bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccination strategies to identify and reach zero-dose and under-immunized children in crisis-affected states in Sudan: a qualitative study
Authors: Sabahelzain Majdi M. , Almaleeh Alaa , Abdelmagid Nada , Abdalla Omayma , Nor Barni , Mounier-Jack Sandra , Singh Neha S.
Published: December 2024

Background

Globally, 21 million children were un- or under-vaccinated with Diphtheria-Tetanus-Pertussis (DTP)-containing vaccines in 2023. Around 20% of zero-dose children, those who had not received any DTP doses, live in conflict-affected settings in low and middle-income countries. There is insufficient evidence on vaccination interventions to identify and reach zero-dose children in these settings. This study aimed to map and assess current vaccination strategies to identify and reach zero-dose and under-vaccinated children in the crisis-affected states of South Kordofan, South Darfur and Blue Nile in Sudan.

Methods

We conducted a cross-sectional qualitative study guided by the (Identify-Reach-Monitor-Measure-Advocate (IRMMA) framework, developed by Gavi, the Vaccine Alliance. We conducted 20 individual semi-structured interviews during November and December 2022. We interviewed governmental and non-governmental vaccination stakeholders at federal, state and locality levels. We used the IRMMA framework to analyze the interview transcripts.

Results

Zero-dose and under-immunized children in the study sites were concentrated in opposition-controlled areas, nomadic communities, and remote rural areas. Zero-dose and under-immunized children in accessible areas were identified through routine vaccination strategies and surveillance reports. Various strategies were used in inaccessible areas. This includes tasking local institutions and individuals trusted by communities to identify and reach children, and infrequent integration and co-delivery of routine vaccines with other health interventions such as COVID-19 vaccination and insecticidal net distribution. There are inaccurate population estimates and a lack of guidance from ministries of health for measuring and monitoring zero-dose and under-immunized children. Respondents conflated advocacy with mobilization, and advocacy was broadly characterized as an ad hoc activity mostly connected to immunization campaigns.

Conclusions

Our study underscored the complexity of vaccinating zero-dose and under-immunized children in crisis-affected states of Sudan. Further research is needed to evaluate these practices and the role of non-governmental organizations (NGOs) and community engagement in improving vaccination coverage. Furthermore, exploring alternative funding methods and using geographic information systems (GIS) could enhance vaccination data and address funding limitations.
Multi-locus investigation of Anopheles-mediated selective pressure on Plasmodium falciparum in Africa
Authors: Gunarathna Isuru , Spear Joseph D. , Carter Tamar E.
Published: December 2024

Background

The high burden of malaria in Africa is largely due to the presence of competent and adapted Anopheles vector species. With invasive Anopheles stephensi implicated in malaria outbreaks in Africa, understanding the genomic basis of vector-parasite compatibility is essential for assessing the risk of future outbreaks due to this mosquito. Vector compatibility with P. falciparum arises from ancient coevolution and involves genes such as Pfs47 in P. falciparum and P47Rec in Anopheles. Questions remain about whether sub-continental vector variation is a selective pressure on current Plasmodium populations.

Methods

We analyzed the genetic diversity in parasite–vector interaction genes in P. falciparum and An. gambiae from 9 and 15 countries in Africa, respectively. Specifically, we looked for evidence of malaria vector-mediated selection within three P. falciparum genes (Pfs47, Pfs16, Pfs37) and conducted association analyses with occurrence probabilities of prominent malaria vectors.

Results

Higher protein haplotype diversities of Pfs47 and Pfs16 were associated with the probability of occurrence of An. arabiensis and An. funestus together. Only Pfs16 carried a signature of positive selection consistently (average Tajima’s D = −2.96), which was associated with the probability of occurrence of An. funestus. These findings support vector-mediated selection on the basis of vector species diversity that may be occurring within Africa. We also employed phylogenetic analyses of An. gambiae interaction genes (P47Rec, APN1, HPX15) to identify significant subspecies diversity as a prerequisite to vector-population-mediated selection. Anopheles gambiaeHPX15 revealed significant within-species differentiation (multiple branches bootstrap > 70) compared with absence of variation in P47Rec, suggesting that further investigation into subspecies-mediated selection on the basis of HPX15 is needed. Finally, we observed five amino acid changes at P47Rec in invasive An. stephensi compared with dominant African Anopheles species, calling for further investigation of the impact these distinct P47Rec variants might have on local African P. falciparumPfs47 diversity.

Conclusions

Overall, these findings suggest that vector variation within Africa could influence P. falciparum diversity and lay a genomic framework for future investigation of invasive An. stephensi’s impact on African malaria.

Graphical Abstract
Developing and disseminating an electronic penicillin allergy de-labelling tool using the model for improvement framework
Authors: Saravanabavan Sujen , McKernan Patrick , Cameron Scott , Kwan Natasha , Kang Kristopher T. , Roberts Ashley , Carr Roxane , Mak Raymond , Elwood Chelsea , Paquette Vanessa , Stimpson Rochelle , Abrahams Bethina , Chan Edmond S. , Slayter Kathryn , Rahier Alicia , Sainchuk Irina , Olsen Sharla , Kucey Melissa , Shamseddine Jinan , Babiker Zahir Osman Eltahir , Wong Tiffany
Published: December 2024

Background

Many clinicians feel uncomfortable with de-labelling penicillin allergies despite ample safety data. Point of care tools effectively support providers with de-labelling. This study’s objective was to increase the number of providers intending to pursue a penicillin oral challenge by 15% by February 2023.

Methods

A validated de-labelling algorithm was translated into an electronic point of care tool and disseminated to eight healthcare institutions. Applying the Model for Improvement Framework, three PDSA cycles were conducted, where collected data and completed surveys were analysed to implement changes. Number of providers intending to pursue an oral challenge, tool usage as well as number of clinicians who felt satisfied with the tool and felt confident in its ability to risk-stratify patients was collected.

Results

50.4% of providers intended to give an oral challenge of penicillin with version 1, which improved to 65.5% with version 2, representing a 15.1% increase. With version 1 of the tool, there was an average of 61.3 counts of tool usage per month. 73.1% of providers felt satisfied with the tool and 76.9% felt confident in its ability to risk-stratify patients. With version 2 of the tool, after implementing changes through three PDSA cycles, monthly usage counts increased to an average of 98.6. Furthermore, 100.0% of providers felt satisfied with the tool and 98.1% felt confident with the tool’s ability to risk-stratify patients.

Conclusion

Our quality improvement approach demonstrated improvement in the percentage of providers that intended to pursue an oral challenge and felt satisfied and confident in the risk-stratification capabilities of penicillin allergy de-labelling tool. Electronic tools should be further incorporated into institutional penicillin de-labelling protocols.
Attenuated sex-related DNA methylation differences in cancer highlight the magnitude bias mediating existing disparities
Authors: Zhou Jiaqi , Li Miao , Chen Yu , Wang Shangzi , Wang Danke , Suo Chen , Chen Xingdong
Published: December 2024

Background

DNA methylation (DNAm) influences both sex differences and cancer development, yet the mechanisms connecting these factors remain unclear.

Methods

Utilizing data from The Cancer Genome Atlas, we conducted a comprehensive analysis of sex-related DNAm effects in nine non-reproductive cancers, compared to paired normal adjacent tissues (NATs), and validated the results using independent datasets. First, we assessed the extent of sex differential DNAm between cancers and NATs to explore how sex-related DNAm differences change in cancerous tissues. Next, we employed a multivariate adaptive shrinkage approach to model the covariance of cancer-related DNAm effects between sexes, aiming to elucidate how sex impacts aberrant DNAm patterns in cancers. Finally, we investigated correlations between the methylome and transcriptome to identify key signals driving sex-biased DNAm regulation in cancers.

Results

Our analysis revealed a significant attenuation of sex differences in DNAm within cancerous tissues compared to baseline differences in normal tissues. We identified 3,452 CpGs (Pbonf < 0.05) associated with this reduction, with 72% of the linked genes involved in X chromosome inactivation. Through covariance analysis, we demonstrated that sex differences in cancer are predominantly driven by variations in the magnitude of shared DNAm signals, referred to as “amplification.” Based on these patterns, we classified cancers into female- and male-biased groups and identified key CpGs exhibiting sex-specific amplification. These CpGs were enriched in binding sites of critical transcription factors, including P53, SOX2, and CTCF. Integrative multi-omics analyses uncovered 48 CpG-gene-cancer trios for females and 380 for males, showing similar magnitude differences in DNAm and gene expression, pointing to a sex-specific regulatory role of DNAm in cancer risk. Notably, several genes regulated by these trios were previously identified as drug targets for cancers, highlighting their potential as sex-specific therapeutic targets.

Conclusions

These findings advance our understanding of how sex, DNAm, and gene expression interact in cancer, offering insights into the development of sex-specific biomarkers and precision medicine.
Predictors of intention to stay in the profession among novice nurses: a cross-sectional study
Authors: Savitsky Bella , Shvartsur Rachel , Kagan Ilya
Published: December 2024

Background

Preserving new graduate nurses in the profession is an essential step for addressing the nursing shortage and sustaining the future of the profession. This study aimed to examine the relationship between employment characteristics and job satisfaction of novice nurses and their willingness to stay in the nursing profession in the next 5 years.

Methods

Novice nurses’ intention to stay in the profession was assessed, considering demographics, employment characteristics, and components of job satisfaction. Among the sample of 216 novice nurses (93% response rate), four components of job satisfaction were extracted and included in the multivariable logistic regression model with the intention to stay in the profession as a dependent variable.

Results

Professional self-accomplishment was significantly and positively associated with the intention to stay in the profession, with an elevation of one standard deviation in this component associated with more than a two-fold increase in the odds of staying (OR = 2.3, 95% CI 1.3–3.9). This component contributed 10% to the variance in intention to stay. Independently, managerial support also contributed 10% to the variance and was significantly associated with willingness to stay (OR = 1.9, 95% CI 1.2–3.0). Overall, self-accomplishment, managerial support, and healthier organizational culture were significantly associated with novice nurses’ intention to stay, whereas work conditions and rewards were not. The multivariable analysis model explained 38.0% of the variance in the intention to stay in the profession.

Conclusions

This study found that novice nurses’ intention to stay in the profession is highly associated with their self-accomplishment and better managerial support. Thus, to enhance the retention of novice nurses, managers must establish an environment that fosters professional development and support. This involves providing engaging work assignments, facilitating the seamless integration of novice nurses into the team, and offering managerial support and guidance.
Automated surveillance for surgical site infections (SSI) in hospitals and surveillance networks–expert perspectives for implementation
Authors: Denkel Luisa A. , Arnaud Isabelle , Brekelmans Manon , Puig-Asensio Mireia , Amin Hoger , Gubbels Sophie , Iversen Pernille , Abbas Mohamed , Presterl Elisabeth , Astagneau Pascal , van Rooden Stephanie ,   PRAISE SSI working group, Aghdassi Seven , Düsseldorf Heike , Mertens Karl , van Mourik Maaike S. M. , van der Werff Suzanne D.
Published: December 2024

Background

This work aims at providing practical recommendations for implementing automated surveillance (AS) of surgical site infections (SSI) in hospitals and surveillance networks. It also provides an overview of the steps, choices, and obstacles that need to be taken into consideration when implementing such surveillance. Hands-on experience with existing automated surveillance systems of SSI (AS SSI systems) in Denmark, France, the Netherlands and Spain is described regarding trend monitoring, benchmarking, quality control, and research for surveillance purposes.

Methods

Between April and October 2023, specific aspects/options of various surveillance purposes for AS SSI were identified during regular meetings of the SSI working group in the PRAISE (Providing a Roadmap for Automated Infection Surveillance in Europe) network. Expert discussions provided the basis for this perspective article.

Results

Decisions for implementation of AS SSI systems highly depend on the purpose of the surveillance. AS SSI systems presented here differ according to study population, setting, central or local implementation; the level of automation, design, and the data sources used. However, similarities were found for the rationales of automation, design principles and obstacles that were identified. There was consensus among all the experts that shortcomings in interoperability of databases, limited time, a want of commitment on the part of stakeholders, and a shortage of resources for information technology (IT) specialists represent the main obstacles for implementing AS SSI. To overcome obstacles, various solutions were reported, including training in the development of AS systems and the interpretation of AS SSI results, early consultation of end-users, and regular exchanges between management levels, IT departments, infection prevention and control (IPC) teams, and clinicians.

Conclusion

Clarity on the intended application (e.g. purpose of surveillance) and information on the availability of electronic and structured data are crucial first steps necessary for guiding decisions on the design of AS systems. Adequate resources for IT specialists and regular communication between management, IT departments, IPC teams, and clinicians were identified as essential for successful implementation. This perspective article may be helpful for a wider implementation of more homogeneous AS SSI systems in Europe.
Differential seasonal performance of C3-epi-D3 level and proportion on multiple metabolic disorders in patients with type 2 diabetes mellitus
Authors: Chen Xiaohong , Peng Bi , Ye Wenchun , Wu Bitao , Yang Qiang , Tang Jie , Yang Yuwei
Published: December 2024

Background and aim

Recent Mendelian randomization and meta analysis suggest a controversial causality between C3-epimer of 25 hydroxyvitamin D3 (C3-epi-D3) and type 2 diabetes mellitus (T2DM). The clinical evidence regarding the impact of C3-epi-D3 on the progression of T2DM is currently insufficient. This study aims to investigate whether C3-epi-D3 has any effect on metabolic disorders of T2DM patients.

Methods

A total of 1222 patients with T2DM were prospectively enrolled in this study and followed up every 1 to 2 months for 3 to 6 months. Kidney biomarkers, lipids, electrolytes, and 25 hydroxyvitamin D (25-OHD) metabolites were measured as required during follow-up, to investigate the association of C3-epi-D3 levels and %C3-epi-D3 with metabolic disorders, including dyslipidemia, chronic kidney disease (CKD), and calcium-phosphorus metabolic disorder.

Results

Among these T2DM patients, there were age and seasonal differences in C3-epi-D3 levels (χ2 = 10.419 and 19.609, P = 0.034 and < 0.001), but only seasonal difference in %C3-epi-D3 (χ2 = 79.299, P < 0.001). C3-epi-D3 levels showed an evident correlation with calcium-phosphorus product during autumn and winter (ρ = − 0.336 and − 0.304, both P < 0.001), and was confirmed as an independent factor on calcium-phosphorus metabolic disorder during autumn and winter by subsequent partial correlation analysis (rpartial = − 0.300 and − 0.319, both P < 0.001). Both C3-epi-D3 levels and %C3-epi-D3 showed evident correlation with the severity of chronic kidney disease (CKD) in summer (ρ = 0.344 and 0.445, both P < 0.001). But subsequent multinomial logistic regression confirmed that only %C3-epi-D3 independently associated with moderate CKD severity in summer (OR = 1.348, P < 0.001), as well as serious CKD severity in spring, summer, and autumn (OR = 1.324, 1.342, and 1.698, all P < 0.001). Additionally, no evident correlation was observed between C3-epi-D3 and dyslipidemia.

Conclusion

Our study releases a seasonally differential impact of C3-epi-D3 levels and proportions on metabolic disorders of T2DM patients, considering to be potentially related to their pathogenesis of different metabolic disorders. The independent association between %C3-epi-D3 and CKD suggests a potential pathological relevance involving C3-epi-D3 itself.
Exchange rate pass-through at high and low frequencies in Turkey: a continuous wavelet transform model approach
Authors: Bilgili Faik , Kuşkaya Sevda , Gençoğlu Pelin , Ünlü Fatma , Magazzino Cosimo
Published: December 2024

This paper investigates the effect of the exchange rate on prices through wavelet analysis for the period 2010:01-2019:12 in Turkey. The Wavelet Transform outcomes reveal that at a higher frequency, an upsurge in the Consumer Price Index (CPI) is associated with an increase in the exchange rate, for the period 2011:03-2013:12, and an increase in the exchange rate is accompanied by a higher CPI during the 2015:02-2018:10 period. Moreover, at a lower frequency, an increase in CPI is accompanied by a rise in the exchange rate during the 2014:01-2017:12 period. These results highlight that the pass-through effect is empirically confirmed in Turkey. It is also shown that the power of the pass-through effect might vary from one sub-sample period to another with different frequencies.
Inverting vertical gravity anomaly gradients using multidirectional data from a mean sea surface model: the case of the Arabian Sea
Authors: Zhou Ruichen , Liu Xin , Guo Jinyun , Hwang Cheinway , Jia Yongjun , Chang Xiaotao , Sun Heping
Published: December 2024

Advancements in satellite altimetry have significantly enhanced high-resolution mean sea surface (MSS) models, enabling the computation of high-resolution vertical gravity anomaly gradient (VGAG) models. This study focused on the methodology for computing VGAG models using MSS models, introducing innovative improvements to established techniques. Using the SDUST2020 MSS model within the Arabian Sea research area, the DTU22 and CNES-CLS22 mean dynamic topography (MDT) models, and the XGM2019e_2159 Earth gravity field model for the remove–restore process, the short-wavelength geoid was derived. To harness the extensive marine gravity field information within the MSS model, the study considered the complex marine environment and calculated the second-order derivatives of the geoid in multiple directions. These derivatives were then used to determine their north–south and east–west components through the least squares method, resulting in the computation of the short-wavelength VGAG. By restoring the long-wavelength VGAG, a VGAG model for the study area was established. Finally, the results were analyzed using the SIO V32.1 VGAG model (named curv). Experimental results demonstrated that this approach effectively extracted marine gravity field information from the MSS model using multidirectional data, mitigating the amplification of geoid uncertainties caused by second-order derivatives.

Graphical Abstract
Assessment of MGMT promoter methylation status in glioblastoma using deep learning features from multi-sequence MRI of intratumoral and peritumoral regions
Authors: Yu Xuan , Zhou Jing , Wu Yaping , Bai Yan , Meng Nan , Wu Qingxia , Jin Shuting , Liu Huanhuan , Li Panlong , Wang Meiyun
Published: December 2024

Objective

This study aims to evaluate the effectiveness of deep learning features derived from multi-sequence magnetic resonance imaging (MRI) in determining the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status among glioblastoma patients.

Methods

Clinical, pathological, and MRI data of 356 glioblastoma patients (251 methylated, 105 unmethylated) were retrospectively examined from the public dataset The Cancer Imaging Archive. Each patient underwent preoperative multi-sequence brain MRI scans, which included T1-weighted imaging (T1WI) and contrast-enhanced T1-weighted imaging (CE-T1WI). Regions of interest (ROIs) were delineated to identify the necrotic tumor core (NCR), enhancing tumor (ET), and peritumoral edema (PED). The ET and NCR regions were categorized as intratumoral ROIs, whereas the PED region was categorized as peritumoral ROIs. Predictive models were developed using the Transformer algorithm based on intratumoral, peritumoral, and combined MRI features. The area under the receiver operating characteristic curve (AUC) was employed to assess predictive performance.

Results

The ROI-based models of intratumoral and peritumoral regions, utilizing deep learning algorithms on multi-sequence MRI, were capable of predicting MGMT promoter methylation status in glioblastoma patients. The combined model of intratumoral and peritumoral regions exhibited superior diagnostic performance relative to individual models, achieving an AUC of 0.923 (95% confidence interval [CI]: 0.890 – 0.948) in stratified cross-validation, with sensitivity and specificity of 86.45% and 87.62%, respectively.

Conclusion

The deep learning model based on MRI data can effectively distinguish between glioblastoma patients with and without MGMT promoter methylation.
Regional Hereditary Cancer Program in Chile: A scalable model of genetic counseling and molecular diagnosis to improve clinical outcomes for patients with hereditary cancer across Latin America
Authors: Landeros Natalia , Vargas-Roig Laura , Denita Silvina , Mampel Alejandra , Hasbún Rafael , Araya Hernán , Castillo Iván , Valdes Camila , Flores Marcela , Salter Juan Salgado , Vasquez Katherin , Romero Jacqueline , Pérez-Castro Ramón
Published: December 2024

Background

Breast cancer is a leading cause of cancer-related mortality worldwide, with hereditary forms accounting for approximately 10% of cases. In Chile, significant gaps exist in genetic counseling and testing, particularly within the public health system. This study presents the implementation and outcomes of the first regional hereditary cancer program in the Maule region of Chile, aimed at improving detection and management of hereditary breast cancer.

Methods

A cohort of 48 high-risk breast cancer patients from the Hospital Regional de Talca received genetic counseling and underwent Next-Generation Sequencing multigene panel testing. The program was established through collaboration between multiple institutions, leveraging telemedicine and outsourcing sequencing analysis to address regional gaps.

Results

Pathogenic or likely pathogenic variants were identified in 12% of patients, including in BRCA1, BRCA2, TP53, and PALB2. Notably, novel pathogenic variants in BRCA1 (rs80357505) and TP53 (rs1131691022) were discovered, highlighting the unique genetic landscape of the Chilean population. Additionally, 70 variants of uncertain significance were found across 42 genes, particularly in FAN1, MSH6, and FANCI, underscoring the need for further research. The program’s collaborative approach effectively bridged critical gaps in genetic services, providing high-quality care within the public health system despite limited resources.

Conclusions

The Regional Hereditary Cancer Program addresses significant gaps in genetic counseling and testing in Chile’s public health system. This scalable model enhances early detection and personalized treatment for hereditary cancer patients and could be adapted to other regions across Latin America.
Option value, investment costs and deployment levels of smart grid technologies
Authors: Giannelos Spyros , Borozan Stefan , Konstantelos Ioannis , Strbac Goran
Published: December 2024

The global effort to mitigate the effects of climate change has triggered the need for significant changes in electricity grids, including the deployment of smart grid technologies. This paper explores key smart grid economics such as the investment cost of smart technologies, their level of deployment in the grid, as well as their option value. An extensive sensitivity analysis carried out using a stochastic optimization model studies how the investment cost affects the level of deployment of smart grid technologies and their option value. The analysis focuses on smart technologies, including the soft open point, smart charging of electric vehicles, dynamic line rating, energy storage, and soft open point. The results demonstrate an inverse relationship between the option value of smart technologies, the investment cost as well as the extent of conventional network reinforcement, underscoring the trade-offs in economic decision-making for energy systems.
Exploring trauma and resilience of Urban South Sudanese refugees in Sudan
Authors: Bashir Shima , Eltayeb Shahla , Badri Alia
Published: December 2024

This study aims to explore the lived experiences of South Sudanese refugees in White Nile state, Sudan, focusing on the impact of pre-refugee life, war-related trauma, and current camp conditions on their mental health. Additionally, it aims to emphasize the strategies used by refugees to cope with challenges and highlight deficiencies in services offered by humanitarian agencis. The study used a qualitative analysis approach and conducted in-depth interviews with 15 refugees from South Sudan residing in White Nile State refugee camps in Sudan. Participants were recruited from the two refugee camps, ensuring diversity in age and gender. All focus group discussions were audio-recorded, and detailed transcripts were generated. The transcribed data were subjected to thematic analysis. The investigation revealed a number of patterns. First, participants recalled a pre-refugee life marked by safety, joy, and community cohesion, which sharply contrasted with their subsequent experiences of violence and displacement. Furthermore, refugees have conveyed substantial psychological distress resulting from their exposure to violence, suffering physical mistreatment, and the loss of their dear ones. These experiences have left profound psychological trauma and feelings of anxiety. Furthermore, the existing circumstances in the refugee camps intensified their psychological distress, as they faced challenges in having access to basic needs, job, schooling, and preserving their cultural traditions. Coping strategies of the refugees predominantly relied on cultural practices, family support, and religious prayer. By incorporating refugees’ resilience and community engagement as factors that promote long-term stability in South Sudanese refugee communities, this study underscores the urgent need for humanitarian organizations to redesign a more holistic approach that includes immediate mental health needs, socioeconomic factors, educational accessibility, and gainful employment. Ultimately, this study advocates a paradigm shift in humanitarian efforts to prioritize mental health services for refugees by addressing the interlinked nature of mental health and broader socioeconomic factors.
Development and evaluation of deuterated [18F]JHU94620 isotopologues for the non-invasive assessment of the cannabinoid type 2 receptor in brain
Authors: Gündel Daniel , Maqbool Mudasir , Teodoro Rodrigo , Ludwig Friedrich-Alexander , Heerklotz Anne , Toussaint Magali , Deuther-Conrad Winnie , Bormans Guy , Brust Peter , Kopka Klaus , Moldovan Rareş-Petru
Published: December 2024

Background

The cannabinoid type 2 receptors (CB2R) represent a target of increasing importance in neuroimaging due to its upregulation under various neuropathological conditions. Previous evaluation of [18F]JHU94620 for the non-invasive assessment of the CB2R availability by positron emission tomography (PET) revealed favourable binding properties and brain uptake, however rapid metabolism, and generation of brain-penetrating radiometabolites have been its main limitations. To reduce the bias of CB2R quantification by blood–brain barrier (BBB)-penetrating radiometabolites, we aimed to improve the metabolic stability by developing -d4 and -d8 deuterated isotopologues of [18F]JHU94620.

Results

The deuterated [18F]JHU94620 isotopologues showed improved metabolic stability avoiding the accumulation of BBB-penetrating radiometabolites in the brain over time. CB2R-specific binding with KD values in the low nanomolar range was determined across species. Dynamic PET studies revealed a CB2R-specific and reversible uptake of [18F]JHU94620-d8 in the spleen and to a local hCB2R(D80N) protein overexpression in the striatal region in rats.

Conclusion

These results support further investigations of [18F]JHU94620-d8 in pathological models and tissues with a CB2R overexpression as a prerequisite for clinical translation.
Merits of 18F-FDG PET/CT metabolic tumor volume for prediction of occult axillary lymph node metastasis in luminal early breast cancer patients with clinical and radiologically negative axilla
Authors: Sayed Mohamed H. M. , Tawfik Ahmed Ibrahim , Mohamadien Nsreen R. A.
Published: December 2024

Background

To see if pre-treatment 18F-FDG PET/CT metabolic tumor volume (MTV) might predict occult axillary lymph node metastases (ALNM) in luminal early breast cancer (BC) with negative axilla on clinical examination, radiological studies, and conventional 18F-FDG PET/CT interpretation.

Methods

Out of 330 consecutive patients with early BC who were referred for preoperative staging, only 110 female patients with luminal early BC who had biopsy-proven axillary lymph node (ALN) status and negative axilla on clinical examination, radiological studies, and conventional 18F-FDG PET/CT interpretation, were eligible for analysis. Maximum standardized uptake value (SUVmax), SUVmean, MTV, total lesion glycolysis (TLG), and clinicopathological features were determined. Via ROC analysis, we determined the optimal cutoff values for SUVmax, SUVmean, MTV, and TLG of the primary tumor to predict ALNM. Univariate and multivariate regression analyses were performed to identify the most potent PET metabolic parameters to predict ALNM.

Results

Pathologic ALNM was identified in 29.1% of cases; 40.6% of them had lymphovascular invasion (LVI) compared to 9% of the ALN-negative group (P < 0.0001). The median MTV of tumors with ALNM was significantly higher than that of the ALN-negative group (P = 0.049). The best cutoff value of MTV was > 4.83. In univariate analysis, MTV (P = 0.005) and LVI (P < 0.0001) were significantly associated with ALNM, and in multivariate analysis, both MTV (P = 0.002) and LVI (P < 0.0001) were confirmed to be independent predictors for ALNM.

Conclusions

In early luminal BC with clinically and radiologically negative axilla, including negative conventional interpretation of PET/CT, the inclusion of MTV has an added value in predicting ALNM.
Effect of platelet-rich plasma on recurrence of sinonasal polyps after endoscopic sinus surgery: a randomized clinical trial
Authors: Samiea Alaa Mohamed Abd El , Elkady Ahmed Soliman , Elnagdy Ahmed Abdelrahman Ibrahim , Ghallab Abdelhakim Foaad
Published: December 2024

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory condition that often requires surgical intervention. Despite advances in endoscopic sinus surgery (ESS), recurrence rates remain significant. Platelet-rich plasma (PRP), known for its regenerative properties, has been suggested to reduce inflammation and promote healing.

Methodology

This prospective randomized controlled clinical trial was carried out on 40 patients which aims to evaluate the effectiveness of PRP in reducing the recurrence and healing of sinonasal polyps after functional endoscopic sinus surgery (FESS) after 6 months follow-up. Patients aged over 18 years and under 60 years old, with more than 3 months of CRS symptoms with endoscopic evidence of polyps and/or mucosal changes on a CT scan were included in our study. Previous sinus surgery, systemic vasculitis, immune deficiency, allergic fungal rhinosinusitis, patients with uncontrolled systemic diseases or coagulopathy, history of asthma, aspirin sensitivity, cystic fibrosis, and congenital mucociliary problems were excluded from our study.

Results

Both groups showed improvement in Lund-Kennedy scores and SNOT-22 scores postoperatively. However, Group 1 demonstrated significantly greater improvement at 3 months (median Lund-Kennedy score: 4.0 vs. 6.0, p < 0.001) and 6 months (median Lund-Kennedy score: 4.5 vs. 6.0, p < 0.001) compared to Group 2. Additionally, the percent change in Lund-Kennedy scores was significantly higher in Group 1 (median 40.18% vs. 14.29%, p < 0.001). Group 1 also exhibited a substantial reduction in SNOT-22 scores at 6 months (median score: 7.0 vs. 45.0, p < 0.001) with a higher median percent change (90.91% vs. 43.65%, p < 0.001). Notably, relapse rates were lower in Group 1 (15.0%) compared to Group 2 (50.0%) at 6 months (p = 0.018).

Conclusions

PRP injection during FESS significantly reduces the recurrence of sinonasal polyps and improves clinical outcomes in patients with CRSwNP. These findings suggest PRP as a promising adjunctive treatment to enhance surgical outcomes and reduce healthcare burdens associated with recurrent sinonasal polyposis.
Epidemiological surveillance and economic impact analysis of different porcine reproductive and respiratory syndrome virus infection statuses in 23 breeding pig farms in Hubei, China
Authors: Zhao Huifeng , Zhou Jingwei , Zhang Min , Yang Xiutao , Xi Zhaofang , Gao Qingxia , Fang Rui , Zhao Pengfei , Zhao Junlong
Published: December 2024

Porcine reproductive and respiratory syndrome virus (PRRSV) has emerged as a significant threat to the pig farming industry worldwide, resulting in considerable economic losses. However, few reports detail its economic impact on the pig farming sector. A study was conducted on 23 breeding pig farms in Hubei Province from January 2021 to December 2023, and the PRRSV infection status and associated economic losses were monitored to address this gap. PRRSV antigens and antibodies were identified through enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Additional monthly production data and weaning costs were gathered. The Kruskal-Wallis nonparametric test was used to assess the differences in production efficiency and weaning costs across various PRRSV infection statuses. Dunn’s test was used to compare multiple groups. The parameter distributions of various variables were determined via @RISK (V. 8.5.2) software. Models were developed to evaluate the economic impact of PRRSV infection status on breeding pig farms and assess the losses from a PRRSV outbreak in either provisional PRRSV-negative or PRRSV-positive stable farms. A total of 754 months of monitoring was conducted across 23 breeding pig farms, which included 131 months (17.37%) classified as PRRSV provisional negative, 298 months (39.52%) as PRRSV-positive stable, and 325 months (43.11%) as PRRSV-positive unstable. The production efficiency and weaning costs were similar between provisional PRRSV-negative farms and PRRSV-positive stable farms, revealing no significant differences. However, these metrics varied significantly compared with those of PRRSV-positive unstable farms. With respect to provisional PRRSV-negative farms, PRRSV-positive stable farms and unstable farms faced additional annual losses of ¥3,135.17 and ¥4,898.79 per sow, respectively. Compared with PRRSV-positive stable farms, PRRSV-positive unstable farms incurred an extra annual loss of ¥1,763.62 per sow. Upon a PRRSV outbreak on a swine farm, followed by a return to preoutbreak conditions, the average economic loss per sow on provisional PRRSV-negative farms is approximately ¥3,061.21. Conversely, PRRSV-positive stable farms face an average loss of approximately ¥508.42 per sow. This study provides a systematic evaluation of the economic impact of PRRSV on Chinese pig farms, offering data to support the quantitative assessment of economic losses stemming from PRRSV within the domestic pig farming industry.
Epidemiological study of lamb and kid morbidity and mortality rates and associated risk factors in an extensive management system in the Dalocha district, Silte Zone, Central Ethiopia
Authors: Anwar Redwan , Abebe Rahmeto , Sheferaw Desie
Published: December 2024

Small ruminants are vital to the economy of Ethiopia and significantly contribute to the livelihoods of resource-poor farmers. However, poor management practices and high mortality rates among young lambs and kids have hindered their economic potential. A prospective cohort study was conducted in three rural villages in Dalocha district with the aim of estimating morbidity and mortality rates among these animals and identifying associated risk factors. The study monitored 130 lambs and kids every 15 days from birth to three months and recorded health events and deaths. Data analysis utilized Kaplan‒Meier survival analysis, log-rank tests, and multivariate Cox proportional hazard regression. The results revealed an overall morbidity rate of 0.58 and a mortality rate of 0.2 cases per 100 lamb days at risk for lambs, whereas the rates of morbidity and mortality for kids were 0.27 and 0.1 cases per 100 kid days, respectively. Respiratory issues were the leading health problem, accounting for 35.9% of morbidity cases, whereas diarrhea accounted for 38.5% of deaths. The hazard of morbidity was 2.1 times greater for lambs than for kids (HR = 2.1; p = 0.039). Additionally, the morbidity hazard was significantly greater in lambs and kids from multiparous dams (HR = 3.8, p = 0.017) but 89% lower in vaccinated flocks (HR = 0.11, p = 0.001). The identified risk factors for mortality included litter size and maternal behavior. Twin-born lambs and kids presented a mortality hazard that was 6.31 times greater than that of singletons (HR = 6.31; p = 0.025), whereas offspring from dams with poor mothering presented a mortality hazard that was more than 24 times greater (HR = 24.56; p = 0.006) than that of offspring from normal mothers. This study underscores the need for improved maternal care, access to colostrum, better bonding, and suitable environments for multiple births to reduce morbidity and mortality rates among lambs and kids. Further research into the specific causes of these issues is recommended.
Short and long-term outcome of levamisole in early versus late steroid responsive nephrotic syndrome: A single centre experience
Authors: Saima Kashif  , Khemchand N Moorani
Published: December 2024

Objectives: To determine the effectiveness of Levamisole (Leva) in maintaining short-term and long-term remission in early steroid responders (ESRs) and late steroid responders (LSRs).
Methods: This retrospective study on 106 cohorts, aged 2-14 years with frequent-relapsing (FR) and steroid-dependent nephrotic syndrome (SDNS) who received Leva over 10-years (2012-2023), was carried out at tertiary care centre, Karachi from January-August 2023. Patients were categorized based on steroid response during first episode of NS as ESRs if complete remission (CR) was achieved within two weeks of daily steroid and LSRs if CR achieved between two-four weeks. Leva was administered after inducing remission with daily steroid after labelling as FRNS and SDNS. Low-dose steroid was continued during Leva-therapy. Short-term outcome was assessed at completion of Leva and long-term outcome in terms of CR, relapse frequency, alternative immunosuppressive agents (ISAs) use and compliance was assessed at six, 12 and 36-months’ follow-up while off levamisole therapy.
Results: Leva was used in 106 patients (male 67%) for 20.4±8months during the study period. The mean age at Leva-initiation was 6.3±3 years. Eighty-three were FRNS and 23 SDNS. ESRs were 64 and 42 were LSRs. Overall, Leva was effective in maintaining short-term CR (73%) at end of Leva and it was effective in both ESRs (75%) and LSRs (69%, p=0.51) as well as in FRNS (72%) and SDNS (74%), P=0.08). Post-Leva follow-up duration was 36±31 months. Long-term Leva was effective in both ESRs and LSRs (p=0.51). Complete remission in 22,17 and 26%; infrequent relapses in 50,40 and 5% and alternate ISAs use in 24,39 and 55% at six,12 and 36 months follow-up respectively.
Conclusion: Levamisole was effective in maintaining short-term and long-term remission in early and late initial steroid responsive nephrotic syndrome.
doi: https://doi.org/10.12669/pjms.41.1.10184
How to cite this: Kashif S, Moorani KN. Short and long-term outcome of levamisole in early versus late steroid responsive nephrotic syndrome: A single centre experience. Pak J Med Sci. 2025;41(1):64-70. doi: https://doi.org10.12669/pjms.41.1.10184
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Prophylactic vs therapeutic blood transfusions impact on pregnant sickle cell patients
Authors: Imran Iffat , Nazir Imran , J Al Rfaai Rakan Tariq , Khalil Khalid
Published: December 2024

Objective: To observe the fetomaternal outcome of therapeutic versus prophylactic blood transfusions in patients with sickle cell disease (SCD) during pregnancy.
Method: This single-center retrospective observational study was conducted on consecutive pregnant women with SCD between January 2018 and December 2020. All the pregnant women with SCD were included in this study. Sickler women carrying sickle cell traits (HbAS, HbAC), multiple pregnancy, or other medical diseases were excluded from the study. We used non-random, convenience sampling and collected their demographic details, medical history, course of SCD before & during pregnancy, maternal/fetal outcome, laboratory parameters, and other information using the questionnaire. Patients were sub-grouped into three according to blood transfusion categories (therapeutic, prophylactic, or not transfused) during the pregnancy. Descriptive data were represented as numbers and mean ± SD values. The medical and obstetrical complications and fetomaternal outcomes among the three groups were analyzed by Chi-square/Fisher’s Extract test.
Results: The study included 62 patients, 37 were in the therapeutic group, 11 were in the prophylactic group, and 14 were in the non-transfusion group. Hemolytic crises, painful crises, acute chest syndrome, pregnancy-induced hypertension (PIH), preeclampsia, preterm births, intrauterine growth retardation (IUGR), and neonatal ICU admission were significantly lower among the prophylactic group (P = 0.000, p = 0.000, p = 0.001, p = 0.002, p = 0.009, p = 0.007, p =0.001 & p= 0.016 respectively) compared with other two groups.
Conclusions: Our study demonstrates that prophylactic blood transfusion in SCD positively alters the course of pregnancy by reducing fetomaternal complications.
doi: https://doi.org/10.12669/pjms.41.1.9783
How to cite this: Imran I, Nazir I, Al Rfaai RTJ, Khalil K. Prophylactic vs therapeutic blood transfusions impact on pregnant sickle cell patients. Pak J Med Sci. 2025;41(1):44-48. doi: https://doi.org/10.12669/pjms.41.1.9783
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Omega-3 long chain fatty acids and their metabolites in pregnancy outcomes for the modulation of maternal inflammatory- associated causes of preterm delivery, chorioamnionitis and preeclampsia
Authors: Regidor Pedro Antonio , Eiblwieser Johanna , Steeb Theresa , Rizo Jose Miguel
Published: December 2024

Preterm birth is a major cause of perinatal complications and neonatal deaths. Furthermore, in the field of obstetrics many clinical entities like uterine contractions or the occurrence of pre- eclampsia remain to be serious complications during pregnancy and represent a major psychological, financial, and economic burden for society. Several published guidelines, studies and recommendations have highlighted the importance of supplementation of omega-3 long chain polyunsaturated fatty acids (PUFAs) during pregnancy. This narrative review aims at giving an overview on the modern perception of inflammatory processes and the role of specialized pro-resolving mediators (SPMs) in their resolution, especially in obstetrics. Additionally, we highlight the possible role of SPMs in the prevention of obstetric complications through oral supplementation using enriched marine oil nutritional’s. The intake of PUFAs may result in an overall improvement of pregnancy outcomes by contributing to fetal brain growth and neurological development but more importantly though modulation of inflammation-associated pathologies. Especially the use of SPMs represents a promising approach for the management of obstetric and perinatal complications. SPMs are monohydroxylates derived from enriched marine oil nutritional’s that involve certain pro-resolutive metabolites of omega-3 long chains PUFAs and may contribute to an attenuation of inflammatory diseases. This may be obtained through various mechanisms necessary for a proper resolution of inflammation such as the termination of neutrophil tissue infiltration, initiation of phagocytosis, downregulation of pro-inflammatory cytokines or tissue regeneration. In this way, acute and chronic inflammatory diseases associated with serious obstetrical complications can be modulated, which might contribute to an improved pregnancy outcome.