bluuebunny/crossref_metadata_2025 huggingface dataset:
Sophora genomes provide insight into the evolution of alkaloid metabolites along with small-scale gene duplication
Authors: Kang Yang Jae , Park Halim , Lee Yejin , Yoon Sanghwa , Kwak Myounghai
Published: August 2023

The genus Sophora (Fabaceae) includes medicinal plants that have been used in East Asian countries since antiquity. Sophora flavescens is a perennial herb indigenous to China, India, Japan, Korea, and Russia. Its dried roots have antioxidant, anti-inflammatory, antibacterial, apoptosis-modulating, and antitumor efficacy. The congeneric S. koreensis is endemic to Korea and its genome is less than half the size of that of S. flavescens. Nevertheless, this discrepancy can be used to assemble and validate the S. flavescens genome. A comparative genomic study of the two genomes can disclose the recent evolutionary divergence of the polymorphic phenotypic profiles of these species. Here, we used the PacBio sequencing platform to sequence and assemble the S. koreensis and S. flavescens genomes. We inferred that it was mainly small-scale duplication that occurred in S. flavescens. A KEGG analysis revealed pathways that might regulate the pharmacologically important secondary metabolites in S. flavescens and S. koreensis. The genome assemblies of Sophora spp. could be used in comparative genomics and data mining for various plant natural products.
Factors related to dietary quality among older stroke high-risk population in Tianjin community, China: a multicenter study
Authors: Gu Yumeng , Gao Decheng , Xia Xiaoshuang , Xue Juanjuan , Wang Dongliang , Wei Zhiqiang , Tian Xiaolin , Li Xin
Published: August 2023

Background

Stroke is a common and frequently-occurring disease in older people. It has the characteristics of high morbidity, high mortality, high recurrence rate and high disability rate. Most stroke risk studies are based on pathophysiology, however psychosocial factors such as diet quality are often understudied. The aim of this study was to assess stroke risk in urban community residents in Tianjin and investigate the factors that affect the dietary quality of older stroke high-risk populations.

Methods

Using a cross-sectional, multicenter study, recruit people aged 60 to 80 in Tianjin. Dietary intake data were obtained through a validated food frequency questionnaire, which were used to calculate Alternate Healthy Eating Index-2010 (AHEI-2010) and to analyze its association with sociodemographic characteristics, stroke risk factors and health marker variables.

Results

A total of 1068 participants from 4 community health service centers in Tianjin were recruited, including 300 low-risk individuals and 768 high-risk individuals. Compared with the low-risk group (62.75 ± 3.59), the AHEI-2010 mean score of the high-risk group (56.83 ± 6.54) was significantly lower. The top three most common risk factors among participants were dyslipidemia (80.3%), hypertension (60.6%), and physical inactivity (58.2%). Multiple logistic regression showed that diet quality was independently and significantly associated with stroke risk (OR = 0.765; 95%CI: 0.690–0.848, p < 0.001).

Conclusion

The diet quality of high-risk stroke population in Tianjin is far from ideal. At the same time, public health knowledge needs to be disseminated and educated, especially among those at high risk of cerebrovascular disease, with a focus on improving psychosocial factors such as diet quality.
A case of meningitis caused by Ralstonia insidiosa, a rare opportunistic pathogen
Authors: Liao Lindan , Lin Dan , Liu Zhiqiang , Gao Yan , Hu Kezhang
Published: August 2023

Background

Ralstonia is a genus of Gram-negative opportunistic bacteria that can survive in many kinds of solutions and cause a variety of infections. Ralstonia spp. have increasingly been isolated and reported to cause infections in recent years, thanks to the development of identification methods such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and gene sequencing. However, infections caused by Ralstonia insidiosa are still rare. Only a few cases of respiratory infections and bloodstream infections have been reported, none of which involved meningitis. To the best of our knowledge, this is the first reported case of meningitis caused by R. insidiosa worldwide. It is necessary to report and review this case.

Case presentation

We report a case of meningitis caused by R. insidiosa following lumbar surgery in China. The patient exhibited symptoms of headache, dizziness, and recurrent fever. The fever remained unresolved after empiric antibiotic therapy with intravenous cefotaxime and vancomycin in the initial days. Cerebrospinal fluid (CSF) culture yielded Gram-negative non-fermentative bacteria, which were identified as R. insidiosa. As there was a lack of antibiotic susceptibility testing results, clinical pharmacists conducted a literature review to select appropriate antibiotics. The patient’s condition improved after receiving effective treatment with intravenous cefepime and levofloxacin.

Conclusions

Uncommon pathogens, such as R. insidiosa, should be considered in postoperative central nervous system (CNS) infections, particularly in cases with unsatisfactory results of empiric anti-infective therapy. This is the first reported case of meningitis caused by R. insidiosa worldwide. MALDI-TOF MS provides rapid and accurate identification of this pathogen. The antibiotic susceptibility testing results of R. indiosa may be interpreted based on the breakpoints for Pseudomonas spp., Burkholderia cepacia spp., and Acinetobacter spp. Our case presents a potential option for empiric therapy against this pathogen, at least in the local area. This is crucial to minimize the severity and mortality rates associated with meningitis. Standardized antibiotic susceptibility testing and breakpoints for the Ralstonia genus should be established in the future as cases accumulate. Cefepime and levofloxacin may be potential antibiotics for infections caused by R. indiosa.
Association between serum phosphate levels and anemia in non-dialysis patients with chronic kidney disease: a retrospective cross-sectional study from the Fuji City CKD Network
Authors: Kato Kazuhiko , Nakashima Akio , Ohkido Ichiro , Kasai Kenji , Yokoo Takashi
Published: August 2023

Background

Patients with chronic kidney disease (CKD) present high mortality and morbidity rates despite the availability of various therapies. Although CKD-mineral and bone disorder (MBD) and renal anemia are important factors in patients with CKD, only few studies have analyzed the relationship between them. Therefore, this study aimed to evaluate the relationship between CKD-MBD and anemia in patients with CKD who did not receive erythropoiesis-stimulating agent or iron therapies.

Methods

This retrospective cross-sectional study included patients with CKD aged ≥ 20 years with estimated glomerular filtration rate (eGFR) categories G2a to G5 who were referred to the Fuji City General Hospital between April 2018 and July 2019. The exclusion criterion was ongoing treatment for CKD-MBD and/or anemia.

Results

The data of 300 patients with CKD were analyzed in this study. The median age of patients was 71 (range, 56.5–79) years. The median eGFR was 34 (range, 20–48) mL/min/1.73 m2, and the mean hemoglobin (Hb) level was 12.7 g/dL (standard deviation, 2.3), which decreased as the CKD stage increased. In a multivariate linear regression analysis of anemia-related factors, including age, renal function (eGFR), nutritional status, inflammation, and iron dynamics (serum iron level, total iron-binding capacity, ferritin levels), the serum phosphate levels were significantly associated with the Hb levels (coefficient [95% confidence interval], -0.73 [-1.1, -0.35]; P < 0.001). Subgroup analysis revealed a robust association between serum phosphate levels and Hb levels in the low-ferritin (coefficient [95% confidence interval], -0.94 [-1.53, -0.35]; P = 0.002) and advanced CKD groups (coefficient [95% confidence interval], -0.89 [-1.37, -0.41]; P < 0.001).

Conclusions

We found an association between high serum phosphate levels and low Hb levels in patients with CKD not receiving treatment for anemia. These results underscore the possibility of a mechanistic overlap between CKD-MBD and anemia.
COVID-19 deaths on weekends
Authors: Manzoor Fizza , Redelmeier Donald A.
Published: August 2023

Background

Mortality statistics about daily deaths might change on weekends due to delays in reporting, uneven staffing, a different mix of personnel, or decreased efficiency. We hypothesized that reported deaths for COVID-19 might increase on weekends compared to weekdays.

Methods

We collected data from the World Health Organization COVID-19 database. All deaths from March 7, 2020 to March 7, 2022 were included (two years). The primary analysis evaluated mean daily deaths on weekends compared to the preceding five workdays. Analyses were replicated in ten individual countries: United States, United Kingdom, France, Germany, Italy, Spain, Russia, India, Brazil, and Canada.

Results

The mean COVID-19 daily deaths was higher on weekends compared to weekdays (8,532 vs. 8,083 p < 0.001), equal to a 6% relative increase (95% confidence interval 3% to 8%). The highest absolute increase was in the United States (1,483 vs. 1,220 deaths, p < 0.001). The second highest absolute increase was in Brazil (1,061 vs. 823 deaths, p < 0.001). The increase in deaths on weekends remained significant during the earlier and later months of the pandemic, as well as during the greater and lesser weeks of the pandemic.

Conclusions

The apparent increased COVID-19 deaths reported on weekends might potentially reflect patient care, confound community trends, and affect the public perception of risk.
Effect of an educational intervention on nurses’ competence in activities of daily living support in end-of-life care using a pretest–posttest repeated measures design
Authors: Gattinger Heidrun , Ott Stefan , Maurer Carola , Marty-Teuber Brigitte , Hantikainen Virpi , Fringer André
Published: August 2023

Background

Most patients in specialized palliative care units need nursing support to perform activities of daily living (ADL), such as using a toilet or transferring out of a bed or chair. To deliver high-quality ADL support that facilitates patients’ movement and protects nurses’ musculoskeletal health, nurses need appropriate knowledge and skills. The objective of this study is to investigate the impact of education based on the “Advanced Kinaesthetics in Palliative care (AdKinPal) program” on the competence in Kinaesthetics, self-efficacy regarding ADL support in end-of-life care and musculoskeletal complaints of nurses from specialist palliative care units.

Methods

A pretest–posttest repeated measures design was applied. The study took place in three specialised units for palliative care in Switzerland between June 2018 and April 2020. All the nurses who worked in participating wards (n = 62) and fulfilled the inclusion criteria were asked to participate. The intervention – the AdKinPal program – is an education-based training program conducted for six months. We took measurements using self-administered questionnaires at three points before and after the intervention. Using descriptive statistics, repeated measurement analysis of variance (ANOVA) and independent-samples t-tests, we analysed the participants’ demographic characteristics as well as developments over time and relationships between the three outcome variables: Kinaesthetics competence, self-efficacy regarding ADL support in end-of-life care and musculoskeletal complaints.

Results

Fifty-nine nurses and one physiotherapist participated, and 38 participants (63%) responded to all three questionnaires. The AdKinPal training improved the nurses’ perceived Kinaesthetics competence and self-efficacy regarding ADL support in end-of-life care. Participants who reported lower back, neck or shoulder pain had a significantly lower Kinaesthetics competence.

Conclusions

The AdKinPal program can raise nurses’ Kinaesthetics competence. Thereby, patients’ autonomy and quality of life could be supported, and symptom management could be enhanced in a holistic manner. Furthermore, the AdKinPal program fosters nurses’ self-efficacy in ADL support in end-of-life care. A strong sense of self-efficacy enhances professional well-being in many ways. Additionally, the nursing staff’s musculoskeletal health can be promoted by enhancing their Kinaesthetics competence.

Trial registration

DRKS00015908. Registration Date 23.11.2018.
Jatrophone: a cytotoxic macrocylic diterpene targeting PI3K/AKT/NF-κB pathway, inducing apoptosis and autophagy in resistant breast cancer cells
Authors: Shari Khawlah , El Gedaily Rania A. , Allam Rasha M. , Meselhy Khaled M. , Khaleel Amal E. , Abdel-Sattar Essam
Published: August 2023

Background

Breast cancer is a prevalent malignant tumor that affects women worldwide. The primary challenge in treating breast cancer is combating drug resistance, which contributes to relapse and metastasis. Jatrophone is a unique macrocyclic jatrophane diterpene found in various Jatropha and Euphorbia species. It possesses diverse biological and pharmacological activities, including anticancer activity. However, it is unclear whether jatrophone can overcome drug resistance in breast cancer.

Methods

This study includes the investigation of the cytotoxicity of jatrophone on doxorubicin-resistant breast cancer cells (MCF-7ADR) and the underlying molecular mechanisms. The effects of jatrophone on cell viability were determined using the sulforhodamine B (SRB) assay, while flow cytometry was used to evaluate cell cycle progression, apoptosis, and autophagy. A scratch assay was conducted to observe cell migration, and western blotting was used to measure downstream protein levels (PI3K, AKT, and NF-κB). Unpaired Student’s t-tests were used for comparison between the two groups and the results were analyzed by one-way ANOVA with Tukey- Kremer post hoc test.

Results

It was shown that jatrophone exhibited potent cytotoxic activity on MCF-7ADR cells in a dose-dependent manner, with an IC50 value of 1.8 µM. It also significantly induced cell cycle S and G/M phase arrest. Interestingly, jatrophone induced both early and late apoptotic cell death, as well as autophagic cell death, with negligible necrosis. Furthermore, jatrophone treatment diminished the migration of MCF-7ADR cells. At the molecular level, jatrophone treatment significantly down-regulated the expression levels of PI3K, AKT, and NF-κB. β.

Conclusions

The results of the study suggest that jatrophone decreases the proliferation of MCF-7/ADR cells at a low micromolar concentration; induces cell cycle arrest; promotes apoptotic, and autophagic cell death; inhibits migration and EMT; and works on resistance by a mechanism involving the inhibition of the PI3K/Akt/ NF-κB pathway. These findings provide evidence of the potential of jatrophone to be a promising lead compound for targeting doxorubicin-resistant breast cancer cells and could be further investigated for its clinical application as a chemotherapy adjuvant.
Medical students’ knowledge and attitude towards tele-education and associated factors at University of Gondar, Ethiopia, 2022: mixed method
Authors: Hailemariam Rorisa Tadele , Nigatu Araya Mesfin , Melaku Mequannent Sharew
Published: August 2023

Background

Tele-education is the use of ICTs to conduct remote learning. It has been utilized to deliver ongoing training for many years. The world’s modern culture is increasingly reliant on the use of information technology to enhance standards of education. However, in order to deploy successful e-learning systems in a developing nation, understanding of user characteristics is required in the creation and usage of e-learning systems. Thus, this study will enable us to understand the user’s level of knowledge and attitude towards tele-education.

Methods

An institution-based quantitative cross-sectional study supported by qualitative design was used 397 medical students at University of Gondar from May to June 2022. A pre-tested self-administered structured questionnaires and in-depth interview were used to collect quantitative and qualitative data respectively. Thematic-content analysis was conducted using open-code software for analyzing qualitative data. Quantitative data was entered to Epi-data version 4.6 and exported to SPSS version 25 software for further statistical analysis. Binary logistic regression was conducted. The adjusted odds ratio(AOR) was used to measure the association between the dependent and independent variables.

Results

A total of 397 medical students were participated in this study with a response rate of 93.63%. In this study nearly six out of ten 230(57.9%) of study participants had good knowledge towards tele-education. More than half. 211(53.1%) of medical students participated on the study also had a favorable attitude towards tele-education. Factors associated with knowledge about tele-education is training related to ICT (AOR = 2.27 95% CI; (1.13,4.55)), knowledge of medical education digitization (AOR = 3.80 95% CI; (2.12,6.84)), high computer literacy (AOR = 2.82 95% CI; (1.68,4.72)) and favorable attitude towards tele-education (AOR = 3.52 95% CI; (2.12,5.84)). Factors associated with attitude towards tele-education is age group > 21 (AOR = 3.89, 95% CI; (1.33,11.39)) and good knowledge towards tele-education (AOR = 3.42,95%CI;(2.06,5.66)).

Conclusion

The study revealed that the knowledge of the medical students was good and nearly five out of ten of them had a favorable attitude towards tele-education. The study shows that training related to ICT, knowledge of medical education digitization, high computer literacy and favorable attitude towards tele-education were associated significantly with knowledge of tele-education. In this study age group > 21 and good knowledge towards tele-education of study participants were associated significantly with attitude towards tele-education.
Trend and spatial clustering of medical education in Brazil: an ecological study of time series from 2010 to 2021
Authors: Guimarães Rafael Alves , de França e Silva Ana Luísa Guedes , de Souza Marizélia Ribeiro , Guimarães Adriana Moura , de Souza Lauro Marcos Eduardo , Naghettini Alessandra Vitorino , Neves Heliny Carneiro Cunha , Arantes Manso Fernanda Paula , Júnior Cândido Vieira Borges , de Castro Alessandra Rodrigues Moreira , Bento Victor Gonçalves , da Cruz Lima Pablo Leonardo Mendes
Published: August 2023

Context

Studies that analyze the temporal trend and spatial clustering of medical education indicators are scarce, especially in developing countries such as Brazil. This analysis is essential to subsidize more equitable policies for the medical workforce in the states and regions of Brazil. Thus, this study aimed to analyze the temporal trend and identify spatial clusters of medical education indicators in Brazil disaggregated by public and private education, states, and regions.

Methods

A time-series ecological study was conducted using data from the Higher Education Census of the Ministry of Education from 2010 to 2021. The study analyzed vacancy density indicators of active and former students/100,000 population, disaggregated by public and private education, 27 states, and 5 regions in Brazil. Prais-Winsten regression was used for trend analyses of indicators. Hot Spot Analysis (Getis-Ord Gi*) was used to identify spatial clusters of indicators.

Results

The number of medical schools increased by 102.2% between 2010 and 2021. A total of 366 medical schools offered 54,870 vacancies at the end of 2021. Vacancy density and active and former students increased significantly in the period, but this increase was greater in private institutions. Most states and regions showed an increasing trend in the indicators, with higher increase percentages in private than in public schools. Hot spot spaces changed over time, concentrated in the southeast, center-west, and north at the end of 2021. Medical education remains uneven in Brazil, with a low provision in regions with low socioeconomic development, academic structure, and health services, represented by regions in the north and northeast.

Conclusions

There is a growing trend in medical education indicators in Brazil, especially in the private sector. Spatial clusters were found predominantly in the southeast, center-west, and north. These results indicate the need for more equitable medical education planning between the regions.
Assessing the accuracy of electronic health record gender identity and REaL data at an academic medical center
Authors: Proumen Rachael , Connolly Hannah , Debick Nadia Alexandra , Hopkins Rachel
Published: August 2023

Background

Collection of accurate patient race, ethnicity, preferred language (REaL) and gender identity in the electronic health record (EHR) is essential for equitable and inclusive care. Misidentification of these factors limits quality measurement of health outcomes in at-risk populations. Therefore, the aim of our study was to assess the accuracy of REaL and gender identity data at our institution.

Methods

A survey was administered to 117 random patients, selected from prior day admissions at a large academic medical center in urban central New York. Patients (or guardians) self-reported REaL and gender identity data, selecting from current EHR options. Variables were coded for the presence or absence of a difference from data recorded in the EHR.

Results

Race was misreported in the EHR for 13% of patients and ethnicity for 6%. For most White and Black patients, race was concordant. However, self-identified data for all multiracial patients were discordant with the EHR. Most Non-Hispanic patients had ethnicity correctly documented. Some Hispanic patients were misidentified. There was a significant association between reporting both a race and an ethnicity which differed from the EHR on chi square analysis (P < 0.001). Of those who reported an alternative ethnicity, 71.4% also reported an alternative race. Gender identity was missing for most patients and 11% of the gender-identity entries present in the EHR were discordant with the patient’s self-identity. Preferred language was 100% concordant with the EHR.

Conclusions

At an academic medical center, multiracial and Hispanic patients were more likely to have their demographics misreported in the EHR, and gender identity data were largely missing. Healthcare systems need strategies that support accurate collection of patients’ self-reported ReAL and gender identity data to improve the future ability to identify and address healthcare disparities.
Cost of illness for colorectal cancer in Japan - a time trend and future projections (1996–2035) based on governmental statistics
Authors: Matsumoto Kunichika , Hatakeyama Yosuke , Seto Kanako , Onishi Ryo , Hirata Koki , Wu Yinghui , Hasegawa Tomonori
Published: August 2023

Background

In Japan, the crude mortality rate of colorectal cancer is the second highest among men and highest among women by site. We aimed to calculate the social burden of colorectal cancer using the cost of illness (COI) method and identify the main factors that drove changes in the COI.

Methods

From 1996 to 2020, the COI was estimated by summing direct, morbidity, and mortality costs. In addition, the COI by 2035 was projected by fitting approximate curves obtained from historical data to health-related indicators by sex and age. Future projections of the number of patients by the stage of disease were also made to explore the factors that changed the COI.

Results

The number of deaths and incidence from colorectal cancer was expected to continue increasing due to population aging. However, the COI was projected to rise from 850.3 billion yen in 1996 to 1.451 trillion yen in 2020, and peaked at 1.478 trillion yen in 2023 before it declined.

Conclusion

Although the increased number of deaths associated with population aging increased COI, it was expected that the COI would decrease around 2023 due to a decrease in the human capital value of the deceased. In addition, the mortality rate was expected to decrease in the future due to an increase in the percentage of early detection of colorectal cancer via widespread screening and advances in medical technology.
Red blood cells: a potential delivery system
Authors: Chen Mengran , Leng Yamei , He Chuan , Li Xuefeng , Zhao Lei , Qu Ying , Wu Yu
Published: August 2023

Red blood cells (RBCs) are the most abundant cells in the body, possessing unique biological and physical properties. RBCs have demonstrated outstanding potential as delivery vehicles due to their low immunogenicity, long-circulating cycle, and immune characteristics, exhibiting delivery abilities. There have been several developments in understanding the delivery system of RBCs and their derivatives, and they have been applied in various aspects of biomedicine. This article compared the various physiological and physical characteristics of RBCs, analyzed their potential advantages in delivery systems, and summarized their existing practices in biomedicine.

Graphical Abstract
Clinicopathological features and differential diagnosis of gastric metastases
Authors: Chen Wen , Liu Chengyu , Liu Yuejiao , Yuan Jing , Wang Zhanbo
Published: August 2023

Objective

Due to the rarity and non-specificity of symptoms, gastric metastases are often misdiagnosed, and patients are not treated promptly. The aim of this study was to study the clinicopathological features and differential diagnosis of gastric metastases.

Methods

From 2004 to 2021, 14 patients were diagnosed with gastric metastases not resulting from direct invasion (GMNDI) in our hospital, and their imaging and clinicopathological features were analyzed.

Results

PET-CT examination showed hypermetabolic nodules in the stomach. Under gastroscopy, GMNDI showed eminence, nodular or vegetable pattern mass, and ulcer. Microscopically, GMNDI showed similar pathological features and immunophenotypes to the primary tumor. In our study, the most common primary tumors were malignant melanoma (4 cases), small cell lung cancer (3 cases), and hepatocellular carcinoma (3 cases). Immunohistochemistry contributed to the pathological diagnosis and differential diagnosis of gastric metastases. Malignant melanoma expressed HMB45, MelanA, and S-100; small cell lung cancer expressed TTF-1, CD56, and CgA; hepatocellular carcinoma expressed GPC-3, hepatocyte, and Sall4. In a few cases, tumor cells may lose immune markers during metastasis. Therefore, it is necessary to combine medical history, imaging examination, and other clinical diagnosis methods in the pathological diagnosis.

Conclusion

An in-depth understanding of GMNDI is conducive to better diagnosis and treatment planning for gastric metastases and subsequent improvement in patient prognosis.
Elevated serum IFN-γand IFN-γ/IL-6 ratio in Kikuchi-Fujimoto disease
Authors: He Tingyan , Shen Zixuan , Ling Jiayun , Zhu Xiaona , Yang Jun
Published: August 2023

Background

Kikuchi-Fujimoto disease (KFD) is typically a benign, self-limiting inflammatory disease. The diagnosis of KFD can be challenging for nonspecific symptoms, laboratory or imaging findings. In this study, we aimed to describe the clinical manifestations of patients with KFD and to access the potential role of serum cytokines in the diagnosis of this disease.

Methods

Patients with KFD were retrospectively enrolled from January 2015 to November 2021 at Shenzhen Children’s Hospital. Clinical data were collected from inpatient or outpatient medical records. Serum cytokines were detected by the Flowcytomix technique. Serum levels of cytokines were compared between patients with KFD and SJIA, or patients with KFD and KD. The data of patients without MAS were further analyzed. A receiver operating characteristic (ROC) curve analysis was further performed to access the potential role of serum cytokines in the diagnosis of KFD.

Results

Serum cytokines were detected in 25 (43.8%, 25/57) patients with a histological diagnosis of KFD. Compared to SJIA or KD patients, the KFD group had a significantly higher IFN-γ/IL-6 ratio and much lower levels of serum IL-6. The median level of serum IFN-γ in KFD was 41.65 pg/ml (range, 21.04–70.74 pg/ml), which was much higher than that in SJIA (median: 3.33 pg/ml, p = 0.16) or KD (median: 2.6 pg/ml, p = 0.01). After excluding patients with MAS, there was statistical significance in all comparisons of serum IFN-γ, IFN-γ/IL-6 ratio, and serum IL-6. The cutoff values of serum IFN-γ, IL-6, and IFN-γ/IL-6 ratio for differentiating KFD from SJIA were > 8.48 pg/ml, < 47.42 pg/ml, and > 0.45, respectively. The cutoff values of serum IFN-γ, IL-6, and IFN-γ/IL-6 ratio for differentiating KFD from KD were > 8.56 pg/ml, < 50.45 pg/ml, and > 0.45, respectively. The specificity of all those cutoff values for differentiating KFD from SJIA or KD was ≥ 94.7%.

Conclusions

For patients with fever of unknown etiology and lymphadenopathy, after excluding HLH or MAS, serum IFN-γ > 8.56 pg/mL and IFN-γ/IL-6 ratio > 0.45 may highly suggest the diagnosis of KFD; serum IL-6 > 50.45 pg/mL indicates that the probability of KFD may be small, and sJIA, KD, and acute infection should be excluded first.
Amorphous silica nanoparticles cause abnormal cytokinesis and multinucleation through dysfunction of the centralspindlin complex and microfilaments
Authors: Xiao Liyan , Pang Jinyan , Qin Hua , Dou Liyang , Yang Man , Wang Ji , Zhou Xianqing , Li Yang , Duan Junchao , Sun Zhiwei
Published: August 2023

Background

With the large-scale production and application of amorphous silica nanoparticles (aSiNPs), its adverse health effects are more worthy of our attention. Our previous research has demonstrated for the first time that aSiNPs induced cytokinesis failure, which resulted in abnormally high incidences of multinucleation in vitro, but the underlying mechanisms remain unclear. Therefore, the purpose of this study was firstly to explore whether aSiNPs induced multinucleation in vivo, and secondly to investigate the underlying mechanism of how aSiNPs caused abnormal cytokinesis and multinucleation.

Methods

Male ICR mice with intratracheal instillation of aSiNPs were used as an experimental model in vivo. Human hepatic cell line (L-02) was introduced for further mechanism study in vitro.

Results

In vivo, histopathological results showed that the rate of multinucleation was significantly increased in the liver and lung tissue after aSiNPs treatment. In vitro, immunofluorescence results manifested that aSiNPs directly caused microfilaments aggregation. Following mechanism studies indicated that aSiNPs increased ROS levels. The accumulation of ROS further inhibited the PI3k 110β/Aurora B pathway, leading to a decrease in the expression of centralspindlin subunits MKLP1 and CYK4 as well as downstream cytokines regulation related proteins Ect2, Cep55, CHMP2A and RhoA. Meanwhile, the particles caused abnormal co-localization of the key mitotic regulatory kinase Aurora B and the centralspindlin complex by inhibiting the PI3k 110β/Aurora B pathway. PI3K activator IGF increased the phosphorylation level of Aurora B and improved the relative ratio of the centralspindlin cluster. And ROS inhibitors NAC reduced the ratio of multinucleation, alleviated the PI3k 110β/Aurora B pathway inhibition, and then increased the expression of MKLP1, CYK4 and cytokinesis-related proteins, whilst NAC restored the clustering of the centralspindlin.

Conclusion

This study demonstrated that aSiNPs led to multinucleation formation both in vivo and in vitro. ASiNPs exposure caused microfilaments aggregation and inhibited the PI3k 110β/Aurora B pathway through excessive ROS, which then hindered the centralspindlin cluster as well as restrained the expression of centralspindlin subunits and cytokinesis-related proteins, which ultimately resulted in cytokinesis failure and the formation of multinucleation.
Identification of TRPM2 as a prognostic factor correlated with immune infiltration in ovarian cancer
Authors: Huang Wei , Wu Yuliang , Luo Ning , Shuai Xueqian , Guo Jing , Wang Chunyan , Yang Fanchun , Liu Li , Liu Shupeng , Cheng Zhongping
Published: August 2023

Introduction

Ovarian cancer (OC) is one of the most common gynecologic malignant cancers with the current survival rate remaining low. TRPM2 has been reported as a survival predictor in various cancers but not in OC. The aim of this study is to explore the role and its underlying mechanism of TRPM2 in OC.

Methods

The transcriptome data and clinical data were obtained from TCGA, GTEx, and GEO (GSE17260). DriverDBv3 and PrognoScan were used to analyze survival correlations. GSEA analysis was performed to uncover the underlying mechanism. The correlations between TRPM2 and immune score, immune cell infiltration were analyzed by TIMER2.0.

Results

TRPM2 was highly expressed in OC and high TRPM2 expression was related to the poor prognosis based on the Kaplan-Meier curves, univariate and multivariate analysis. The enrichment analysis suggested that TRPM2 was involved in immune-related pathways. Positive correlations were also observed between TRPM2 expression and immune score and immune cells covering B cells, T cells, macrophage, neutrophil, and myeloid dendritic cells. We also found that TRPM2 was positively related to immune checkpoints including ICOSLG, CD40, CD86, etc. TRPM2 expression had a positive correlation with M2 macrophage, but not with M1 macrophage. Besides, TRPM2 showed a strong positive correlation with pyroptosis-related genes including NLRP3, NLRC4, NOD2, NOD1, IL1B, GSDMD.

Conclusion

Our study demonstrated that TRPM2 is a poor prognostic prediction factor in ovarian cancer and is correlated to the immune microenvironment and pyroptosis. TRPM2 may act as a new immunotherapy target, which promoted the survival rate of OC patients.
Pre-hospital and retrieval medicine in Scotland: a retrospective cohort study of the workload and outcomes of the emergency medical retrieval service in the first decade of national coverage
Authors: McHenry Ryan D , Moultrie Christopher EJ , Cadamy Andrew J , Corfield Alasdair R , Mackay Daniel F , Pell Jill P
Published: August 2023

Background

The Emergency Medical Retrieval Service (EMRS) has provided national pre-hospital critical care and aeromedical retrieval in Scotland since 2010. This study investigates trends in the service and patients attended over the last decade; and factors associated with clinical deterioration and pre-hospital death.

Methods

A retrospective cohort study was conducted of all service taskings over ten years (2011–2020 inclusive). The EMRS electronic database provided data on location, sociodemographic factors, diagnoses, physiological measurements, clinical management, and pre-hospital deaths. Binary logistic regression models were used to determine change in physiology in pre-hospital care, and factors associated with pre-hospital death. Geospatial modelling, using road and air travel time models, was used to explore transfer times.

Results

EMRS received 8,069 taskings over the study period, of which 2,748 retrieval and 3,633 pre-hospital critical care missions resulted in patient contact. EMRS was more commonly dispatched to socioeconomically deprived areas for pre-hospital critical care incidents (Spearman’s rank correlation, r(8)=-0.75, p = 0.01). In multivariate analysis, systolic blood pressure < 90mmHg, respiratory rate < 6/min or > 30/min, and Glasgow Coma Score ≤ 14 were associated with pre-hospital mortality independent of demographic factors. Geospatial modelling suggested that aeromedical retrieval reduced the mean time to a critical care unit by 1 h 46 min compared with road/ferry transportation.

Conclusion

EMRS continues to develop, delivering Pre-Hospital and Retrieval Medicine across Scotland and may have a role in addressing health inequalities, including socioeconomic deprivation and geographic isolation. Age, specific distances from care, and abnormal physiology are associated with death in pre-hospital critical care.
WLCD: a dataset of lifestyle in relation with women’s cancer
Authors: Ardalani Alireza , Daneshvar Mojtaba
Published: August 2023

Objectives

Social media text mining has been widely used to extract information about the experiences and needs of patients regarding various diseases, especially cancer. Understanding these issues is necessary for further management in primary care. Researchers have identified that lifestyle factors such as diet, exercise, alcohol, and Smoking are associated with cancer risks, particularly women’s cancer. Considering the growing trend in the global burden of women’s cancer, it is essential to monitor up-to-date data sources using text mining.

Data description

We have prepared six independent datasets regarding lifestyle components and women’s cancer: (1) a dataset of nutrition containing 10,161 tweets; (2) a dataset of exercise containing 9412 tweets; (3) a dataset of alcohol containing 2132 tweets; (4) a dataset of Smoking containing 4316 tweets; and (5) a dataset of lifestyle (term) containing 1861 tweets. We also construct an additional dataset: (6) a dataset by summing other components containing 27,882 tweets. These data are provided to discover people’s perspectives, knowledge, and experiences regarding lifestyle and women’s cancer. Hence, it should be valuable for healthcare providers to develop more efficient patient management approaches.
Neurophysiological alterations in mice and humans carrying mutations in APP and PSEN1 genes
Authors: van Heusden Fran C. , van Nifterick Anne M. , Souza Bryan C. , França Arthur S. C. , Nauta Ilse M. , Stam Cornelis J. , Scheltens Philip , Smit August B. , Gouw Alida A. , van Kesteren Ronald E.
Published: August 2023

Background

Studies in animal models of Alzheimer’s disease (AD) have provided valuable insights into the molecular and cellular processes underlying neuronal network dysfunction. Whether and how AD-related neurophysiological alterations translate between mice and humans remains however uncertain.

Methods

We characterized neurophysiological alterations in mice and humans carrying AD mutations in the APP and/or PSEN1 genes, focusing on early pre-symptomatic changes. Longitudinal local field potential recordings were performed in APP/PS1 mice and cross-sectional magnetoencephalography recordings in human APP and/or PSEN1 mutation carriers. All recordings were acquired in the left frontal cortex, parietal cortex, and hippocampus. Spectral power and functional connectivity were analyzed and compared with wildtype control mice and healthy age-matched human subjects.

Results

APP/PS1 mice showed increased absolute power, especially at higher frequencies (beta and gamma) and predominantly between 3 and 6 moa. Relative power showed an overall shift from lower to higher frequencies over almost the entire recording period and across all three brain regions. Human mutation carriers, on the other hand, did not show changes in power except for an increase in relative theta power in the hippocampus. Mouse parietal cortex and hippocampal power spectra showed a characteristic peak at around 8 Hz which was not significantly altered in transgenic mice. Human power spectra showed a characteristic peak at around 9 Hz, the frequency of which was significantly reduced in mutation carriers. Significant alterations in functional connectivity were detected in theta, alpha, beta, and gamma frequency bands, but the exact frequency range and direction of change differed for APP/PS1 mice and human mutation carriers.

Conclusions

Both mice and humans carrying APP and/or PSEN1 mutations show abnormal neurophysiological activity, but several measures do not translate one-to-one between species. Alterations in absolute and relative power in mice should be interpreted with care and may be due to overexpression of amyloid in combination with the absence of tau pathology and cholinergic degeneration. Future studies should explore whether changes in brain activity in other AD mouse models, for instance, those also including tau pathology, provide better translation to the human AD continuum.
Clinical efficacy and safety of multipotent adult progenitor cells (invimestrocel) for acute respiratory distress syndrome (ARDS) caused by pneumonia: a randomized, open-label, standard therapy–controlled, phase 2 multicenter study (ONE-BRIDGE)
Authors: Ichikado Kazuya , Kotani Toru , Kondoh Yasuhiro , Imanaka Hideaki , Johkoh Takeshi , Fujimoto Kiminori , Nunomiya Shin , Kawayama Tomotaka , Sawada Masanori , Jenkins Eric , Tasaka Sadatomo , Hashimoto Satoru
Published: August 2023

Background

Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung injury with high mortality; no approved medication exists. Efficacy and safety of bone marrow–derived, allogeneic, multipotent adult progenitor cells (invimestrocel) plus standard treatment in patients with ARDS caused by pneumonia was evaluated.

Methods

A randomized, open-label, standard therapy–controlled, phase 2 study (January 2019–September 2021) conducted in 29 centers in Japan. Patients with ARDS caused by pneumonia, with extensive early fibroproliferation on high-resolution computed tomography and low risk of systemic organ failure identified by an Acute Physiology and Chronic Health Evaluation (APACHE II) score were included. Patients were randomized 2:1 to receive a single intravenous infusion of 9.0 × 108 cells of invimestrocel (administered at a rate of up to 10 mL/min over 30–60 min by free flow) plus standard treatment (N = 20) or standard treatment (N = 10) consistent with the clinical practice guidelines of the Japanese Respiratory Society for the management of ARDS. Primary endpoint was ventilator-free days (VFDs) through day 28 after study treatment. Analysis of covariance was performed with treatment group, age, partial pressure arterial oxygen/fraction of inspired oxygen ratio, and APACHE II score as covariates.

Results

Median (interquartile range) number of VFDs was numerically higher in the invimestrocel group versus standard group (20.0 [0.0–24.0] vs 11.0 [0.0–14.0]) but was not statistically significantly different (least square [LS] means [95% confidence interval (CI)]: invimestrocel group, 11.6 [6.9–16.3]; standard group, 6.2 [− 0.4 to 12.8]; LS mean difference [95% CI], 5.4 [− 1.9 to 12.8]; p = 0.1397). Ventilator weaning rate at day 28 was 65% (13/20) versus 30% (3/10), and mortality rate was 21% (4/19) versus 29% (2/7) at day 28 and 26% (5/19 patients) versus 43% (3/7 patients) at day 180, for the invimestrocel and standard groups, respectively. No allergic or serious adverse reactions were associated with invimestrocel.

Conclusions

In Japanese patients with ARDS caused by pneumonia, invimestrocel plus standard treatment resulted in no significant difference in the number of VFDs but may result in improved survival compared with standard treatment. Invimestrocel was well tolerated.

Trial registration: ClinicalTrials.gov, Identifier: NCT03807804; January 8, 2019; https://clinicaltrials.gov/ct2/show/NCT03807804.
Tramadol for chronic pain in adults: protocol for a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials
Authors: Barakji J. , Korang S. K. , Feinberg J. B. , Maagaard M. , Mathiesen O. , Gluud C. , Jakobsen J. C.
Published: August 2023

Background

Chronic pain in adults is a frequent clinical symptom with a significant impact on patient well-being. Therefore, sufficient pain management is of utmost importance. While tramadol is a commonly used pain medication, the quality of evidence supporting its use has been questioned considering the observed adverse events. Our objective will be to assess the benefits and harms of tramadol compared with placebo or no intervention for chronic pain.

Methods/design

We will conduct a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis to assess the beneficial and harmful effects of tramadol in any dose, formulation, or duration. We will accept placebo or no intervention as control interventions. We will include adult participants with any type of chronic pain, including cancer-related pain. We will systematically search the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, and BIOSIS for relevant literature. We will follow the recommendations by Cochrane and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The risk of systematic errors (‘bias’) and random errors (‘play of chance’) will be assessed. The certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Discussion

Although tramadol is often being used to manage chronic pain conditions, the beneficial and harmful effects of this intervention are unknown. The present review will systematically assess the current evidence on the benefits and harms of tramadol versus placebo or no intervention to inform clinical practice and future research.

Systematic review registration

PROSPERO CRD42019140334.
Community capacity for prevention and health promotion: a scoping review on underlying domains and assessment methods
Authors: Birgel Vera , Decker Lea , Röding Dominik , Walter Ulla
Published: August 2023

Background

Building community capacity is an essential health promotion approach, which refers to the characteristics of communities that affect their ability to identify and address social and public health problems. Despite general agreement about certain capacity domains and frameworks, there is no comprehensive and consistent assessment of community capacity. Therefore, the aim of this scoping review is to identify the domains and methods used to assess community capacity related to community-based prevention and health promotion.

Methods

A scoping search was performed on 06/02/2022 via PubMed, Web of Science, and Science Direct, with supplemental searches via Google Scholar. The review included studies published in English from 1990 to 2022 that explicitly described how community capacity was assessed in health promotion and prevention interventions. Furthermore, studies had to meet at least two of the three following criteria for capacity assessment: a theoretical foundation, a participatory approach, or a field test of the assessment tool.

Results

From 4779 records, 38 studies were included after applying exclusion criteria. Nineteen studies used mixed, eleven qualitative and eight quantitative methods to assess community capacity. The various domains used to assess community capacity were identified and reassembled into nine comprehensive domains: community participation, knowledge and skills, resources, leadership, community power, sense of community, collaboration, critical awareness and problem-solving, and community structure. The review also identified four sub-domains, which include commitment, communication, shared values and goals, and sustainability.

Discussion

This scoping review provides an overview of the domains and methods used to assess community capacity, which can facilitate the development of a comprehensive approach to capacity assessment in future research.