bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural history of type 1 diabetes on an immunodysregulatory background with genetic alteration in B-cell activating factor receptor: A case report
Authors: Di Lorenzo Biagio , Pacillo Lucia , Milardi Giulia , Jofra Tatiana , Di Cesare Silvia , Gerosa Jolanda , Marzinotto Ilaria , Zapparoli Ettore , Rivalta Beatrice , Cifaldi Cristina , Barzaghi Federica , Giancotta Carmela , Zangari Paola , Rapini Novella , Deodati Annalisa , Amodio Giada , Passerini Laura , Carrera Paola , Gregori Silvia , Palma Paolo , Finocchi Andrea , Lampasona Vito , Cicalese Maria Pia , Schiaffini Riccardo , Di Matteo Gigliola , Merelli Ivan , Barcella Matteo , Aiuti Alessandro , Piemonti Lorenzo , Cancrini Caterina , Fousteri Georgia
Published: August 2022

The immunological events leading to type 1 diabetes (T1D) are complex and heterogeneous, underscoring the necessity to study rare cases to improve our understanding. Here, we report the case of a 16-year-old patient who showed glycosuria during a regular checkup. Upon further evaluation, stage 2 T1D, autoimmune thrombocytopenic purpura (AITP), and common variable immunodeficiency (CVID) were diagnosed. The patient underwent low carb diet, losing > 8 kg, and was placed on Ig replacement therapy. Anti-CD20 monoclonal antibody (Rituximab, RTX) was administered 2 years after diagnosis to treat peripheral polyneuropathy, whereas an atypical mycobacteriosis manifested 4 years after diagnosis and was managed with prolonged antibiotic treatment. In the fifth year of monitoring, the patient progressed to insulin dependency despite ZnT8A autoantibody resolution and IA-2A and GADA autoantibody decline. The patient had low T1D genetic risk score (GRS = 0.22817) and absence of human leukocyte antigen (HLA) DR3/DR4-DQ8. Genetic analysis identified the monoallelic mutation H159Y in TNFRSF13C, a gene encoding B-cell activating factor receptor (BAFFR). Significant reduced blood B-cell numbers and BAFFR levels were observed in line with a dysregulation in BAFF–BAFFR signaling. The elevated frequency of PD-1+ dysfunctional Tfh cells composed predominantly by Th1 phenotype was observed at disease onset and during follow-up. This case report describes a patient progressing to T1D on a BAFFR-mediated immunodysregulatory background, suggesting a role of BAFF–BAFFR signaling in islet-specific tolerance and T1D progression.
Differential distribution and prognostic value of CD4+ T cell subsets before and after radioactive iodine therapy in differentiated thyroid cancer with varied curative outcomes
Authors: Shi Zhi-Yong , Zhang Sheng-Xiao , Li Cai-Hong , Fan Di , Xue Yan , Cheng Zhe-Hao , Wu Li-Xiang , Lu Ke-Yi , Wu Zhi-Fang , Li Xiao-Feng , Liu Hai-Yan , Li Si-Jin
Published: August 2022

Differentiated thyroid cancer is the most frequently diagnosed endocrine tumor. While differentiated thyroid cancers often respond to initial treatment, little is known about the differences in circulating immune cells amongst patients who respond differently. A prospective study of 39 patients with differentiated thyroid cancer was conducted. Serum thyroglobulin levels and thyroid and immunological functions were tested before and after radioactive iodine treatment (RAIT). Efficacy assessments were performed 6 to 12 months after radioactive iodine treatment. Most patients showed an excellent response to radioactive iodine treatment. Before radioactive iodine treatment, the excellent response group had considerably fewer circulating CD4+ T cell subsets than the non-excellent response group. Both the excellent response and non-excellent response groups had considerably lower circulating CD4+ T lymphocyte subsets 30 days after radioactive iodine treatment, but those of the excellent response group were still lower than those of the non-excellent response group. All circulating CD4+ T cell subsets in the excellent response group rose by varying degrees by the 90th day, but only Treg cell amounts increased in the non-excellent response group. Interestingly, in the non-excellent response group, we noticed a steady drop in Th1 cells. However, the bulk of circulating CD4+ T cell subsets between the two groups did not differ appreciably by the 90th day. Finally, we discovered that CD4+ T cell subsets had strong predictive potential, and we thus developed high-predictive-performance models that deliver more dependable prognostic information. In conclusion, in individuals with differentiated thyroid cancer, there is great variation in circulating immune cells, resulting in distinct treatment outcomes. Low absolute CD4+ T cell counts is linked to improved clinical outcomes as well as stronger adaptive and resilience capacities.
Immune responses in COVID-19 and tuberculosis coinfection: A scoping review
Authors: Flores-Lovon Kevin , Ortiz-Saavedra Brando , Cueva-Chicaña Luis A. , Aperrigue-Lira Shalom , Montes-Madariaga Elizbet S. , Soriano-Moreno David R. , Bell Brett , Macedo Rodney
Published: August 2022

Background and aim

Patients with COVID-19 and tuberculosis coinfection are at an increased risk of severe disease and death. We therefore sought to evaluate the current evidence which assessed the immune response in COVID-19 and tuberculosis coinfection

Methods

We searched Pubmed/MEDLINE, EMBASE, Scopus, and Web of Science to identify articles published between 2020 and 2021. We included observational studies evaluating the immune response in patients with tuberculosis and COVID-19 compared to patients with COVID-19 alone.

Results

Four cross-sectional studies (372 participants) were identified. In patients with asymptomatic COVID-19 and latent tuberculosis (LTBI), increased cytokines, chemokines, growth factors and humoral responses were found. In addition, patients with symptomatic COVID-19 and LTBI had higher leukocytes counts and less inflammation. Regarding patients with COVID-19 and active tuberculosis (aTB), they exhibited decreased total lymphocyte counts, CD4 T cells specific against SARS-CoV-2 and responsiveness to SARS-CoV-2 antigens compared to patients with only COVID-19.

Conclusion

Although the evidence is limited, an apparent positive immunomodulation is observed in patients with COVID-19 and LTBI. On the other hand, patients with COVID-19 and aTB present a dysregulated immune response. Longitudinal studies are needed to confirm these findings and expand knowledge.
Ridges and riblets: Shark skin surfaces versus biomimetic models
Authors: Gabler-Smith Molly K. , Lauder George V.
Published: August 2022

Shark skin has been an inspiration for biomimetic materials and structures due to its role in reducing drag and enhancing thrust, properties believed to be due to the textured surface composed of ridges on the surface of individual tooth-like scales (denticles). Attempts to replicate the hydrodynamic performance of shark skin have involved manufacturing both engineered riblets and fabrics with textured surfaces. However, there are no studies that compare the surface ornamentation of shark denticles to bioinspired materials. Using three-dimensional surface profilometry we analyzed the cross-sectional profile of the surface of shark denticles at two locations on 17 species and compared these data to values obtained from engineered structures (e.g., riblets) and competition swimsuits that are often proposed as having a comparable surface texture to shark skin. Of the variables measured, crown aspect ratio (p = 0.007), ridge height, ridge spacing, ridge aspect ratio, and ridge bumpiness (all p < 0.001) differed among the three materials. Overall, engineered riblet surfaces were very different than biological shark skin. Some of the competition swimsuit materials were more shark-like, with the fabric texture having similar height variation, but with irregular ridge spacing. Cross-sectional profile, which includes pathlength and aspect ratio in addition to ridge spacing and height, is an important feature of the skin’s surface, affecting water flow over the individual denticles, and future research will address these parameters. Quantitative 3D analysis of the surface of real shark denticle ridges enables the design of more biomimetic engineered shark skin surfaces.
Seasonal variability of upper ocean primary production along the Kuroshio off Japan: Roles of eddy-driven nutrient transport
Authors: Zhang Xu , Uchiyama Yusuke , Masunaga Eiji , Suzue Yota , Yamazaki Hidekatsu
Published: August 2022

We assessed spatial and seasonal variabilities of eddy-driven vertical nutrient fluxes, which are essential for maintaining primary production in the upper ocean. A climatological model based on a Regional Oceanic Modeling System (Regional Oceanic Modeling System) coupled with a Nutrient Phytoplankton Zooplankton and Detritus (NPZD) biogeochemical model at a submesoscale eddy-permitting resolution was used to investigate the mechanisms driving such variabilities around the Kuroshio, off the coast of Japan. The model realistically reproduced the spatial segmentations in primary production on both sides of the Kuroshio path with a higher chlorophyll-a concentration on the northern side than the southern side. In winter, downward eddy-induced nitrate flux is predominantly provoked in the upstream Kuroshio region (KR), while upward nitrate fluxes prevail in the downstream Kuroshio Extension (KE) region, due to both shear and baroclinic instabilities. Baroclinic instability plays a crucial role in inducing seasonal variability, leading to enhancement (reduction) of the eddy flux in winter (summer), particularly in regions away from the Kuroshio axis. Furthermore, we found that the influence of the Izu-Ogasawara Ridge, located in the KR, on regional dynamics and resultant spatial variability of the biogeochemical response are mostly confined in the KR. The Kuroshio is less turbulent in the upstream of the ridge, while it becomes unstable to shed mesoscale eddies in laterally wider and vertically deeper regions downstream. Consequently, although the near-surface nitrate concentration is lower downstream, the upward eddy-driven nitrate flux is more effective in maintaining active primary production due to the shear and baroclinic instabilities in winter.
Acute changes in free and extracellular vesicle-associated circulating miRNAs and myokine profile in professional sky-runners during the Gran Sasso d’Italia vertical run
Authors: Faraldi M. , Sansoni V. , Perego S. , Gomarasca M. , Gerosa L. , Ponzetti M. , Rucci N. , Banfi G. , Lombardi G.
Published: August 2022

The modification of gene expression profile, a first step in adaptation to exercise, leads to changes in the level of molecules associated with skeletal muscle activity and energy metabolism—such as myokines—as well as those involved in their transcriptional regulation, like microRNA. This study aimed to investigate the influence of strenuous exercise on circulating microRNAs and their possible association with myokine response. Pre-competition and post-competition plasma samples were collected from 14 male athletes participating in a vertical run (+1,000 m gain, 3,600 m length). Circulating total (t-miRNA) and extracellular vesicle-associated (EV-miRNA) miRNAs were extracted from the pooled plasma. Nanoparticle tracking analysis was performed to investigate pre- and post-competition EV concentration and size distribution. A panel of 179 miRNAs was assayed by qPCR and analyzed by Exiqon GenEx v6 normalized on the global mean. t-miRNA and EV-miRNAs whose level was ≥5-fold up- or down-regulated were validated for each single subject. Target prediction on MirWalk v3.0, Gene-Ontology, and pathway enrichment analysis on Panther v17.0 were performed to define the potential biological role of the identified miRNAs. A panel of 14 myokines was assayed in each sample by a multiplex immunoassay. In whole plasma, five miRNAs were upregulated and two were downregulated; in the EV fraction, five miRNAs were upregulated and three were downregulated. Nanoparticle tracking analysis revealed a similar EV size distribution in pre- and post-competition samples and a decreased concentration in post-competition samples related to pre-competition samples. Gene-Ontology and pathway enrichment analysis revealed that the identified t-miRNAs and EV-miRNAs were potentially involved in metabolism regulation in response to exercise. Correlation between fold-change of the post-competition relative to pre-competition plasma level of both t-miRNAs and EV-miRNAs and myokines further confirmed these results. This study provides an example of a systemic response to acute endurance exercise, in which circulating miRNAs play a pivotal role.
Comparison of extraction methods for intracellular metabolomics of human tissues
Authors: Andresen Carolin , Boch Tobias , Gegner Hagen M. , Mechtel Nils , Narr Andreas , Birgin Emrullah , Rasbach Erik , Rahbari Nuh , Trumpp Andreas , Poschet Gernot , Hübschmann Daniel
Published: August 2022

Analyses of metabolic compounds inside cells or tissues provide high information content since they represent the endpoint of biological information flow and are a snapshot of the integration of many regulatory processes. However, quantification of the abundance of metabolites requires their careful extraction. We present a comprehensive study comparing ten extraction protocols in four human sample types (liver tissue, bone marrow, HL60, and HEK cells) aiming to detect and quantify up to 630 metabolites of different chemical classes. We show that the extraction efficiency and repeatability are highly variable across protocols, tissues, and chemical classes of metabolites. We used different quality metrics including the limit of detection and variability between replicates as well as the sum of concentrations as a global estimate of analytical repeatability of the extraction. The coverage of extracted metabolites depends on the used solvents, which has implications for the design of measurements of different sample types and metabolic compounds of interest. The benchmark dataset can be explored in an easy-to-use, interactive, and flexible online resource (R/shiny app MetaboExtract: http://www.metaboextract.shiny.dkfz.de) for context-specific selection of the optimal extraction method. Furthermore, data processing and conversion functionality underlying the shiny app are accessible as an R package: https://cran.r-project.org/package=MetAlyzer.
The influence of mindfulness-based interventions on the academic performance of students measured by their GPA. A systematic review and meta-analysis
Authors: Ostermann Thomas , Pawelkiwitz Martin , Cramer Holger
Published: August 2022

Objective: Mindfulness-based interventions are increasingly used in health, economic and educational systems. There are numerous studies demonstrating the effectiveness of mindfulness-based interventions in the educational sectors (primary, secondary, and tertiary). This systematic review and meta-analysis assessed the current state of research on the effectiveness of mindfulness-based interventions on the academic performance of students as measured by their grade point average (GPA).

Methods: Literature search was conducted in Psychology and Behavioral Sciences Collection, PsycARTICLES, PubMed, and Google Scholar through March 2022. The inclusion criteria were: (1) the use of GPA as a measure of students’ academic performance, (2) a sample that was subjected to a mindfulness-based intervention without medical indication, (3) the student status of the subjects. Meta-analysis was conducted using a random effects model with the generic inverse variance method.

Results: The search included a total of 759 studies, of which six randomized controlled trials met the inclusion criteria. In these trials, significant group differences for GPA were found with effect sizes ranging from d = 0.16–1.62 yielding a significant overall effect of d = 0.42 (95% CI: 0.15–0.69) and a low magnitude of heterogeneity of I2 = 37%.

Discussion: In conclusion, the first results of this emerging research field seem promising. However, the exact mechanisms of action are still unclear.
Bilateral Dysfunction of Otolith Pathway in Patients With Unilateral Idiopathic BPPV Detected by ACS-VEMPs
Authors: Niu Xiaorong , Han Peng , Duan Maoli , Chen Zichen , Hu Juan , Chen Yanfei , Xu Min , Ren Pengyu , Zhang Qing
Published: August 2022

Objective

To observe the functional status of the otolith pathway in patients with unilateral idiopathic benign paroxysmal positional vertigo (BPPV) by combining air-conducted sound elicited cervical vestibular-evoked myogenic potential (ACS-cVEMP) and ocular vestibular-evoked myogenic potential (ACS-oVEMP).

Methods

One hundred and eighty patients with BPPV were recruited for conventional cVEMP and oVEMP tests. The abnormal rates of VEMPs were compared between BPPV patients and control participants.

Results

The abnormal rates of cVEMP and oVEMP in BPPV patients were 46.7% (84/180) and 57.2% (103/180) in affected ears, respectively, and 45.0% (81/180) and 56.7% (102/180) in unaffected ears, respectively; both were significantly higher than the abnormal rates of cVEMP and oVEMP in normal control ears. Compared with normal subjects, the cVEMP response rate was lower in affected and unaffected ears in BPPV patients. The abnormal rates of cVEMP and oVEMP were 48.1% (76/158) and 57.6% (91/158) in patients with posterior semicircular canal BPPV, and 36.4% (8/22) and 54.5% (12/22) in lateral semicircular canal BPPV. There was no significant difference in VEMP abnormalities between posterior semicircular canal BPPV and lateral semicircular canal BPPV.

Conclusion

The prevalence of abnormal cVEMPs and oVEMPs in both affected and unaffected ears of patients with BPPV was significantly higher than that observed in the control group. The pathological mechanism of unilateral idiopathic BPPV may be associated with bilateral degeneration of otolith pathways.
Unequal Efficacy of Different Infarct Location in Predicting Futile Recanalization of Patients With Acute Ischemic Stroke
Authors: Li Zhao-shuo , Zhong Hai-long , Zhou Teng-fei , He Ying-kun , Li Qiang , Wang Zi-liang , Zhu Liang-fu , Wen Chang-ming , Han Jian-feng , Li Tian-xiao
Published: August 2022

Objectives

Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) caused by large vessel occlusion, while futile recanalization is the main factor influencing the prognosis. The present study aimed to investigate the efficacy of different infarct sites in predicting futile recanalization of patients with AIS.

Methods

Data were obtained from two multicenter, prospective, randomized, and controlled trials, which were concurrently conducted in China. Cases achieving a successful recanalization and with complete data of preoperative Alberta Stroke Program Early CT score (ASPECTS) and 90-day follow-up were included. The ASPECTS subregions were used to mark different infarct locations in the two cerebral hemispheres. First, the distribution of each ASPECTS subregion in the left and right hemispheres and the whole brain was analyzed, respectively. Then, the regions associated with futile recanalization were initially assessed by a univariate model. Afterward, a multivariate logistic regression model was used to identify the efficacy of different infarct sites in predicting futile recanalization.

Results

A total of 336 patients were included in this study with a median age of 65 years (IQR: 51–74), of whom 210 (62.50%) patients were male, and 189 (56.25%) met the definition of futile recanalization. The correlation between each ASPECTS subregion and poor outcome was different when it was restricted to a specific cerebral hemisphere. Moreover, in the left hemisphere, the internal capsule region (OR: 1.42, 95%CI: 1.13–1.95, P = 0.03) and the M3 region (OR: 2.26, 95%CI: 1.36–3.52, P = 0.001), and in the right hemisphere, M6 region (OR: 2.24, 95%CI: 1.32–3.36, P = 0.001) showed significantly higher efficacy in predicting futile recanalization.

Conclusion

The efficacy of different infarct locations in predicting futile recanalization is different. Different preoperative patterns of the high-efficiency regions in the infarction core or penumbra can guide the thrombectomy decision-making.
The relationship of alpha-synuclein to mitochondrial dynamics and quality control
Authors: Thorne Naomi J. , Tumbarello David A.
Published: August 2022

Maintenance of mitochondrial health is essential for neuronal survival and relies upon dynamic changes in the mitochondrial network and effective mitochondrial quality control mechanisms including the mitochondrial-derived vesicle pathway and mitophagy. Mitochondrial dysfunction has been implicated in driving the pathology of several neurodegenerative diseases, including Parkinson’s disease (PD) where dopaminergic neurons in the substantia nigra are selectively degenerated. In addition, many genes with PD-associated mutations have defined functions in organelle quality control, indicating that dysregulation in mitochondrial quality control may represent a key element of pathology. The most well-characterized aspect of PD pathology relates to alpha-synuclein; an aggregation-prone protein that forms intracellular Lewy-body inclusions. Details of how alpha-synuclein exerts its toxicity in PD is not completely known, however, dysfunctional mitochondria have been observed in both PD patients and models of alpha-synuclein pathology. Accordingly, an association between alpha-synuclein and mitochondrial function has been established. This relates to alpha-synuclein’s role in mitochondrial transport, dynamics, and quality control. Despite these relationships, there is limited research defining the direct mechanisms linking alpha-synuclein to mitochondrial dynamics and quality control. In this review, we will discuss the current literature addressing this association and provide insight into the proposed mechanisms promoting these functional relationships. We will also consider some of the alternative mechanisms linking alpha-synuclein with mitochondrial dynamics and speculate what the relationship between alpha-synuclein and mitochondria might mean both physiologically and in relation to PD.
Analysis of serum fatty acid, amino acid, and organic acid profiles in gestational hypertension and gestational diabetes mellitus via targeted metabolomics
Authors: Kong Xiangju , Zhu Qiushuang , Dong Yuanjie , Li Yuqiao , Liu Jinxiao , Yan Qingna , Huang Mingli , Niu Yucun
Published: August 2022

This study aimed to characterize metabolite differences and correlations between hypertensive disorders of pregnancy (HP) and gestational diabetes mellitus (GDM) using univariate, multivariate analyses, RF, and pathway analyses in a cross-sectional study. Dietary surveys were collected and targeted metabolomics was applied to measure levels of serum fatty acids, amino acids, and organic acids in 90 pregnant women at 24–28 weeks gestation at the First Affiliated Hospital of Harbin Medical University. Principal components analysis (PCA) and partial least squares-discriminatory analysis (PLS-DA) models were established to distinguish HP, GDM, and healthy, pregnant control individuals. Univariate and multivariate statistical analyses and Random Forest (RF) were used to identify and map co-metabolites to corresponding pathways in the disease states. Finally, risk factors for the disease were assessed by receiver operating characteristics (ROC) analysis. Dietary survey results showed that HP and GDM patients consumed a high-energy diet and the latter also consumed a high-carbohydrate and high-fat diet. Univariate analysis of clinical indices revealed HP and GDM patients had glycolipid disorders, with the former possessing more severe organ dysfunction. Subsequently, co-areas with significant differences identified by basic discriminant analyses and RF revealed lower levels of pyroglutamic acid and higher levels of 2-hydroxybutyric acid and glutamic acid in the GDM group. The number of metabolites increased in the HP group as compared to the healthy pregnant control group, including pyroglutamic acid, γ-aminobutyric acid (GABA), glutamic acid, oleic acid (C18:1), and palmitic acid (C16:0). ROC curves indicated that area under curve (AUC) for pyroglutamic acid in the GDM group was 0.962 (95% CI, 0.920–1.000), and the AUC of joint indicators, including pyroglutamic acid and GABA, in the HP group was 0.972 (95% CI, 0.938–1.000). Collectively, these results show that both GDM and HP patients at mid-gestation possessed dysregulated glucose and lipid metabolism, which may trigger oxidative stress via glutathione metabolism and biosynthesis of unsaturated fatty acids.
Microwave ablation plus camrelizumab monotherapy or combination therapy in non-small cell lung cancer
Authors: Huang Yahan , Wang Jiao , Hu Yanting , Cao Pikun , Wang Gang , Cai Hongchao , Wang Meixiang , Yang Xia , Wei Zhigang , Ye Xin
Published: August 2022

Purpose

Immunotherapy has become widely applied in non-small cell lung cancer (NSCLC) patients. However, the relatively low response rate of immunotherapy monotherapy restricts its application. Combination therapy improves the response rate and prolongs patient survival; however, adverse events (AEs) associated with immunotherapies increase with combination therapy. Therefore, exploring combination regimens with equal efficacy and fewer AEs is urgently required. The aim of this study was to evaluate the efficacy and safety of microwave ablation (MWA) plus camrelizumab monotherapy or combination therapy in NSCLC.

Materials and methods

Patients with pathologically confirmed, epidermal growth factor receptor/anaplastic lymphoma kinase-wild-type NSCLC were retrospectively enrolled in this study. Patients underwent MWA to the pulmonary lesions first, followed by camrelizumab monotherapy or combination therapy 5–7 days later. Camrelizumab was administered with the dose of 200 mg every 2 to 3 weeks. Treatment was continued until disease progression or intolerable toxicities. The technical success and technique efficacy of ablation, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), complications of ablation, and AEs were recorded.

Results

From January 1, 2019 to December 31, 2021, a total of 77 patients underwent MWA and camrelizumab monotherapy or combination therapy. Technical success was achieved in all patients (100%), and the technique efficacy was 97.4%. The ORR was 29.9%. The PFS and OS were 11.8 months (95% confidence interval, 9.5–14.1) and not reached, respectively. Smoking history and response to camrelizumab were correlated with PFS, and response to camrelizumab was correlated with OS in both the univariate and multivariate analyses. No periprocedural deaths due to ablation were observed. Complications were observed in 33 patients (42.9%). Major complications included pneumothorax (18.2%), pleural effusion (11.7%), pneumonia (5.2%), bronchopleural fistula (2.6%), and hemoptysis (1.3%). Grade 3 or higher AEs of camrelizumab, including reactive capillary endothelial proliferation, fatigue, pneumonia, edema, and fever, were observed in 10.4%, 6.5%, 5.2%, 2.6%, and 2.6% of patients, respectively.

Conclusion

MWA combined with camrelizumab monotherapy or combination therapy is effective and safe for the treatment of NSCLC.
Recurrent paraganglioma of the vulva: A rare case report and review of the literature
Authors: Kong Wenzhi , Qu Qingxi , Zhang Shiqian
Published: August 2022

Purpose

Vulva paragangliomas are rare and usually misdiagnosed or missed, especially in juveniles. Our aim was to summarize the clinical characteristics and treatments of vulva paragangliomas.

Methods and results

We present a case of a 17-year-old Chinese patient with functional paraganglioma from the vulva that was misdiagnosed as clear cell carcinoma. She had suffered from severe headaches, palpitations, sweating, pallor and hypertension. The vaginal wall was invaded by this mass. The tumour was surgically removed smoothly. However, the disease recurred 7 years after surgery, and the patient was treated again. Personalized genetic testing was performed while recovering, and the results suggested that the patient had a germline mutation in the Succinate Dehydrogenase subunit B (SDHB) gene. Now, the patient has been discharged successfully, her blood pressure has returned to normal and some of her clinical symptoms disappeared. A review of the literature concerning the topic is also presented, there have been only 2 cases of paraganglioma of the vulva and 11 cases of vaginal paraganglioma since 1955.

Conclusion

Our case describes a recurrent vulvovaginal paraganglioma with SDHB gene mutation and the largest tumor diameter to date. The diagnosis and treatment process of this case can provide reference for the management of other similar patients.
Bile is a reliable and valuable source to study cfDNA in biliary tract cancers
Authors: Li Zhanghui , Liu Yelei , Fu Junhui , Mugaanyi Joseph , Yan Junrong , Lu Caide , Huang Jing
Published: August 2022

Objective

The aim of this study is to determine the clinical efficacy of bile-derived liquid biopsy compared with plasma and tumor tissue biopsy in patients with biliary tract carcinoma (BTC).

Methods

A total of 13 patients with BTC were enrolled in this cohort. Tumor tissue, bile, and plasma samples were obtained and analyzed using next-generation sequencing for genomic profiling.

Results

Bile and plasma samples were collected from all 13 patients, and 11 patients also had matched tumor tissues available. The cell-free DNA (cfDNA) concentration was significantly higher in the bile supernatant than in plasma (median: 1918 vs. 63.1 ng/ml, p = 0.0017). The bile supernatant and pellet had a significantly higher mean mutation allele frequency (MF) than plasma (median: 3.84% vs. 4.22% vs. 0.16%; p < 0.001). Genomic alterations were predominantly missense. Both bile supernatant and pellet had significantly more genomic alterations than plasma (average: 9.3 vs. 7.2 vs. 2.3 alterations per sample; p < 0.01). Among the top 10 most frequent genomic alterations, the consistency between bile supernatant and tumor tissue was 90.00% (18/20), that between bile pellet and tumor tissue was 85.00% (17/20), and that between the plasma and tissue was only 35.00% (7/20). MAF of both bile supernatant and pellet was positively correlated with that in tissue samples (ρ < 0.0001, spearman r = 0.777, and ρ < 0.0001, spearman r = 0.787, respectively), but no significant correlation with tissue was found in the plasma (ρ = 0.966, spearman r = 0.008). Furthermore, additional genomic alterations could be detected in bile supernatant and pellet than in tissue. Potential targets for targeted therapy were identified in bile supernatant and pellet. Regarding copy number variation (CNV) and chromosomal instability (CIN) detection, four additional CNVs from two patients were detected in the bile supernatant that was not detected in tissues (i.e., amplification of TERC, IL7R, RICTOR, and TERT). CIN was significantly higher in tumor tissue than in plasma. The CIN of the bile was also significantly higher than that of plasma. There was no significant difference in CIN between the tissue and the bile supernatant.

Conclusion

The consistency of all genomic alterations and tumor tissue-determined genomic alteration in the bile supernatant/pellet was significantly higher than in plasma. Bile supernatants/pellets are better for genetic sequencing and may also have potential clinical value to guide targeted therapy and evaluate prognosis. Bile cfDNA may be a feasible substitute for tumor tissue in the genetic testing of patients with BTC.
Preoperative supplementation of calcitriol and calcium relieves symptom and extent of hypocalcemia in patients undergoing total thyroidectomy and bilateral central compartment neck dissection: A prospective, randomized, open-label, parallel-controlled clinical study
Authors: Li Dapeng , Tian Mengran , Zhang Yan , Yu Yang , Cheng Wenyuan , Li Yigong , Wang Junyi , Wei Songfeng , Wang Xin , Yang Xiaoyong , Zhao Jingzhu , Yun Xinwei , Zhang Wei , Song Jiayin , Zhang Huan , Zheng Xiangqian , Gao Ming
Published: August 2022

Background

Hypocalcemia is the most common complication that challenges surgeons performing total thyroidectomy. Conventional postoperative calcium and calcitriol supplement has been reportedly effective; however, a time lag has been reported before taking effect. Therefore, the role of preoperative strategy is yet to be determined.

Study design

In this prospective, randomized, open-label, parallel-controlled phase II clinical study (registration number: ChiCTR2200059815), a short-term preoperative administration of calcitriol and calcium was proposed in 210 patients undergoing total thyroidectomy and bilateral central compartment neck dissection. Patients were recruited and randomized (1:1:1) into three groups: (A) combined (preoperative calcitriol and calcium), (B) calcium only (preoperative calcium only), and (C) control (no preoperative intervention). Finally, a total of 172 patients were qualified for final analysis.

Results

Our data showed that 16 of 63 patients (25.4%) in the combined group had symptomatic hypocalcemia, whereas more patients from the control group (25 of 57 patients, 43.9%, P = 0.033) had symptomatic hypocalcemia. Further, the postoperative calcium level in the combined group is higher than in the control group (2.15 ± 0.15 vs. 2.09 ± 0.15 mmol/L, P = 0.031). Moreover, patients from the combined group showed lower calcium rates of <2.00 mmol/L (12.7% vs. 28.1%, P = 0.036). Remarkably, compared with the control group, patients with transient hypoparathyroidism in the combined group showed fewer rates for both symptomatic and biochemical hypocalcemia (28.6% vs. 61.1% for symptomatic hypocalcemia; 47.6% vs. 75% for biochemical hypocalcemia). Patients without transient hypoparathyroidism in all three groups showed no significant difference in rates for either symptomatic or biochemical hypocalcemia, indicating that this preoperative strategy is only effective for patients with transient hypoparathyroidism. We did not observe such beneficial effects in patients from the calcium group.

Conclusions

Preoperative administration of calcitriol and calcium could reduce symptomatic and biochemical hypocalcemia, especially for those with transient hypoparathyroidism. Moreover, this maneuver could be recommended as a clinical routine in patients undergoing total thyroidectomy and bilateral central compartment neck dissection.

Clinical Trial Registration

http://www.chictr.org.cn/edit.aspx?pid=164316&htm=4, identifier ChiCTR2200059815.
Characteristics and survival in bone metastatic breast cancer patients with different hormone receptor status: A population-based cohort study
Authors: Jiang Xiaofan , Chen Guanglei , Sun Lisha , Liu Chao , Zhang Yu , Liu Mingxin , Liu Caigang
Published: August 2022

Background

Accumulating preclinical evidence has uncovered the indispensable role of steroid hormone and their receptors, namely, estrogen receptor (ER) and progesterone receptor (PR), in the development of bone metastases in breast cancer. Limited data are available regarding the survival difference between different hormone receptor (HR) subgroups, and its prognostic significance is uncertain now. Such data are important for risk stratification and needed to formulate specialized regimen for bone metastatic breast cancer.

Methods

From the year of diagnosis 2010 to 2018, 554,585 breast cancer patients, among which are 19,439 with bone metastasis and 10,447 with bone-only metastasis, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier survival analysis was performed to compare the survival difference between the different HR status subgroups. Univariate and multivariate Cox proportional hazard regression was used to validate the prognostic role of HR status and identify other prognostic factors in bone metastatic breast cancer.

Results

ER-positive/PR-positive breast cancer patients with bone metastasis showed the best breast cancer-specific survival (BCSS) and overall survival (OS) than those with other HR statuses, while single PR-positive bone metastatic breast cancers manifest similar survival with ER-negative/PR-negative ones. Adjusted Cox regression analysis demonstrated that patients with older age, male, black race, ILC, higher tumor grade, T3–T4, HER2-negative status, absence of surgery or adjuvant treatment, and HR status other than ER-positive/PR-positive tended to have worse outcomes. Further subgroup analysis based on HER2 status showed that within HER2-positive breast cancers, ER-positive/PR-positive ones still manifest better survival than the other three HR status subgroups, which are similar in survival outcomes.

Conclusion

Although collectively viewed as HR-positive breast cancers, certain distinctions exist between bone metastatic breast cancers with different HR statuses in survival outcome. Our findings indicate that despite metastasizing to the same location, the different survival rate is determined by the HR status of breast cancer. The selection and intensity of the regimen should consider HR status, and HER2 status occasionally, when treating bone metastatic breast cancer.
Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma
Authors: Bian Sicheng , Zhang Xialin , Lin Leilei , Sun Lili , Guo Zhibo , Pan Jie , Cui Jiangxia , Yao Hanbing , Xu Jing , Hao Zhuanghui , Wang Yuzhu , Tong Liguo , Bu Xingpeng , Kong Desheng , Liu Nianjiao , Li Yinghua
Published: August 2022

Background

Hypercalcemia induced by multiple myeloma (MM) affects the biological functions of excitable and non-excitable cells. However, red blood cells (RBCs) regulatory effect on calcium in hypercalcemia is still not fully understood.

Methods

A total of 113 patients with MM osteolytic lesions were studied retrospectively. Flow cytometry and atomic absorption spectroscopy were used to detect calcium content. Immunofluorescence and Western blotting were used to investigate protein expression. GEO and miRNA databases were used to screen miRNAs. Exosomal miR-4261 migration was investigated by Transwell assay. Dual-luciferase assays confirmed the targeting relationship between miR-4261 and ATP2B4. An RBC oxidative stress model was constructed, and Omega-Agatoxin IVA was used to study the role of plasma membrane Ca2+-ATPase 4 (PMCA4) in RBCs.

Results

The results showed that MM RBCs had calcium overload, and serum calcium levels increased as the number of RBCs decreased. The expression of PMCA4 in MM RBCs was significantly lower than in normal RBCs. The exosomal miR-4261 produced by MM cells could be transferred to RBCs to downregulate the expression of ATP2B4.

Conclusions

Studies have confirmed that RBCs experience calcium overload in MM with osteolytic lesions, which is related to the downregulation of ATP2B4 by MM exosomal miR-4261.
On and off signaling pathways in the retina and the visual system
Authors: Ichinose Tomomi , Habib Samar
Published: August 2022

Visual processing starts at the retina of the eye, and signals are then transferred primarily to the visual cortex and the tectum. In the retina, multiple neural networks encode different aspects of visual input, such as color and motion. Subsequently, multiple neural streams in parallel convey unique aspects of visual information to cortical and subcortical regions. Bipolar cells, which are the second-order neurons of the retina, separate visual signals evoked by light and dark contrasts and encode them to ON and OFF pathways, respectively. The interplay between ON and OFF neural signals is the foundation for visual processing for object contrast which underlies higher order stimulus processing. ON and OFF pathways have been classically thought to signal in a mirror-symmetric manner. However, while these two pathways contribute synergistically to visual perception in some instances, they have pronounced asymmetries suggesting independent operation in other cases. In this review, we summarize the role of the ON–OFF dichotomy in visual signaling, aiming to contribute to the understanding of visual recognition.
Necrotizing pneumonia in children: Chest computed tomography vs. lung ultrasound
Authors: Carrard Johann , Bacher Sebastien , Rochat-Guignard Isabelle , Knebel Jean-François , Alamo Leonor , Meuwly Jean-Yves , Tenisch Estelle
Published: August 2022

Background

The utilization of contrast-enhanced computed tomography (CT) of the chest for the diagnosis of necrotizing pneumonia (NP), a complication of community-acquired pneumonia, is controversial because of the inherent ionizing radiation involved. Over the past few years, the growing availability of bedside Lung Ultrasound (LUS) devices has led to increased use of this nonionizing imaging method for diagnosing thoracic pathology, including pneumonia.

Objective

The objectives of this study were as follows: first, to compare the performance of LUS vs. CT in the identification of certain radiological signs of NP, and second, to determine whether LUS could replace CT in the diagnosis of NP.

Materials and methods

We compared retrospectively the CT and LUS images of 41 patients between 2005 and 2018 in whom at least one contrast-injected chest CT scan and one LUS had been undertaken fewer than 7 days apart.

Results

Pleural effusions were demonstrated almost systematically (100% on CT vs. 95.8% on LUS). Visualization of septations in pleural effusions was clearly superior on LUS (20.4% on CT vs 62.5% on LUS). Concerning the detection of necrosis, we observed a strong correlation between LUS and the gold-standard CT (95.8% on LUS vs. 93.7% on CT). Parenchymal cavities were more easily detected on CT than on LUS (79.1 vs. 35.4%).

Conclusion

LUS has shown to be as effective as CT in the diagnosis of NP. The use of CT in patients with NP could be limited to the detection of complications such as bronchopleural fistulae in unfavorably evolving diseases.
Rotavirus vaccination and the risk of type 1 diabetes and celiac disease: A systematic review and meta-analysis
Authors: Zhang Xue , Xu Xiang-fei , Jin Jie
Published: August 2022

Background

Rotavirus vaccination has been proven to effectively protect against rotavirus gastroenteritis. However, there are concerns about the relationship between rotavirus vaccination and the risk of autoimmune disorders. Thus, we conducted a systematic review and meta-analysis to comprehensively assess the association between rotavirus vaccination and type 1 diabetes (T1D) or celiac disease (CD) risk.

Methods

A systematic review and meta-analysis were conducted to evaluate the type 1 diabetes or celiac disease associated with rotavirus vaccination. The following journal databases were searched to identify potential studies for inclusion: PubMed, Embase, and Cochrane Library databases.

Results

Seven articles involving more than 5,793,055 children were included. Our results showed that rotavirus vaccination does not alter the subsequent risk of T1D (RR 0.94, 95% CI: 0.82–1.09) or CD (RR 0.86, 95% CI: 0.64–1.17) after vaccination. Furthermore, the risk of T1D was not increased or decreased for children fully exposed to rotavirus vaccination (RR 0.86, 95% CI, 0.54–1.36) and for children partially exposed to rotavirus vaccination (RR 1.05, 95% CI, 0.87–1.26). However, younger (<5 years) vaccinated children at the end of study (RR 0.84, 95% CI = 0.75–0.95) may be at a lower risk for T1D than older (≥5 years) vaccinated children (RR 0.93, 95% CI, 0.81–1.07).

Conclusion

The findings of this study suggest that rotavirus vaccination does not appear to be associated with T1D or CD in children. The protective effect of rotavirus vaccination on T1D may be presented by time dependent.
Successful treatment of pleural empyema and necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus infection following influenza A virus infection: A case report and literature review
Authors: Han Chunjiao , Zhang Tongqiang , Zhao Yidi , Dong Lili , Li Xiaole , Zheng Jiafeng , Guo Wei , Xu Yongsheng , Cai Chunquan
Published: August 2022

With the rapid increase in the number of infections, children with Staphylococcus aureus (S. aureus) infection secondary to Influenza A virus (IAV), appear to have a great possibility of causing severe complications and illness. Despite some cases and research findings regarding the death of children with IAV and S. aureus, coinfection included, there were few details about successful treatment of pleural empyema and necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) infection following IAV. In this case report, we describe the clinical symptoms and treatment of a teenager with pleural empyema and necrotizing pneumonia related to S. aureus secondary infection who was initially infected by IAV. This case highlights the importance of early recognition and application of thoracoscopy for this potentially fatal pleural empyema caused by MRSA and IAV coinfection. We conclude that this is a significant case that contributes to raising awareness regarding rarely occurring severe respiratory infections by MRSA in a child with normal immune function after IAV. In addition, further studies are needed to explore risk factors for IAV coinfection with S. aureus.
Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
Authors: Lee Da Eun , Kang Hyeon Woong , Kim So Yi , Kim Myeong Jin , Jeong Jae Woong , Hong Woosol Chris , Fang Sungsoon , Kim Hyung Sun , Lee Yun Sun , Kim Hyo Jung , Park Joon Seong
Published: August 2022

Pancreatic cancer is an aggressive cancer characterized by high mortality and poor prognosis, with a survival rate of less than 5 years in advanced stages. Ivermectin, an antiparasitic drug, exerts antitumor effects in various cancer types. This is the first study to evaluate the anticancer effects of the combination of ivermectin and gemcitabine in pancreatic cancer. We found that the ivermectin–gemcitabine combination treatment suppressed pancreatic cancer more effectively than gemcitabine alone treatment. The ivermectin–gemcitabine combination inhibited cell proliferation via G1 arrest of the cell cycle, as evidenced by the downregulation of cyclin D1 expression and the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT-3) signaling pathway. Ivermectin–gemcitabine increased cell apoptosis by inducing mitochondrial dysfunction via the overproduction of reactive oxygen species and decreased the mitochondrial membrane potential. This combination treatment also decreased the oxygen consumption rate and inhibited mitophagy, which is important for cancer cell death. Moreover, in vivo experiments confirmed that the ivermectin–gemcitabine group had significantly suppressed tumor growth compared to the gemcitabine alone group. These results indicate that ivermectin exerts synergistic effects with gemcitabine, preventing pancreatic cancer progression, and could be a potential antitumor drug for the treatment of pancreatic cancer.
Rashba effect on linear and nonlinear optical properties of a cylindrical core/shell heterojunction quantum dot
Authors: Kria M. , Nautiyal Vijit V. , Lakaal K. , El Hamdaoui J. , Pérez L. M. , Varsha  , Laroze D. , Prasad V. , Long G. , Feddi E.
Published: August 2022

Rashba effect may play an important role in the nonlinear optical properties of heterojunction quantum dots. In this work, we have theoretically examined the effects of Rashba spin-orbit interaction on an electron in a cylindrical core/shell quantum dot (CCSQD). The modifications of various properties of cylindrical core/shell quantum dot such as transition energies, dipole transition matrix elements and linear and nonlinear optical properties due to change in Rashba coupling parameter, magnetic field and effective Rydberg energy were studied. We solved the Schrödinger equation using numerical methods and obtained energy eigenvalues as functions of the aforementioned parameters. It was observed that, the magnetic field has a considerable effect on absorption coefficients and refractive index. It was also observed that increasing the magnetic field shifts the resonances towards higher energies. Additionally, increasing in the Rashba coupling coefficient (αR) was found out to result an increase in absorption coefficients and refractive index. Our results demonstrated that, we can manipulate optical properties of cylindrical core/shell quantum dot using an external magnetic field.