bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of non-invasive brain stimulation on cognitive and motor functions in multiple sclerosis: A systematic review and meta-analysis
Authors: Li Shuiyan , Zhang Qi , Zheng Shuqi , Li Gege , Li Shilin , He Longlong , Zeng Yuting , Chen Ling , Chen Shuping , Zheng Xiaoyan , Zou Jihua , Zeng Qing
Published: January 2023

Objective

In this study, we aimed to investigate the effects of non-invasive brain stimulation (NIBS) on cognitive and motor functions in patients with multiple sclerosis (pwMS).

Methods

A literature search was performed in the Cochrane Library, Embase, PubMed, Web of Science, Medline, CNKI, and Wan fang. The time interval used for database construction was up to December 2022, and the language was not limited. The collected trials were subsequently screened, the data were extracted, the quality was evaluated, and the effect sizes were computed using STATA/MP Version 13 for outcome analysis. Standard mean difference (SMD) and 95% confidence interval (CI) were calculated for domain of interest.

Results

In total, 17 articles that examined 364 patients with multiple sclerosis were included in this analysis. Non-invasive brain stimulation did not improve the overall cognitive function [SMD = 0.18, 95% CI (−0.32, 0.69), P = 0.475] but helped improve motor function in patients [SMD = 0.52, 95% CI (0.19, 0.85), P = 0.002]. Moreover, this study specifically indicated that non-invasive brain stimulation improved alerting [SMD = 0.68, 95% CI (0.09, 1.26), P = 0.02], whereas non-invasive brain stimulation intervention improved motor function in patients aged <45 years [SMD = 0.67, 95% CI (0.23, 1.10), P = 0.003] and in patients with expanded disability status scale scores (EDSS) <3.5 [SMD = 0.82, 95% CI (0.22, 1.42), P = 0.007]. In particular, NIBS contributed to the improvement of spasticity in pwMS [SMD = 0.68, 95% CI (0.13, 1.23), P = 0.015].

Conclusion

These results of this present study provide evidence that non-invasive brain stimulation could improve alertness in pwMS. Furthermore, NIBS may help pwMS with motor function and those who are under 45 years of age or with EDSS < 3.5 improve their motor function. For the therapeutic use of NIBS, we recommend applying transcranial magnetic stimulation as an intervention and located on the motor cortex M1 according to the subgroup analysis of motor function. These findings warrant verification.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022301012.
Case report: A rare case of massive peripheral nerve melanotic schwannoma and review of the literature
Authors: Wang Han , Shi Lin , Tian Tong , Xian Hang , Song Zhao , Cong Rui , Zhao Rui
Published: January 2023

Melanotic schwannoma is a rare tumor with indeterminate biologic behavior and varying treatment recommendations. Just about 200 cases have been reported worldwide, in which occurred in peripheral nerves has even less reported. Due to the lack of cognition of melanotic schwannoma, it is easy to be misdiagnosed and mistreatment in primary hospitals. Herein, we presented a case of massive melanotic schwannoma growing in the brachial plexus of an elderly male patient. First, the patient underwent a left forearm tumor resection in the local primary hospital because a painless lump was found there in 2017, of which details remain unclear. After this operation, the patient developed the symptoms of left median nerve injury. Thus, he came to our hospital and underwent a second operation. During this operation, we found that a part of the median nerve was absent at the left forearm, and the remanent median nerve, from the broken end to the elbow, was totally turned black, which was accompanied by petroleum-like exudate. Losing the opportunity for nerve repair, the black nerve was removed extensively and thoroughly. Postoperative pathological diagnosis revealed that the tumor was melanotic schwannoma. Then 4 years later, the tumor recurrence again, which led to the paralysis of the whole left arm and severe nerve pain, and the pulmonary metastasis of the tumor was detected at the same time. The black nerve was resected again in our hospital, and the nerve pain was partially relieved after the operation. To the best of our knowledge, it is the first time to report a melanotic schwannoma case that happened in the peripheral nerve trunk and then spread to the whole brachial plexus. There were many questions that worthy of discussion could be invited from this case, and we analyzed and discussed them based on the relevant literature. In conclusion, we reported a rare case of melanotic schwannoma that happened in the brachial plexus and illustrated the problems of the diagnosis and treatment of it based on the analysis of the relevant literature, which is helpful for the cognition of this rare nerve tumor.
Different gut microbiota in U.S. formula-fed infants consuming a meat vs. dairy-based complementary foods: A randomized controlled trial
Authors: Tang Minghua , Ma Cheng , Weinheimer-Haus Eileen M. , Robertson Charles E. , Kofonow Jennifer M. , Berman Lillian M. , Waljee Akbar , Zhu Ji , Frank Daniel N. , Krebs Nancy F.
Published: January 2023

Objective

This project aimed to evaluate the impact of meat- vs. dairy-based complementary foods on gut microbiota and whether it relates to growth.

Design

Full-term, formula-fed infants were recruited from the metro Denver area (Colorado, US) and randomized to a meat- or dairy-based complementary diet from 5 to 12 months of age. Infant’s length and weight were measured, and stool samples were collected at 5, 10, and 12 months for 16S rRNA gene sequencing and short-chain fatty acids (SCFAs) quantification.

Results

Sixty-four infants completed the dietary intervention (n = 32/group). Weight-for-age Z (WAZ) scores increased in both groups and length-for-age Z scores (LAZ) increased in the meat group only, which led to a significant group-by-time interaction (P = 0.02) of weight-for-length Z (WLZ) score. Microbiota composition (Beta-diversity) differed between groups at 12 months (weighted PERMANOVA P = 0.01) and had a group-by-time interaction of P = 0.09. Microbial community richness (Chao1) increased in the meat group only. Genus Akkermansia had a significant group-by-time interaction and increased in the dairy group and decreased in the meat group. A significant fold change of butyric acid from 5 to 12 months was found in the meat group (+1.75, P = 0.011) but not in the dairy group. Regression analysis showed that Chao1 had a negative association with WLZ and WAZ. Several genera also had significant associations with all growth Z scores.

Conclusion

Complementary feeding not only impacts infant growth but also affects gut microbiota maturation. Complementary food choices can affect both the gut microbiota diversity and structures and these changes in gut microbiota are associated with infant growth.
Nutrient transfer and antioxidant effect of adzuki bean before and after GABA enrichment
Authors: Jiang Xiujie , Xu Qingpeng , Zhang Jiayu , Li Zhijiang , Tang Huacheng , Cao Dongmei , Zhang Dongjie
Published: January 2023

In order to study the nutritional changes of γ-aminobutyric acid (GABA) enrichment in adzuki bean germination, vacuum combined with monosodium glutamate (MSG) was used as the germination stress of adzuki bean. The nutrient transfer before and after GABA enrichment in adzuki bean germination under vacuum combined with MSG stress were studied by means of chromatography and scanning electron microscope (SEM). The antioxidant activity and hypoglycemic effect of different solvent extracts before and after germination of adzuki bean were evaluated by experiments in vitro. The results showed that the nutritional characteristics of adzuki bean rich in GABA changed significantly (P < 0.05), the total fatty acids decreased significantly (P < 0.05), and the 21 amino acids detected increased significantly. After germination, the starch granules of adzuki bean became smaller and the surface was rough Germination stress significantly increased the antioxidant and hypoglycemic activities of the extracts from different solvents (P < 0.05), and the water extracts had the best effect on DPPH and ⋅OH radical scavenging rates of 88.52 and 83.56%, respectively. The results indicated that the germinated adzuki bean rich in GABA was more nutritious than the raw adzuki bean and had good antioxidant activity. It hoped to provide technical reference for rich food containing GABA.
Dose accumulation for MR-guided adaptive radiotherapy: From practical considerations to state-of-the-art clinical implementation
Authors: McDonald Brigid A. , Zachiu Cornel , Christodouleas John , Naser Mohamed A. , Ruschin Mark , Sonke Jan-Jakob , Thorwarth Daniela , Létourneau Daniel , Tyagi Neelam , Tadic Tony , Yang Jinzhong , Li X. Allen , Bernchou Uffe , Hyer Daniel E. , Snyder Jeffrey E. , Bubula-Rehm Edyta , Fuller Clifton D. , Brock Kristy K.
Published: January 2023

MRI-linear accelerator (MR-linac) devices have been introduced into clinical practice in recent years and have enabled MR-guided adaptive radiation therapy (MRgART). However, by accounting for anatomical changes throughout radiation therapy (RT) and delivering different treatment plans at each fraction, adaptive radiation therapy (ART) highlights several challenges in terms of calculating the total delivered dose. Dose accumulation strategies—which typically involve deformable image registration between planning images, deformable dose mapping, and voxel-wise dose summation—can be employed for ART to estimate the delivered dose. In MRgART, plan adaptation on MRI instead of CT necessitates additional considerations in the dose accumulation process because MRI pixel values do not contain the quantitative information used for dose calculation. In this review, we discuss considerations for dose accumulation specific to MRgART and in relation to current MR-linac clinical workflows. We present a general dose accumulation framework for MRgART and discuss relevant quality assurance criteria. Finally, we highlight the clinical importance of dose accumulation in the ART era as well as the possible ways in which dose accumulation can transform clinical practice and improve our ability to deliver personalized RT.
The regulatory mechanisms of proline and hydroxyproline metabolism: Recent advances in perspective
Authors: Phang James M.
Published: January 2023

For diverse human tumors, growth and metastasis are dependent on proline synthesis, but the mechanisms underlying this association are not clear. Proline incorporated into collagen is primarily synthesized from glutamine. Thus, rates of collagen synthesis are modulated by the enzymes of proline synthesis. On the other hand, the hydroxylation of collagen proline requires αKG, ascorbate and ferrous iron, substrates necessary for the epigenetic demethylation of DNA and histones. The metabolic relationship of proline and hydroxyproline degradation are initiated by distinct dehydrogenases but the respective oxidized products, P5C and OH-P5C are substrates for P5C Reductase and P5C Dehydrogenase allowing for mutual competition. This provides a model by which proline synthesis in cancer plays a role in reprogramming gene expression. The metabolism of proline and hydroxyproline are also linked to the HIF response to hypoxia. Hypoxia increased the expression of ALDH18A1, which is the limiting step in proline and collagen synthesis. Hydroxyproline increases levels of HIF-1α presumably by inhibiting its degradation. These new findings allow the suggestion that there is a regulatory axis from glutamine to proline and collagen synthesis, and the release of free hydroxyproline can feed back on the HIF pathway.
Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients
Authors: Zhang Hui , Hu Yi , Wang Yan , Song Xia , Hu Ying , Ma Li , Yang Xinjie , Li Kun , Qin Na , Wang Jinghui , Lv Jialin , Li Xi , Zhang Xinyong , Zhang Quan , Wu Yuhua , Yao Guangyin , Zhang Shucai
Published: January 2023

Background/Objective

The third-generation epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitor (TKIs), such as osimertinib, designed for targeting the acquired drug-resistant mutation of EGFR T790M, was approved as the first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Thus, detection of the EGFR T790M mutation for NSCLC is crucial. However, tissue samples are often difficult to obtain, especially in patients at advanced stages. This study assessed the performances of droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing (NGS) in detecting EGFR T790M status and abundance in the plasma ctDNA samples of patients with NSCLC. We also explored the association between T790M status and abundance and the response to third-generation EGFR-TKIs.

Methods

A total of 201 plasma samples with matched tissues, 821 plasma samples, and 56 patients who received third-generation EGFR-TKIs with response evaluation were included in this study. ddPCR and NGS were used to detect the mutation status and abundance of T790M in the tissues and/or blood samples.

Results

The results showed that the sensitivity and the specificity of EGFR T790M mutation status detected by ddPCR in plasma samples were 81.82% and 91.85%, respectively, compared with the tissue samples, with a consistency coefficient of 0.740. Among the 821 plasma samples, the positive rates of EGFR T790M detected by ddPCR and NGS were 34.2% (281/821) and 22.5% (185/821), respectively. With NGS results as the reference, the sensitivity and the specificity of ddPCR were 100% and 84.91%, respectively, and the consistency coefficient of the two methods was 0.717. In addition, we found that a higher EGFR T790M abundance was linked to a higher treatment response rate to the third-generation EGFR-TKIs regardless of the classification of the median value of 0.43% (P = 0.016) or average value of 3.16% (P = 0.010).

Conclusion

Taking these data together, this study reveals that ddPCR is an alternatively potent method for the detection of EGFR T790M in the plasma samples of NSCLC patients.
Lymphoid aggregates in the bone marrow biopsies of patients with myelodysplastic syndromes – A potential prognostic marker?
Authors: Book Reut , Ben-Ezra Jonathan , Glait Santar Chen , Kay Sigi , Stemer Galia , Oster Howard S. , Mittelman Moshe
Published: January 2023

Background

Lymphoid aggregates (LA) are occasionally seen in bone marrow biopsies (BMB) of myelodysplastic syndromes (MDS) patients. Our aim was to evaluate their incidence and association with prognosis.

Methods

We compared BMB reports of MDS patients treated at the Tel Aviv Sourasky Medical Center (2011-2018), and controls (2015-2017, normal BMB), and examined the charts of the MDS patients (LA+ and LA-). Categorical, normally and non-normally distributed continuous variables were compared using Fisher’s exact, independent t and Mann-Whitney tests respectively. Adjusted [age, gender, lymphocytes, white blood cells (WBC) and diabetes mellitus (DM)] Cox proportional hazard model examined survival at 12 and 24 months.

Results

MDS patients (N=140) were older than controls (N=38; 74.1 vs 69.2 years, p=0.005); 34 MDS (24.3%) and 5 controls (13.2%) had LA+ (P=0.141). CD20/CD3 staining suggested LA polyclonality. MDS/LA+ (vs MDS/LA-) patients were younger, with a trend (not statistically significant) towards poor prognostic parameters: lower Hb, WBC, and platelets, higher LDH, BM cellularity, and IPSS-R score. The incidence of cardiovascular disease was similar, but MDS/LA+ had twice the incidence of DM (38.2% vs 19.0%, p=0.022). Similar trend for cancer (26.5% vs 14.3%, p=0.102). Twelve-month survival: 24/34 (70.6%) MDS/LA+; 88/106 (83.0%) MDS/LA- (p=0.140). This trend, seen in Kaplan-Meier curves, disappeared at 24 months. The hazard ratio for LA was 2.283 (p=0.055) for 12 months.

Conclusion

These preliminary data suggest LA are relatively common (24%) in MDS BMB, and might indicate poor prognosis. This may reflect involvement of the immune system in MDS. Future studies will examine larger groups, to clarify the incidence, significance and the pathophysiology.
Screening versus multidimensional assessment of symptoms and psychosocial distress in cancer patients from the time of incurability
Authors: Solar Stefanie , Wieditz Johannes , Lordick Florian , Mehnert-Theuerkauf Anja , Oechsle Karin , van Oorschot Birgitt , Thomas Michael , Asendorf Thomas , Nauck Friedemann , Alt-Epping Bernd
Published: January 2023

Objective

Previous symptom prevalence studies show a diverse spectrum of symptoms and a large diversity in symptom intensities in patients being just diagnosed as having incurable cancer. It is unclear, how physical symptoms and psychosocial burden should be recorded in order to determine the variable need for palliative care and further support. Therefore, we compared two different strategies for detecting physical symptoms and psychosocial burden of patients with newly diagnosed incurable cancer and their effects on the further course of the disease.

Methods

SCREBEL is a controlled, randomized, non-blinded, longitudinal study of the research network of the Palliative Medicine Working Group (APM) of the German Cancer Society (DKG). We compared: a less complex repeated brief screening for symptoms and burden in patients using the NCCN Distress Thermometer and IPOS questionnaire versus a multidimensional comprehensive assessment using the FACT-G and their entity-specific questionnaires, the PHQ4 scales, SCNS-34-SF, IPOS and NCCN Distress Thermometer. The primary study endpoint was quality of life (QoL), measured using FACT-G, after six months. Secondary study endpoints were QoL by using evaluation of secondary scores (NCCN DT, IPOS, PHQ4, SCNS-SF-34G) at time 6 months, the number of hospital days, the utilization of palliative care, emergency services, and psychosocial care structures. To assess effects and differences, multiple linear regression models were fitted and survival analyses were conducted.

Results

504 patients were included in the study. 262 patients were lost to follow-up, including 155 fatalities. There were no significant differences between the low-threshold screening approach and a comprehensive assessment with respect to symptoms and other aspects of QoL. Using the IPOS, we were able to measure an improvement in the quality of life in the low-threshold screening arm by a decrease of 0.67 points (95%-CI: 0.34 to 0.99) every 30 days. (p<0.001). Data on the involvement of emergency facilities and on supportive services were insufficient for analysis.

Conclusion

A comprehensive, multidimensional assessment did not significantly differ from brief screening in preserving several dimensions of quality of life. These findings may positively influence the implementation of structured low-threshold screening programs for supportive and palliative needs in DKG certified cancer centers.

DRKS -No. DRKS00017774 https://drks.de/search/de/trial/DRKS00017774.
Brain tumours in the time of COVID-19: An online survey on patients’ disease experience in one Italian region
Authors: Abete-Fornara Giorgia , Mameli Francesca , Ruggiero Fabiana , Meessen Jennifer , Blanda Adriana , Ampollini Antonella , Locatelli Marco , Salmaggi Andrea , Di Cristofori Andrea , Mauri Ilaria , Caroli Manuela
Published: January 2023

Background

Since the outbreak, in 2019, of COVID-19, the world has experienced marked changes in daily habits, partly reflecting the exceptional social restrictions and health measures adopted to contain the disease. All these measures significantly affected not only peoples’s daily lives and psychological well-being but also the possibility for the healthcare system to function properly. In this setting, brain tumour patients were at risk due to their higher physical and mental fragility and their need for regular care. The aim of the present study was to assess, using a self-reported online questionnaire, the patients’s perceptions regarding their disease experience.

Materials and methods

We developed an online anonymous self-report survey to assess patients’s disease experience during the pandemic. We investigated the impact of the COVID-19 pandemic on patients’s cancer care schedules, their psychological distress and emotions felt during the pandemic, their levels of worry about COVID-19, and their oncological conditions.

Results

107 patients answered our survey, most of them suffering from a glioma. Less than one-third of the sample had their appointments cancelled, delayed or converted into online visits due to the pandemic. Of the patients who answered the survey, 95% declared they were satisfied with their Institute’s oncological management. The feelings reported most often were peacefulness or anxiety/worry; the majority of the sample reported high levels of loneliness, which tended to increase with age, whilst the psychological distress was correlated with age and with having a recurrence of the disease. Half of the sample declared severe worry about their oncological condition, in particular subjects with a recurrence or who were receiving adjuvant therapies. Patients with recurrence tended to worry more about the possibility of contracting COVID-19, and its effects.

Conclusion

Our findings illustrate how fragile and in need of care patients with a brain tumour may be, especially those with more severe clinical conditions. These data may help boost healthcare professionals’s knowledge about brain tumour patients’s needs and fears, so as to be able to offer them a better hospital experience and improve their clinical management, while possibly also reducing the psychological burden on patients and their families.
The efficacy of neoadjuvant EGFR-TKI therapy combined with radical surgery for stage IIIB lung adenocarcinoma harboring EGFR mutations: A retrospective analysis based on single center
Authors: Xiong Yicheng , Bian Dongliang , Huang Zhida , Yu Huansha , Huang Jie , Zhang Peng , He Wenxin , Liu Hongcheng
Published: January 2023

Background

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could provide survival benefits for locally advanced EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC). However, the role of radical surgery for EGFR-TKI treated stage IIIB EGFRm NSCLC remains controversial. This study attempted to assess the feasibility of neoadjuvant EGFR-TKI followed by radical surgery for stage IIIB EGFRm NSCLC.

Patients and Methods

Between 2013 and 2020, EGFRm lung adenocarcinoma (LUAD) patients in clinical stage IIIB undergoing neoadjuvant EGFR-TKI followed by surgery (T-S-Arm) and EGFR-TKI alone (T-Arm) were reviewed retrospectively in Shanghai Pulmonary Hospital (SPH). The chi-square test, Student’s t-test or Fisher’s exact test was performed for analysis of baseline characteristics. Progression-free survival (PFS) was estimated using the Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify independent predictors of progression.

Results

A total of 43 patients were divided into T-S-Arm (n = 21) and T-Arm (n = 22). Patients were well-balanced between the two arms. The majority of patients were female (n = 25, 58.1%), non-smokers (n = 35, 81.4%), first-generation of EGFR-TKI treatment (n = 39, 90.7%), and exon 19 deletions (19-DEL) (n = 26, 60.5%). The median diagnostic age was 63.0 years [interquartile range (IQR), 54.0-67.5 years). At the cut-off date with June 30th 2022, median follow-up time was 28 months (IQR, 20-39 months). Neoadjuvant EGFR-TKI treatment followed by radical surgery could significantly improve the median PFS compared with patients underwent EGFR-TKI alone (23.0 months vs 14.5 months, P = 0.002). Multivariate Cox regression analysis demonstrated that radical surgery (T-S-Arm vs. T-Arm, HR: 0.406; 95% CI: 0.207-0.793, P = 0.027) was the only independent predictor for disease progression. The stratified analysis demonstrated patients with N2 disease could benefit from radical surgery (HR, 0.258; 95% CI, 0.107-0.618), especially for patients harboring L858R mutation (HR, 0.188; 95% CI, 0.059-0.604).

Conclusions

For stage IIIB EGFRm NSCLC patients, the prognosis might be improved by neoadjuvant EGFR-TKI followed by radical surgery versus EGFR-TKI alone, especially for those with N2 disease and harboring L858R mutation.
PIMREG is a prognostic biomarker involved in immune microenvironment of clear cell renal cell carcinoma and associated with the transition from G1 phase to S phase
Authors: Yao Huibao , Lyu Feifei , Ma Jian , Sun Fengze , Tang Gonglin , Wu Jitao , Zhou Zhongbao
Published: January 2023

Background

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the world and affects human health seriously. PIMREG is a mitotic regulator which is essential to the metaphase-to-anaphase transition in cell cycle. Although PIMREG plays a crucial role in the malignant progression of tumors, there are few reports on its role in ccRCC.

Methods

The transcriptional expression profile and clinical data of PIMREG were downloaded from TCGA database and verified by qRT-PCR. Kaplan-Meier plotter was used to analyze the effect of PIMREG on overall survival (OS), disease specific survival (DSS) and progression-free interval (PFI) of patients with ccRCC. Univariable and multivariable Cox regression analysis were used to determine the independent prognostic factors of ccRCC. The effects of PIMREG on cell migration and invasion were detected by wound healing assay and transwell invasion assay, and CCK-8 assay, colony formation assay and cell cycle assay were used to detect the effect of PIMREG on cell proliferation. In addition, the changes in cell cycle related proteins were detected by western blot.

Results

PIMREG was highly expressed in human ccRCC and was positively correlated with pathologic stage, TNM stage and histologic grade. In addition, patients with high expression of PIMREG had a poor prognosis. Univariable and multivariable Cox regression analysis identified that PIMREG was an independent prognostic factor of ccRCC. Additionally, PIMREG was also closely related to immune cell infiltration. Experiments in vitro identified that the knockdown of PIMREG could significantly inhibit the proliferation, migration and invasion abilities of ccRCC. The expression of cyclin D1, CDK4 and CDK6 was also significantly reduced after PIMREG knockdown.

Conclusions

PIMREG plays a vital role in the development of ccRCC and may become a potential therapeutic target in the future.
MiR-495-3p regulates cell migration and invasion in papillary thyroid carcinoma
Authors: Alves Letícia Ferreira , Geraldo Murilo Vieira
Published: January 2023

Background

Papillary thyroid carcinoma (PTC) is the most prevalent histotype of thyroid cancer and the presence of BRAFV600E mutation in these tumors is related to the malignancy and prognosis of the disease. In recent years attention has been focused on the role of microRNAs in the biology of PTC cells, especially in their role in the modulation of pathways related to tumorigenesis. DLK1-DIO3-derived miRNAs have been shown to play important roles in tumor context and are globally downregulated in PTC.

Methods

Based on a previous in silico target prediction and gene enrichment analysis, we identified miR-495-3p as the candidate with the highest tumor suppressor potential role in PTC among DLK1-DIO3-derived miRNAs. We used bioinformatics and an in vitro model of miR-495-3p overexpression to further understand the influence of this molecule on the tumorigenic processes of PTC.

Results

Overexpression of miR-495-3p impaired cell migration and invasion of PTC cells harboring the BRAFV600E mutation and affected the expression of targets predicted in the bioinformatic analysis, such as TGFB2, EREG and CCND1.

Conclusion

Overall, our results indicate that the loss of miR-495-3p expression during PTC development might play an important role in its progression.
COMMD proteins function and their regulating roles in tumors
Authors: You Guangqiang , Zhou Chen , Wang Lei , Liu Zefeng , Fang He , Yao Xiaoxao , Zhang Xuewen
Published: January 2023

The COMMD proteins are a highly conserved protein family with ten members that play a crucial role in a variety of biological activities, including copper metabolism, endosomal sorting, ion transport, and other processes. Recent research have demonstrated that the COMMD proteins are closely associated with a wide range of disorders, such as hepatitis, myocardial ischemia, cerebral ischemia, HIV infection, and cancer. Among these, the role of COMMD proteins in tumors has been thoroughly explored; they promote or inhibit cancers such as lung cancer, liver cancer, gastric cancer, and prostate cancer. COMMD proteins can influence tumor proliferation, invasion, metastasis, and tumor angiogenesis, which are strongly related to the prognosis of tumors and are possible therapeutic targets for treating tumors. In terms of molecular mechanism, COMMD proteins in tumor cells regulate the oncogenes of NF-κB, HIF, c-MYC, and others, and are related to signaling pathways including apoptosis, autophagy, and ferroptosis. For the clinical diagnosis and therapy of malignancies, additional research into the involvement of COMMD proteins in cancer is beneficial.
Bibliometric analysis of single-cell sequencing researches on immune cells and their application of DNA damage repair in cancer immunotherapy
Authors: Zhao Yu , Xiao Yuanxun , Hu Zhengbo , Wang Ji , Xu Zhiguang , Mo Yizhang , Qi Guojun , Chen Kebing , Wu Wu , Ma Weiying
Published: January 2023

Introduction

In recent decades, single-cell sequencing technology has developed rapidly and used widely in various fields of life sciences, especially for the detection of immune cells. A bibliometric analysis of single-cell sequencing research work on immune cells published during the 2011-2021 period should provide new insight on the use of single-cell sequencing.

Methods

We screened 1,460 publications on single-cell sequencing on immune cells according to the publication date, article type, language, and country.

Reults

The United States published the first and largest number of articles, while China’s research started relatively late, but ranked second in the number of publications. T cells were the most commonly studied immune cells by single-cell sequencing, followed by mononuclear macrophages. Cancer biology was the most common field of immune cell research by single-cell sequencing. Single-cell sequencing studies using γδ T cells were mainly in the fields of cancer biology and cell development, and focused over time from cell surface receptor to cell function. Through in-depth analysis of the articles on single-cell sequencing of T cells in the oncology field, our analysis found that immunotherapy and tumor microenvironment were the most popular research directions in recent years.

Discussion

The combination of DNA damage repair and immunotherapy seems to provide a new strategy for cancer therapy.
SLC-0111, an inhibitor of carbonic anhydrase IX, attenuates hepatoblastoma cell viability and migration
Authors: Eloranta Katja , Pihlajoki Marjut , Liljeström Emmi , Nousiainen Ruth , Soini Tea , Lohi Jouko , Cairo Stefano , Wilson David B. , Parkkila Seppo , Heikinheimo Markku
Published: January 2023

Background

In response to hypoxia, tumor cells undergo transcriptional reprogramming including upregulation of carbonic anhydrase (CA) IX, a metalloenzyme that maintains acid-base balance. CAIX overexpression has been shown to correlate with poor prognosis in various cancers, but the role of this CA isoform in hepatoblastoma (HB) has not been examined.

Methods

We surveyed the expression of CAIX in HB specimens and assessed the impact of SLC-0111, a CAIX inhibitor, on cultured HB cells in normoxic and hypoxic conditions.

Results

CAIX immunoreactivity was detected in 15 out of 21 archival pathology HB specimens. The CAIX-positive cells clustered in the middle of viable tumor tissue or next to necrotic areas. Tissue expression of CAIX mRNA was associated with metastasis and poor clinical outcome of HB. Hypoxia induced a striking upregulation of CAIX mRNA and protein in three HB cell models: the immortalized human HB cell line HUH6 and patient xenograft-derived lines HB-295 and HB-303. Administration of SLC-0111 abrogated the hypoxia-induced upregulation of CAIX and decreased HB cell viability, both in monolayer and spheroid cultures. In addition, SLC-0111 reduced HB cell motility in a wound healing assay. Transcriptomic changes triggered by SLC-0111 administration differed under normoxic vs. hypoxic conditions, although SLC-0111 elicited upregulation of several tumor suppressor genes under both conditions.

Conclusion

Hypoxia induces CAIX expression in HB cells, and the CAIX inhibitor SLC-0111 has in vitro activity against these malignant cells.
The full range of ophthalmological clinical manifestations in systemic lupus erythematosus
Authors: Kedia Nikita , Theillac Vincent , Paez-Escamilla Manuel , Indermill Chad , Gallagher Denise S. , Adam Raphaël , Qu-Knafo Anne Lise , Amari Fatima , Bottin Caroline , Chotard Géraldine , Caillaux Violaine , Strého Maté , Sedira Neila , Héron Emmanuel , Becherel Pierre-André , Bodaghi Bahram , Mrejen-Uretski Sarah , Sahel Alain-José , Saadoun David , Errera Marie-Hélène
Published: January 2023

Purpose

To determine the full range of ophthalmological clinical manifestations in systemic lupus erythematosus (SLE) and to compare the systemic features associated with them.

Methods

Files of 13 patients with ocular SLE (n = 20 eyes) diagnosed as per the American College of Rheumatology (ACR) 2012 revised criteria were retrospectively reviewed.

Results

The following clinical manifestations were found: keratoconjunctivitis sicca (n = three patients), anterior uveitis associated with an inflammatory pseudo-tumor orbital mass (n = one patient, one eye), episcleritis and periorbital edema (n = one patient, two eyes), posterior scleritis (n = one patient, two eyes), bilateral papillary edema in the context of idiopathic intracranial hypertension (n = one patient, one eye), inflammatory optic neuritis (n = one patient, one eye), and lupus retinopathies with varying degrees of capillary occlusions mainly arteriolar (n = seven patients, 13 eyes) and larger arteries or veins (retinal arteries occlusions and retinal veins occlusions) (n = one patient, two eyes). Some patients presented with combined ophthalmological manifestations.

Systemic SLE was discovered by its ophthalmic manifestation in three cases (23%) and was previously known in the other 10 cases (77%). On average, ocular symptoms were seen 8 years after the initial diagnosis of SLE. Other systemic SLE disorders included cutaneous disorders (77%), joint disorders (38%), central nervous system (CNS) disorders (23%), renal disorders (38%), and oral ulcers (23%).

Treatment of the ophthalmic system manifestations of lupus included local steroid therapies along with systemic immunosuppression.

The most common laboratory ACR criteria were: high levels of antinuclear antibodies (ANA) (100%), positive anti-Sm (64%), anti-dsDNA (27%), low complement levels (27%), and positive antiphospholipid (APL) antibodies (18%).

Discussion

SLE activity in the ophthalmic system is characterized by its functional severity and the range of involvement can be categorized by anatomical involvement: presence of anterior uveitis, episcleritis, scleritis, periorbital edema, posterior uveitis with retinal vascular ischemia, or papillary edema. Not currently part of the diagnosis criteria of the SLE ACR given its rarity, the ocular localization of the pathology led to the diagnosis of SLE in three cases; thus, developing a greater understanding of ocular lupus may help in identifying and treating systemic manifestations of lupus earlier.
Stent implantation in severe aortic coarctation in a pediatric patient with Turner syndrome: Case report and literature review
Authors: Lin Yuese , Zhu Ling , Li Xuandi , Ba Hongjun , He Xiufang , Li Shujuan
Published: January 2023

Background

Turner syndrome is a rare systemic disease and a significant proportion of these patients experience aortic coarctation. Selection of optimal therapy for aortic coarctation in patients with Turner syndrome is difficult due to the pathologic change of the systemic vessel.

Case presentation

We report one successful case of covered stent implantation for the treatment of severe native coarctation of the aorta in a 15-year-old patient with Turner syndrome weighing 36 kg. A covered stent was implanted in this patient. After the stent implantation, the peak systolic pressure gradient immediately decreased from 48 mmHg to 14 mmHg. The aortic diameter at the coarctation site increased from 3 mm to 10 mm after stenting. A femoral arterial complication occurred in this case, and we stabilized the situation finally.

Results

During a follow-up of 3 years, no restenosis of aortic coarctation was observed and the patient no longer experienced hypertension. The dissection of the right femoral artery remained stable.

Conclusion

A covered stent implantation for severe aortic coarctation in patients with Turner syndrome could be safe and effective. However, caution should be taken when using the technique to prevent complications.
Associations Between Maternal Distress During Early Life Periods and Offspring Respiratory Infections and Allergic Outcomes
Authors: Lau Hui Xing , Kee Michelle Zhi Ling , Yap Qai Ven , Tham Elizabeth Huiwen , Chan Yiong Huak , Goh Anne Eng Neo , Teoh Oon Hoe , Eriksson Johan Gunnar , Godfrey Keith M. , Gluckman Peter D. , Chong Yap Seng , Chan Jerry Kok Yen , Van Bever Hugo , Lee Bee Wah , Shek Lynette Pei-chi , Meaney Michael J. , Loo Evelyn Xiu Ling
Published: January 2023

Background

Increasing evidence suggests that maternal distress is a risk factor for development of respiratory infections and allergic diseases in the offspring. We aim to evaluate the link between maternal distress during critical periods in early life, namely the preconception, pregnancy and postnatal periods, and development of respiratory infections and allergic diseases in the offspring from the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohort.

Methods

Maternal perceived distress was evaluated using validated questionnaires including Beck Depression Inventory-II (BDI-II) administered during three time periods: preconception (three months apart at four timepoints), pregnancy (during each trimester) and postnatal (3 and 6 months post-delivery). Child eczema, rhinitis and wheeze outcomes were evaluated using a modified ISAAC questionnaire at ages 3, 6, 12, and 18 months. Child allergic sensitization was determined by skin prick testing at 18 months.

Results

Among 332 mother-child pairs studied, higher maternal distress during preconception and pregnancy increased the risks of wheeze development in the first 18 months; for example, preconception and pregnancy BDI-II scores ≥20 were associated with increased risks of wheeze by 18 months [adjusted risk ratios 3.2 (95%CI 1.1–9.4) and 2.5 (1.0–5.9), respectively]. Emotional and practical support from family during preconception decreased the risks of offspring wheeze. No associations were observed between maternal distress and offspring eczema, rhinitis and allergic sensitization.

Conclusion

Maternal distress during critical early life periods was associated with offspring wheeze in the first 18 months of life. Supporting maternal mental health even before pregnancy could reduce the risk of offspring wheeze.
PAnno: A pharmacogenomics annotation tool for clinical genomic testing
Authors: Liu Yaqing , Lin Zipeng , Chen Qingwang , Chen Qiaochu , Sang Leqing , Wang Yunjin , Shi Leming , Guo Li , Yu Ying
Published: January 2023

Introduction: Next-generation sequencing (NGS) technologies have been widely used in clinical genomic testing for drug response phenotypes. However, the inherent limitations of short reads make accurate inference of diplotypes still challenging, which may reduce the effectiveness of genotype-guided drug therapy.

Methods: An automated Pharmacogenomics Annotation tool (PAnno) was implemented, which reports prescribing recommendations and phenotypes by parsing the germline variant call format (VCF) file from NGS and the population to which the individual belongs.

Results: A ranking model dedicated to inferring diplotypes, developed based on the allele (haplotype) definition and population allele frequency, was introduced in PAnno. The predictive performance was validated in comparison with four similar tools using the consensus diplotype data of the Genetic Testing Reference Materials Coordination Program (GeT-RM) as ground truth. An annotation method was proposed to summarize prescribing recommendations and classify drugs into avoid use, use with caution, and routine use, following the recommendations of the Clinical Pharmacogenetics Implementation Consortium (CPIC), etc. It further predicts phenotypes of specific drugs in terms of toxicity, dosage, efficacy, and metabolism by integrating the high-confidence clinical annotations in the Pharmacogenomics Knowledgebase (PharmGKB). PAnno is available at https://github.com/PreMedKB/PAnno.

Discussion: PAnno provides an end-to-end clinical pharmacogenomics decision support solution by resolving, annotating, and reporting germline variants.
Case report: An autopsy case of pilsicainide poisoning
Authors: Takei Sella , Kinoshita Hiroshi , Kumihashi Mitsuru , Jamal Mostofa , Abe Hiroko , Kimura Shoji
Published: January 2023

We present a fatal case of pilsicainide poisoning. Quantitative toxicological analysis revealed that the concentrations of pilsicainide in femoral blood and urine samples were 17.5 μg/mL and 136.9 μg/mL, respectively. No morphological changes due to poisoning were observed. Based on the autopsy findings, results of the toxicological examination, and investigation by the authorities, we concluded that the cause of death was due to pilsicainide poisoning.
Sesquiterpene lactones-enriched fractions from Xanthium mongolicum Kitag alleviate RA by regulating M1 macrophage polarization via NF-κB and MAPK signaling pathway
Authors: Han Jing , Wang Jingwen , Wang Yicun , Zhu Zhiqi , Zhang Siwang , Wu Bingrong , Meng Mingsong , Zhao Jianning , Wang Dongsheng
Published: January 2023

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by activated M1-like macrophage in the joint. Xanthium mongolicum Kitag (X. mongolicum) is a traditional medicinal plant that has long been used to treat RA and other immune diseases in China.

Methods: Fractions of X. mongolicum were separated based on polarity. Anti-RA activity of the fractions were screened by LPS-stimulated RAW264.7 macrophage in vitro. The major active compounds were identified by UPLC-MS and quantified by HPLC. The anti-RA effects of the active fraction was evaluated in complete freund’s adjuvant (CFA)-induced arthritis and collagen-induced arthritis (CIA) mouse models in vivo and LPS-stimulated macrophage in vitro.

Results: Sesquiterpene lactones-enriched fraction from X. mongolicum (SL-XM) exhibited the strongest anti-RA activity among all components in vitro. Five major constituents i.e., Xanthinosin (1), Xanthatin (2), Mogolide D (3), Mogolide E (4), and Mogolide A (5) were identified as major compounds of SL-XM. SL-XM ameliorated symptoms of CFA and CIA induced arthritis mice model. Furthermore, SL-XM treatment inhibited LPS-induced M1 macrophages polarization. In addition, SL-XM inhibited the phosphorylation of NF-κB and MAPK signaling pathways in LPS-induced macrophage and CIA-challenged mice.

Discussion: The main anti-RA active fraction of X. mongolicum may be the Sesquiterpene lactones, which includes five key compounds. SL-XM may exert its anti-RA effect by suppressing M1 macrophage polarization via the NF-κB and MAPK signaling pathway.
NArCoS: The new hodoscope for neutrons and charged particles
Authors: Pagano E. V. , De Filippo E. , Russotto P. , Cardella G. , Castoldi A. , Geraci E. , Gnoffo B. , Guazzoni C. , Lanzalone G. , Maiolino C. , Martorana N. S. , Pagano A. , Pirrone S. , Politi G. , Risitano F. , Rizzo F. , Trimarchi M.
Published: January 2023

Proper detection of neutrons and charged particles is motivated by the recent efforts to construct new facilities for radioactive ion beams (RIBs) worldwide. Detection of neutrons is an important opportunity to improve our understanding of nuclear spectroscopy and reaction dynamics, with the possibility of constraining theoretical models of the nuclear equation of state (NEoS) and investigating in-medium nuclear interactions. This topic also has important implications in the study of astrophysical objects, such as neutron stars. In this work, the state-of-the-art of Neutron Array for Correlation Studies (NArCoS), a new hodoscope for neutron and charged particles under construction in Catania (INFN), is briefly reviewed.
Underwater environment laser ghost imaging based on Walsh speckle patterns
Authors: Yang Mochou , Wu Yi , Feng Guoying
Published: January 2023

Underwater imaging is a challenging task because of the effects of scattering and absorption in water. Ghost imaging (GI) has attracted increasing attention because of its simple structure, long range, and achievability under weak light intensity. In an underwater environment, conventional imaging is limited by low sensitivity, resulting in fuzzy images, while ghost imaging can solve this problem. This study proposes underwater laser ghost imaging based on Walsh speckle patterns. According to the simulated and experimental results, noise resistance and a low sampling rate of ghost imaging based on Walsh speckle patterns are proved. As the turbidity of the underwater environment increases, the imaging quality of ghost imaging based on Walsh speckle patterns decreases. However, it remains much better than that of ghost imaging based on random speckle patterns and Hadamard speckle patterns, whereas conventional imaging is no longer distinguishable. Ghost imaging based on Walsh speckle patterns can be performed with a sampling rate lower than 10%, and the peak signal-to-noise ratio and the structural similarity of the results increase by 150.15% and 396.66%, respectively, compared with random speckle pattern ghost imaging. An identifiable image of ghost imaging based on Walsh speckle patterns can be reconstructed with a sampling rate of 6% in a turbid water environment, which is simulated with the concentration of the milk powder not higher than 11.0 g/L. This method promotes the further development of optical imaging technology for underwater targets with a low sampling rate based on ghost imaging.