bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cas9/guide RNA-based gene-drive dynamics following introduction and introgression into diverse anopheline mosquito genetic backgrounds
Authors: Tushar Taylor , Pham Thai Binh , Parker Kiona , Crepeau Marc , Lanzaro Gregory C. , James Anthony A. , Carballar-Lejarazú Rebeca 
Published: November 2024

Abstract
Background
Novel technologies are needed to combat anopheline vectors of malaria parasites as the reductions in worldwide disease incidence has stalled in recent years. Gene drive-based approaches utilizing Cas9/guide RNA (gRNA) systems are being developed to suppress anopheline populations or modify them by increasing their refractoriness to the parasites. These systems rely on the successful cleavage of a chromosomal DNA target site followed by homology-directed repair (HDR) in germline cells to bias inheritance of the drive system. An optimal drive system should be highly efficient for HDR-mediated gene conversion with minimal error rates. A gene-drive system, AgNosCd-1, with these attributes has been developed in the Anopheles gambiae G3 strain and serves as a framework for further development of population modification strains. To validate AgNosCd-1 as a versatile platform, it must perform well in a variety of genetic backgrounds.

Results
We introduced or introgressed AgNosCd-1 into different genetic backgrounds, three in geographically-diverse Anopheles gambiae strains, and one each in an An. coluzzii and An. arabiensis strain. The overall drive inheritance, determined by presence of a dominant marker gene in the F2 hybrids, far exceeded Mendelian inheritance ratios in all genetic backgrounds that produced viable progeny. Haldane’s rule was confirmed for AgNosCd-1 introgression into the An. arabiensis Dongola strain and sterility of the F1 hybrid males prevented production of F2 hybrid offspring. Back-crosses of F1 hybrid females were not performed to keep the experimental design consistent across all the genetic backgrounds and to avoid maternally-generated mutant alleles that might confound the drive dynamics. DNA sequencing of the target site in F1 and F2 mosquitoes with exceptional phenotypes revealed drive system-generated mutations resulting from non-homologous end joining events (NHEJ), which formed at rates similar to AgNosCd-1 in the G3 genetic background and were generated via the same maternal-effect mechanism.

Conclusions
These findings support the conclusion that the AgNosCd-1 drive system is robust and has high drive inheritance and gene conversion efficiency accompanied by low NHEJ mutation rates in diverse An. gambiae s.l. laboratory strains.
Management of giant left atrial thrombus late after transcatheter mitral valve-in-ring replacement using a transcatheter aortic valve: a case report
Authors: Maloku A. , Hamadanchi A. , Bäz L. , Richter M. , Bargenda S. , Möbius-Winkler S. , Schulze P. C. , Franz Marcus 
Published: November 2024

Abstract
Background
In symptomatic high-risk patients with severe mitral valve regurgitation (MR), who are not eligible for surgery, Transcatheter edge-to-edge repair (TEER) or transcatheter mitral valve replacement (TMVR) may be an option, especially when surgical mitral valve repair by annuloplasty has been performed earlier. After TMVR, the appropriate anticoagulation regimen is still matter of debate.

Case presentation
We here report on a 78-year-old frail lady with heart failure and atrial fibrillation who underwent surgical reconstruction of the mitral valve nine years ago. Due to high surgical risk and after heart team discussion, TMVR using a transcatheter aortic valve prosthesis (valve-in-ring concept) was performed successfully via the transapical access route. Several months later, an excellent result could be confirmed. Since surgical excision of the left atrial appendage was carried out during first surgery, oral anticoagulation was withdrawn. Two months later, the patient presented with a massive LA thrombus mass and severe stenosis of the mitral valve prosthesis requiring re-do surgery.

Conclusions
Management of anticoagulation in patients with atrial fibrillation and successfully performed LAA excision is still a matter of debate, in particular after transcatheter heart valve implantation in mitral position. TMVR devices may be very thrombogenic. Thus, caution should be used whenever discontinuing oral anticoagulation in these patients. Despite the lack of evidence, withdrawal of anticoagulation should be avoided here, especially in the absence of bleeding complications. Left atrial appendage closure or excision should not influence this decision.
Isolation and identification of antifungal, antibacterial and nematocide agents from marine bacillus gottheilii MSB1
Authors: Shehata Ahmed. S. , Samy Marwa A. , Sobhy Sherien E. , Farag Aida M. , El-Sherbiny Ibrahim M. , Saleh Ahmed A. , Hafez Elsayed E. , Abdel-Mogib Mamdouh , Aboul-Ela Haiam M. 
Published: November 2024

AbstractPathogenic fungi employ numerous strategies to colonize plants, infect them, reduce crop yield and quality, and cause significant losses in agricultural production. The increasing use of chemical pesticides has led to various ecological and environmental issues, including the emergence of resistant weeds, soil compaction, and water pollution, all negatively impacting agricultural sustainability. Additionally, the extensive development of synthetic fungicides has adverse effects on animal and human health, prompting the exploration of alternative approaches and green strategies for phytopathogen control. Microorganisms living in sponges represent a promising source of novel bioactive secondary metabolites, potentially useful in developing new nematicidal and antimicrobial agents. This study focuses on extracting bioactive compounds from endosymbiotic bacteria associated with the marine sponge Hyrtios erect sp. (collected from NIOF Station, Hurghada, Red Sea, Egypt) using various organic solvents. Bacillus sp. was isolated and identified through 16 S rRNA gene sequencing. The biocidal activity of Bacillus gotheilii MSB1 extracts was screened against plant pathogenic bacteria, fungi, and nematodes. The n-butanol extract showed significant potential as a biological fungicide against Alternaria alternata and Fusarium oxysporum. Both n-hexane and ethyl acetate extracts exhibited negative impacts against the plant pathogenic bacteria Erwinia carotovora and Ralstonia solanacearum, whereas the n-butanol extract had a positive effect. Regarding nematicidal activity, ethyl acetate and n-butanol extracts demonstrated in-vitro activity against the root-knot nematode Meloidogyne incognita, which causes serious vegetable crop diseases, but the n-hexane extract showed no positive effects. The findings suggest that bioactive compounds from endosymbiotic bacteria associated with marine sponges, particularly B. gotheilii MSB1, hold significant potential as alternative biological control agents against plant pathogens. The n-butanol extract, in particular, displayed promising biocidal activities against various plant pathogenic fungi, bacteria, and nematodes. These results support further exploration and development of such bioactive compounds as sustainable, environmentally friendly alternatives to synthetic pesticides and fungicides in agricultural practices.
Adapting and pilot testing a tool to assess the accessibility of primary health facilities for people with disabilities in Luuka District, Uganda
Authors: Mactaggart Islay , Ssemata Andrew Sentoogo , Menya Abdmagidu , Smythe Tracey , Rotenberg Sara , Marks Sarah , Bannink Mbazzi Femke , Kuper Hannah 
Published: November 2024

Abstract
Background
People with disabilities frequently experience barriers in seeking healthcare that lead to poorer health outcomes compared to people without disabilities. To overcome this, it is important to assess the accessibility of primary health facilities – broadly defined to include a disability-inclusive service provision – so as to document present status and identify areas for improvement. We aimed to identify, adapt and pilot test an appropriate tool to assess the accessibility of primary health facilities in Luuka District, Uganda.

Methods
We conducted a rapid literature review to identify appropriate tools, selecting the Disability Awareness Checklist (DAC) on account of its relative brevity and development as a sensitization and action tool. We undertook three rounds of adaptation, working together with youth researchers (aged 18–35) with disabilities who then underwent 2 days of training as DAC facilitators. The adapted tool comprised 71 indicators across four domains and 12 sub-domains. We also developed a structured feedback form for facilitators to complete with healthcare workers. We calculated median accessibility scores overall, per domain and per sub-domain, and categorised feedback form suggestions by type and presumed investment level. We pilot-tested the adapted tool in 5 primary health facilities in one sub-district of Luuka, nested within a pilot healthcare worker training on disability.

Results
The median overall facility accessibility score was 17.8% (range 12.3–28.8). Facility scores were highest in the universal design and accessibility domain (25.8%, 22.6–41.9), followed by reasonable accommodation (20.0%, 6.7–33.3). Median scores for capacity of facility staff (6.67%, 6.7–20.0), and linkages to other services were lower (0.0%, 0–25.0). Within the feedback forms, there were a median of 21 suggestions (range 14–26) per facility. Most commonly, these were categorised as minor structural changes (20% of suggestions), with a third categorised as no (2%) or low (33%) cost, and the majority (40%) medium cost.

Conclusions
Overall accessibility scores were low, with many opportunities for low-cost improvement at the facility level. We did not identify any issues with the implementation of the tool, suggesting few further adaptations are required for its future use in this setting.
Predicting steroid-induced osteonecrosis of the femoral head: role of lipid metabolism biomarkers and radiomics in young and middle-aged adults
Authors: Jia Daqi , Zhang Yue , Li Huaqiang , Guo Chunfang , Wu Yipeng , Shi Xiangwen , Yang Li , Mo Jieyu , Liu Xia , Xu Yongqing 
Published: November 2024

Abstract
Background
Femoral head necrosis is a common orthopedic disease that results in significant physical disability in patients. Early prediction and diagnosis of steroid-induced osteonecrosis of the femoral head (SONFH) are crucial for the prevention and treatment of this condition.

Methods
In this study, initial CT images and clinical data of patients with SONFH, admitted from January 2019 to December 2022, were collected. Patients were grouped as follows: (1) those diagnosed with SONFH at the initial diagnosis (control group), and (2) those with high-risk factors but no symptoms at first diagnosis, who developed SONFH two years later (experimental group). CT imaging histological features, clinical characteristics, and transcriptome screening for differentially expressed genes, pathway enrichment, and immune infiltration analyses were performed.

Results
Significant differences were found in triglyceride (TG) levels between the training and validation groups. Age, sex, alkaline phosphatase (ALP), and hemoglobin levels differed between the training and internal validation groups, while HDL and red blood cell counts varied between the training and external validation groups. Univariate analysis showed that age, TG, HDL, and Radiomics scores influenced SONFH, while multivariate analysis revealed TG, HDL, and Radiomics scores were closely related to SONFH. Transcriptomic analysis showed associations with sphingolipid and adipocyte signaling pathways, along with immune cell involvement, linking SONFH to lipid metabolism and atherosclerosis.

Conclusions
These findings indicate a significant association between steroid-induced osteonecrosis of the femoral head and age, with TG and HDL serving as indicators of lipid metabolism closely correlated with the occurrence of SONFH. Radiomics scores were also found to correlate with SONFH occurrence, supported by transcriptomic and CT imaging findings. However, this study has limitations, including its retrospective design and a relatively limited sample size, which may impact the generalizability of the results. Further prospective studies with larger, more diverse populations are needed to validate and enhance the predictive model.
Bacteriocin Microcin J25’s antibacterial infection effects and novel non-microbial regulatory mechanisms: differential regulation of dopaminergic receptors
Authors: Shang Lijun , Yang Fengjuan , Chen Qingyun , Dai Ziqi , Yang Guangxin , Zeng Xiangfang , Qiao Shiyan , Yu Haitao 
Published: November 2024

Abstract
Background
The antibacterial and immunomodulatory activities of bacteriocins make them attractive targets for development as anti-infective drugs. Although the importance of the enteric nervous system (ENS) in the struggle against infections of the intestine has been demonstrated, whether it is involved in bacteriocins anti-infective mechanisms is poorly defined.

Results
Here, we demonstrated that the bacteriocin Microcin J25 (J25) significantly alleviated diarrhea and intestinal inflammation in piglets caused by enterotoxigenic Escherichia coli (ETEC) infection. Mechanistically, macrophage levels were significantly downregulated after J25 treatment, and this was replicated in a mouse model. Omics analysis and validation screening revealed that J25 treatment induced significant changes in the dopaminergic neuron pathway, but little change in microbial structure. The alleviation of inflammation may occur by down-regulating dopamine receptor (DR) D1 and the downstream DAG-PKC pathway, thus inhibiting arachidonic acid decomposition, and the inhibition of macrophages may occur through the up-regulation of DRD5 and the downstream cAMP-PKA pathway, thus inhibiting NF-κB.

Conclusions
Our studies’ findings provide insight into the changes and possible roles of the ENS in J25 treatment of ETEC infection, providing a more sophisticated foundational understanding for developing the application potential of J25.
Fallacy of paleoproductivity signals by the recycled biogenic components: case study in the Central Basin of the northwestern Ross Sea
Authors: Khim Boo-Keun , Kim Sunghan , Lee Min Kyung , Sohn Young Kwan , Lee Jae Il , Yoo Kyu-Cheul 
Published: November 2024

AbstractCore LC42, retrieved from the Central Basin of the northwestern Ross Sea, contains three distinct sediment facies (IRD (ice-rafted debris)-poor bioturbated sandy mud, IRD-rich massive sandy mud, and laminated mud) that are interleaved with each other and deposited over the last 1 Ma. The biogenic components (biogenic opal, total organic carbon, and total nitrogen) of the laminated mud layers are consistently higher than the other two facies throughout the core. Based on the depositional succession of sediment facies and IRD-related depositional processes in the Antarctic continental margin, the laminated mud layers without IRD have been deposited during the glacial periods, but the enhanced paleoproductivity in terms of biogenic components during the mud deposition is unexpected. Backscattered electron imagery substantiates distinctly different componentry of the alternating light and dark laminae in the laminated mud. In particular, the light laminae contain scattered diatom fragments and eroded sand-sized lumps of fossil-bearing mud, whereas the dark laminae are clayey and diatomaceous. Both laminae thus are characterized by the high biogenic components, but they are interpreted to have been principally recycled from older deposits because diatom fragments are mostly reworked and old and their archives are poorly preserved. During the glacial periods, these laminated muds were deposited downward by milky plumes of meltwater discharged underneath the advancing glaciers that scoured the earlier-deposited and semi-consolidated diatom-rich sediments. Our study thus highlights that the recycling of biogenic particles should be precautious to avoid the fallacy of paleoclimatic interpretation in formulating climate-productivity models in the Antarctic continental margin.
What shapes statistical and data literacy research in K-12 STEM education? A systematic review of metrics and instructional strategies
Authors: Friedrich Anja , Schreiter Saskia , Vogel Markus , Becker-Genschow Sebastian , Brünken Roland , Kuhn Jochen , Lehmann Jessica , Malone Sarah 
Published: November 2024

AbstractThe pervasive digitization of society underscores the crucial role of data and its significant impact on decision-making across various domains. As a result, it is essential for individuals to acquire competencies in handling data. This need is particularly pertinent in K-12 education, where early engagement with data and statistics can lay a foundational understanding for future academic and professional endeavors. Additionally, K-12 education should provide students with critical skills necessary for navigating the complexities of daily life and making informed decisions in a data-rich society. This systematic review examines the state of research on statistical and data literacy in K-12 STEM (Science, Technology, Engineering, and Mathematics) education. It focuses specifically on cognitive, affective, and behavioral metrics and pedagogical approaches empirically investigated in this context. Using a rigorous selection process, we identified and synthesized 83 original empirical papers. Additionally, we invited the authors of these studies to share their perspectives on future strategies for addressing statistical and data literacy. The results indicate that the included studies primarily focus on the construct of statistical literacy, which is operationalized through a diverse array of metrics, predominantly within the context of mathematics education. We identified effective pedagogical approaches, such as authentic problem-solving and the integration of real-world data. The researchers surveyed emphasized the importance of interdisciplinary teaching, adapted curricula, and improved professional development for pre- and in-service teachers. Our findings underscore the growing relevance of this field, but suggest that integrated perspectives on statistical and data literacy within STEM subjects are limited.
In vitro antifungal activities of medicinal plants used for treatment of candidiasis in Pader district, Northern Uganda
Authors: Akwongo Betty , Kakudidi Esezah K. , Nsubuga Anthony M. , Andama Morgan , Namaganda Mary , Tugume Patience , Asiimwe Savina , Anywar Godwin , Katuura Esther 
Published: November 2024

Abstract
Background
The emergence of multidrug resistant Candida species to available drugs has led to renewed interest in the use of herbal medicines globally. This study scientifically verified antifungal effectiveness of five commonly used plant species in Pader district, against selected pathogenic candida strains.

Methods
Powdered roots of Momordica foetida, Sansevieria dawei and Distimake dissectus; and stem barks of Khaya anthotheca and Mitragyna rubrostipulata were extracted sequentially using petroleum ether and methanol, respectively; and total water extraction at 24.4 °C (maceration), 60 °C (decoction) and boiling water at 87 °C (hot water infusion). Extracts and their combinations, positive controls (amphotericin B, and fluconazole) and negative control (80% dimethyl sulfoxide, verified to be tolerable concentration to the tested Candida species) were screened and verified for their antifungal activity against Candida albicans (ATCC: American Type Culture Collection reference strain 10231, ATCC 90028, 0770a and 0796), C. glabrata (VVc 004, ATCC 2950) and C. tropicalis (ATCC 750 and 0210) using agar well diffusion and broth micro-dilution, respectively.

Results
Aqueous extract (24.4 °C) of M. rubrostipulata (ZOI: 18.00 ± 1.00 to 38.33 ± 0.17; MIC: 3.13 ± 0.00 to 20.83 ± 4.17; MFC: 12.50 ± 0.00 to 200.00 ± 0.00), methanol extract of K. anthotheca (10.11 ± 0.31 to 15.11 ± 0.65; 1.04 ± 0.26 to 12.50 ± 0.00; 12.50 ± 0.00 to 100.00 ± 0.00), and combination of aqueous extract (60 °C) of D. dissectus + methanol extract of K. anthotheca (7.89 ± 0.26 to 19.67 ± 0.37; 0.78 ± 0.00 to 50.00 ± 0.00; 12.50 ± 0.00 to 200.00 ± 0.00) exhibited broad spectrum antifungal activities and were fungistatic against all tested Candida species, which comprised 8 clinical/control and susceptible/resistant strains. None of the conventional drugs used demonstrated broad spectrum antifungal activity across all tested Candida species/strains.

Conclusion
Methanol extract of K. anthotheca, aqueous extract (24.4 °C) of M. rubrostipulata, and combination of aqueous extract (60 °C) of D. dissectus + methanol extract of K. anthotheca could be effective in the treatment of candidiasis. They demonstrated potential broad spectrum antifungal activity against different species and strains of tested Candida than the fluconazole and amphotericin B drugs. Their fungistatic nature showed their ability to inhibit fungal growth. Hence, these extracts/extract combination can offer better treatment option for candidiasis if they are standardized and also their active curative compounds isolated and made into antifungal drugs.
Prevalence of potential drug‒drug interactions and associated factors among elderly patients in Ethiopia: a systematic review and meta-analysis
Authors: Alemayehu Tekletsadik Tekleslassie , Wassie Yilkal Abebaw , Bekalu Abaynesh Fentahun , Tegegne Addisu Afrassa , Ayenew Wondim , Tadesse Gebresilassie , Getachew Demis , Yazie Abebaw Setegn , Teketelew Bisrat Birke , Mekete Mekonnen Derese , Fentahun Setegn , Abebe Tesfaye Birhanu , Minwagaw Tefera , Geremew Gebremariam Wulie 
Published: November 2024

Abstract
Background
The occurrence of potential drug‒drug interactions (pDDIs) is a serious global issue that affects all age groups, with the elderly population being the most vulnerable. This is due to their relatively high rates of comorbidity and polypharmacy, as well as physiological changes that can increase the potential for DDIs and the likelihood of adverse drug reactions. The aim of this study was to estimate the prevalence of pDDIs and associated factors among elderly patients in Ethiopia.

Methods
A comprehensive literature search using the preferred reporting items for systematic review and meta-analysis statement was conducted on HINARI, Science Direct, Embase, PubMed/MEDLINE, Google Scholar, and Research Gate. Data were extracted via a Microsoft Excel spreadsheet and analyzed via STATA version 11.0. Egger regression tests and funnel plot analysis were used to check publication bias, and the I2 statistic was used to evaluate statistical heterogeneity. Sensitivity and subgroup analyses were also conducted to identify potential causes of heterogeneity.

Results
Seven articles were analyzed, and a total of 1897 pDDIs were identified in 970 patients, resulting in an average of 1.97 DDIs per patient. The number of DDIs per patient ranged from 0.18 to 5.86. The overall prevalence of pDDIs among elderly patients was 50.69% (95% CI 18.77–82.63%). However, the prevalence of pDDIs ranged widely from 2.80 to 90.1%. When the severity of the interactions was considered, the prevalence of potential DDIs was found to be 28.74%, 70.68%, and 34.20% for major, moderate, and minor pDDIs, respectively. Polypharmacy and long hospital stays were identified as factors associated with pDDIs among elderly patients in Ethiopia.

Conclusions
The overall prevalence of pDDIs among elderly patients was high, with a wide range of prevalence rates. Moderate-severity interactions were the most prevalent. Polypharmacy and long hospital stays were identified as factors associated with pDDIs among elderly patients. The study suggests that DDIs identification database itself could have modified the DDIs prevalence rate. As a result, a single DDIs identification database needs to be authorized; otherwise, clinical knowledge should be taken into account when interpreting the information obtained.