bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of intensive education on stroke prevention and management ability of community doctors: a cross-sectional study
Authors: Zhong Xue-min , Huang Yao , He Lanying , Wang Jian
Published: January 2022

Background

Prevention and treatment of stroke are extremely important to reduce the incidence of stroke-related disability and the associated death. This study aimed to investigate the current ability of community doctors in stroke management in the Jinjiang district of Chengdu, China, and the effect of intensive education on stroke prevention and management ability of these doctors.

Methods

A self-designed questionnaire was used to investigate the current status of stroke management by community doctors in the Jinjiang district. Subsequently, a series of intensive stroke management education courses for community doctors was designed according to the relevant guidelines for cerebrovascular accident prevention and treatment in China. All community doctors were trained, and their ability to treat and prevent stroke was reassessed using the self-designed questionnaire.

Results

Of the 450 questionnaires issued, 370 (82.2%) and 389 (86.4%) community doctors were enrolled before and after intensive education, respectively. The results showed that only 37.8% of the community doctors in the Jinjiang district knew the guidelines for the prevention and treatment of cerebrovascular diseases, and only 45.9% thought they had stroke management ability. The stroke management ability of community doctors improved after intensive education (p < 0.05), including pre-hospital identification and management of stroke, and management of its risk factors.

Conclusions

The capacity of community doctors in the Jinjiang district of Chengdu is far from meeting the requirements of stroke prevention and treatment. However, the stroke management ability of the community doctors was greatly improved by promoting intensive education.
Histone H4 induces heparan sulfate degradation by activating heparanase in chlorine gas-induced acute respiratory distress syndrome
Authors: Zhang Yanlin , Xu Fei , Guan Li , Chen Ming , Zhao Yiran , Guo Lixia , Li Xiao , Zheng Yimu , Gao Ai , Li Shuqiang
Published: January 2022

Background

Heparan sulfate (HS) degradation mediates pulmonary endothelial hyper-permeability and acute pulmonary edema during acute respiratory distress syndrome (ARDS). The aim of this study was to examine whether histone H4 induced HS degradation by activating heparanase (HPSE) in chlorine gas (Cl2)-induced ARDS.

Methods

Acute lung injury was induced by Cl2 exposure or histone H4 injection in C57BL/6 mice. Histone H4 in bronchoalveolar lavage fluid (BALF) and plasma was measured by ELISA. HS degradation was measured by immunostaining, ELISA, and flow cytometry. HPSE mRNA and protein were measured by real-time qPCR and western blot analysis, respectively, at preset timepoints. The HPSE inhibitor OGT2115 and specific siRNAs were used to study the role of HPSE during HS degradation caused by Cl2 exposure or histone H4 challenge. Blocking antibodies against TLR1, TLR2, TLR4, or TLR6 were used in vitro to investigate which signaling pathway was involved. The transcriptional regulation of HPSE was studied vis-à-vis NF-κB, which was assessed by nuclear translocation of NF-κB p65 and phosphorylation of I-κBα protein.

Results

Histone H4 in BALF and plasma increased evidently after Cl2 inhalation. Cl2 exposure or histone H4 challenge caused obvious acute lung injury in mice, and the pulmonary glycocalyx was degraded evidently as observed from endothelial HS staining and measurement of plasma HS fragments. Pretreatment with OGT2115, an HPSE inhibitor, relieved the acute lung injury and HS degradation caused by Cl2 exposure or histone H4 challenge. Targeted knockdown of HPSE by RNA interference (RNAi) significantly inhibited histone H4 induced HS degradation in HPMECs, as measured by immunofluorescence and flow cytometry. By inducing phosphorylation of I-κB α and nuclear translocation of NF-κB p65, histone H4 directly promoted mRNA transcription and protein expression of HPSE in a dose-dependent manner. Additionally, a blocking antibody against TLR4 markedly inhibited both activation of NF-κB and expression of HPSE induced by histone H4.

Conclusions

Histone H4 is a major pro-inflammatory mediator in Cl2-induced ARDS in mice, and induces HS degradation by activating HPSE via TLRs- and NF-κB-signaling pathways.
Inequalities in access to healthcare by local policy model among newly arrived refugees: evidence from population-based studies in two German states
Authors: Wenner Judith , Biddle Louise , Gottlieb Nora , Bozorgmehr Kayvan
Published: January 2022

Background

Access to healthcare is restricted for newly arriving asylum seekers and refugees (ASR) in many receiving countries, which may lead to inequalities in health. In Germany, regular access and full entitlement to healthcare (equivalent to statutory health insurance, SHI) is only granted after a waiting time of 18 months. During this time of restricted entitlements, local authorities implement different access models to regulate asylum seekers’ access to healthcare: the electronic health card (EHC) or the healthcare voucher (HV). This paper examines inequalities in access to healthcare by comparing healthcare utilization by ASR under the terms of different local models (i.e., regular access equivalent to SHI, EHC, and HV).

Methods

We used data from three population-based, cross-sectional surveys among newly arrived ASR (N=863) and analyzed six outcome measures: specialist and general practitioner (GP) utilization, unmet needs for specialist and GP services, emergency department use and avoidable hospitalization. Using logistic regression, we calculated odds ratios (OR) and 95% confidence intervals for all outcome measures, while considering need by adjusting for socio-demographic characteristics and health-related covariates.

Results

Compared to ASR with regular access, ASR under the HV model showed lower needs-adjusted odds of specialist utilization (OR=0.41 [0.24-0.66]) while ASR under the EHC model did not differ from ASR with regular access in any of the outcomes. The comparison between EHC and HV model showed higher odds for specialist utilization under the EHC model as compared to the HV model (OR=2.39 [1.03-5.52]). GP and emergency department utilization, unmet needs and avoidable hospitalization did not show significant differences in any of the fully adjusted models.

Conclusion

ASR using the HV are disadvantaged in their access to healthcare compared to ASR having either an EHC or regular access. Given equal need, they use specialist services less. The identified inequalities constitute inequities in access to healthcare that could be reduced by policy change from HV to the EHC model during the initial 18 months waiting time, or by granting ASR regular healthcare access upon arrival. Potential patterns of differences in GP utilization, unmet needs, emergency department use and avoidable hospitalization between the models deserve further exploration in future studies.
Recombinant anti-Müllerian hormone in the maturation medium improves the in vitro maturation of human immature (GV) oocytes after controlled ovarian hormonal stimulation
Authors: Bedenk Jure , Režen Tadeja , Železnik Ramuta Taja , Jančar Nina , Vrtačnik Bokal Eda , Geršak Ksenija , Virant Klun Irma
Published: January 2022

Background

In vitro maturation (IVM) of oocytes is a laboratory method that allows the maturation of immature (GV) oocytes retrieved from patients enrolled in the in vitro fertilization (IVF) programme. However, this method is still sparsely researched and used in clinical practice, leading to suboptimal clinical results. Anti-Müllerian hormone (AMH) is an important hormone with known effects on human ovaries, especially on follicles (follicular cells) during folliculogenesis. In contrast, the effect of AMH on the human oocyte itself is unknown. Therefore, we wanted to determine whether human oocytes express AMH receptor 2 (AMHR2) for this hormone. Recombinant AMH was added to the IVM medium to determine whether it affected oocyte maturation.

Methods

In total, 247 human oocytes (171 immature and 76 mature) were collected from patients enrolled in the intracytoplasmic sperm injection (ICSI) programme who were aged 20 to 43 years and underwent a short antagonist protocol of ovarian stimulation. The expression of AMHR2 protein and AMHR2 gene was analysed in immature and mature oocytes. Additionally, maturation of GV oocytes was performed in vitro in different maturation media with or without added AMH to evaluate the effect of AMH on the oocyte maturation rate.

Results

Immunocytochemistry and confocal microscopy revealed that AMHR2 protein is expressed in both immature and mature human oocytes. AMHR2 was expressed in a spotted pattern throughout the whole oocyte. The IVM procedure revealed that AMH in maturation medium improved GV oocyte maturation in vitro, as all oocytes were successfully matured in maturation medium containing recombinant AMH only. Furthermore, antagonism between AMH and follicle-stimulating hormone (FSH) during the maturation process was observed, with fewer oocytes maturing when both AMH and FSH were added to the maturation medium. Finally, AMHR2 gene expression was found in immature and in vitro matured oocytes but absent in mature oocytes.

Conclusions

The positive AMHR2 protein and AMHR2 gene expression in human oocytes shows that AMH could directly act on human oocytes. This was further functionally confirmed by the IVM procedure. These findings suggest the potential clinical application of recombinant AMH to improve IVM of human oocytes in the future.
Strategies for the implementation of clinical practice guidelines in public health: an overview of systematic reviews
Authors: Pereira Viviane C. , Silva Sarah N. , Carvalho Viviane K. S. , Zanghelini Fernando , Barreto Jorge O. M.
Published: January 2022

Background

As a source of readily available evidence, rigorously synthesized and interpreted by expert clinicians and methodologists, clinical guidelines are part of an evidence-based practice toolkit, which, transformed into practice recommendations, have the potential to improve both the process of care and patient outcomes. In Brazil, the process of development and updating of the clinical guidelines for the Brazilian Unified Health System (Sistema Único de Saúde, SUS) is already well systematized by the Ministry of Health. However, the implementation process of those guidelines has not yet been discussed and well structured. Therefore, the first step of this project and the primary objective of this study was to summarize the evidence on the effectiveness of strategies used to promote clinical practice guideline implementation and dissemination.

Methods

This overview used systematic review methodology to locate and evaluate published systematic reviews regarding strategies for clinical practice guideline implementation and adhered to the PRISMA guidelines for systematic review (PRISMA).

Results

This overview identified 36 systematic reviews regarding 30 strategies targeting healthcare organizations, healthcare providers and patients to promote guideline implementation. The most reported interventions were educational materials, educational meetings, reminders, academic detailing and audit and feedback. Care pathways—single intervention, educational meeting—single intervention, organizational culture, and audit and feedback—both strategies implemented in combination with others—were strategies categorized as generally effective from the systematic reviews. In the meta-analyses, when used alone, organizational culture, educational intervention and reminders proved to be effective in promoting physicians' adherence to the guidelines. When used in conjunction with other strategies, organizational culture also proved to be effective. For patient-related outcomes, education intervention showed effective results for disease target results at a short and long term.

Conclusion

This overview provides a broad summary of the best evidence on guideline implementation. Even if the included literature highlights the various limitations related to the lack of standardization, the methodological quality of the studies, and especially the lack of conclusion about the superiority of one strategy over another, the summary of the results provided by this study provides information on strategies that have been most widely studied in the last few years and their effectiveness in the context in which they were applied. Therefore, this panorama can support strategy decision-making adequate for SUS and other health systems, seeking to positively impact on the appropriate use of guidelines, healthcare outcomes and the sustainability of the SUS.
CT-based radiomics nomograms for preoperative prediction of diffuse-type and signet ring cell gastric cancer: a multicenter development and validation cohort
Authors: Chen Tao , Wu Jing , Cui Chunhui , He Qinglie , Li Xunjun , Liang Weiqi , Liu Xiaoyue , Liu Tianbao , Zhou Xuanhui , Zhang Xifan , Lei Xiaotian , Xiong Wei , Yu Jiang , Li Guoxin
Published: January 2022

Background

The prevalence of diffuse-type gastric cancer (GC), especially signet ring cell carcinoma (SRCC), has shown an upward trend in the past decades. This study aimed to develop computed tomography (CT) based radiomics nomograms to distinguish diffuse-type and SRCC GC preoperatively.

Methods

A total of 693 GC patients from two centers were retrospectively analyzed and divided into training, internal validation and external validation cohorts. Radiomics features were extracted from CT images, and the Lauren radiomics model was established with a support vector machine (SVM) classifier to identify diffuse-type GC. The Lauren radiomics nomogram integrating radiomics features score (Rad-score) and clinicopathological characteristics were developed and evaluated regarding prediction ability. Further, the SRCC radiomics nomogram designed to identify SRCC from diffuse-type GC was developed and evaluated following the same procedures.

Results

Multivariate analysis revealed that Rad-scores was significantly associated with diffuse-type GC and SRCC (p < 0.001). The Lauren radiomics nomogram showed promising prediction performance with an area under the curve (AUC) of 0.895 (95%CI, 0.957–0.932), 0.841 (95%CI, 0.781–0.901) and 0.893 (95%CI, 0.831–0.955) in each cohort. The SRCC radiomics nomogram also showed good discrimination, with AUC of 0.905 (95%CI,0.866–0.944), 0.845 (95%CI, 0.775–0.915) and 0.918 (95%CI, 0.842–0.994) in each cohort. The radiomics nomograms showed great model fitness and clinical usefulness by calibration curve and decision curve analysis.

Conclusion

Our CT-based radiomics nomograms had the ability to identify the diffuse-type and SRCC GC, providing a non-invasive, efficient and preoperative diagnosis method. They may help guide preoperative clinical decision-making and benefit GC patients in the future.
Increasing motor cortex activation during grasping via novel robotic mirror hand therapy: a pilot fNIRS study
Authors: Kim Dong Hyun , Lee Kun-Do , Bulea Thomas C. , Park Hyung-Soon
Published: January 2022

Background

Mirror therapy (MT) has been used for functional recovery of the affected hand by providing the mirrored image of the unaffected hand movement, which induces neural activation of the cortical hemisphere contralateral to the affected hand. Recently, many wearable robots assisting the movement of the hand have been developed, and several studies have proposed robotic mirror therapy (RMT) that uses a robot to provide mirrored movements of the unaffected hand to the affected hand with the robot controlled by measuring electromyography or posture of the unaffected hand. In some cases of RMT a mirror is placed to allow the person to observe only the unaffected hand but in others users simply observe the robotically assisted hand performing the mirrored movements, as was the case in this study. There have been limited evaluations of the cortical activity during RMT compared to MT and robotic therapy (RT) providing passive movements despite the difference in the modality of sensory feedback and the involvement of motor intention, respectively.

Methods

This paper analyzes bilateral motor cortex activation in nine healthy subjects and five chronic stroke survivors during a pinching task performed in MT, RT, and RMT conditions using functional near infrared spectroscopy (fNIRS). In the MT condition, the person moved the unaffected hand and observed it in a mirror while the affected hand remained still. In RT condition passive movements were provided to the affected hand with a cable-driven soft robotic glove, while, in RMT condition, the posture of the unaffected hand was measured by a sensing glove and the soft robotic glove mirrored its movement on the affected hand.

Results

For both groups, the RMT condition showed the greatest mean cortical activation on the motor cortex contralateral to the affected (non-dominant for the healthy group) hand compared to other conditions. Individual results indicate that RMT induces similar or greater neural activation on the motor cortex compared to MT and RT conditions. The interhemispheric activations of both groups were balanced in RMT condition. In MT condition, significantly greater activation was shown on the hemisphere ipsilateral to the affected (dominant for the healthy group) hand for both subject groups, while the contralateral side showed significantly greater activation for the healthy group in RT condition.

Conclusion

The experimental results indicate that combining visual feedback, somatosensory feedback, and motor intention are important for greater stimulation on the contralateral motor cortex of the affected hand. RMT that includes these factors is hypothesized to achieve a more effective functional rehabilitation due to greater and more balanced cortical activation.
Human papillomavirus E6E7 mRNA and TERC lncRNA in situ detection in cervical scraped cells and cervical disease progression assessment
Authors: Zhao Hui , He Yue , Fan Bei , Wang Yan , Wu Yu-Mei
Published: January 2022

Background

Human papillomavirus screen in female cervical cells has demonstrated values in clinical diagnosis of precancerous lesions and cervical cancers. Human papillomavirus tests of cervical cells by utilizing Polymerase Chain Reaction (PCR) method provides human papillomavirus infection status however no further virus in situ information. Although it is well known that the tests of human papillomavirus E6/E7 RNA location in infected cervical cells and cell internal malignancy molecular will provide clues for gynecologists to evaluate disease progression, there are technique difficulties to preserve RNAs in cervical scraped cells for in situ hybridization.

Methods

In current study, after developing a cervical cell collection and preparation method for RNA in situ hybridization, we captured the chance to screen 98 patient cervical cell samples and detected human papillomavirus E6/E7 mRNAs of high-risk subtypes, low-risk subtypes and long non-coding RNA (lncRNA) TERC in the cells.

Results

There were 69 samples exhibited consistence between human papillomavirus PCR and human papillomavirus RNA in situ hybridization results in cervical collected cells. Among them, 23 were both positive and 46 were both negative. In the rest 29 samples, 8 were HPV RNAscope positive, either high risk or low risk subtypes, however HPV PCR negative. Another 9 samples were HPV PCR results positive whereas RNAscope negative. The last 12 samples were HPV positive detected by both RNAscope and PCR methods, however inconsistent between high-risk and low-risk subtypes. In RNAscope positive samples, viral E6/E7 mRNAs were observed to distribute in cervical scraped cell nucleus and cytoplasm. Moreover, HPV viral RNA gathered clusters were observed outside of cells through human papillomavirus RNA in situ hybridization detection. Varied numbers of human papillomavirus infective cells were detected by RNAscope assay in different patients even though they were all human papillomavirus high-risk subtype positive discovered by human papillomavirus PCR results. A cell malignancy related long non-coding RNA, TERC, has been detected in seven patient samples. The patient follow-up information was further analyzed with RNAscope results which indicated a combination of RNAscope positive signals of TERC and human papillomavirus high risk signals in more than 10 cells (cytoplasm or nucleus) may connect with cervical lesion fast progression which deserves further studies in the future.C

Conclusions

Taken together, current study has provided an observable clue for gynecologists to evaluate human papillomavirus infection stage and cell malignancy status which may contribute for assessment of cervical disease progression.
Molecular features of glioblastomas in long-term survivors compared to short-term survivors—a matched-pair analysis
Authors: Sommerlath Vivien N. , Buergy Daniel , Etminan Nima , Brehmer Stefanie , Reuss David , Sarria Gustavo R. , Guiot Marie-Christin , Hänggi Daniel , Wenz Frederik , Petrecca Kevin , Giordano Frank A.
Published: January 2022

Background

Although glioblastoma (GB) is associated with a devastating prognosis, a small proportion of patients achieve long-term survival rates. We herein present a matched-pair analysis of molecular factors found in long- and short-term survivors (LTS, STS).

Methods

We performed a cross-institutional analysis of 262 patient records and matched a group of 91 LTS (≥ 3 years) with two groups of STS (STS-1, n = 91; STS-2, n = 80). Matching was performed according to age, Karnofsky Performance Status, initial therapy and adjuvant therapy. Molecular factors were compared between LTS (total of 91 patients) v. STS-1, and LTS (subgroup of 80 patients) v. STS-2. We included glial fibrillary acidic protein (GFAP), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase 1 (IDH-1); furthermore, the proliferation index was analyzed (Ki-67/MIB-1).

Results

IDH-1 and decreased Ki-67 were numerically associated with LTS but the difference was only significant compared to STS-1 (n.s. v. STS-2). LTS was associated with MGMT promoter hypermethylation (p = 0.013 and p = 0.022) and GFAP expression (p < 0.001 and p = 0.001). Positivity for both factors combined compared to negativity for one factor occurred more often in the LTS group (p = 0.002 and p = 0.006); negativity for both factors combined did not occur in the LTS group.

Conclusion

In this retrospective analysis, GFAP expression and MGMT promoter methylation were associated with LTS. Given the hypothesis-generating nature of our study, these observations should be confirmed in prospective clinical trials.
Pseudo-hypoaldosteronism secondary to infantile urinary tract infections: role of ultrasound
Authors: Graziano Noemi , Agostoni Carlo , Chiaraviglio Francesca , Betti Céline , Piffer Arianna , Bianchetti Mario G. , Milani Gregorio P.
Published: January 2022

Background

The biochemical hallmarks of transient pseudo-hypoaldosteronism associated with a pyelonephritis include hyponatremia, hyperkalemia, and acidosis. We tested if the kidney-urinary tract ultrasound helps in predicting the diagnosis of overt pseudo-hypoaldosteronism in infants with a pyelonephritis.

Cases presentation

Between 2013 and 2020, we managed 71 previously healthy infants 4 weeks to 24 months of age with a pyelonephritis (42 males and 29 females) and made the biochemical diagnosis of pseudo-hypoaldosteronism in 17 (24%). Infants with and without pseudo-hypoaldosteronism did not significantly differ with respect to the prevalence of kidney-urinary tract ultrasound abnormalities, graded by means of the UTD classification system of urinary tract abnormalities.

Conclusions

Kidney-urinary tract ultrasound is almost routinely obtained in children with a febrile urinary tract infection. Our experience does not support the hypothesis that ultrasound might be relevant for the diagnosis of overt transient pseudo-hypoaldosteronism in babies affected by a urinary tract infection. Our data confirm the assumption that negative studies may be important for advancing clinical practice.
Nanopore adaptive sampling: a tool for enrichment of low abundance species in metagenomic samples
Authors: Martin Samuel , Heavens Darren , Lan Yuxuan , Horsfield Samuel , Clark Matthew D. , Leggett Richard M.
Published: January 2022

Adaptive sampling is a method of software-controlled enrichment unique to nanopore sequencing platforms. To test its potential for enrichment of rarer species within metagenomic samples, we create a synthetic mock community and construct sequencing libraries with a range of mean read lengths. Enrichment is up to 13.87-fold for the least abundant species in the longest read length library; factoring in reduced yields from rejecting molecules the calculated efficiency raises this to 4.93-fold. Finally, we introduce a mathematical model of enrichment based on molecule length and relative abundance, whose predictions correlate strongly with mock and complex real-world microbial communities.
Open chromatin interaction maps reveal functional regulatory elements and chromatin architecture variations during wheat evolution
Authors: Yuan Jingya , Sun Haojie , Wang Yijin , Li Lulu , Chen Shiting , Jiao Wu , Jia Guanghong , Wang Longfei , Mao Junrong , Ni Zhongfu , Wang Xiue , Song Qingxin
Published: January 2022

Background

Bread wheat (Triticum aestivum) is an allohexaploid that is generated by two subsequent allopolyploidization events. The large genome size (16 Gb) and polyploid complexity impede our understanding of how regulatory elements and their interactions shape chromatin structure and gene expression in wheat. The open chromatin enrichment and network Hi-C (OCEAN-C) is a powerful antibody-independent method to detect chromatin interactions between open chromatin regions throughout the genome.

Results

Here we generate open chromatin interaction maps for hexaploid wheat and its tetraploid and diploid relatives using OCEAN-C. The anchors of chromatin loops show high chromatin accessibility and are concomitant with several active histone modifications, with 67% of them interacting with multiple loci. Binding motifs of various transcription factors are significantly enriched in the hubs of open chromatin interactions (HOCIs). The genes linked by HOCIs represent higher expression level and lower coefficient expression variance than the genes linked by other loops, which suggests HOCIs may coordinate co-expression of linked genes. Thousands of interchromosomal loops are identified, while limited interchromosomal loops (0.4%) are identified between homoeologous genes in hexaploid wheat. Moreover, we find structure variations contribute to chromatin interaction divergence of homoeologs and chromatin topology changes between different wheat species. The genes with discrepant chromatin interactions show expression alteration in hexaploid wheat compared with its tetraploid and diploid relatives.

Conclusions

Our results reveal open chromatin interactions in different wheat species, which provide new insights into the role of open chromatin interactions in gene expression during the evolution of polyploid wheat.
Frequency of obesity and metabolic syndrome in childhood leukemia and lymphoma survivors
Authors: Kartal İbrahim , Alaçam Abdurrahman , Dağdemir Ayhan , Kara Cengiz , Dinçer Oğuz Salih , Albayrak Canan , Elli Murat
Published: January 2022

Objectives

In this study, it was aimed to determine the prevalence and clinical features of obesity and metabolic syndrome, which are long-term effects of survivors after treatment in children with leukemia and lymphoma.

Patients and Methods

Patients with leukemia and lymphoma, who were diagnosed between 2000 and 2012 (at least 2 two years after remission) were included. Data obtained through reviewing the family history, demographic characteristics, anthropometric measurements, and laboratory parameters (blood glucose, lipid, and insulin levels) were analyzed and compared at the time of diagnosis, after the treatment and at time of the study.

Results

Eighty nine patients (45 boys, 44 girls) were included (mean age: 14.7 ± 4.3 years): 77.5% had acute lymphoblastic leukemia, 11.2% had acute myeloid leukemia, and 11.2% had lymphoma. Overall, 46% patients had received radiotherapy, 7% had undergone surgery, and 2.2% had received stem cell transplantation in addition to chemotherapy. The mean duration of treatment was 2.4 years, and the time elapsed after treatment was 4.9 years. While only one had obesity at the diagnosis, a significant increase in obesity (20%), hypertension (15.7%), hyperglycemia (15%), insulin resistance (35%) were observed at the time of study, and family history of hypertension, dyslipidemia, and cardiovascular diseases were significantly higher in this subgroup.

Conclusion

The prevalence of metabolic syndorme is higher in children with leukemia and lymphoma after treatment, and begins to increase with the initiation of treatment and continues to increase over time. These children should be followed-up for late-effects including metabolic syndrome through life-long period.
A proposed magnetic resonance imaging grading system for the spectrum of central neonatal parasagittal hypoxic–ischaemic brain injury
Authors: Misser Shalendra Kumar , Lotz Jan Willem , Zaharie Stefan-Dan , Mchunu Nobuhle , Archary Moherndran , Barkovich Anthony James
Published: January 2022

Aim

To describe the spectrum of parasagittal injury on MRI studies performed on children following severe perinatal term hypoxia–ischaemia, using a novel MRI grading system, and propose a new central pattern correlated with neuropathologic features.

Methods

MR scans of 297 patients with perinatal term hypoxia–ischaemia were evaluated for typical patterns of brain injury. A total of 83 patients that demonstrated the central/basal ganglia–thalamus and perirolandic pattern of injury were categorised according to the degree of severity. The perirolandic injury was graded by the degree of interhemispheric widening, paracentral lobule involvement and perirolandic cortex destruction leading to a tiered categorisation. Of these 83 patients, 19 had the most severe subtype of injury. A detailed analysis of the clinical data of a subset of 11 of these 19 patients was conducted.

Results

We demonstrated the mild subtype in 21/83(25%), the moderate subtype in 22/83(27%) and the severe subtype in 21/83(25%). A fourth pattern was identified in 19/83(23%) patients with a diamond-shaped expansion of the interhemispheric fissure, concomitant thalamic, putaminal, hippocampal and other smaller substrate involvement indicative of the most destructive subtype.

Conclusions

We propose a new MR grading system of injury at the parasagittal perirolandic region related to severe, sustained central perinatal term hypoxia–ischaemia. We also introduce a previously undescribed pattern of injury, the most severe form of this spectrum, seen especially after prolongation of the second stage of labour. This constellation of high metabolic substrate, targeted tissue destruction is consistently demonstrated by MRI, termed the massive paramedian injury pattern.
Adhesion-related small bowel obstruction: deep learning for automatic transition-zone detection by CT
Authors: Vanderbecq Quentin , Ardon Roberto , De Reviers Antoine , Ruppli Camille , Dallongeville Axel , Boulay-Coletta Isabelle , D’Assignies Gaspard , Zins Marc
Published: January 2022

Background

To train a machine-learning model to locate the transition zone (TZ) of adhesion-related small bowel obstruction (SBO) on CT scans.

Materials and methods

We used 562 CTs performed in 2005–2018 in 404 patients with adhesion-related SBO. Annotation of the TZs was performed by experienced radiologists and trained residents using bounding boxes. Preprocessing involved using a pretrained model to extract the abdominopelvic region. We modeled TZ localization as a binary classification problem by splitting the abdominopelvic region into 125 patches. We then trained a neural network model to classify each patch as containing or not containing a TZ. We coupled this with a trained probabilistic estimation of presence of a TZ in each patch. The models were first evaluated by computing the area under the receiver operating characteristics curve (AUROC). Then, to assess the clinical benefit, we measured the proportion of total abdominopelvic volume classified as containing a TZ for several different false-negative rates.

Results

The probability of containing a TZ was highest for the hypogastric region (56.9%). The coupled classification network and probability mapping produced an AUROC of 0.93. For a 15% proportion of volume classified as containing TZs, the probability of highlighted patches containing a TZ was 92%.

Conclusion

Modeling TZ localization by coupling convolutional neural network classification and probabilistic localization estimation shows the way to a possible automatic TZ detection, a complex radiological task with a major clinical impact.
Stem cell-derived and circulating exosomal microRNAs as new potential tools for diabetic nephropathy management
Authors: Peng Lei , Chen Yu , Shi Shaoqing , Wen Heling
Published: January 2022

Background

Despite major advances in the treatment of diabetic nephropathy (DN) in recent years, it remains the most common cause of end-stage renal disease. An early diagnosis and therapy may slow down the DN progression. Numerous potential biomarkers are currently being researched. Circulating levels of the kidney-released exosomes and biological molecules, which reflect the DN pathology including glomerular and tubular dysfunction as well as mesangial expansion and fibrosis, have shown the potential for predicting the occurrence and progression of DN. Moreover, many experimental therapies are currently being investigated, including stem cell therapy and medications targeting inflammatory, oxidant, or pro-fibrotic pathways activated during the DN progression. The therapeutic potential of stem cells is partly depending on their secretory capacity, particularly exosomal microRNAs (Exo-miRs). In recent years, a growing line of research has shown the participation of Exo-miRs in the pathophysiological processes of DN, which may provide effective therapeutic and biomarker tools for DN treatment.

Methods

A systematic literature search was performed in MEDLINE, Scopus, and Google Scholar to collect published findings regarding therapeutic stem cell-derived Exo-miRs for DN treatment as well as circulating Exo-miRs as potential DN-associated biomarkers.

Findings

Glomerular mesangial cells and podocytes are the most important culprits in the pathogenesis of DN and, thus, can be considered valuable therapeutic targets. Preclinical investigations have shown that stem cell-derived exosomes can exert beneficial effects in DN by transferring renoprotective miRs to the injured mesangial cells and podocytes. Of note, renoprotective Exo-miR-125a secreted by adipose-derived mesenchymal stem cells can improve the injured mesangial cells, while renoprotective Exo-miRs secreted by adipose-derived stem cells (Exo-miR-486 and Exo-miR-215-5p), human urine‐derived stem cells (Exo-miR-16-5p), and bone marrow-derived mesenchymal stem cells (Exo-miR-let-7a) can improve the injured podocytes. On the other hand, clinical investigations have indicated that circulating Exo-miRs isolated from urine or serum hold great potential as promising biomarkers in DN.
The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review
Authors: Bian Donghui , Wu Yan , Song Guodong , Azizi Ramyar , Zamani Amir
Published: January 2022

Recently, mesenchymal stromal cells (MSCs) and also their exosome has become a game-changing tool in the context of tissue engineering and regenerative medicine. MSCs due to their competencies to establish skin cells, such as fibroblast and keratinocyte, and also their unique attribute to suppress inflammation in wound site has attracted increasing attention among scholars. In addition, MSC’s other capabilities to induce angiogenesis as a result of secretion of pro-angiogenic factors accompanied with marked anti-fibrotic activities, which mainly mediated by the releases matrix metalloproteinase (MMPs), make them a rational and effective strategy to accelerate wound healing with a small scar. Since the chief healing properties of the MSCs depend on their paracrine effects, it appears that MSCs-derived exosomes also can be an alternative option to support wound healing and skin regeneration as an innovative cell-free approach. Such exosomes convey functional cargos (e.g., growth factor, cytokine, miRNA, etc.) from MSCs to target cells, thereby affecting the recipient skin cells’ biological events, such as migration, proliferation, and also secretion of ECM components (e.g., collagen). The main superiorities of exosome therapy over parental MSCs are the diminished risk of tumor formation and also lower immunogenicity. Herein, we deliver an overview of recent in vivo reports rendering the therapeutic benefits of the MSCs-based therapies to ease skin wound healing, and so improving quality of life among patients suffering from such conditions.
The role and therapeutic potential of stem cells in skeletal muscle in sarcopenia
Authors: Cai Zijun , Liu Di , Yang Yuntao , Xie Wenqing , He Miao , Yu Dengjie , Wu Yuxiang , Wang Xiuhua , Xiao Wenfeng , Li Yusheng
Published: January 2022

Sarcopenia is a common age-related skeletal muscle disorder featuring the loss of muscle mass and function. In regard to tissue repair in the human body, scientists always consider the use of stem cells. In skeletal muscle, satellite cells (SCs) are adult stem cells that maintain tissue homeostasis and repair damaged regions after injury to preserve skeletal muscle integrity. Muscle-derived stem cells (MDSCs) and SCs are the two most commonly studied stem cell populations from skeletal muscle. To date, considerable progress has been achieved in understanding the complex associations between stem cells in muscle and the occurrence and treatment of sarcopenia. In this review, we first give brief introductions to sarcopenia, SCs and MDSCs. Then, we attempt to untangle the differences and connections between these two types of stem cells and further elaborate on the interactions between sarcopenia and stem cells. Finally, our perspectives on the possible application of stem cells for the treatment of sarcopenia in future are presented. Several studies emerging in recent years have shown that changes in the number and function of stem cells can trigger sarcopenia, which in turn leads to adverse influences on stem cells because of the altered internal environment in muscle. A better understanding of the role of stem cells in muscle, especially SCs and MDSCs, in sarcopenia will facilitate the realization of novel therapy approaches based on stem cells to combat sarcopenia.
Sin3a drives mesenchymal-to-epithelial transition through cooperating with Tet1 in somatic cell reprogramming
Authors: Feng Jiabao , Zhu Fugui , Ye Dan , Zhang Qingquan , Guo Xudong , Du Changsheng , Kang Jiuhong
Published: January 2022

Background

Identifying novel regulatory factors and uncovered mechanisms of somatic cell reprogramming will be helpful for basic research and clinical application of induced pluripotent stem cells (iPSCs). Sin3a, a multifunctional transcription regulator, has been proven to be involved in the maintenance of pluripotency in embryonic stem cells (ESCs), but the role of Sin3a in somatic cell reprogramming remains unclear.

Methods

RNA interference of Sin3a during somatic cell reprogramming was realized by short hairpin RNAs. Reprogramming efficiency was evaluated by the number of alkaline phosphatase (AP)-positive colonies andOct4-GFP-positive colonies. RNA sequencing was performed to identify the influenced biological processes after Sin3a knockdown and further confirmed by quantitative RT-PCR (qRT-PCR), western blotting and flow cytometry. The interaction between Sin3a and Tet1 was detected by coimmunoprecipitation. The enrichment of Sin3a and Tet1 at the epithelial gene promoters was measured by chromatin immunoprecipitation. Furthermore, DNA methylation patterns at the gene loci were investigated by hydroxymethylated DNA immunoprecipitation. Finally, Sin3a mutants that disrupt the interaction of Sin3a and Tet1 were also introduced to assess the importance of the Sin3a–Tet1 interaction during the mesenchymal-to-epithelial transition (MET) process.

Results

We found that Sin3a was gradually increased during OSKM-induced reprogramming and that knockdown of Sin3a significantly impaired MET at the early stage of reprogramming and iPSC generation. Mechanistic studies showed that Sin3a recruited Tet1 to facilitate the hydroxymethylation of epithelial gene promoters. Moreover, disrupting the interaction of Sin3a and Tet1 significantly blocked MET and iPSC generation.

Conclusions

Our studies revealed that Sin3a was a novel mediator of MET during early reprogramming, where Sin3a functioned as an epigenetic coactivator, cooperating with Tet1 to activate the epithelial program and promote the initiation of somatic cell reprogramming. These findings highlight the importance of Sin3a in the MET process and deepen our understanding of the epigenetic regulatory network of early reprogramming.
Ontology-based identification and prioritization of candidate drugs for epilepsy from literature
Authors: Müller Bernd , Castro Leyla Jael , Rebholz-Schuhmann Dietrich
Published: January 2022

Background

Drug repurposing can improve the return of investment as it finds new uses for existing drugs. Literature-based analyses exploit factual knowledge on drugs and diseases, e.g. from databases, and combine it with information from scholarly publications. Here we report the use of the Open Discovery Process on scientific literature to identify non-explicit ties between a disease, namely epilepsy, and known drugs, making full use of available epilepsy-specific ontologies.

Results

We identified characteristics of epilepsy-specific ontologies to create subsets of documents from the literature; from these subsets we generated ranked lists of co-occurring neurological drug names with varying specificity. From these ranked lists, we observed a high intersection regarding reference lists of pharmaceutical compounds recommended for the treatment of epilepsy. Furthermore, we performed a drug set enrichment analysis, i.e. a novel scoring function using an adaptive tuning parameter and comparing top-k ranked lists taking into account the varying length and the current position in the list. We also provide an overview of the pharmaceutical space in the context of epilepsy, including a final combined ranked list of more than 70 drug names.

Conclusions

Biomedical ontologies are a rich resource that can be combined with text mining for the identification of drug names for drug repurposing in the domain of epilepsy. The ranking of the drug names related to epilepsy provides benefits to patients and to researchers as it enables a quick evaluation of statistical evidence hidden in the scientific literature, useful to validate approaches in the drug discovery process.
Dihydromyricetin alleviates Escherichia coli lipopolysaccharide-induced hepatic injury in chickens by inhibiting the NLRP3 inflammasome
Authors: Shi Chenxi , Wang Jiaqi , Zhang Ruichen , Ishfaq Muhammad , Li Ying , Zhang Ruihui , Si Chuanbiao , Li Rui , Li Changwen , Liu Fangping
Published: January 2022

Dihydromyricetin (DHM), a flavonoid in vine tea, has many pharmacological activities, including anti-inflammatory and antibacterial effects. Lipopolysaccharide is the key inducer of inflammation in avian pathogenic Escherichia coli (E. coli) infection; however, the effect of DHM on E. coli lipopolysaccharide-induced hepatic injury remains unknown. The present study aimed to explore the role of the NLRP3 inflammasome in hepatic injury and the possible protective mechanisms of DHM against hepatic injury in chickens. The results showed that when chickens were administered lipopolysaccharide, liver damage was observed, accompanied by increased levels of serum transaminases and direct bilirubin. Additionally, hepatic expression levels of NLRP3 and caspase-1 p20, the subunit of caspase-1 that is cleaved after NLRP3 activation, significantly increased in liver injury. We found that treatment with MCC950, a specific NLRP3 inhibitor, significantly decreased serum transaminase activities, direct bilirubin content, and hepatic NLRP3 and caspase-1 p20 expression levels. DHM significantly reduced serum transaminase activities and direct bilirubin content and ameliorated histopathological and ultrastructural changes in the liver. DHM decreased hepatic levels of H2O2 and malondialdehyde and increased the activities of superoxide dismutase and glutathione peroxidase. Furthermore, DHM significantly decreased the expression levels of NLRP3, pro-caspase-1 and caspase-1 p20. Moreover, DHM reduced serum lactate dehydrogenase, IL-1β and IL-18 levels and repressed hepatic IL-1β, IL-18 and gasdermin A expression. The results demonstrated that the NLRP3 inflammasome was involved in the mechanism of lipopolysaccharide-induced hepatic injury. Furthermore, DHM could inhibit NLRP3 inflammasome activation and subsequent pyroptosis, eventually ameliorating E. coli lipopolysaccharide-induced liver injury.
African swine fever virus MGF360-11L negatively regulates cGAS-STING-mediated inhibition of type I interferon production
Authors: Yang Kaidian , Xue Ying , Niu Hui , Shi Chunwei , Cheng Mingyang , Wang Jianzhong , Zou Boshi , Wang Junhong , Niu Tianming , Bao Meiying , Yang Wentao , Zhao Dandan , Jiang Yanlong , Yang Guilian , Zeng Yan , Cao Xin , Wang Chunfeng
Published: January 2022

The type I interferon (IFN-I) signaling pathway is an important part of the innate immune response and plays a vital role in controlling and eliminating pathogens. African swine fever virus (ASFV) encodes various proteins to evade the host’s natural immunity. However, the molecular mechanism by which the ASFV-encoded proteins inhibit interferon production remains poorly understood. In the present study, ASFV MGF360-11L inhibited cGAS, STING, TBK1, IKKε, IRF7 and IRF3-5D mediated activation of the IFN-β and ISRE promoters, accompanied by decreases in IFN-β, ISG15 and ISG56 mRNA expression. ASFV MGF360-11L interacted with TBK1 and IRF7, degrading TBK1 and IRF7 through the cysteine, ubiquitin–proteasome and autophagy pathways. Moreover, ASFV MGF360-11L also inhibited the phosphorylation of TBK1 and IRF3 stimulated by cGAS-STING overexpression. Truncation mutation analysis revealed that aa 167-353 of ASFV MGF360-11L could inhibit cGAS-STING-mediated activation of the IFN-β and ISRE promoters. Finally, the results indicated that ASFV MGF360-11L plays a significant role in inhibiting IL-1β, IL-6 and IFN-β production in PAM cells (PAMs) infected with ASFV. In short, these results demonstrated that ASFV MGF360-11L was involved in regulating IFN-I expression by negatively regulating the cGAS signaling pathway. In summary, this study preliminarily clarified the molecular mechanism by which the ASFV MGF360-11L protein antagonizes IFN-I-mediated antiviral activity, which will help to provide new strategies for the treatment and prevention of ASF.