bluuebunny/crossref_metadata_2025 huggingface dataset:
EEG spectral power during REM sleep in patients with frontal brain tumor
Authors: Ortega-Leonard Laura Victoria , del Río-Portilla Yolanda
Published: May 2023

Background

The main objective of this research was to analyze the characteristics of electrical activity in the brain during REM (Rapid Eye Movements) sleep, by using an experimental model a pathology that affects the frontal lobes, such as brain tumors. In addition to determining the impact of variables such as the frontal area (dorsolateral, medial and orbital), laterality and size of the lesion; as well as the demographic and clinical characteristics of the patients evaluated.

Methods

By using polysomnographic recordings, 10 patients were evaluated. We obtained power spectra through a homemade program. For quantitative EEG (Electroencephalogram) (qEEG) analysis, the Fast Fourier Transform (FFT) algorithm was used to obtain the spectral power of each participant, channel, and frequency band.

Results

Sleep architecture and spectral power was found to be modified in patients compared to normative values. Other sociodemographic and clinical characteristics of the patients were also influenced, such as age range and antiepileptic drugs.

Conclusions

Brain tumors in the frontal lobe can modify the rhythmogenesis of REM sleep, possibly due to changes of brain plasticity as an effect of the pathology. In addition to this, through this study we were able to show the association between neuroanatomical and functional changes, on the characteristics of brain electrical activity in patients with frontal brain tumor. Finally, this qEEG analysis technique allows, on the one hand, to deepen the knowledge and relationship between psychophysiological processes and, on the other hand, to be able to guide therapeutic decisions.
Apatinib plus etoposide in pretreated patients with advanced triple-negative breast cancer: a phase II trial
Authors: Cao Mengru , Lu Hailing , Yan Shi , Pang Hui , Sun Lichun , Li Chunhong , Chen Xuesong , Liu Wei , Hu Jing , Huang Jian , Xing Ying , Zhang Ningzhi , Chen Yingqi , He Ting , Zhao Danni , Sun Yuanyuan , Zhao Lin , Liu Xiaomeng , Cai Li
Published: May 2023

Background

Treatment options for pretreated triple-negative breast cancer (TNBC) are limited. This study aimed to evaluate the efficacy and safety of apatinib, an antiangiogenic agent, in combination of etoposide for pretreated patients with advanced TNBC.

Methods

In this single-arm phase II trial, patients with advanced TNBC who failed to at least one line of chemotherapy were enrolled. Eligible patients received oral apatinib 500 mg on day 1 to 21, plus oral etoposide 50 mg on day 1 to 14 of a 3-week cycle until disease progression or intolerable toxicities. Etoposide was administered up to six cycles. The primary endpoint was progression-free survival (PFS).

Results

From September 2018 to September 2021, 40 patients with advanced TNBC were enrolled. All patients received previous chemotherapy in the advanced setting, with the median previous lines of 2 (1–5). At the cut-off date on January 10, 2022, the median follow-up was 26.8 (1.6–52.0) months. The median PFS was 6.0 (95% confidence interval [CI]: 3.8–8.2) months, and the median overall survival was 24.5 (95%CI: 10.2–38.8) months. The objective response rate and disease control rate was 10.0% and 62.5%, respectively. The most common adverse events (AEs) were hypertension (65.0%), nausea (47.5%) and vomiting (42.5%). Four patients developed grade 3 AE, including two with hypertension and two with proteinuria.

Conclusions

Apatinib combined with oral etoposide was feasible in pretreated advanced TNBC, and was easy to administer.

Clinical trial registration

Chictr.org.cn, (registration number: ChiCTR1800018497, registration date: 20/09/2018)
Reliability and validity of Chengdu pediatric emergency triage criteria: case study of a single center in China
Authors: Zhao Yingying , He Liqing , Hu Juan , Zhao Jing , Yi Xiaolan , Huang Humin
Published: May 2023

Background

We aimed to examine the reliability and validity of Chengdu pediatric emergency triage criteria in order to provide a reference for the development of pediatric emergency triage within other hospitals.

Methods

We developed Chengdu pediatric emergency triage criteria based on the conditions/symptom, vital signs, and the Pediatric Early Warning Score system within our hospital using the Delphi method in 2020. The simulation scenario triage and real-life triage which were conducted in our hospital during January - March 2021, and the retrospective study of triage records extracted from our hospital’s health information system in February 2022, were used to measure the agreement in triage decisions between the triage nurses, and between the triage nurses and the expert team.

Results

For the 20 simulation cases, the Kappa value of triage decisions between the triage nurses was 0.6 (95% CI 0.352–0.849), and the Kappa value of triage decisions between the triage nurses and the expert team was 0.73 (95% CI 0.540–0.911). For the 252 cases in the real-life triage, the Kappa value of triage decisions between the triage nurses and the expert team was 0.824 (95% CI 0.680–0.962). For the 20,540 cases selected for the retrospective study of triage records, the Kappa value of triage decisions between the triage nurses was 0.702 (95% CI 0.691–0.713); that between Triage Nurse 1 and the expert team was 0.634 (95% CI 0.623–0.647); and that between Triage Nurse 2 and the expert team was 0.725 (95% CI 0.713–0.736). The overall agreement rate in triage decisions between the triage nurses and the expert team in the simulation scenario triage was 80%; that between the triage nurses and the expert team in the real-life triage was 97.6%; and that between the triage nurses in the retrospective study was 91.9%. In the retrospective study, the agreement rates in triage decisions between Triage Nurse 1 and the expert team, and between Triage Nurse 2 and the expert team, were 88.0% and 92.3%, respectively.

Conclusion

Chengdu pediatric emergency triage criteria that developed within our hospital is reliable and valid, and can promote rapid and effective triage by triage nurses.
Influence of distance to health facilities on clinical breast cancer screening behaviour among women in five sub-Saharan African countries
Authors: Addo Isaac Y. , Acquah Evelyn , Ayebeng Castro , Dickson Kwamena S.
Published: May 2023

Background

Regular breast screening is one of the most effective ways to detect early signs of breast cancer but travel distance to cancer-diagnostic facilities can affect breast screening attendance. Yet, limited studies have examined the impact of distance to cancer-diagnostic facilities on clinical breast screening behaviour among women in sub-Saharan Africa (SSA). This study examined the influence of travel distance to a health facility on clinical breast screening behaviour in five SSA countries: Namibia, Burkina Faso, Cote D’Ivoire, Kenya, and Lesotho. The study further assessed variations in clinical breast screening behaviour across diverse socio-demographic characteristics of women.

Methods

A sample of 45,945 women was drawn from the most recent Demographic and Health Surveys (DHS) for the included countries. The DHS uses 2-stage stratified cluster sampling to select nationally representative samples of women (15–49) and men (15–64) via a cross-sectional design. Proportions and binary logistic regression were used to examine associations between the women’s socio-demographic characteristics and breast screening attendance.

Results

The overall proportion of survey participants who underwent clinical breast cancer screening was 16.3%. Travel distance to a health facility had a significant (p < 0.001) impact on clinical breast screening behaviour as 18.5% of participants who self-reported distance as “not a big problem” attended clinical breast screening compared to 10.8% who self-reported distance as “a big problem”. The study further found that various socio-demographic factors were significantly associated with breast cancer screening uptake, including age, education level, media exposure, wealth status, parity, contraceptive use, health insurance coverage, and marital status. The multivariate analysis controlling for other factors confirmed the strong association between distance to health facilities and screening uptake.

Conclusions

The study found that travel distance is a significant factor affecting clinical breast screening attendance among women in the selected SSA countries. Furthermore, the likelihood of breast screening attendance varied depending on different women’s characteristics. It is crucial to prioritise breast screening interventions, particularly among the disadvantaged women identified in this study, to achieve maximum public health benefits.
The role of the California tier system in controlling population mobility during the COVID-19 pandemic
Authors: Schwarz Emilie , Schwarz Lara , Teyton Anaïs , Crist Katie , Benmarhnia Tarik
Published: May 2023

Background

Policies to restrict population mobility are a commonly used strategy to limit the transmission of contagious diseases. Among measures implemented during the COVID-19 pandemic were dynamic stay-at-home orders informed by real-time, regional-level data. California was the first state in the U.S. to implement this novel approach; however, the effectiveness of California’s four-tier system on population mobility has not been quantified.

Methods

Utilizing data from mobile devices and county-level demographic data, we evaluated the impact of policy changes on population mobility and explored whether demographic characteristics explained variability in responsiveness to policy changes. For each California county, we calculated the proportion of people staying home and the average number of daily trips taken per 100 persons, across different trip distances and compared this to pre-COVID-19 levels.

Results

We found that overall mobility decreased when counties moved to a more restrictive tier and increased when moving to a less restrictive tier, as the policy intended. When placed in a more restrictive tier, the greatest decrease in mobility was observed for shorter and medium-range trips, while there was an unexpected increase in the longer trips. The mobility response varied by geographic region, as well as county-level median income, gross domestic product, economic, social, and educational contexts, the prevalence of farms, and recent election results.

Conclusions

This analysis provides evidence of the effectiveness of the tier-based system in decreasing overall population mobility to ultimately reduce COVID-19 transmission. Results demonstrate that socio-political demographic indicators drive important variability in such patterns across counties.
Patient-reported outcome (PRO)-based symptom assessment in patients with advanced lung cancer receiving first-line combination immunotherapy: a protocol for a multicenter, prospective, observational study
Authors: Deng Yuanle , Hu Han , Jia Rong , Dai Wei , Wang Dengfeng , Zhang Purong , Zhang Peng , Cheng Kai , Tang Jianning , Wen Yan , Zhou Xiang , Shi Qiuling , Xiong Zhujuan , Zhou Jin
Published: May 2023

Background

Immunotherapy is currently applied in the first-line treatment regimens for numerous advanced cancers, especially advanced lung cancer. Immune-related adverse events (irAEs) resulting from immunotherapy can vary in severity and cause a substantial symptom burden to patients. However, there are limited data on symptom burden in patients with advanced lung cancer following immunotherapy. To address this deficit, this study aims to provide insight into the symptom burden and severity through patient-reported outcome measurements and conduct an analysis of temporal trends and clinical consequences of symptom burden in patients with advanced lung cancer receiving combination immunotherapy.

Methods

We will prospectively recruit 168 eligible patients from 14 hospitals in China. Eligible patients will be aged ≥ 18 years, pathologically diagnosed with locally advanced or stage IV primary lung cancer without surgical indications, and agreed to receive immunotherapy in combination with other therapies. The primary outcome of this study is the symptom burden of patients during the immunotherapy course. Longitudinal symptom data will be collected using the MD Anderson Symptom Inventory–Lung Cancer module (MDASI-LC) and the symptomatic irAEs scale at baseline (once before treatment) and weekly after treatment, until 1 month after the last treatment cycle has been completed. The trajectory of symptom burden following combination immunotherapy will be depicted, and by linking it to clinical outcomes (the secondary outcome and exploratory outcome of this study), the consequence of symptom burden in patients with advanced lung cancer receiving combination immunotherapy will be examined further.

Discussion

This study intends to establish longitudinal symptom trajectories in patients with lung cancer receiving immunotherapy, and explore its association with clinical outcomes. These findings may serve as an important reference for clinicians in the symptomatic management of patients with lung cancer receiving immunotherapy.

Trial registration number

ChiCTR2200061540. Registered on June 28, 2022.
Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery
Authors: Yang Xue , Wu Yonglin , Xu Shaojie , Li Hanning , Peng Chengcheng , Cui Xiaoqing , Dhoomun Deenraj Kush , Wang Ge , Xu Tao , Dong Menglu , Li Xingrui , Du Yaying
Published: May 2023

Background

Recurrent and metastatic thyroid cancer is more invasive and can transform to dedifferentiated thyroid cancer, thus leading to a severe decline in the 10-year survival. The thyroid-stimulating hormone receptor (TSHR) plays an important role in differentiation process. We aim to find a therapeutic target in redifferentiation strategies for thyroid cancer.

Methods

Our study integrated the differentially expressed genes acquired from the Gene Expression Omnibus database by comparing TSHR expression levels in the Cancer Genome Atlas database. We conducted functional enrichment analysis and verified the expression of these genes by RT-PCR in 68 pairs of thyroid tumor and paratumor tissues. Artificial intelligence-enabled virtual screening was combined with the VirtualFlow platform for deep docking.

Results

We identified five genes (KCNJ16, SLC26A4, TG, TPO, and SYT1) as potential cancer treatment targets. TSHR and KCNJ16 were downregulated in the thyroid tumor tissues, compared with paired normal tissues. In addition, KCNJ16 was lower in the vascular/capsular invasion group. Enrichment analyses revealed that KCNJ16 may play a significant role in cell growth and differentiation. The inward rectifier potassium channel 5.1 (Kir5.1, encoded by KCNJ16) emerged as an interesting target in thyroid cancer. Artificial intelligence-facilitated molecular docking identified Z2087256678_2, Z2211139111_1, Z2211139111_2, and PV-000592319198_1 (-7.3 kcal/mol) as the most potent commercially available molecular targeting Kir5.1.

Conclusion

This study may provide greater insights into the differentiation features associated with TSHR expression in thyroid cancer, and Kir5.1 may be a potential therapeutic target in the redifferentiation strategies for recurrent and metastatic thyroid cancer.
Neonatal reference intervals for thyroid stimulating hormone and free thyroxine assayed on a Siemens Atellica® IM analyzer: a cross sectional study
Authors: Omuse Geoffrey , Kawalya David , Mugaine Patrick , Chege Assumpta , Maina Daniel
Published: May 2023

Background

Deriving population specific reference intervals (RIs) or at the very least verifying any RI before adoption is good laboratory practice. Siemens has provided RIs for thyroid stimulating hormone (TSH) and free thyroxine (FT4) determined on their Atellica® IM analyzer for all age groups except the neonatal age group which provides a challenge for laboratories that intend to use it to screen for congenital hypothyroidism (CH) and other thyroid disorders in neonates. We set out to determine RIs for TSH and FT4 using data obtained from neonates undergoing routine screening for CH at the Aga Khan University Hospital, Nairobi, Kenya.

Methodology

TSH and FT4 data for neonates aged 30 days and below were extracted from the hospital management information system for the period March 2020 to June 2021. A single episode of testing for the same neonate was included provided both TSH and FT4 were done on the same sample. RI determination was performed using a non-parametric approach.

Results

A total of 1243 testing episodes from 1218 neonates had both TSH and FT4 results. A single set of test results from each neonate was used to derive RIs. Both TSH and FT4 declined with increase in age with a more marked decline seen in the first 7 days of life. There was a positive correlation between logFT4 and logTSH (rs (1216) = 0.189, p = < 0.001). We derived TSH RIs for the age groups 2–4 days (0.403–7.942 µIU/mL) and 5–7 days (0.418–6.319 µIU/mL), and sex specific RIs for males (0.609–7.557 µIU/mL) and females (0.420–6.189 µIU/mL) aged 8–30 days. For FT4, separate RIs were derived for the age groups 2–4 days (1.19–2.59 ng/dL), 5–7 days (1.21–2.29 ng/dL) and 8–30 days (1.02–2.01 ng/dL).

Conclusion

Our neonatal RIs for TSH and FT4 are different from those published or recommended by Siemens. The RIs will serve as a guide for the interpretation of thyroid function tests in neonates from sub-Saharan Africa where routine screening for congenital hypothyroidism using serum samples is done on the Siemens Atellica® IM analyzer.
Retrospective analysis of dental implants immediately placed in extraction sockets with periapical pathology: immediate implant placement in infected areas
Authors: Çolak Sefa , Demïrsoy Mustafa Sami
Published: May 2023

Background

The aim of this study is to examine the survival rates of immediate implants placed in extraction sockets with chronic periapical pathology.

Methods

69 patients and 124 immediate implants were included in the study. The patients included in the study were examined in 3 groups. Group 1: Patients who underwent tooth extraction with periapical pathology and immediate implant placement. Group 2: patients who underwent tooth extraction with periapical pathology, immediate implant placement and guided bone regeneration. Group 3: Patients who underwent tooth extraction with periapical pathology, sinus lift procedure and immediate implant placement. In statistical analysis, t-test and Anova analysis were used in the evaluation of quantitative data, cross-tables and chi-square (χ2) test were used in the evaluation of classified qualitative data. Statistical significance was determined as p < 0.05.

Results

It was observed that 116 (95.55%) of 124 implants were successful and 8 (4.45%) failed. The success rate was 97.2% in Group 1, 93.5% in Group 2 and 81.8% in Group 3. A significant correlation was found between the study groups and implant success in terms of χ2 test (p = 0.037). A significant relationship was found between smoking and success in terms of the χ2 test (p = 0.015).

Conclusions

High survival rates are observed for immediate implant placement in sockets with periapical pathology. The success rates observed in guided bone regenerations simultaneously with immediate implant placement are at satisfactory levels. In cases where simultaneous sinus lifting procedures are required, the success rates were observed to be significantly lower. In case of adequate curettage and debridement in sockets with periapical pathology, high implant survival rates are observed. As the complexity of the surgical procedure increases, treatment protocols may progress in safer ways.
The effects of virtual logotherapy on health-promoting lifestyle among single-parent adolescent girls during the coronavirus disease 2019 pandemic: a randomized clinical trial
Authors: Hosseinzadeh Fatemeh , Negarandeh Reza , Sadat-Hoseini Akram Sadat , Pashaeypoor Shahzad
Published: May 2023

Single-parent adolescents are vulnerable individuals and it is necessary to improve their health, particularly during epidemics. This study aimed to investigate the effects of virtual logotherapy (VL) on health-promoting lifestyle (HPL) among single-parent adolescent girls during the COVID-19 pandemic. This single-blind randomized clinical trial was conducted on 88 single-parent adolescent girls recruited from the support organization for vulnerable individuals in Tehran, Iran. They were randomly allocated to a control and an intervention group through block randomization. Participants in the intervention group received VL in three–five person groups in 90 min biweekly sessions. The Adolescent Health Promotion Short-Form was used to assess HPL. Data were analyzed using the SPSS software (v. 26.0) and through the independent-sample t, Chi-square, Fisher’s exact, and Mann–Whitney U tests. There was no significant difference between the intervention and the control groups respecting the pretest mean score of HPL (73.58±16.74 vs. 72.80±9.30; P=0.085). However, the posttest mean score of HPL in the intervention group (82 with an interquartile range of 78–90) was significantly more than the control group (71.50 with an interquartile range of 63.25–84.50) (P=0.001). Moreover, after adjusting the effects of the significant between-group differences respecting pretest mean scores, the pretest–posttest differences of the mean scores of HPL and all its dimensions in the intervention group were significantly more than the control group (P<0.05). VL is effective in significantly improving HPL among single-parent adolescent girls. Healthcare authorities are recommended to use VL for health promotion among single-parent adolescents.

Trial registration

This research was registered (17/05/2020) in the www.thaiclinicaltrials.org with registration number: TCTR20200517001.
The effects of normal vaginal birth simulation training on the clinical skills of midwifery students: a quasi-experiment study
Authors: Pajohideh Zahra Sadat , Mohammadi Solmaz , Keshmiri Fatemeh , Jahangirimehr Azam , Honarmandpour Azam
Published: May 2023

Background

Vaginal birth management is vital to midwifery education and practice in which midwives are most likely to be directly involved. This situation requires strong cognitive, technical, communicational, and teamwork skills. Therefore, the present study was conducted to evaluate the effect of normal vaginal birth simulation training before formal clinical education on the clinical skills of midwifery students compared with routine clinical education.

Methods

This quasi-experimental study was conducted at the Shoushtar Faculty of Medical Sciences from September 2018 to August 2021. Sixty-one midwifery students participated in the intervention group (n = 31) and in the control group (n = 30). The intervention group participated in the simulation-based training before entering the formal clinical education courses. The control group received no simulation-based training before their formal clinical education. The clinical skills of these students for performing normal vaginal birth in the real field were evaluated by observational examination in the three years (fourth, fifth, and sixth semesters). Data were analyzed by descriptive (mean, SD, and percentage) and inferential statistics (independent t-test and chi-square). A P-value less than 0.05 was considered significant.

Results

The mean score of midwives’ skills in the control group was (28.10 ± 3.42) and in the intervention group, it was (31.15 ± 4.30). The difference in the skill score between the groups was statistically significant (3.40 ± 0.68). The results showed that in the intervention group, 29 students (93.93%) were evaluated from a good to an excellent level, while only ten students (32.71%) in the control group achieved a good level, and others (n = 30) were evaluated at a low level (p < .001).

Conclusion

The results of the present study indicated that the simulation situation for critical skills, such as vaginal birth skills, was significantly more effective than workplace-based learning situations.
”Putting words to their feelings”– civic communicators’ perceptions and experiences of an in-depth course on mental health for newly settled refugee migrants in Sweden
Authors: Al-Adhami Maissa , Wångdahl Josefin , Salari Raziye , Åkerman Eva
Published: May 2023

Background

Newly settled refugee migrants face psychological stressors stemming from pre-, during- and post-migration experiences. In Sweden, mental health promotion is part of the health module in the civic orientation classes for newly settled refugee migrants. Training courses are offered to civic communicators and workshop leaders to facilitate communication about mental health; however, the training is seldom evaluated. In the current study, we aim to explore civic communicators’ perceptions and experiences of an in-depth mental health training course in relation to observed needs among newly settled refugee migrants.

Method

We interviewed ten civic communicators that had partaken in the in-depth training course on mental health. All respondents had prior migratory experience and worked as civic communicators in their native languages. The interviews were semi-structured and data were analyzed using thematic analysis.

Results

Three themes were identified: (1) Intertwined mental health needs related to migration, (2) Multi-layered barriers to addressing mental health, and (3) Becoming aware of the mental health journey. One overarching theme was arrived at through synthesizing the three themes ‘Acquired new tools to lead reflective conversations about mental health and well-being’.

Conclusion

The in-depth mental health training course led to the attainment of new knowledge and new tools enabling civic communicators to lead reflective conversations about mental health and well-being with newly settled refugee migrants. Mental health needs were related to pre- and post-migration experiences. Barriers to talking about mental health included stigma and a lack of arenas to promote the mental health of refugee migrants. Increasing knowledge among civic communicators can facilitate the promotion of mental self-help capacity and resilience among newly settled refugee migrants.
Analysis and validation of aging-related genes in prognosis and immune function of glioblastoma
Authors: Mu Jianhua , Gong Jianan , Shi Miao , Zhang Yinian
Published: May 2023

Background

Glioblastoma (GBM) is a common malignant brain tumor with poor prognosis and high mortality. Numerous reports have identified the correlation between aging and the prognosis of patients with GBM. The purpose of this study was to establish a prognostic model for GBM patients based on aging-related gene (ARG) to help determine the prognosis of GBM patients.

Methods

143 patients with GBM from The Cancer Genomic Atlas (TCGA), 218 patients with GBM from the Chinese Glioma Genomic Atlas (CGGA) of China and 50 patients from Gene Expression Omnibus (GEO) were included in the study. R software (V4.2.1) and bioinformatics statistical methods were used to develop prognostic models and study immune infiltration and mutation characteristics.

Results

Thirteen genes were screened out and used to establish the prognostic model finally, and the risk scores of the prognostic model was an independent factor (P < 0.001), which indicated a good prediction ability. In addition, there are significant differences in immune infiltration and mutation characteristics between the two groups with high and low risk scores.

Conclusion

The prognostic model of GBM patients based on ARGs can predict the prognosis of GBM patients. However, this signature requires further investigation and validation in larger cohort studies.
Bloodstream infections due to Carbapenem-Resistant Enterobacteriaceae in hematological patients: assessment of risk factors for mortality and treatment options
Authors: Zhang Lining , Zhen Sisi , Shen Yuyan , Zhang Tingting , Wang Jieru , Li Jia , Lin Qingsong , Xiao Zhijian , Zheng Yizhou , Jiang Erlie , Han Mingzhe , Wang Jianxiang , Feng Sizhou
Published: May 2023

Purpose

Bloodstream infection (BSI) caused by Carbapenem-Resistant Enterobacteriaceae (CRE) are associated with poor outcomes in hematological patients. The aim of this study was to identify risk factors for mortality and evaluate the value of epidemiological feature of carbapenemases in guiding antimicrobial treatment options.

Methods

Hematological patients with monomicrobial CRE BSI between January 2012 and April 2021 were included. The primary outcome was all-cause mortality 30 days after BSI onset.

Results

A total of 94 patients were documented in the study period. Escherichia coli was the most common Enterobacteriaceae, followed by Klebsiella pneumoniae. 66 CRE strains were tested for carbapenemase genes, and 81.8% (54/66) were positive, including NDM (36/54), KPC (16/54), IMP (1/54). Besides, one E. coli isolate was found to express both NDM and OXA-48-like genes. Overall, 28 patients received an antimicrobial treatment containing ceftazidime-avibactam (CAZ-AVI), of which 21 cases were combined with aztreonam. The remaining 66 patients were treated with other active antibiotics (OAAs). The 30-day mortality rate was 28.7% (27/94) for all patients, and was only 7.1% ((2/28) for patients treated with CAZ-AVI. In multivariate analysis, the presence of septic shock at BSI onset (OR 10.526, 95% CI 1.376–76.923) and pulmonary infection (OR 6.289, 95% CI 1.351–29.412) were independently risk factors for 30-day mortality. Comparing different antimicrobial regimens, CAZ-AVI showed a significant survive benefit than OAAs (OR 0.068, 95% CI 0.007–0.651).

Conclusion

CAZ-AVI-containing regimen is superior to OAAs for CRE BSI. As the predominance of blaNDM in our center, we recommend the combination with aztreonam when choose CAZ-AVI.
Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy
Authors: Li Zhenxian , Zhu Haimei , Liu Hao , Liu Dayue , Liu Jianhe , Jiang Jiazheng , Zhang Yi , Qin Zhang , Xu Yijia , Peng Yuan , Liu Bin , Long Yun
Published: May 2023

PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE−/− mice.
Integrating automated liquid handling in the separation workflow of extracellular vesicles enhances specificity and reproducibility
Authors: Van Dorpe Sofie , Lippens Lien , Boiy Robin , Pinheiro Cláudio , Vergauwen Glenn , Rappu Pekka , Miinalainen Ilkka , Tummers Philippe , Denys Hannelore , De Wever Olivier , Hendrix An
Published: May 2023

Background

Extracellular vesicles (EV) are extensively studied in human body fluids as potential biomarkers for numerous diseases. Major impediments of EV-based biomarker discovery include the specificity and reproducibility of EV sample preparation as well as intensive manual labor. We present an automated liquid handling workstation for the density-based separation of EV from human body fluids and compare its performance to manual handling by (in)experienced researchers.

Results

Automated versus manual density-based separation of trackable recombinant extracellular vesicles (rEV) spiked in PBS significantly reduces variability in rEV recovery as quantified by fluorescent nanoparticle tracking analysis and ELISA. To validate automated density-based EV separation from complex body fluids, including blood plasma and urine, we assess reproducibility, recovery, and specificity by mass spectrometry-based proteomics and transmission electron microscopy. Method reproducibility is the highest in the automated procedure independent of the matrix used. While retaining (in urine) or enhancing (in plasma) EV recovery compared to manual liquid handling, automation significantly reduces the presence of body fluid specific abundant proteins in EV preparations, including apolipoproteins in plasma and Tamm-Horsfall protein in urine.

Conclusions

In conclusion, automated liquid handling ensures cost-effective EV separation from human body fluids with high reproducibility, specificity, and reduced hands-on time with the potential to enable larger-scale biomarker studies.

Graphical Abstract
Small extracellular vesicle-mediated metabolic reprogramming: from tumors to pre-metastatic niche formation
Authors: Jiang Chuwen , Jiang Zhengting , Sha Gengyu , Wang Daorong , Tang Dong
Published: May 2023

Metastasis, the spread of a tumor or cancer from the primary site of the body to a secondary site, is a multi-step process in cancer progression, accounting for various obstacles in cancer treatment and most cancer-related deaths. Metabolic reprogramming refers to adaptive metabolic changes that occur in cancer cells in the tumor microenvironment (TME) to enhance their survival ability and metastatic potential. Stromal cell metabolism also changes to stimulate tumor proliferation and metastasis. Metabolic adaptations of tumor and non-tumor cells exist not only in the TME but also in the pre-metastatic niche (PMN), a remote TME conducive for tumor metastasis. As a novel mediator in cell-to-cell communication, small extracellular vesicles (sEVs), which have a diameter of 30–150 nm, reprogram metabolism in stromal and cancer cells within the TME by transferring bioactive substances including proteins, mRNAs and miRNAs (microRNAs). sEVs can be delivered from the primary TME to PMN, affecting PMN formation in stroma rewriting, angiogenesis, immunological suppression and matrix cell metabolism by mediating metabolic reprogramming. Herein, we review the functions of sEVs in cancer cells and the TME, how sEVs facilitate PMN establishment to trigger metastasis via metabolic reprogramming, and the prospective applications of sEVs in tumor diagnosis and treatment.
Physiological and pathological consequences of exosomes at the blood–brain-barrier interface
Authors: Salimi Leila , Seyedaghamiri Fatemehsadat , Karimipour Mohammad , Mobarak Halimeh , Mardi Narges , Taghavi Maryam , Rahbarghazi Reza
Published: May 2023

Blood–brain barrier (BBB) interface with multicellular structure controls strictly the entry of varied circulating macromolecules from the blood-facing surface into the brain parenchyma. Under several pathological conditions within the central nervous system, the integrity of the BBB interface is disrupted due to the abnormal crosstalk between the cellular constituents and the recruitment of inflammatory cells. Exosomes (Exos) are nano-sized extracellular vesicles with diverse therapeutic outcomes. These particles transfer a plethora of signaling molecules with the potential to modulate target cell behavior in a paracrine manner. Here, in the current review article, the therapeutic properties of Exos and their potential in the alleviation of compromised BBB structure were discussed.
Synergistic immunotherapy targeting cancer-associated anemia: prospects of a combination strategy
Authors: Yuan Ting , Jia Qingzhu , Zhu Bo , Chen Degao , Long Haixia
Published: May 2023

Cancer-associated anemia promotes tumor progression, leads to poor quality of life in patients with cancer, and even obstructs the efficacy of immune checkpoint inhibitors therapy. However, the precise mechanism for cancer-associated anemia remains unknown and the feasible strategy to target cancer-associated anemia synergizing immunotherapy needs to be clarified. Here, we review the possible mechanisms of cancer-induced anemia regarding decreased erythropoiesis and increased erythrocyte destruction, and cancer treatment-induced anemia. Moreover, we summarize the current paradigm for cancer-associated anemia treatment. Finally, we propose some prospective paradigms to slow down cancer-associated anemia and synergistic the efficacy of immunotherapy.
Aquaporin-4 IgG antibodies: predictors of positivity and their relationship with neuropsychiatric disorders and white matter lesions in Juvenile systemic lupus erythematosus
Authors: Shaaban Yasmeen , EL-Marsafawy Hala , El-Farahaty Reham M , El-Ziny Sherine , EL-Refaey Ahmed M
Published: May 2023

Background

This study aimed to describe the prevalence of the various clinical features and severity of juvenile systemic lupus erythematosus (jSLE) and to assess predictors of AQP4-Ab positivity in jSLE. In addition, we assessed the relationship of AQP4-Abs with neuropsychiatric disorders and white matter lesions in jSLE.

Method

For 90 patients with jSLE, demographic data, clinical manifestations, and treatments received were recorded, and all of the patients were underwent clinical examinations, including assessments for the neurological manifestations of jSLE and neuropsychiatric disorders; Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score evaluations; laboratory investigations, including serum AQP4-Ab assays; and 1.5 Tesla brain MRI. Echocardiography and renal biopsy were performed for the indicated patients.

Result

Fifty-six patients (62.2%) tested positive for AQP4-Abs. These patients were more likely to have higher disease activity scores (p < 0.001); discoid lesions (p = 0.039); neurological disorders (p = 0.001), mainly psychosis and seizures (p = 0.009 and p = 0.032, respectively); renal and cardiac involvement (p = 0.004 and p = 0.013, respectively); lower C3 levels (p = 0.006); white matter hyperintensities (p = 0.008); and white matter atrophy (p = 0.03) than patients who were negative for AQP4-Abs. Furthermore, AQP4-Ab-positive patients were more likely to have received cyclophosphamide (p = 0.028), antiepileptic drugs (p = 0.032) and plasma exchange therapy (p = 0.049).

Conclusion

jSLE patients with higher severity scores, neurological disorders, or white matter lesions could develop antibodies against AQP4. We recommend more studies for systematic screening of AQP4-Ab positivity in jSLE patients to confirm its relationship with neurological disorders.
Study on association of serum uric acid levels with bipolar disorder: systematic review and meta-analysis in Chinese patients
Authors: Chen Haihan , Sun Fengli , Jin Weidong
Published: May 2023

Background

The purine system represented by uric acid may be involved in the pathogenesis of bipolar disorder, This study intends to explore the association of serum uric acid levels with bipolar disorder in Chinese patients through meta-analysis.

Methods

Electronic databases, including PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI), searching from inception to December 2022. Randomized Controlled Trials that reported serum uric acid levels and bipolar disorder were included. Two investigators independently extracted data and RevMan5.4 and Stata14.2 were used for statistical analyses.

Results

Twenty-eight studies with 4482 bipolar disorder, 1568 depression, 785 schizophrenia, and 2876 healthy control subjects were included in this meta-analysis. The results of the meta-analysis showed that serum uric acid levels in the bipolar disorder group were significantly higher than those in depression [SMD 0.53 (0.37, 0.70),p < 0.00001], schizophrenia [SMD 0.27 (0.05, 0.49),p = 0.02] and healthy control group [SMD 0.87 (0.67, 1.06),p < 0.00001]. Subgroup-analysis showed that in Chinese people with bipolar disorder, uric acid levels of the manic episode were higher than the depressed episode [SMD 0.31 (0.22, 0.41),p < 0.00001].

Conclusion

Our results indicated a strong association between serum uric acid levels and bipolar disorder in Chinese patients, but further studies about whether uric acid levels can be a biomarker for bipolar disorder still need to investigate.
Bearing the mark of pain: mystery in medicine
Authors: Celie Karel-Bart , Paris John J.
Published: May 2023

Dostoevsky wrote that love in action is a harsh and terrible thing compared to love in dreams. That reality is particularly evident in medicine, where there is an almost universal, involuntary participation of physicians and other healthcare workers in the suffering of their patients. This paper explores this phenomenon through the paradigm of ‘mystery’ as explained by the French existentialist philosopher Gabriel Marcel. A mystery is different from a problem in the sense that the former requires the active immersion of the person involved in order to be truly experienced. It is a ‘meta-problem’ that cannot be analyzed objectively and separately from the person that it affects, without changing the nature of the thing experienced. The authors contend that the human suffering encountered in medicine is one such phenomenon, and the paper draws on illustrations of this concept in art and literature. Awareness of the subtle but important difference between mystery and problem may help physicians better understand their personal entanglement with the suffering of patients.
Complex duodenal fistulae: a surgical nightmare
Authors: Leppäniemi Ari , Tolonen Matti , Mentula Panu
Published: May 2023

Introduction

A common feature of external duodenal fistulae is the devastating effect of the duodenal content rich in bile and pancreatic juice on nearby tissues with therapy-resistant local and systemic complications. This study analyzes the results of different management options with emphasis on successful fistula closure rates.

Methods

A retrospective single academic center study of adult patients treated for complex duodenal fistulas over a 17-year period with descriptive and univariate analyses was performed.

Results

Fifty patients were identified. First line treatment was surgical in 38 (76%) cases and consisted of resuture or resection with anastomosis combined with duodenal decompression and periduodenal drainage in 36 cases, rectus muscle patch, and surgical decompression with T-tube in one each. Fistula closure rate was 29/38 (76%). In 12 cases, the initial management was nonoperative with or without percutaneous drainage. The fistula was closed without surgery in 5/6 patients (1 patient died with persistent fistula). Among the remaining 6 patients eventually operated, fistula closure was achieved in 4 cases. There was no difference in successful fistula closure rates among initially operatively versus nonoperatively managed patients (29/38 vs. 9/12, p = 1.000). However, when considering eventually failed nonoperative management in 7/12 patients, there was a significant difference in the fistula closure rate (29/38 vs. 5/12, p = 0.036). The overall in-hospital mortality rate was 20/50 (40%).

Conclusions

Surgical closure combined with duodenal decompression in complex duodenal leaks offers the best chance of successful outcome. In selected cases, nonoperative management can be tried, accepting that some patients may require surgery later.
The PRESIDE (PhaRmacogEnomicS In DEpression) Trial: a double-blind randomised controlled trial of pharmacogenomic-informed prescribing of antidepressants on depression outcomes in patients with major depressive disorder in primary care
Authors: Saya Sibel , Chondros Patty , Abela Anastasia , Mihalopolous Cathrine , Chatterton Mary Lou , Gunn Jane , Chen Timothy F. , Polasek Thomas M. , Dettmann Elise , Brooks Rachel , King Michelle , Spencer Luke , Alphonse Pavithran , Milton Shakira , Ramsay Georgia , Siviour Zoe , Liew Jamie , Ly Philip , Thoenig Matthew , Seychell Raushaan , La Rocca Floriana , Hesson Luke B. , Mejias Nydia , Sivertsen Terri , Galea Melanie Anne , Bousman Chad , Emery Jon
Published: May 2023

Background

The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs.

Methods

The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18–65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention.

Discussion

This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care.

Trial registration

Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021.
Transcriptomic and metabolomic analyses revealed regulation mechanism of mixotrophic Cylindrotheca sp. glycerol utilization and biomass promotion
Authors: Wang Song , Zhou Xiyi , Wu Sha , Zhao Mengkai , Hu Zhangli
Published: May 2023

Background

Diatoms have been viewed as ideal cell factories for production of some high-value bioactive metabolites, such as fucoxanthin, but their applications are restrained by limited biomass yield. Mixotrophy, by using both CO2 and organic carbon source, is believed effective to crack the bottleneck of biomass accumulation and achieve a sustainable bioproduct supply.

Results

Glycerol, among tested carbon sources, was proved as the sole that could significantly promote growth of Cylindrotheca sp. with illumination, a so-called growth pattern, mixotrophy. Biomass and fucoxanthin yields of Cylindrotheca sp., grown in medium with glycerol (2 g L−1), was increased by 52% and 29%, respectively, as compared to the autotrophic culture (control) without compromise in photosynthetic performance. As Cylindrotheca sp. was unable to use glycerol without light, a time-series transcriptomic analysis was carried out to elucidate the light regulation on glycerol utilization. Among the genes participating in glycerol utilization, GPDH1, TIM1 and GAPDH1, showed the highest dependence on light. Their expressions decreased dramatically when the alga was transferred from light into darkness. Despite the reduced glycerol uptake in the dark, expressions of genes associating with pyrimidine metabolism and DNA replication were upregulated when Cylindrotheca sp. was cultured mixotrophically. Comparative transcriptomic and metabolomic analyses revealed amino acids and aminoacyl-tRNA metabolisms were enhanced at different timepoints of diurnal cycles in mixotrophic Cylindrotheca sp., as compared to the control.

Conclusions

Conclusively, this study not only provides an alternative for large-scale cultivation of Cylindrotheca, but also pinpoints the limiting enzymes subject to further metabolic manipulation. Most importantly, the novel insights in this study should aid to understand the mechanism of biomass promotion in mixotrophic Cylindrotheca sp.