bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-occurrence of relapsing polychondritis and autoimmune thyroid diseases
Authors: Nakajima Toshiki , Yoshifuji Hajime , Yamano Yoshihisa , Yurugi Kimiko , Miura Yasuo , Maekawa Taira , Yoshida Tsuneyasu , Handa Hiroshi , Ohmura Koichiro , Mimori Tsuneyo , Terao Chikashi 
Published: May 2022

Abstract
Background
Relapsing polychondritis (RP) is a rare inflammatory disease characterized by recurrent inflammation and destruction of cartilaginous tissues. RP has characteristics of autoimmune disease and some reports have noted co-occurrence with autoimmune thyroid disease (AITD), consisting of Graves’ disease (GD) and Hashimoto thyroiditis (HT). However, there have been no detailed studies on the co-occurrence of RP and AITD. In this study, we aimed to determine whether patients with RP tend to be complicated with AITD. We also analyzed the clinical and genetic profiles of patients in whom these diseases co-occur.

Methods
We recruited 117 patients with RP and reviewed their medical records. Furthermore, we genotyped Human Leucocyte Antigen (HLA)-A, B Cw, DRB1, DQB1, and DPB1 alleles for 93 of the 117 patients. The prevalence of AITD among the patients with RP was compared with that among the general Japanese population. We also analyzed the clinical and genetic features of the patients with both RP and AITD.

Results
The prevalence of GD among the patients with RP was 4.3% (5 among 117 patients), significantly higher than that among Japanese (0.11%) (p = 2.44 × 10–7, binomial test). RP patients with GD tended to have nasal involvement (p = 0.023) (odds ratio (OR) 2.58) and HLA-DPB1*02:02 (p = 0.035, OR 10.41). We did not find significant enrichment of HT in patients with RP.

Conclusions
Patients with RP appear to be at elevated risk of GD. Nasal involvement and HLA-DPB1*02:02 characterize the subset of RP patients with GD, which may guide attempts to characterize a distinct subtype of RP for precision medicine.
Consensus statement on enzyme replacement therapy for mucopolysaccharidosis IVA in Central and South-Eastern European countries
Authors: Magner Martin , Almássy Zsuzsanna , Gucev Zoran , Kieć-Wilk Beata , Plaiasu Vasilica , Tylki-Szymańska Anna , Zafeiriou Dimitrios , Zaganas Ioannis , Lampe Christina 
Published: May 2022

Abstract
Background
Mucopolysaccharidosis IVA (MPS IVA), or Morquio A syndrome, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. A progressive systemic skeletal chondrodysplasia, leading to significant morbidity and reduced life expectancy is the main clinical feature of this multisystemic disease. Although enzyme replacement therapy with elosulfase alfa is established in Europe, the rarity of disease and other factors still set hurdles in having patients treated in some countries. Aim of this statement is to provide evidence-based guidance for the enzyme replacement treatment of Morquio A patients, harmonizing recommendations from published guidelines with the real-life clinical practice in the Central and South-Eastern European region.

Participants
The Consensus Group, convened by 8 Steering Committee (SC) members from 7 Central and South-Eastern European countries, consisted of a multidisciplinary group of 17 experts in the management of MPS in Central and South-Eastern Europe.

Consensus process
The SC met in a first virtual meeting with an external scientific coordinator, to discuss on clinical issues to be analyzed in guidance statements. Statements were developed by the scientific coordinator, evaluated by the SC members in a first modified-Delphi voting and adapted accordingly, to be submitted to the widest audience in the Consensus Conference. Following discussion and further modifications, all participants contributed to a second round of modified-Delphi voting.

Results
Nine of ten statements, concerning general guidelines for management of MPS IVA patients and specific recommendations for treatment, received final consensus.

Conclusions
European guidelines and evidence-based recommendations for Morquio A patients should be considered in the real life of Central and South-Eastern European countries and adapted to unique clinical practice approaches and criteria for patients’ access to treatment and reimbursement in the region.
Fisetin-induced cell death in human ovarian cancer cell lines via zbp1-mediated necroptosis
Authors: Liu Yaxian , Cao Hongwen , Zhao Yanhui , Shan Lijuan , Lan Shuhai 
Published: May 2022

Abstract
Background
Among reproductive cancers, ovarian cancer leads to the highest female mortality rate. Fisetin, a natural flavonoid, exerts pharmacological effects, inhibiting cancer growth with various origins. Although multiple mechanisms are involved in regulating cell death, it is still unclear whether and how fisetin exhibits anticancer effects on ovarian cancer. The present study aimed to evaluate cell apoptotic and necroptotic processes occurring in ovarian carcinoma (OC) cell lines induced by fisetin.

Methods
Cell growth was evaluated by MTT assay in OC cell lines treated with or without fisetin. Annexin V/propidium iodide staining followed by flow cytometry was used to characterize fisetin-induced cell death. The apoptotic process was suppressed by z-VAD intervention, and cell necroptosis was assessed by introducing ZBP1-knockdown OC cell lines coupled with fisetin intervention. The expression of necroptosis-related mediators and the migration capability of the respective cells were evaluated by Western blotting and in vitro cell invasion assay.

Result
Fisetin successfully reduced cell growth in both OC cell lines in a dose-dependent manner. Both apoptosis and necroptosis were induced by fisetin. Suppression of the cell apoptotic process failed to enhance the proliferation of fisetin-treated cells. The induced cell death and robust expression of the necroptotic markers RIP3 and MLKL were alleviated by knocking down the expression of the ZBP1 protein in both OC cell lines.

Conclusion
The present study provided in vitro evidence supporting the involvement of both apoptosis and necroptosis in fisetin-induced OC cell death, while ZBP1 regulates the necroptotic process via the RIP3/MLKL pathway.
Wip1 suppresses angiogenesis through the STAT3-VEGF signalling pathway in serous ovarian cancer
Authors: Yin Sheng , Yang Lina , Zheng Yiyan , Zang Rongyu 
Published: May 2022

AbstractMultifaceted functions of the so-called “oncogene” Wip1 have been reported in a previous study, while its actual role remains to be explored in serous ovarian cancer (SOC). In this study, by performing bioinformatic analysis with a public database and immunohistochemical staining of Wip1 in tumour tissue from SOC, we concluded that decreased expression of Wip1 was associated with a higher rate of tumour metastasis and platinum-based therapy resistance and increased ascites volume, which led to poorer prognosis in SOC patients. We also found that overexpression of Wip1 in SKOV3 cells decreased the levels of several cytokines, including VEGF, by secretome profiling analysis, and Wip1 overexpression suppressed angiogenesis both in vitro and in vivo. Mechanistic studies indicated that overexpression of Wip1 decreased the expression of VEGF at both the protein and mRNA levels and that the inhibitory effect was mediated by dephosphorylation of STAT3 at Ser727. Our study uncovered the role of Wip1 in SOC and provides a novel therapeutic strategy for suppressing angiogenesis.
Refining colorectal cancer classification and clinical stratification through a single-cell atlas
Authors: Khaliq Ateeq M. , Erdogan Cihat , Kurt Zeyneb , Turgut Sultan Sevgi , Grunvald Miles W. , Rand Tim , Khare Sonal , Borgia Jeffrey A. , Hayden Dana M. , Pappas Sam G. , Govekar Henry R. , Kam Audrey E. , Reiser Jochen , Turaga Kiran , Radovich Milan , Zang Yong , Qiu Yingjie , Liu Yunlong , Fishel Melissa L. , Turk Anita , Gupta Vineet , Al-Sabti Ram , Subramanian Janakiraman , Kuzel Timothy M. , Sadanandam Anguraj , Waldron Levi , Hussain Arif , Saleem Mohammad , El-Rayes Bassel , Salahudeen Ameen A. , Masood Ashiq 
Published: May 2022

Abstract
Background
Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples and analyze multiple independent external cohorts for a total of 487,829 single cells enabling high-resolution depiction of the cellular diversity and heterogeneity within the tumor and microenvironmental cells.

Results
Tumor cells recapitulate individual CMS subgroups yet exhibit significant intratumoral CMS heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs and microsatellite stable (MSS) CRC demonstrate similar pathway activations at the tumor epithelial level. However, CD8+ cytotoxic T cell phenotype infiltration in MSI-H CRCs may explain why these tumors respond to immune checkpoint inhibitors. Cellular transcriptomic profiles in CRC exist in a tumor immune stromal continuum in contrast to discrete subtypes proposed by studies utilizing bulk transcriptomics. We note a dichotomy in tumor microenvironments across CMS subgroups exists by which patients with high cancer-associated fibroblasts (CAFs) and C1Q+TAM content exhibit poor outcomes, providing a higher level of personalization and precision than would distinct subtypes. Additionally, we discover CAF subtypes known to be associated with immunotherapy resistance.

Conclusions
Distinct CAFs and C1Q+ TAMs are sufficient to explain CMS predictive ability and a simpler signature based on these cellular phenotypes could stratify CRC patient prognosis with greater precision. Therapeutically targeting specific CAF subtypes and C1Q + TAMs may promote immunotherapy responses in CRC patients.
Apolipoprotein C-III in patients with systemic lupus erythematosus
Authors: Martín-González Candelaria , Ferrer-Moure Carmen , Carlos Quevedo-Abeledo Juan , de Vera-González Antonia , González-Delgado Alejandra , Sánchez-Martín Julio , González-Gay Miguel Á. , Ferraz-Amaro Iván 
Published: May 2022

Abstract
Background
Systemic lupus erythematosus (SLE) has been associated with atherosclerotic cardiovascular disease (CV) and an altered lipid profile. High levels of apolipoprotein C-III (ApoC3) are associated with elevated triglyceride levels and an increased risk of CV. In the present study, we aimed to study circulating ApoC3 in patients with SLE and describe its relationship with the manifestations of the disease.

Methods
This is a cross-sectional study that included 186 patients with SLE. Disease-related data, CV comorbidity, full lipid profile, and serum levels of ApoC3 were assessed. A multivariable regression analysis was performed to study how ApoC3 was related to SLE features.

Results
Classic CV risk factors were significantly and strongly associated with circulating ApoC3. After a fully multivariable analysis that included classic CV risk factors and lipid profile molecules, SLICC damage (beta coef. 0.10 [95% CI 0.02–0.19] mg/dl, 0.020) and Katz severity (beta coef. 0.11 [95% CI 0.03–0.19] mg/dl, p = 0.011) indices and SLEDAI activity score (beta coef. 0.05 [95% CI 0.05–0.08] mg/dl, p = 0.004) were all independently associated with higher levels of circulating ApoC3.

Conclusion
Among SLE patients, disease activity, severity, and disease damage are independently associated with higher ApoC3 serum levels.
Video capsule endoscopy in patients with iron deficiency anaemia: experience at a regional Australian service
Authors: Furner Maddison , Nagel Robyn , Pinidiyapathirage Janani 
Published: May 2022

Abstract
Objective
The objective of this study was to identify the diagnostic performance of video capsule endoscopy (VCE) among patients presenting with iron deficiency anaemia (IDA) and negative bidirectional endoscopy to a gasteroendoscopy practice in regional Australia. The secondary objectives were to identify the distribution of findings and factors predictive of positive findings in a regional setting.

Results
In total 123 procedures were included in the study. Mean age of the patients was 67.9 years. Females made up 60.2% (n = 74) of the study population. Mean haemoglobin and ferritin levels were 93.3 g/L and 11.9 ug/L, respectively. Positive findings were present in 67 procedures (54.5%) with the most frequent finding being small bowel angiodysplasia (53.7%, n = 36/67), followed by ulceration/significant erosion (26.8%, n = 18/67), fresh blood (20.8%, n = 14/67) and tumour/polyp (16.4%, n = 11/67). Haemoglobin level was the only variable associated with positive findings (p = 0.005) in the study population. Of the procedures reporting positive findings outside the small bowel, the majority (80%) were within reach of conventional upper endoscopy and may have implications for future practice, particularly when allocating health resources in a rural setting.
Dialogue as a tool of nutrition literacy in an agricultural intervention programme in Odisha, India
Authors: Narayanan Rama , Panda Akshaya Kumar , Nithya D. J. , Bhavani R. V. 
Published: May 2022

Abstract
Background
An ongoing action research nutrition literacy programme based on Freire’s approach of raising critical consciousness through the use of dialogue as a pedagogic tool is being implemented as part of a nutrition sensitive agricultural intervention in tribal Odisha. One hundred and eight adults, referred to as Community Hunger Fighters (CHFs) underwent two modules of a residential training programme of two and a half days each, spread over two months. Through discussion they explored the reasons behind the lack of diversity in their daily diets and identified the social, economic and cultural barriers to food intake in the context of their own poverty. They undertook collective exercises in nutrition sensitive agricultural planning. The transformative behaviour of the CHFs was captured through observation, interviews and focus group discussion with a set of qualitative indicators.

Results
The methodology of dialogue as a pedagogic tool generated a discussion about food security among the community. CHFs identified key messages and shared them with fellow villagers in imaginative ways. The process of critical reflection and analysis helped understand gender disparities, the bottlenecks in food production, brought in life style changes to improve food intake and created a demand for technical training for improving agricultural productivity. Thirty eight had started a nutri-garden and several took on leadership roles on other issues of importance besides food security.

Conclusion
Dialogue as a pedagogic tool for nutrition literacy in an agricultural intervention programme has the potential to facilitate a process of critical reflection on the socio cultural and economic barriers to food production and consumption thereby leading to transformative action.
International Comparisons of Clinical Demographics and Outcomes in the International Society of Pediatric Oncology Wilms Tumor 2001 Trial and Study
Authors: de Aguirre-Neto Joaquim Caetano , de Camargo Beatriz , van Tinteren Harm , Bergeron Christophe , Brok Jesper , Ramírez-Villar Gema , Verschuur Arnauld , Furtwängler Rhoikos , Howell Lisa , Saunders Daniel , Olsen Oystein , Coulomb Aurore , Vokuhl Christian , Godzinski Jan , Smets Anne M. , Vujanic Gordan M. , van den Heuvel-Eibrink Marry M. , Graf Norbert , Pritchard-Jones Kathy 
Published: May 2022

PURPOSE International comparisons of patient demographics, tumor characteristics, and survival can shed light on areas for health care system improvement. The International Society of Pediatric Oncology Wilms Tumor 2001 trial/study registered patients through national clinical study groups in Western Europe and Brazil. This retrospective post hoc analysis of the International Society of Pediatric Oncology Wilms Tumor 2001 database aims to make visible and suggest reasons for any variations in outcomes. METHODS All patients with unilateral Wilms tumor (WT), age > 6 months, treated with preoperative chemotherapy as per protocol, and registered between 2001 and 2011 were eligible. Countries were grouped to give comparable case numbers and geographical representation. Cox univariable and multivariable (MVA) statistics were applied, with the German collaborative group (Gesellschaft für Pädiatrische Onkologie und Hämatologie—Austria, Germany, and Switzerland) as reference for hazard ratios for event-free survival (EFS) and overall survival (OS). RESULTS A total of 3,176 eligible patients were registered from 24 countries assigned into six groups. Age and histologic risk group distribution were similar across all groupings. The distribution of WT stage varied by country grouping, with 14.9% (range, 11.1%-18.2%) metastatic at diagnosis. Median follow-up was 78.9 months. For localized WT, 5-year EFS varied from 80% (Brazilian group) to 91% (French group; P < .0001), retaining significance only for Brazil in MVA ( P = .001). Five-year OS varied from 89% (Brazilian group) to 98% (French group; P < .0001). In MVA, only superior OS in France was significant ( P = .001). Five-year EFS/OS for stage IV did not vary significantly. High-risk histology and tumor volume at surgery were significantly associated with increased risk of death in MVA for metastatic disease. CONCLUSION International benchmarking of survival rates from WT within a large trial/study database has demonstrated statistically significant differences. Clinical interpretation should take account of variation in tumor stage but also treatment factors.
Paracrine Regulation of Adipose Tissue Macrophages by Their Neighbors in the Microenvironment of Obese Adipose Tissue
Authors: Wang Kai , Wang Yuan-Yuan , Wu Liang-Liang , Jiang Li-Yan , Hu Yin , Xiao Xin-Hua , Wang Ya-Di 
Published: May 2022

Abstract
Obesity has recently been defined as a chronic low-grade inflammatory disease. Obesity-induced inflammation of adipose tissue (AT) is an essential trigger for insulin resistance (IR) and related metabolic diseases. Although the underlying molecular basis of this inflammation has not been fully identified, there is consensus that the recruited and activated macrophages in AT are the most important culprits of AT chronic inflammation. Adipose tissue macrophages (ATMs) are highly plastic and could be polarized from an anti-inflammatory M2 to proinflammatory M1 phenotypes on stimulation by microenvironmental signals from obese AT. Many efforts have been made to elucidate the molecular signaling pathways of macrophage polarization; however, the upstream drivers governing and activating macrophage polarization have rarely been summarized, particularly regulatory messages from the AT microenvironment. In addition to adipocytes, the AT bed also contains a variety of immune cells, stem cells, as well as vascular, neural, and lymphatic tissues throughout, which together orchestrate the AT microenvironment. Here, we summarize how the aforesaid neighbors of ATMs in the AT microenvironment send messages to ATMs and thus regulate its phenotype during obesity. Deciphering the biology and polarization of ATMs in the obese environment is expected to provide a precise immunotherapy for adipose inflammation and obesity-related metabolic diseases.
Firearm-Related Pediatric Head Trauma: A Scoping Review
Authors: Gadot Ron , LoPresti Melissa A. , Smith David N. , Ouellette Lara , Lam Sandi 
Published: May 2022

BACKGROUND:
Firearm-related injury is a significant cause of morbidity and mortality in pediatric populations. Despite a disproportionate role in the most morbid outcomes in both traumatic brain injury and firearm-related injury populations, firearm-related traumatic brain injury (frTBI) is an understudied epidemiological entity. There is need to increase understanding and promote interventions that reduce this burden of disease.

OBJECTIVE:
To assess the evidence characterizing pediatric frTBI to highlight trends and gaps regarding burden of disease and interventions to reduce frTBI.

METHODS:
We conducted a scoping review under Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review (PRISMA-ScR) guidelines on peer-reviewed studies across 5 databases (Medline OVID, EMBASE, Web of Science Legal Collection, PsychINFO, and Academic Search Complete). English studies examining pediatric frTBI epidemiology, prevention, and/or social or legal policy advocacy were included. Articles were excluded if they more generally discussed pediatric firearm-related injury without specific analysis of frTBI.

RESULTS:
Six studies satisfied inclusion criteria after screening and full-text assessment. Limited studies specifically addressed the burden of disease caused by frTBI. There was an increased risk for both injury and death from frTBI in men, preteenage and teenage youths, minorities, and individuals in firearm-owning households. Further study is required to ascertain if suggested methods of targeted patient screening, firearm-injury prevention counseling, and advocacy of safety-oriented policy tangibly affect rates or outcomes of pediatric frTBI.

CONCLUSION:
By understanding published epidemiological data and areas of intervention shown to reduce frTBIs, neurosurgeons can become further engaged in public health and prevention rather than strictly treatment after injury.
CONSTRUÇÕES GRAMATICAIS E PONTO DE VISTA AS CONCESSIVAS [EMBORA P, Q] E AS CONDICIONAIS CONCESSIVAS [SE P, Q]
Authors: Ferrari Lilian Vieira , Ribeiro Gabriela Silva 
Published: May 2022

Este trabalho contrasta construções concessivas [Embora P, Q] e condicionais concessivas [Se P, Q] em textos jornalísticos do português brasileiro. Com base no Princípio de Não-Sinonímia (GOLDBERG, 1995), evidencia-se que essas construções apresentam diferenças pragmáticas que podem ser explicadas a partir da alternância de ponto de vista na rede de espaços mentais na qual se inserem (FAUCONNIER, 1994, 1997; CUTRER, 1994; DANCYGIER & SWEETSER, 2012). A análise destaca que, nas concessivas [Embora P,Q], o ponto de vista é alocado no espaço Base, referente ao aqui e agora do jornalista. Já nas condicionais concessivas [Se P, Q], o ponto de vista é deslocado para um espaço de discurso reportado, referente à fala de uma terceira pessoa reportada anteriormente no discurso. Associadas às diferentes estratégias de sinalização de ponto de vista, essas construções também refletem posturas epistêmicas distintas. As concessivas refletem postura epistêmica positiva e, portanto, comprometimento do jornalista com a factualidade do evento descrito na cláusula introduzida por “embora”, enquanto as condicionais concessivas refletem postura epistêmica neutra, indicando que o jornalista expressa neutralidade com relação à factualidade do evento reportado na prótase condicional introduzida por “se”.