bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can preoperative ureteral stents reduce the incidence of ureteral stricture after radiotherapy in patients with cervical cancer?
Authors: Liu Liang , Yu Chunhong , Sun Fuzhen , Yang Tao , Wei Dong , Wang Gang , Li Shoubin , Liu Junjiang 
Published: July 2022

Abstract
Objective
To determine the impact of preoperative stent placement on postradiotherapy stricture rate in patients with cervical cancer after radical resection.

Methods
This study was a retrospective analysis of data collected from 55 cervical cancer patients treated with radiotherapy between June 2016 and June 2020. Patients were divided into the stent and control groups. After 3 months, the stricture rate and the complications related to stent placement between the two groups were compared.

Results
There were 12 (46.2%) and 10 (34.5%) cases of ureteral stricture in the stent (n = 26) and control (n = 29) groups, respectively, three months after the end of radiotherapy. The incidence rates of ureter stricture in the two groups were not significantly different (P = 0.378). Moreover, there were 20 units (38.5%) and 15 units (25.9%) ureteral strictures in the stent and control groups, respectively. No significant difference in the incidence rates of ureteral strictures was found between the two groups (P = 0.157). There were 13 (50.0%) and 10 (34.5%) cases of ureteral stricture in the stent (n = 26) and control (n = 29) groups, respectively, six months after the end of the radiotherapy. The incidence rates of ureter stricture in the two groups were not significantly different (P = 0.244). Moreover, there were 21 units (40.4%) and 15 units (25.9%) ureteral strictures in the stent and control groups, respectively. No significant difference in the incidence rates of ureteral strictures was found between the two groups (P = 0.105). Complications related to stent placement such as urinary tract infections and bladder irritation were statistically significant (P = 0.006 and P = 0.036) between the two groups; while the other complications were not significantly different (P = 0.070, P = 0.092 and P = 0.586).

Conclusions
Ureteral stents may not reduce the incidence of ureteral stricture after radiotherapy in patients with cervical cancer. The stent needs to be replaced regularly, and the complications related to stent placement may occur at any time. Thus, preoperative stent placement should be cautious for the clinical management of cervical cancer patients treated with postoperative radiotherapy.
Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae
Authors: Qi Jianzhao , Han Haiyan , Sui Dan , Tan Shengnan , Liu Changli , Wang Pengchao , Xie Chunliang , Xia Xuekui , Gao Jin-ming , Liu Chengwei 
Published: July 2022

Abstract
Background
Cyclic dipeptides are an important class of natural products owing to their structural diversity and biological activities. In fungi, the cyclo-ring system is formed through the condensation of two α-amino acids via non-ribosomal peptide synthetase (NRPS). However, there are few investigations on the functional identification of this enzyme. Additionally, information on how to increase the production of cyclic dipeptide molecules is relatively scarce.

Results
We isolated the Eurotium cristatum NWAFU-1 fungus from Jing-Wei Fu brick tea, whose fermentation metabolites contain echinulin-related cyclic dipeptide molecules. We cloned the cirC gene, encoding an NRPS, from E. Cristatum NWAFU-1 and transferred it into the heterologous host Aspergillus oryzae. This transformant produced a novel metabolite possessing an l-tryptophan-l-alanine cyclic dipeptide backbone (Cyclo-TA). Based on the results of heterologous expression and microsomal catalysis, CriC is the first NRPS characterized in fungi that catalyzes the formation of a cyclic dipeptide from l-tryptophan and l-alanine. After substrate feeding, the final yield reached 34 mg/L. In this study, we have characterized a novel NRPS and developed a new method for cyclic dipeptide production.

Conclusions
In this study we successfully expressed the E. Cristatum NWAFU-1 criC gene in A. oryzae to efficiently produce cyclic dipeptide compounds. Our findings indicate that the A. oryzae heterologous expression system constitutes an efficient method for the biosynthesis of fungal Cyclic dipeptides.
Adherence to a healthy and potentially sustainable Nordic diet is associated with child development in The Norwegian Mother, Father and Child Cohort Study (MoBa)
Authors: Vejrup Kristine , Agnihotri Neha , Bere Elling , Schjølberg Synnve , LeBlanc Marissa , Hillesund Elisabet Rudjord , Øverby Nina Cecilie 
Published: July 2022

AbstractBackgroundThe rapid neurodevelopment that occurs during the first years of life hinges on adequate nutrition throughout fetal life and early childhood. Therefore, adhering to a dietary pattern based on healthy foods during pregnancy and the first years of life may be beneficial for future development. The aim of this paper was to investigate the relationship between adherence to a healthy and potentially sustainable Nordic diet during pregnancy and in early childhood and child development.MethodsThis study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). In 83,800 mother-child pairs, maternal pregnancy diet and child diet at 6 months, 18 months and 3 years were scored according to adherence to the New Nordic Diet (NND). NND scores were calculated both as a total score and categorized into low, medium, or high adherence. Child communication and motor development skills were reported by parents at 6 months, 18 months, 3 and 5 years, using short forms of the Ages and Stages Questionnaire and the Child Development Inventory. Associations of NND adherence with child development were estimated with linear and logistic regression in crude and adjusted models.ResultsWhen examining the NND and child developmental scores as percentages of the total scores, we found positive associations between the NND scores (both maternal pregnancy diet and child diet) and higher scoring on child development (adjusted$$\hat{\beta}$$β^s [95% confidence intervals] ranging from 0.007 [0.004, 0.009] to 0.045 [0.040, 0.050]). We further found that low and medium adherence to NND were associated with higher odds of later emerging developmental skills compared to high NND adherence at nearly all measured timepoints (odds ratios [95% CI] ranging from significant values 1.15 [1.03–1.29] to 1.79 [1.55, 2.06] in adjusted analyses).ConclusionsOur findings support that adherence to a healthy and potentially sustainable diet early in life is important for child development every step of the way from pregnancy until age 5 years.
Effects of macrophages on the proliferation and cardiac differentiation of human induced pluripotent stem cells
Authors: Long Canling , Guo Rui , Han Ruijuan , Li Kang , Wan Yanbing , Xu Jiqing , Gong Xiaoyu , Zhao Yanqiu , Yao Xinhuang , Liu Jia 
Published: July 2022

Abstract
Background
Macrophage phenotypes switch from proinflammatory (M1) to anti-inflammatory (M2) following myocardial injury. Implanted stem cells (e.g., induced pluripotent stem cells (iPSCs)) for cardiomyogenesis will inevitably contact the inflammatory environment at the myocardial infarction site. To understand how the macrophages affect the behavior of iPSCs, therefore, improve the therapeutic efficacy, we generated three macrophage subtypes and assessed their effects on the proliferation, cardiac differentiation, and maturation of iPSCs.

Methods
M0, M1, and M2 macrophages were polarized using cytokines, and their properties were confirmed by the expression of specific markers using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The effects of macrophages on iPSCs were studied using Transwell co-culture models. The proliferative ability of iPSCs was investigated by cell counting and CCK-8 assays. The cardiac differentiation ability of iPSCs was determined by the cardiomyocyte (CM) yield. The maturation of CM was analyzed by the expression of cardiac-specific genes using RT-qPCR, the sarcomere organization using immunofluorescence, and the mitochondrial function using oxidative respiration analysis.

Results
The data showed that the co-culture of iPSCs with M0, M1, or M2 macrophages significantly decreased iPSCs’ proliferative ability. M2 macrophages did not affect the CM yield during the cardiac differentiation of iPSCs. Still, they promoted the maturation of CM by improving sarcomeric structures, increasing contractile- and ion transport-associated gene expression, and enhancing mitochondrial respiration. M0 macrophages did not significantly affect the cardiomyogenesis ability of iPSCs during co-culture. In contrast, co-culture with M1 macrophages significantly reduced the cardiac differentiation and maturation of iPSCs.

Conclusions
M1- or M2-polarized macrophages play critical roles in the proliferation, cardiac differentiation, and maturation of iPSCs, providing knowledge to improve the outcomes of stem cell regeneration therapy.
Phagocytosis converts infiltrated monocytes to microglia-like phenotype in experimental brain ischemia
Authors: Ju Hyunwoo , Park Keun Woo , Kim Il-doo , Cave John W. , Cho Sunghee 
Published: July 2022

Abstract
Background
Monocyte-derived macrophages (MDMs) and microglia elicit neural inflammation and clear debris for subsequent tissue repair and remodeling. The role of infiltrating MDMs in the injured brain, however, has been controversial due to overlapping antigen expression with microglia. In this study, we define the origin and function of MDMs in cerebral ischemia.

Methods
Using adoptive transfer of GFP+ splenocytes into adult asplenic mice subjected to transient middle cerebral artery occlusion, we compared the role of CD11b+/CD45+/NK1.1−/Ly6G− MDMs and microglia in the ischemic brain. The phagocytic activities of MDMs and microglia were measured by the uptake of fluorescent beads both in vivo with mice infused with GFP+ splenocytes and ex vivo with cultures of isolated brain immune cells.

Results
Stroke induced an infiltration of MDMs [GFP+] into the ipsilateral hemisphere at acute (3 days) and sub-acute phases (7 days) of post-stroke. At 7 days, the infiltrating MDMs contained both CD45High and CD45Low subsets. The CD45High MDMs in the injured hemisphere exhibited a significantly higher proliferation capacity (Ki-67 expression levels) as well as higher expression levels of CD11c when compared to CD45Low MDMs. The CD45High and CD45Low MDM subsets in the injured hemisphere were approximately equal populations, indicating that CD45High MDMs infiltrating the ischemic brain changes their phenotype to CD45Low microglia-like phenotype. Studies with fluorescent beads reveal high levels of MDM phagocytic activity in the post-stroke brain, but this phagocytic activity was exclusive to post-ischemic brain tissue and was not detected in circulating monocytes. By contrast, CD45Low microglia-like cells had low levels of phagocytic activity when compared to CD45High cells. Both in vivo and ex vivo studies also show that the phagocytic activity in CD45High MDMs is associated with an increase in the CD45Low/CD45High ratio, indicating that phagocytosis promotes MDM phenotype conversion.

Conclusions
This study demonstrates that MDMs are the predominant phagocytes in the post-ischemic brain, with the CD45High subset having the highest phagocytic activity levels. Upon phagocytosis, CD45High MDMs in the post-ischemic brain adopt a CD45Low phenotype that is microglia-like. Together, these studies reveal key roles for MDMs and their phagocytic function in tissue repair and remodeling following cerebral ischemia.
Subacute and chronic proteomic and phosphoproteomic analyses of a mouse model of traumatic brain injury at two timepoints and comparison with chronic traumatic encephalopathy in human samples
Authors: Morin Alexander , Davis Roderick , Darcey Teresa , Mullan Michael , Mouzon Benoit , Crawford Fiona 
Published: July 2022

AbstractRepetitive mild traumatic brain injury (r-mTBI) is the most widespread type of brain trauma worldwide. The cumulative injury effect triggers long-lasting pathological and molecular changes that may increase risk of chronic neurodegenerative diseases. R-mTBI is also characterized by changes in the brain proteome, where the majority of molecules altered early post-TBI are different from those altered at more chronic phases. This differentiation may contribute to the heterogeneity of available data on potential therapeutic targets and may present an obstacle in developing effective treatments. Here, we aimed to characterize a proteome profile of r-mTBI in a mouse model at two time points – 3 and 24 weeks post last TBI, as this may be a more relevant therapeutic window for individuals suffering negative consequences of r-mTBI. We identified a great number of proteins and phosphoproteins that remain continuously dysregulated from 3 to 24 weeks. These proteins may serve as effective therapeutic targets for sub-acute and chronic stages of post r-mTBI. We also compared canonical pathway activation associated with either total proteins or phosphoproteins and revealed that they both are upregulated at 24 weeks. However, at 3 weeks post-TBI, only pathways associated with total proteins are upregulated, while pathways driven by phosphoproteins are downregulated. Finally, to assess the translatability of our data, we compared proteomic changes in our mouse model with those reported in autopsied human samples of Chronic Traumatic Encephalopathy (CTE) patients compared to controls. We observed 39 common proteins that were upregulated in both species and 24 common pathways associated with these proteins. These findings support the translational relevance of our mouse model of r-mTBI for successful identification and translation of therapeutic targets.
Feasibility and discriminatory value of tissue motion annular displacement in sepsis-induced cardiomyopathy: a single-center retrospective observational study
Authors: Song Jieqiong , Yao Yao , Lin Shilong , He Yizhou , Zhu Duming , Zhong Ming 
Published: July 2022

Abstract
Background
There is no formal diagnostic criterion for sepsis-induced cardiomyopathy (SICM), but left ventricular ejection fraction (LVEF) < 50% was the most commonly used standard. Tissue motion annular displacement (TMAD) is a novel speckle tracking indicator to quickly assess LV longitudinal systolic function. This study aimed to evaluate the feasibility and discriminatory value of TMAD for predicting SICM, as well as prognostic value of TMAD for mortality.

Methods
We conducted a single-center retrospective observational study in patients with sepsis or septic shock who underwent echocardiography examination within the first 24 h after admission. Basic clinical information and conventional echocardiographic data, including mitral annular plane systolic excursion (MAPSE), were collected. Based on speckle tracking echocardiography (STE), global longitudinal strain (GLS) and TMAD were, respectively, performed offline. The parameters acquisition rate, inter- and intra-observer reliability, time consumed for measurement were assessed for the feasibility analysis. Areas under the receiver operating characteristic curves (AUROC) values were calculated to assess the discriminatory value of TMAD/GLS/MAPSE for predicting SICM, defined as LVEF < 50%. Kaplan–Meier survival curve analysis was performed according to the cutoff values in predicting SICM. Cox proportional hazards model was performed to determine the risk factors for 28d and in-hospital mortality.

Results
A total of 143 patients were enrolled in this study. Compared with LVEF, GLS or MAPSE, TMAD exhibited the highest parameter acquisition rate, intra- and inter-observer reliability. The mean time for offline analyses with TMAD was significantly shorter than that with LVEF or GLS (p < 0.05). According to the AUROC analysis, TMADMid presented an excellent discriminatory value for predicting SICM (AUROC > 0.9). Patients with lower TMADMid (< 9.75 mm) had significantly higher 28d and in-hospital mortality (both p < 0.05). The multivariate Cox proportional hazards model revealed that BMI and SOFA were the independent risk factors for 28d and in-hospital mortality in sepsis cases, but TMAD was not.

Conclusion
STE-based TMAD is a novel and feasible technology with promising discriminatory value for predicting SICM with LVEF < 50%.
Feasibility of radiology online structured oral examination for undergraduate medical students
Authors: Alharbi Fawaz , Alamer Ali 
Published: July 2022

Abstract
Background
Online summative assessment has emerged during the COVID-19 pandemic as an alternative to traditional examinations, bringing opportunities and challenges. The study aims to evaluate the feasibility and effectiveness of online structured oral examination (SOE) in radiology clerkships. The study identifies measures taken to successfully implement online SOE and minimize chances of cheating. It also discusses the challenges encountered and how they were addressed.

Methods
SOE percent scores of fourth-year medical students from two institutions were correlated with students’ grade point average (GPA). The scores were compared among different institutions, students’ genders, students’ batches, examination versions, and examiners with different experience levels. Students’ perceived satisfaction and concerns were captured using anonymous self-administered questionnaire. Technical problems and success rate of SOE implementation were recorded. Results were analyzed using descriptive and inferential statistics.

Results
A total of 79 students participated in the study, out of which 81.0% (n = 64) responded to the survey. SOE scores showed poor positive correlation with the students’ GPAs (r = 0.22, and p = .09). Scores showed no significant difference between the two institutions or genders. Scores were also not significantly different between students who were examined by junior or senior examiners. All but one version of examination showed no significant difference in students’ scores. No significant difference was observed in students’ scores between each two subsequent batches who were exposed to the same examination version.

Conclusion
Online summative SOE is a feasible alternative whenever face-to-face SOE could not be implemented provided that appropriate measures are taken to ensure its successful execution.
Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells
Authors: Kim Seong-Min , Kwon Eun-Ji , Kim Yun-Jeong , Go Young-Hyun , Oh Ji-Young , Park Seokwoo , Do Jeong Tae , Kim Keun-Tae , Cha Hyuk-Jin 
Published: July 2022

Abstract
Background
The requirement of the Mek1 inhibitor (iMek1) during naïve pluripotency maintenance results from the activation of the Mek1-Erk1/2 (Mek/Erk) signaling pathway upon leukemia inhibitory factor (LIF) stimulation.

Methods
Through a meta-analysis of previous genome-wide screening for negative regulators of naïve pluripotency, Ptpn11 (encoding the Shp2 protein, which serves both as a tyrosine phosphatase and putative adapter), was predicted as one of the key factors for the negative modulation of naïve pluripotency through LIF-dependent Jak/Stat3 signaling. Using an isogenic pair of naïve and primed mouse embryonic stem cells (mESCs), we demonstrated the differential role of Shp2 in naïve and primed pluripotency.

Results
Loss of Shp2 increased naïve pluripotency by promoting Jak/Stat3 signaling and disturbed in vivo differentiation potential. In sharp contrast, Shp2 depletion significantly impeded the self-renewal of ESCs under primed culture conditions, which was concurrent with a reduction in Mek/Erk signaling. Similarly, upon treatment with an allosteric Shp2 inhibitor (iShp2), the cells sustained Stat3 phosphorylation and decoupled Mek/Erk signaling, thus iShp2 can replace the use of iMek1 for maintenance of naïve ESCs.

Conclusions
Taken together, our findings highlight the differential roles of Shp2 in naïve and primed pluripotency and propose the usage of iShp2 instead of iMek1 for the efficient maintenance and establishment of naïve pluripotency.
Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs
Authors: Yao Genhong , Qi Jingjing , Li Xiaojing , Tang Xiaojun , Li Wenchao , Chen Weiwei , Xia Nan , Wang Shiying , Sun Lingyun 
Published: July 2022

Abstract
Objective
The mechanism by which mesenchymal stem cell (MSC) transplantation alleviates atherosclerosis in systemic lupus erythematosus (SLE) remains elusive. In this study, we aim to explore the efficacy and mechanism of MSC in ameliorating atherosclerosis in SLE.

Methods
ApoE−/− and Fas−/− mice on the B6 background were cross-bred to generate SLE mice with atherosclerosis. Myeloid-derived suppressor cells (MDSCs) were sorted and quantified. The apoE−/−Fas−/− mice were either treated with anti-Gr antibody or injected with MDSCs. The lupus-like autoimmunity and atherosclerotic lesions were evaluated. Furthermore, the apoE−/−Fas−/− mice were transplanted with MSCs and lupus-like autoimmunity and atherosclerotic lesions were assessed.

Results
MDSCs in peripheral blood, spleen, draining lymph nodes increased in apoE−/−Fas−/− mice compared with B6 mice. Moreover, the adoptive transfer of MDSCs aggravated both atherosclerosis and SLE pathologies, whereas depleting MDSCs ameliorated those pathologies in apoE−/−Fas−/− mice. MSC transplantation in apoE−/−Fas−/− mice decreased the percentage of MDSCs, alleviated the typical atherosclerotic lesions, including atherosclerotic lesions in aortae and liver, and reduced serum cholesterol, triglyceride and low-density lipoprotein levels. MSC transplantation also reduced SLE pathologies, including splenomegaly, glomerular lesions, anti-dsDNA antibody in serum, urine protein and serum creatinine. Moreover, MSC transplantation regulated the generation and function of MDSCs through secreting prostaglandin E 2 (PGE2).

Conclusion
Taken together, these results indicated that the increased MDSCs contributed to atherosclerosis in SLE. MSC transplantation ameliorated the atherosclerosis and SLE through reducing MDSCs by secreting PGE2.

Graphical Abstract
RA signaling pathway combined with Wnt signaling pathway regulates human-induced pluripotent stem cells (hiPSCs) differentiation to sinus node-like cells
Authors: Yin Lin , Wang Feng-yuan , Zhang Wei , Wang Xi , Tang Yan-hong , Wang Teng , Chen Yu-ting , Huang Cong-xin 
Published: July 2022

Abstract
Background
The source of SAN is debated among researchers. Many studies have shown that RA and Wnt signaling are involved in heart development. In this study, we investigated the role of retinoic acid (RA) and Wnt signaling in the induction of sinus node-like cells.

Methods
The experimental samples were divided into four groups: control group (CHIR = 0), CHIR = 3, RA + CHIR = 0 andRA + CHIR = 3. After 20 days of differentiation, Western blot, RT-qPCR, immunofluorescence and flow cytometry were performed to identify sinus node-like cells. Finally, whole-cell patch clamp technique was used to record pacing funny current and action potential (AP) in four groups.

Results
The best intervention method used in our experiment was RA = 0.25 µmol/L D5-D9 + CHIR = 3 µmol/L D5-D7. Results showed that CHIR can increase the expression of ISL-1 and TBX3, while RA mainly elevated Shox2. Immunofluorescence assay and flow cytometry further illustrated that combining RA with CHIR can induce sinus node-like cells (CTNT+Shox2+Nkx2.5−). Moreover, CHIR might reduce the frequency of cell beats, but in conjunction with RA could partly compensate for this side effect. Whole cell patch clamps were able to record funny current and the typical sinus node AP in the experimental group, which did not appear in the control group.

Conclusions
Combining RA with Wnt signaling within a specific period can induce sinus node-like cells.