bluuebunny/crossref_metadata_2025 huggingface dataset:
An algorithm for spectrally matching bi-directional ground motions to a target RotD100 spectrum while maintaining the radial spectral acceleration pattern
Authors: Zhou Jian , Igarashi Akira
Published: June 2023

An integrated algorithm to spectrally match two seed-recorded horizontal bi-directional ground motion components to a maximum-direction response spectrum (RotD100) while maintaining the radial spectral acceleration pattern (RadSAP) at target natural periods is presented. The algorithm is based on the complex-discrete-Fourier-transform (CDFT) and iterative manipulation of the seed-recorded bi-directional ground motions. Initially, a population of candidate bi-directional ground motion pairs is generated, and the candidate resulting in the minimum error in RadSAP is picked. Subsequently, the CDFT coefficients of the picked bi-directional ground motion near the target natural periods are rotated to modify the orientation angle, which contributes to the modification of RadSAP. Then, a double iterative method is introduced to modify the bi-directional ground motion after CDFT coefficients rotation to be spectral and envelope shape compatible in the frequency and time domain. In order to show the effectiveness of the proposed algorithm, two target response spectra are determined following the current ASCE/SEI 7-16 and CJJ 166-2011 specifications, and 10 bi-directional ground motions are selected based on the resemblance in response spectrum for each target spectrum. It is shown that with the proposed algorithm, the RotD100 response spectra estimated from the modified bi-directional ground motions closely match the smooth target RotD100 response spectrum, and the RadSAPs at these target natural periods show an improved match with the seed-recorded bi-directional ground motions than the previous version method. Furthermore, the waveforms of the results obtained using the proposed method are similar to that of the scaled seed records in terms of acceleration, velocity, and displacement. Thus, the generated bi-directional ground motions can be used for future seismic risk assessment of buildings considering the directionality effects.
Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: a 3-year follow-up
Authors: Zinzani Pier Luigi , Santoro Armando , Gritti Giuseppe , Brice Pauline , Barr Paul M. , Kuruvilla John , Cunningham David , Kline Justin , Johnson Nathalie A. , Mehta-Shah Neha , Lisano Julie , Wen Rachael , Akyol Alev , Moskowitz Alison J.
Published: June 2023

Patients with relapsed/refractory primary mediastinal large B-cell lymphoma (R/R PMBL) have poor responses to salvage therapy. Nivolumab and brentuximab vedotin (BV) showed promising early efficacy in patients with R/R PMBL in the phase 1/2 open-label, multicenter CheckMate 436 study; we report safety and efficacy findings from the 3-year follow-up. Patients who were eligible were aged ≥15 years with R/R PMBL previously treated with either high-dose chemotherapy plus autologous hematopoietic cell transplantation (HCT) or ≥2 prior multiagent chemotherapies, and had Eastern Cooperative Oncology Group performance status scores of 0 to 1 and CD30 expression of ≥1%. Patients were treated with nivolumab 240 mg and BV 1.8 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. Primary end point was objective response rate (ORR); secondary end points included complete response rate, duration of response, progression-free survival (PFS), and overall survival (OS). Safety was monitored throughout. At final database lock (30 March 2022), 29 patients had received nivolumab plus BV; median follow-up was 39.6 months. Investigator-assessed ORR was 73.3%; median time to response was 1.3 months (range, 1.1-4.8). Median PFS was 26.0 months; median OS was not reached. PFS and OS rates at 24 months were 55.5% (95% confidence interval [CI], 32.0-73.8) and 75.5% (95% CI, 55.4-87.5), respectively. The most frequently occurring grade 3/4 treatment-related adverse event was neutropenia. Consolidative HCT was received by 12 patients, with a 100-day complete response rate of 100.0%. This 3-year follow-up showed long-term efficacy for nivolumab plus BV in R/R PMBL, with no new safety signals. This trial was registered at www.clinicaltrials.gov as #NCT02581631.
High genome heterozygosity revealed vegetative propagation over the sea in Moso bamboo
Authors: Nishiyama Norihide , Shinozawa Akihisa , Matsumoto Takashi , Izawa Takeshi
Published: June 2023

Background

Moso bamboo (Phyllostachys edulis) is a typical East Asian bamboo that does not flower for > 60 years and propagates without seed reproduction. Thus, Moso bamboo can be propagated vegetatively, possibly resulting in highly heterozygous genetic inheritance. Recently, a draft genome of Moso bamboo was reported, followed by whole genome single nucleotide polymorphisms (SNP) analysis, which showed that the genome of Moso bamboo in China has regional characteristics. Moso bamboo in Japan is thought to have been introduced from China over the sea in 1736. However, it is unclear where and how Moso bamboo was introduced in Japan from China. Here, based on detailed analysis of heterozygosity in genome diversity, we estimate the spread of genome diversity and its pedigree of Moso bamboo.

Results

We sequenced the whole genome of Moso bamboo in Japan and compared them with data reported previously from 15 regions of China. Only 4.1 million loci (0.37% of the analyzed genomic region) were identified as polymorphic loci. We next narrowed down the number of polymorphic loci using several filters and extracted more reliable SNPs. Among the 414,952 high-quality SNPs, 319,431 (77%) loci were identified as heterozygous common to all tested samples. The result suggested that all tested samples were clones via vegetative reproduction. Somatic mutations may accumulate in a heterozygous manner within a single clone. We examined common heterozygous loci between samples from Japan and elsewhere, from which we inferred that an individual closely related to the sample from Fujian, China, was introduced to Japan across the sea without seed reproduction. In addition, we collected 16 samples from four nearby bamboo forests in Japan and performed SNP and insertion/deletion analyses using a genotyping by sequencing (GBS) method. The results suggested that a small number of somatic mutations would spread within and between bamboo groves.

Conclusions

High heterozygosity in the genome-wide diversity of Moso bamboo implies the vegetative propagation of Moso bamboo from China to Japan, the pedigree of Moso bamboo in Japan, and becomes a useful marker to approach the spread of genome diversity in clonal plants.
Alcohol consumption may be associated with postoperative delirium in the elderly: the PNDABLE study
Authors: Wu Xiaoyue , Zhang Ning , Zhou Bin , Liu Siyu , Wang Fei , Wang Jiahan , Tang Xinhui , Lin Xu , Wang Bin , Bi Yanlin
Published: June 2023

Objectives

This study aimed to reveal the relationship between alcohol consumption and Postoperative delirium (POD) in the elderly.

Methods

We selected 252 patients from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE ) study. Patients in the PNDABLE database have been measured for Alzheimer-related biomarkers in CSF (Aβ40, Aβ42, P-tau, and tau protein). Mini-Mental State Examination (MMSE) was used to assess the preoperative mental status of patients. POD was diagnosed using the Confusion Assessment Method (CAM) and assessed for severity using the Memorial Delirium Assessment Scale (MDAS). Logistic regression analysis was utilized to explore the association of alcohol consumption with POD. Linear regression analysis was used to study the relationship between alcohol consumption and CSF biomarkers. Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects. Finally, we constructed the receiver operating characteristic (ROC) curve and the nomogram model to evaluate the efficacy of alcohol consumption and CSF biomarkers in predicting POD. 

Result

The incidence of POD was 17.5%. Logistic regression showed that alcohol consumption (OR = 1.016, 95%CI 1.009–1.024, P < 0.001) is a risk factor for POD. What’s more, Aβ42 is a protective factor for POD (OR = 0.993, 95%CI 0.989–0.997, P < 0.05), and P-Tau was a risk factor for POD (OR = 1.093, 95%CI 1.022–1.168, P < 0.05). Linear regression analysis revealed that alcohol consumption was negatively associated with CSF Aβ42 (β = -0.638, P < 0.001) in POD patients. Mediation analyses showed that alcohol consumption is likely to partially mediate POD through Aβ42 (proportion:14.21%). ROC curve showed that alcohol consumption (AUC = 0.904; P < 0.001) exhibited a relatively better discriminatory ability in POD prediction compared to Aβ42 (AUC = 0.798; P < 0.001). The calibration curve indicated a good nomogram prediction (P = 0.797).

Conclusion

Alcohol consumption is a risk factor for POD (particularly for those with > 24 g a day on average) in the elderly, and contributes to POD through the mediation of Aβ42.
HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins
Authors: Li Jiawen , Tang Xiaofang , Xu Jingjing , Liu Ru , Jiang Lin , Xu Lianjun , Tian Jian , Feng Xinxing , Wu Yajie , Zhang Yin , Wang Dong , Sun Kai , Xu Bo , Zhao Wei , Hui Rutai , Gao Runlin , Song Lei , Yuan Jinqing , Zhao Xueyan
Published: June 2023

Background

To investigate the association of HMGCR and NPC1L1 gene polymorphisms with residual cholesterol risk (RCR) in patients with premature triple-vessel disease (PTVD).

Methods

Three SNPs within HMGCR including rs12916, rs2303151, and rs4629571, and four SNPs within NPC1L1 including rs11763759, rs4720470, rs2072183, and rs2073547 were genotyped. RCR was defined as achieved low-density lipoprotein cholesterol (LDL-C) concentrations after statins higher than 1.8 mmol/L (70 mg/dL).

Results

Finally, a total of 609 PTVD patients treated with moderate-intensity statins were included who were divided into two groups: non-RCR group (n = 88) and RCR group (n = 521) according to LDL-C concentrations. Multivariate logistic regression showed the homozygotes for the minor allele of rs12916 within HMGCR gene (CC) were associated with a 2.08 times higher risk of RCR in recessive model [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.16–3.75]. In codominant model, the individuals homozygous for the minor allele of rs12916 (CC) were associated with a 2.26 times higher risk of RCR (OR: 2.26, 95% CI: 1.16–4.43) while the heterozygous individuals (CT) were not, compared with the individuals homozygous for the major allele of rs12916 (TT). There was no significant association between the SNPs within NPC1L1 gene and RCR in various models.

Conclusions

We first reported that the variant homozygous CC of rs12916 within HMGCR gene may incur a significantly higher risk of RCR in PTVD patients treated with statins, providing new insights into early individualized guidance of precise lipid-lowering treatment.
Homocysteine induces ferroptosis in endothelial cells through the systemXc−/GPX4 signaling pathway
Authors: Shi Jiahao , Chen Di , Wang Zilin , Li Shaolin , Zhang Shuying
Published: June 2023

Objectives

To investigate whether ferroptosis is involved in HCY-induced endothelial injury and the possible mechanism of HCY-induced ferroptosis.

Methods

EA. hy926 cells were cultured in vitro. Cells were intervened using HCY and Fer-1. The cells were divided into Control groups, HCY (4 mM), HCY (8 mM), HCY + Fer-1 (4 mM HCY + 0.5/2.5/5 µM Fer-1). CCK-8 assay was used to detect cell viability; Flow Cytometry was used to detect cellular Lip-ROS, TBA and Microplate assay was used to detect MDA&GSH, Western blot was used to detect the expression of ferroptosis-related proteins GPX4 and SLC7A11.

Results

HCY can inhibited the proliferation of EA. hy926 cells in a time- and concentration-dependent manner; Fer-1 inhibits HCY-induced ferroptosis in EA.hy926 cells in a concentration-dependent manner; Compared with the control group, the cell viability and GSH content in the HCY group was significantly decreased (p < 0.05), and the Lip-ROS and MDA were significantly increased (p < 0.05); After co-culture of HCY and Fer-1, compared with the HCY (4 mM) group, the cell viability and GSH content in the co-culture group were significantly increased (p < 0.05), and the Lip-ROS and MDA were significantly decreased (p < 0.05) in a concentration-dependent manner; Western blotting results showed that the protein expression levels of ferroptosis-related proteins GPX4 and SLC7A11 in each experimental were significantly decreased after HCY treatment (p < 0.05), and Fer-1 could significantly reverse this effect.

Conclusions

(1) HCY can induce ferroptosis in vascular endothelial cells. (2) HCY may induce vascular endothelial cell ferroptosis through the system Xc–GSH-GPX4 signaling pathway.
Clinical characteristics, management, and 5-year survival compared between no standard modifiable risk factor (SMuRFless) and ≥ 1 SMuRF ACS cases: an analysis of 15,051 cases from Pakistan
Authors: Sheikh Sana , Peerwani Ghazal , Hanif Bashir , Virani Salim
Published: June 2023

Background

There has been an increase in Acute Coronary Syndrome (ACS) patients without standard modifiable risk factors i.e. hypertension, diabetes, dyslipidemia, and tobacco use (SMuRFless) compared to the patients with ≥ 1 SMuRF but this has not been studied in South Asia despite them being a high-risk population. We conducted a comparative analysis of first episodes of ACS cases admitted to a tertiary cardiac center in Pakistan between SMuRFless and ≥ 1 SMuRF patients for clinical presentation, management, in-hospital, and 5-year mortality.

Methods

We undertook a retrospective study and data of 15,051 patients admitted at Tabba Heart Institute (THI) with the first episode of ACS was extracted from Chest Pain-MI™, and the CathPCI Registry® registry affiliated with the National Cardiovascular Data Registry (NCDR®), USA. Logistic regression and Cox proportional algorithm yielded odds ratio (OR) and hazard ratios (HR) with 95% confidence interval (CI) for associated factors of in-patient and 5-year mortality.

Results

There were 15% SMuRFless cases and in-hospital mortality was 4.1% in SMuRFless vs. 3.9% in the ≥ 1 SMuRF group (p-0.59), the difference remained insignificant after adjusting for age, gender, Killip class, multivessel disease, type of ACS, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) (Adjusted OR:1.1 [0.8, 1.3]. Unadjusted 5-year mortality was 40% lower in the SMuRFless group but the difference was insignificant after adjusting for age, gender, disease at presentation, its severity, and management (Adjusted HR 0.7 95% CI[0.5, 1.0]). STEMI, NSTEMI, Killip class, and multivessel disease increased the risk of overall 5-year mortality.

Conclusion

In-hospital and 5-year mortality was not different between the SMuRFless and ≥ 1 SMuRF group, there is a need to understand mediators of immediate and long-term mortality risk in SMuRFless patients.
“They want you to know who they really are inside of the old visage”—biographical storytelling as a methodological tool to explore emotional challenges in old age
Authors: Fang Chao , Comery Alastair , Carr Sam
Published: June 2023

Background

Growing older is often associated with resilience, contentedness and inner growth. Older people however are also at risk of confronting unique emotional challenges as a result of varied ageing-related experiences. By employing a biographical lens, we aim to introduce storytelling as a methodological tool to more holistically explore older people’s emotional challenges and to improve their wellbeing.

Methods

Building upon theoretical understandings about the narrative construction of identity across the life span, we draw upon a qualitative study about older people’s loneliness as an example to showcase the methodological value and feasibility of biographical storytelling. We aim to better understand the nuanced and sometimes painful emotional experiences that can be encountered alongside ageing.

Results

Findings from the qualitative study we showcase, highlight that unique emotional pains and the (in)ability to deal with such in old age could be deeply rooted in older people’s earlier lives. These findings contextualise people’s emotional challenges and needs within their identity, as a narrative thread that links their past, present and expected future. As such, our example study shows that emotional challenges in old age are not only ageing-related, but can be more fundamentally connected to disruptions to the ongoing flow of narrative identity construction.

Conclusion

The highly retrospective and reflexive nature of these findings illustrates the methodological merit of biographical storytelling. We argue that the impact of biographical storytelling can go further than both conventional semi-structured narrative interviews and existing interventional tools. Instead, it is a particularly useful research methodology to explore human experiences and needs in the unique context of ageing. This methodological development thus provides an insightful analytical lens to explore how older people’s earlier life experiences may be carried forward and confronted to shape their emotional stability in the present and future stages of their ageing lives. Beyond the methodological significance, we further demonstrate the benefits of empowering older people to reconstruct their ageing lives in the context of their biography.
The value of enhanced multiparameteric MRI diagnostic model for preoperatively predicting surgical methods of inferior vena cava in patients with renal tumors and inferior vena cava tumor thrombus
Authors: Pei Xinlong , Lu Min , Liu Zhuo , Liu Baohua , Deng Yuhan , Yuan Huishu , Ma Lulin
Published: June 2023

Background

Inferior vena cava tumor thrombus (IVCTT) invading the IVC wall majorly affects the surgical method choice and prognosis in renal tumors. Enhanced multiparameteric MRI plays an important role in preoperative evaluation. In this work, an MRI-based diagnostic model for IVCTT was established so as to guide the preoperative decisions.

Methods

Preoperative MR images of 165 cases of renal tumors with IVCTT were retrospectively analyzed, and imaging indicators were analyzed, including IVCTT morphology and Mayo grade, IVCTT diameter measurements, bland thrombosis, primary MRI-based diagnosis of renal tumor, and involvement of contralateral renal vein. The indicators were analyzed based on intraoperative performance and resection scope of the IVC wall. Multivariate logistic regression analysis was used to establish the diagnostic model.

Results

The morphological classification of the IVCTT, primary MRI-based diagnosis of renal tumors, maximum transverse diameter of IVCTT, and length of the bland thrombus were the main indexes predicting IVC wall invasion. The MRI-based diagnostic model established according to these indexes had good diagnostic efficiency. The prediction probability of 0.61 was set as the cutoff value. The area under the curve of the test set was 0.88, sensitivity was 0.79, specificity was 0.85, and prediction accuracy was 0.79 under the optimal cutoff value.

Conclusion

The preoperative MRI-based diagnostic model could reliably predict IVC wall invasion, which is helpful for better prediction of IVC-associated surgical operations.
Role of body mass index in the relationship between adverse childhood experiences, resilience, and mental health: a multivariate analysis
Authors: Zhang Yi , Li Yonghan , Jiang Tian , Zhang Qiu
Published: June 2023

Objectives

Depression among adolescents is a global concern. Adverse childhood experiences (ACEs) have been correlated with negative physical and mental health such as obesity and depression; however, increasing evidence has suggested that their correlation might be moderated by BMI and resilience. In this study, we aim to explore (1) whether resilience moderate the risk of mental health by ACEs; (2) whether BMI is a moderator of this relationship.

Study Design

Adolescents were obtained from 4 grade college students by a multi-stage convenience sampling method in the period of May to Jun, 2022.

Methods

We use the Connor-Davidson Resilience scale, Depression, Anxiety and Stress Scale-21 Item (DASS-21) questionnaires to measure the ACEs, BMI, resilience and mental health. The primary exposure was ACEs and the primary outcome was mental health; while resilience and BMI were moderators. Multivariable linear regression model was used to establish the relationship of ACEs, resilience and BMI against mental health status. Moderate analysis was employed by PROCESS method to explore the relationship between these variables.

Results

A total of 3600 individuals were initially enrolled, after excluding 22 with invalid questionnaires, 3578 adolescents were finally included. The mean age was (20.53 ± 1.65) years old. After adjusted for covariates, multivariable linear regression suggest that the high level ACEs (, β =0.58, , 95%CI:0.54,0.62, P < 0.01), resilience (, β=-0.27, 95%CI: , 95%CI: -0.28,-0.26, P < 0.01) were associated with higher depression symptoms, and BMI (, β =0.073, 95%CI: 0.002–0.15, P < 0.05) was associated with higher depression symptoms. There is also the interaction between resilience, ACEs and mental health (depression, anxiety and stress symptoms). In the relationship between ACEs and mental health, resilience and BMI played a moderator role.

Conclusions

The moderate analysis also provided further evidence of a link between resilience, ACEs, BMI and mental health. The findings shed new light on potential mechanisms between ACEs and mental health, including the effects of the co-interaction of resilience and BMI, adding to previous literature. ACEs may be a profound variable to measure adolescents’ psychosocial environment to influence mental health, and resilience moderate this effect and is also moderated by BMI.
Barriers and facilitating factors to healthcare accessibility among Nepalese migrants during COVID-19 crisis in Japan: an exploratory sequential mixed methods study
Authors: Paudel Sushila , K C Bhandari Aliza , Gilmour Stuart , Lee Hyeon Ju , Kanbara Sakiko
Published: June 2023

Background

The COVID-19 pandemic has highlighted the need for global unity and timely access to healthcare for all including multilingual and intercultural societies. This study aimed to identify barriers to healthcare access due to the COVID-19 crisis among Nepalese migrants in Japan and explore ways to counter these barriers, both in routine and crisis situations.

Methods

This study used an exploratory sequential mixed-methods study design. The researchers conducted 11 focus group discussions including 89 participants and an online survey involving 937 respondents. The integration of focus group discussions and logistic regression analysis from the survey was reported via a ‘joint display’.

Results

Twenty-six themes on barriers to and six on facilitators of healthcare accessibility were identified by the focus group discussions among which 17 barriers like lack of knowledge of health insurance, language barriers, lack of hotline services, unawareness of available services, fear of discrimination etc. had significant association in our logistic regression analysis after adjusting for all confounders. Similarly, the only facilitator that had a significant impact, according to the multivariable logistic regression analysis, was receiving health information from Nepali healthcare professionals (OR = 1.36, 95% CI = (1.01 – 1.82), p-value < 0.05).

Conclusion

The study suggests the need for a crisis information hub which could be coordinated by the Nepal embassy or concerned authorities, flexible policies for active deployment of Nepalese health workers and volunteers, accessible hotlines in the Nepali language, and incorporation of Nepali telehealth services in Japan.
A risk score model based on endoplasmic reticulum stress related genes for predicting prognostic value of osteosarcoma
Authors: Zhao Yong , Gao Jijian , Fan Yong , Xu Hongyu , Wang Yun , Yao Pengjie
Published: June 2023

Background

We aimed to establish an osteosarcoma prognosis prediction model based on a signature of endoplasmic reticulum stress-related genes.

Methods

Differentially expressed genes (DEGs) between osteosarcoma with and without metastasis from The Cancer Genome Atlas (TCGA) database were mapped to ERS genes retrieved from Gene Set Enrichment Analysis to select endoplasmic reticulum stress-related DEGs. Subsequently, we constructed a risk score model based on survival-related endoplasmic reticulum stress DEGs and a nomogram of independent survival prognostic factors. Based on the median risk score, we stratified the samples into high- and low-risk groups. The ability of the model was assessed by Kaplan–Meier, receiver operating characteristic curve, and functional analyses. Additionally, the expression of the identified prognostic endoplasmic reticulum stress-related DEGs was verified using real-time quantitative PCR (RT-qPCR).

Results

In total, 41 endoplasmic reticulum stress-related DEGs were identified in patients with osteosarcoma with metastasis. A risk score model consisting of six prognostic endoplasmic reticulum stress-related DEGs (ATP2A3, ERMP1, FBXO6, ITPR1, NFE2L2, andUSP13) was established, and the Kaplan–Meier and receiver operating characteristic curves validated their performance in the training and validation datasets. Age, tumor metastasis, and the risk score model were demonstrated to be independent prognostic clinical factors for osteosarcoma and were used to establish a nomogram survival model. The nomogram model showed similar performance of one, three, and five year-survival rate to the actual survival rates. Nine immune cell types in the high-risk group were found to be significantly different from those in the low-risk group. These survival-related genes were significantly enriched in nine Kyoto Encyclopedia of Genes and Genomes pathways, including cell adhesion molecule cascades, and chemokine signaling pathways. Further, RT-qPCR results demonstrated that the consistency rate of bioinformatics analysis was approximately 83.33%, suggesting the relatively high reliability of the bioinformatics analysis.

Conclusion

We established an osteosarcoma prediction model based on six prognostic endoplasmic reticulum stress-related DEGs that could be helpful in directing personalized treatment.
Understanding pediatric palliative care within interdisciplinary palliative programs: a qualitative study
Authors: Rico-Mena Patricia , Güeita-Rodríguez Javier , Martino-Alba Ricardo , Chocarro-Gonzalez Lourdes , Sanz-Esteban Ismael , Palacios-Ceña Domingo
Published: June 2023

Purpose

To describe the process of delivery of pediatric palliative care from the perspective of a pediatric interdisciplinary team and the children’s parents.

Methods

A qualitative descriptive case study was conducted. Purposeful sampling took place within a specialized pediatric palliative care Unit in Madrid (Spain), located at the Niño Jesus Hospital. The study participants included a specialized pediatric palliative care team from Madrid's pediatric palliative care program, other professional teams involved in interdisciplinary care and parents of children under pediatric palliative care. Data were collected via semi-structured interviews, focus groups and researchers’ field notes. A thematic analysis was performed.

Results

This study included 28 participants (20 women, 8 men), of whom 18 were professionals who belonged to the pediatric palliative care interdisciplinary team, 4 professionals were from other units that collaborated with the pediatric palliative care, and 6 were parents (5 women, 1 man). The mean age of the pediatric palliative care members was 38.2 years (SD ± 7.9), that of the collaborating professionals was 40.5 (SD ± 6.8), and that of the parents was 44.2 (SD ± 5.4). Two main themes emerged: a) Pediatric palliative care has a distinct identity, associated with life. It represents the provision of special care in highly complex children, in the context of the home, far from the hospital environment; b) The team is key: its interdisciplinary organization provides a more comprehensive view of the child and their family, fosters communication among professionals, and improves coordination with other services involved in the care of children. The mindset shift experienced by ID-PPC professionals towards a palliative approach makes them more sensitive to the needs of their patients and leads them to develop specific skills in areas such as communication, decision-making, and adaptability that were identified as differentiating aspects of pediatric palliative care.

Conclusions

Describing pediatric palliative care from the professional and parental perspective helps to establish realistic and comprehensive goals for the care of children and their parents. The findings of this study may help with the establishment of a pediatric palliative care team, as a necessary organizational change in a health care system that cares for children with complex and life-threatening conditions. Promoting training in pediatric palliative care, prioritizing more horizontal organizations, providing tools and spaces for coordination and communication between professionals from different services, together with the creation of a position of case coordinator in the care process of children could enhance the understanding of pediatric palliative care services.
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

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

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

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

Background

Ethiopia 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.

Methods

Malaria–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.

Results

El 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.

Conclusion

Malaria–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

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

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

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