bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical efficacy and safety of tigecycline based on therapeutic drug monitoring for carbapenem-resistant Gram-negative bacterium pneumonia in intensive care units
Authors: Bai Xiang-rong , Wang Zhi-zhou , Li Wen-chao , Wang Yan-gai , Lou Ran , Qu Xin , Fan Linlin , Zhang Wei , Wu Yan-chuan , Yan Su-ying , Zhang Lan
Published: November 2023

Background

We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit.

Methods

This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline’s clinical efficacy and safety were performed to control confounding factors.

Results

For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 μg/mL in the HD group, which was higher than in the SD group (0,21 μg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005–1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755–1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline.

Conclusions

Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient’s age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.
Quantitative CT parameters combined with preoperative systemic inflammatory markers for differentiating risk subgroups of thymic epithelial tumors
Authors: Gao Rongji , Zhou Jian , Zhang Juan , Zhu Jianzhong , Wang Tiantian , Yan Chengxin
Published: November 2023

Background

Thymic epithelial tumors (TETs) are the most common primary neoplasms of the anterior mediastinum. Different risk subgroups of TETs have different prognosis and therapeutic strategies, therefore, preoperative identification of different risk subgroups is of high clinical significance. This study aims to explore the diagnostic efficiency of quantitative computed tomography (CT) parameters combined with preoperative systemic inflammatory markers in differentiating low-risk thymic epithelial tumors (LTETs) from high-risk thymic epithelial tumors (HTETs).

Methods

74 Asian patients with TETs confirmed by biopsy or postoperative pathology between January 2013 and October 2022 were collected retrospectively and divided into two risk subgroups: LTET group (type A, AB and B1 thymomas) and HTET group (type B2, B3 thymomas and thymic carcinoma). Statistical analysis were performed between the two groups in terms of quantitative CT parameters and preoperative systemic inflammatory markers. Multivariate logistic regression analysis was used to determine the independent predictors of risk subgroups of TETs. The area under curve (AUC) and optimal cut-off values were calculated by receiver operating characteristic (ROC) curves.

Results

47 TETs were in LTET group, while 27 TETs were in HTET group. In addition to tumor size and CT value of the tumor on plain scan, there were statistical significance comparing in CT value of the tumor on arterial phase (CTv-AP) and venous phase (CTv-VP), and maximum enhanced CT value (CEmax) of the tumor between the two groups (for all, P < 0.05). For systemic inflammatory markers, HTET group was significantly higher than LTET group (for all, P < 0.05), including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). Multivariate logistic regression analysis showed that NLR (odds ratio [OR] = 2.511, 95% confidence interval [CI]: 1.322–4.772, P = 0.005), CTv-AP (OR = 0.939, 95%CI: 0.888–0.994, P = 0.031) and CTv-VP (OR = 0.923, 95%CI: 0.871–0.979, P = 0.008) were the independent predictors of risk subgroups of TETs. The AUC value of 0.887 for the combined model was significantly higher than NLR (0.698), CTv-AP (0.800) or CTv-VP (0.811) alone. The optimal cut-off values for NLR, CTv-AP and CTv-VP were 2.523, 63.44 Hounsfeld Unit (HU) and 88.29HU, respectively.

Conclusions

Quantitative CT parameters and preoperative systemic inflammatory markers can differentiate LTETs from HTETs, and the combined model has the potential to improve diagnostic efficiency and to help the patient management.
Comparison of the new self-contained darkroom refractive screener versus table-top autorefractor and cycloplegia retinoscopy in detecting refractive error
Authors: Wei Xianxian , Li Lili , Jiang Li , Lu Haiyan , Huang Huiyao , Zhong Dedong , Pan Liang , Wei Diefeng , Han Yun , Lin Hong , Chen Qi
Published: November 2023

Purpose

By comparing the results of the new self-contained darkroom refractive screener (YD-SX-A) versus table-top autorefractor and cycloplegic retinoscopy, to evaluate the performance of the YD-SX-A in detecting refractive error in children and adolescents and then judge whether it can be used in refractive screening.

Methods

Cross-sectional study. 1000 participants between the ages of 6 and 18 who visited the Optometry Center of the People's Hospital of Guangxi Zhuang Autonomous Region from June to December 2022 were selected. First, participants were instructed to measure their diopter with a table-top autorefractor (Topcon KR8800) and YD-SX-A in a noncycloplegic setting. After cycloplegia, they were retinoscopy by a professional optometrist. The results measured by three methods were collected respectively. To avoid deviation, only the right eye (1000 eyes) data were used in the statistical analysis. The Bland–Altman plots were used to evaluate the agreement of diopters measured by the three methods. The receiver operating characteristic (ROC) curves was used to analysis effectiveness of detecting refractive error of YD-SX-A.

Results

The average age of participants was 10.77 ± 3.00 years, including 504 boys (50.4%) and 496 girls (49.6%). When YD-SX-A and cycloplegia retinoscopy (CR) were compared in the myopia group, there was no statistical difference in spherical equivalent (SE) (P > 0.05), but there was a statistical difference in diopter spherical (DS) and diopter cylinder (DC) (P < 0.05). Comparing the diopter results of Topcon KR8800 and CR, the difference between each test value in the myopia group was statistically significant (P < 0.05). In the hyperopia group, the comparison between YD-SX-A and CR showed no statistically significant differences in the DC (P > 0.05), but there were significant differences in the SE and DS (P < 0.05). In the astigmatism group, the SE, DS, and DC were statistically different, and the DC of YD-SX-A was lower than that of CR and Topcon KR8800. Bland–Altman plots indicated that YD-SX-A has a moderate agreement with CR and Topcon KR8800. The sensitivity and specificity of YD-SX-A for detecting myopia, hyperopia and astigmatism were 90.17% and 90.32%, 97.78% and 87.88%, 84.08% and 74.26%, respectively.

Conclusion

This study has identified that YD-SX-A has shown good performance in both agreement and effectiveness in detecting refractive error when compared with Topcon KR8800 and CR. YD-SX-A could be a useful tool for large-scale population refractive screening.
Introduction of pediatric laparoscopic inguinal hernia repair in Guatemala
Authors: Cóbar Juan P. , Nichol Peter F.
Published: November 2023

Purpose

Introducing new surgical techniques in a developing country can be challenging. Inguinal hernias in children are a common surgical problem, and open repair is the standard surgical approach. Laparoscopic repair has gained popularity in developed countries because of similar results. This study aimed to determine the outcomes following the introduction of laparoscopic repairs in Guatemala.

Methods

This retrospective analysis of prospectively collected data from all patients under 18 years who underwent laparoscopic repair at Corpus Christi Hospital in Patzun, Guatemala, from September 5th to September 8th, 2022.

Results

A total of 14 patients were included in the study. A board-certified pediatric surgeon and a Guatemalan physician performed all cases. The mean patient age was 7.6 years; 7 boys and 7 girls. All patients were interviewed at 7 days, 30 days, and 6 months. There were no postoperative infections, pain requiring re-evaluation, gonadal atrophy, or hernia recurrence.

Conclusion

Under controlled circumstances with limited but proper equipment and disposables, laparoscopic inguinal hernia repairs can be introduced and performed in a developing country with a risk complication profile comparable to that in developed countries. This study provides promising evidence of laparoscopic repair feasibility and safety where surgical resources are limited.
A prediction model for identifying high-risk lymph node metastasis in clinical low-risk papillary thyroid microcarcinoma
Authors: Huang Hui , Liu Yunhe , Ni Song , Liu Shaoyan
Published: November 2023

Background

The presence of high-volume lymph node metastasis (LNM) and extranodal extension (ENE) greatly increases the risk of recurrence in patients with low-risk papillary thyroid microcarcinoma (PTMC). The goal of this research was to analyze the factors that contribute to high-risk lymph node metastasis in patients with low-risk PTMC.

Methods

We analyzed the records of 7344 patients who were diagnosed with low-risk PTMC and treated at our center from January 2013 to June 2018.LNM with a high volume or ENE was classified as high-risk lymph node metastasis (hr-LNM). A logistic regression analysis was conducted to identify the risk factors associated with hr-LNM. A nomogram was created and verified using risk factors obtained from LASSO regression analysis, to predict the likelihood of hr-LNM.

Results

The rate of hr-LNM was 6.5%. LASSO regression revealed six variables that independently contribute to hr-LNM: sex, age, tumor size, tumor location, Hashimoto’s thyroiditis (HT), and microscopic capsular invasion. A predictive nomogram was developed by integrating these risk factors, demonstrating its excellent performance. Upon analyzing the receiver operating characteristic (ROC) curve for predicting hr-LNM, it was observed that the area under the curve (AUC) had a value of 0.745 and 0.730 in the training and testing groups showed strong agreement, affirming great reliability.

Conclusion

Sex, age, tumor size, tumor location, HT, and microscopic capsular invasion were determined to be key factors associated with hr-LNM in low-risk PTMC. Utilizing these factors, a nomogram was developed to evaluate the risk of hr-LNM in patients with low-risk PTMC.
ITRAQ-based proteomics analysis of human ectopic endometrial stromal cells treated by Maqian essential oil
Authors: Zhang Liu-yang , Huang Ting-ting , Li Li-ping , Liu Dan-ping , Luo Yong , Lu Wan , Huang Ning , Ma Peng-peng , Liu Yan-qiu , Zhang Ping , Yang Bi-cheng
Published: November 2023

Background

Endometriosis is a common and complex syndrome characterized by the presence of endometrial-like tissue outside the uterus. Chinese medicine has been recently found to show good efficacy in treating endometriosis. Our previous results revealed that Maqian fruit essential oil (MQEO) could inhibit the proliferation and induce apoptosis of ectopic endometrial stromal cells (EESCs), but the mechanisms remain unclear. In this study, we aim to explore the molecular mechanism of MQEO’s specific effects in EESCs.

Methods

We conducted a quantitative proteomics analysis by iTRAQ on EESCs treated with MQEO or DMSO. Then deep analysis was performed based on differentially expressed proteins, including Gene Ontology enrichment analysis, pathway enrichment analysis and protein interaction analysis. Candidate protein targets were subsequently verified by western blotting.

Results

Among 6575 identified proteins, 435 proteins exhibited altered expression levels in MQEO-treated EESCs. Of these proteins, most were distributed in signal transduction as well as immune system and the most significantly altered pathway was complement and coagulation cascades. Moreover, two differentially expressed proteins (Heme oxygenase 1 and Acyl-CoA 6-desaturase) were verified and they can be potential biomarkers for endometriosis treatment.

Conclusions

Our proteomic analysis revealed distinct protein expression patterns induced by MQEO treatment in EESCs, highlighting the potential of MQEO for endometriosis treatment and biomarker discovery.
Assessor discomfort and failure to fail in clinical performance assessments
Authors: Scarff Catherine E , Bearman Margaret , Chiavaroli Neville , Trumble Stephen
Published: November 2023

Background

Assessment of trainee performance in the workplace is critical to ensuring high standards of clinical care. However, some supervisors find the task to be challenging, and may feel unable to deliver their true judgement on a trainee’s performance. They may ‘keep MUM’ (that is, keep mum about undesirable messages) and fail to fail an underperforming trainee. In this study, we explore the effect of discomfort on assessors.

Methods

Using a survey method, supervisors of trainees in the Australasian College of Dermatologists were asked to self-report experiences of discomfort in various aspects of trainee workplace assessment and for their engagement in MUM behaviours including failure to fail.

Results

Sixty-one responses were received from 135 eligible assessors. 12.5% of assessors self-reported they had failed to fail a trainee and 18% admitted they had grade inflated a trainee’s score on a clinical performance assessment in the previous 12-month period. Assessors who reported higher levels of discomfort in the clinical performance assessment context were significantly more likely to report previously failing to fail a trainee. The study did not reveal significant associations with assessor demographics and self-reports of discomfort or MUM behaviours.

Conclusions

This study reveals the impact of assessor discomfort on the accuracy of assessment information and feedback to trainees, including as a contributing factor to the failure to fail phenomenon. Addressing assessor experience of discomfort offers one opportunity to impact on the complex and multifactorial issue that failure to fail represents.
Job preference of preventive medicine students during the COVID-19 pandemic: a discrete choice experiment survey in Shandong Province, China
Authors: Tian Zhuang , Guo Wei , Zhai Min , Li Hongmin
Published: November 2023

Background

Public health workers are a crucial part of the health workforce, particularly during the coronavirus disease (COVID-19) pandemic. They play an important role in achieving universal health coverage and sustainable development goals. Human resources in public health in China are in short supply, their distribution is unequal, and their turnover rate is high. A discrete choice experiment (DCE) was applied to investigate preventive medicine students’ preferred job choice criteria and trends in trade-offs by calculating the marginal rate of substitution between these criteria. This study identified the properties of jobs primarily selected by preventive medicine students and estimated the monetary value of each attribute.

Methods

Based on discussions and in-depth interviews with preventive medicine students and a literature review, we developed a DCE that assessed how students’ stated preferences for a certain choice were influenced by several job attributes, including location, salary, bianzhi, career development opportunities, working environment, and workload. We applied this DCE to preventive medicine students in Shandong Province, China, using a brief, structured questionnaire. Conditional logit models were used to estimate the utility of each job’s attributes. Willingness to pay (WTP) was estimated as the ratio of the value of the coefficient of interest to the negative value of the cost attribute.

Results

A total of 307 respondents completed the questionnaire, and 261 passed the internal consistency test. All the attributes were statistically significant. Career development opportunities and work locations were the most important factors for the respondents. Preference heterogeneity existed among respondents, e.g., 3-year medical education college students placed a higher value on jobs with bianzhi compared to 5-year medical education college students. Furthermore, rural students’ WTP for a job located in the county or city is much lower than that of urban students.

Conclusions

The heterogeneity of attributes indicates the complexity of job preferences. Monetary and nonmonetary job characteristics significantly influenced the job preferences of preventive medicine students in China. A more effective policy intervention to attract graduates to work in rural areas should consider both job incentives and the backgrounds of preventive medicine graduates.
METTL3-mediated HOTAIRM1 promotes vasculogenic mimicry icontributionsn glioma via regulating IGFBP2 expression
Authors: Wu Zhangyi , Wei Nan
Published: November 2023

Background

HOTAIRM1 is revealed to facilitate the malignant progression of glioma. Vasculogenic mimicry (VM) is critically involved in glioma progression. Nevertheless, the molecular mechanism of HOTAIRM1 in regulating glioma VM formation remains elusive. Thus, we attempted to clarify the role and mechanism of HOTAIRM1 in VM formation in glioma.

Methods

qRT-PCR and western blot assays were used to evaluate the gene and protein expression levels of HOTAIRM1 in glioma patient tissue samples and cell lines. The role of HOTAIRM1 in glioma cell progression and VM formation was explored using a series of function gain-and-loss experiments. RNA-binding protein immunoprecipitation (RIP), RNA pull-down, and mechanism experiments were conducted to assess the interaction between HOTAIRM1/METTL3/IGFBP2 axis. Furthermore, rescue assays were conducted to explore the regulatory function of HOTAIRM1/METTL3/IGFBP2 in glioma cell cellular processes and VM formation.

Results

We found that HOTAIRM1 presented up-regulation in glioma tissues and cells and overexpression of HOTAIRM1 facilitated glioma cell proliferation, migration, invasion, and VM formation. Furthermore, overexpression of HOTAIRM1 promoted glioma tumor growth and VM formation capacity in tumor xenograft mouse model. Moreover, HOTAIRM1 was demonstrated to interact with IGFBP2 and positively regulated IGFBP2 expression. IGFBP2 was found to promote glioma cell malignancy and VM formation. Mechanistically, METTL3 was highly expressed in glioma tissues and cells and was bound with HOTAIRM1 which stabilized HOTAIRM1 expression. Rescue assays demonstrated that METTL3 silencing counteracted the impact of HOTAIRM1 on glioma cell malignancy and VM formation capacity.

Conclusion

HOTAIRM1, post-transcriptionally stabilized by METTL3, promotes VM formation in glioma via up-regulating IGFBP2 expression, which provides a new direction for glioma therapy.

Graphical Abstract
Microfluidic models of the neurovascular unit: a translational view
Authors: Wevers Nienke R. , De Vries Helga E.
Published: November 2023

The vasculature of the brain consists of specialized endothelial cells that form a blood-brain barrier (BBB). This barrier, in conjunction with supporting cell types, forms the neurovascular unit (NVU). The NVU restricts the passage of certain substances from the bloodstream while selectively permitting essential nutrients and molecules to enter the brain. This protective role is crucial for optimal brain function, but presents a significant obstacle in treating neurological conditions, necessitating chemical modifications or advanced drug delivery methods for most drugs to cross the NVU. A deeper understanding of NVU in health and disease will aid in the identification of new therapeutic targets and drug delivery strategies for improved treatment of neurological disorders.

To achieve this goal, we need models that reflect the human BBB and NVU in health and disease. Although animal models of the brain’s vasculature have proven valuable, they are often of limited translational relevance due to interspecies differences or inability to faithfully mimic human disease conditions. For this reason, human in vitro models are essential to improve our understanding of the brain’s vasculature under healthy and diseased conditions. This review delves into the advancements in in vitro modeling of the BBB and NVU, with a particular focus on microfluidic models. After providing a historical overview of the field, we shift our focus to recent developments, offering insights into the latest achievements and their associated constraints. We briefly examine the importance of chip materials and methods to facilitate fluid flow, emphasizing their critical roles in achieving the necessary throughput for the integration of microfluidic models into routine experimentation. Subsequently, we highlight the recent strides made in enhancing the biological complexity of microfluidic NVU models and propose recommendations for elevating the biological relevance of future iterations.

Importantly, the NVU is an intricate structure and it is improbable that any model will fully encompass all its aspects. Fit-for-purpose models offer a valuable compromise between physiological relevance and ease-of-use and hold the future of NVU modeling: as simple as possible, as complex as needed.
Testing the association between shoulder pain prevalence and occupational, physical activity, and mental health factors in two generations of Australian adults
Authors: Hodgetts Christopher J. , Jacques Angela , Daffin Lee , Learmonth Yvonne C.
Published: November 2023

Background

Shoulder pain is common among the adult population, but it appears to reduce in prevalence around retirement age. Associations between shoulder pain and work-place exposures, physical activity, or mental health status are unclear and may change with age. This study aimed to determine the prevalence of self-reported shoulder pain in Australian adults across two generations and test the association with occupational factors, physical activity, and mental health.

Methods

In this cross-sectional study we used data from a longitudinal Australian pregnancy cohort (the Raine Study). We analysed data from the children (Gen2) at the 22-year follow-up (N = 1128) and parents (Gen1) at the 26-year follow-up (N = 1098). Data were collected on self-reported shoulder pain, occupational factors (employment status and work description), physical activity, and mental health at the respective follow-ups. Prevalence rates were provided as percentages with 95% confidence intervals. Univariate analysis for group comparisons included chi squared for categorical comparisons. The association of predictor variables and shoulder pain was assessed using logistical regression.

Results

In Gen1 31.4% of adults aged 40–80 reported the presence of shoulder pain in the last month, with no significant difference between females and males. Gen1 participants younger than 65 reported more shoulder pain (OR[95%CI] = 1.80 [1.04–3.09]). Gen2 females (14.7%) reported shoulder pain in either shoulder more frequently than males (7.7%) and bilateral shoulder pain (8.0%) more frequently than males (1.9%). Gen1 had increased odds of reporting shoulder pain if their work was “physical or heavy manual” compared to “sedentary” (OR [95% CI] = 1.659 [1.185–2.323]) and when categorised with depression (OR [95% CI] = 1.940 [1.386–2.715]) or anxiety (OR [95% CI] = 1.977 [1.368–2.857]). Gen2 participants with depression (OR [95% CI] = 2.356 [1.620–3.427]) or anxiety (OR [95% CI] = 2.003 [1.359–2.952]) reported more shoulder pain.

Conclusion

Overall, shoulder pain was more prevalent in young females than males and was more prevalent in those under the age of 65. Cross-sectional associations were established between some occupational factors in older adults and depression in all adults, and shoulder pain.
Engaging youth as leaders and partners can improve substance use prevention: a call to action to support youth engagement practice and research
Authors: Ballard Parissa J. , Kennedy Heather K. , Collura Jessica J. , Vidrascu Elena , Torres Chelsey Garcia
Published: November 2023

Background

As a subfield of prevention science, substance use prevention researchers and professionals are increasingly focused on translating research into practice, developing the workforce of prevention specialists, and creating a robust prevention infrastructure. One critical need for professional development among the substance use prevention workforce is training and technical assistance around how to include young people in developing, implementing, and evaluating substance use prevention programs.

Main body

Amplifying youth voices can increase the quality and responsiveness of youth prevention research and practice, as well as hasten and improve the translation of prevention interventions into practice while also benefiting youth themselves. Yet, youth engagement is multi-layered and nuanced. Training prevention professionals who work with youth in youth development and youth/adult partnerships is critical to support meaningful youth engagement efforts. We assert that the substance use prevention workforce needs at least three specific competencies to engage youth meaningfully in prevention: 1) understand adolescent development and the core elements of youth-adult partnerships; 2) apply this knowledge to program design and practice; and 3) implement relational practices to share power with young people.

Conclusion

Incorporating the insights of young people can improve substance use prevention. The substance use prevention workforce should be supported in developing competencies to meaningfully engage youth. These competencies require training, and resources must be devoted to support appropriate training.
A prospective single-arm study on the relationship between dose-volume parameters of pelvic functional bone marrow and acute hematological toxicities during intensity-modulated radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer
Authors: Chen Hongbo , Zhong Qian , Liu Yujie , Li Jinyan , Deng Wenjing , Wang Jie , Zhou Shuquan , Yu Zengrong , Huang Xianzhan , Huang Yuanqiong , Zhen Bo , Wei Jihong , Zhang Weijian , Ruan Xiaohong , Xiao Lin
Published: November 2023

Background

FLT-PET/CT can accurately identify and locate functional bone marrow (FBM) with hematopoietic capability, the FBM were divided into two levels as FBM1 (strongest hemopoietic ability region)and FBM2 (moderate hemopoietic ability region) via FLT-PET/CT. The purpose of this study was to explore the relationship between dose-volume parameters of pelvic FBM and hematologic toxicity (HT) during radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer.

Methods

From December 2016 to September 2021, ninety-seven uterine cervical/endometrial cancer patients received intensity-modulated radiation therapy were prospectively recruited in this single-arm, prospective, phase II trial. Blood counts were reviewed weekly during radiotherapy. Single- and multifactor regression methods were used to analyze the relationships between dose-volume parameters of FBM1/2 and grade ≥ 2 HT. ROC curves were used to determine the cutoff values for the dose-volume parameters of FBM1/2.

Results

The incidence of grade ≥ 2 leukopenia, neutropenia, thrombocytopenia and anemia in patients during radiotherapy was 63.9%, 45.4%, 19.6% and 38.8% respectively, and the median occurrence time was the 29th, 42th, 35th and 31th day, respectively. Multivariate regression analysis showed that the Dmax of FBM1 was significantly related to grade ≥ 2 leukopenia (OR = 1.277 95% CI 1.067–1.528, P = 0.008), Dmean of FBM2 was significantly related to grade ≥ 2 thrombocytopenia (OR = 1.262 95% CI 1.066–1.494, P = 0.007), and V10 of FBM1 was significantly related to grade ≥ 2 anemia (OR = 1.198 95% CI 1.003–1.431, P = 0.046). The incidence of grade ≥ 2 leukopenia for patients with FBM1 Dmax < 53 Gy was lower than that for patients with FBM1 Dmax ≥ 53 Gy (53.4% vs. 95.8%, P < 0.001). The incidence of grade ≥ 2 thrombocytopenia in patients with FBM2 Dmean < 33 Gy was lower than that in patients with FBM2 Dmean ≥ 33 Gy (0 vs. 28.4%, P < 0.001). The incidence of grade ≥ 2 anemia for patients with FBM1 V10 < 95% was lower than that in patients with FBM1 V10 ≥ 95% (24.4% vs. 57.1%, P = 0.003).

Conclusions

Grade ≥ 2 HT usually occurs in the 4th week of radiotherapy for patients with uterine cervical/endometrial cancer. The Dmax and V10 of FBM1 and the Dmean of FBM2 were significantly associated with the occurrence of grade ≥ 2 HT. The recommended optimal dose constraints were FBM1 Dmax < 53 Gy, V10 < 95%, and FBM2 Dmean <33 Gy.
Aortic isthmus massive calcifications: an unusual case of secondary hypertension
Authors: Soukeur Sadia , Cosset Benoit , Farhat Fadi
Published: November 2023

We present the case of a 63-year-old woman who was hospitalized five times in 4 months for episodes of heart failure, associated with a sustained hypertension despite a fivefold therapy. The pathophysiological mechanism of the hypertension was a secondary hyperaldosteronism linked to a renal hypoperfusion due to the narrowing of the thoracic aorta by a huge calcified plaque, mimicking an aortic coarctation.
Time in range and complications of diabetes: a cross-sectional analysis of patients with Type 1 diabetes
Authors: Bezerra Marta Fernandes , Neves Celestino , Neves João Sérgio , Carvalho Davide
Published: November 2023

Background/ objective

To evaluate the association of CGM parameters and HbA1c with diabetes complications in patients with Type 1 Diabetes (T1D).

Methods

Patients with T1D using the CGM system Freestyle Libre were included in this analysis. The association of CGM-metrics and HbA1c with diabetes complications (any complication, microvascular complications, or macrovascular complications) was assessed using logistic regression unadjusted and adjusted for age, sex, and diabetes duration (model 1), and further adjusted for hypertension and dyslipidemia (model 2).

Results

One hundred and sixty-one patients with T1D were included. The mean (± SD) age was 37.4 ± 13.4 years old and the median T1D duration was 17.7 ± 10.6 years. Time in range (TIR) was associated with any complication and microvascular complications in the unadjusted model and in the adjusted models. TIR was associated with retinopathy in the unadjusted model as well as in model 1, and was associated with macrovascular complications only in the unadjusted model. HbA1c was associated with any complications, microvascular complications, and retinopathy in the unadjusted model but not in the adjusted models. HbA1c was associated with macrovascular complications in the unadjusted model and in the adjusted model 1.

Conclusions

In this cross-sectional analysis of patients with T1D using intermittent scanned CGM, TIR, and HbA1c were associated with complications of diabetes. TIR may be a better predictor than HbA1c of any complication and microvascular complications, while HbA1c may be a better predictor of macrovascular complications.
Disclosing the molecular profile of the human amniotic mesenchymal stromal cell secretome by filter-aided sample preparation proteomic characterization
Authors: Muntiu Alexandra , Papait Andrea , Vincenzoni Federica , Vitali Alberto , Lattanzi Wanda , Romele Pietro , Cargnoni Anna , Silini Antonietta , Parolini Ornella , Desiderio Claudia
Published: November 2023

Background

The secretome of mesenchymal stromal cells isolated from the amniotic membrane (hAMSCs) has been extensively studied for its in vitro immunomodulatory activity as well as for the treatment of several preclinical models of immune-related disorders. The bioactive molecules within the hAMSCs secretome are capable of modulating the immune response and thus contribute to stimulating regenerative processes. At present, only a few studies have attempted to define the composition of the secretome, and several approaches, including multi-omics, are underway in an attempt to precisely define its composition and possibly identify key factors responsible for the therapeutic effect.

Methods

In this study, we characterized the protein composition of the hAMSCs secretome by a filter-aided sample preparation (FASP) digestion and liquid chromatography-high resolution mass spectrometry (LC–MS) approach. Data were processed for gene ontology classification and functional protein interaction analysis by bioinformatics tools.

Results

Proteomic analysis of the hAMSCs secretome resulted in the identification of 1521 total proteins, including 662 unique elements. A number of 157 elements, corresponding to 23.7%, were found as repeatedly characterizing the hAMSCs secretome, and those that resulted as significantly over-represented were involved in immunomodulation, hemostasis, development and remodeling of the extracellular matrix molecular pathways.

Conclusions

Overall, our characterization enriches the landscape of hAMSCs with new information that could enable a better understanding of the mechanisms of action underlying the therapeutic efficacy of the hAMSCs secretome while also providing a basis for its therapeutic translation.
Application of patient-derived induced pluripotent stem cells and organoids in inherited retinal diseases
Authors: Liang Yuqin , Sun Xihao , Duan Chunwen , Tang Shibo , Chen Jiansu
Published: November 2023

Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making efforts to cure blindness imperative. Transgenic animals mimicking human genetic diseases have long been used as a primary research tool to decipher the underlying pathogenesis, but there are still some obvious limitations. As an alternative strategy, patient-derived induced pluripotent stem cells (iPSCs), particularly three-dimensional (3D) organoid technology, are considered a promising platform for modeling different forms of IRDs, including retinitis pigmentosa, Leber congenital amaurosis, X-linked recessive retinoschisis, Batten disease, achromatopsia, and best vitelliform macular dystrophy. Here, this paper focuses on the status of patient-derived iPSCs and organoids in IRDs in recent years concerning disease modeling and therapeutic exploration, along with potential challenges for translating laboratory research to clinical application. Finally, the importance of human iPSCs and organoids in combination with emerging technologies such as multi-omics integration analysis, 3D bioprinting, or microfluidic chip platform are highlighted. Patient-derived retinal organoids may be a preferred choice for more accurately uncovering the mechanisms of human retinal diseases and will contribute to clinical practice.
Energy efficiency performance in RIS-based integrated satellite–aerial–terrestrial relay networks with deep reinforcement learning
Authors: Li Jiao , Xue Huajian , Wu Min , Wang Fucheng , Gao Tieliang , Zhou Feng
Published: November 2023

Integrated satellite–aerial–terrestrial relay networks (ISATRNs) play a vital role in next-gen networks, particularly those with high-altitude platforms (HAP). This study introduces a new model for hybrid optical/RF-based HAP-enabled ISATRNs, incorporating reconfigurable intelligent surfaces (RIS) on unmanned aerial vehicles (UAVs) to optimize access in dense urban areas. Non-orthogonal multiple access is employed for improved spectrum efficiency. The objective is to jointly optimize UAV trajectory, RIS phase shift, and active transmit beamforming while considering energy consumption. A deep reinforcement learning approach using LSTM-DDQN framework is proposed. Numerical results show the effectiveness of our algorithm over traditional DDQN, with higher single-step exploration reward and evaluation metrics.
Genetic alterations that deregulate RB and PDGFRA signaling pathways drive tumor progression in IDH2-mutant astrocytoma
Authors: Tateishi Kensuke , Miyake Yohei , Nakamura Taishi , Iwashita Hiromichi , Hayashi Takahiro , Oshima Akito , Honma Hirokuni , Hayashi Hiroaki , Sugino Kyoka , Kato Miyui , Satomi Kaishi , Fujii Satoshi , Komori Takashi , Yamamoto Tetsuya , Cahill Daniel P. , Wakimoto Hiroaki
Published: November 2023

In IDH-mutant astrocytoma, IDH2 mutation is quite rare and biological mechanisms underlying tumor progression in IDH2-mutant astrocytoma remain elusive. Here, we report a unique case of IDH2 mutant astrocytoma, CNS WHO grade 3 that developed tumor progression. We performed a comprehensive genomic and epigenomic analysis for primary and recurrent tumors and found that both tumors harbored recurrent IDH2R172K and TP53R248W mutation with CDKN2A/B hemizygous deletion. We also found amplifications of CDK4 and MDM2 with PDGFRA gain in the recurrent tumor and upregulated protein expressions of these genes. We further developed, for the first time, a xenograft mouse model of IDH2R172K and TP53R248W mutant astrocytoma from the recurrent tumor, but not from the primary tumor. Consistent with parent recurrent tumor cells, amplifications of CDK4 and MDM2 and PDGFRA gain were found, while CDKN2A/B was identified as homozygous deletion in the xenografts, qualifying for integrated diagnosis of astrocytoma, IDH2-mutant, CNS WHO grade 4. Cell viability assay found that CDK4/6 inhibitor and PDGFR inhibitor potently decreased cell viability in recurrent tumor cells, as compared to primary tumor cells. These findings suggest that gene alterations that activate retinoblastoma (RB) signaling pathways and PDGFR may drive tumor progression and xenograft formation in IDH2-mutant astrocytoma, which is equivalent to progressive IDH1-mutant astrocytoma. Also, our findings suggest that these genomic alterations may represent therapeutic targets in IDH2-mutant astrocytoma.
Current status of carbon monoxide dehydrogenases (CODH) and their potential for electrochemical applications
Authors: Bährle Rebecca , Böhnke Stefanie , Englhard Jonas , Bachmann Julien , Perner Mirjam
Published: November 2023

Anthropogenic carbon dioxide (CO2) levels are rising to alarming concentrations in earth’s atmosphere, causing adverse effects and global climate changes. In the last century, innovative research on CO2 reduction using chemical, photochemical, electrochemical and enzymatic approaches has been addressed. In particular, natural CO2 conversion serves as a model for many processes and extensive studies on microbes and enzymes regarding redox reactions involving CO2 have already been conducted. In this review we focus on the enzymatic conversion of CO2 to carbon monoxide (CO) as the chemical conversion downstream of CO production render CO particularly attractive as a key intermediate. We briefly discuss the different currently known natural autotrophic CO2 fixation pathways, focusing on the reversible reaction of CO2, two electrons and protons to CO and water, catalyzed by carbon monoxide dehydrogenases (CODHs). We then move on to classify the different type of CODHs, involved catalyzed chemical reactions and coupled metabolisms. Finally, we discuss applications of CODH enzymes in photochemical and electrochemical cells to harness CO2 from the environment transforming it into commodity chemicals.
The impact of COVID-19 on PRO development, collection and implementation: views of UK and Ireland professionals
Authors: Holch Patricia , Turner Grace , Keetharuth Anju D , Gibbons E , Cocks Kim , Absolom Kate L
Published: November 2023

Background

PROs are valuable tools in clinical care to capture patients’ perspectives of their health, symptoms and quality of life. However the COVID-19 pandemic has had profound impacts on all aspects of life, in particular healthcare and research. This study explores the views of UK and Irish health professionals, third sector and pharmaceutical industry representatives and academic researchers on the impact of COVID-19 on PRO collection, use and development in clinical practice.

Methods

A volunteer sample took part in a 10 question cross sectional qualitative survey, on the impact of COVID-19, administered online via Qualtrics. Demographic data was descriptively analysed, and the qualitative free text response data was subject to thematic analysis and summarised within the Strengths, Weaknesses, Opportunities and Threats (SWOT) framework.

Results

Forty nine participants took part located in a range of UK settings and professions. Participants highlighted staff strengths during the pandemic including colleagues’ flexibility and ability to work collaboratively and the adoption of novel communication tools. Weaknesses were a lack of staff capacity to continue or start PRO projects and insufficient digital infrastructure to continue studies online. Opportunities included the added interest in PROs as useful outcomes, the value of electronic PROs for staff and patients particularly in relation to integration into systems and the electronic patient records. However, these opportunities came with an understanding that digital exclusion may be an issue for patient groups. Threats identified included that the majority of PRO research was stopped or delayed and funding streams were cut.

Conclusions

Although most PRO research was on hold during the pandemic, the consensus from participants was that PROs as meaningful outcomes were valued more than ever. From the opportunities afforded by the pandemic the development of electronic PROs and their integration into electronic patient record systems and clinical practice could be a lasting legacy from the COVID-19 pandemic.
The day after intracerebral hemorrhage: platelet mass index as predictor of survival—a retrospective cohort study
Authors: Avramidou Despoina , Goulimari Rengina , Stergiou Anastasios , Papadopoulos Vasileios
Published: November 2023

Background

Platelets are implicated in the pathophysiology of intracerebral hemorrhage (ICH). Platelet count (PLT) is affected by platelet loss, while mean platelet volume (MPV) by platelet replenishment. Whether platelet mass index (PMI), the product of PLT and MPV, might predict survival after ICH, remains unknown.

Methods

All first-ever ICH patients, admitted to Xanthi General Hospital between January 2018 and May 2020 and met eligibility criteria, were enrolled in this retrospective cohort study. Demographics, medical record, first-symptom-to-admission time, vital signs, modified Rankin Scale, ICH score, arterial blood gas test, complete blood count, blood biochemistry, and CT scan test were collected for each patient. PMI values on day 1 (admission; PMI1), day 2 (PMI2), and day 7 (PMI7), along with PLT, MPV, platelet distribution width (PDW), and platelet large cell ratio (P-LCR), were evaluated as potential predictors of 12-month survival using Repeated Measures General Linear Model. Binary discretization of predictors was based on optimal scaling and evaluated using binary regression.

Results

From 59 patients enrolled (aged 75.7 ± 12.0 years; 31 females), 29 were still alive 12 months after ICH. Age, arterial hypertension, diabetes mellitus, hemoglobin level (Hb), and oxygen saturation (O2Sat) were correlated with 12-month survival. After adjustment for these parameters, PMI1 and PMI2 were independently correlated with 12-month survival (P = 0.048 and P = 0.004, respectively), while PMI7 was not (P = 0.332). PMI2 ≥ 2,400 fL/μL was best to discriminate survivors from non-survivors (age, arterial hypertension, diabetes mellitus, Hb, and O2Sat adjusted OR 0.123 with 95% CI: 0.023–0.694; P = 0.018).

Conclusions

PMI within the first day after admission for ICH might be used as early predictors of survival. Properly designed prospective studies are needed to further evaluate their contribution as such.
Acceleration of sporadic Creutzfeldt–Jakob disease progression by COVID requires evidence from appropriately designed studies
Authors: Finsterer Josef
Published: November 2023

The aim of this letter to the editor is to discuss the influence of SARS-CoV-2 infection on the progression of sporadic Creutzfeldt–Jakob disease (sCJD). A 73-year-old male was diagnosed with sCJD based on the clinical presentation, cerebral MRI, FDG–PET, and elevated 14-3-3 in cerebrospinal fluid. One month earlier he had suffered a slight COVID-19 infection. It was concluded that COVID-19 can lead to accelerated pathogenesis and exaggerated manifestations of sCJD.
Characterization and genomic analysis of a novel E. coli lytic phage with extended lytic activity against S. Enteridis and S. Typhimurium
Authors: Zhong Zhaoxin , Wang Yanyan , Li Huimin , Zhang Hui , Zhou Yan , Wang Ran , Bao Hongduo
Published: November 2023

In order to effectively use of phages as antimicrobial agents for controlling multidrug-resistant E. coli, it is important to understand phage biology. The isolation and research of novel bacteriophages are urgently needed for food safety and animal health. Phage is considered as a novel alternative antibacterial agents and a new way of prevent, control and treat pathogens. In this paper, we isolated and characterized a novel lytic phage from chicken samples, named vB_EscP_vE20 (in brief vE20). We identified vE20 as belonging to the Podoviridae family through morphological and phylogenetic analysis. It had lytic activities against 24 out of 51 different serotypes of clinical E. coli strains, interestingly it also can lyse Salmonella species, such as Salmonella Enteritidis (S. Enteritidis) and Samonella Typhimurium (S. Typhimurium). One step growth curve showed that the latent period and lysis period was 10 min and 60 min, respectively. The burst size of vE20 was about 60 PFU/cell. The phage vE20 survived in a wide range of temperatures (30–60 °C) and pH (3–11). The whole genome size of phage vE20 is 77,938 bps, which is double stranded DNA. There are 121 Open reading frame (ORFs) in total, and the GC-content is 42.17%, without virulence-associated, antibiotic and lysogeny related genes. Phage vE20 has high bactericidal activity in killing E. coli EXG20-1 in cultures containing 4 × 109 cfu/mL in several MOIs culture. The results revealed the promising potential of phage vE20 as attractive candidates for the control of E. coli infections.

Graphical Abstract
Pulmonary tumor embolism secondary to urothelial carcinoma of urinary bladder: case report and literature review
Authors: Bouchaala Abderrahmane , Khalek Ihssane , Kerrouani Oualid , Mouine Najat , Lakhal Zouhair , Benyass Aatif
Published: November 2023

Background

Tumor embolism is the least well-described cause of pulmonary embolism, taking into account the non-specificity of radiographic and nuclear imaging results, the necessity of anatomopathological evidence and the frequency of deep venous thrombosis in the course of solid tumors, suggesting thus thromboembolism.

Case presentation

We report a rare case of urothelial carcinoma of the urinary bladder associated with persistent pulmonary embolism despite being on different anticoagulation regimens, the patient was ultimately found to have tumor thrombus in the pulmonary trunk secondary to tumoral extension. We provide a literature review as well about the diagnosis, evaluation and prognosis and of this rare clinical entity.

Conclusions

Our case highlights the importance of keeping this unusual etiology in mind, particularly when faced with pulmonary embolism occurring in the context of a solid tumor and the ineffectiveness of various anticoagulation protocols. Furthermore, it emphasizes the pivotal role of cytology in confirming diagnosis and guiding therapy.