bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-22 regulates endometrial regeneration by enhancing tight junctions and orchestrating extracellular matrix
Authors: Ganieva Umida , Schneiderman Sylvia , Bu Pengli , Beaman Kenneth , Dambaeva Svetlana
Published: August 2022

The uterine endometrium uniquely regenerates after menses, postpartum, or after breaks in the uterine layer integrity throughout women’s lives. Direct cell–cell contacts ensured by tight and adherens junctions play an important role in endometrial integrity. Any changes in these junctions can alter the endometrial permeability of the uterus and have an impact on the regeneration of uterine layers. Interleukin 22 (IL-22) is a cytokine that is recognized for its role in epithelial regeneration. Moreover, it is crucial in controlling the inflammatory response in mucosal tissues. Here, we studied the role of IL-22 in endometrial recovery after inflammation-triggered abortion. Fecundity of mice was studied in consecutive matings of the same animals after lipopolysaccharide (LPS) (10 µg per mouse)-triggered abortion. The fecundity rate after the second mating was substantially different between IL-22 knockout (IL-22−/−) (9.1%) and wild-type (WT) (71.4%) mice (p < 0.05), while there was no difference between the groups in the initial mating, suggesting that IL-22 deficiency might be associated with secondary infertility. A considerable difference was observed between IL-22−/− and WT mice in the uterine clearance following LPS-triggered abortion. Gross examination of the uteri of IL-22−/− mice revealed non-viable fetuses retained inside the horns (delayed clearance). In contrast, all WT mice had completed abortion with total clearance after LPS exposure. We also discovered that IL-22 deficiency is associated with a decreased expression of tight junctions (claudin-2 and claudin-10) and cell surface pathogen protectors (mucin-1). Moreover, IL-22 has a role in the remodeling of the uterine tissue in the inflammatory environment by regulating epithelial–mesenchymal transition markers called E- and N-cadherin. Therefore, IL-22 contributes to the proper regeneration of endometrial layers after inflammation-triggered abortion. Thus, it might have a practical significance to be utilized as a treatment option postpartum (enhanced regeneration function) and in secondary infertility caused by inflammation (enhanced barrier/protector function).
Abnormal B cell glycosylation in autoimmunity: A new potential treatment strategy
Authors: Morel Marie , Pochard Pierre , Echchih Wiam , Dueymes Maryvonne , Bagacean Cristina , Jousse-Joulin Sandrine , Devauchelle-Pensec Valérie , Cornec Divi , Jamin Christophe , Pers Jacques-Olivier , Bordron Anne
Published: August 2022

Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are two autoimmune diseases characterised by the production of pathogenic autoreactive antibodies. Their aetiology is poorly understood. Nevertheless, they have been shown to involve several factors, such as infections and epigenetic mechanisms. They also likely involve a physiological process known as glycosylation. Both SLE T cell markers and pSS-associated autoantibodies exhibit abnormal glycosylation. Such dysregulation suggests that defective glycosylation may also occur in B cells, thereby modifying their behaviour and reactivity. This study aimed to investigate B cell subset glycosylation in SLE, pSS and healthy donors and to extend the glycan profile to serum proteins and immunoglobulins. We used optimised lectin-based tests to demonstrate specific glycosylation profiles on B cell subsets that were specifically altered in both diseases. Compared to the healthy donor B cells, the SLE B cells exhibited hypofucosylation, whereas only the pSS B cells exhibited hyposialylation. Additionally, the SLE B lymphocytes had more galactose linked to N-acetylglucosamine or N-acetylgalactosamine (Gal-GlcNAc/Gal-GalNAc) residues on their cell surface markers. Interestingly, some similar alterations were observed in serum proteins, including immunoglobulins. These findings indicate that any perturbation of the natural glycosylation process in B cells could result in the development of pathogenic autoantibodies. The B cell glycoprofile can be established as a preferred biomarker for characterising pathologies and adapted therapeutics can be used for patients if there is a correlation between the extent of these alterations and the severity of the autoimmune diseases.
Life cycle assessment of auto-tropically cultivated economic microalgae for final products such as food, total fatty acids, and bio-oil
Authors: Zhang Dan , An Siyuan , Yao Rao , Fu Wen , Han Yujie , Du Ming , Chen Zixi , Lei Anping , Wang Jiangxin
Published: August 2022

Life cycle assessment (LCA) is a powerful tool to evaluate environmentally sustainable production or consumption of various goods or services. Microalgae are single-celled green factories and good resources of biofuels, bioactive products, food ingredients, and degradable biomaterials. Currently, microalgae are also valuable for mitigating elevated greenhouse gases like CO2 levels and treatment of wastewater. LCA evaluation was limited and separated, majorly in microalgal biofuels and heterotrophic cultivation. Comparative LCA for different final algal products such as algal powder, bio-oil, total fatty acid, and residue recycling is still limited, especially autotrophic algal cultivation for products other than bio-oils and biofuels. Thus, we chose several autotrophic cultivated microalgae and made a comparative LCA among these selected species and a detailed step-by-step production in Chlorella sp. Results indicated that we could significantly reduce the production cost and lower environmental impacts by selecting algal species and final products, optimizing methods for algal cultivation, biomass separation, and drying process, and land selection plus electricity renewable energy, together with thermal power plants nearby for CO2 or flu gas. It shed light on the insight of microalgal consumption selection under current international requirements and challenges for carbon sequestration.
Femtosecond laser-assisted arcuate keratotomy for the management of corneal astigmatism in patients undergoing cataract surgery: Comparison with conventional cataract surgery
Authors: Ahn Hyunmin , Jun Ikhyun , Seo Kyoung Yul , Kim Eung Kweon , Kim Tae-im
Published: August 2022

Purpose

To assess the effects of femtosecond laser arcuate keratotomy with femtosecond laser-assisted cataract surgery in the management of corneal astigmatism, compared with conventional phacoemulsification cataract surgery.

Design

Retrospective comparative interventional case series.

Methods

A total of 2,498 eyes of consecutive patients who presented with 3.00 diopters (D) or under of astigmatism were included. The patients were treated with conventional phacoemulsification cataract surgery (conventional group) and femtosecond laser arcuate keratotomy with femtosecond laser-assisted cataract surgery (femtosecond group).

Results

Surgically induced astigmatism (SIA) was higher in the femtosecond group than the conventional group (0.215, p < 0.001). Difference vector (DV) was lower in the femtosecond group (-0.136, p < 0.001). The cut-off value of the overcorrection in the femtosecond group was 0.752 D of target induced astigmatism (TIA). For patients with TIA 0.75 D or under, DV and the value of index of success (TIA into DV) were significantly higher in the femtosecond group (p = 0.022 and < 0.001). The overcorrection ratios were 48.8% in the conventional and 58.9% in the femtosecond group. (p < 0.001). For patients with TIA over 0.75 D, SIA and correction index (TIA into SIA) was higher in femtosecond group (0.310 and 0.250, p < 0.001 and < 0.001, respectively). Absolute angle of error was 20.612 ± 18.497 in the femtosecond group and higher than the conventional group (2.778, p = 0.010).

Conclusion

Femtosecond laser arcuate keratotomy in cataract surgery was effective in SIA between 0.75 to 3.00 D of corneal astigmatism. However, the overcorrection in the lower astigmatism and angle of error in the higher astigmatism were due to the postoperative corneal astigmatism not decreasing as much as SIA. Overcoming these challenges will lead to better management of corneal astigmatism.
Striatal dopaminergic lesions contributed to the disease severity in progressive supranuclear palsy
Authors: Chen Ming-Jia , Lu Jia-Ying , Li Xin-Yi , Jiao Fang-Yang , Zuo Chuan-Tao , Wang Jian , Liu Feng-Tao , Yang Yu-Jie
Published: August 2022

Background

Reduced dopamine transporter (DAT) binding in the striatum has been reported in patients with progressive supranuclear palsy (PSP). However, the relationship between striatal dopaminergic lesions and the disease severity of PSP remains to be explored.

Objective

To investigate the contributions of striatal dopaminergic lesions to the disease severity of PSP.

Methods

One hundred patients with clinically diagnosed PSP were consecutively enrolled in this study. The disease severity was systemically assessed using the PSP rating scale (PSPrs), and the dopaminergic lesions were assessed using the 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane positron emission tomography (11C-CFT PET) imaging. To explore the correlations between striatal DAT bindings and the disease severity, both the region-wise and voxel-wise analysis were adopted. Partial correlations and multiple linear regressions were performed to investigate the contribution of striatal dopaminergic lesions to the disease severity in PSP.

Results

Sixty-three patients of PSP with Richardson’s syndrome (PSP-RS) and 37 patients with PSP-non-RS were finally included. The disease severity in PSP-RS was much heavier than that in the PSP-non-RS. The DAT bindings in the caudate and anterior putamen correlated significantly with the PSPrs total scores, mainly in the domains of history, mentation, bulbar, and ocular motor symptoms. The striatal DAT bindings (caudate) contributed significantly to the disease severity of PSP, independent of the motor, cognition, emotion and behavioral dysfunctions.

Conclusion

Our study highlighted the independent contribution of striatal dopaminergic lesions to the disease severity in PSP.
Deep attention super-resolution of brain magnetic resonance images acquired under clinical protocols
Authors: Li Bryan M. , Castorina Leonardo V. , Valdés Hernández Maria del C. , Clancy Una , Wiseman Stewart J. , Sakka Eleni , Storkey Amos J. , Jaime Garcia Daniela , Cheng Yajun , Doubal Fergus , Thrippleton Michael T. , Stringer Michael , Wardlaw Joanna M.
Published: August 2022

Vast quantities of Magnetic Resonance Images (MRI) are routinely acquired in clinical practice but, to speed up acquisition, these scans are typically of a quality that is sufficient for clinical diagnosis but sub-optimal for large-scale precision medicine, computational diagnostics, and large-scale neuroimaging collaborative research. Here, we present a critic-guided framework to upsample low-resolution (often 2D) MRI full scans to help overcome these limitations. We incorporate feature-importance and self-attention methods into our model to improve the interpretability of this study. We evaluate our framework on paired low- and high-resolution brain MRI structural full scans (i.e., T1-, T2-weighted, and FLAIR sequences are simultaneously input) obtained in clinical and research settings from scanners manufactured by Siemens, Phillips, and GE. We show that the upsampled MRIs are qualitatively faithful to the ground-truth high-quality scans (PSNR = 35.39; MAE = 3.78E−3; NMSE = 4.32E−10; SSIM = 0.9852; mean normal-appearing gray/white matter ratio intensity differences ranging from 0.0363 to 0.0784 for FLAIR, from 0.0010 to 0.0138 for T1-weighted and from 0.0156 to 0.074 for T2-weighted sequences). The automatic raw segmentation of tissues and lesions using the super-resolved images has fewer false positives and higher accuracy than those obtained from interpolated images in protocols represented with more than three sets in the training sample, making our approach a strong candidate for practical application in clinical and collaborative research.
Big data analytics frameworks for the influence of gut microbiota on the development of tic disorder
Authors: Fan Fei , Bian Zhaoxiang , Zhang Xuan , Wu Hongwei , Wang Simeng , Zhang Si , Wang Qiong , Han Fei
Published: August 2022

The association between gut microbiota and psychiatric disorders has received increasing research attention. Meanwhile, big data analysis has been utilized in many filed including business, human healthcare analysis, etc. The primary objective of this article was to provide insights into Big Data Analytics (BDA) to clarify the association between gut microbiota and TD (Tic disorder). Specifically, we investigated the recent studies related to gut microbiota composition differences in patients with TD compared to health people. We searched on PubMed and Embase (Ovid) databases for relevant published articles until June 15, 2021. A total of 78 TD and 62 health control stool samples were examined. Case-control design was applied in all the studies. No consensus was evident in α-diversity and β-diversity. The abundance of phyla Bacteroidetes and Firmicutes was predominant at the taxa level. Gut microbiota taxonomic differences were found between TD cases and controls, though inconsistently across studies. Further studies are needed to reveal the underlying pathophysiology of TD and correlation between TD and gut microbiota composition.
Effectiveness of gastrodin for migraine: A meta-analysis
Authors: Zhou Xiu , Shao Jingyi , Xie Xiuzhen , Xu Yingqi , Shao Tianyu , Jin Zhuqing
Published: August 2022

Background

Gastrodia elata Blume (GEB), a traditional Chinese medicine, has been widely used to treat dizziness, numbness of limbs, and infantile convulsion, among other issues. Gastrodin is the main component of GEB. This meta-analysis aimed to evaluate the efficacy and safety of gastrodin in the treatment of migraine.

Methods

Ten electronic databases, namely the Cochrane Library, Embase, EBSCO, PubMed, Web of Science, CENTRAL, CNKI (China National Knowledge Infrastructure), CBM (Chinese Biomedicine Database), WanFang, and VIP (Chinese Scientific Journals Database), were searched for randomized controlled trials (RCTs) of gastrodin for migraine published before September 2021. The data were analyzed by RevMan 5.3 software and evaluated by GRADEpro.

Results

A total of 1,332 subjects were included in 16 RCTs. The meta-analysis showed that gastrodin was significantly effective in treating migraine (RR = 1.21, 95%CI = [1.17, 1.27]), reducing the pain degree (MD = −1.65, 95% CI = [−2.28, −1.02]), reducing the frequency of migraine attack (SMD = −2.77, 95% CI = [−3.92, −1.62]), shortening the duration of migraine attack (SMD = −1.64, 95% CI = [−2.35, −0.93]), and slowing average arterial cerebral blood flow velocity (SMD = −3.19, 95% CI = [−5.21, −1.17]), as well as being safe.

Conclusions

This systematic review revealed gastrodin is effective and safe in the treatment of migraine.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=197094, identifier: CRD42020197094.
Predictive role of shock index in the early formation of cerebral infarction in patients with TBI and cerebral herniation
Authors: Hu Xiaofang , Tian Jun , Xie Jinhua , Zheng Shaorui , Wei Liangfeng , Zhao Lin , Wang Shousen
Published: August 2022

Background and purpose

Traumatic brain injury (TBI) with brain herniation predisposes to posttraumatic cerebral infarction (PTCI), which in turn seriously affects the prognosis of patients. At present, there is a lack of effective indicators that can accurately predict the occurrence of PTCI. We aimed to find possible risk factors for the development of PTCI by comparing the preoperative and postoperative clinical data of TBI patients with brain herniation.

Methods

The clinical data of 120 patients with craniocerebral trauma and brain herniation were retrospectively analyzed. Among them, 54 patients had cerebral infarction within 3–7 days after injury. The two groups of patients were compared through univariate and multivariate logistic regression analysis, and a classification tree model and a nomogram model were constructed. Finally, receiver operating characteristic curve analysis and decision curve analysis were conducted to analyze the clinical utility of the prediction model.

Results

Logistic regression analysis showed that factors like the Glasgow Coma Scale (GCS) score (P = 0.002), subarachnoid hemorrhage (SAH) (P = 0.005), aspiration pneumonia (P < 0.001), decompressive craniectomy (P < 0.05), intracranial pressure (ICP) monitoring (P = 0.006), the shock index (SI) (P < 0.001), the mean arterial pressure (MAP) (P = 0.005), and blood glucose (GLU) (P < 0.011) appeared to show a significant statistical correlation with the occurrence of infarction (P < 0.05), while age, sex, body temperature (T), D-dimer levels, and coagulation tests were not significantly correlated with PTCI after cerebral herniation. Combined with the above factors, Classification and Regression Tree was established, and the recognition accuracy rate reached 76.67%.

Conclusions

GCS score at admission, no decompressive craniectomy, no ICP monitoring, combined SAH, combined aspiration pneumonia, SI, MAP, and high GLU were risk factors for infarction, of which SI was the primary predictor of PTCI in TBI with an area under the curve of 0.775 (95% CI = 0.689–0.861). Further large-scale studies are needed to confirm these results.
A real-time fMRI neurofeedback system for the clinical alleviation of depression with a subject-independent classification of brain states: A proof of principle study
Authors: Pereira Jaime A. , Ray Andreas , Rana Mohit , Silva Claudio , Salinas Cesar , Zamorano Francisco , Irani Martin , Opazo Patricia , Sitaram Ranganatha , Ruiz Sergio
Published: August 2022

Most clinical neurofeedback studies based on functional magnetic resonance imaging use the patient's own neural activity as feedback. The objective of this study was to create a subject-independent brain state classifier as part of a real-time fMRI neurofeedback (rt-fMRI NF) system that can guide patients with depression in achieving a healthy brain state, and then to examine subsequent clinical changes. In a first step, a brain classifier based on a support vector machine (SVM) was trained from the neural information of happy autobiographical imagery and motor imagery blocks received from a healthy female participant during an MRI session. In the second step, 7 right-handed female patients with mild or moderate depressive symptoms were trained to match their own neural activity with the neural activity corresponding to the “happiness emotional brain state” of the healthy participant. The training (4 training sessions over 2 weeks) was carried out using the rt-fMRI NF system guided by the brain-state classifier we had created. Thus, the informative voxels previously obtained in the first step, using SVM classification and Effect Mapping, were used to classify the Blood-Oxygen-Level Dependent (BOLD) activity of the patients and converted into real-time visual feedback during the neurofeedback training runs. Improvements in the classifier accuracy toward the end of the training were observed in all the patients [Session 4–1 Median = 6.563%; Range = 4.10–27.34; Wilcoxon Test (0), 2-tailed p = 0.031]. Clinical improvement also was observed in a blind standardized clinical evaluation [HDRS CE2-1 Median = 7; Range 2 to 15; Wilcoxon Test (0), 2-tailed p = 0.016], and in self-report assessments [BDI-II CE2-1 Median = 8; Range 1–15; Wilcoxon Test (0), 2-tailed p = 0.031]. In addition, the clinical improvement was still present 10 days after the intervention [BDI-II CE3-2_Median = 0; Range −1 to 2; Wilcoxon Test (0), 2-tailed p = 0.50/ HDRS CE3-2 Median = 0; Range −1 to 2; Wilcoxon Test (0), 2-tailed p = 0.625]. Although the number of participants needs to be increased and a control group included to confirm these findings, the results suggest a novel option for neural modulation and clinical alleviation in depression using noninvasive stimulation technologies.
Solving the spike feature information vanishing problem in spiking deep Q network with potential based normalization
Authors: Sun Yinqian , Zeng Yi , Li Yang
Published: August 2022

Brain-inspired spiking neural networks (SNNs) are successfully applied to many pattern recognition domains. The SNNs-based deep structure has achieved considerable results in perceptual tasks, such as image classification and target detection. However, applying deep SNNs in reinforcement learning (RL) tasks is still a problem to be explored. Although there have been previous studies on the combination of SNNs and RL, most focus on robotic control problems with shallow networks or using the ANN-SNN conversion method to implement spiking deep Q networks (SDQN). In this study, we mathematically analyzed the problem of the disappearance of spiking signal features in SDQN and proposed a potential-based layer normalization (pbLN) method to train spiking deep Q networks directly. Experiment shows that compared with state-of-art ANN-SNN conversion method and other SDQN works, the proposed pbLN spiking deep Q networks (PL-SDQN) achieved better performance on Atari game tasks.
Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer’s disease
Authors: Rudajev Vladimir , Novotny Jiri
Published: August 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder that is one of the most devastating and widespread diseases worldwide, mainly affecting the aging population. One of the key factors contributing to AD-related neurotoxicity is the production and aggregation of amyloid β (Aβ). Many studies have shown the ability of Aβ to bind to the cell membrane and disrupt its structure, leading to cell death. Because amyloid damage affects different parts of the brain differently, it seems likely that not only Aβ but also the nature of the membrane interface with which the amyloid interacts, helps determine the final neurotoxic effect. Because cholesterol is the dominant component of the plasma membrane, it plays an important role in Aβ-induced toxicity. Elevated cholesterol levels and their regulation by statins have been shown to be important factors influencing the progression of neurodegeneration. However, data from many studies have shown that cholesterol has both neuroprotective and aggravating effects in relation to the development of AD. In this review, we attempt to summarize recent findings on the role of cholesterol in Aβ toxicity mediated by membrane binding in the pathogenesis of AD and to consider it in the broader context of the lipid composition of cell membranes.
Phytosterol intake and overall survival in newly diagnosed ovarian cancer patients: An ambispective cohort study
Authors: Zhao Jun-Qi , Hao Ying-Ying , Gong Ting-Ting , Wei Yi-Fan , Zheng Gang , Du Zong-Da , Zou Bing-Jie , Yan Shi , Liu Fang-Hua , Gao Song , Wu Qi-Jun , Zhao Yu-Hong
Published: August 2022

Background

Phytosterol is a bioactive compound existing in all plant foods, which might have anticancer properties. The aim of this study was to first assess the impact of the pre-diagnosis phytosterol intake on overall survival (OS) of patients with ovarian cancer (OC).

Materials and methods

This ambispective cohort study recruited 703 newly diagnosed OC patients to investigate the aforementioned associations. Dietary intake was assessed using a validated 111-item food frequency questionnaire. Deaths were ascertained until March 31, 2021, through active follow-up and medical records. Cox proportional hazards regression models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

During the median follow-up of 37.17 months, 130 deaths occurred. The median age at diagnosis of 703 OC patients was 53.00 (interquartile: 48.00–60.00) years. Of these, almost half patients (48.08%) were diagnosed in advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III-IV). Additionally, more than half patients were serous carcinoma (68.14%), poorly differentiated (85.21%), and no residual lesions (78.66%). Patients consumed the highest tertile of dietary campesterol (HR = 0.54, 95% CI = 0.31–0.94, P trend < 0.05), stigmasterol (HR = 0.60, 95% CI = 0.37–0.98), and β-sitosterol (HR = 0.63, 95% CI = 0.40–0.99) were significantly associated with better OS compared with those with the lowest tertile of intake. The curvilinear associations were observed between total phytosterols and β-sitosterol intake and OC survival (P non-linear < 0.05). Significant associations were generally consistent across different subgroups stratified by demographical, clinical, and immunohistochemical characteristics. Moreover, there were significant interactions between phytosterol intake and age at diagnosis, body mass index, as well as expressions of Wilms’ tumor-1 and Progestogen Receptor (all P interaction < 0.05).

Conclusion

Pre-diagnosis higher campesterol, stigmasterol, and β-sitosterol intake were associated with better survival among OC patients.
Non-nutritive sweeteners and their impacts on the gut microbiome and host physiology
Authors: Richardson Irene L. , Frese Steven A.
Published: August 2022

Non-nutritive sweeteners (NNS) are broadly incorporated into foods, especially those representing a growing share of the beverage market. NNS are viewed as a noncaloric and desirable alternative to sugar-based sweeteners and are thought to contribute to reducing overall caloric intake. While these compounds have been studied extensively and have long been considered inert, new research has presented a different view and raises new questions about the effects of NNS on human physiology. Namely, the influence on glucose responses, the gastrointestinal epithelium, and the gut microbiome. As the gut microbiome is now recognized as a major mediator of human health and perturbations to this community are generally associated with negative health trajectories or overt disease, interactions between NNS and the gut microbiome are of increasing interest to clinicians and researchers. Several NNS compounds are now hypothesized to affect human physiology by modulating the gut microbiome, though the mechanism for this action remains unclear. The purpose of this review is to discuss the history and current knowledge of NNS, their reported utility and effects on host physiology and the gut microbiome, and describes a model for investigating the underlying mechanism behind reported effects of NNS on the gut microbiome.
An integrated somatic and germline approach to aid interpretation of germline variants of uncertain significance in cancer susceptibility genes
Authors: Schwartz Alison , Manning Danielle K. , Koeller Diane R. , Chittenden Anu , Isidro Raymond A. , Hayes Connor P. , Abraamyan Feruza , Manam Monica Devi , Dwan Meaghan , Barletta Justine A. , Sholl Lynette M. , Yurgelun Matthew B. , Rana Huma Q. , Garber Judy E. , Ghazani Arezou A.
Published: August 2022

Genomic profiles of tumors are often unique and represent characteristic mutational signatures defined by DNA damage or DNA repair response processes. The tumor-derived somatic information has been widely used in therapeutic applications, but it is grossly underutilized in the assessment of germline genetic variants. Here, we present a comprehensive approach for evaluating the pathogenicity of germline variants in cancer using an integrated interpretation of somatic and germline genomic data. We have previously demonstrated the utility of this integrated approach in the reassessment of pathogenic germline variants in selected cancer patients with unexpected or non-syndromic phenotypes. The application of this approach is presented in the assessment of rare variants of uncertain significance (VUS) in Lynch-related colon cancer, hereditary paraganglioma-pheochromocytoma syndrome, and Li-Fraumeni syndrome. Using this integrated method, germline VUS in PMS2, MSH6, SDHC, SHDA, and TP53 were assessed in 16 cancer patients after genetic evaluation. Comprehensive clinical criteria, somatic signature profiles, and tumor immunohistochemistry were used to re-classify VUS by upgrading or downgrading the variants to likely or unlikely actionable categories, respectively. Going forward, collation of such germline variants and creation of cross-institutional knowledgebase datasets that include integrated somatic and germline data will be crucial for the assessment of these variants in a larger cancer cohort.
Exploring the origin of the cancer stem cell niche and its role in anti-angiogenic treatment for glioblastoma
Authors: Akindona Funto A. , Frederico Stephen C. , Hancock John C. , Gilbert Mark R.
Published: August 2022

Cancer stem cells are thought to be the main drivers of tumorigenesis for malignancies such as glioblastoma (GBM). They are maintained through a close relationship with the tumor vasculature. Previous literature has well-characterized the components and signaling pathways for maintenance of this stem cell niche, but details on how the niche initially forms are limited. This review discusses development of the nonmalignant neural and hematopoietic stem cell niches in order to draw important parallels to the malignant environment. We then discuss what is known about the cancer stem cell niche, its relationship with angiogenesis, and provide a hypothesis for its development in GBM. A better understanding of the mechanisms of development of the tumor stem cell niche may provide new insights to potentially therapeutically exploit.
Circular RNAs regulate parental gene expression: A new direction for molecular oncology research
Authors: Wang Haicun , Gao Xin , Yu Shaobo , Wang Weina , Liu Guanglin , Jiang Xingming , Sun Dongsheng
Published: August 2022

CircRNAs have been the focus of research in recent years. They are differentially expressed in various human tumors and can regulate oncogenes and tumor suppressor genes expression through various mechanisms. The diversity, stability, evolutionary conservatism and cell- or tissue-specific expression patterns of circRNAs also endow them with important regulatory roles in promoting or inhibiting tumor cells malignant biological behaviors progression. More interestingly, emerging studies also found that circRNAs can regulate not only other genes expression, but also their parental gene expression and thus influence tumors development. Apart from some conventional features, circRNAs have a certain specificity in the regulation of parental gene expression, with a higher proportion affecting parental gene transcription and easier translation into protein to regulate parental gene expression. CircRNAs are generally thought to be unable to produce proteins and therefore the protein-coding ability exhibited by circRNAs in regulating parental gene expression is unique and indicates that the regulatory effects of parental gene expression by circRNAs are not only a competitive binding relationship, but also a more complex molecular relationship between circRNAs and parental gene, which deserves further study. This review summarizes the molecular mechanisms of circRNAs regulating parental gene expression and their biological roles in tumorigenesis and development, aiming to provide new ideas for the clinical application of circRNAs in tumor-targeted therapy.
Rare pulmonary embolism in a pregnant patient: A primary diffused pulmonary artery myxofibrosarcoma case report
Authors: Xiang Kanghui , Liu Lu , Li Hui-Jun , Zhang Guang-Wei
Published: August 2022

A 37-year-old female patient presented with shortness of breath, cough, and chest pain complaints from the 12th week of her first pregnancy. At the 28th week, labor induction had to be performed because of severe dyspnea and hyoxemia. Thereafter, a diffused pulmonary embolism was detected by echocardiography and CT angiography, without histological diagnosis. Pulmonary endarterectomy was performed, and it was found during operation that a huge, lobular mass originated in the posterior wall and extended throughout the vasculature of both lungs, and a mucinous pellicle covered the entire pulmonary endothelium. Pathology revealed a low-grade myxofibrosarcoma with positive vimentin and SMA, partially positive CD-34.
The Sinai Robotic Surgery Trial in HPV-related oropharyngeal squamous cell carcinoma (SIRS 2.0 trial) – study protocol for a phase II non-randomized non-inferiority trial
Authors: Chai Raymond L. , Ferrandino Rocco M. , Barron Christine , Donboli Kianoush , Roof Scott A. , Khan Mohemmed N. , Teng Marita S. , Posner Marshall R. , Bakst Richard L. , Genden Eric M.
Published: August 2022

Background

Human papillomavirus associated oropharyngeal squamous cell carcinoma (HPVOPSCC) usually affects a younger patient population. As such, the risk for long term toxicity associated with therapy is an important consideration. Multiple trials focused on de-escalation of therapy to preserve survival outcomes while minimizing treatment toxicity are currently in progress, however the question of which patients are ideal candidates for de-escalation remains unanswered. Circulating tumor DNA (cfHPVDNA) has emerged as a means of monitoring disease in patients with HPVOPSCC. Undetectable postoperative cfHPVDNA levels portend a better prognosis and by extension, may identify ideal candidates for de-escalation therapy. We propose an overview and rationale for a new institutional clinical trial protocol focusing on the use of cfHPVDNA to risk stratify patients for adjuvant therapy. We hypothesize that many surgical patients currently receiving radiation therapy may be clinically observed without adjuvant therapy.

Methods

Patients with measurable cfHPVDNA and clinically resectable HPVOPSCC will undergo TORS resection of tumors and neck dissection. Patients with undetectable cfHPVDNA at 3 weeks post-op will be allocated to low or high-risk treatment protocol groups. The low risk group consists of patients with <4 positive lymph nodes, ≤2 mm extranodal extension (ENE), and perineural invasion (PNI) or lymphovascular invasion (LVI) alone. The high-risk group is made up of patients with ≥4 positive lymph nodes, gross ENE, positive margins, N2c disease and/or the combination of both PNI and LVI. The low-risk group will be allocated to an observation arm, while the high-risk group will receive 46 Gy of adjuvant radiotherapy and weekly cisplatin therapy. The primary outcome of interest is 2-year disease recurrence with secondary outcomes of 2-year disease free survival, locoregional control, overall survival, and quality of life measures. A sample of 126 patients in the low-risk group and 73 patients in the high-risk group will be required to evaluate non-inferiority to the standard of care.

Discussion

This study will provide much needed recurrence and survival data for patients that undergo primary TORS followed by observation or de-escalated adjuvant therapy. Additionally, it will help delineate the role of cfHPVDNA in the risk stratification of patients that undergo treatment de-intensification.
Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells
Authors: Basilico Bernadette , Palamà Ilaria Elena , D’Amone Stefania , Lauro Clotilde , Rosito Maria , Grieco Maddalena , Ratano Patrizia , Cordella Federica , Sanchini Caterina , Di Angelantonio Silvia , Ragozzino Davide , Cascione Mariafrancesca , Gigli Giuseppe , Cortese Barbara
Published: August 2022

The complexity of the microenvironment effects on cell response, show accumulating evidence that glioblastoma (GBM) migration and invasiveness are influenced by the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition (EMT) is a well-recognized driving force of the invasive behavior of cancer. However, the primary mechanisms of EMT initiation and progression remain unclear. We have previously showed that certain substrate stiffness can selectively stimulate human GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies several known EMT mediators to uncover the reason of the regulation and response to these stiffnesses. Our results revealed that changing the rigidity of the mechanical environment tuned the response of both cell lines through change in morphological features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions in an interrelated manner. Specifically, a stiffer microenvironment induced a mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic ROS expression and lower mitochondrial ROS. Finally, we observed that cells more motile showed a more depolarized mitochondrial membrane potential. Unravelling the process that regulates GBM cells’ infiltrative behavior could provide new opportunities for identification of new targets and less invasive approaches for treatment.
Protective effect of inhaled corticosteroid on children with asthma with Mycoplasma pneumoniae pneumonia
Authors: Wei Bing , Dang Yan-Hong , Liu Xiang-Ping , Li Miao
Published: August 2022

Background

The aim of this study was to determine the differences in the characteristics of Mycoplasma pneumoniae pneumonia (MPP) in children with and without asthma and in children with asthma with and without inhaled corticosteroid (ICS) therapy in order to determine the risk factors for asthma exacerbation and the effect of regular ICS therapy on children with asthma with MPP.

Materials and methods

Children with MPP were divided into two groups according to whether they had a history of asthma. Children with asthma were further divided into an ICS therapy group and a group without ICS therapy. The clinical characteristics, laboratory test results, and pulmonary images were compared between the children with and without asthma. Differences in the severity of acute exacerbation were compared between the children with asthma in the ICS therapy and without ICS therapy groups. Multivariable logistic regression was used to determine the risk factors for exacerbation of MPP in children with asthma.

Results

In children with MPP, the differences in the eosinophil counts; total immunoglobulin E (IgE), C-reactive protein, procalcitonin (PCT), and lactate dehydrogenase (LDH) levels; and fever duration, wheezing, extrapulmonary complications, oxygen saturation < 92%, severe pneumonia, pleural effusion, co-infection with other pathogens, and lobar pneumonia between children with and without asthma were statistically significant. Among children with asthma with MPP, those in the ICS therapy group were less likely to experience an exacerbation, and exacerbations were less severe than those in the without ICS therapy group. The multivariable logistic regression analysis showed that the ICS therapy was an independent protective factor against exacerbation.

Conclusion

Among children with MPP, the chance of wheezing was higher in children with asthma than in children without asthma. The ICS therapy was a protective factor against exacerbation in children with asthma with MPP.
Case report and literature review: A de novo pathogenic missense variant in ACTN4 gene caused rapid progression to end-stage renal disease
Authors: He Zhechi , Wu Ke , Xie Wenqing , Chen Jianghua
Published: August 2022

Background

Focal segmental glomerulosclerosis (FSGS) is a histopathological diagnosis of the sclerosis of glomeruli and the damage to renal podocytes. FSGS affects the filtration function of the kidneys and results in nephrotic syndrome (NS) in children and adults. FSGS is a clinically and genetically heterogeneous disorder. FSGS-1 [OMIM #603278] is one of the progressive hereditary renal diseases. It is caused by heterozygous variants of theactinin alpha 4(ACTN4) [OMIM*604638] gene on chromosome 19q13.2 in a dominant inheritance (AD) manner. With the recent development of whole-exome sequencing (WES), 22 (including our case) pathogenic or likely pathogenic variants have been identified inACTN4gene.

Case presentation

We reported a 17-year-old Chinese girl who was hospitalized with foamy urine, nausea and vomiting. Laboratory tests revealed increased levels of serum creatinine and urea nitrogen. Ultrasonography demonstrated bilaterally reduced size of kidneys. The primary diagnoses were NS and chronic kidney disease stage 5 (CKD5). The hemodialysis was initiated in 48 h after admission. After 4 months of treatment, the patient received an allogeneic kidney transplantation from her father. A novel heterozygous missense variant c.494C > T (p.A165V) in theACTN4gene was found by WES in the patient. This variant was confirmed by Sanger sequencing. The computational simulation of the stability of mutant protein (p.A165V) was decreased. Interatomic interactions of the p.A165V site were increased, and it might be associated with the increased ubiquitylation in the vicinity of the mutant site.

Conclusion

As per the guidelines of the American College of Medical Genetics and Genomics for interpreting sequence variants, the novel heterozygous missense variant was pathogenic (PS2 + PM1 + PM2 + PP3 + PP4). It should be noted that the early onset of severe proteinuria with a poor prognosis is an important and universal symptom for most genetic FSGS. If necessary, genetic screening is recommended.
Clinical evaluation of acute necrotizing encephalopathy in children
Authors: Fan Xiaowei , Huang Li , Li Suyun , Yang Sida , Song Yongling , Chen Qinglian , Xiong Yumei , Peng Qiuyan , Ma Wencheng , Hu Dandan , Li Peiqing
Published: August 2022

Objective

Acute necrotizing encephalopathy (ANE) is a rare but severe encephalopathy and is associated with a high morbidity and mortality. We aimed to analyze and compare the clinical features and predictive indicators of pediatric ANE.

Materials and methods

This retrospective study included children with ANE diagnosed at Guangzhou Women and Children’s Medical Center between November 2018 and January 2020. Pediatric patients’ information, including clinical characteristics, laboratory tests, neuroelectrophysiology and brain magnetic resonance imaging (MRI) findings, MRI score, brainstem auditory evoked potential (BAEP) grades, ANE severity scores (ANE-SS), and modified Rankin scale (mRS), were collected.

Results

Twelve ANE patients were included. Among them, one patient (8.3%) died from brainstem dysfunction, one (8.3%) recovered and 10 (83.3%) experienced neurological sequelae. All patients had an initial viral infection and neurological symptoms such as acute disturbance of consciousness (ADOC) or seizure, and the interval from onset of the disease to neurological manifestations was 3 (1.25–3) days. MRI score-I ranged from 1 to 3 (1.8 ± 0.7), MRI score-II ranged from 1 to 4 (2.5 ± 1.1). ANE-SS varied from 1 to 6 (3.9 ± 1.3). The scores of mRS were from 0 to 6 (2.9 ± 1.7). Higher MRI score were associated with worse outcomes, while the BAEP grade and ANE-SS score were not significantly associated with mRS.

Conclusion

ANE is a severe encephalopathy syndrome with rapid progression, resulting in serious neurological sequelae. Compared with BAEP grade and ANE-SS, brain MRI shows more comprehensive advantages in predicting the prognosis of ANE patients. More in-depth research and better indicators are still needed to support the evaluation and treatment of ANE.
Every breath counts: Lessons learned in developing a training NICU in Northern Tanzania
Authors: Swanson Stephen J. , Martinez Kendra K. , Shaikh Henna A. , Philipo Godbless M. , Martinez Jarian , Mushi Evelyine J.
Published: August 2022

Introduction

Neonatal mortality rates in resource-limited hospitals of Sub-Saharan Africa (SSA) remain disproportionately high and are likely underestimated due to misclassification of extremely preterm births as “stillbirths” or “abortions”, incomplete death registries, fear of repercussions from hospital and governmental authorities, unrecorded village deaths, and cultural beliefs surrounding the viability of premature newborns. While neonatology partnerships exist between high income countries and hospitals in SSA, efforts have largely been directed toward improving newborn survival through neonatal resuscitation training and provision of equipment to nascent neonatal intensive care units (NICUs). These measures are incomplete and fail to address the challenges which NICUs routinely face in low-resource settings. We draw on lessons learned in the development of a low-technology referral NICU in Tanzania that achieved an overall 92% survival rate among infants.

Lessons learned

Achieving high survival rates among critically ill and preterm neonates in SSA is possible without use of expensive, advanced-skill technologies like mechanical ventilators. Evidence-based protocols adapted to low-resource hospitals, mentorship of nurses and physicians, changes in hierarchal culture, improved nurse-infant staffing ratios, involvement of mothers, improved procurement of consumables and medications, and bedside diagnostics are necessary steps to achieving high survival rates. Our NICU experience indicates that low-technology solutions of thermoregulation, respiratory support via continuous positive airway pressure, feeding protocols and infection control measures can ensure that infants not only survive, but thrive.

Conclusions

Neonatal mortality and survival of preterm newborns can be improved through a long-term commitment to training NICU staff, strengthening basic neonatal care practices, contextually appropriate protocols, and limited technology.
Device-measured physical activity and cardiovascular disease risk in adolescent childhood cancer survivors. A physical activity in childhood cancer survivors (PACCS) study
Authors: Bratteteig Mari , Anderssen Sigmund Alfred , Rueegg Corina Silvia , Ruud Ellen , Torsvik Ingrid Kristin , Kriemler Susi , Grydeland May
Published: August 2022

Objectives

We aimed to compare cardiovascular disease (CVD) risk factors in childhood cancer survivors (CCS) with age- and sex-stratified reference material and examine the association between physical activity (PA) intensities and CVD risk factors in CCS.

Materials and methods

Within the cross-sectional, multicenter Physical Activity in Childhood Cancer Survivors (PACCS) study, we collected data on CVD risk factors [VO2–peak (mL⋅kg–1⋅min–1), body mass index (BMI, kg/m2), systolic blood pressure (SBP, mmHg), and total-cholesterol/HDL-cholesterol (Total/HDL)] among CCS aged 9–18 years. CVD risk factors were compared to references with immediate t-tests. We transformed CVD risk factors into z-scores based on international references and generated an individual CVD risk score: [inverse ZVO2–peak + ZBMI + ZSBP + ZTotal/HDL)/4]. Multivariable mixed linear regression models were used to analyze the associations between device-measured PA intensities and CVD risk factors.

Results

We included 157 CCS aged on average 13.4 years at inclusion and 8.2 years from diagnosis. Male CCS had lower VO2–peak compared to references (45.4 vs. 49.4 mL⋅kg–1⋅min–1, P = 0.001), higher diastolic BP (67 vs. 63 mmHg, P < 0.001), lower HDL (1.35 vs. 1.44 mmol/L, P = 0.012), as well as a tendency to higher CVD risk score (z-score=0.14 vs. 0.00, P = .075). Female CCS’ CVD risk factors were comparable to references. Vigorous-intensity PA (VPA) was associated with CVD risk factors. A 10-min increase in VPA was associated with higher VO2–peak (β = 4.9, 95% CI, 2.1–7.7), lower Total/HDL (β = −0.3, 95% CI, −0.6 to −0.1) and a lower CVD risk score (β = −0.4, 95% CI, −0.6 to −0.2).

Conclusion

Male adolescent CCS had less favorable values of CVD risk factors compared to references. VPA in adolescent CCS is associated with clinically meaningful favorable values of CVD risk factors.