bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-18 and IL-18 binding protein are related to disease severity and parasitemia during falciparum malaria
Authors: Otterdal Kari , Berg Aase , Michelsen Annika E. , Yndestad Arne , Patel Sam , Gregersen Ida , Halvorsen Bente , Ueland Thor , Langeland Nina , Aukrust Pål 
Published: October 2021

Abstract
Background
Several inflammatory molecules participate in the immune response to malaria. Interleukin (IL)-18 is an inflammatory cytokine activated by NLRP3 inflammasomes. In clinical falciparum malaria, with and without HIV co-infection, data on IL-18 and in particular on its binding protein, IL-18bp, is scarce.

Methods
Clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) HIV co-infection, from HIV-infected patients with similar symptoms without malaria (n = 58) and from healthy controls (n = 52). In vitro studies were performed in endothelial cells using hemozoin crystals.

Results
(i) IL-18 and IL-18bp were markedly up-regulated during falciparum malaria with particular high levels in malaria patients co-infected with HIV and severe malaria disease. (ii) In the malaria group as a whole, both IL-18 and IL-18bp were positively correlated with disease severity, parasitemia, and endothelial cell activation as assessed by vWF in plasma. (iii) Whereas there was no change in IL-18 levels in malaria patients co-infected with HIV during follow-up, the patients with malaria only had slightly increased IL-18 levels. Further, the IL-18pb levels declined and thereby contributed to an increase in IL-18/IL-18bp ratio in all subgroups of malaria patients. (iv) IL-27, previously shown to be up-regulated in this malaria cohort, markedly induced a release of IL-18bp from endothelial cells in vitro, and notably, this presumably anti-inflammatory effect was counteracted by hemozoin.

Conclusions
Our findings suggest that the IL-18 system could be an important mediator in the immune pathogenesis during falciparum malaria, potentially also representing a target for therapy.
Exploring the clinical value of preoperative serum gamma-glutamyl transferase levels in the management of patients with hepatocellular carcinoma receiving postoperative adjuvant transarterial chemoembolization
Authors: Ke Qiao , Xiang Fu , Xiao Chunhong , Huang Qizhen , Liu Xiaolong , Zeng Yongyi , Wang Lei , Liu Jingfeng 
Published: October 2021

Abstract
Background
Preoperative serum gamma-glutamyl transferase (γ-GT) levels is significantly related to the prognosis of hepatocellular carcinoma (HCC), but its clinical value in the management of postoperative adjuvant transarterial chemoembolization (PA-TACE) has rarely been explored. This study aimed to investigate whether γ-GT levels could be taken as a biomarker to guide the management of PA-TACE in resectable HCC.

Methods
HCC patients receiving radical resection were identified through the primary liver cancer big data (PLCBD) from December 2012 to December 2015. Prognostic factors of overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate cox analyses, and subgroup analysis was conducted between PA-TACE group and non-TACE stratified by γ-GT levels before and after 1:1 propensity score matching (PSM).

Results
γ-GT level was found to be an independent risk factor of OS and DFS in 1847 HCC patients receiving radical resection (both P < 0.05), and patients with elevated γ-GT(> 54.0 U/L) have a shortened median OS and DFS, compared with those with normal γ-GT (both P < 0.001). In the subgroup of patients with normal γ-GT, there were no significant differences between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P > 0.05), and PA-TACE was not a significant prognostic factor of both OS and DFS before and after PSM (all P > 0.05). In the subgroup of patients with elevated γ-GT, significant differences were found between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P < 0.05), and PA-TACE was an independent prognostic factor of both OS and DFS (all P < 0.05).

Conclusion
Currently, we concluded that patients with more advanced HCC also have more elevated γ-GT, and these patients with elevated γ-GT would be benefited more from PA-TACE after radical resection.
TFEB, SIRT1, CARM1, Beclin-1 expression and PITX2 methylation in breast cancer chemoresistance: a retrospective study
Authors: Bertozzi Serena , Londero Ambrogio P. , Viola Luigi , Orsaria Maria , Bulfoni Michela , Marzinotto Stefania , Corradetti Bruna , Baccarani Umberto , Cesselli Daniela , Cedolini Carla , Mariuzzi Laura 
Published: October 2021

AbstractBackgroundBreast cancer chemoresistance is attributed to a wide variety of mechanisms, including autophagy. Transcription factor EB (TFEB) has been recently identified and characterized as one major regulator of autophagy and lysosomal genesis.ObjectiveThis study aims to evaluate the prognostic impact of TFEB and its pathway in breast cancer chemoresistance.MethodsThis retrospective study analyzes the expression of TFEB, CARM1, SIRT1, and Beclin-1 and the methylation of PITX2 in breast carcinoma. A group of breast cancer patients treated with chemotherapy, who relapsed within 12 months from treatment initiation, were compared to a sub-cohort of chemo-treated patients who did not recur within 12 months of follow-up. The expression of TFEB, CARM1, SIRT1, and Belcin-1 was analyzed using immunohistochemistry or RT-PCR on formalin-fixed paraffin-embedded samples. PITX2 methylation was tested with the diagnostic CE-marked kit Therascreen PITX2 RGQ PCR. In the final model, 136 cases of chemo-treated breast cancer were included.ResultsA higher TFEB and Beclin-1 expression correlate with shorter survival in patients with chemo-treated invasive breast cancer (respectively HR 3.46, CI.95 1.27–9.47,p < 0.05 and 7.11, CI.95 2.54–19.9). TFEB, CARM1, and SIRT1 are positively correlated with Beclin-1. The protein expression of SIRT1 is significantly associated with TFEB and CARM1 so that a very low SIRT1 expression (lower than the first quartile of the H-score distribution) correlates with a low expression of TFEB and CARM1 and with longer survival. SIRT1 seems to have a lower H-score in the basal-like and HER2-enriched tumors than the luminal subtypes. Beclin-1 and TFEB seem to have a higher H-score in the basal-like and HER2-enriched tumors than the luminal subtypes. PITX2 methylation analysis was feasible only in 65% of the selected samples, but no significant differences between cases and controls were found, and there was also no correlation with the expression of the TFEB pathway.ConclusionsTFEB, SIRT1, and Beclin-1 seem to have a potential prognostic significance in patients with chemo-treated breast cancer, likely because of their role in the regulation of autophagy. In addition, no correlation between TFEB and PITX2 methylation was found, likely because they perform two different roles within the autophagy process.
Evaluating the impact of 18F-FDG-PET-CT on risk stratification and treatment adaptation for patients with muscle-invasive bladder cancer (EFFORT-MIBC): a phase II prospective trial
Authors: Verghote Flor , Poppe Lindsay , Verbeke Sofie , Dirix Piet , Albersen Maarten , De Meerleer Gert , Berghen Charlien , Ost Piet , Villeirs Geert , De Visschere Pieter , De Man Kathia , De Maeseneer Daan , Rottey Sylvie , Van Praet Charles , Decaestecker Karel , Fonteyne Valérie 
Published: October 2021

Abstract
Background
The outcome of patients with muscle-invasive bladder cancer (MIBC) remains poor, despite aggressive treatments. Inadequate primary staging, classically performed by computed tomography (CT)-imaging, could lead to inappropriate treatment and might contribute to these poor results. Although not (yet) adapted by international guidelines, several reports have indicated the superiority of 18F-fluorodeoxyglucose-positron emission tomography-CT (18F-FDG-PET-CT) compared to CT in the detection of lymph node and distant metastases. Thereby the presence of extra-vesical disease on 18F-FDG-PET-CT has been correlated with a worse overall survival. This supports the hypothesis that 18F-FDG-PET-CT is useful in stratifying MIBC patients and that adapting the treatment plan accordingly might result in improved outcome.

Methods
EFFORT-MIBC is a multicentric prospective phase II trial aiming to include 156 patients. Eligible patients are patients with histopathology-proven MIBC or ≥ T3 on conventional imaging treated with MIBC radical treatment, without extra-pelvic metastases on conventional imaging (thoracic CT and abdominopelvic CT/ magnetic resonance imaging (MRI)). All patients will undergo radical local therapy and if eligible neo-adjuvant chemotherapy. An 18F-FDG-PET-CT will be performed in addition to and at the timing of the conventional imaging. In case of presence of extra-pelvic metastasis on 18F-FDG-PET-CT, appropriate intensification of treatment with metastasis-directed therapy (MDT) (in case of ≤3 metastases) or systemic immunotherapy (> 3 metastases) will be provided. The primary outcome is the 2-year overall survival rate. Secondary endpoints are progression-free survival, distant metastasis-free survival, disease-specific survival and quality of life. Furthermore, the added diagnostic value of 18F-FDG-PET-CT compared to conventional imaging will be evaluated and biomarkers in tumor specimen, urine and blood will be correlated with primary and secondary endpoints.

Discussion
This is a prospective phase II trial evaluating the impact of 18F-FDG-PET-CT in stratifying patients with primary MIBC and tailoring the treatment accordingly. We hypothesize that the information on the pelvic nodes can be used to guide local treatment and that the presence of extra-pelvic metastases enables MDT or necessitates the early initiation of immunotherapy leading to an improved outcome.

Trial registration
The Ethics Committee of the Ghent University Hospital (BC-07456) approved this study on 11/5/2020. The trial was registered on ClinicalTrials.gov (NCT04724928) on 21/1/2021.
Modelling the impact of travel restrictions on COVID-19 cases in Hong Kong in early 2020
Authors: Kwok Wang-Chun , Wong Chun-Ka , Ma Ting-Fung , Ho Ka-Wai , Fan Louis Wai-Tong , Chan King-Pui Florence , Chan Samuel Shung-Kay , Tam Terence Chi-Chun , Ho Pak-Leung 
Published: October 2021

Abstract
Background
Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease.

Objective
To apply a metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration to investigate the effect of border restriction as a public health measure to limit outbreak of coronavirus disease 2019.

Methods
We apply a modified metapopulation SEIR model with inspected migration with simulating population migration, and incorporating parameters such as efficiency of custom inspection in blocking infected travelers in the model. The population sizes were retrieved from government reports, while the number of COVID-19 patients were retrieved from Hong Kong Department of Health and China Centre for Disease Control (CDC) data. The R0 was obtained from previous clinical studies.

Results
Complete border closure can help to reduce the cumulative COVID-19 case number and mortality in Hong Kong by 13.99% and 13.98% respectively. To prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1.6 was necessary, apart from having complete border closure.

Conclusions
Early complete travel restriction is effective in reducing cumulative cases and mortality. However, additional anti-COVID-19 measures to reduce local R0 to below 1.6 are necessary to prevent COVID-19 cases from overwhelming hospital isolation facilities.
Analysis of the relationship between the HbA1c screening results and the development and worsening of diabetes among adults aged over 40 years: a 4-year follow-up study of 140,000 people in Japan – the Shizuoka study
Authors: Nomura Shuhei , Sakamoto Haruka , Rauniyar Santosh Kumar , Shimada Koki , Yamamoto Hiroyuki , Kohsaka Shun , Ichihara Nao , Kumamaru Hiraku , Miyata Hiroaki 
Published: October 2021

Abstract
Background
Hemoglobin A1c (HbA1c) levels are routinely measured during health check-ups and are used as an indicator of glycemic control in Japan. However, only a few studies have followed up individuals to assess the risk of diabetes development and worsening based on HbA1c screening results. This study evaluated the relationship between HbA1c screening results and the risk of diabetes development and worsening.

Methods
Data were collected from the Shizuoka Kokuho Database, a Japanese administrative claims database of insured individuals aged > 40 years. We included individuals available for follow-up from April 2012 to March 2018 who had not received any diabetes treatment before March 2014. HbA1c screening results were categorized into 4 groups based on the HbA1c levels at the 2012 and 2013 health check-ups: group A, those whose HbA1c levels were < 6.5% in 2012 and 2013; group B, those whose HbA1c levels > 6.5% in 2012 but < 6.5% in 2013; group C, those whose HbA1c levels were > 6.5% in 2012 and 2013; and group D, those whose HbA1c levels were < 6.5% in 2012 and > 6.5% in 2013. Logistic regression models were used to analyze diabetes development and worsening, defined as the initiation of diabetes treatment by March 2018 and the use of injection drugs by participants who initiated diabetes treatment by March 2018.

Results
Overall, 137,852 individuals were analyzed. After adjusting for covariates, compared with group A, group B was more likely to initiate treatment within 4 years (odds ratio: 22.64; 95% confidence interval: 14.66–34.99). In patients who initiated diabetes treatment by March 2018, injection drugs were less likely used by group D than by group A (odds ratio: 0.28; 95% confidence interval: 0.12–0.61).

Conclusions
Our study suggests that although HbA1c levels measured during health check-ups were correlated with the risk of diabetes development and worsening, HbA1c levels in a single year may not necessarily provide sufficient information to consider these future risks.
Measurements of quality of village-level care and patients’ healthcare-seeking behaviors in rural China
Authors: Rao Sihang , Xue Hao , Teuwen Dirk E. , Shi Haonan , Yi Hongmei 
Published: October 2021

Abstract
Background
Although the progress in global health initiatives has improved the availability of primary health care (PHC), unqualified healthcare remains a serious challenge in low- and middle-income countries, where PHC is often underutilized. This study examines factors associated with patients’ healthcare-seeking behaviors in rural Chin—seeking healthcare at village-level PHC providers, at higher-level health facilities, self-medicating, and refraining from seeking medical help. We focus on provider-side factors, including (1) the unobservable quality indicator, (2) the observable quality indicator, and (3) the observable signal indicator.

Methods
We analyzed 1578 episodes of healthcare-seeking behaviors of patients with diarrhea or cough/runny nose symptom from surveys conducted in July 2017 and January 2018 in 114 villages of the Yunnan province. We investigated the correlation between quality-related factors with patients’ healthcare-seeking behaviors by multinomial logit regression.

Results
We found that rural patients were insensitive to the unobservable quality of healthcare providers, as measured by standardized clinical vignettes, which might be attributable to the credence nature of PHC. The observable quality indicator, whether the clinician has received full-time junior college formal medical education, was associated with patients’ healthcare choices. Patients, however, were more likely to select healthcare based on the observable signal indicator, which was measured by the availability of medicines. Additionally, the observable signal indicator had no significant association with two quality indicators. Notably, socioeconomically-disadvantaged patients relied more on the village-level PHC, which emphasized the role of PHC in promoting the welfare of rural populations.

Conclusions
Our study found an inconsistency between objective quality of healthcare provided by providers and subjective quality perceived by patients. Patients could not identify the actual quality of PHC precisely, while they were more likely to make decisions based on the observable signal indicator. Therefore, the quality of PHC should be more observable to patients. This study not only supplements the literature on healthcare-seeking choices by examining four types of behaviors simultaneously but also clarifies rural patients’ perceptions of the quality of PHC for policy decision-making on increasing the utilization of PHC and improving the medical welfare of the vulnerable.
Role of psychosocial factors on the effect of physical activity on physical function in patients after lumbar spine surgery
Authors: Master Hiral , Castillo Renan , Wegener Stephen T. , Pennings Jacquelyn S. , Coronado Rogelio A. , Haug Christine M. , Skolasky Richard L. , Riley Lee H. , Neuman Brian J. , Cheng Joseph S. , Aaronson Oran S. , Devin Clinton J. , Archer Kristin R. 
Published: October 2021

Abstract
Background
The purpose of this study was to investigate the longitudinal postoperative relationship between physical activity, psychosocial factors, and physical function in patients undergoing lumbar spine surgery.

Methods
We enrolled 248 participants undergoing surgery for a degenerative lumbar spine condition. Physical activity was measured using a triaxial accelerometer (Actigraph GT3X) at 6-weeks (6wk), 6-months (6M), 12-months (12M) and 24-months (24M) following spine surgery. Physical function (computerized adaptive test domain version of Patient-Reported Outcomes Measurement Information System) and psychosocial factors (pain self-efficacy, depression and fear of movement) were assessed at preoperative visit and 6wk, 6M, 12M and 24M after surgery. Structural equation modeling (SEM) techniques were utilized to analyze data, and results are represented as standardized regression weights (SRW). Overall SRW were computed across five imputed datasets to account for missing data. The mediation effect of each psychosocial factor on the effect of physical activity on physical function were computed [(SRW for effect of activity on psychosocial factor X SRW for effect of psychosocial factor on function) ÷ SRW for effect of activity on function]. Each SEM model was tested for model fit by assessing established fit indexes.

Results
The overall effect of steps per day on physical function (SRW ranged from 0.08 to 0.19, p<0.05) was stronger compared to the overall effect of physical function on steps per day (SRW ranged from non-existent to 0.14, p<0.01 to 0.3). The effect of steps per day on physical function and function on steps per day remained consistent after accounting for psychosocial factors in each of the mediation models. Depression and fear of movement at 6M mediated 3.4% and 5.4% of the effect of steps per day at 6wk on physical function at 12M, respectively. Pain self-efficacy was not a statistically significant mediator.

Conclusions
The findings of this study suggest that the relationship between physical activity and physical function is stronger than the relationship of function to activity. However, future research is needed to examine whether promoting physical activity during the early postoperative period may result in improvement of long-term physical function. Since depression and fear of movement had a very small mediating effect, additional work is needed to investigate other potential mediating factors such as pain catastrophizing, resilience and exercise self-efficacy.
Right pneumonectomy for primary large acinic cell carcinoma (AciCC) with severe mediastinal deviation: a case report and literature review
Authors: Chen Xueyu , Zhang Yajie , Luo Fangxiu , Li Hecheng 
Published: October 2021

Abstract
Background
Primary lung acinic cell carcinoma is very rare. Here we report a young female patient who suffered the largest primary lung acinic cell carcinoma with severe mediastinal deviation which has never been reported before. We also reviewed data and features of 20 previously reported cases of primary lung acinic cell carcinoma who underwent lobectomy.

Case presentation
A 27-year-old female patient presented with recurrent coughing and hemoptysis for more than 10 years came to our hospital. A chest computed tomography (CT) showed a giant space-occupying lesion in the hilum of right lung. After a thorough and detailed preoperative examination, the patient then was performed a radical right pneumonectomy with mediastinal lymph node dissection. The size of the tumor was about 8.6 × 4.5 × 4.4 cm. The pathological results demonstrated a primary acinic cell carcinoma of right lung. The immunohistochemistry of the tumor showed AE1/AE3 (+), Ki-67 (2% +), CK7 (+), Vimentin (+), CK19 (+), α1-ACT (+), AB-PAS (+), S-100 (−), TTF-1 (−). The patient was discharged less than 2 weeks after the operation. So far, the patient has been followed-up for 2 years, and no evidence of tumor recurrence or metastasis was observed.

Conclusions
The primary acinic cell carcinoma of lung in this case is the biggest one ever reported and also the first case treated with radical right pneumonectomy. In addition, the patient had a very rare condition of severe mediastinal deviation at the same time. After surgical treatment, the patient recovered uneventfully and had stable disease without recurrence and metastasis after 2 years of follow-up. This case together with the reported case indicate that primary acinic cell carcinoma of lung is of low malignancy, the prognosis and therapy effect of surgical treatment are relatively satisfactory.
Deterioration of diabetic nephropathy via stimulating secretion of cytokines by atrial natriuretic peptide
Authors: Liu Chenxiao , Li Qi , Feng Xiu , Zhu Jian , Li Qian 
Published: October 2021

Abstract
Background
Atrial natriuretic peptide (ANP) is a cardiovascular and metabolic hormone that has been identified recently as being associated with chronic kidney disease (CKD) without diabetes. Cytokines such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and adiponectin (ADP) contribute to the development of type 2 diabetes (T2DM). The aim here was to investigate the relationships of ANP with cytokine levels and clinical variables in T2DM nephropathy patients.

Methods
A total of 81 participants with T2DM were recruited, including 37 patients with normoalbuminuria, 23 patients with microalbuminuria and 21 patients with macroalbuminuria. Serum concentrations of ANP and cytokines were measured using enzyme-linked immunosorbent assay (ELISA) kits. The correlations between ANP and clinical variables were analyzed. Multiple linear regression and logistic regression models were constructed to test the associations between ANP and the severity and presence of albuminuria.

Results
The macroalbuminuria patients exhibited higher plasma levels of ANP, TNF-α, IL-6, and ADP; higher serum creatinine (Cr) and blood urea nitrogen (BUN); and longer duration of diabetes mellitus (DM) than the patients with normoalbuminuria and microalbuminuria. Plasma ANP level was significantly associated with TNF-α (r = 0.876, p < 0.001), IL-6 (r = 0.816, p < 0.001) and ADP (r = 0.772, p < 0.001), independent of the duration of DM or the BUN concentration.

Conclusion
ANP is higher in type 2 diabetes mellitus nephropathy subjects, especially those who have macroalbuminuria, which is associated with compensatory responses to inflammation.