bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical comparison between thoracoscopic and thoracotomy repair of Gross type C esophageal atresia
Authors: Yang Shen , Wang Peize , Yang Zhi , Li Siqi , Liao Junmin , Hua Kaiyun , Zhang Yanan , Zhao Yong , Gu Yichao , Li Shuangshuang , Chen Yongwei , Huang Jinshi
Published: November 2021

Background

To compare the clinical outcomes between thoracoscopic approach and thoracotomy surgery in patients with Gross type C Esophageal atresia (EA) and tracheoesophageal fistula (TEF).

Methods

Patients with Gross type C EA/TEF who underwent surgery from January 2007 to January 2020 at Beijing Children’s Hospital were retrospectively analyzed. The patients were divided into two groups according to surgical approaches. The perioperative factors and postoperative complications were compared among the two groups.

Results

One hundred and ninety patients (132 boys and 58 girls) with a median birth weight of 2975 (2600, 3200) g were included. The primary operations were performed via thoracoscopic (n = 62) and thoracotomy (n = 128) approach. After comparison of clinical characteristics between the two groups, we found that there were statistically significant differences in associated anomalies, method of fistula closure, duration of mechanical ventilation after surgery, feeding option before discharge, management of pneumothorax, and prognosis (all P < 0.05). To a certain extent, thoracoscopic surgery reduced the incidence of anastomotic leakage and increased the incidence of anastomotic stricture in this study. However, there were no statistically significant differences between the two groups in terms of operative time, postoperative pneumothorax, anastomotic leakage, anastomotic stricture, and recurrent tracheoesophageal fistula (all P > 0.05).

Conclusions

Thoracoscopy surgery for Gross type C EA/TEF is a safe and effective, minimally invasive technique with comparable operative time and incidence of postoperative complications.
Decomposition of outpatient health care spending by disease - a novel approach using insurance claims data
Authors: Stucki Michael , Nemitz Janina , Trottmann Maria , Wieser Simon
Published: November 2021

Background

Decomposing health care spending by disease, type of care, age, and sex can lead to a better understanding of the drivers of health care spending. But the lack of diagnostic coding in outpatient care often precludes a decomposition by disease. Yet, health insurance claims data hold a variety of diagnostic clues that may be used to identify diseases.

Methods

In this study, we decompose total outpatient care spending in Switzerland by age, sex, service type, and 42 exhaustive and mutually exclusive diseases according to the Global Burden of Disease classification. Using data of a large health insurance provider, we identify diseases based on diagnostic clues. These clues include type of medication, inpatient treatment, physician specialization, and disease specific outpatient treatments and examinations. We determine disease-specific spending by direct (clues-based) and indirect (regression-based) spending assignment.

Results

Our results suggest a high precision of disease identification for many diseases. Overall, 81% of outpatient spending can be assigned to diseases, mostly based on indirect assignment using regression. Outpatient spending is highest for musculoskeletal disorders (19.2%), followed by mental and substance use disorders (12.0%), sense organ diseases (8.7%) and cardiovascular diseases (8.6%). Neoplasms account for 7.3% of outpatient spending.

Conclusions

Our study shows the potential of health insurance claims data in identifying diseases when no diagnostic coding is available. These disease-specific spending estimates may inform Swiss health policies in cost containment and priority setting.
Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression
Authors: He Rong-Zhang , Jiang Jing , Hu Xinglin , Lei Ming , Li Jia , Luo Weihao , Duan Lili , Hu Zheng , Mo Yin-Yuan , Luo Di-Xian , Peng Wan-Xin
Published: November 2021

Background

UCA1 is frequently upregulated in a variety of cancers, including CRC, and it can play an oncogenic role by various mechanisms. However, how UCA1 is regulated in cancer is largely unknown. In this study, we aimed to determine whether RNA methylation at N6-methyladenosine (m6A) can impact UCA1 expression in colorectal cancer (CRC).

Methods

qRT-PCR was performed to detect the level of UCA1 and IGF2BP2 in CRC samples. CRISPR/Cas9 was employed to knockout (KO) UCA1, METTL3 and WTAP in DLD-1 and HCT-116 cells, while rescue experiments were carried out to re-express METTL3 and WTAP in KO cells. Immunoprecipitation using m6A antibody was performed to determine the m6A modification of UCA1. In vivo pulldown assays using S1m tagging combined with site-direct mutagenesis was carried out to confirm the recognition of m6A-modified UCA1 by IGF2BP2. Cell viability was measured by MTT and colony formation assays. The expression of UCA1 and IGF2BP2 in TCGA CRC database was obtained from GEPIA (http://gepia.cancer-pku.cn).

Results

Our results revealed that IGF2BP2 serves as a reader for m6A modified UCA1 and that adenosine at 1038 of UCA1 is critical to the recognition by IGF2BP2. Importantly, we showed that m6A writers, METTL3 and WTAP positively regulate UCA1 expression. Mechanically, IGF2BP2 increases the stability of m6A-modified UCA1. Clinically, IGF2BP2 is upregulated in CRC tissues compared with normal tissues.

Conclusion

These results suggest that m6A modification is an important factor contributing to upregulation of UCA1 in CRC tissues.
Risk of non-melanoma skin cancer with biological therapy in common inflammatory diseases: a systemic review and meta-analysis
Authors: Liu Ruolin , Wan Qianyi , Zhao Rui , Xiao Haitao , Cen Ying , Xu Xuewen
Published: November 2021

Background

Most previous studies compared the risk for non-melanoma skin cancer (NMSC) in biologic-treated common inflammatory diseases with the general population. Whether the increased NMSC risk is caused by the disease itself, the biologics, or both remains unknown.

Methods

We systematically searched PubMed, Embase, Medline, Web of Science, and Cochrane Library from inception to May 2021. Studies were included if they assessed the risk of NMSC for rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis patients treated with biologics compared with patients not receiving biologics. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model.

Results

The current meta-analysis included 12 studies. Compared with patients with the inflammatory disease without biologics, patients receiving biological therapy were associated with an increased risk for NMSC (RR 1.25, 95% CI 1.14 to 1.37), especially in patients with RA (RR 1.24, 95% CI 1.13 to 1.36) and psoriasis (RR 1.28, 95% CI 1.07 to 1.52), but not in patients with IBD (RR 1.49, 95% CI 0.46 to 4.91). The risks for squamous cell skin cancer and basal cell skin cancer were both increased for patients receiving biologics. However, the risk of NMSC did not increase in patients treated with biologics less than 2 years.

Conclusions

Current evidence suggests that increased risk of NMSC was identified in RA and psoriasis treated with biologics compared with patients not receiving biologics, but not in patients with IBD. The inner cause for the increased risk of NMSC in IBD patients should be further discussed.
Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia
Authors: Chu Ming-qiang , Zhang Liu-chao , Yuan Qian , Zhang Ting-juan , Zhou Jing-dong
Published: November 2021

Background

There is mounting evidence that demonstrated the association of aberrantNEDD4Lexpression with diverse human cancers. However, the expression pattern and clinical implication ofNEDD4Lin acute myeloid leukemia (AML) remains poorly defined.

Methods

We systemically determinedNEDD4Lexpression with its clinical significance in AML by both public data and our research cohort. Moreover, biological functions ofNEDD4Lin leukemogenesis were further tested by in vitro experiments.

Results

By the public data, we identified that lowNEDD4Lexpression was correlated with AML among diverse human cancers. Expression ofNEDD4Lwas remarkably decreased in AML compared with controls, and was confirmed by our research cohort. Clinically, low expression ofNEDD4Lwas correlated with greatly lower age, higher white blood cells, and higher bone marrow/peripheral blood blasts. Moreover,NEDD4Lunderexpression was positively correlated with normal karyotype,FLT3andNPM1mutations, but negatively associated with complex karyotype andTP53mutations. Importantly, the association betweenNEDD4Lexpression and survival was also discovered in cytogenetically normal AML patients. Finally, a number of 1024 RNAs and 91 microRNAs were identified to be linked toNEDD4Lexpression in AML. Among the negatively correlated microRNAs,miR-10awas also discovered as a microRNA that may directly targetNEDD4L. Further functional studies revealed thatNEDD4Lexhibited anti-proliferative and pro-apoptotic effects in leukemic cell line K562.

Conclusions

Our findings indicated thatNEDD4Lunderexpression, as a frequent event in AML, was associated with genetic abnormalities and prognosis in AML. Moreover,NEDD4Lexpression may be involved in leukemogenesis with potential therapeutic target value.
Hydroxypropylmethylcellulose as a film and hydrogel carrier for ACP nanoprecursors to deliver biomimetic mineralization
Authors: Wang Zhe , Zhou Zihuai , Fan Jiayan , Zhang Leiqing , Zhang Zhixin , Wu Zhifang , Shi Ying , Zheng Haiyan , Zhang Zhengyi , Tang Ruikang , Fu Baiping
Published: November 2021

Demineralization of hard tooth tissues leads to dental caries, which cause health problems and economic burdens throughout the world. A biomimetic mineralization strategy is expected to reverse early dental caries. Commercially available anti-carious mineralizing products lead to inconclusive clinical results because they cannot continuously replenish the required calcium and phosphate resources. Herein, we prepared a mineralizing film consisting of hydroxypropylmethylcellulose (HPMC) and polyaspartic acid-stabilized amorphous calcium phosphate (PAsp-ACP) nanoparticles. HPMC which contains multiple hydroxyl groups is a film-forming material that can be desiccated to form a dry film. In a moist environment, this film gradually changes into a gel. HPMC was used as the carrier of PAsp-ACP nanoparticles to deliver biomimetic mineralization. Our results indicated that the hydroxyl and methoxyl groups of HPMC could assist the stability of PAsp-ACP nanoparticles and maintain their biomimetic mineralization activity. The results further demonstrated that the bioinspired mineralizing film induced the early mineralization of demineralized dentin after 24 h with increasing mineralization of the whole demineralized dentin (3–4 µm) after 72–96 h. Furthermore, these results were achieved without any cytotoxicity or mucosa irritation. Therefore, this mineralizing film shows promise for use in preventive dentistry due to its efficient mineralization capability.

Graphical Abstract
A systems approach to the exploration of research activity and relationships within a local authority
Authors: Fynn Judith F. , Jones John , Jones Andy
Published: November 2021

Background

Organizations with responsibilities for public health are increasingly required to use evidence-based practice to inform programme delivery, requiring research to generate relevant evidence, and dissemination and use of evidence to inform decisions and practices. Understanding how relationships between organizational structures, systems and processes influence evidence-based practices is critical to improving practice at both an institutional and system level, yet how these relationships should best operate is not well understood. Understanding how to better support research within local authorities, the elected administrative bodies responsible for services including public health at a regional level in the United Kingdom, is a priority for the National Institute for Health Research (NIHR) Public Health Research. This study is based on Norfolk County Council, a local authority in the east of England. We aimed to apply a systems perspective to develop a better understanding of the structures, systems and processes that support a local authority in becoming research-active, identifying gaps in understanding and recommendations for action to address them.

Methods

Taking a participatory action research approach, we applied qualitative methods to explore research activity and relationships in Norfolk County Council. We surveyed employees and used network analysis to map individuals, departments and external partners involved in research activities and the connections between them. We then applied participatory approaches to conduct a series of focus groups and semi-structured interviews to explore stakeholders’ experiences and perceptions of being involved in research at, or with, the authority, and their ideas for recommendations for future actions.

Results

A range of research activity is undertaken at the local authority, with an emphasis on applied work to improve service delivery. We identified several examples of effective practice and models of research collaboration in some departments. Challenges such as limitations in resources, capacity and knowledge exchange were evident, yet there was a readiness amongst key stakeholders to develop and implement actions that may better support the authority in becoming more research-active.

Conclusion

In large complex organizations, a key challenge is how to share learning across teams and implement good practice at an organizational and system level. Our findings highlight the potential for developing improved collaborative partnership models and systems to support sustainable processes and practices for research and knowledge exchange at an institutional and interorganizational level. The insights gained and shared will support other local authorities and similar large, multilevel organizations with responsibilities for evidence-based public health to explore their own setting and implement change where needed, and provide stimulus for further research into system-level change.
Ibrutinib protects T cells in patients with CLL from proliferation-induced senescence
Authors: Davis Joanne E. , Sharpe Chia , Mason Kylie , Tam Constantine S. , Koldej Rachel M. , Ritchie David S.
Published: November 2021

Background

The development of Bruton’s tyrosine kinase inhibitors (BTKi) for the treatment of chronic lymphocytic leukaemia (CLL) has provided a highly effective and relatively non-toxic alternative to conventional chemotherapy. Some studies have shown that BTKi can also lead to improvements in T cell immunity in patients despite in vitro analyses suggesting an immunosuppressive effect of BTKi on T cell function.

Methods

In this study, we examined both the in vitro effect and long-term in vivo effect of two clinically available BTKi, ibrutinib and zanubrutinib. Additional in vitro assessments were undertaken for a third BTKi, acalabrutinib. Immune subset phenotyping, cytokine secretion, T cell degranulation and proliferation assays were performed on peripheral blood mononuclear cells isolated from untreated CLL patients, and CLL patients on long-term (> 12 months) BTKi treatment.

Results

Similar to prior studies we observed that long-term BTKi treatment normalises lymphocyte subset frequency and reduces PD-1 expression on T cells. We also observed that T cells from patients taken prior to BTKi therapy showed an abnormal hyper-proliferation pattern typical of senescent T cells, which was normalised by long-term BTKi treatment. Furthermore, BTKi therapy resulted in reduced expression of the T cell exhaustion markers PD-1, TIM3 and LAG3 in late generations of T cells undergoing proliferation.

Conclusions

Collectively, these findings indicate that there are critical differences between the in vitro effects of BTKi on T cell function and the effects derived from long-term BTKi exposure in vivo. Overall long-term exposure to BTKi, and particularly ibrutinib, resulted in improved T cell fitness in part due to suppressing the abnormal hyper-proliferation of CLL T cells and the associated development of T cell senescence.
Six splice site variations, three of them novel, in the ABO gene occurring in nine individuals with ABO subtypes
Authors: Hong Xiaozhen , Ying Yanling , Zhang Jingjing , Chen Shu , Xu Xianguo , He Ji , Zhu Faming
Published: November 2021

Background

Nucleotide mutations in theABOgene may reduce the activity of glycosyltransferase, resulting in lower levels of A or B antigen expression in red blood cells. Six known splice sites have been identified according to the database of red cell immunogenetics and the blood group terminology of the International Society of Blood Transfusion. Here, we describe six distinct splice site variants in individuals with ABO subtypes.

Methods

The ABO phenotype was examined using a conventional serological method. A polymerase chain reaction sequence-based typing method was used to examine the whole coding sequence of theABOgene. TheABOgene haplotypes were studied using allele-specific primer amplification or cloning technology. In silico analytic tools were used to assess the functional effect of splice site variations.

Results

Six distinct variants in theABOgene splice sites were identified in nine individuals with ABO subtypes, including c.28 + 1_2delGT, c.28 + 5G > A, c.28 + 5G > C, c.155 + 5G > A, c.204-1G > A and c.374 + 5G > A. c.28 + 1_2delGT was detected in an Awindividual, while c.28 + 5G > A, c.28 + 5G > C, and c.204-1G > A were detected in Belindividuals. c.155 + 5G > A was detected in one B3and two AB3individuals, whereas c.374 + 5G > A was identified in two Aelindividuals. Three novel splice site variants (c.28 + 1_2delGT, c.28 + 5G > A and c.28 + 5G > C) in theABOgene were discovered, all of which resulted in low antigen expression. In silico analysis revealed that all variants had the potential to alter splice transcripts.

Conclusions

Three novel splice site variations in theABOgene were identified in Chinese individuals, resulting in decreased A or B antigen expression and the formation of ABO subtypes.
Computer-assisted cannulated screw internal fixation versus conventional cannulated screw internal fixation for femoral neck fractures: a systematic review and meta-analysis
Authors: Cheng Qing-hao , Li Peng-biao , Lu Ting-ting , Guo Shi-fang , Di Wen-fei , Yang Ke-hu , Qian Yao-wen
Published: November 2021

Objective

To compare the effects between computer-assisted and traditional cannulated screw internal fixation on treating femoral neck fracture.

Methods

The search was conducted in Embase, Pubmed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Database from the beginning to August 2020. RevMan5.4 software, which was provided by the International Cochrane Group, was used for the meta-analysis comparing the differences in operation time, intraoperative bleeding volume, fluoroscopy frequency, fracture healing time, total drilling times, Harris score, fracture healing rate, and femoral head necrosis rate between computer-assisted and traditional methods groups.

Results

A total of 1028 patients were included in 16 studies. Primary outcome indicators: Compared with the traditional method group, the computer-assisted group had less operative time (2RCTs,P < 0.00001; 8 non-RCTs,P = 0.009; Overall,P < 0.00001), intraoperative bleeding (1 RCTs,P < 0.00001; 9non-RCTs,P < 0.00001; Overall,P < 0.00001), femoral head necrosis rate (1 RCT,P = 0.11;7 non-RCTs,P = 0.09; Overall,P = 0.02) and higher Harris scores (1 RCT,P < 0.0001; 9 non-RCTs,P = 0.0002; Overall,P < 0.0001), and there were no significant differences in fracture healing rate between the two groups (5 non-RCTs,P = 0.17). Secondary outcomes indicators: The computer-assisted group had a lower frequency of intraoperative fluoroscopy and total number of drills compared with the traditional method group, while there was no significant difference in fracture healing time.

Conclusion

Compared with the traditional hollow screw internal fixation on the treatment of femoral neck fracture, computer-assisted percutaneous cannulated screw fixation can shorten the operation time and improve the operation efficiency and reduce the X-ray injury of medical staff and help patients obtain a better prognosis. Therefore, computer-assisted percutaneous cannulated screw fixation is a better choice for the treatment of femoral neck fracture.

Study registrationPROSPERO registration number CRD42020214493.
A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation
Authors: Wu Chao , Huang Zhi-Hong , Meng Zi-Qi , Fan Xiao-Tian , Lu Shan , Tan Ying-Ying , You Lei-Ming , Huang Jia-Qi , Stalin Antony , Ye Pei-Zhi , Wu Zhi-Shan , Zhang Jing-Yuan , Liu Xin-Kui , Zhou Wei , Zhang Xiao-Meng , Wu Jia-Rui
Published: November 2021

Background

Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated.

Methods

Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis.

Results

The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes (NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92andSFN) associated with the development of PC, and survival analysis found 5 genes (TSPOAP1, ADGRG6, GPR87, FAM111BandMMP28) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found thatCDK1,JAK1,EGFR,MAPK1andMAPK3served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis.

Conclusions

Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI.
CCR5 antagonist reduces HIV-induced amyloidogenesis, tau pathology, neurodegeneration, and blood-brain barrier alterations in HIV-infected hu-PBL-NSG mice
Authors: Bhargavan Biju , Woollard Shawna M. , McMillan Jo Ellyn , Kanmogne Georgette D.
Published: November 2021

Background

Neurocognitive impairment is present in 50% of HIV-infected individuals and is often associated with Alzheimer’s Disease (AD)-like brain pathologies, including increased amyloid-beta (Aβ) and Tau hyperphosphorylation. Here, we aimed to determine whether HIV-1 infection causes AD-like pathologies in an HIV/AIDS humanized mouse model, and whether the CCR5 antagonist maraviroc alters HIV-induced pathologies.

Methods

NOD/scid–IL-2Rγcnull mice engrafted with human blood leukocytes were infected with HIV-1, left untreated or treated with maraviroc (120 mg/kg twice/day). Human cells in animal’s blood were quantified weekly by flow cytometry. Animals were sacrificed at week-3 post-infection; blood and tissues viral loads were quantified using p24 antigen ELISA, RNAscope, and qPCR. Human (HLA-DR+) cells, Aβ-42, phospho-Tau, neuronal markers (MAP 2, NeuN, neurofilament-L), gamma-secretase activating protein (GSAP), and blood-brain barrier (BBB) tight junction (TJ) proteins expression and transcription were quantified in brain tissues by immunohistochemistry, immunofluorescence, immunoblotting, and qPCR. Plasma Aβ-42, Aβ-42 cellular uptake, release and transendothelial transport were quantified by ELISA.

Results

HIV-1 significantly decreased human (h)CD4+ T-cells and hCD4/hCD8 ratios; decreased the expression of BBB TJ proteins claudin-5, ZO-1, ZO-2; and increased HLA-DR+ cells in brain tissues. Significantly, HIV-infected animals showed increased plasma and brain Aβ-42 and phospho-Tau (threonine181, threonine231, serine396, serine199), associated with transcriptional upregulation of GSAP, an enzyme that catalyzes Aβ formation, and loss of MAP 2, NeuN, and neurofilament-L. Maraviroc treatment significantly reduced blood and brain viral loads, prevented HIV-induced loss of neuronal markers and TJ proteins; decreased HLA-DR+ cells infiltration in brain tissues, significantly reduced HIV-induced increase in Aβ-42, GSAP, and phospho-Tau. Maraviroc also reduced Aβ retention and increased Aβ release in human macrophages; decreased the receptor for advanced glycation end products (RAGE) and increased low-density lipoprotein receptor–related protein-1 (LRP1) expression in human brain endothelial cells. Maraviroc induced Aβ transendothelial transport, which was blocked by LRP1 antagonist but not RAGE antagonist.

Conclusions

Maraviroc significantly reduced HIV-induced amyloidogenesis, GSAP, phospho-Tau, neurodegeneration, BBB alterations, and leukocytes infiltration into the CNS. Maraviroc increased cellular Aβ efflux and transendothelial Aβ transport via LRP1 pathways. Thus, therapeutically targeting CCR5 could reduce viremia, preserve the BBB and neurons, increased brain Aβ efflux, and reduce AD-like neuropathologies.
Bevacizumab confers significant improvements in survival for ovarian cancer patients with low miR-25 expression and high miR-142 expression
Authors: Li Jun , Yue Huiran , Li Wenzhi , Zhu Guohua , Zhu Tingting , Chen Ruifang , Lu Xin
Published: November 2021

Background

Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients.

Methods

The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset.

Results

We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status.

Conclusion

In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.
Pediatric eosinophilic esophagitis: a review for the clinician
Authors: Barni Simona , Arasi Stefania , Mastrorilli Carla , Pecoraro Luca , Giovannini Mattia , Mori Francesca , Liotti Lucia , Saretta Francesca , Castagnoli Riccardo , Caminiti Lucia , Cianferoni Antonella , Novembre Elio
Published: November 2021

Eosinophilic esophagitis (EoE) is a chronic clinical-pathologic disease characterized by eosinophilic infiltration of the esophageal epithelium with esophageal dysfunction symptoms.

EoE can occur at any age and has different clinical manifestations depending on the age onset.

To date, esophago-gastroduodenal endoscopy (EGD) with biopsy is the gold-standard for EoE diagnosis.

According to the recent consensus guidelines, proton pump inhibitors, corticosteroids and elimination diets could be a first-line therapy option. The aim of the treatment is clinical and histological remission for preventing long-lasting untreatable fibrosis.

A multidisciplinary approach (allergist, gastroenterology, dietitian, and pathologist) is recommended for managing patients affected by EoE, given the complexity of its treatment.

This review will provide a practical guide to assist pediatricians treating children with EoE.

Moreover, it highlights the unmet needs in diagnosis and treatment that require urgent attention from the scientific community in the aim of improving the management of patients with EoE.
Neighborhood disadvantage and individual-level life stressors in relation to breast cancer incidence in US Black women
Authors: Barber Lauren E. , Zirpoli Gary R. , Cozier Yvette C. , Rosenberg Lynn , Petrick Jessica L. , Bertrand Kimberly A. , Palmer Julie R.
Published: November 2021

Background

Research on psychosocial stress and risk of breast cancer has produced conflicting results. Few studies have assessed this relation by breast cancer subtype or specifically among Black women, who experience unique chronic stressors.

Methods

We used prospective data from the Black Women’s Health Study, an ongoing cohort study of 59,000 US Black women, to assess neighborhood- and individual-level psychosocial factors in relation to risk of breast cancer. We used factor analysis to derive two neighborhood score variables after linking participant addresses to US Census data (2000 and 2010) on education, employment, income and poverty, female-headed households, and Black race for all households in each residential block group. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for established breast cancer risk factors.

Results

During follow-up from 1995 to 2017, there were 2167 incident invasive breast cancer cases (1259 estrogen receptor positive (ER +); 687 ER negative (ER−)). For ER− breast cancer, HRs were 1.26 (95% CI 1.00–1.58) for women living in the highest quartile of neighborhood disadvantage relative to women in the lowest quartile, and 1.24 (95% CI 0.98–1.57) for lowest versus highest quartile of neighborhood socioeconomic status (SES). For ER+ breast cancer, living in the lowest quartile of neighborhood SES was associated with a reduced risk of ER+ breast cancer (HR = 0.83, 95% CI 0.70–0.98). With respect to individual-level factors, childhood sexual abuse (sexual assault ≥ 4 times vs. no abuse: HR = 1.35, 95% CI 1.01–1.79) and marital status (married/living together vs. single: HR = 1.29, 95% CI 1.08–1.53) were associated with higher risk of ER+, but not ER− breast cancer.

Conclusion

Neighborhood disadvantage and lower neighborhood SES were associated with an approximately 25% increased risk of ER− breast cancer in this large cohort of Black women, even after control for multiple behaviors and lifestyle factors. Further research is need to understand the underlying reasons for these associations. Possible contributing factors are biologic responses to the chronic stress/distress experienced by individuals who reside in neighborhoods characterized by high levels of noise, crime and unemployment or the direct effects of environmental toxins.
Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways
Authors: Labrèche Cédrik , Cook David P. , Abou-Hamad John , Pascoal Julia , Pryce Benjamin R. , Al-Zahrani Khalid N. , Sabourin Luc A.
Published: November 2021

Background

Breast cancer is a highly heterogeneous disease with multiple drivers and complex regulatory networks. Periostin (Postn) is a matricellular protein involved in a plethora of cancer types and other diseases. Postn has been shown to be involved in various processes of tumor development, such as angiogenesis, invasion, cell survival and metastasis. The expression of Postn in breast cancer cells has been correlated with a more aggressive phenotype. Despite extensive research, it remains unclear how epithelial cancer cells regulate Postn expression.

Methods

Using murine tumor models and human TMAs, we have assessed the proportion of tumor samples that have acquired Postn expression in tumor cells. Using biochemical approaches and tumor cell lines derived from Neu+ murine primary tumors, we have identified major regulators of Postn gene expression in breast cancer cell lines.

Results

Here, we show that, while the stromal compartment typically always expresses Postn, about 50% of breast tumors acquire Postn expression in the epithelial tumor cells. Furthermore, using an in vitro model, we show a cross-regulation between FGFR, TGFβ and PI3K/AKT pathways to regulate Postn expression. In HER2-positive murine breast cancer cells, we found that basic FGF can repress Postn expression through a PKC-dependent pathway, while TGFβ can induce Postn expression in a SMAD-independent manner. Postn induction following the removal of the FGF-suppressive signal is dependent on PI3K/AKT signaling.

Conclusion

Overall, these results reveal a novel regulatory mechanism and shed light on how breast tumor cells acquire Postn expression. This complex regulation is likely to be cell type and cancer specific as well as have important therapeutic implications.
COVID-19 vaccine preferences among university students in Hong Kong: a discrete choice experiment
Authors: Li Xue , Chong Man Yui , Chan Ching Yui , Chan Vindy Wing Sum , Tong Xinning
Published: November 2021

Objective

To promote public health and resume university activities, COVID-19 vaccination has been mandated from an increasing number of universities worldwide. The objective of the study is to understand the factors that impact preference and willingness to take the vaccine among university students in Hong Kong universities utilizing an online questionnaire. The findings will be imperative for health education and the success of the vaccination program.

Results

We conducted a discrete choice experiment survey among university students in Hong Kong and applied conditional logit regression to estimate their vaccine preference and the weight of each attribute. Regression results showed adverse reactions, efficacy, origin of the vaccine, required number of doses and out-of-pocket price are significant determinants for the choice of vaccine, ranked from the most to least important. Similar preference weighting results were observed after adjusting age, sex, monthly household income, studying medical-related subjects and recent influenza vaccination. Safety, efficacy and origin of the vaccine are key drivers for vaccination decisions among young adults in Hong Kong. Health education and communication focused on these factors are urgently needed to overcome vaccine hesitancy and improve the vaccine uptake.
Multiocular organoids from human induced pluripotent stem cells displayed retinal, corneal, and retinal pigment epithelium lineages
Authors: Isla-Magrané Helena , Veiga Anna , García-Arumí José , Duarri Anna
Published: November 2021

Background

Recently, great efforts have been made to design protocols for obtaining ocular cells from human stem cells to model diseases or for regenerative purposes. Current protocols generally focus on isolating retinal cells, retinal pigment epithelium (RPE), or corneal cells and fail to recapitulate the complexity of the tissue during eye development. Here, the generation of more advanced in vitro multiocular organoids from human induced pluripotent stem cells (hiPSCs) is demonstrated.

Methods

A 2-step method was established to first obtain self-organized multizone ocular progenitor cells (mzOPCs) from 2D hiPSC cultures within three weeks. Then, after the cells were manually isolated and grown in suspension, 3D multiocular organoids were generated to model important cellular features of developing eyes.

Results

In the 2D culture, self-formed mzOPCs spanned the neuroectoderm, surface ectoderm, neural crest, and RPE, mimicking early stages of eye development. After lifting, mzOPCs developed into different 3D multiocular organoids composed of multiple cell lineages including RPE, retina, and cornea, and interactions between the different cell types and regions of the eye system were observed. Within these organoids, the retinal regions exhibited correct layering and contained all major retinal cell subtypes as well as retinal morphological cues, whereas the corneal regions closely resembled the transparent ocular-surface epithelium and contained of corneal, limbal, and conjunctival epithelial cells. The arrangement of RPE cells also formed organoids composed of polarized pigmented epithelial cells at the surface that were completely filled with collagen matrix.

Conclusions

This approach clearly demonstrated the advantages of the combined 2D-3D construction tissue model as it provided a more ocular native-like cellular environment than that of previous models. In this complex preparations, multiocular organoids may be used to model the crosstalk between different cell types in eye development and disease.

Graphical abstract
Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency
Authors: Sonoda Soichiro , Yoshimaru Koichiro , Yamaza Haruyoshi , Yuniartha Ratih , Matsuura Toshiharu , Yamauchi-Tomoda Erika , Murata Sara , Nishida Kento , Oda Yoshinao , Ohga Shouichi , Tajiri Tasturo , Taguchi Tomoaki , Yamaza Takayoshi
Published: November 2021

Background

Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are palliative; thus, innovation in BA therapy is urgent.

Methods

To examine whether BA-specific post-natal stem cells are feasible for autologous cell source for BA treatment, we isolated from human exfoliated deciduous teeth, namely BA-SHED, using a standard colony-forming unit fibroblast (CFU-F) method and compared characteristics as mesenchymal stem cells (MSCs) to healthy donor-derived control SHED, Cont-SHED. BA-SHED and Cont-SHED were intrasplenically transplanted into chronic carbon tetrachloride (CCl4)-induced liver fibrosis model mice, followed by the analysis of bile drainage function and donor integration in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile ducts in the recipient’s liver using anti-human specific keratin 19 (KRT19) antibody.

Results

BA-SHED formed CFU-F, expressed MSC surface markers, and exhibited in vitro mesenchymal multipotency similar to Cont-SHED. BA-SHED showed less in vitro hepatogenic potency than Cont-SHED. Cont-SHED represented in vivo bile drainage function and KRT19-positive biliary regeneration in chronic carbon tetrachloride-induced liver fibrosis model mice. BA-SHED failed to show in vivo biliary potency and bile drainage function compared to Cont-SHED.

Conclusion

These findings indicate that BA-SHED are not feasible source for BA treatment, because BA-SHED may epigenetically modify the underlying prenatal and perinatal BA environments. In conclusion, these findings suggest that BA-SHED-based studies may provide a platform for understanding the underlying molecular mechanisms of BA development and innovative novel modalities in BA research and treatment.
Scattering strength at active volcanoes in Japan as inferred from the peak ratio analysis of teleseismic P waves
Authors: Ganefianto Gugi , Nakahara Hisashi , Nishimura Takeshi
Published: November 2021

Small-scale seismic velocity heterogeneity has been studied through the calculation of peak amplitude ratio as a means to quantify the strength of seismic wave scattering at volcanoes in Japan. This ratio is defined as the ratio of the maximum (peak) P wave energy in the transverse component seismogram envelope over that of the three-component sum seismogram envelope (transverse + radial + vertical). According to the previous study using Japan’s Hi-net seismometer network, the peak ratio is observed to be larger near the (active) quaternary volcanoes. However, these Hi-net stations are not positioned on the volcanoes themselves. This study systematically examines the peak ratios at 47 active volcanoes across Japan, using seismometers operated by the Japan Meteorological Agency (JMA). Analyses were performed at four frequency bands: 0.5–1, 1–2, 2–4, and 4–8 Hz. We found that the JMA stations yield higher peak ratios than the Hi-net stations. Their differences are statistically significant at the 99.9% confidence level in all frequency bands. We also examined the differences between the ground surface and borehole stations of the JMA network. The former shows larger peak ratios, and for most frequency bands, the differences are also statistically significant at the 99.9% confidence level. This suggests an intensification of small-scale medium heterogeneities especially at shallow depths at active volcanoes, and that scattering might have been enhanced at the very shallow parts.

Graphical Abstract
Inferior vena cava collapsibility index as a predictor of fluid responsiveness in sepsis-related acute circulatory failure
Authors: Nagi Ahmed Ibrahim , Shafik Azza Mohamed , Fatah Amr Mohamed Abdel , Selima Wessam Zaher , Hefny Amira Fathy
Published: November 2021

Background

Assessing fluid responsiveness is the key to successful resuscitation of critically-ill sepsis patients. The use of IVC variation is favored among the dynamic methods of fluid responsiveness assessment in the ICU because it is non-invasive and inexpensive; moreover, it does not demand a high level of training. The aim of this study is to determine the value of the IVC respiratory variability for predicting fluid responsiveness in spontaneously breathing sepsis patients with acute circulatory failure.

Results

In this prospective observational study, fifty-eight spontaneously breathing sepsis patients admitted in the ICU were enrolled after the approval of the departmental Research Ethical Committee, and the informed written consent had been taken from the patients. Ultrasonographic and echocardiographic parameters were measured “IVC parameters and stroke volume (SV)” with calculation of the inferior vena cava collapsibility index (IVCCI) and cardiac output. These values were obtained before (baseline) and after volume expansion with a fluid bolus. The study showed that twenty-nine patients (50%) were considered to be responders, with an increase in CO by 10% or more after fluid challenge. There was a significant difference between responders and non-responders in baseline IVCCI (p value < 0.001). There were no significant differences between responders and non-responders in terms of demographic and baseline clinical characteristics. Also, there was statistically significantly larger maximum (IVC max) and minimum (IVC min) inferior vena cava diameters before volume expansion in non-responders than in responders with p value 0.037 and 0.001 respectively. The suggested cut off value regarding baseline IVCCI to predict response to fluid infusion is 0.32 with a high chance of response above this figure (a sensitivity of 72.41% and a specificity of 82.76%).

Conclusions

Inferior vena cava collapsibility index assessment can be a sensitive and a good predictor of fluid responsiveness, being based on a safe and a non-invasive technique compared to other methods such as central venous pressure (CVP) measurement and pulmonary artery catheter insertion.
Voluminous, Repetitive, and Intractable
Authors: Boianovsky Mauro
Published: November 2021

In the late 1970s Paul Samuelson drafted the outline of a paper, never published, with a critical assessment of the theoretical innovations of postwar development economics. He found it a “vital” but essentially “not tractable” subject, with a “voluminous” and “repetitive” literature. This article discusses how that assessment fits in Samuelson’s published writings on economic development, throughout several editions of his textbook Economics, and in papers he wrote before and after that assessment. Increasing returns posed a main analytical hurdle, together with the elusive attempt to provide “laws of motion” of economic development. Samuelson’s notion of “tractability” may be traced back to Peter Medawar’s well-known definition of science as the “art of the soluble.”
Dialing for Change: Organizing Call Center Workers in the 1990s
Authors: Goldman Debbie
Published: November 2021

This article contrasts two Communications Workers of America (CWA) strategic organizing campaigns at Sprint and Southwestern Bell wireless in the 1990s. In the first case, the NLRA failed to protect Sprint workers after their employer closed the call center to avoid a union election, despite a complaint filed by a Mexican union under labor provisions of the North American Free Trade Agreement. In the second case, the CWA's “bargain to organize” strategy neutralized Southwestern Bell's opposition, and 40,000 wireless workers chose CWA representation under a negotiated neutrality/card-check recognition process. This article demonstrates how neoliberal regulatory changes in the telecommunications sector in combination with weak labor laws fostered the decline in union representation in this vitally important and dynamic sector of the economy.
Cultural Politics and Conquest Culture
Authors: Aksoy Asu , Robins Kevin
Published: November 2021

In this article, the authors explore recent developments in urban regeneration in Istanbul, and specifically in the important historic district of Beyoğlu. In one respect, these developments, which are linked to the promotion of cruise ship tourism, are on the same predictable lines as neoliberal projects in other cities across the world. Significantly, in the Istanbul context, local agency is being sidelined, and projects are being financed and managed through the intervention of the central state. In this Turkish version of urban transformation, however, there is a locally distinctive aspect that merits attention. Istanbul is a city that was conquered by the Ottomans in 1453, and the discourse of conquest has remained significant within the urban imaginary. And at the present time, it is being mobilized by the state and its cultural ministry, in the cause of creating a new urban image conforming to its Islamist principles. The key project involves the establishment of what is called the Beyoğlu Cultural Route, which is essentially a touristic itinerary. The authors argue that the state's initiatives, and the route project in particular, involve an erasure—a conquest—of Beyoğlu's legacy of cosmopolitan values. This discussion explores what has been of civic and cultural value in the lifeworld of Beyoğlu, past and present. Resistance to the state's control of resources and institutions, and to its conquest ideology, needs to be grounded in civic principles open to diversity and difference in the city.