bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of solid lipid nanocarrier containing methyl urolithin A by coating folate-bound chitosan and evaluation of its anti-cancer activity
Authors: Al-Fatlawi Ilham Naeem Abd Ali , Pouresmaeil Vahid , Davoodi-Dehaghani Fatemeh , Pouresmaeil Aida , Akhtari Ali , Tabrizi Masoud Homayouni 
Published: April 2024

Abstract
Background
Nanotechnology-based drug delivery systems have received much attention over the past decade. In the present study, we synthesized Methyl Urolithin A-loaded solid lipid nanoparticles decorated with the folic acid-linked chitosan layer called MuSCF-NPs and investigated their effects on cancer cells.

Methods
MuSCF-NPs were prepared using a high-pressure homogenization method and characterized using FTIR, FESEM, DLS, and zeta potential methods. Drug encapsulation was assessed by spectrophotometry and its cytotoxic effect on various cancer cells (MDA-MB231, MCF-7, PANC, AGS, and HepG2) by the MTT method. Antioxidant activity was assessed by the ABTS and DPPH methods, followed by expression of genes involved in oxidative stress and apoptosis by qPCR and flow cytometry.

Results
The results showed the formation of monodisperse and stable round nanoparticles with a size of 84.8 nm. The drug loading efficiency in MuSCF-NPs was reported to be 88.6%. MuSCF-NPs exhibited selective cytotoxicity against MDA-MB231 cells (IC50 = 40 μg/mL). Molecular analysis showed a significant increase in the expression of Caspases 3, 8, and 9, indicating that apoptosis was occurring in the treated cells. Moreover, flow cytometry results showed that the treated cells were arrested in his SubG1 phase, confirming the pro-apoptotic effect of the nanoparticles. The results indicate a high antioxidant effect of the nanoparticles with IC50 values ​​of 45 μg/mL and 1500 μg/mL against ABTS and DPPH, respectively. The reduction of catalase gene expression confirmed the pro-oxidant effect of nanoparticles in cancer cells treated at concentrations of 20 and 40 μg/mL.

Conclusions
Therefore, our findings suggest that the MuSCF-NPs are suitable candidates, especially for breast cancer preclinical studies.
Procedural skills workshops for primary care physicians in Israel: a comprehensive analysis
Authors: Rosenblum Omer , Yehoshua Ilan , Adler Limor , Liran Ori 
Published: April 2024

Abstract
Background
Some of the most common complaints addressed by primary care physicians (PCPs) require manual procedures, such as lacerations repair, abscesses drainage, ingrown toenails removal, dry needling for myofascial pain syndrome, and Epley maneuver for treating benign paroxysmal positional vertigo (BPPV). The aim of this study was to describe the procedural skills workshops program for PCPs implemented in Maccabi Healthcare Services and to investigate how many PCPs have participated and used the skills since the program’s inception in 2017.

Methods
In this observational study, we followed all participants in courses from 2017 to 2021. We extracted all procedures performed during these years by PCPs who learned the skill in MHS.

Results
During the study period, 620 PCPs participated in workshops for dry needling, soft-tissue and joint injections, BPPV treatment, minor surgical procedures, and spirometry. Most procedures performed were dry needling (average annual number 3,537) and minor surgical procedures (average annual number 361). The average annual use per physician was highest for dry needling (annual average use per physician who used the learned skill was 50.9), followed by soft tissue and joint injections (16.8), minor surgical procedures (14.8), and BPPV treatment (7.5).

Conclusion
procedural skills workshops may expand PCPs’ therapeutic arsenal, thus empowering PCPs and providing more comprehensive care for patients. Some manual skills, such as dry needling, soft tissue injections, and the Epley maneuver, were more likely to be used by participants than other skills, such as spirometry and soft tissue injections.
Medical students’ AI literacy and attitudes towards AI: a cross-sectional two-center study using pre-validated assessment instruments
Authors: Laupichler Matthias Carl , Aster Alexandra , Meyerheim Marcel , Raupach Tobias , Mergen Marvin 
Published: April 2024

Abstract
Background
Artificial intelligence (AI) is becoming increasingly important in healthcare. It is therefore crucial that today’s medical students have certain basic AI skills that enable them to use AI applications successfully. These basic skills are often referred to as “AI literacy”. Previous research projects that aimed to investigate medical students’ AI literacy and attitudes towards AI have not used reliable and validated assessment instruments.

Methods
We used two validated self-assessment scales to measure AI literacy (31 Likert-type items) and attitudes towards AI (5 Likert-type items) at two German medical schools. The scales were distributed to the medical students through an online questionnaire. The final sample consisted of a total of 377 medical students. We conducted a confirmatory factor analysis and calculated the internal consistency of the scales to check whether the scales were sufficiently reliable to be used in our sample. In addition, we calculated t-tests to determine group differences and Pearson’s and Kendall’s correlation coefficients to examine associations between individual variables.

Results
The model fit and internal consistency of the scales were satisfactory. Within the concept of AI literacy, we found that medical students at both medical schools rated their technical understanding of AI significantly lower (MMS1 = 2.85 and MMS2 = 2.50) than their ability to critically appraise (MMS1 = 4.99 and MMS2 = 4.83) or practically use AI (MMS1 = 4.52 and MMS2 = 4.32), which reveals a discrepancy of skills. In addition, female medical students rated their overall AI literacy significantly lower than male medical students, t(217.96) = -3.65, p <.001. Students in both samples seemed to be more accepting of AI than fearful of the technology, t(745.42) = 11.72, p <.001. Furthermore, we discovered a strong positive correlation between AI literacy and positive attitudes towards AI and a weak negative correlation between AI literacy and negative attitudes. Finally, we found that prior AI education and interest in AI is positively correlated with medical students’ AI literacy.

Conclusions
Courses to increase the AI literacy of medical students should focus more on technical aspects. There also appears to be a correlation between AI literacy and attitudes towards AI, which should be considered when planning AI courses.
Oncologists’ perspective on advance directives, a French national prospective cross-sectional survey – the ADORE study
Authors: Cambriel Amélie , Serey Kevin , Pollina-Bachellerie Adrien , Cancel Mathilde , Michalet Morgan , Bay Jacques-Olivier , Bouleuc Carole , Lotz Jean-Pierre , Philippart Francois 
Published: April 2024

Abstract
Background
The often poor prognosis associated with cancer necessitates empowering patients to express their care preferences. Yet, the prevalence of Advance Directives (AD) among oncology patients remains low. This study investigated oncologists' perspectives on the interests and challenges associated with implementing AD.

Methods
A French national online survey targeting hospital-based oncologists explored five areas: AD information, writing support, AD usage, personal perceptions of AD's importance, and respondent's profile. The primary outcome was to assess how frequently oncologists provide patients with information about AD in daily clinical practice. Additionally, we examined factors related to delivering information on AD.

Results
Of the 410 oncologists (50%) who responded to the survey, 75% (n = 308) deemed AD relevant. While 36% (n = 149) regularly inform patients about AD, 25% (n = 102) remain skeptical about AD. Among the respondents who do not consistently discuss AD, the most common reason given is the belief that AD may induce anxiety (n = 211/353; 60%). Of all respondents, 90% (n = 367) believe patients require specific information to draft relevant AD. Physicians with experience in palliative care were more likely to discuss AD (43% vs 32.3%, p = 0.027). Previous experience in critical care was associated with higher levels of distrust towards AD (31.5% vs 18.8%, p = 0.003), and 68.5% (n = 281) of the respondents expressed that designating a “person of trust” would be more appropriate than utilizing AD.

Conclusion
Despite the perceived relevance of AD, only a third of oncologists regularly apprise their patients about them. Significant uncertainty persists about the safety and relevance of AD.
Alerta Cannabis: A Tailored-Computer Web-Based Program for the Prevention of Cannabis Use in Adolescents: A Cluster-Randomized Controlled Trial Protocol
Authors: Lima-Serrano Marta , Barrera-Villalba Carmen , Mac-Fadden Isotta , Mesters Ilse , de Vries Hein 
Published: April 2024

AbstractBackgroundThe growing use of cannabis in adolescence is a public health problem that must be addressed through prevention. In Spain, the average age of initiation of cannabis use in the adolescent population is 14.8 years. At 14 years, the lifetime prevalence of cannabis use is 11.7%, which increases to 51.,5% at the age of 18; the prevalence of cannabis use in the population aged 14 to 18 years is 28.6%, a figure that must be tried to reduce, that is why this school prevention program is proposed: Alerta Cannabis.MethodsThe Alerta Cannabis research project consists of design, implementation, and evaluation. In the first phase, a computer-tailored eHealth program (Alerta Cannabis) is developed based on the I-Change Model, an integrated model based on three main behavioral change processes: awareness, motivation, and action. This program consists of four 30-minute sessions that will provide culturally adapted and personalized advice to motivate students not to use cannabis through text feedback, animations, and gamification techniques. This phase will also include usability testing. In the implementation phase, secondary school students from Western Andalusia, Spain (Seville, Cádiz, Huelva, and Córdoba) and Eastern Andalusia (Jaén, Málaga, and Granada) will be randomized to an experimental condition (EC) or a control condition (CC) for a cluster randomized clinical trial (CRCT). Each condition will have 35 classes within 8 schools. GI will receive the online intervention Alerta Cannabis. EC and CC will have to fill out a questionnaire at baseline, six months, and twelve months of follow-up. In the last phase, the effect of Alerta Cannabis is evaluated. The primary outcomes are the lifetime prevalence of cannabis use and its use in the last 30 days and at 6 months. At 12 months of follow-up, the prevalence in the last 12 months will also be assessed. The secondary outcome is the intention to use cannabis.DiscussionThe study tests the effect of the innovative program specifically aimed to reduce the use of cannabis in the adolescent population through eHealth in Spain. The findings aim to develop and implement evidence-based cannabis prevention interventions, which could support school prevention, for instance, the assistance of school nurses. If the program proves to be effective, it could be useful to prevent cannabis use on a national and international scale.Trial registrationNCT05849636. Date of registration: March 16, 2023.
Loss of ZNF451 mediates fibroblast activation and promotes lung fibrosis
Authors: Peng Hong , Zhang Yu , Min Jiali , Tan Yuexin , Liu Shanshan 
Published: April 2024

Abstract
Background
No effective therapies for pulmonary fibrosis (PF) exist because of the unclear molecular pathogenesis and the lack of effective therapeutic targets. Zinc finger protein 451 (ZNF451), a transcriptional regulator, plays crucial roles in the pathogenesis of several diseases. However, its expression pattern and function in PF remain unknown. This study was designed to investigate the role of ZNF451 in the pathogenesis of lung fibrosis.

Methods
GEO dataset analysis, RT‒PCR, and immunoblot assays were used to examine the expression of ZNF451 in PF; ZNF451 knockout mice and ZNF451-overexpressing lentivirus were used to determine the importance of ZNF451 in PF progression; and migration assays, immunofluorescence staining, and RNA-seq analysis were used for mechanistic studies.

Results
ZNF451 is downregulated and negatively associated with disease severity in PF. Compared with wild-type (WT) mice, ZNF451 knockout mice exhibited much more serious PF changes. However, ZNF451 overexpression protects mice from BLM-induced pulmonary fibrosis. Mechanistically, ZNF451 downregulation triggers fibroblast activation by increasing the expression of PDGFB and subsequently activating PI3K/Akt signaling.

Conclusion
These findings uncover a critical role of ZNF451 in PF progression and introduce a novel regulatory mechanism of ZNF451 in fibroblast activation. Our study suggests that ZNF451 serves as a potential therapeutic target for PF and that strategies aimed at increasing ZNF451 expression may be promising therapeutic approaches for PF.
Valorisation of cotton post-industrial textile waste into lactic acid: chemo-mechanical pretreatment, separate hydrolysis and fermentation using engineered yeast
Authors: Simonetti Marta , Butti Pietro , Di Lorenzo Raffaella Desiré , Mapelli Valeria , Branduardi Paola 
Published: April 2024

Abstract
Background
The textile industry has several negative impacts, mainly because it is based on a linear business model that depletes natural resources and produces excessive amounts of waste. Globally, about 75% of textile waste is disposed of in landfills and only 25% is reused or recycled, while less than 1% is recycled back into new garments. In this study, we explored the valorisation of cotton fabric waste from an apparel textile manufacturing company as valuable biomass to produce lactic acid, a versatile chemical building block.

Results
Post-industrial cotton patches were pre-treated with the aim of developing a methodology applicable to the industrial site involved. First, a mechanical shredding machine reduced the fabric into individual fibres of maximum 35 mm in length. Afterwards, an alkaline treatment was performed, using NaOH at different concentrations, including a 16% (w/v) NaOH enriched waste stream from the mercerisation of cotton fabrics. The combination of chemo-mechanical pre-treatment and enzymatic hydrolysis led to the maximum recovery yield of 90.46 ± 3.46%, corresponding to 74.96 ± 2.76 g/L of glucose released, which represents a novel valorisation of two different side products (NaOH enriched wastewater and cotton textile waste) of the textile industry. The Saccharomyces cerevisiae strain CEN.PK m850, engineered for redirecting the natural alcoholic fermentation towards a homolactic fermentation, was then used to valorise the glucose-enriched hydrolysate into lactic acid. Overall, the process produced 53.04 g/L ± 0.34 of l-lactic acid, with a yield of 82.7%, being the first example of second-generation biomass valorised with this yeast strain, to the best of our knowledge. Remarkably, the fermentation performances were comparable with the ones obtained in the control medium.

Conclusion
This study validates the exploitation of cotton post–industrial waste as a possible feedstock for the production of commodity chemicals in microbial cell-based biorefineries. The presented strategy demonstrates the possibility of implementing a circular bioeconomy approach in manufacturing textile industries.

Graphical Abstract
The troglitazone derivative EP13 disrupts energy metabolism through respiratory chain complex I inhibition in breast cancer cells and potentiates the antiproliferative effect of glycolysis inhibitors
Authors: Muller Claire , Lacroix-Malgras Victorine , Kluza Jérôme , Laine William , Güler Yonca , Bost Frédéric , Boisbrun Michel , Mazerbourg Sabine , Flament Stéphane 
Published: April 2024

Abstract
Background
The metabolism of cancer cells generally differs from that of normal cells. Indeed, most cancer cells have a high rate of glycolysis, even at normal oxygen concentrations. These metabolic properties can potentially be exploited for therapeutic intervention. In this context, we have developed troglitazone derivatives to treat hormone-sensitive and triple-negative breast cancers, which currently lack therapeutic targets, have an aggressive phenotype, and often have a worse prognosis than other subtypes. Here, we studied the metabolic impact of the EP13 compound, a desulfured derivative of Δ2-troglitazone that we synthetized and is more potent than its parent compounds.

Methods
EP13 was tested on two triple-negative breast cancer cell lines, MDA-MB-231 and Hs578T, and on the luminal cell line MCF-7. The oxygen consumption rate (OCR) of the treated cell lines, Hs578T mammospheres and isolated mitochondria was measured using the XFe24 Seahorse analyser. ROS production was quantified using the MitoSOX fluorescent probe. Glycolytic activity was evaluated through measurement of the extracellular acidification rate (ECAR), glucose consumption and lactate production in extracellular medium. The synergistic effect of EP13 with glycolysis inhibitors (oxamate and 2-deoxyglucose) on cell cytotoxicity was established using the Chou-Talalay method.

Results
After exposure to EP13, we observed a decrease in the mitochondrial oxygen consumption rate in MCF7, MDA-MB-231 and Hs578T cells. EP13 also modified the maximal OCR of Hs578T spheroids. EP13 reduced the OCR through inhibition of respiratory chain complex I. After 24 h, ATP levels in EP13-treated cells were not altered compared with those in untreated cells, suggesting compensation by glycolysis activity, as shown by the increase in ECAR, the glucose consumption and lactate production. Finally, we performed co-treatments with EP13 and glycolysis inhibitors (oxamate and 2-DG) and observed that EP13 potentiated their cytotoxic effects.

Conclusion
This study demonstrates that EP13 inhibits OXPHOS in breast cancer cells and potentiates the effect of glycolysis inhibitors.
Constitutive knockout of interleukin-6 ameliorates memory deficits and entorhinal astrocytosis in the MRL/lpr mouse model of neuropsychiatric lupus
Authors: Reynolds Joshua , Huang Michelle , Li Yaxi , Meineck Myriam , Moeckel Tamara , Weinmann-Menke Julia , Mohan Chandra , Schwarting Andreas , Putterman Chaim 
Published: April 2024

Abstract
Background
Neuropsychiatric lupus (NPSLE) describes the cognitive, memory, and affective emotional burdens faced by many lupus patients. While NPSLE’s pathogenesis has not been fully elucidated, clinical imaging studies and cerebrospinal fluid (CSF) findings, namely elevated interleukin-6 (IL-6) levels, point to ongoing neuroinflammation in affected patients. Not only linked to systemic autoimmunity, IL-6 can also activate neurotoxic glial cells the brain. A prior pre-clinical study demonstrated that IL-6 can acutely induce a loss of sucrose preference; the present study sought to assess the necessity of chronic IL-6 exposure in the NPSLE-like disease of MRL/lpr lupus mice.

Methods
We quantified 1308 proteins in individual serum or pooled CSF samples from MRL/lpr and control MRL/mpj mice using protein microarrays. Serum IL-6 levels were plotted against characteristic NPSLE neurobehavioral deficits. Next, IL-6 knockout MRL/lpr (IL-6 KO; n = 15) and IL-6 wildtype MRL/lpr mice (IL-6 WT; n = 15) underwent behavioral testing, focusing on murine correlates of learning and memory deficits, depression, and anxiety. Using qPCR, we quantified the expression of inflammatory genes in the cortex and hippocampus of MRL/lpr IL-6 KO and WT mice. Immunofluorescent staining was performed to quantify numbers of microglia (Iba1 +) and astrocytes (GFAP +) in multiple cortical regions, the hippocampus, and the amygdala.

Results
MRL/lpr CSF analyses revealed increases in IL-17, MCP-1, TNF-α, and IL-6 (a priori p-value < 0.1). Serum levels of IL-6 correlated with learning and memory performance (R2 = 0.58; p = 0.03), but not motivated behavior, in MRL/lpr mice. Compared to MRL/lpr IL-6 WT, IL-6 KO mice exhibited improved novelty preference on object placement (45.4% vs 60.2%, p < 0.0001) and object recognition (48.9% vs 67.9%, p = 0.002) but equivalent performance in tests for anxiety-like disease and depression-like behavior. IL-6 KO mice displayed decreased cortical expression of aif1 (microglia; p = 0.049) and gfap (astrocytes; p = 0.044). Correspondingly, IL-6 KO mice exhibited decreased density of GFAP + cells compared to IL-6 WT in the entorhinal cortex (89 vs 148 cells/mm2, p = 0.037), an area vital to memory.

Conclusions
The inflammatory composition of MRL/lpr CSF resembles that of human NPSLE patients. Increased in the CNS, IL-6 is necessary to the development of learning and memory deficits in the MRL/lpr model of NPSLE. Furthermore, the stimulation of entorhinal astrocytosis appears to be a key mechanism by which IL-6 promotes these behavioral deficits.
A basaloid carcinoma with multilocular thymic cyst mimicking a mediastinal teratoma
Authors: Su Chen , Zhu Xiaobo , Wang Qiang , Zhang Junjie 
Published: April 2024

AbstractThis case report details a rare thymic basaloid carcinoma initially misinterpreted as a mediastinal teratoma, underscoring the diagnostic challenges posed by such tumors. A 71-year-old female presented with an asymptomatic anterior mediastinal tumor discovered incidentally during a routine health examination. Surgical intervention, followed by pathological and immunohistochemical analysis including CK-pan, p63, p40, and CD117 molecules, led to a definitive diagnosis of basaloid carcinoma of the thymus. This case highlights the critical importance of differential diagnosis in mediastinal lesions, especially those presenting with multilocular thymic cysts on chest CT. The subxiphoid video-assisted thoracoscopic surgery enabled complete tumor resection with minimal trauma and favorable postoperative outcomes. The patient opted against further radiotherapy or chemotherapy and she has survived for over eight months without recurrence. This case report contributes to the growing understanding of thymic basaloid carcinoma, a rare and potentially aggressive thymic carcinoma subtype. It emphasizes the necessity for precise surgical techniques and enhanced diagnostic acumen among cardiothoracic surgeons and oncologists.
Management of left atrial myxoma in pregnant women: a case series
Authors: Liu Yanli , Wang Haiping , Huang Huanlei , Han Fengzhen , Zhuang Jian , Ou Yanqiu , Lin Yanyan , Zhang Weina 
Published: April 2024

Abstract
Background
Left atrial myxoma during pregnancy is rare. We present three cases in order to aid in the management.

Case Presentation
Three cases of left atrial myxoma during pregnancy were presented in this article. Three patients all received multidisciplinary team work and acquired good outcomes. The case 1 had no symptoms and delivered before traditional cardiac surgery. The case 2 and case 3 undergone totally endoscopic minimally invasive cardiac surgery during pregnancy. The case 3 maintained pregnancy to term and gave birth to a healthy baby via vaginal delivery. No relapse of the tumor was observed.

Conclusions
The management of left atrial myxoma during pregnancy ought to be individualized and combined with the gestational age. If the diagnosis was made in the first two trimesters of pregnancy, totally endoscopic minimally invasive cardiac surgery during pregnancy would be an optimal choice. The patients can benefit from the multidisciplinary team work.