bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphocyte migration regulation related proteins in urine exosomes may serve as a potential biomarker for lung cancer diagnosis
Authors: Jin Shuai , Liu Tianci , Wang Weiwei , Li Tao , Liu Zhefeng , Zhang Man
Published: November 2023

Background

The migration of lymphocytes shares many similarities in mode and mechanism with the metastasis of lung cancer tumor cells. But changes in the expression of lymphocyte migration regulation related proteins in urine exosomes remain unclear. This study is to investigate the expression changes of lymphocyte migration regulation related proteins in urine exosomes of lung cancer patients, and further verify their correlation with the development and progression of lung cancer.

Methods

Urine exosomes were collected from lung cancer patients and healthy people aged 15–79 years. Mass spectrometry was used to screen and explore the expression changes of lymphocyte migration regulation related proteins in healthy people of different ages. Enzyme-linked immunosorbent assay and western blotting were used to detect the expression changes of lymphocyte migration regulation related proteins in lung cancer patients.

Results

Analyzing the data of urine exosome proteomics, a total of 12 lymphocyte related proteins were identified, 5 of which were lymphocyte migration regulation related proteins. Among these proteins, WASL and STK10 proteins showed a gradual decrease in expression with age, and WNK1 protein showed a gradual increase. Lung cancer patients had reduced expression of WASL and increased expression of STK10 and WNK1 proteins in urine exosomes compared to normal people. Urine exosome WASL, STK10, and WNK1 were diagnosed with lung cancer, with a combined AUC of 0.760.

Conclusions

Lymphocyte migration regulation related proteins were differentially expressed in the urine exosome of lung cancer patients, and WASL, STK10 and WNK1 may serve as potential biomarkers for lung cancer diagnosis.
Analysis of genetic testing in fetuses with congenital heart disease of single atria and/or single ventricle in a Chinese prenatal cohort
Authors: Li Min , Ye Baoying , Chen Yiyao , Gao Li , Wu Yi , Cheng Weiwei
Published: November 2023

Objective

This study aimed to investigate the genetic etiologies of fetuses with single atria and/or ventricle (SA or/and SV) using different genetic detection methods in a Chinese prenatal cohort.

Methods

In this retrospective study, the various genetic results of 44 fetuses with SA and/or SV were analyzed. All 44 cases were tested by chromosomal microarray analysis (CMA) and karyotyping simultaneously, and 8 underwent whole exome sequencing (WES). Data on the pregnancy outcomes and neonatal prognoses were collected from medical records and postnatal follow-up.

Results

The whole cohort of 44 fetuses included 14 SA cases (31.8%), 12 SV cases (27.3%), and 18 SA and SV cases (40.9%). A total of 9 pathogenic genetic results were detected by conventional karyotyping, CMA and trio-WES, indicating an overall detection rate of 20.5% (9/44). Six pathogenic chromosomal abnormalities were identified by CMA among the 44 cases, showing a detection rate of 13.6% (6/44). Two microdeletions being missed by karyotyping were diagnosed by CMA, showing an additional diagnostic yield of 4.5% for CMA in present cohort(2/44). Three pathogenic variants in two fetuses were identified by WES, indicating an incremental diagnostic yield of 4.5%(2/44) for WES in fetuses with SA or/and SV.

Conclusion

In this study, WES achieved an additional diagnostic yield of 4.5% in fetuses with SA or/and SV. WES is valuable for fetal prognosis assessment and could add diagnostic value for fetuses with SA and/or SV when CMA is negative. It would be a valuable technique for the identification of underlying pathogenic variants in prenatal cohorts.
Population impact of fine particulate matter on tuberculosis risk in China: a causal inference
Authors: Mao Jun-Jie , Chen Hong-Lin , Li Chun-Hu , Lu Jia-Wang , Gu Yuan-Yuan , Feng Jian , Zhang Bin , Ma Jun-Feng , Qin Gang
Published: November 2023

Background

Previous studies have suggested the potential association between air pollution and tuberculosis incidence, but this association remains inconclusive and evidence to assess causality is particularly lacking. We aimed to draw causal inference between fine particulate matter less than 2.5 μm in diameter (PM2.5) and tuberculosis in China.

Methods

Granger causality (GC) inference was performed within vector autoregressive models at levels and/or first-differences using annual national aggregated data during 1982–2019, annual provincial aggregated data during 1982–2019 and monthly provincial aggregated data during 2004–2018. Convergent cross-mapping (CCM) approach was used to determine the backbone nonlinear causal association based on the monthly provincial aggregated data during 2004–2018. Moreover, distributed lag nonlinear model (DLNM) was applied to quantify the causal effects.

Results

GC tests identified PM2.5 driving tuberculosis dynamics at national and provincial levels in Granger sense. Empirical dynamic modeling provided the CCM causal intensity of PM2.5 effect on tuberculosis at provincial level and demonstrated that PM2.5 had a positive effect on tuberculosis incidence. Then, DLNM estimation demonstrated that the PM2.5 exposure driven tuberculosis risk was concentration- and time-dependent in a nonlinear manner. This result still held in the multi-pollutant model.

Conclusions

Causal inference showed that PM2.5 exposure driving tuberculosis, which showing a concentration gradient change. Air pollutant control may have potential public health benefit of decreasing tuberculosis burden.
Home-based exercise program and Health education in patients with patellofemoral pain: a randomized controlled trial
Authors: Hong Qiao-Mei , Wang Hao-Nan , Liu Xi-Hui , Zhou Wen-Qi , Zhang Xiao , Luo Xiao-Bing
Published: November 2023

Background

Patellofemoral pain (PFP) is one of the most common disorders of the knee joint. Home-based exercise is an effective intervention to achieve self-management for chronic diseases. This study evaluated the effects of home-based exercise and health education in patients with PFP.

Methods

Patients who had PFP were randomly allocated to an intervention group (IG) or control group (CG). Patients in the IG received a 6-week tailored home-based exercise program with health education via remote support, while patients in the CG group only received health education. Clinical outcomes were compared using the Anterior Knee Pain Scale (AKPS) to measure function and the Visual Analog Scale (VAS) to measure “worst pain” and “pain with daily activity”. Muscle strength was measured according to the peak torque of the knee muscles using an isokinetic system.

Results

Among a total of 112 participants screened for eligibility, 38 were randomized and analyzed, including 19 participants in the intervention group and 19 participants in the control group. There were no significant differences in baseline characteristics between the groups. At 6-week follow-up, the intervention group showed a greater worst pain reduction (between-group difference, -19.3 [95%CI, -23.2 to -15.5]; P < 0.01) and pain with daily activity (between-group difference, -22.9 [95%CI, -28.3 to -17.4]; P < 0.01) than the control group. Similarly, the intervention group had better improvements in AKPS (between-group difference, 9.0 [95%CI, 4.1 to 13.9]; P < 0.01) and knee extensor strength (between-group difference, 20.1 [95%CI, 14.5 to 25.8]; P < 0.01), compared to the control group. No adverse events were reported.

Conclusion

Home-based exercise and health education resulted in less pain, better function, and higher knee muscle strength compared with no exercise in patients with PFP. A large randomized controlled trial with long-term follow-up is required to confirm these findings.

Trial registration

Chinese Clinical Trial Registry, ChiCTR2200056224 (https://www.chictr.org.cn/showproj.aspx?proj=135506). Registered on February 1, 2022.
Calcium phosphate cement promotes the stability of osteoporotic lumbar pedicle screw by enhancer-injecters with different number of holes
Authors: Fu Suochao , Zhang Yu , Wang Renkai , Zou Xiaobao , Ai Fuzhi , Wang Jianhua , Ma Xiangyang , Xia Hong , Lei Wei
Published: November 2023

Backgrounds

This study aimed to compare whether Calcium phosphate cement (CPC) promotes the stability of osteoporotic lumbar pedicle screw by enhancer-injecters with different number of holes.

Methods

Through a self-designed bone cement injection device, the pedicle screw canal was strengthened with calcium phosphate bone cement, and divided into 4-hole group, 6-hole group, 8-hole group, straight pore group and the control group. The screw was inserted into the mechanical test module, the Maximum insertion torque and Maximum axial pull-out strength were recorded, and the distribution of calcium phosphate bone cement was analyzed by CT and X-ray. The data results were analyzed using SPSS19.0 statistical software package.

Results

The distribution of bone cement in different reinforcement groups was different and showed regularity. The bone cement in the 4-hole group was roughly located in the head 1/3 of the screw, the 6-hole group was located in the middle 1/3 of the screw, and the 8-hole group was located in the caudal 1/3 of the screw. Compared with the control group, the maximum axial pull-out force of screws in the lateral hole and full screw tunnel reinforcement group was significantly increased. There was no significant difference between the 4-hole, 6-hole and straight pore groups. There was no difference in the screw-in torque between the reinforcement groups, and they all increased significantly compared with the control group, and the difference was statistically significant. After the screw was pulled out, the interface between the bone cement and the polyurethane material was fractured, and a tight package was formed with the screw.

Conclusions

Enhancer syringes with different hole numbers combined with CPC bone cement injection can significantly increase the maximum screw pull-out force. The 8-hole group has a smaller pull-out force and is relatively prone to leakage of reinforcing material, which lacks safety in use. The local reinforcement of 4-hole and 6-hole sheath can play a similar role to that of total nail tunnel reinforcement.
Benefit and harm of lymphadenectomy in intermediate risk prostate cancer: comparison of five nomograms
Authors: Lodeta Branimir , Baric Hrvoje , Hatz Dominik , Jozipovic Danijel , Augustin Herbert
Published: November 2023

Background

Pelvic lymph node dissection (PLND) is recommended method for detecting prostate cancer (PCa) nodal metastases although associated with serious complications. In this study, we aimed to assess benefit/harm of routine PLND in intermediate risk PCa patients and to compare diagnostic yield of five different nomograms in predicting lymph node invasion (LNI).

Methods

Retrospective analysis of consecutive PCa patients with intermediate risk of biochemical recurrence who underwent open radical prostatectomy (RP) with bilateral PLND between January 2017 and December 2019 at our institution. Partin, 2012-Briganti, 2018-Briganti, Cagiannos and Memorial Sloan Kettering Cancer Center (MSKCC) values were calculated. To compare accuracy, sensitivity, specificity, and area under receiver-operating curve (AUC) were calculated and then optimal cutoff values were estimated, analyses repeated and compared. To assess benefit and harm of PLND, relative risk (RR) and number need to treat (NNT) with LNI and complications set as outcome were calculated.

Results

Total 309 subjects. Average age 62.2 years, average PSA 7.2 ng/mL; 18 (5.8%) had LNI; 88 (28.5%) suffered Clavien-Dindo grade 3–5 complication. AUC for predicting LNI: 0.729 for 2012-Briganti, 0.660 for MSKCC, 0.521 for 2018-Briganti, 0.486 for Cagiannos, and 0.424 for Partin. None of pairwise AUC comparisons based on default and newly established cutoff values were statistically significant. Lowest NNT was for Partin and Cagiannos with default cutoff (≥ 5%). Risks of serious complications between higher/lower than cutoff values were non-significant across nomograms.

Conclusions

2012-Briganti nomogram outperforms, although not significantly, MSKCC, 2018-Briganti, Cagiannos, and Partin nomograms in classifying LNI in intermediate risk PCa patients. Routine PLND in these patients should be avoided, due to high rate and severity of complications.
The success rate of small renal mass core needle biopsy and its impact on lowering benign resection rate
Authors: Gao Haijuan , Nowroozizadeh Behdokht , Zepeda Joaquin Ponce , Landman Jaime , Farzaneh Ted , Johnson Cary , Hosseini Hirad , Han Min
Published: November 2023

Background

Small renal mass (SRM) biopsy remains under-utilized due to stigma. Meanwhile, the alarmingly high benign findings in resected kidney masses highlight the need for improved preoperative diagnosis and patient selection.

Methods

The purpose of this study is to review the success rate of SRM biopsy and to evaluate its impact on patient management. A total of 168 percutaneous image-guided core needle biopsies (CNBs) of SRMs were retrieved at a tertiary academic center between 2015 and 2019. Subsequent treatment choices, side effects and outcomes were retrospectively reviewed.

Results

The diagnostic rate of CNB was 86.9%. Benign neoplasms accounted for a significant portion (14.3%) of SRM. Renal cell carcinomas (RCCs) were the most common diagnoses (69.6%) as expected. In biopsy-resection correlation, the positive predictive value of CNB was 100%. Tumor typing and subtyping by CNB were highly accurate, 100% and 98.3% respectively. Nuclear grading for clear cell RCC was accurate in 83.8% cases. The CNB results had significant impact on treatment. Most patients with RCCs underwent either resection (54.1%) or ablation (33.9%), in contrast to observation in benign neoplasms (90.5%). Most importantly, the benign resection rate (3.2%) in this series was much lower than the national average.

Conclusion

CNB provided accurate diagnoses for the majority of SRMs and revealed benign diagnoses in a subset of clinically suspicious lesions. Employment of CNB in suspicious SRM may help avoid overtreatment for benign lesions.
Development and assessment of a self-management intervention for urinary incontinence among patients with prostate cancer: protocol for a randomized feasibility study
Authors: Chien Ching Hui , Liu Kuan Lin , Wu Chun Te , Chuang Cheng Keng , Yu Kai Jie , Lin Po Hung , Huang Xuan Yi , Pang See Tong
Published: November 2023

Background

Urinary incontinence is a common complication among patients with prostate cancer who have undergone radical prostatectomy. Guided by social cognitive theory and a framework for the recovery of health and well-being, we propose to develop and test a self-management intervention for patients with prostate cancer who experience urinary incontinence after undergoing radical prostatectomy.

Methods

In this study, a self-management intervention for urinary incontinence (SMI-UI) is developed, comprising a mobile self-management application, a self-management handbook, and professional support. The feasibility, acceptability, and effectiveness of this intervention will be assessed. Patient data from the urology departments of two hospitals will be collected through convenience sampling by adopting an experimental, parallel, and random assignment research design. Patients experiencing urinary incontinence after undergoing radical prostatectomy will be invited to participate. After completing the pretest questionnaire, patients will be randomly divided into the experimental and attention control groups. The experimental group will undergo a 12-week SMI-UI, whereas the attention control group will receive an intervention consisting of a single dietetic education information package. The two groups will be tested 12 and 16 weeks after the pretest. In this study, we recorded the sociodemographic and clinical variables; recruitment rate; retention rate; satisfaction with the intervention; cancer-related self-efficacy; urination symptoms and disturbance; social participation and satisfaction; resilience; and demoralization.

Trial Registration

ClinicalTrials.gov ID: NCT05335967 [date of registration 04-04-2022].
The effectiveness of Carie-Care™, chemomechanical caries removal technique in primary teeth: randomized controlled clinical trial
Authors: Ghanem Alaa Y. , Talaat Dalia M. , Essawy Marwa M. , Bakry Niveen
Published: November 2023

Background

Chemomechanical techniques for caries removal have been introduced to overcome the shortcomings of the conventional rotatory instruments. This study aimed to clinically evaluate the effectiveness of the chemomechanical method of caries removal (Carie-Care™) over mechanical caries removal through the Atraumatic Restorative Technique in pediatric patients.

Methods

A randomized controlled clinical trial was conducted. Fifty children fulfilling inclusion criteria were recruited from the outpatient clinic of Pediatric and Dental Public health department, Faculty of Dentistry, Alexandria University. Fifty open carious primary molars were randomly assigned into 2 equal groups according to the method of caries removal. In Group I (test group), caries was removed using the Carie-Care™ system and in Group II (control group), by using mechanical caries removal through the atraumatic restorative technique. Resin modified glass ionomer was used for teeth restoration, the two techniques were compared in each child according to time taken for caries removal, efficacy of caries removal, pain assessment, and child behavior.

Results

The mean time taken for caries removal in the Carie-Care™ treatment group was (575.6 ± 114.8) seconds which was statistically significant higher as compared with the ART treatment group (346.1 ± 97.4) seconds (p < 0.001). The mean score of efficacy in caries removal was (0.6 ± 0.8) in the Carie-Care™ group, and (1.3 ± 0.7) in the ART treatment group. When compared to ART, Carie-Care™ was significantly more efficient in caries removal (p < 0.002). When pain was assessed by the SEM scale, it was observed that the Carie-Care™ caries removal technique showed statistically significantly more comfort during the procedure compared with the ART procedure (p < 0.001).Moreover, children in the Carie-Care™ group enjoyed the process and showed more cooperative behavior when assessed at the end of procedure than those in the ART group with statistically significant difference (p = 0.002).

Conclusions

Removal of carious tissue in primary teeth using Chemomechanical Carie-Care™ gel proved to be more time consuming than ART, but on the other hand it was more efficient, comfortable, and accepted by the pediatric patients.
A scoping review on the links between sustainable development goal 14 and early childhood caries
Authors: Folayan Morenike Oluwatoyin , Ayouni Imen , Nguweneza Arthemon , Al-Batayneh Ola Barakat , Virtanen Jorma I. , Gaffar Balgis , Duangthip Duangporn , Sun Ivy Guo Fang , Onyejaka Nneka Kate , Daryanavard Hamideh , Mfolo Tshepiso , Feldens Carlos A. , Schroth Robert J. , Tantawi Maha El
Published: November 2023

Background

The Sustainable Development Goal (SDG) 14 addresses life below the waters, an important source of protein and contributor to global food security and economic development. Our aim was to explore possible evidence on the links between life below water and early childhood caries (ECC).

Methods

This scoping review identified articles on the link between life below water and caries according to the PRISMA-ScR guidelines. Three electronic databases (PubMed, Web of Science, and Scopus) were systematically searched in January 2023, using specific search terms. Studies written in English, with full text available, addressing life under water, focusing on dental caries in humans, with results that can be extrapolated to control ECC in children less than 6 years of age were included in the review. Descriptive statistics were used to summarize the retrieved papers and graphical presentation was used for visualization.

Results

There were 224 publications retrieved of which 13 studies, published between 1960 and 2022, were included in the analysis. The papers originated from Asia (7/13), North America (3/13), Europe (1/13), and 2/13 had multi-country authorship. Also, four laboratory studies extracted agents from marine products to determine their efficacy in preventing caries formation and preventing/slowing plaque formation; four letters discussed the caries prevention potential of sea salt as a source of fluoride; and two review articles about the positive effects of extracted marine products for caries prevention. Most (11/13) studies addressed target 14.1 concerned with enriching the marine environment with nutrients and minerals; two addressed target 14.4 focused on ensuring fish stocks are within biologically sustainable levels; two addressed target 14.7 aimed at increasing the economic benefits through sustainable use of marine resources such as fisheries; and one focused on target 14.5 aimed at conserving marine areas by increasing protected areas. In addition, one ecological study assessed the association between the ecosystem and ECC.

Conclusions

Currently, there is little known about the impact of protection of marine and coastal ecosystem from pollution and ocean acidification on the risk of ECC. Further evidence on possible associations between life below water and ECC management is needed.
Pelvic floor muscle training with biofeedback or feedback from a physiotherapist for urinary and anal incontinence after childbirth - a systematic review
Authors: Höder Amanda , Stenbeck Josefin , Fernando Mia , Lange Elvira
Published: November 2023

Background

Childbirth is one of the biggest risk factors for incontinence. Urinary and anal incontinence can cause pain and social limitations that affect social life, cohabitation, and work. There is currently no up-to-date literature study on the effect of pelvic floor muscle training with feedback from a physiotherapist, which involves verbal instructions based on vaginal and anal digital palpation, compared to treatment without feedback (e.g., recommendations for pelvic floor muscle training).

Aim

The objective of this systematic review was to examine the scientific evidence regarding the impact of pelvic floor muscle training (PFMT) with feedback from a physiotherapist and/or biofeedback on urinary and anal incontinence in women during the first six months following vaginal delivery, compared to treatment without feedback.

Methods

The literature search was conducted in the databases PubMed, Cochrane, and CINAHL. In addition, a manual search was conducted. The search terms consisted of MeSH terms and synonyms in the respective search block including population, intervention, and study design, as well as the terms pelvic floor and postpartum. An evaluation of each included study was conducted for methodological quality, evidence value, and clinical relevance.

Results

Eight studies were included, three of which showed a significant difference between groups, in favor of the intervention group that received pelvic floor muscle training with feedback from a physiotherapist and/or biofeedback. Due to the varying results and insufficient quality for the majority of the studies, the scientific basis was considered insufficient.

Conclusion

The scientific evidence for pelvic floor muscle training with feedback from a physiotherapist or biofeedback on postpartum urinary and anal incontinence compared to treatment without feedback is considered insufficient. Further research on the subject is needed. The study is registered in PROSPERO CRD42022361296.
First description study on molecular characterization of Hemiclepsis khankiana (Hirudinea: Glossiphoniidae) in China
Authors: He Yongcai , Li Zengkui , Jin Wenjie , Li Changzhong , Wang Guojie , Wang Zhengji , Kang Ming , Li Jiquan , Wang Jianlin , Hu Xiaoyu , Jiang Shuo , Chen Qiang , Li Haolin , Gao Dong , Liu Peiqi , Li Ying
Published: November 2023

Background

Leeches are an integral component of aquatic biocenosis and can be found in a wide range of ecosystems such as freshwater, saltwater, flowing, and still-water ecosystems. It especially plays an important role in the freshwater benthic community and is an important part of the food web. In this study, a leech species was found in the mantle cavity of wild freshwater mussels in Zigong City, Sichuan Province, China, and its identity was determined through morphological analysis and molecular biological analysis.

Results

The leech is Hemiclepsis khankiana, a new species of Hemiclepsis that has been discovered in Russia in recent years. Through morphological analysis, the current survey observed that the morphological characteristics of Hemiclepsis khankiana eyespots were significantly different from the first reported description. The first pair of eyespots on the leech were separated and clear, while it had been reduced to unclear shadows in the previous report. The phylogenetic tree based on the COI gene showed that the COI gene sequence obtained in this study was in the same evolutionary branch as Hemiclepsis khankiana (MN295420, MN295421). Genetically, it was most closely related to Hemiclepsis kasmiana (mean COI p-distance = 3.98%).

Conclusions

The current study reported on the new distribution range of Hemiclepsis khankiana, which was initially discovered in China. This study indicates that the distribution range of the leech species has expanded, laying a foundation for further studies in China.
Non-invasive assessment of oxygenation status using the oxygen reserve index in dogs
Authors: Zanusso Francesca , De Benedictis Giulia Maria , Zemko Polina , Bellini Luca
Published: November 2023

Background

The oxygen reserve index (ORi) is a real-time, continuous index measured with multi-wavelength pulse CO-oximetry technology. It estimates mild hyperoxemia in humans, which is defined as a partial pressure of oxygen (PaO2) level between 100 and 200 mmHg. The objectives of this study were to assess the correlation between ORi and PaO2, as well as to determine its ability in detecting mild hyperoxemia in dogs.

Methods

This prospective observational study enrolled 37 anaesthetised and mechanically ventilated dogs undergoing elective procedures. Simultaneous measurements of ORi and PaO2 were collected, using a multi-wavelength pulse CO-oximeter with a probe placed on the dog’s tongue, and a blood gas analyser, respectively. A mixed-effects model was used to calculate the correlation (r2) between simultaneous measurements of ORi and PaO2. The trending ability of ORi to identify dependable and proportional changes of PaO2 was determined. The diagnostic performances of ORi to detect PaO2 ≥ 150 mmHg and ≥ 190 mmHg were estimated using the area under the receiver operating characteristic curve (AUROC). The effects of perfusion index (PI), haemoglobin (Hb), arterial blood pH and partial pressure of carbon dioxide (PaCO2) on AUROC for PaO2 ≥ 150 mmHg were evaluated.

Results

A total of 101 paired measurements of ORi and PaO2 were collected. PaO2 values ranged from 74 to 258 mmHg. A strong positive correlation (r2 = 0.52, p < 0.001) was found between ORi and PaO2. The trending ability ORi was 90.7%, with 92% sensitivity and 89% specificity in detecting decreasing PaO2. An ORi value ≥ 0.53 and ≥ 0.76 indicated a PaO2 ≥ 150 and ≥ 190 mmHg, respectively, with ≥ 82% sensitivity, ≥ 77% specificity and AUROC ≥ 0.75. The AUROC of ORi was not affected by PI, Hb, pH and PaCO2.

Conclusions

In anaesthetised dogs, ORi may detect mild hyperoxaemia, although it does not replace blood gas analysis for measuring the arterial partial pressure of oxygen. ORi monitoring could be used to non-invasively assess oxygenation in dogs receiving supplemental oxygen, limiting excessive hyperoxia.
The diagnostic/prognostic roles and biological function of the IFIT family members in acute myeloid leukemia
Authors: Zhao YiFan , Zhang Yi , Lu WenYi , Sun Rui , Guo RuiTing , Cao XinPing , Liu Xingzhong , Lyu Cuicui , Zhao MingFeng
Published: November 2023

Background

The Interferon-induced protein with tetratricopeptide repeat (IFIT) family, IFIT1/2/3/5, play an important role in different tumors progression. However, the prognosis significance and biological role of IFIT family members in acute myeloid leukemia (AML) remains unclear.

Methods

We obtained the gene expression data and clinical information of 173 AML patients from The Cancer Genome Atlas (TCGA) database. Several databases were used in our study, including GEPIA, MethSurv, STRING, GSCA and GeneMANIA database.

Results

The mRNA expression of IFIT1/2/3/5 was elevated in AML patients and had a high ability to distinguish AML from controls based on the receiver operating characteristic (ROC) curve (AUC > 0.9). Kaplan–Meier survival analysis showed that higher levels of IFIT2/3/5 expression predict poor prognosis in AML patients. Besides, the DNA methylation analysis suggested that 7 CpG sites of IFIT2, 4 CpG sites of IFIT3 and 10 CpG sites of IFIT5 were significantly associated with the prognosis of AML patients. In addition, IFIT2/3/5 expression was significantly positively associated with the immune cell infiltration and immune checkpoint expression, such as CTLA4, PDCD1, LAG3, and TIGIT. Finally, drug sensitivity analysis revealed that AML patients with high expression of IFIT2/3/5 were resistant to multiple drugs, but sensitive to dasatinib.

Conclusion

IFIT family genes might serve as biomarkers for diagnosis, prognosis and drug sensitivity in AML patients. The activation or blocking of IFIT-related signaling pathways may provide novel insights into immunotherapy for patients with AML.
Health Equity Impact Assessment (HEIA) reporting tool: developing a checklist for policymakers
Authors: Olyaeemanesh Alireza , Takian Amirhossein , Mostafavi Hakimeh , Mobinizadeh Mohammadreza , Bakhtiari Ahad , Yaftian Fateme , Vosoogh-Moghaddam Abbass , Mohamadi Efat
Published: November 2023

Introduction

Health Equity Impact Assessment (HEIA) is a decision support tool that shows users how a new program, policy, or innovation affects health equity in different population groups.Various HEIA reporting and dissemination tools are available, nevertheless, a practical standard tool to present the results of HEIA in an appropriate period to policymakers is lacking. This work reports the development of a tool (a checklist) for HEIA reporting at the decision-making level, aiming to promote the application of HEIA evidence for improving health equity.

Methods

This is a mixed-method study that was carried out over four stages in 2022–2023: 1) identifying HEIA models, checklists, and reporting instruments; 2) development of the initial HEIA reporting checklist; 3) checklist validation; and 4) piloting the checklist. We also analyzed the Face, CVR, and CVI validity of the tool.

Results

We developed the initial checklist through analysis of 53 included studies and the opinions of experts. The final checklist comprised five sections: policy introduction (eight subsections), managing the HEIA of policy (seven subsections), scope of the affected population (three subsections), HEIA results (seven subsections), and recommendations (three subsections).

Conclusion

Needs assessment, monitoring during implementation, health impact assessment, and other tools such as monitoring outcome reports, appraisals, and checklists are all methods for assessing health equity impact. Other equity-focused indicators, such as the equity lens and equity appraisal, may have slightly different goals than the HEIA. Similarly, the formats for presenting and publishing HEIA reports might vary, depending on the target population and the importance of the report.
ACT001 Alleviates chronic kidney injury induced by a high-fat diet in mice through the GPR43/AMPK pathway
Authors: Zhou Yibing , Chen Ze , Zhou Hui , Niu Bin , Liu Jing , Li Yinglun , Mi Yuqiang , Li Ping
Published: November 2023

Background

Roughly 10 -15% of global populace suffer from Chronic Kidney Disease(CKD). A major secondary disease that can progress to end-stage renal disease (ESRD) is obesity-associated kidney disease (ORG). Although clinical management strategies are currently available, morbidity and mortality rates are increasing. Thus, new solutions are needed. Intestinal permeability, systemic inflammation, and aberrant intestinal metabolites have all been linked to ORG.

Purpose

ACT001 has anti-inflammatory, redox-regulatory and antitumour activities. The current study was designed to examine how ACT001 affects ORG and analyze the fundamental processes.

Methods

A high-fat diet (HFD) was used to generate ORG in female C57BL/6 J mice.

ORG mice were divided into three groups at random: HFD, HFD + ACT001, HFD + polyphosphocholine (PPC). To assess renal and colonic damage, periodic acid-Schiff (PAS) and hematoxylin–eosin (HE) staining were used. Following that, renal inflammation, oxidative stress, lipid deposition, colonic inflammation, and intestinal permeability were evaluated by protein blotting, polymerase chain reaction (PCR), immunohistochemistry, and immunofluorescence staining. Lastly, the SCFAs content was assessed by gas chromatographymass spectrometry.

Results

Mice in the HFD group displayed more severe albuminuria, glomerular hypertrophy, renal oxidative damage, inflammation, and lipid accumulation than mice with the normal diet (ND) group, as well as lower levels of intestinal SCFA valproic acid, colonic inflammation, and tight junction protein downregulation. ACT001 treatment restores the content of valproic acid in intestinal SCFAs, promotes the binding of SCFAs to renal GPR43, activates the AMPK signalling pathway. Therefore, it promotes the Nrf2-Keap1 signalling pathway and inhibits the NF-κB signalling pathway. SCFAs, additionally, augment colonic GPR43 concentrations, diminishing NLRP3 inflammasome expression and restoring ZO-1 and occludin protein levels.

Conclusion

This study is the first to look at ACT001's potential as a treatment for obesity-related kidney disease. Regulating GPR43 and AMPK signalling pathways, By controlling the GPR43 and AMPK signalling pathways, ACT001 improves colitis and the intestinal mucosal barrier, decreases renal lipid deposition, and suppresses inflammation and oxidative stress in the kidneys. According to this study, ACT001 could be a viable ORG therapy option.
Advancing personalized medicine in brain cancer: exploring the role of mRNA vaccines
Authors: Lin Feng , Lin Emma Z. , Anekoji Misa , Ichim Thomas E. , Hu Joyce , Marincola Francesco M. , Jones Lawrence D. , Kesari Santosh , Ashili Shashaanka
Published: November 2023

Advancing personalized medicine in brain cancer relies on innovative strategies, with mRNA vaccines emerging as a promising avenue. While the initial use of mRNA vaccines was in oncology, their stunning success in COVID-19 resulted in widespread attention, both positive and negative. Regardless of politically biased opinions, which relate more to the antigenic source than form of delivery, we feel it is important to objectively review this modality as relates to brain cancer. This class of vaccines trigger robust immune responses through MHC-I and MHC-II pathways, in both prophylactic and therapeutic settings. The mRNA platform offers advantages of rapid development, high potency, cost-effectiveness, and safety. This review provides an overview of mRNA vaccine delivery technologies, tumor antigen identification, combination therapies, and recent therapeutic outcomes, with a particular focus on brain cancer. Combinatorial approaches are vital to maximizing mRNA cancer vaccine efficacy, with ongoing clinical trials exploring combinations with adjuvants and checkpoint inhibitors and even adoptive cell therapy. Efficient delivery, neoantigen identification, preclinical studies, and clinical trial results are highlighted, underscoring mRNA vaccines' potential in advancing personalized medicine for brain cancer. Synergistic combinatorial therapies play a crucial role, emphasizing the need for continued research and collaboration in this area.
Pretreatment of UC-MSCs with IFN-α2 improves treatment of liver fibrosis by recruiting neutrophils
Authors: Xie Ye , Yao Jia , Yan Mengchao , Lin Yan , Wei Jiayun , Wang Haiping , Mao Yongcui , Liu Pinyan , Li Xun
Published: November 2023

Background

The use of umbilical cord mesenchymal stem cells (UC-MSCs) is a burgeoning method for the treatment of liver cirrhosis. However, the secretory phenotype and regulatory ability of UC-MSCs are easily affected by their microenvironment. Ensuring a specific microenvironment to enhance the UC-MSCs phenotype is a potential strategy for improving their therapeutic efficacy. The aim of this study was to explore therapeutic UC-MSCs phenotypes for improving liver fibrosis.

Methods

RNA-sequencing was used to analyze the response pattern of UC-MSCs after exposure to the serum of cirrhotic patients with HBV. Using immunohistochemistry, quantitative polymerase chain reaction, and immunofluorescence techniques, we evaluated the therapeutic effect of UC-MSCs pretreated with interferon alpha 2 (IFN-α2) (pre-MSCs) in an animal model of cirrhosis. Immunoblotting, ELISA, and other techniques were used to analyze the signaling pathways underlying the IFN-induced changes in UC-MSCs.

Results

UC-MSCs exposed to the serum of patients with hepatitis B-induced cirrhosis showed an enhanced response to type I IFN. The activated type I IFN signal induced the highest secretion of colony-stimulating factor 3 (CSF-3), interleukin (IL)-8, and chemokine (C–C motif) ligand 20 (CCL20) by the UC-MSCs. Pre-MSCs showed a higher therapeutic efficacy than untreated UC-MSCs in an animal model of liver fibrosis. Immunohistochemical analysis revealed that pre-MSCs could recruit neutrophils resulting in an increase in the secretion of matrix metalloprotease 8 that alleviated fibrosis. When neutrophils in animals were depleted, the therapeutic effect of pre-MSCs on fibrosis was inhibited. IFN-α2 altered the secretory phenotype of UC-MSCs by activating phosphorylated signal transducer and activator of transcription 1 and 2 (p-STAT1 and p-STAT2).

Conclusions

Pre-MSCs exhibited enhanced secretion of CSF-3, IL-8, and CCL20 and recruited neutrophils to alleviate fibrosis. This new strategy can improve cell therapy for liver cirrhosis.

Graphical abstract
Evaluation of a community-based intervention package to improve knowledge of obstetric danger signs, birth preparedness, and institutional delivery care utilization in Arba Minch Zuria District, Ethiopia: a cluster-randomized trial
Authors: Gurara Mekdes Kondale , Draulans Veerle , Jacquemyn Yves , Van Geertruyden Jean-Pierre
Published: November 2023

Introduction

Maternal healthcare utilization, particularly the institutional delivery, is disproportionately low in rural Ethiopia. This study aimed to evaluate the effectiveness of an integrated package of community-based interventions on the improved knowledge of obstetric danger signs, birth preparedness, and institutional delivery services utilization in rural areas of Gamo zone, southern Ethiopia.

Methods

We conducted cluster-randomized controlled trial (NCT05385380) from 2019 to 2021 at the Arba Minch Health and Demographic Surveillance System site. We randomly assigned the 10 kebele clusters to intervention and control arm. We used a package of interventions, which included providing information on safe motherhood via video and/or audio with a birth preparedness card for pregnant women, training for community volunteers and health extension workers, and improving maternity waiting home services. Women in the control arm received routine services only. We used generalized mixed-effects logistic regression models to evaluate the effectiveness of the intervention on the outcome variables.

Results

The study enrolled 727 pregnant women across the 10 clusters, with a 617 (84.9%) successful follow-up rate. The proportion of institutional delivery in the intervention arm was increased by 16.1% from 36.4% (174/478) at the baseline to 52.5% (224/427) at the endline (Adjusted odds ratio [AOR] for McNemar’s Test = 1.5; 95% confidence interval [CI]: 1.1 to 2; p < 0.001). In the control arm, however, there was a 10.3% fall in the proportion of institutional delivery (from 164/249 to 105/190). Pregnant women who received the intervention were significantly more likely to give birth in a health institution than those who did not (AOR 2.8; 95% CI: 1.2, 6.4).

Conclusion

The study demonstrates that an integrated community-based intervention package that included video-based storytelling and upgrading maternity waiting homes increased institutional delivery care utilization among rural women. We recommend that audio-visual storytelling, starting during pregnancy and continuing postpartum, be incorporated into routine maternal healthcare services to address access to care inequalities in rural settings.

Trial registration: The study protocol was registered in the clinicaltrials.gov with registry number NCT05385380.
Boosting brain–computer interfaces with functional electrical stimulation: potential applications in people with locked-in syndrome
Authors: Canny Evan , Vansteensel Mariska J. , van der Salm Sandra M. A. , Müller-Putz Gernot R. , Berezutskaya Julia
Published: November 2023

Individuals with a locked-in state live with severe whole-body paralysis that limits their ability to communicate with family and loved ones. Recent advances in brain–computer interface (BCI) technology have presented a potential alternative for these people to communicate by detecting neural activity associated with attempted hand or speech movements and translating the decoded intended movements to a control signal for a computer. A technique that could potentially enrich the communication capacity of BCIs is functional electrical stimulation (FES) of paralyzed limbs and face to restore body and facial movements of paralyzed individuals, allowing to add body language and facial expression to communication BCI utterances. Here, we review the current state of the art of existing BCI and FES work in people with paralysis of body and face and propose that a combined BCI-FES approach, which has already proved successful in several applications in stroke and spinal cord injury, can provide a novel promising mode of communication for locked-in individuals.
Overloaded vertebral body: a unique radiographic phenomenon following multilevel anterior cervical discectomy and fusion
Authors: Chen Shihao , Huang Kangkang , Liu Hao , Wu Tingkui , He Junbo , Yao Minghe , Wang Beiyu
Published: November 2023

Purpose

Because previous studies have not focused on postoperative cervical collapse, the purpose of the present study was to introduce the overloaded vertebral body (OVB) phenomenon following multilevel zero-profile anterior cervical discectomy and fusion (ACDF) as well as to investigate its effects on radiographic outcomes.

Methods

We conducted a retrospective study involving patients who underwent ACDF. A total of 55 patients were included in the analysis, including 110 OVB and 110 non-OVB. The evaluated vertebral parameters included the vertebral cross-sectional area (CSA), wedge angle (WA), vertebral height [anterior (AH) and posterior (PH)] and anterior–posterior vertebral diameter [upper (UD) and lower (LD)].

Results

The CSA and WA were significantly lower in the OVB group than in the non-OVB group at 3, 6, and 12 months after surgery as well as at the final follow-up (p < 0.01). The AH of the OVB group was significantly lower at 3, 6, and 12 months after surgery as well as at the final follow-up compared to 1 week after surgery (p < 0.01).

Conclusions

OVB, a new phenomenon following multilevel ACDF, is defined as the cervical vertebral body located in the middle of the surgical segments in multilevel anterior cervical spine surgery. Statistical analysis of vertebral parameters, including CSA, WA, AH, PH, UD, and LD, showed that OVB occurs mainly at the anterior edge of the vertebra and that its largest radiographic manifestation is the loss of height at the anterior edge of the vertebra in the early postoperative period.
Effects of MAP4K inhibition on neurite outgrowth
Authors: Lasham Di Ja , Arta Reza K. , Hadi Abdul Fuad , Egawa Jun , Lemmon Vance P. , Takasugi Toshiyuki , Igarashi Michihiro , Someya Toshiyuki
Published: November 2023

Protein kinases are responsible for protein phosphorylation and are involved in important intracellular signal transduction pathways in various cells, including neurons; however, a considerable number of poorly characterized kinases may be involved in neuronal development. Here, we considered mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), related to as candidate regulators of neurite outgrowth and synaptogenesis, by examining the effects of a selective MAP4K inhibitor PF06260933. PF06260933 treatments of the cultured neurons reduced neurite lengths, not the number of synapses, and phosphorylation of GAP43 and JNK, relative to the control. These results suggest that MAP4Ks are physiologically involved in normal neuronal development and that the resultant impaired neurite outgrowth by diminished MAP4Ks’ activity, is related to psychiatric disorders.
Microbial production of the plant flavanone hesperetin from caffeic acid
Authors: Hanko Erik K. R. , Correia João , Souza Caio S. , Green Alison , Chromy Jakub , Stoney Ruth , Yan Cunyu , Takano Eriko , Lousa Diana , Soares Cláudio M. , Breitling Rainer
Published: November 2023

Objective

Hesperetin is an important O-methylated flavonoid produced by citrus fruits and of potential pharmaceutical relevance. The microbial biosynthesis of hesperetin could be a viable alternative to plant extraction, as plant extracts often yield complex mixtures of different flavonoids making it challenging to isolate pure compounds. In this study, hesperetin was produced from caffeic acid in the microbial host Escherichia coli. We combined a previously optimised pathway for the biosynthesis of the intermediate flavanone eriodictyol with a combinatorial library of plasmids expressing three candidate flavonoid O-methyltransferases. Moreover, we endeavoured to improve the position specificity of CCoAOMT7, a flavonoid O-methyltransferase from Arabidopsis thaliana that has been demonstrated to O-methylate eriodictyol in both the para- and meta-position, thus leading to a mixture of hesperetin and homoeriodictyol.

Results

The best performing flavonoid O-methyltransferase in our screen was found to be CCoAOMT7, which could produce up to 14.6 mg/L hesperetin and 3.8 mg/L homoeriodictyol from 3 mM caffeic acid in E. coli 5-alpha. Using a platform for enzyme engineering that scans the mutational space of selected key positions, predicting their structures using homology modelling and inferring their potential catalytic improvement using docking simulations, we were able to identify a CCoAOMT7 mutant with a two-fold higher position specificity for hesperetin. The mutant’s catalytic activity, however, was considerably diminished. Our findings suggest that hesperetin can be created from central carbon metabolism in E. coli following the introduction of a caffeic acid biosynthesis pathway.