bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge, perception, and attitudes of medical students towards antimicrobial resistance and stewardship: an observational cross-sectional study from Palestine
Authors: Abuawad Mohammad , Ziyadeh-Isleem Azza , Mahamid Aya , Quzmar Saja , Ammar Enas , Shawahna Ramzi
Published: March 2024

Background

Antimicrobial resistance is a global health concern that contributes to significant mortality and morbidity. This study investigated knowledge, perceptions, and attitudes of medical students in Palestinian universities towards antimicrobial resistance and stewardship. The study also investigated associations between variables of students with their knowledge, perceptions, and attitudes.

Methods

A questionnaire was used in this cross-sectional study. Medical students in Palestinian universities were surveyed in this study. In addition to the demographic variables of the medical students, the questionnaire measured knowledge, perceptions, and attitudes of medical students in Palestinian universities towards antimicrobial resistance and stewardship.

Results

In this study, 384 medical students returned complete questionnaires. Of the medical students, 269 (70.1%) were female, 215 (56.0%) lived in urban areas, and 244 (63.5%) were in their clinical training years. Medical students in the clinical phase demonstrated higher knowledge about microbial resistance compared to preclinical students as evidenced by a mean score of 89.7 ± 15.9 compared to 74.0 ± 26.4, respectively (p < 0.05). Similarly, clinical students displayed higher score regarding antimicrobial resistance perception, with a mean score of 85.7 ± 15.6, contrasted with 72.6 ± 24.1 among preclinical students. In terms of knowledge pertaining to antimicrobial stewardship, clinical students scored higher with a mean of 63.4 ± 28.5 compared to 54.5 ± 31.5 among preclinical students. Regarding attitudes, clinical students also demonstrated a higher mean score of 67.6 ± 22.6 in contrast to 61.1 ± 24.6 among preclinical students.

Conclusion

The medical students are the future workforce of physicians in any healthcare system. Therefore, increasing knowledge of the medical students about and how to combat antimicrobial resistance can help save lives and improve patient outcomes. More studies are needed to find the best ways to increase knowledge, perceptions, and attitudes of medical students towards antimicrobial resistance and antimicrobial stewardship.
An automated ICU agitation monitoring system for video streaming using deep learning classification
Authors: Dai Pei-Yu , Wu Yu-Cheng , Sheu Ruey-Kai , Wu Chieh-Liang , Liu Shu-Fang , Lin Pei-Yi , Cheng Wei-Lin , Lin Guan-Yin , Chung Huang-Chien , Chen Lun-Chi
Published: March 2024

Objective

To address the challenge of assessing sedation status in critically ill patients in the intensive care unit (ICU), we aimed to develop a non-contact automatic classifier of agitation using artificial intelligence and deep learning.

Methods

We collected the video recordings of ICU patients and cut them into 30-second (30-s) and 2-second (2-s) segments. All of the segments were annotated with the status of agitation as “Attention” and “Non-attention”. After transforming the video segments into movement quantification, we constructed the models of agitation classifiers with Threshold, Random Forest, and LSTM and evaluated their performances.

Results

The video recording segmentation yielded 427 30-s and 6405 2-s segments from 61 patients for model construction. The LSTM model achieved remarkable accuracy (ACC 0.92, AUC 0.91), outperforming other methods.

Conclusion

Our study proposes an advanced monitoring system combining LSTM and image processing to ensure mild patient sedation in ICU care. LSTM proves to be the optimal choice for accurate monitoring. Future efforts should prioritize expanding data collection and enhancing system integration for practical application.
Translation and psychometric evaluation of the Persian version of the nurses’ quality of life scale: a validation study in Iran
Authors: Yousefnezhad Mehrdad , Shareinia Habib , Kheirkhah Elahe Lal , Sajjadi Moosa
Published: March 2024

Background

The quality of life for nurses can be significantly impacted by various occupational factors that Influence their working conditions and professional performance. The current study aimed to translate and validate the Persian version of the Nurses’ Quality of Life Scale.

Material and method

In this cross-sectional research, the Nurses’ Quality of Life Scale (NQOLS) was utilized to assess the quality of life among 500 employed nurses in hospitals in the cities of Gonabad and Sabzevar. The translation process of the NQOLS followed the model proposed by Wild et al. The content validity of the Persian version of the scale was evaluated using the Content Validity Index (CVI) and Content Validity Ratio (CVR). Structural validity was assessed using exploratory and confirmatory factor analyses. Internal consistency reliability was assessed using Cronbach’s alpha, while test-retest reliability was determined using the Intraclass Correlation Coefficient (ICC). Data analysis was conducted using SPSS version 26 and LISREL version 8.8 software.

Results

The exploratory factor analysis of the Persian version of NQOLS revealed six factors that accounted for 62.15% of the total variance. The structural validity of the extracted factors was confirmed through confirmatory factor analysis. The Cronbach’s alpha coefficient and ICC for the entire questionnaire were 0.91 and 0.95, respectively.

Conclusion

The findings of the present study suggest that the Persian version of the NQOLS exhibits sufficient validity and reliability. Therefore, it can be used as an effective tool for measuring and examining the quality of life among nurses in Iran.
A mixed methods analysis of the medication review intervention centered around the use of the ‘Systematic Tool to Reduce Inappropriate Prescribing’ Assistant (STRIPA) in Swiss primary care practices
Authors: Jungo Katharina Tabea , Deml Michael J. , Schalbetter Fabian , Moor Jeanne , Feller Martin , Lüthold Renata Vidonscky , Huibers Corlina Johanna Alida , Sallevelt Bastiaan Theodoor Gerard Marie , Meulendijk Michiel C , Spruit Marco , Schwenkglenks Matthias , Rodondi Nicolas , Streit Sven
Published: March 2024

Background

Electronic clinical decision support systems (eCDSS), such as the ‘Systematic Tool to Reduce Inappropriate Prescribing’ Assistant (STRIPA), have become promising tools for assisting general practitioners (GPs) with conducting medication reviews in older adults. Little is known about how GPs perceive eCDSS-assisted recommendations for pharmacotherapy optimization. The aim of this study was to explore the implementation of a medication review intervention centered around STRIPA in the ‘Optimising PharmacoTherapy In the multimorbid elderly in primary CAre’ (OPTICA) trial.

Methods

We used an explanatory mixed methods design combining quantitative and qualitative data. First, quantitative data about the acceptance and implementation of eCDSS-generated recommendations from GPs (n = 21) and their patients (n = 160) in the OPTICA intervention group were collected. Then, semi-structured qualitative interviews were conducted with GPs from the OPTICA intervention group (n = 8), and interview data were analyzed through thematic analysis.

Results

In quantitative findings, GPs reported averages of 13 min spent per patient preparing the eCDSS, 10 min performing medication reviews, and 5 min discussing prescribing recommendations with patients. On average, out of the mean generated 3.7 recommendations (SD=1.8). One recommendation to stop or start a medication was reported to be implemented per patient in the intervention group (SD=1.2). Overall, GPs found the STRIPA useful and acceptable. They particularly appreciated its ability to generate recommendations based on large amounts of patient information. During qualitative interviews, GPs reported the main reasons for limited implementation of STRIPA were related to problems with data sourcing (e.g., incomplete data imports), preparation of the eCDSS (e.g., time expenditure for updating and adapting information), its functionality (e.g., technical problems downloading PDF recommendation reports), and appropriateness of recommendations.

Conclusions

Qualitative findings help explain the relatively low implementation of recommendations demonstrated by quantitative findings, but also show GPs’ overall acceptance of STRIPA. Our results provide crucial insights for adapting STRIPA to make it more suitable for regular use in future primary care settings (e.g., necessity to improve data imports).

Trial registration

Clinicaltrials.gov NCT03724539, date of first registration: 29/10/2018.
The effect of selenium on the proliferation of bovine endometrial epithelial cells in a lipopolysaccharide-induced damage model
Authors: Li Hanqing , Wang Heng , Cui Luying , Liu Kangjun , Guo Long , Li Jianji , Dong Junsheng
Published: March 2024

Background

Endometritis is a common bovine postpartum disease. Rapid endometrial repair is beneficial for forming natural defense barriers and lets cows enter the next breeding cycle as soon as possible. Selenium (Se) is an essential trace element closely related to growth and development in animals. This study aims to observe the effect of Se on the proliferation of bovine endometrial epithelial cells (BEECs) induced by lipopolysaccharide (LPS) and to elucidate the possible underlying mechanism.

Results

In this study, we developed a BEECs damage model using LPS. Flow cytometry, cell scratch test and EdU proliferation assay were used to evaluate the cell cycle, migration and proliferation. The mRNA transcriptions of growth factors were detected by quantitative reverse transcription-polymerase chain reaction. The activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin pathways were detected by Western blotting and immunofluorescence. The results showed that the cell viability and BCL-2/BAX protein ratio were significantly decreased, and the cell apoptosis rate was significantly increased in the LPS group. Compared with the LPS group, Se promoted cell cycle progression, increased cell migration and proliferation, and significantly increased the gene expressions of TGFB1, TGFB3 and VEGFA. Se decreased the BCL-2/BAX protein ratio, promoted β-catenin translocation from the cytoplasm to the nucleus and activated the Wnt/β-catenin and PI3K/AKT signaling pathways inhibited by LPS.

Conclusions

In conclusion, Se can attenuate LPS-induced damage to BEECs and promote cell proliferation and migration in vitro by enhancing growth factors gene expression and activating the PI3K/AKT and Wnt/β-catenin signaling pathways.
A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome
Authors: Sun Haojie , Xu Xinda , Chen Binjun , Wang Yanmei , Lyu Jihan , Guo Luo , Yuan Yasheng , Ren Dongdong
Published: March 2024

Background

Treacher Collins syndrome (TCS; OMIM 154500) is a craniofacial developmental disorder.

Methods

To investigate the genetic features of a four-generation Chinese family with TCS, clinical examinations, hearing tests, computed tomography, whole-exome sequencing (WES), Sanger sequencing, reverse transcription (RT)-PCR, and the Minigene assay were performed.

Results

The probands, an 11-year-old male and his cousin exhibited typical clinical manifestations of TCS including conductive hearing loss, downward slanting palpebral fissures, and mandibular hypoplasia. Computed tomography revealed bilateral fusion of the anterior and posterior stapedial crura and malformation of the long crura of the incus. WES of both patients revealed a novel heterozygous intronic variant, i.e., c.4342 + 5_4342 + 8delGTGA (NM_001371623.1) in TCOF1. Minigene expression analysis revealed that the c.4342 + 5_4342 + 8delGTGA variant in TCOF1 caused a partial deletion of exon 24 (c.4115_4342del: p.Gly1373_Arg1448del), which was predicted to yield a truncated protein. The deletion was further confirmed via RT-PCR and sequencing of DNA from proband blood cells. A heterozygous variant in the POLR1C gene (NM_203290; exon6; c.525delG) was found almost co-segregated with the TCOF1 pathogenic variant.

Conclusions

In conclusion, we identified a heterozygous TCOF1 splicing variant c.4342 + 5_4342 + 8delGTGA (splicing) in a Chinese TSC family with ossicular chain malformations and facial anomalies. Our findings broadened the spectrum of TCS variants and will facilitate diagnostics and prognostic predictions.
Postpartum weight retention and the early evolution of cardiovascular risk over the first 5 years after pregnancy
Authors: Kramer Caroline K. , Ye Chang , Hanley Anthony J , Connelly Philip W , Sermer Mathew , Zinman Bernard , Retnakaran Ravi
Published: March 2024

Background

The cumulative effect of postpartum weight retention from each pregnancy in a woman’s life may contribute to her risk of ultimately developing type 2 diabetes and cardiovascular disease. However, there is limited direct evidence supporting this hypothesis. Thus, we sought to characterize the impact of postpartum weight retention on the trajectories of cardiovascular risk factors over the first 5-years after pregnancy.

Methods

In this prospective observational cohort study, 330 women (mean age 35.7 ± 4.3 years, mean pre-pregnancy body mass index 25.2 ± 4.8 kg/m2, 50.9% primiparous) underwent serial cardiometabolic characterization (anthropometry, blood pressure, lipids, oral glucose tolerance test, insulin sensitivity/resistance (Matsuda index, HOMA-IR), C-reactive protein (CRP), adiponectin) at 1-year, 3-years, and 5-years postpartum. Based on the magnitude of weight change between pre-pregnancy and 5-years postpartum, they were stratified into the following 3 groups: weight loss (n = 100), weight gain 0–6% (n = 110), and weight gain ≥ 6% (n = 120).

Results

At 1-year postpartum, cardiovascular risk factors did not differ between the groups. However, an adverse risk factor profile progressively emerged in the weight retention groups at 3- and 5-years. Indeed, after covariate adjustment, there was stepwise worsening (from the weight loss group to weight gain 0–6% to weight gain ≥ 6% group) of the following cardiovascular risk factors at 5-years: triglycerides (p = 0.001), HDL (p = 0.02), LDL (p = 0.01), apolipoprotein-B (p = 0.003), Matsuda index (p < 0.0001), HOMA-IR (p < 0.0001), fasting glucose (p = 0.07), and CRP (p = 0.01). Moreover, on logistic regression analyses, weight gain ≥ 6% emerged as an independent predictor of pre-diabetes/diabetes at 5-years (adjusted OR = 3.40, 95%CI: 1.63–7.09).

Conclusion

Postpartum weight retention predicts trajectories of worsening cardiovascular risk factors and glucose intolerance over the first 5-years after delivery, consistent with its postulated contribution to future vascular disease in women.
Effectiveness and safety of the combination of sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies
Authors: Ahmad Aftab , Sabbour Hani
Published: March 2024

Background

Randomized controlled trials and real-world studies suggest that combination therapy with sodium–glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and total cholesterol levels. However, a systematic review of available real-world evidence may facilitate clinical decision-making in the real-world scenario. This meta-analysis assessed the safety and effectiveness of combinations of SGLT2is + GLP-1RAs with a focus on their cardioprotective effects along with glucose-lowering ability in patients with type 2 diabetes mellitus (T2DM) in a real-world setting.

Methods

Electronic searches were performed in the PubMed/MEDLINE, PROQuest, Scopus, CINAHL, and Google Scholar databases. Qualitative analyses and meta-analyses were performed using the Joanna Briggs Institute SUMARI software package and Review Manager v5.4, respectively.

Results

The initial database search yielded 1445 articles; of these, 13 were included in this study. The analyses indicated that SGLT2is + GLP-1RAs combinations were associated with significantly lower all-cause mortality when compared with individual therapies (odds ratio [95% confidence interval [CI] 0.49 [0.41, 0.60]; p < 0.00001). Significant reductions in BMI (− 1.71 [− 2.74, − 0.67]; p = 0.001), SBP (− 6.35 [− 10.17, − 2.53]; p = 0.001), HbA1c levels (− 1.48 [− 1.75, − 1.21]; p < 0.00001), and FPG (− 2.27 [− 2.78, − 1.76]; p < 0.00001) were associated with the simultaneous administration of the combination. Changes in total cholesterol levels and differences between simultaneous and sequential combination therapies for this outcome were not significant.

Conclusion

This systematic review and meta-analysis based on real-world data suggests that the combination of SGLT2is + GLP-1RAs is associated with lower all-cause mortality and favorable improvements in cardiovascular, renal, and glycemic measurements. The findings drive a call-to–action to incorporate this combination early and simultaneously in managing T2DM patients and achieve potential cardiovascular benefits and renal protection.

Graphical Abstract
Perceived life threat in children during the COVID-19 pandemic: associations with posttraumatic stress, anxiety, and depressive symptoms
Authors: Danzi BreAnne A. , Kelly Jessica T. , Knowles Ellen A. , Burdette Evan T. , La Greca Annette M.
Published: March 2024

Defining children’s “trauma exposure” in the context of the COVID-19 pandemic has been a source of debate. Children were exposed to threatening messaging about COVID-19 but might interpret this information differently than adults. Perceived life threat (PLT), the belief that one’s life is in danger, has been identified as a robust predictor of posttraumatic stress symptoms (PTSS), and may be a better predictor of PTSS than actual life threat (ALT). This study investigated parent reports of children’s self-PLT (belief that they might die from COVID-19) and family-PLT (belief that a family member might die from COVID-19). The aims were to compare PLT to ALT, evaluate their associations with children’s psychological functioning, and identify risk factors associated with PLT. We hypothesized an association between PLT and children’s psychological functioning in the context of the COVID-19 pandemic. Parents (N = 140) reported on their child’s (M age = 9.81 years, 47% female) pandemic experiences, psychological functioning, and both self-PLT and family-PLT. Results revealed self-PLT for 10% of the children and family-PLT for 43% of the children, yet only 6% experienced ALT (i.e., they or their parent tested positive for COVID-19). Children with reported self- or family-PLT had higher PTSS, depressive symptoms, anxiety symptoms, and functional impairment compared to children without these reported beliefs. PLT, but not ALT, was associated with psychological outcomes. Children with only PLT had greater PTSS and impairment than children with ALT. There were differences in parental functioning and pandemic-related information/media exposure between children with and without PLT. Children’s perceptions, rather than objective experiences, may be more central to their psychological functioning. This has implications for screening for pandemic-related symptomatology in children as traditional trauma exposure measures may not adequately identify distressed children.
Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling
Authors: Zhang Leiyi , Gong Xiaoxiang , Tan Juan , Zhang Rongsen , Li Mingxia , Liu Cong , Wu Chenhao , Li Xiaojing
Published: March 2024

Background

This study seeks to investigate the impacts of Lactobacillus reuteri (L. reuteri) on hepatic ischemia-reperfusion (I/R) injury and uncover the mechanisms involved.

Methods

Mice in the I/R groups were orally administered low and high doses of L.reuteri (L.reuteri-low and L. reuteri-hi; 1 × 1010 CFU/d and 1 × 1011 CFU/d), for 4 weeks prior to surgery. Following this, mice in the model group were treated with an Nrf2 inhibitor (ML-385), palmitoylcarnitine, or a combination of both.

Results

After treatment with L. reuteri, mice exhibited reduced levels of serum aminotransferase (ALT), aspartate aminotransferase (AST), and myeloperoxidase (MPO) activity, as well as a lower Suzuki score and apoptosis rate. L. reuteri effectively reversed the I/R-induced decrease in Bcl2 expression, and the significant increases in the levels of Bax, cleaved-Caspase3, p-p65/p65, p-IκB/IκB, p-p38/p38, p-JNK/JNK, and p-ERK/ERK. Furthermore, the administration of L. reuteri markedly reduced the inflammatory response and oxidative stress triggered by I/R. This treatment also facilitated the activation of the Nrf2/HO-1 pathway. L. reuteri effectively counteracted the decrease in levels of beneficial gut microbiota species (such as Blautia, Lachnospiraceae NK4A136, and Muribaculum) and metabolites (including palmitoylcarnitine) induced by I/R. Likewise, the introduction of exogenous palmitoylcarnitine demonstrated a beneficial impact in mitigating hepatic injury induced by I/R. However, when ML-385 was administered prior to palmitoylcarnitine treatment, the previously observed effects were reversed.

Conclusion

L. reuteri exerts protective effects against I/R-induced hepatic injury, and its mechanism may be related to the promotion of probiotic enrichment, differential metabolite homeostasis, and the Nrf2/HO-1 pathway, laying the foundation for future clinical applications.
The plant-like protein phosphatase PPKL regulates parasite replication and morphology in Toxoplasma gondii
Authors: Wu Xi-Ting , Gao Xu-Wen , Wang Qiang-Qiang , He Kai , Bilal Muhammad Saqib , Dong Hui , Tang Yi-Dan , Ding Hui-Yong , Li Yue-Bao , Tang Xiao-Yan , Long Shaojun
Published: March 2024

Background

The protozoan parasite Toxoplasma gondii encodes dozens of phosphatases, among which a plant-like phosphatase absent from mammalian genomes named PPKL, which is involved in regulating brassinosteroid signaling in Arabidopsis, was identified in the genome. Among the Apicomplexa parasites, T. gondii is an important and representative pathogen in humans and animals. PPKL was previously identified to modulate the apical integrity and morphology of the ookinetes and parasite motility and transmission in another important parasite, Plasmodium falciparum. However, the exact function of PPKL in the asexual stages of T. gondii remains unknown.

Methods

The plant auxin-inducible degron (AID) system was applied to dissect the phenotypes of PPKL in T. gondii. We first analyzed the phenotypes of the AID parasites at an induction time of 24 h, by staining of different organelles using their corresponding markers. These analyses were further conducted for the parasites grown in auxin for 6 and 12 h using a quantitative approach and for the type II strain ME49 of AID parasites. To further understand the phenotypes, the potential protein interactions were analyzed using a proximity biotin labeling approach. The essential role of PPKL in parasite replication was revealed.

Results

PPKL is localized in the apical region and nucleus and partially distributed in the cytoplasm of the parasite. The phenotyping of PPKL showed its essentiality for parasite replication and morphology. Further dissections demonstrate that PPKL is required for the maturation of daughter parasites in the mother cells, resulting in multiple nuclei in a single parasite. The phenotype of the daughter parasites and parasite morphology were observed in another type of T. gondii strain ME49. The substantial defect in parasite replication and morphology could be rescued by genetic complementation, thus supporting its essential function for PPKL in the formation of parasites. The protein interaction analysis showed the potential interaction of PPKL with diverse proteins, thus explaining the importance of PPKL in the parasite.

Conclusions

PPKL plays an important role in the formation of daughter parasites, revealing its subtle involvement in the proper maturation of the daughter parasites during division. Our detailed analysis also demonstrated that depletion of PPKL resulted in elongated tubulin fibers in the parasites. The important roles in the parasites are potentially attributed to the protein interaction mediated by kelch domains on the protein. Taken together, these findings contribute to our understanding of a key phosphatase involved in parasite replication, suggesting the potential of this phosphatase as a pharmaceutic target.

Graphical Abstract
Rapid classification of epidemiologically relevant age categories of the malaria vector, Anopheles funestus
Authors: Mwanga Emmanuel P. , Siria Doreen J. , Mshani Issa H. , Mwinyi Sophia H. , Abbasi Said , Jimenez Mario Gonzalez , Wynne Klaas , Baldini Francesco , Babayan Simon A. , Okumu Fredros O.
Published: March 2024

Background

Accurately determining the age and survival probabilities of adult mosquitoes is crucial for understanding parasite transmission, evaluating the effectiveness of control interventions and assessing disease risk in communities. This study was aimed at demonstrating the rapid identification of epidemiologically relevant age categories of Anopheles funestus, a major Afro-tropical malaria vector, through the innovative combination of infrared spectroscopy and machine learning, instead of the cumbersome practice of dissecting mosquito ovaries to estimate age based on parity status.

Methods

Anopheles funestus larvae were collected in rural south-eastern Tanzania and reared in an insectary. Emerging adult females were sorted by age (1–16 days old) and preserved using silica gel. Polymerase chain reaction (PCR) confirmation was conducted using DNA extracted from mosquito legs to verify the presence of An. funestus and to eliminate undesired mosquitoes. Mid-infrared spectra were obtained by scanning the heads and thoraces of the mosquitoes using an attenuated total reflection–Fourier transform infrared (ATR–FT-IR) spectrometer. The spectra (N = 2084) were divided into two epidemiologically relevant age groups: 1–9 days (young, non-infectious) and 10–16 days (old, potentially infectious). The dimensionality of the spectra was reduced using principal component analysis, and then a set of machine learning and multi-layer perceptron (MLP) models were trained using the spectra to predict the mosquito age categories.

Results

The best-performing model, XGBoost, achieved overall accuracy of 87%, with classification accuracy of 89% for young and 84% for old An. funestus. When the most important spectral features influencing the model performance were selected to train a new model, the overall accuracy increased slightly to 89%. The MLP model, utilizing the significant spectral features, achieved higher classification accuracy of 95% and 94% for the young and old An. funestus, respectively. After dimensionality reduction, the MLP achieved 93% accuracy for both age categories.

Conclusions

This study shows how machine learning can quickly classify epidemiologically relevant age groups of An. funestus based on their mid-infrared spectra. Having been previously applied to An. gambiae, An. arabiensis and An. coluzzii, this demonstration on An. funestus underscores the potential of this low-cost, reagent-free technique for widespread use on all the major Afro-tropical malaria vectors. Future research should demonstrate how such machine-derived age classifications in field-collected mosquitoes correlate with malaria in human populations.

Graphical Abstract
Relationship between genetic diversity and morpho-functional characteristics of flight-related traits in Triatoma garciabesi (Hemiptera: Reduviidae)
Authors: Verly Thaiane , Pita Sebastián , Carbajal-de-la-Fuente Ana Laura , Burgueño-Rodríguez Gabriela , Piccinali Romina V. , Fiad Federico G. , Ríos Néstor , Panzera Francisco , Lobbia Patricia , Sánchez-Casaccia Paz , Rojas de Arias Antonieta , Cavallo María José , Gigena Gisel V. , Rodríguez Claudia S. , Nattero Julieta
Published: March 2024

Background

Triatoma garciabesi, a potential vector of the parasitic protozoan Trypanosoma cruzi, which is the causative agent of Chagas disease, is common in peridomestic and wild environments and found throughout northwestern and central Argentina, western Paraguay and the Bolivian Chaco. Genetic differentiation of a species across its range can help to understand dispersal patterns and connectivity between habitats. Dispersal by flight is considered to be the main active dispersal strategy used by triatomines. In particular, the morphological structure of the hemelytra is associated with their function. The aim of this study was to understand how genetic diversity is structured, how morphological variation of dispersal-related traits varies with genetic diversity and how the morphological characteristics of dispersal-related traits may explain the current distribution of genetic lineages in this species.

Methods

Males from 24 populations of T. garciabesi across its distribution range were examined. The cytochrome c oxidase I gene (coI) was used for genetic diversity analyses. A geometric morphometric method based on landmarks was used for morpho-functional analysis of the hemelytra. Centroid size (CS) and shape of the forewing, and contour of both parts of the forewing, the head and the pronotum were characterised. Length and area of the forewing were measured to estimate the aspect ratio.

Results

The morphometric and phylogenetic analysis identified two distinct lineages, namely the Eastern and Western lineages, which coincide with different ecological regions. The Eastern lineage is found exclusively in the eastern region of Argentina (Chaco and Formosa provinces), whereas the Western lineage is prevalent in the rest of the geographical range of the species. CS, shape and aspect ratio of the hemelytra differed between lineages. The stiff portion of the forewing was more developed in the Eastern lineage. The shape of both portions of the hemelytra were significantly different between lineages, and the shape of the head and pronotum differed between lineages.

Conclusions

The results provide preliminary insights into the evolution and diversification of T. garciabesi. Variation in the forewing, pronotum and head is congruent with genetic divergence. Consistent with genetic divergence, morphometry variation was clustered according to lineages, with congruent variation in the size and shape of the forewing, pronotum and head.

Graphical Abstract
Investigations of the tick burden on passeriform, water-associated and predatory birds reveal new tick–host associations and habitat-related factors of tick infestation
Authors: Pitó Andor , Bukor Boglárka , Győrig Előd , Brlík Vojtěch , Kontschán Jenő , Keve Gergő , Takács Nóra , Hornok Sándor
Published: March 2024

Background

Previous studies on the tick infestation of birds in the Carpathian Basin focused on songbirds (Passeriformes). Thus, the primary aim of the present work was to extend the scope of previous studies, i.e. to include aquatic (water-associated) bird species in a similar context, especially considering that these birds are usually long-distance migrants.

Methods

Between March 2021 and August 2023, 11,919 birds representing 126 species were checked for the presence of ticks. From 352 birds belonging to 40 species, 905 ixodid ticks were collected. Tick species were identified morphologically and/or molecularly.

Results

Ticks from avian hosts belonged to seven species: Ixodes ricinus (n = 448), I. frontalis (n = 31), I. festai (n = 2), I. arboricola (n = 36), I. lividus (n = 4), Haemaphysalis concinna (n = 382) and Dermacentor reticulatus (n = 2). Nymphs of I. ricinus occurred with a single activity peak around March–May, whereas its larvae typically infested birds in May, June or July. By contrast, H. concinna usually had its activity maximum during the summer (nymphs in June–July, larvae later in July–August). Interestingly, two ornithophilic species, I. frontalis and I. arboricola, were most active around winter months (between October and April). A significantly lower ratio of aquatic birds was found tick-infested than songbirds. Several new tick–host associations were revealed, including I. ricinus from Greylag Goose (Anser anser) and D. reticulatus from Great Egret (Ardea alba) and Sedge Warbler (Acrocephalus schoenobaenus). Ticks were collected for the first time in Europe from two species of predatory birds as well as from Little Bittern (Ixobrychus minutus). Bird species typically inhabiting reedbeds were most frequently infested with H. concinna, and most ticks localized at their throat, as opposed to forest-dwelling avian hosts, on which I. ricinus predominated and ticks were more evenly distributed.

Conclusions

In the evaluated region, aquatic birds appear to be less important in tick dispersal than songbirds. However, newly revealed tick-host associations in this category attest to their hitherto neglected contribution. The results suggest that the habitat type will have significant impact not only on the species composition but also on the feeding location of ticks on birds.

Graphical Abstract
Exploring a multiparameter MRI–based radiomics approach to predict tumor proliferation status of serous ovarian carcinoma
Authors: Liu Li , Zhao Ling , Jing Yang , Li Dan , Linghu Hua , Wang Haiyan , Zhou Linyi , Fang Yuan , Li Yongmei
Published: March 2024

Objectives

To develop a multiparameter magnetic resonance imaging (MRI)-based radiomics approach that can accurately predict the tumor cell proliferation status of serous ovarian carcinoma (SOC).

Materials and methods

A total of 134 patients with SOC who met the inclusion and exclusion criteria were retrospectively screened from institution A, spanning from January 2016 to March 2022. Additionally, an external validation set comprising 42 SOC patients from institution B was also included. The region of interest was determined by drawing each ovarian mass boundaries manually slice-by-slice on T2-weighted imaging fat-suppressed fast spin-echo (T2FSE) and T1 with contrast enhancement (T1CE) images using ITK-SNAP software. The handcrafted radiomic features were extracted, and then were selected using variance threshold algorithm, SelectKBest algorithm, and least absolute shrinkage and selection operator. The optimal radiomic scores and the clinical/radiological independent predictors were integrated as a combined model.

Results

Compared with the area under the curve (AUC) values of each radiomic signature of T2FSE and T1CE, respectively, the AUC value of the radiomic signature (T1CE-T2FSE) was the highest in the training set (0.999 vs. 0.965 and 0.860). The homogeneous solid component of the ovarian mass was considered the only independent predictor of tumor cell proliferation status among the clinical/radiological variables. The AUC of the radiomic–radiological model was 0.999.

Conclusions

The radiomic–radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can accurately predict tumor cell proliferation status of SOC which has high repeatability and may enable more targeted and effective treatment strategies.

Critical relevance statement

The proposed radiomic–radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can predict tumor cell proliferation status of SOC which has high repeatability and may guide individualized treatment programs.

Key points

• The radiomic–radiological nomogram may guide individualized treatment programs of SOC.

• This radiomic–radiological nomogram showed a favorable prediction ability.

• Homogeneous slightly higher signal intensity on T2FSE is vital for Ki-67.

Graphical Abstract
Fractal analysis of left ventricular trabeculae in post-STEMI: from acute to chronic phase
Authors: Shi Ruo-Yang , Wu Rui , Ran Jinjun , Tang Lang-Lang , Wesemann Luke , Hu Jiani , Du Liang , Zhang Wei-Jun , Xu Jian-Rong , Zhou Yan , Zhao Lei , Pu Jun , Wu Lian-Ming
Published: March 2024

Purpose

The temporal evolution of ventricular trabecular complexity and its correlation with major adverse cardiovascular events (MACE) remain indeterminate in patients presenting with acute ST elevation myocardial infarction (STEMI).

Methods

This retrospective analysis enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for acute STEMI, possessing cardiac magnetic resonance (CMR) data in the acute (within 7 days), subacute (1 month after pPCI), and chronic phases (6 months after pPCI) from January 2015 to January 2020 at the three participating sites. Fractal dimensions (FD) were measured for the global, infarct, and remote regions of left ventricular trabeculae during each phase. The potential association of FD with MACE was analyzed using multivariate Cox regression.

Results

Among the 200 analyzed patients (182 men; median age, 61 years; age range, 50–66 years), 37 (18.5%) encountered MACE during a median follow-up of 31.2 months. FD exhibited a gradual decrement (global FD at acute, subacute, and chronic phases: 1.253 ± 0.049, 1.239 ± 0.046, 1.230 ± 0.045, p < 0.0001), with a more pronounced decrease observed in patients subsequently experiencing MACE (p < 0.001). The global FD at the subacute phase correlated with MACE (hazard ratio 0.89 (0.82, 0.97), p = 0.01), and a global FD value below 1.26 was associated with a heightened risk.

Conclusion

In patients post-STEMI, the global FD, serving as an indicator of left ventricular trabeculae complexity, independently demonstrated an association with subsequent major adverse cardiovascular events, beyond factors encompassing left ventricular ejection fraction, indexed left ventricular end-diastolic volume, infarct size, heart rate, NYHA class, and post-pPCI TIMI flow.

Critical relevance statement

In patients who have had an ST-segment elevation myocardial infarction, global fractal dimension, as a measure of left ventricular trabeculae complexity, provided independent association with subsequent major adverse cardiovascular event.

Key points

• Global and regional FD decreased after STEMI, and more so in patients with subsequent MACE.

• Lower global FD at the subacute phase and Δglobal FD from acute to subacute phase were associated with subsequent MACE besides clinical and CMR factors.

• Global FD at the subacute phase independently correlated with MACE and global FD value below 1.26 was associated with higher risk.

Graphical Abstract
MR-guided percutaneous microwave coagulation of small breast tumors
Authors: Ji Ying , Zhuo Yaoyao , Li Ting , Lian Jingge , Wang Zilin , Guo Xinyu , Kong Dexing , Li Kangan
Published: March 2024

Background

To evaluate the technical success and patient safety of magnetic resonance-guided percutaneous microwave coagulation (MR-guided PMC) for breast malignancies.

Methods

From May 2018 to December 2019, 26 patients with breast tumors measuring 2 cm or less were recruited to participate in a prospective, single-institution clinical study. The primary endpoint of this study was the evaluation of treatment efficacy for each patient. Histochemical staining with α-nicotinamide adenine dinucleotide and reduced (NADH)-diaphorase was used to determine cell viability following and efficacy of PMC. The complications and self-reported sensations from all patients during and after ablation were also assessed. The technical success of the PMC procedure was defined when the area of the NADH-diaphorase negative region fully covered the hematoxylin–eosin (H&E) staining region in the tumor.

Results

All patients had a complete response to ablation with no residual carcinoma on histopathological specimen. The mean energy, ablation duration, and procedure duration per tumor were 36.0 ± 4.2 kJ, 252.9 ± 30.9 S, and 104.2 ± 13.5 min, respectively. During the ablation, 14 patients underwent prolonged ablation time, and 1 patient required adjusting of the antenna position. Eleven patients had feelings of subtle heat or swelling, and 3 patients experienced slight pain. After ablation, one patient took two painkillers because of moderate pain, and no patients had postoperative oozing or other complications after PMC. Induration around the ablation area appeared in 16 patients.

Conclusion

MR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future.

Critical relevance statement

MR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future.

Key points

• MR-guided PMC of small breast tumors is feasible.

• PMC was successfully performed for all patients.

• All patients were satisfied with the final cosmetic result.

Graphical Abstract
iMSC-mediated delivery of ACVR2B-Fc fusion protein reduces heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva
Authors: Gao Pan , Inada Yoshiko , Hotta Akitsu , Sakurai Hidetoshi , Ikeya Makoto
Published: March 2024

Background

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease caused by a gain-of-function mutation in ACVR1, which is a bone morphogenetic protein (BMP) type I receptor. Moreover, it causes progressive heterotopic ossification (HO) in connective tissues. Using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) and mouse models, we elucidated the underlying mechanisms of FOP pathogenesis and identified a candidate drug for FOP.

Methods

In the current study, healthy mesenchymal stem/stromal cells derived from iPSCs (iMSCs) expressing ACVR2B-Fc (iMSCACVR2B-Fc), which is a neutralizing receptobody, were constructed. Furthermore, patient-derived iMSCs and FOP mouse model (ACVR1R206H, female) were used to confirm the inhibitory function of ACVR2B-Fc fusion protein secreted by iMSCACVR2B-Fc on BMP signaling pathways and HO development, respectively.

Results

We found that secreted ACVR2B-Fc attenuated BMP signaling initiated by Activin-A and BMP-9 in both iMSCs and FOP-iMSCs in vitro. Transplantation of ACVR2B-Fc-expressing iMSCs reduced primary HO in a transgenic mouse model of FOP. Notably, a local injection of ACVR2B-Fc-expressing iMSCs and not an intraperitoneal injection improved the treadmill performance, suggesting compound effects of ACVR2B-Fc and iMSCs.

Conclusions

These results offer a new perspective for treating FOP through stem cell therapy.
89Zr-labeled ImmunoPET targeting the cancer stem cell antigen CD133 using fully-human antibody constructs
Authors: Wyszatko Kevin , Janzen Nancy , Silva Luis Rafael , Kwon Luke , Komal Teesha , Ventura Manuela , Venugopal Chitra , Singh Sheila K. , Valliant John F. , Sadeghi Saman
Published: March 2024

Background

Cancer stem cells play an important role in driving tumor growth and treatment resistance, which makes them a promising therapeutic target to prevent cancer recurrence. Emerging cancer stem cell-targeted therapies would benefit from companion diagnostic imaging probes to aid in patient selection and monitoring response to therapy. To this end, zirconium-89-radiolabeled immunoPET probes that target the cancer stem cell-antigen CD133 were developed using fully human antibody and antibody scFv-Fc scaffolds.

Results

ImmunoPET probes [89Zr]-DFO-RW03IgG (CA = 0.7 ± 0.1), [89Zr]-DFO-RW03IgG (CA = 3.0 ± 0.3), and [89Zr]-DFO-RW03scFv − Fc (CA = 2.9 ± 0.3) were radiolabeled with zirconium-89 (radiochemical yield 42 ± 5%, 97 ± 2%, 86 ± 12%, respectively) and each was isolated in > 97% radiochemical purity with specific activities of 120 ± 30, 270 ± 90, and 200 ± 60 MBq/mg, respectively. In vitro binding assays showed a low-nanomolar binding affinity of 0.6 to 1.1 nM (95% CI) for DFO-RW03IgG (CA = 0.7 ± 0.1), 0.3 to 1.9 nM (95% CI) for DFO-RW03IgG (CA = 3.0 ± 0.3), and 1.5 to 3.3 nM (95% CI) for DFO-RW03scFv − Fc (C/A = 0.3). Biodistribution studies found that [89Zr]-DFO-RW03scFv − Fc (CA = 2.9 ± 0.3) exhibited the highest tumor uptake (23 ± 4, 21 ± 2, and 23 ± 4%ID/g at 24, 48, and 72 h, respectively) and showed low uptake (< 6%ID/g) in all off-target organs at each timepoint (24, 48, and 72 h). Comparatively, [89Zr]-DFO-RW03IgG (CA = 0.7 ± 0.1) and [89Zr]-DFO-RW03IgG (CA = 3.0 ± 0.3) both reached maximum tumor uptake (16 ± 3%ID/g and 16 ± 2%ID/g, respectively) at 96 h p.i. and showed higher liver uptake (10.2 ± 3%ID/g and 15 ± 3%ID/g, respectively) at that timepoint. Region of interest analysis to assess PET images of mice administered [89Zr]-DFO-RW03scFv − Fc (CA = 2.9 ± 0.3) showed that this probe reached a maximum tumor uptake of 22 ± 1%ID/cc at 96 h, providing a tumor-to-liver ratio that exceeded 1:1 at 48 h p.i. Antibody-antigen mediated tumor uptake was demonstrated through biodistribution and PET imaging studies, where for each probe, co-injection of excess unlabeled RW03IgG resulted in > 60% reduced tumor uptake.

Conclusions

Fully human CD133-targeted immunoPET probes [89Zr]-DFO-RW03IgG and [89Zr]-DFO-RW03scFv − Fc accumulate in CD133-expressing tumors to enable their delineation through PET imaging. Having identified [89Zr]-DFO-RW03scFv − Fc (CA = 2.9 ± 0.3) as the most attractive construct for CD133-expressing tumor delineation, the next step is to evaluate this probe using patient-derived tumor models to test its detection limit prior to clinical translation.
Drug shortages in Israel, revisited: a bitter pill to swallow
Authors: Schwartzberg Eyal , Marom Eli , Vishkautzan Alla , Gorelik Einat , Shani Segev
Published: March 2024

Background

In 2017, we published an article addressing drug shortages (DS) in Israel, exploring regulatory perspectives, challenges, and potential solutions. Since then, DS remain a significant concern for patients, healthcare providers, and policymakers globally. In this updated article, we revisit the topic, providing new insights, data, and analysis on the current DS landscape in Israel, efforts to mitigate them, and propose strategies to combat this escalating issue.

Methods

We conducted a comprehensive search of the Israeli Ministry of Health (MOH) DS database, spanning from 2014 to the present. We extracted DS numbers and their reasons. Further searches on the Israeli MOH website, pharmaceutical division archives, and the internet yielded official MOH publications and correspondence regarding regulatory responses to DS from 2017 onwards. Additionally, two specific cases of DS were examined to analyze their handling. Recent activities and publications from the Israeli MOH aimed at reducing DS were also reviewed.

Results

Between 2014 and 2022, DS surged 2.66-fold. Total DS were 3228; 672 due to commercial reasons, and 2556 to operational reasons (20.5% and 79.5% respectively). The average duration of intermittent DS increased 1.56-fold, from 85 to 133 days. Manufacturers informed the MOH 22 days prior to actual shortage on average. Analyzing 2022's DS (640) by ATC groups, prominent categories included nervous system drugs (18%), drugs acting on the alimentary tract and metabolism (14%), and dermatologicals (11%). Operational DS in 2022 (n = 564) were primarily due to stock delivery delays (38%), stock over-utilization (12%), and raw material shortages (9%). Sixteen official MOH publications on DS were identified from 2017 onwards. Moreover, two high-impact DS case studies were examined.

Conclusion

Despite routine monitoring by the Israeli MOH and updating the DS policy throughout this period, DS persist, intensifying annually and posing serious health risks. This trend mirrors international patterns, affecting countries globally. In Israel's uniquely structured healthcare system, with its swift stakeholder cooperation and implementation capabilities, more effective DS management is conceivable. We propose ten universally applicable rules to address DS challenges.