.

Methods

A two-parallel-arm, single-centre, placebo-controlled, blinding feasibility trial. Adults were randomised to active SMT (n = 40) or placebo SMT (n = 41). Participants attended two study visits for their assigned intervention, on average seven days apart. The primary outcome was participant blinding (beliefs about assigned intervention) using the Bang blinding index (BI) at two study visits. The Bang BI is arm-specific, chance-corrected, and ranges from − 1 (all incorrect beliefs) to 1 (all correct beliefs), with 0 indicating equal proportions of correct and incorrect beliefs. Secondary outcomes included factors contributing to beliefs about the assigned intervention.

Results

Of 85 adults screened, 81 participants were randomised (41 [51%] with SMT lifetime experience; 29 [39%] with recent LBP), and 80 (99%) completed follow-up. At study visit 1, 50% of participants in the active SMT arm (Bang BI: 0.50 [95% confidence interval (CI), 0.26 to 0.74]) and 37% in the placebo SMT arm (0.37 [95% CI, 0.10 to 0.63]) had a correct belief about their assigned intervention, beyond chance. At study visit 2, BIs were 0.36 (0.08 to 0.64) and 0.29 (0.01 to 0.57) for participants in the active and placebo SMT arms, respectively. BIs among outcome assessors suggested adequate blinding at both study visits (active SMT: 0.08 [− 0.05 to 0.20] and 0.03 [− 0.11 to 0.16]; placebo SMT: − 0.12 [− 0.24 to 0.00] and − 0.07 [− 0.21 to 0.07]). BIs varied by participant levels of SMT lifetime experience and recent LBP. Participants and outcome assessors described different factors contributing to their beliefs.

Conclusions

Adequate blinding of participants assigned to active SMT may not be feasible with the intervention protocol studied, whereas blinding of participants in the placebo SMT arm may be feasible. Blinding of outcome assessors seemed adequate. Further methodological work on blinding of SMT is needed.

Trial registration number

NCT05778396.
How Delphi studies in the health sciences find consensus: a scoping review
Authors: Schifano Julia , Niederberger Marlen
Published: January 2025

Background

Delphi studies are primarily used in the health sciences to find consensus. They inform clinical practice and influence structures, processes, and framework conditions of healthcare. The practical research—how Delphi studies are conducted—has seldom been discussed methodologically or documented systematically. The aim of this scoping review is to fill this research gap and to identify shortcomings in the methodological presentation in the literature. On the basis of the analysis, we derive recommendations for the quality-assured implementation of Delphi studies.

Methods

Forming the basis of this scoping review are publications on consensus Delphi studies in the health sciences between January 1, 2018, and April 21, 2021, in the databases Scopus, MEDLINE via PubMed, CINAHL, and Epistemonikos. Included were publications in German and English containing the words “Delphi” in the title and “health” and “consensus” in the title or abstract. The practical research was analyzed for the qualitative content of the publications according to three deductive main categories, to which an influence on the result of Delphi studies can be imputed (expert panel, questionnaire design, process and feedback design).

Results

A total of 287 consensus Delphi studies were included in the review, whereby 43% reported having carried out a modified Delphi. In most cases, heterogeneous expert groups from research, clinical practice, health economics, and health policy were surveyed. In about a quarter of the Delphi studies, affected parties, such as patients, were part of the expert panel. In the Delphi questionnaires it was most common for standardized Likert scales to be combined with open-ended questions. Which method was used to analyze the open-ended responses was not reported in 62% of the Delphi studies. Consensus is largely (81%) defined as percentage agreement.

Conclusions

The results show considerable differences in how Delphi studies are carried out, making assessments and comparisons between them difficult. Sometimes an approach points to unintended effects, or biases in the individual judgments of the respondents and, thus, in the overall results of Delphi studies. For this reason, we extrapolate suggestions for how certain comparability and quality assurance can be achieved for Delphi studies.
A framework for the continuous monitoring of person-centred hospital care: validation of a checklist for participatory service improvement
Authors: Cardinali F. , Carzaniga S. , Martini L. , Loiudice M. T. , Carinci Fabrizio
Published: January 2025

Background

In 2018, a nationwide survey carried out in 387 acute care hospitals from 16 out of 21 Italian regions, allowed defining an extended checklist for the participatory evaluation of person-centredness in hospital care. We aimed to validate a reduced set of core items for continuous use across the country.

Methods

Factor analysis was used to validate the construct of the checklist. Varimax rotation with eigenvalues > 1 was used to optimize factor structure. Items with an item-total correlation > 0.30 and factor loadings > 0.4 were attributed to individual factors. Items with inter-item correlation coefficient > 0.70 were submitted to expert opinion for final decision. Overall internal consistency was assessed through Cronbach’s alpha.

Results

A total of 183 out of 243 items in the original checklist were submitted to factor analysis. A subgroup of 67 items was retained in 4 main areas, allocated as follows: 16 items in 4 sub-areas of “Person-oriented organizational and care processes”, 16 items in 4 sub-areas of “Physical accessibility, liveability and comfort of the facilities”, 15 items in 3 sub-areas of “Access to information, streamlining and transparency”, and 20 items in 4 sub-areas of “Taking care of the relationship with patients and citizens”. Overall values of Cronbach’s alpha ranged between 0.77 and 0.90, showing high consistency.

Conclusions

This study validated a “core” checklist that can be routinely used to monitor the implementation of person-centred care in Italian hospitals. The tool can be applied more widely by multiple stakeholders as a measurement instrument for the participatory evaluation of person-centredness.
Characterization of liver, adipose, and fecal microbiome in obese patients with MASLD: links with disease severity and metabolic dysfunction parameters
Authors: Schwenger Katherine J. P. , Copeland Julia K. , Ghorbani Yasaman , Chen Lina , Comelli Elena M. , Guttman David S. , Fischer Sandra E. , Jackson Timothy D. , Okrainec Allan , Allard Johane P.
Published: January 2025

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a range of histological findings from the generally benign simple steatosis to steatohepatitis (MASH) which can progress to fibrosis and cirrhosis. Several factors, including the microbiome, may contribute to disease progression.

Results

Here, we demonstrate links between the presence and abundance of specific bacteria in the adipose and liver tissues, inflammatory genes, immune cell responses, and disease severity. Overall, in MASLD patients, we observed a generalized obesity-induced translocation of gut bacteria to hepatic and adipose tissues. We identified microbial patterns unique to more severely diseased tissues. Specifically, Enterococcus, Granulicatella, and Morganellaceae abundance is positively correlated with immune cell counts and inflammatory gene expression levels, and both genera are significantly enriched in MASH patients. Brevibacterium is enriched in adipose tissues of patients with liver fibrosis.

Conclusion

Together, these results provide further insight into the microbial factors that may be driving disease severity.
Monkeypox: a re-emergent virus with global health implications – a comprehensive review
Authors: Naga Nourhan G. , Nawar Enas A. , Mobarak A’laa A. , Faramawy Aya G. , Al-Kordy Hend M. H.
Published: January 2025

Monkeypox virus (MPXV) is an enclosed, double-stranded DNA virus from the Orthopoxvirus genus, which also contains variola, vaccinia, and cowpox. MPXV, which was once confined to West and Central Africa, has recently had a rebound, spreading beyond its original range since 2017. The virus is distinguished by its unique morphology, which includes an oval or brick-shaped structure and a complex lipid and protein makeup. The current multi-country outbreak designated a public health emergency in 2022, has highlighted MPXV’s shifting epidemiology and ability to spread rapidly over the globe. ‘No one is safe until everyone is safe’ is a slogan we often heard during the COVID-19 pandemic, which is now also required for the growing global and regional mpox outbreaks. The epidemic is divided into two clades: Clade I and Clade II, which have distinct pathogenic characteristics. Diagnostic approaches have developed with advances in molecular techniques, yet problems persist in resource-constrained situations. This overview summarizes the virus’s history, epidemiology, morphology, and clinical characteristics, offering insights into its recent comeback and current global response efforts.
Comparison of the asymmetric multifractal behavior of green and U.S. bonds against benchmark financial assets
Authors: Kristjanpoller Werner , Tabak Benjamin Miranda
Published: January 2025

Presently, financial portfolio managers lack a solid basis for building a reliable risk management strategy for green debt instrument investments due to the lack of compelling growth and resilience data. Therefore, this study assesses the role of green bonds in financial markets by assessing and correlating their complex scaling behaviors across multiple periods with those of key benchmark assets (e.g., conventional bonds, high-yield bonds, Euro-Dollar exchange, Dow Jones Industrial Index, Bitcoin, and Gold). Specifically, we explore linear and nonlinear correlation patterns using cross-correlation tests and the dynamic conditional correlation model, focusing on bond interactions under various degrees of freedom. Our analysis reveals that although most assets exhibit nonlinear correlations, Bitcoin uniquely aligns linearly with U.S. bonds under certain conditions. Green bonds, however, display nonlinear correlations with Bitcoin and stand out for their distinct upward financial persistence. We find also that green bonds are primary drivers in the financial domain, highlighted by their pronounced interactions and the consistent cross-correlation with the Euro-Dollar exchange rate. Moreover, green bonds have the lowest multifractality, showing persistent upward trends and antipersistent downward trends, rendering them quite resilient during periods of high volatility. These results imply that green bonds may be advantageous to portfolio risk management strategies, especially during crises when diversification and hedging tactics are needed.
The nexus between the financial development and CO2 emissions: fresh evidence through time–frequency analyses
Authors: Bilgili Faik , Muğaloğlu Erhan , Kuşkaya Sevda , Cifuentes-Faura Javier , Khan Kamran , Alnour Mohammed
Published: January 2025

Climate change and environmental degradation threaten the world and global economic conditions. As one of countries’ most important economic components, the financial sector might be an effective tool for reducing and even reversing environmental degradation. The financial sector can affect sustainability through its lending and investment practices. The sector can play a role in financing sustainable projects and businesses, helping reduce CO2 emissions. By aligning its financial objectives with environmental protection, the financial sector can support the transition to a more sustainable future by helping reduce environmental degradation’s negative impacts. This paper examines the domestic financial sector’s impact on CO2 emissions in the United States over the 1990:Q1–2022:Q3 period. In this research, the nexus between the domestic financial sector (total debt securities, loans, liabilities, and total financial assets) and Carbon dioxide emissions in the U.S. is investigated by Morlet wavelet analysis. Rest of the world: sector discrepancy transactions, rest of the world: debt securities and loans, gross domestic product, and the square of the gross domestic product, are control variables in the estimated models. Partial wavelet coherency analyses prove that the financial sector reduces CO2 emissions at the 5–8-year frequency band during different subsample periods. The financial sector’s instruments can be effective in struggling with climate change.
Decoding systemic risks across commodities and emerging market stock markets
Authors: Ghallabi Fahmi , Ghorbel Ahmed , Karim Sitara
Published: January 2025

This study explores correlations and risk spillovers, essential concepts for financial risk management, among commodities (crude oil, gold, and a global commodities index) and emerging stock markets. Using the Asymmetric Dynamic Conditional Correlation–Conditional Value-at-Risk (ADCC-CoVaR) model and a bootstrapped Kolmogorov–Smirnov (KS) test, we analyze the period from December 30, 2005, to February 28, 2024, examining correlations, downside and upside risk spillovers, and highlighting the effects of major events such as the global financial crisis of 2008, the COVID-19 pandemic, and the Russia-Ukraine war. The results show heightened correlations during crises and significant risk spillovers across market pairs, with downside risks often outweighing upside risks. Gold displays minimal risk spillover, highlighting its unique role as a haven asset. We find that spillovers between gold, global commodities, and stocks increased during the pandemic and the Russia-Ukraine conflict, while those involving crude oil remained stable. These findings provide valuable guidance for portfolio managers in navigating volatile markets.
Evaluation of the impact of the state of emergency during the COVID-19 pandemic on childhood immunizations in Benguela Province, Angola
Authors: Imamura Tadatsugu , Mochida Keiji , Olukunmi Balogun , Tchicondingosse Lino , Sapalalo Pedro , Francisco Ketha Rubuz , Aoki Ai , Ishiguro Akira , Takehara Kenji
Published: January 2025

Background

The impact of public health measures against the coronavirus disease 2019 on the rate of childhood immunization has not yet been fully defined. Particularly, measures which directly affect health-seeking behaviors (e.g., the State of Emergency; SoE) drew public health attention. We aim to describe this impact in Benguela Province, Angola, by comparing the immunization rates between infants who had their immunizations before and after the SoE, which was declared on March 27, 2020.

Methods

We retrospectively reviewed the epidemiological data of infants born between November 2019 and February 2020 in Benguela Province, Angola. Immunization rates (i.e., the number of immunized infants divided by the number of infants in the group of same months of birth and residential areas) were calculated for 11 vaccines that infants received from at birth to the 4th month after birth. The rates for the 2nd month vaccines were compared between infants immunized before the SoE (post-SoE), and after the SoE (pre-SoE).

Results

Among 9,595 infants, the overall immunization rates were higher in the post-SoE (71.9–77.8%) than in the pre-SoE groups (66.0–73.8%). The overall immunization rates were higher in the post-SoE group than in the pre-SoE group in both urban and rural municipalities, although the rates were > 20% higher in urban than in rural municipalities. The immunization rates in the recommended month showed a similar trend, except for the stratified analysis for rural municipalities, where the rates were 2.3–4.1% lower in the post-SoE than in the pre-SoE groups.

The most common reason for missing immunization was vaccine unavailability at health units (19.9%, 684/3,440). Less than 10% of missed immunizations were due to the SoE, which occurred mostly in infants born in rural municipalities in February 2020 (9.8%, 52/532). Less than 2% of missed immunizations were due to health units not being open, and was highest in rural municipalities in January 2020 (1.6%, 27/1,673).

Conclusions

Our study suggested that the disruptive impacts of public health measures against pandemics on rates of childhood immunization can be mitigated, and support is needed for areas with vulnerable health systems, such as rural areas.
Effects of population aging on quality of life and disease burden: a population-based study
Authors: Xi Jun-Yan , Liang Bo-Heng , Zhang Wang-Jian , Yan Bo , Dong Hang , Chen Yuan-Yuan , Lin Xiao , Gu Jing , Hao Yuan-Tao
Published: January 2025

Background

As population aging intensifies, it becomes increasingly important to elucidate the casual relationship between aging and changes in population health. Therefore, our study proposed to develop a systematic attribution framework to comprehensively evaluate the health impacts of population aging.

Methods

We used health-adjusted life expectancy (HALE) to measure quality of life and disability-adjusted life years (DALY) to quantify the burden of disease for the population of Guangzhou. The HALE and DALY projections were generated using both the Bayesian age-period-cohort models and the population prediction models. Changes in HALE and DALY between 2010–2020 and 2020–2030 were decomposed to isolate the effects of population aging. Three scenarios were analyzed  to examine the relative relationship between disease burden and population aging. In Scenarios 1 and 2, the disease burden rates in 2030 were assumed to  either remain at 2020 levels or follow historical trends. In Scenario 3, it was assumed that the absolute numbers of years of life lost (YLL) and years lived with disability (YLD) in 2030 would remain unchanged from the 2020 levels.

Results

Between 2010 and 2020, 56.24% [69.73%] of the increase in male [female, values in brackets] HALE was attributable to the mortality effects in the population aged 60 and over, while − 3.74% [− 9.29%] was attributable to the disability effects. The increase in DALY caused by changes in age structure accounted for 72.01% [46.68%] of the total increase in DALY. From 2020 to 2030, 61.43% [69.05%] of the increase in HALE is projected to result from the mortality effects in the population aged 60 and over, while − 3.88% [4.73%] will be attributable to the disability effects. The increase in DALY due to changes in age structure is expected to account for 102.93% [100.99%] of the total increase in DALY. In Scenario 1, YLL are projected to increase by 45.0% [54.7%], and YLD by 31.8% [33.8%], compared to 2020. In Scenario 2, YLL in 2030 is expected to decrease by − 2.9% [− 1.3%], while YLD will increase by 12.7% [14.7%] compared to 2020. In Scenario 3, the expected YLL rates and YLD rates in 2030 would need to be reduced by 15.3% [15.4%] and 15.4% [15.6%], respectively, compared to 2020.

Conclusions

The disability effects among the elderly population hinder improvements in quality of life, while changes in age structure are the primary driver of disease burden accumulation. To mitigate the excess disease burden caused by population aging, it is essential to achieve a reduction of more than 15% in the disease burden by 2030 compared to 2020. Our proposed attribution framework evaluates the health impacts of population aging across two dimensions: quality of life and disease burden. This framework enables comparisons of these effects over time and across different regions.
Selection of appropriate probiotic yeasts for use in dairy products: a narrative review
Authors: Kazemi Sanaz , Homayouni-Rad Aziz , Samadi Kafil Hossien , Sarabi-aghdam Vahideh , Zeynolabedini Payam , pour Agha Bahareh , Allah Madadi Sevda
Published: January 2025

Yeasts, with a history of approximately 5,000 years in food and medicinal applications, play a vital role in various industries. The advantages of these microorganisms include probiotic effects, phytate biodegradation, mycotoxin breakdown, and adsorption capabilities. Traditionally, research on probiotics has primarily focused on lactic acid bacteria and bifidobacteria; however, there is a growing global interest in incorporating yeast as a probiotic supplement. Notably, yeast species such as Saccharomyces, Candida, Debaryomyces, Yarrowia, and Kluyveromyces have been identified for their probiotic potential. These probiotic yeasts are commonly introduced into dairy products, including kefir, yogurt, kumis, and cheese. However, the compatibility of probiotic yeasts with dairy matrices, as well as the factors influencing their viability and functionality, remains a critical area of study. Ongoing research focused on exploring techniques to enhance yeast viability during processing, given that different strains may exhibit varying survival rates and probiotic properties. Consequently, probiotic yeasts represent a promising avenue for augmenting the health benefits of dairy products. This development prompts essential discussions regarding selecting suitable probiotic yeasts for specific dairy applications. This paper comprehensively examines the historical discovery, types, properties, and applications of probiotic yeasts in dairy products. It aims to shed light on their health effects while addressing the challenges associated with selecting the appropriate probiotic yeast to optimize the enhancement of dairy products.

Graphical Abstract
Awareness and attitudes of pregnant women concerning genetic disorders and pregnancy termination in northeastern Iran
Authors: Todarbary Nafiseh , Irandegani Abouzar , Meshkat Mojtaba , Gholoobi Aida , Hamzehloei Tayebeh
Published: January 2025

Background

Genetic disorders are common in the Eastern Mediterranean region due to the high prevalence of consanguineous marriages. This study explores the awareness and attitudes of pregnant women in Mashhad, the biggest city in northeastern Iran, toward genetic disorders and the decision-making process regarding pregnancy termination. This study included 297 pregnant women across five hospitals in Mashhad, Iran. They filled out a checklist comprised of demographic data and questions about abortion decisions facing a child with various genetic disorders or undesired gender.

Results

The majority (75%) agreed with abortion in cases of anencephaly, while only 19% accepted it for undesired gender. Education level was associated with abortion agreement for various conditions, including cleft lip or palate, Alzheimer’s disease, Turner syndrome, cystic fibrosis, phenylketonuria, Huntington’s disease, autism, fragile X syndrome, and epilepsy. Additionally, the number of children was correlated with congenital blindness, Duchenne muscular dystrophy, autism, Proteus syndrome, Klinefelter syndrome, anencephaly, mental retardation (MR), quadriplegia, and severe learning disability and mental health (LDMH). Age was associated with conditions such as epilepsy, congenital blindness, schizophrenia, and severe LDMH. Furthermore, a history of anomalies in previous pregnancies was linked to Klinefelter syndrome, Turner syndrome, dwarfism, and quadriplegia. The number of pregnancies was also correlated with severe LDMH, dwarfism, and Klinefelter syndrome, while job status was related to epilepsy, Alzheimer’s disease, and dwarfism.

Conclusion

The findings emphasize the importance of comprehensive genetic counseling, informed decision-making in prenatal care, advocating for policy reviews, and culturally sensitive guidelines in Iran.
Early applicability of retinopathy of prematurity score (ROPScore) and serum insulin growth factor-1 (IGF-1) for predicting treatment-requiring retinopathy of prematurity: a prospective cohort study
Authors: Ali Aliaa Adel , Gomaa Nancy Abd El-Salam Ahmed , Kamil Basma Samir , Awadein Ahmed , Baz Heba , Elmazzahy Esraa Ahmed
Published: January 2025

Background

Retinopathy of prematurity is a leading cause of blindness especially in developing countries where the accessibility to screening may not be available. Therefore, early prediction could help reallocate the resources for those at high risk.

Objectives

This study aimed to evaluate the accuracy of the retinopathy of prematurity score (ROPScore) and serum insulin-like growth factor-1 (IGF-1) for predicting treatment-requiring retinopathy of prematurity.

Methods

This prospective cohort study included 87 preterm neonates (≤ 32 weeks). Neonates were screened using digital fundus photography with indirect ophthalmoscopy performed when retinopathy of prematurity changes was detected. Serum insulin-like growth factor-1 was measured in the 3rd week of life.

Results

Nine cases (10.3%) developed treatment-requiring retinopathy of prematurity, while 78 patients had mild retinopathy of prematurity. According to logistic regression analysis, lower birth weight and longer duration of assisted ventilation were independent risk factors for treatment-requiring retinopathy of prematurity. At the 2nd week of life, cut-off value of 14.95 for the retinopathy of prematurity score showed a sensitivity of 100% and a specificity of 67.9% for predicting treatment-requiring retinopathy of prematurity. Moreover, serum insulin-like growth factor-1 was significantly lower in patients with treatment-requiring retinopathy of prematurity (p < 0.001).

Conclusions

ROPScore applied at week 2 and week 6 of life showed the same sensitivity and specificity to predict treatment-requiring retinopathy of prematurity. Furthermore, serum insulin-like growth factor-1 in the 3rd week of life was significantly lower in patients with treatment-requiring retinopathy of prematurity.
Stability indicating eco-friendly HPLC method development and validation for the estimation of bisoprolol fumarate and telmisartan
Authors: Darji Hitanshi , Prajapati Pratima , Dedania Zarna , Dedania Ronak
Published: January 2025

Background

Telmisartan and bisoprolol fumarate together are two medications that diminish arterial pressure. The current study comprises an evaluation of the proposed methodology's greenness regarding the HPLC method used to govern the medication mixture regardless of dose form A novel stability suggesting HPLC method's environmental effect was evaluated using the greenness metrics. Stress conditions comprising acidic, alkaline, oxidative, thermal, and photolytic degradation were applied for both of the medications.

Results

The RP—HPLC method employing a reversed-phase C18 column with a gradient approach, the HPLC chromatography was carried out. The mobile phase consisted of acetonitrile, methanol, and phosphate buffer (60:35:5, %v/v/v), with the stationary phase being the Unisphere C18 column Agela Tech. The RP-HPLC method uses UV detection at 224 nm with chromatographic purification spanning linearities of 2.5–12.5 μg/mL for bisoprolol fumarate and 40.0–200.0 μg/mL for telmisartan, correspondingly. The procedure is accurate and precise, as demonstrated by an outcome that % RSD inside the permissible range. Additionally, various stressors were introduced to the medications. The approach's green credentials with respect to solvent utilization, chemical substances, expenditure of energy, and waste formation have been verified by the greenness data collected during the evaluation. No chromatographic or spectrum impediments caused by formulation additives have been observed.

Conclusion

Bisoprolol fumarate and telmisartan could be measured simultaneously using the devised RP-HPLC method, which was simple, quick, sensitive, accurate, precise, linear, and stability indicating. The proposed approach showed ecological friendliness, robustness, sensitivity, and ease of use. As a result, the devised method could be applied to the regular quality checking of tablets and bulk medications.
Validation of Clinical Dynamic Contrast-Enhanced Magnetic Resonance Imaging Perfusion Modeling and Neoadjuvant Chemotherapy Response Prediction in Breast Cancer Using
18
FDG and
64
Cu-DOTA-Trastuzumab Positron Emission Tomography Studies
Authors: Whitman John , Adhikarla Vikram , Tumyan Lusine , Mortimer Joanne , Huang Wei , Rockne Russell , Peterson Joesph R. , Cole John
Published: January 2025

PURPOSE

Perfusion modeling presents significant opportunities for imaging biomarker development in breast cancer but has historically been held back by the need for data beyond the clinical standard of care (SoC) and uncertainty in the interpretability of results. We aimed to design a perfusion model applicable to breast cancer SoC dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) series with results stable to low temporal resolution imaging, comparable with published results using full-resolution DCE-MRI, and correlative with orthogonal imaging modalities indicative of biophysical markers.

METHODS

Subsampled high-temporal-resolution DCE-MRI series were run through our perfusion model and resulting fits were compared for consistency. The fits were also compared against previously published results from institutions using the full resolution series. The model was then evaluated on a separate cohort for validity of biomarker indications. Finally, the model was used as a fundamental part of predicting response to neoadjuvant chemotherapy (NACT).

RESULTS

Temporally subsampled DCE-MRI series yield perfusion fit variations on the scale of 1% of the tumor median value when input frames are varied. Fits generated from pseudoclinical series are within the variation range seen between imaging sites (ρ = 0.55), voxel-wise. The model also demonstrates significant correlations with orthogonal positron emission tomography imaging, indicating potential for use as a biomarker proxy. Specifically, using the perfusion fits as the grounding for a biophysical simulation of response, we correctly predict the pathologic complete response status after NACT in 15 of 18 patients, for an accuracy of 0.83, with a specificity and sensitivity of 0.83 as well.

CONCLUSION

Clinical DCE-MRI data may be leveraged to provide stable perfusion fit results and indirectly interrogate the tumor microenvironment. These fits can then be used downstream for prediction of response to NACT with high accuracy.
mRNA Expression of Mineralocorticoid and Glucocorticoid Receptors in Human and Mouse Sensory Neurons of the Dorsal Root Ganglia
Authors: Qualls Katherine A. , Kadakia Feni K. , Serafin Elizabeth K. , Lückemeyer Debora De Nardin , Davidson Steve , Strong Judith A. , Zhang Jun-Ming
Published: January 2025

BACKGROUND:

Corticosteroid receptors, including mineralocorticoid receptor (MR) and glucocorticoid receptor (GR), play important roles in inflammatory pain in the dorsal root ganglion (DRG). Although it is widely known that activating the GR reduces inflammatory pain, it has recently been shown that MR activation contributes to pain and neuronal excitability in rodent studies. Moreover, little is known about the translation of this work to humans, or the mechanisms through which corticosteroid receptors regulate inflammatory pain.

METHODS:

Corticosteroid receptor expression in human and mouse DRGs was characterized. RNAscope was used to perform high-resolution in situ hybridization for GR and MR mRNAs and to examine their colocalization with markers for nociceptors (SCN10A, NaV1.8 mRNA) and Aβ mechanoreceptors (KCNS1, Kv9.1 mRNA) in human DRG and C57BL/6J mouse DRG samples.

RESULTS:

GR and MR mRNAs are expressed in almost all DRG neurons across species. The 2 receptors colocalize in 99.2% of human DRG neurons and 95.9% of mouse DRG neurons (P = .0004, Fisher exact test). In both human and mouse DRGs, the large-diameter KCNS1+ Aβ mechanoreceptors showed a significantly higher MR/GR ratio (MR-leaning) compared to KCNS1− neurons (human: 0.23 vs 0.04, P = .0002; mouse: 0.35 vs −0.24, P < .0001; log ratios, unpaired t test), whereas small-diameter SCN10A+ nociceptive neurons showed a significantly lower MR/GR ratio (GR-leaning) compared to SCN10A− neurons (human: −0.02 vs 0.18, P = .0001; mouse: −0.16 vs 0.08, P < .0001; log ratios, unpaired t test).

CONCLUSIONS:

These findings indicate that mouse corticosteroid receptor mRNA expression reflects human expression in the DRG, and that mice could be a suitable model for studying corticosteroid receptor involvement in pain. Additionally, this study supports the translatability of rodent data to humans for the use of more selective corticosteroids at the DRG in pain treatments.