bluuebunny/crossref_metadata_2025_split huggingface dataset:
2-phenylacetamide Separated from the seed of Lepidium apetalum Willd. inhibited renal fibrosis via MAPK pathway mediated RAAS and oxidative stress in SHR Rats
Authors: Yuan Pei-pei , Li Meng , Zhang Qi , Zeng Meng-nan , Ke Ying-ying , Wei Ya-xin , Fu Yang , Zheng Xiao-ke , Feng Wei-sheng 
Published: June 2023

Abstract
Background
Renal fibrosis with Renin–angiotensin–aldosterone system (RAAS) activation and oxidative stress are one of the major complications in hypertension. 2-phenylacetamide (PA), a major active component of Lepidium apetalum Willd. (L.A), has numerous pharmacological effects. Its analogues have the effect of anti-renal fibrosis and alleviating renal injury. This study aims to explore the underlying mechanism of PA for regulating the renal fibrosis in SHR based on the MAPK pathway mediated RAAS and oxidative stress.

Methods
The SHR rats were used as the hypertension model, and the WKY rats were used as the control group. The blood pressure (BP), urine volume were detected every week. After PA treatment for 4 weeks, the levels of RAAS, inflammation and cytokines were measured by Enzyme-Linked Immunosorbnent Assay (ELISA). Hematoxylin–Eosin staining (HE), Masson and Immunohistochemistry (IHC) were used to observe the renal pathology, collagen deposition and fibrosis. Western blot was used to examine the MAPK pathway in renal. Finally, the SB203580 (p38 MAPK inhibitor) antagonism assay in the high NaCl-induced NRK52e cells was used, together with In-Cell Western (ICW), Flow Cytometry (FCM), High Content Screening (HCS) and ELISA to confirm the potential pharmacological mechanism.

Results
PA reduced the BP, RAAS, inflammation and cytokines, promoted the urine, and relieved renal pathological injury and collagen deposition, repaired renal fibrosis, decreased the expression of NADPH Oxidase 4 (NOX4), transforming growth factor-β (TGF-β), SMAD3 and MAPK signaling pathway in SHR rats. Meanwhile,,the role of PA could be blocked by p38 antagonist SB203580 effectively in the high NaCl-induced NRK52e cells. Moreover, molecular docking indicated that PA occupied the ligand binding sites of p38 MAPK.

Conclusion
PA inhibited renal fibrosis via MAPK signalling pathway mediated RAAS and oxidative stress in SHR Rats.
The effect of lemon inhalation aromatherapy on pain, nausea, as well as vomiting and neurovascular assessment in patients for lower extremity fracture surgery: a randomized trial
Authors: Rambod Masoume , Pasyar Nilofar , Karimian Zahra , Farbood Arash 
Published: June 2023

Abstract
Background
Complementary and integrative medicine may be effective for postoperative outcomes. This study aimed to determine the effect of lemon inhalation aromatherapy on pain, nausea, and vomiting and neurovascular assessment in patients for lower extremity fracture surgery.

Methods
This is a randomized clinical trial study. Ninety patients who had undergone lower extremity fracture surgery were randomly assigned to the intervention (lemon aromatherapy) and control groups. Lemon aromatherapy was started in the morning of the surgery and extended at two-hour intervals until the end of the surgery, in the recovery room, and 16 h after surgery. Numerical pain and nausea and vomiting scales, the Rhodes Index of Nausea, Vomiting, and Retching, and the WACHS Neurovascular Observation Chart were used to assess the outcomes before and after the intervention (in the recovery room and 4, 8, 12, and 16 h post-surgery). The data were analyzed using the Wilcoxon test, ANCOVA, and Repeated Measure ANCOVA.

Results
A significant difference was observed between the groups in terms of the intensity of pain (P < 0.001) and nausea and vomiting (P = 0.001) during the study period. Moreover, a significant difference was found between groups as to the frequency and severity of nausea, vomiting, and retching. The amount and duration of postoperative vomiting and nausea were significantly lower in the intervention group compared to the control group. In addition, lemon inhalation aromatherapy decreased the frequency of anti-emetic drug administration in the recovery room (P = 0.04) and 16 h post-surgery (P = 0.03).

Conclusions
This study indicated that aromatherapy reduced pain intensity, postoperative nausea, vomiting, and retching, as well as the incidence of anti-emetic drug administration. Therefore, using lemon inhalation aromatherapy to relieve pain and reduce nausea and vomiting is suggested for lower extremity fracture patients who have undergone surgery.

Trial registration
This study was registered in the Iranian Registry of Clinical Trail (Number = 57,331, IRCT20130616013690N10, approved 24/07/2021) (https://www.irct.ir/trial/57331).
Teaching and learning pharmacology in Brazil before COVID-19 pandemic: a case study in Rio de Janeiro
Authors: Fidalgo-Neto Antonio Augusto , Lopes Renato Matos , Ribeiro Ricardo Riedel Martins , de Souza Cristina Alves Magalhães , de Souza Cavalcanti Raul Luiz , da Silva Ferreira Natiele Carla , Alves Luiz Anastacio 
Published: June 2023

Abstract
Background
Knowledge of pharmacology is crucial for physicians to perform rational and safe medicine. Medical professionals are responsible for prescribing drugs and a weak performace of those can result in medication errors leading to disability, hospitalization, and death, among other situations. It occurs worldwide, including in Brazil, so that learning pharmacology impacts on public health service. We aim to investigate the current pharmacology educational practices in medical schools in the state of Rio de Janeiro, Brazil.

Methods
We surveyed 14 of 22 medical schools in Rio de Janeiro. Pharmacology teachers (n=16) and medical students (n=89) answered a semi-structured questionnaire that included questions about the staff characteristics, pharmacology content, teacher’s concepts, and common practices and resources that were used in pharmacology classes.

Results
Our results revealed that the medical schools had similar overall curriculums. Pharmacology teachers work more than 30hs a week (75%) and conducted both research and teaching (62.5%). We also found that the multimedia projector was the most common resource (71.9%), and passive pedagogical methodologies (e.g., expository classes) remain a current strategy in pharmacology classes (89.9%). In general, medical students are poorly motivated (55%), which may be related to their performance in assessments. In addition, students believe that pharmacology is a complex (52%) or very complex subject (46%) since for its full understanding the student needs concepts from other disciplines, which can have an impact on the performance and motivation of students. As a result, these medical students do not fully understand the integration between pharmacology’s basic concepts and their clinical applications.

Conclusion
These data seem to demonstrate that the adopted teaching and learning pharmacology strategies and methodologies can be improved in Rio de Janeiro.
El Niño and other climatic drivers of epidemic malaria in Ethiopia: new tools for national health adaptation plans
Authors: Woyessa Adugna , Siebert Asher , Owusu Aisha , Cousin Rémi , Dinku Tufa , Thomson Madeleine C. 
Published: June 2023

AbstractBackgroundEthiopia has a history of climate related malaria epidemics. An improved understanding of malaria–climate interactions is needed to inform malaria control and national adaptation plans.MethodsMalaria–climate associations in Ethiopia were assessed using (a) monthly climate data (1981–2016) from the Ethiopian National Meteorological Agency (NMA), (b) sea surface temperatures (SSTs) from the eastern Pacific, Indian Ocean and Tropical Atlantic and (c) historical malaria epidemic information obtained from the literature. Data analysed spanned 1950–2016. Individual analyses were undertaken over relevant time periods. The impact of the El Niño Southern Oscillation (ENSO) on seasonal and spatial patterns of rainfall and minimum temperature (Tmin) and maximum temperature (Tmax) was explored using NMA online Maprooms. The relationship of historic malaria epidemics (local or widespread) and concurrent ENSO phases (El Niño, Neutral, La Niña) and climate conditions (including drought) was explored in various ways. The relationships between SSTs (ENSO, Indian Ocean Dipole and Tropical Atlantic), rainfall, Tmin, Tmax and malaria epidemics in Amhara region were also explored.ResultsEl Niño events are strongly related to higher Tmax across the country, drought in north-west Ethiopia during the July–August–September (JAS) rainy season and unusually heavy rain in the semi-arid south-east during the October–November–December (OND) season. La Niña conditions approximate the reverse. At the national level malaria epidemics mostly occur following the JAS rainy season and widespread epidemics are commonly associated with El Niño events when Tmax is high, and drought is common. In the Amhara region, malaria epidemics were not associated with ENSO, but with warm Tropical Atlantic SSTs and higher rainfall.ConclusionMalaria–climate relationships in Ethiopia are complex, unravelling them requires good climate and malaria data (as well as data on potential confounders) and an understanding of the regional and local climate system. The development of climate informed early warning systems must, therefore, target a specific region and season when predictability is high and where the climate drivers of malaria are sufficiently well understood. An El Niño event is likely in the coming years. Warming temperatures, political instability in some regions, and declining investments from international donors, implies an increasing risk of climate-related malaria epidemics.
How pictorial warnings change parents’ purchases of sugar-sweetened beverage for their children: mechanisms of impact
Authors: Hall Marissa G. , Grummon Anna H. , Queen Tara , Lazard Allison J. , Higgins Isabella C. A. , Richter Ana Paula C. , Taillie Lindsey Smith 
Published: June 2023

Abstract
Background
Pictorial health warnings on sugar-sweetened beverages (SSBs) are a promising policy for preventing diet-related disease in children. A recent study found that pictorial warnings reduced parents’ purchases of SSBs for their children by 17%. However, the psychological mechanisms through which warnings affect parental behavior remain unknown. We aimed to identify the mechanisms that explain how pictorial warnings affect parents’ SSB purchasing behavior for their children using secondary data from a randomized trial.

Methods
In 2020–2021, parents of children ages 2 to 12 years (n = 325) completed a shopping task in a convenience store laboratory in North Carolina, USA. Participants were randomly assigned to a pictorial warnings arm (SSBs displayed pictorial health warnings about type 2 diabetes and heart damage) or a control arm (SSBs displayed a barcode label). Parents then bought a beverage for their child and took a survey measuring 11 potential psychological mediators, selected based on health behavior theories and a model explaining the impact of tobacco warnings. We conducted simple mediation analyses to identify which of the 11 mechanisms mediated the impact of exposure to pictorial warnings on purchasing any SSBs for their children.

Results
Two of the 11 constructs were statistically significant mediators. First, the impact of pictorial warnings on the likelihood of purchasing any SSB was mediated by parents’ perceptions that SSBs were healthier for their child (mediated effect= −0.17; 95% CI = − 0.33, − 0.05). Second, parents’ intentions to serve SSBs to their children also mediated the effect of warnings on likelihood of purchasing any SSB (mediated effect= −0.07, 95% CI=-0.21, − 0.003).

Conclusions
Pictorial warnings reduced parents’ purchases of SSBs for their children by making parents think SSBs are less healthful for their children and reducing their intentions to serve SSBs to their children. Communication approaches that target healthfulness perceptions and intentions to serve SSBs may motivate parents to buy fewer SSBs for their children.
Cuproptosis engages in c-Myc-mediated breast cancer stemness
Authors: Wang Runtian , Xu Kun , Chen Qin , Hu Qin , Zhang Jian , Guan Xiaoxiang 
Published: June 2023

Abstract
Background
Intra-tumoral heterogeneity (ITH) is a distinguished hallmark of cancer, and cancer stem cells (CSCs) contribute to this malignant characteristic. Therefore, it is of great significance to investigate and even target the regulatory factors driving intra-tumoral stemness. c-Myc is a vital oncogene frequently overexpressed or amplified in various cancer types, including breast cancer. Our previous study indicated its potential association with breast cancer stem cell (BCSC) biomarkers.

Methods
In this research, we performed immunohistochemical (IHC) staining on sixty breast cancer surgical specimens for c-Myc, CD44, CD24, CD133 and ALDH1A1. Then, we analyzed transcriptomic atlas of 1533 patients with breast cancer from public database.

Results
IHC staining indicated the positive correlation between c-Myc and BCSC phenotype. Then, we used bioinformatic analysis to interrogate transcriptomics data of 1533 breast cancer specimens and identified an intriguing link among c-Myc, cancer stemness and copper-induced cell death (also known as “cuproptosis”). We screened out cuproptosis-related characteristics that predicts poor clinical outcomes and found that the pro-tumoral cuproptosis-based features were putatively enriched in MYC-targets and showed a significantly positive correlation with cancer stemness.

Conclusion
In addition to previous reports on its oncogenic roles, c-Myc showed significant correlation to stemness phenotype and copper-induced cell toxicity in breast cancer tissues. Moreover, transcriptomics data demonstrated that pro-tumoral cuproptosis biomarkers had putative positive association with cancer stemness. This research combined clinical samples with large-scale bioinformatic analysis, covered description and deduction, bridged classic oncogenic mechanisms to innovative opportunities, and inspired the development of copper-based nanomaterials in targeting highly heterogeneous tumors.
Targeting choroidal vasculopathy via up-regulation of tRNA-derived fragment tRF-22 expression for controlling progression of myopia
Authors: Liu Chang , Li Meiyan , Shen Yaming , Han Xiaoyan , Wei Ruoyan , Wang Yunzhe , Xu Shanshan , Zhou Xingtao 
Published: June 2023

Abstract
Background
Myopia has emerged as a major public health concern globally, which is tightly associated with scleral extracellular matrix (ECM) remodeling and choroidal vasculopathy. Choroidal vasculopathy has gradually been recognized as a critical trigger of myopic pathology. However, the precise mechanism controlling choroidal vasculopathy remains unclear. Transfer RNA-derived fragments (tRFs) are known as a novel class of small non-coding RNAs that plays important roles in several biological and pathological processes. In this study, we investigated the role of tRF-22-8BWS72092 (tRF-22) in choroidal vasculopathy and myopia progression.

Methods
The tRF-22 expression pattern under myopia-related stresses was detected by qRT-PCR. MTT assays, EdU incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of tRF-22 in choroidal endothelial cell function in vitro. Isolectin B4 staining and choroidal sprouting assay ex vivo were conducted to detect the role of tRF-22 in choroidal vascular dysfunction in vivo. Immunofluorescent staining, western blot assays and ocular biometric parameters measurement were performed to examine whether altering tRF-22 expression in choroid affects scleral hypoxia and ECM remodeling and myopia progression in vivo. Bioinformatics analysis and luciferase activity assays were conducted to identify the downstream targets of tRF-22. RNA-sequencing combined with m6A-qPCR assays were used to identify the m6A modified targets of METTL3. Gain-of-function and Loss-of-function analysis were performed to reveal the mechanism of tRF-22/METTL3-mediated choroidal vascular dysfunction.

Results
The results revealed that tRF-22 expression was significantly down-regulated in myopic choroid. tRF-22 overexpression alleviated choroidal vasculopathy and retarded the progression of myopia in vivo. tRF-22 regulated choroidal endothelial cell viability, proliferation, migration, and tube formation ability in vitro. Mechanistically, tRF-22 interacted with METTL3 and blocked m6A methylation of Axin1 and Arid1b mRNA transcripts, which led to increased expression of Axin1 and Arid1b.

Conclusions
Our study reveals that the intervention of choroidal vasculopathy via tRF-22-METTL3- Axin1/Arid1b axis is a promising strategy for the treatment of patients with myopic pathology.

Graphical Abstract
Factors associated with adolescent pregnancy and public health interventions to address in Nigeria: a scoping review
Authors: Alukagberie Majesty Enaworoke , Elmusharaf Khalifa , Ibrahim Nuha , Poix Sébastien 
Published: June 2023

Abstract
Background
Adolescent pregnancy is a global public health and social problem that affects both developed and developing countries. Reducing adolescent pregnancy is central to achieving sustainable development goals. In 2021 Nigeria’s Adolescent pregnancy was 106 per 1000 and showed an increasing rate. This study, therefore, aims to explore the literature to map the risk factors and interventions against adolescent pregnancy in Nigeria.

Method
A scoping review of studies published between January 2007 and December 2022 using PubMed, Web of Science and Africa Journals Online were searched using the keywords' adolescent pregnancy' AND 'Nigeria'. Studies were screened using the eligibility criteria.

Results
A total of 241 articles, of which 229 were identified through the databases and 12 were identified through hand search. After the full-text review, 28 studies met the inclusion criteria and were included in the final review. In Nigeria, the prevalence of adolescent pregnancy is between 7.5 and 49.5%. Associated factors for adolescent pregnancy in Nigeria are multifactorial, including individual, community, societal, school, family, and peer factors. Policies on adolescent sexual and reproductive health exist in Nigeria. Still, the policies need more sponsorship, implementation, and monitoring, while only some interventions on adolescent pregnancy majorly based on contraceptives and education of health providers are available in Nigeria.

Conclusion
Associated factors for adolescent Pregnancy in Nigeria are multidimensional, with educational attainment and wealth index being the highest associated factor. Intervention strategies aimed at the educational level have been identified as a critical factor in curbing adolescent pregnancy. Thus, policies on sexual, reproductive, and mental health development specifically targeting adolescents to reduce the cycle of societal dependence by empowering this group economically and educationally are justifiably warranted.
Development and validation of a two glycolysis-related LncRNAs prognostic signature for glioma and in vitro analyses
Authors: Xu Xiaoping , Zhou Shijun , Tao Yuchuan , Zhong Zhenglan , Shao Yongxiang , Yi Yong 
Published: June 2023

Abstract
Background
Mounting evidence suggests that there is a complex regulatory relationship between long non-coding RNAs (lncRNAs) and the glycolytic process during glioma development. This study aimed to investigate the prognostic role of glycolysis-related lncRNAs in glioma and their impact on the tumor microenvironment.

Methods
This study utilized glioma transcriptome data from public databases to construct, evaluate, and validate a prognostic signature based on differentially expressed (DE)-glycolysis-associated lncRNAs through consensus clustering, DE-lncRNA analysis, Cox regression analysis, and receiver operating characteristic (ROC) curves. The clusterProfiler package was applied to reveal the potential functions of the risk score-related differentially expressed genes (DEGs). ESTIMATE and Gene Set Enrichment Analysis (GSEA) were utilized to evaluate the relationship between prognostic signature and the immune landscape of gliomas. Furthermore, the sensitivity of patients to immune checkpoint inhibitor (ICI) treatment based on the prognostic feature was predicted with the assistance of the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Finally, qRT-PCR was used to verify the difference in the expression of the lncRNAs in glioma cells and normal cell.

Results
By consensus clustering based on glycolytic gene expression profiles, glioma patients were divided into two clusters with significantly different overall survival (OS), from which 2 DE-lncRNAs, AL390755.1 and FLJ16779, were obtained. Subsequently, Cox regression analysis demonstrated that all of these lncRNAs were associated with OS in glioma patients and constructed a prognostic signature with a robust prognostic predictive efficacy. Functional enrichment analysis revealed that DEGs associated with risk scores were involved in immune responses, neurons, neurotransmitters, synapses and other terms. Immune landscape analysis suggested an extreme enrichment of immune cells in the high-risk group. Moreover, patients in the low-risk group were likely to benefit more from ICI treatment. qRT-PCR results showed that the expression of AL390755.1 and FLJ16779 was significantly different in glioma and normal cells.

Conclusion
We constructed a novel prognostic signature for glioma patients based on glycolysis-related lncRNAs. Besides, this project had provided a theoretical basis for the exploration of new ICI therapeutic targets for glioma patients.
Combined electric and magnetic field therapy for bone repair and regeneration: an investigation in a 3-mm and an augmented 17-mm tibia osteotomy model in sheep
Authors: Darwiche Salim E. , Kaczmarek Anna , Schwarzenberg Peter , Inglis Brendan J. , Lechmann Beat , Kronen Peter , Ferguson Stephen J. , Dailey Hannah , von Rechenberg Brigitte , Klein Karina 
Published: June 2023

Abstract
Background
Therapies using electromagnetic field technology show evidence of enhanced bone regeneration at the fracture site, potentially preventing delayed or nonunions.

Methods
Combined electric and magnetic field (CEMF) treatment was evaluated in two standardized sheep tibia osteotomy models: a 3-mm non-critical size gap model and a 17-mm critical size defect model augmented with autologous bone grafts, both stabilized with locking compression plates. CEMF treatment was delivered across the fracture gap twice daily for 90 min, starting 4 days postoperatively (post-OP) until sacrifice (9 or 12 weeks post-OP, respectively). Control groups received no CEMF treatment. Bone healing was evaluated radiographically, morphometrically (micro-CT), biomechanically and histologically.

Results
In the 3-mm gap model, the CEMF group (n = 6) exhibited higher callus mineral density compared to the Control group (n = 6), two-fold higher biomechanical torsional rigidity and a histologically more advanced callus maturity (no statistically significant differences). In the 17-mm graft model, differences between the Control (n = 6) and CEMF group (n = 6) were more pronounced. The CEMF group showed a radiologically more advanced callus, a higher callus volume (p = 0.003) and a 2.6 × higher biomechanical torsional rigidity (p = 0.024), combined with a histologically more advanced callus maturity and healing.

Conclusions
This study showed that CEMF therapy notably enhanced bone healing resulting in better new bone structure, callus morphology and superior biomechanical properties. This technology could transform a standard inert orthopedic implant into an active device stimulating bone tissue for accelerated healing and regeneration.