bluuebunny/crossref_metadata_2025 huggingface dataset:
Public deliberation to assess patient views on biosimilar medication switching for the treatment of inflammatory bowel disease
Authors: Ryan Kerry A. , Cohen-Mekelburg Shirley , Baker Jessica A. , Weinheimer-Haus Eileen M. , Krenz Chris , Hou Jason K. , De Vries Raymond , Waljee Akbar K.
Published: October 2024

Background

Biosimilars are highly similar, but not identical, versions of originator biologic medications. Switching patients to biosimilars presents an opportunity to mitigate rising drug costs and expand patient access to important biologic therapies. However, decreased patient acceptance and adherence to biosimilar medications have been reported, which can lead to loss of treatment response, adverse reactions, and inefficient resource utilization. Understanding patient perceptions of biosimilars and biosimilar switching is needed to inform patient-centered care strategies that promote efficient resource utilization.

Methods

We used democratic deliberation methods to solicit the informed and considered opinions of patients regarding biosimilar switching. Patients with inflammatory bowel disease (IBD; n = 29) from the Veterans Health Administration (VHA) participated in 5-hour deliberation sessions over two days. Following educational presentations with experts, participants engaged in facilitated small group discussions. Transcripts and facilitators’ notes were used to identify key themes. Participants completed surveys pre- and post-deliberation to collect sociodemographic and clinical features as well as to assess IBD treatment knowledge and attitudes toward care and approaches to biosimilar switching.

Results

Five major themes emerged from the small group discussions in the context of biosimilar switching: 1) concerns about adverse consequences and unclear risk-benefit balance; (2) importance of communication and transparency; (3) desire for shared decision making and patient involvement in treatment decisions; (4) balancing cost-saving with competing priorities; and (5) advocating for individualized care and prioritization based on risk levels. These views led participants to favor approaches that prioritize switching the sickest patients last (i.e., those with poorly controlled disease) and that offer patients control and choices around biosimilar switching. Participants also expressed preferences for combining elements of different approaches to maximize fairness.

Conclusions

Approaches to biosimilar switching should consider patients’ desires for transparency and effective communication about biosimilar switching and engagement in their medical decision-making as part of patient-centered care. Incorporating patient preferences around biosimilar switching is critical when navigating the quality and affordability of care in resource constrained settings, both within the VHA and in other healthcare systems.
Treatment patterns and patient journey in progressive pulmonary fibrosis: a cross-sectional survey
Authors: Chaudhuri Nazia , Spagnolo Paolo , Valenzuela Claudia , Amatto Valeria C. , Carter Oliver-Thomas , Lee Lauren , Small Mark , Kreuter Michael
Published: October 2024

Background

For patients with interstitial lung diseases (ILDs) presenting with a progressive pulmonary fibrosis (PPF) phenotype, current knowledge of disease characteristics at diagnosis, patient journey, and treatment is limited. This study aimed to describe demographics and clinical experiences of patients presenting with PPF in a European real-world setting.

Methods

Data were analysed from the Adelphi Real World PPF-ILD Disease Specific Programme™, a cross-sectional survey of pulmonologists and rheumatologists in five European countries (France, Germany, Italy, Spain, United Kingdom) and internal medicine specialists (France) from April to October 2022. Physicians provided data for up to 12 consecutive patients with physician-confirmed ILD with a progressive phenotype other than idiopathic pulmonary fibrosis. Analyses were descriptive.

Results

Overall, 265 physicians reported on 1,335 patients. Mean (standard deviation) age at survey date was 60.4 (11.6) years, 91.2% were white, 58.1% female, 44.0% non-smokers. Most patients (63.3%) first consulted a primary care physician. There was a mean delay of 7.8 (22.7) months between first ILD symptom and healthcare professional visit, and another 7.7 (12.8) months to ILD diagnosis. At survey date, 47.7% of patients had physician-reported moderate ILD, 42.3% had mild ILD and 10.0% had severe ILD. Disease progression was reported in the 12 months prior to the survey for 19.5% of patients; of these, progression was based on worsening symptom in 27.3% and lung function decline in 25.8%. For patients experiencing symptoms prior to ILD diagnosis (72.8%), the most common symptoms were dyspnoea on exertion (80.5%) and cough (57.8%). Overall, 17.4% of patients were misdiagnosed prior to ILD diagnosis, with chronic obstructive pulmonary disease suspected in 39.2% of them. The most frequent comorbidities were anxiety (16.9%) and gastroesophageal reflux (15.5%). Although 77.8% of patients were receiving treatment for ILD at survey date, 15.6% of patients had never been prescribed treatment for ILD.

Conclusions

This real-world study expands our understanding of patients, diagnostic delays and treatment gaps experienced by patients diagnosed with PPF in Europe. There was a mean delay of 15.5 months between first ILD symptoms and ILD diagnosis. Given the progressive nature of PPF, diagnostic delay may lead to poor outcomes, including shorter survival.

Trial registration

N/a.
The relationship between repeated measurements of HbA1c and risk of coronary events among the common haptoglobin phenotype groups: the Action for Health in Diabetes (Look AHEAD) study
Authors: Carew A. S. , Warren R. A. , Bancks M. P. , Espeland M. A. , Bahnson J. L. , Lewis C. L. , Levy A. P. , Sapp J. L. , Urquhart R. , Wang J. L. , Rimm E. B. , Cahill L. E.
Published: October 2024

Background

In the ACCORD study, participants with the haptoglobin (Hp) 2–2 phenotype and glycated hemoglobin (HbA1c) ≥ 8.0% had a higher risk of coronary artery disease (CAD) compared to those with HbA1c 7.0–7.9%. However, this association was not observed in participants without the Hp2-2 phenotype. The optimal glycemic target for CAD prevention for the Hp phenotypes remains uncertain and may vary based on demographic and clinical factors.

Objective

To investigate how reaching clinically relevant HbA1c targets relates to the risk of CAD in different Hp phenotype groups among a diverse cohort of individuals with T2DM (the Look AHEAD study, HbA1c ≤ 11% at baseline).

Methods

Cox regression models with time-varying covariables were used to quantify the association between time-varying achieved HbA1c (< 6.5%, 6.5–6.9%, and ≥ 8.0% compared to 7.0-7.9%), updated at years 1–4, 6, 8, and 10, and incident CAD in the Hp2-2 (n = 1,587) and non-Hp2-2 (n = 2,944) phenotypes separately. Further pre-specified subgroup analyses by age, sex, history of cardiovascular disease (CVD), race, and diabetes duration were performed in each Hp phenotype group separately.

Results

Compared with HbA1c 7.0-7.9%, having HbA1c < 6.5% was associated with a 29% lower CAD risk among participants with the non-Hp2-2 phenotype (adjusted HR 0.71, 95% CI 0.55–0.90). In subgroup analyses, this association was present in participants with the non-Hp2-2 phenotype who were male (0.60, 0.44–0.83), who did not have a history of CVD (0.65, 0.47–0.90), who were aged ≥ 65 years (0.64, 0.44–0.94), who were White (0.68, 0.51–0.91), or who had diabetes duration > 10 years (0.58, 0.35–0.95). HbA1c ≥ 8.0% was associated with CAD risk only among participants with the Hp2-2 phenotype who had a history of CVD (1.79, 1.00-3.20). No associations were found between the other HbA1c targets and CAD risk when participants with the Hp2-2 phenotype were grouped together or divided into subgroups.

Conclusion

The differences in our results compared to our previous findings may be due to variations in the study populations and factors associated with weight loss, making it difficult to draw definitive conclusions. Our current findings should be considered in the context of hypothesis generation, and ideally, will encourage additional research in this field.
Plasma-derived extracellular vesicles miR-335–5p as potential diagnostic biomarkers for fusion-positive rhabdomyosarcoma
Authors: Di Paolo Virginia , Paolini Alessandro , Galardi Angela , Gasparini Patrizia , De Cecco Loris , Colletti Marta , Lampis Silvia , Raieli Salvatore , De Stefanis Cristiano , Miele Evelina , Russo Ida , Di Ruscio Valentina , Casanova Michela , Alaggio Rita , Masotti Andrea , Milano Giuseppe Maria , Locatelli Franco , Di Giannatale Angela
Published: October 2024

Background

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma, with embryonal (ERMS) and alveolar (ARMS) representing the two most common histological subtypes. ARMS shows poor prognosis, being often metastatic at diagnosis. Thus, the discovery of novel biomarkers predictive of tumor aggressiveness represents one of the most important challenges to overcome and may help the development of tailored therapies. In the last years, miRNAs carried in extracellular vesicles (EVs), small vesicles of endocytic origin, have emerged as ideal candidate biomarkers due to their stability in plasma and their tissue specificity.

Methods

EVs miRNAs were isolated from plasma of 21 patients affected by RMS and 13 healthy childrens (HC). We performed a miRNA profile using the Serum/Plasma Focus microRNA PCR panels (Qiagen), and RT-qPCR for validation analysis. Statistically significant (p < 0.05) miRNAs were obtained by ANOVA test.

Results

We identified nine EVs miRNAs (miR-483-5p, miR-132-3p, miR-766-3p, miR-454-3p miR-197-3p, miR-335-3p, miR-17-5p, miR-486-5p and miR-484) highly upregulated in RMS patients compared to HCs. Interestingly, 4 miRNAs (miR-335-5p, miR-17-5p, miR-486-5p and miR-484) were significantly upregulated in ARMS samples compared to ERMS. In the validation analysis performed in a larger group of patients only three miRNAs (miR-483-5p, miR-335-5p and miR-484) were differentially significantly expressed in RMS patients compared to HC. Among these, mir-335-5p was significant also when compared ARMS to ERMS patients. MiR-335-5p was upregulated in RMS tumor tissues respect to normal tissues (p = 0.00202) and upregulated significantly between ARMS and ERMS (p = 0.04). Furthermore, the miRNA expression correlated with the Intergroup Rhabdomyosarcoma Study (IRS) grouping system, (p = 0.0234), and survival (OS, p = 0.044; PFS, p = 0.025). By performing in situ hybridization, we observed that miR-335-5p signal was exclusively in the cytoplasm of cancer cells.

Conclusion

We identified miR-335-5p as significantly upregulated in plasma derived EVs and tumor tissue of patients affected by ARMS. Its expression correlates to stage and survival in patients. Future studies are needed to validate miR-335-5p as prognostic biomarker and to deeply elucidate its biological role.
DNA demethylation triggers cell free DNA release in colorectal cancer cells
Authors: Pessei Valeria , Macagno Marco , Mariella Elisa , Congiusta Noemi , Battaglieri Vittorio , Battuello Paolo , Viviani Marco , Gionfriddo Giulia , Lamba Simona , Lorenzato Annalisa , Oddo Daniele , Idrees Fariha , Cavaliere Alessandro , Bartolini Alice , Guarrera Simonetta , Linnebacher Michael , Monteonofrio Laura , Cardone Luca , Milella Michele , Bertotti Andrea , Soddu Silvia , Grassi Elena , Crisafulli Giovanni , Bardelli Alberto , Barault Ludovic , Di Nicolantonio Federica
Published: October 2024

Background

Liquid biopsy based on cell-free DNA (cfDNA) analysis holds significant promise as a minimally invasive approach for the diagnosis, genotyping, and monitoring of solid malignancies. Human tumors release cfDNA in the bloodstream through a combination of events, including cell death, active and passive release. However, the precise mechanisms leading to cfDNA shedding remain to be characterized. Addressing this question in patients is confounded by several factors, such as tumor burden extent, anatomical and vasculature barriers, and release of nucleic acids from normal cells. In this work, we exploited cancer models to dissect basic mechanisms of DNA release.

Methods

We measured cell loss ratio, doubling time, and cfDNA release in the supernatant of a colorectal cancer (CRC) cell line collection (N = 76) representative of the molecular subtypes previously identified in cancer patients. Association analyses between quantitative parameters of cfDNA release, cell proliferation, and molecular features were evaluated. Functional experiments were performed to test the impact of modulating DNA methylation on cfDNA release.

Results

Higher levels of supernatant cfDNA were significantly associated with slower cell cycling and increased cell death. In addition, a higher cfDNA shedding was found in non-CpG Island Methylator Phenotype (CIMP) models. These results indicate a positive correlation between lower methylation and increased cfDNA levels. To explore this further, we exploited methylation microarrays to identify a subset of probes significantly associated with cfDNA shedding and derive a methylation signature capable of discriminating high from low cfDNA releasers. We applied this signature to an independent set of 176 CRC cell lines and patient derived organoids to select 14 models predicted to be low or high releasers. The methylation profile successfully predicted the amount of cfDNA released in the supernatant. At the functional level, genetic ablation of DNA methyl-transferases increased chromatin accessibility and DNA fragmentation, leading to increased cfDNA release in isogenic CRC cell lines. Furthermore, in vitro treatment of five low releaser CRC cells with a demethylating agent was able to induce a significant increase in cfDNA shedding.

Conclusions

Methylation status of cancer cell lines contributes to the variability of cfDNA shedding in vitro. Changes in methylation pattern are associated with cfDNA release levels and might be exploited to increase sensitivity of liquid biopsy assays.
Transposable Element (TE) insertion predictions from RNAseq inputs and TE impact on RNA splicing and gene expression in Drosophila brain transcriptomes
Authors: Azad Md Fakhrul , Tong Tong , Lau Nelson C.
Published: October 2024

Recent studies have suggested that Transposable Elements (TEs) residing in introns frequently splice into and alter primary gene-coding transcripts. To re-examine the exonization frequency of TEs into protein-coding gene transcripts, we re-analyzed a Drosophila neuron circadian rhythm RNAseq dataset and a deep long RNA fly midbrain RNAseq dataset using our Transposon Insertion and Depletion Analyzer (TIDAL) program. Our TIDAL results were able to predict several TE insertions from RNAseq data that were consistent with previous published studies. However, we also uncovered many discrepancies in TE-exonization calls, such as reads that mainly support intron retention of the TE and little support for chimeric mRNA spliced to the TE. We then deployed rigorous genomic DNA-PCR (gDNA-PCR) and RT-PCR procedures on TE-mRNA fusion candidates to see how many of bioinformatics predictions could be validated. By testing a w1118 strain from which the deeper long RNAseq data was derived and comparing to an OreR strain, only 9 of 23 TIDAL candidates (< 40%) could be validated as a novel TE insertion by gDNA-PCR, indicating that deeper study is needed when using RNAseq data as inputs into current TE-insertion prediction programs. Of these validated calls, our RT-PCR results only supported TE-intron retention. Lastly, in the Dscam2 and Bx genes of the w1118 strain that contained intronic TEs, gene expression was 23 times higher than the OreR genes lacking the TEs. This study's validation approach indicates that chimeric TE-mRNAs are infrequent and cautions that more optimization is required in bioinformatics programs to call TE insertions using RNAseq datasets.
Proteomics analysis reveals the differential protein expression of female and male adult Toxocara canis using Orbitrap Astral analyzer
Authors: Qiu Hui-Jie , Zhou Ya-Jia , Li Zhi-Yu , Lv Yi-Han , Zhu Xing-Quan , Zheng Wen-Bin
Published: October 2024

Background

Toxocara canis, the most prevalent helminth in dogs and other canines, is one of the socioeconomically important zoonotic parasites, particularly affecting pediatric and adolescent populations in impoverished communities. However, limited information is available regarding the proteomes of female and male adult T. canis. To address this knowledge gap, we performed a comprehensive proteomic analysis to identify the proteins with differential abundance (PDAs) and gender-specifically expressed proteins between the two sexes adult T. canis.

Methods

The comparative proteomic analysis was carried out by the Orbitrap mass spectrometry (MS) with asymmetric track lossless (Astral) analyzer. The difference analysis was conducted using t-test and the proteins verification was achieved through parallel reaction monitoring (PRM). The potential biological functions of identified adult T. canis proteins and PDAs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The domain, transcription factor and subcellular localization of the identified proteins and PDAs were analyzed by InterPro, AnimalTFDB 4.0 and Cell-mPLOC 2.0 databases, respectively.

Results

A total of 8565 somatic proteins of adult T. canis were identified. Compared to male adult, 682 up-regulated PDAs and 844 down-regulated PDAs were identified in female adult with P-values < 0.05 and |log2FC| > 1, including 139 proteins exclusively expressed in female and 272 proteins exclusively expressed in male. The GO annotation analysis using all PDAs revealed that the main biological processes, cellular components and molecular functions corresponded to aminoglycan metabolic process, extracellular region and protein tyrosine phosphatase activity, respectively. The KEGG analysis using all PDAs showed that the pathways were mainly associated with adipocytokine signaling pathway, proximal tubule bicarbonate reclamation and PPAR signaling pathway.

Conclusions

This study reveals the differential protein expression between female and male adult T. canis, providing valuable resource for developing the novel intervention strategies against T. canis infection in humans and animals, especially from the perspective of sexual development and reproduction.

Graphical abstract
Skin-permeable gold nanoparticles with modifications azelamide monoethanolamine ameliorate inflammatory skin diseases
Authors: Zhao He , Zhao Han , Tang Yan , Li Mengfan , Cai Yisheng , Xiao Xin , He Fanping , Huang Hongwen , Zhang Yiya , Li Ji
Published: October 2024

Background

Traditional topical drug delivery for treating inflammatory skin diseases suffers from poor skin penetration and long-term side effects. Metal nanoparticles show promising application in topical drug delivery for inflammatory skin diseases.

Methods

Here, we synthesized a new type of nanoparticles, azelamide monoethanolamine-functionalized gold nanoparticles (Au-MEA NPs), based on citrate-capped gold nanoparticles (Au-CA NPs) via the ligand exchange method. The physical and chemical properties of Au-CA NPs and Au-MEA NPs were characterized. In vivo studies were performed using imiquimod-induced psoriasis and LL37-induced rosacea animal models, respectively. For in vitro studies, a model of cellular inflammation was established using HaCaT cells stimulated with TNF-α. In addition, proteomics, gelatin zymography, and other techniques were used to investigate the possible therapeutic mechanisms of the Au-MEA NPs.

Results

We found that Au-MEA NPs exhibited better stability and permeation properties compared to conventional Au-CA NPs. Transcutaneously administered Au-MEA NPs exerted potent therapeutic efficacy against both rosacea-like and psoriasiform skin dermatitis in vivo without overt signs of toxicity. Mechanistically, Au-MEA NPs reduced the production of pro-inflammatory mediators in keratinocytes by promoting SOD activity and inhibiting the activity of MMP9.

Conclusion

Au-MEA NPs have the potential to be a topical nanomedicine for the effective and safe treatment of inflammatory skin diseases.
A systematic scrutiny of artificial intelligence-based air pollution prediction techniques, challenges, and viable solutions
Authors: Malhotra Meenakshi , Walia Savita , Lin Chia-Chen , Aulakh Inderdeep Kaur , Agarwal Saurabh
Published: October 2024

Air is an essential human necessity, and inhaling filthy air poses a significant health risk. One of the most severe hazards to people’s health is air pollution, and appropriate precautions should be taken to monitor and anticipate its quality in advance. Among all the countries, the air quality in India is decreasing daily, which is a matter of concern to the health department. Many studies use machine learning and Deep learning methods to predict atmospheric pollutant levels, prioritizing accuracy over interpretability. Many research studies confuse researchers and readers about how to proceed with further research. This paper aims to give every detail of the considered air pollutants and brief about the techniques used, their advantages, and challenges faced during pollutant prediction, which leads to a better understanding of the techniques before starting any research related to air pollutant prediction. This paper has given numerous prospective questions on air pollution that piqued the study’s interest. This study discussed various machine and deep learning methods and optimization techniques. Despite all the discussed machine learning and deep learning techniques, the paper concluded that more datasets, better learning techniques, and a variety of suggestions would enhance interpretability while maintaining high accuracy for air pollution prediction. The purpose of this review is also to reveal how a family of neural network algorithms has helped researchers across the globe to predict air pollutant(s).
Information quality and students’ academic performance: the mediating roles of perceived usefulness, entertainment and social media usage
Authors: Badr Abdallah M. M. , Al-Abdi Badr Saleh , Rfeqallah Maged , Kasim Rozilah , Ali Faisal A. M.
Published: October 2024

Purpose

This study evaluates the mediating roles of entertainment, perceived usefulness, and social media use on social information (content) and students’ academic performance.

Methodology

Primary data was collected from 445 students at King Khalid University in Saudi Arabia using the snowball sampling strategy was employed. For data analysis, structural equation modeling (PLS-SEM) was used.

Findings

Entertainment partly mediates the link between social information quality “content” (IQ) and social media use (SMU) and SMU mediates the link between IQ and student’s academic performance (SAP). Perceived usefulness mediates the link between IQ and SAP. Suggesting that entertainment and perceived usefulness are crucially necessary for inspiring social media content to obtain optimum performance among graduate students. The study was limited to a single academic institution. Therefore, the results of the investigation cannot be generalized as a whole, and cannot track respondents’ social media activity over time. Thus, longitudinal data may be used in future investigations.

Practical implications

The results of this study indicate that faculties can adapt and adjust their teaching methods and activities to incorporate social media, perceived usefulness, and entertaining content since it affects student performance. Social media (SM) has a significant influence on students’ social and academic performance. Thus, educational stakeholders, such as university authorities, the government, and parents and guardians, should recognize social media as a tool for achieving educational objectives.

Originality/value

The study enhances the application of UTAUT2 by examining how factors that influence the adoption of technology are connected to the subsequent influence of that adoption on students’ learning and conduct.
Investigation of students' use of online information in higher education using eye tracking
Authors: Kunz Ann-Kathrin , Zlatkin-Troitschanskaia Olga , Schmidt Susanne , Nagel Marie-Theres , Brückner Sebastian
Published: October 2024

To successfully learn using freely available (and non-curated) Internet resources, university students need to search for, critically evaluate and select online information, and verify sources (defined as Critical Online Reasoning, COR). Recent research indicates substantial deficits in COR skills among higher education students. To support students in learning how to critically use online information for their learning, it is necessary to better understand the strategies and practices that might elicit less critically-reflective judgments about online information and thus account for such deficits. To this end, using eye tracking data, we investigate how the COR behaviors of students who critically-reflectively evaluate the credibility of online information (‘high performers’) differ from those of students who do not critically-reflectively evaluate it (‘low performers’): 19 students were divided into high and low performers according to their performance in the newly developed Critical Online Reasoning Assessment (CORA). The fixation and dwell times of both groups during CORA task processing were compared regarding time spent on the different processing steps and eye movements on the visited web pages. The results show noticeable differences between the two groups, indicating that low performers indeed approached the task rather heuristically than systematically, and that COR skills require targeted and effective training in higher education.
Dynamic conditions for large shallow intraslab earthquakes: four categories of subduction zones
Authors: Yoshida Masaki
Published: October 2024

Large shallow intraslab earthquakes (LSIEs) of over magnitude-7 rarely occur at shallower depths (≤ 60 km) in the subducting plates of the circum-Pacific and northern margin of the Australian Plate off Indonesia. Previous studies have suggested that most LSIEs occur under surface tectonic conditions with a lateral stress gradient across the back-arc to the fore-arc on the overriding plate based on seismological and geological evidence. In this study, dynamic conditions for the occurrence of LSIEs were studied using the intraslab stress state, stress state of the overriding plate, motion speed of overriding and subducting plates, and trench migration speed determined by plate motion models. LSIEs prefer tectonic conditions under (1) an extensional-to-neutral stress state in the back-arc, (2) a compressional stress state in the fore-arc, and (3) down-dip tension in the shallower part of the subducting plate. The results suggest that the Earth’s subduction zones can be classified into four categories. This categorization is informed by the behavior of underlying mantle flow, i.e., the magnitude of slab suction flow in the mantle under the subducting plates, which is related to the degree of plate-slab coupling, and the scale of return flow in the mantle wedge under the overriding plates, which varies the combination of stress states in the fore-arc and back-arc.
Effect of sequencing platforms on the sensitivity of chemical mutation detection using Hawk-Seq™
Authors: Hosoi Sayaka , Hirose Takako , Matsumura Shoji , Otsubo Yuki , Saito Kazutoshi , Miyazawa Masaaki , Suzuki Takayoshi , Masumura Kenichi , Sugiyama Kei-ichi
Published: October 2024

Background

Error-corrected next-generation sequencing (ecNGS) technologies have enabled the direct evaluation of genome-wide mutations after exposure to mutagens. Previously, we reported an ecNGS methodology, Hawk-Seq™, and demonstrated its utility in evaluating mutagenicity. The evaluation of technical transferability is essential to further evaluate the reliability of ecNGS-based assays. However, cutting-edge sequencing platforms are continually evolving, which can affect the sensitivity of ecNGS. Therefore, the effect of differences in sequencing instruments on mutation data quality should be evaluated.

Results

We assessed the performance of four sequencing platforms (HiSeq2500, NovaSeq6000, NextSeq2000, and DNBSEQ-G400) with the Hawk-Seq™ protocol for mutagenicity evaluation using DNA samples from mouse bone marrow exposed to benzo[a]pyrene (BP). The overall mutation (OM) frequencies per 106 bp in vehicle-treated samples were 0.22, 0.36, 0.46, and 0.26 for HiSeq2500, NovaSeq6000, NextSeq2000, and DNBSEQ-G400, respectively. The OM frequency of NextSeq2000 was significantly higher than that of HiSeq2500, suggesting the difference to be based on the platform. The relatively higher value in NextSeq2000 was a consequence of the G:C to C:G mutations in NextSeq2000 data (0.67 per 106 G:C bp), which was higher than the mean of the four platforms by a ca. of 0.25 per 106 G:C bp. A clear dose-dependent increase in G:C to T:A mutation frequencies was observed in all four sequencing platforms after BP exposure. The cosine similarity values of the 96-dimensional trinucleotide mutation patterns between HiSeq and the three other platforms were 0.93, 0.95, and 0.92 for NovaSeq, NextSeq, and DNBSeq, respectively. These results suggest that all platforms can provide equivalent data that reflect the characteristics of the mutagens.

Conclusions

All platforms sensitively detected mutagen-induced mutations using the Hawk-Seq™ analysis. The substitution types and frequencies of the background errors differed depending on the platform. The effects of sequencing platforms on mutagenicity evaluation should be assessed before experimentation.
Student mobility in Southern Italy: An empirical analysis of preferential patterns
Authors: Genova Vincenzo Giuseppe , Ruiu Gabriele , Attanasio Massimo , Ermacora Matteo , Breschi Marco
Published: October 2024

This paper presents an empirical analysis aimed at identifying chain migration patterns among university students from Sicily, Sardinia, and Apulia. Utilizing data from the national archive of university students enrolled in an Italian university from 2008 to 2017, we construct origin–destination matrixes and calculate residuals from a log-linear model to detect key student routes. Positive residuals between specific origin–destination pairs that persist over time can suggest significant attraction and potential chain migration. The results support a “large to large” and “small to small” city mobility model, particularly for Sicily and Sardinia. Students from Palermo, Catania, Messina, and Cagliari show strong connections with large cities such as Rome and Milan. Furthermore, results show historical links between Sardinia and Tuscany date back to the 1950s, and the enduring connections between Apulian students and universities in Emilia-Romagna, Veneto, and Lombardy have been evident since the 1970s. In Sicily, mobility patterns towards the Polytechnic of Turin began in the 1970s and persist today. These patterns underscore the influence of prior migrants on the mobility decisions of university students in Southern Italy, highlighting a potential chain migration effect.
Water, sanitation, and hygiene (WASH) practices in Africa: exploring the effects on public health and sustainable development plans
Authors: Okesanya Olalekan John , Eshun Gilbert , Ukoaka Bonaventure Michael , Manirambona Emery , Olabode Olaleke Noah , Adesola Ridwan Olamilekan , Okon Inibehe Ime , Jamil Safayet , Singh Amandeep , Lucero-Prisno Don Eliseo , Ali Habib Mohammad , Chowdhury A. B. M. Alauddin
Published: October 2024

Background

Suboptimal water, sanitation, and hygiene (WASH) practices constitute a serious public health risk, affecting one-third of the world's population. Remarkable progress has been made to improve WASH; however, challenges remain, with rapid population growth adding pressure on WASH systems. This study explores the current state of WASH practices and diseases in Africa, identifies challenges, and proposes public health recommendations for sustainable implementation.

Main body

The staggering burden of WASH-related diseases in low- and middle-income countries (LMICs), particularly in Africa, threatens public health, with millions of deaths and disability-adjusted life years (DALYs) attributed to poor WASH practices annually. Notable challenges plaguing WASH practices in the region include poverty, malnutrition, poor data reporting, illiteracy, climate change, and poor healthcare financing. This results in adverse health consequences, including waterborne infections like cholera, typhoid, dysentery, and diarrheal diseases. Additionally, neglected tropical diseases (NTDs) such as intestinal worms, schistosomiasis, trachoma, lost productivity, and environmental pollution from soil and underground water contamination have been implicated. Geographical disparities, cultural norms, and inadequate funding further complicate efforts to improve WASH infrastructure and practices. Globally concerted efforts are required to address these issues and permit WASH practices to protect human health by preventing infectious diseases and contributing to economic growth. Strong financial frameworks, skills training, and tools like WASH Fit are recommended for a stronger WASH approach in Africa.

Conclusion

The consequences of poor WASH extend beyond public health, impacting economic growth, gender equality, and environmental sustainability. WaterAid’s policy recommendations prioritizing government administration, institutional capacity enhancement, and more financial resources are expedient.
Validation of a multi-parameter algorithm for personalized contrast injection protocol in liver CT
Authors: Brat Hugues G. , Dufour Benoit , Heracleous Natalie , Sastre Pauline , Thouly Cyril , Rizk Benoit , Zanca Federica
Published: October 2024

Background

In liver computed tomography (CT), tailoring the contrast injection to the patient’s specific characteristics is relevant for optimal imaging and patient safety. We evaluated a novel algorithm engineered for personalized contrast injection to achieve reproducible liver enhancement centered on 50 HU.

Methods

From September 2020 to August 31, 2022, CT data from consecutive adult patients were prospectively collected at our multicenter premises. Inclusion criteria consisted of an abdominal CT referral for cancer staging or follow-up. For all examinations, a web interface incorporating data from the radiology information system (patient details and examination information) and radiographer-inputted data (patient fat-free mass, imaging center, kVp, contrast agent details, and imaging phase) were used. Calculated contrast volume and injection rate were manually entered into the CT console controlling the injector. Iopamidol 370 mgI/mL or Iohexol 350 mgI/mL were used, and kVp varied (80, 100, or 120) based on patient habitus.

Results

We enrolled 384 patients (mean age 61.2 years, range 21.1–94.5). The amount of administered iodine dose (gI) was not significantly different across contrast agents (p = 0.700), while a significant increase in iodine dose was observed with increasing kVp (p < 0.001) and in males versus females (p < 0.001), as expected. Despite the differences in administered iodine load, image quality was reproducible across patients with 72.1% of the examinations falling within the desirable range of 40–60 HU.

Conclusion

This study validated a novel algorithm for personalized contrast injection in adult abdominal CT, achieving consistent liver enhancement centered at 50 HU.

Relevance statement

In healthcare’s ongoing shift towards personalized medicine, the algorithm offers excellent potential to improve diagnostic accuracy and patient management, particularly for the detection and follow-up of liver malignancies.

Key Points

The algorithm achieves reproducible liver enhancement, promising improved diagnostic accuracy and patient management in diverse clinical settings.

The real-world study demonstrates this algorithm’s adaptability to different variables ensuring high-quality liver imaging.

A personalized algorithm optimizes liver CT, improving the visibility, conspicuity, and follow-up of liver lesions.

Graphical Abstract
Rare primary vasculitis: update on multiple complex diseases and the new kids on the block
Authors: Dantas Joao Gabriel , Biegelmeyer Erika , Zarur Eduarda Bonelli , Pinheiro Frederico Augusto Gurgel
Published: October 2024

Systemic vasculitis is a group of rare diseases that share an essential characteristic: inflammation of blood vessel walls. This injury occurs during the disease course, but specific features vary for each entity. In this paper, we will address relevant aspects of the newest monogenic mutation vasculitis, such as deficiency of adenosine deaminase 2 (ADA2) and VEXAS syndrome (UBA1), and other relevant vasculitis, such as Cogan syndrome and Susac syndrome that may share some similarities with them.
Barriers and enablers to addressing smoking, nutrition, alcohol consumption, physical activity and gestational weight gain (SNAP-W) as part of antenatal care: A mixed methods systematic review
Authors: Dilworth Sophie , Doherty Emma , Mallise Carly , Licata Milly , Hollis Jenna , Wynne Olivia , Lane Cassandra , Wolfenden Luke , Wiggers John , Kingsland Melanie
Published: October 2024

Background

International clinical guidelines recommend that smoking, nutrition, alcohol consumption, physical activity and gestational weight gain (SNAP-W) be addressed as part of routine antenatal care throughout pregnancy. However, guideline recommendations are poorly implemented, and few antenatal care recipients routinely receive the recommended care. There is a need to establish the determinants (barriers and enablers) to care delivery to inform strategies to improve implementation. This systematic review aimed to synthesize qualitative and quantitative evidence of the barriers and enablers to the routine delivery of antenatal care targeting SNAP-W health risks.

Methods

A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seven databases were searched for relevant studies published between January 2001 and November 2023. Study findings were coded and analysed according to the domains of the Theoretical Domains Framework (TDF).

Results

Forty-nine studies were included in the review, 27 qualitative studies and 22 quantitative studies. The studies were conducted in 14 countries. Data were collected from 7146 antenatal care providers (midwives, Aboriginal health workers, obstetricians, medical officers, general practitioners) and 352 barriers and enablers were identified. Across all SNAP-W health risk and antenatal care provider groups, the predominant TDF domain was ‘environmental context and resources’, identified in 96% of studies. Barriers within this domain included insufficient time, limited access to and quality of resources, and limited organisational supports. ‘Beliefs about consequences’ was the second most common TDF domain, reported in 67% of studies, particularly studies of care related to alcohol use, nutrition/ physical activity/ gestational weight gain and those involving midwives, multidisciplinary practitioners and general practitioners. ‘Optimism’ was the second most common TDF domain for studies of smoking-related care and involving obstetricians, gynaecologists, and other mixed medical professions.

Conclusions

It is critical that determinants related to environmental context and resources including time, resources and organisational supports are considered in the development of strategies to support the implementation of recommended antenatal care related to SNAP-W risks. Strategies addressing clinician beliefs about consequences and optimism may also be needed to support the implementation of care related to specific health behaviours and by specific antenatal care provider groups.

Registration

The review protocol was prospectively registered with Prospero: CRD42022353084; 22 October 2022.
Assessment of pulmonary hypertension in patients diagnosed with chronic kidney disease
Authors: Helal Emad H. , Abdella Ali Mohamed Ali , Hantera Mohamed S. , Faraghly Aymen Abdelahmid , Farhat Amgad A.
Published: October 2024

Background

Pulmonary hypertension (PH) represents a condition affecting small arteries of the pulmonary vasculature, inducing progressive blockage that results in increased pulmonary vascular resistance (PVR) as well as pulmonary arterial pressure (PAP), which are defining features of such a disorder. This work was aimed at investigating the PH prevalence among chronic kidney disease (CKD) cases and its linkage to disease severity and the relations between CKD management and PH.

Methods

Our prospective observational descriptive cross-sectional study was conducted on 120 CKD patients at the Chest Department, Tanta University Hospitals and Air Forces Specialized Hospitals from December 2020 to December 2022.

Results

The most frequent diagnosis of PH was Group 1 pulmonary arterial hypertension (36.7%) followed by Group 2 cardiac causes (30%) followed by Group 4 chronic thromboembolic PH (26.7%) and (6.7%) experienced normal pulmonary hemodynamics by RHC. Also, a statistically significant correlation was documented among CKD staging as well as risk assessment of PH (p 0.024). A significant association was documented among treatment as well as risks for developing PH (p 0.034). Patients on medical treatment (60%) showed low risk while (33.3%) of patients depending on dialysis showed high risk.

Conclusions

PH was diagnosed in 28 CKD patients confirmed by right (RT) side cardiac catheterization among 120 CKD patients studied for PH assessment representing 23.5%. Right-side cardiac catheterization is more accurate than echocardiography in confirming the diagnosis of PH. The severity of PH showed significant association with the CKD stage.
Predator traits influence uptake and trophic transfer of nanoplastics in aquatic systems–a mechanistic study
Authors: Ockenden Amy , Mitrano Denise M. , Kah Melanie , Tremblay Louis A. , Simon Kevin S.
Published: October 2024

Predicting the response of aquatic species to environmental contaminants is challenging, in part because of the diverse biological traits within communities that influence their uptake and transfer of contaminants. Nanoplastics are a contaminant of growing concern, and previous research has documented their uptake and transfer in aquatic food webs. Employing an established method of nanoplastic tracking using metal-doped plastics, we studied the influence of biological traits on the uptake of nanoplastic from water and diet in freshwater predators through two exposure assays. We focused on backswimmers (Anisops wakefieldi) and damselfly larvae (Xanthocnemis zealandica) - two freshwater macroinvertebrates with contrasting physiological and morphological traits related to feeding and respiration strategies. Our findings reveal striking differences in nanoplastic transfer dynamics: damselfly larvae accumulated nanoplastics from water and diet and then efficiently eliminated 92% of nanoplastic after five days of depuration. In contrast, backswimmers did not accumulate nanoplastic from either source. Differences in nanoplastic transfer dynamics may be explained by the contrasting physiological and morphological traits of these organisms. Overall, our results highlight the importance and potential of considering biological traits in predicting transfer of nanoplastics through aquatic food webs.
New Insight for Enhanced Topical Targeting of Caffeine for Effective Cellulite Treatment: In Vitro Characterization, Permeation Studies, and Histological Evaluation in Rats
Authors: Fouad Shahinaze A. , Badr Taher A. , Abdelbary Ahmed , Fadel Maha , Abdelmonem Rehab , Jasti Bhaskara R. , El-Nabarawi Mohamed
Published: October 2024

Cellulite (CLT) is one of the commonly known lipodystrophy syndromes affecting post-adolescent women worldwide. It is topographically characterized by an orange-peel, dimpled skin appearance hence, it is an unacceptable cosmetic problem. CLT can be modulated by surgical procedures such as; liposuction and mesotherapy. But, these options are invasive, expensive and risky. For these reasons, topical CLT treatments are more preferred. Caffeine (CA), is a natural alkaloid that is well-known for its prominent anti-cellulite effects. However, its hydrophilicity hinders its cutaneous permeation. Therefore, in the present study CA was loaded into solid lipid nanoparticles (SLNs) by high shear homogenization/ultrasonication. CA-SLNs were prepared using Compritol® 888 ATO and stearic acid as solid lipids, and span 60 and brij™35, as lipid dispersion stabilizing agents. Formulation variables were adjusted to obtain entrapment efficiency (EE > 75%), particle size (PS < 350 nm), zeta potential (ZP < −25 mV) and polydispersity index (PDI < 0.5). CA-SLN-4 was selected and showed maximized EE (92.03 ± 0.16%), minimized PS (232.7 ± 1.90 nm), and optimum ZP (−25.15 ± 0.65 mV) and PDI values (0.24 ± 0.02). CA-SLN-4 showed superior CA release (99.44 ± 0.36%) compared to the rest CA-SLNs at 1 h. TEM analysis showed spherical, nanosized CA-SLN-4 vesicles. Con-LSM analysis showed successful CA-SLN-4 permeation transepidermally and via shunt diffusion. CA-SLN-4 incorporated into Noveon AA−1® hydrogel (CA-SLN-Ngel) showed accepted physical/rheological properties, and in vitro release profile. Histological studies showed that CA-SLN-Ngel significantly reduced mean subcutaneous fat tissue (SFT) thickness with 4.66 fold (p = 0.035) and 4.16 fold (p = 0.0001) compared to CA-gel, at 7th and 21st days, respectively. Also, significant mean SFT thickness reduction was observed compared to untreated group with 4.83 fold (p = 0.0005) and 3.83 fold (p = 0.0043), at 7th and 21st days, respectively. This study opened new avenue for CA skin delivery via advocating the importance of skin appendages. Hence, CA-SLN-Ngel could be a promising nanocosmeceutical gel for effective CLT treatment.

Graphical Abstract