bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma ADAMTS13 and von Willebrand factor in diagnosis and prediction of prognosis in pulmonary arterial hypertension
Authors: Ahmed Abdulla , Ahmed Salaheldin , Rådegran Göran 
Published: August 2021

To improve outcome in pulmonary arterial hypertension, earlier diagnosis and better prognostic assessments are required. We aimed to investigate the diagnostic and prognostic potential of plasma proteins related to pathways recognized in pulmonary arterial hypertension including coagulation, inflammation, and metabolism. Forty‐two proteins were analysed with proximity extension assay from plasma of 20 healthy controls and 150 patients, including (pulmonary arterial hypertension, n = 48, whereof 33 also during early treatment follow‐ups); chronic thromboembolic pulmonary hypertension (CTEPH, n = 20); pulmonary hypertension (PH) due to heart failure (HF) with preserved ejection fraction (HFpEF‐PH, n = 31); PH due to HF with reduced ejection fraction (HFrEF‐PH, n = 36); and HF without PH (Dyspnoea/HF‐non‐PH, n = 15). Patients’ haemodynamics were assessed by right heart catheterization. Plasma ADAMTS13 in incident pulmonary arterial hypertension was lower compared to the healthy controls (p = 0.055), as well as CTEPH (p < 0.0001), HFrEF‐PH (p < 0.0001), HFrEF‐PH (p < 0.0001), and Dyspnoea/HF‐non‐PH (p < 0.0001). Adjusted for age and sex, ADAMTS13 discriminated pulmonary arterial hypertension from the other disease groups with an AUC of 0.91 (sensitivity = 87.5%, and specificity = 78.4%). Higher plasma von Willebrand factor was associated with worse survival (log‐rank p = 0.0029), and a higher mortality rate (adjusted hazard ratio 1.002, 95% confidence interval 1–1.004; p = 0.041). Adjusted for age, sex, and combined with the ESC/ERS risk score, von Willebrand factor predicted mortality (median follow‐up 3.6 years) in pulmonary arterial hypertension with an AUC of 0.94 (sensitivity = 81.3%, and specificity=93.8%). ADAMTS13 may be a promising biomarker for early detection of PAH and von Willebrand factor as a candidate prognostic biomarker. The putative additional value of von Willebrand factor to the European multiparametric risk assessment strategy remains to be elucidated.
Physiological and transcriptomic analyses to reveal underlying phenolic acid action in consecutive monoculture problem of Polygonatum odoratum
Authors: Ni Xianzhi , Jin Chenzhong , Liu Aiyu , Chen Yong , Hu Yihong 
Published: August 2021

Abstract
Background
The root rot of fragrant solomonseal (Polygonatum odoratum) has occurred frequently in the traditional P. odoratum cultivating areas in recent years, causing a heavy loss in yield and quality. The phenolic acids in soil, which are the exudates from the P. odoratum root, act as allelochemicals that contribute to the consecutive monoculture problem (CMP) of the medicinal plant. The aim of this study was to get a better understanding of P. odoratum CMP.

Results
The phenolic acid contents, the nutrient chemical contents, and the enzyme activities related to the soil nutrient metabolism in the first cropping (FC) soil and continuous cropping (CC) soil were determined, and the differentially expressed genes (DEGs) related to the regulation of the phenolic acids in roots were analyzed. The results showed that five low-molecule-weight phenolic acids were detected both in the CC soil and FC soil, but the phenolic acid contents in the CC soil were significantly higher than those in the FC soil except vanillic acid. The contents of the available nitrogen, available phosphorus, and available potassium in the CC soil were significantly decreased, and the activities of urease and sucrase in the CC soil were significantly decreased. The genomic analysis showed that the phenolic acid anabolism in P. odoratum in the CC soil was promoted. These results indicated that the phenolic acids were accumulated in the CC soil, the nutrient condition in the CC soil deteriorated, and the nitrogen metabolism and sugar catabolism of the CC soil were lowered. Meantime, the anabolism of phenolic acids was increased in the CC plant.

Conclusions
The CC system promoted the phenolic acid anabolism in P. odoratum and made phenolic acids accumulate in the soil.
Improving patient self-reporting of antihypertensive adverse drug events in primary care: a stepped wedge cluster randomised trial
Authors: Buchet-Poyau Karine , Occelli Pauline , Touzet Sandrine , Langlois-Jacques Carole , Figon Sophie , Dubois Jean-Pierre , Duclos Antoine , Chanelière Marc , Colin Cyrille , Rabilloud Muriel , Keriel-Gascou Maud 
Published: August 2021

Abstract
Background
About 25% of patients experience adverse drug events (ADE) in primary care, but few events are reported by the patients themselves. One solution to improve the detection and management of ADEs in primary care is for patients to report them to their general practitioner. The study aimed to assess the effect of a booklet designed to improve communication and interaction between patients treated with anti-hypertensive drugs and general practitioners on the reporting of ADEs.

Methods
A cluster randomized controlled cross-sectional stepped wedge open trial (five periods of 3 months) was conducted. A cluster was a group of general practitioners working in ambulatory offices in France. Adults consulting their general practitioner to initiate, modify, or renew an antihypertensive prescription were included. A booklet including information on cardiovascular risks, antihypertensive treatments, and ADE report forms was delivered by the general practitioner to the patient in the intervention group. The primary outcome was the reporting of at least one ADE by the patient to his general practitioner during the three-month period after enrolment. Two clusters were randomised by sequence for a total of 8 to receive the intervention. An intention-to-treat analysis was conducted. A logistic mixed model with random intercept was used.

Results
Sixty general practitioners included 1095 patients (median: 14 per general practitioner; range: 1–103). More patients reported at least one ADE to their general practitioner in the intervention condition compared to the control condition (aOR = 3.5, IC95 [1.2–10.1], p = 0.02). The modification and initiation of an antihypertensive treatment were also significantly associated with the reporting of ADEs (aOR = 4.4, CI95 [1.9–10.0], p <  0.001 and aOR = 11.0, CI95 [4.6–26.4], p <  0.001, respectively). The booklet delivery also improved patient satisfaction on general practitioner communication and high blood pressure management.

Conclusion
A booklet can improve patient self-reporting of ADEs to their general practitioners. Future research should assess whether it can improve general practitioner management of ADEs and patient’s health status.

Trial registration
Trial registry identifier NCT01610817 (2012/05/30).
Maternal psychological distress, education, household income, and congenital heart defects: a prospective cohort study from the Japan environment and children’s study
Authors: Saijo Yasuaki , Yoshioka Eiji , Sato Yukihiro , Azuma Hiroshi , Tanahashi Yusuke , Ito Yoshiya , Kobayashi Sumitaka , Minatoya Machiko , Ait Bamai Yu , Yamazaki Keiko , Itoh Sachiko , Miyashita Chihiro , Ikeda-Araki Atsuko , Kishi Reiko ,   the Japan Environment and Children’s Study (JECS) Group
Published: August 2021

Abstract
Background
The influence of maternal psychological distress on infant congenital heart defects (CHDs) has not been thoroughly investigated. Furthermore, there have been no reports on the combined effect of maternal psychological distress and socioeconomic status on infant CHDs. This study aimed to examine whether maternal psychological distress, socioeconomic status, and their combinations were associated with CHD.

Methods
We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant women between 2011 and 2014. Maternal psychological distress was evaluated using the Kessler Psychological Distress Scale in the first trimester, while maternal education and household income were evaluated in the second and third trimesters. The outcome of infant CHD was determined using the medical records at 1 month of age and/or at birth. Crude- and confounder-adjusted logistic regression analyses were performed to evaluate the association between maternal psychological distress and education and household income on infant CHD.

Results
A total of 93,643 pairs of mothers and infants were analyzed, with 1.1% of infants having CHDs. Maternal psychological distress had a significantly higher odds ratio in the crude analysis but not in the adjusted analysis, while maternal education and household income were statistically insignificant. In the analysis of the combination variable of lowest education and psychological distress, the P for trend was statistically significant in the crude and multivariate model excluding anti-depressant medication, but the significance disappeared in the full model (P = 0.050).

Conclusions
The combination of maternal psychological distress and lower education may be a possible indicator of infant CHD.
Identification of prognostic immune-related gene signature associated with tumor microenvironment of colorectal cancer
Authors: Wang Yuanyuan , Li Wei , Jin Xiaojing , Jiang Xia , Guo Shang , Xu Fei , Su Xingkai , Wang Guiqi , Zhao Zengren , Gu Xiaosong 
Published: August 2021

Abstract
Background
The tumor microenvironment (TME) has significantly correlation with tumor occurrence and prognosis. Our study aimed to identify the prognostic immune-related genes (IRGs)in the tumor microenvironment of colorectal cancer (CRC).

Methods
Transcriptome and clinical data of CRC cases were downloaded from TCGA and GEO databases. Stromal score, immune score, and tumor purity were calculated by the ESTIMATE algorithm. Based on the scores, we divided CRC patients from the TCGA database into low and high groups, and the differentially expressed genes (DEGs) were identified. Immune-related genes (IRGs) were selected by venn plots. To explore underlying pathways, protein-protein interaction (PPI) networks and functional enrichment analysis were used. After utilizing LASSO Cox regression analysis, we finally established a multi-IRGs signature for predicting the prognosis of CRC patients. A nomogram consists of the thirteen-IRGs signature and clinical parameters was developed to predict the overall survival (OS). We investigated the association between prognostic validated IRGs and immune infiltrates by TIMER database.

Results
Gene expression profiles and clinical information of 1635 CRC patients were collected from the TCGA and GEO databases. Higher stromal score, immune score and lower tumor purity were observed positive correlation with tumor stage and poor OS. Based on stromal score, immune score and tumor purity, 1517 DEGs, 1296 DEGs, and 1892 DEGs were identified respectively. The 948 IRGs were screened by venn plots. A thirteen-IRGs signature was constructed for predicting survival of CRC patients. Nomogram with a C-index of 0.769 (95%CI, 0.717–0.821) was developed to predict survival of CRC patients by integrating clinical parameters and thirteen-IRGs signature. The AUC for 1-, 3-, and 5-year OS were 0.789, 0.783 and 0.790, respectively. Results from TIMER database revealed that CD1B, GPX3 and IDO1 were significantly related with immune infiltrates.

Conclusions
In this study, we established a novel thirteen immune-related genes signature that may serve as a validated prognostic predictor for CRC patients, thus will be conducive to individualized treatment decisions.
Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma
Authors: Powles Thomas , Choueiri Toni K. , Motzer Robert J. , Jonasch Eric , Pal Sumanta , Tannir Nizar M. , Signoretti Sabina , Kaldate Rajesh , Scheffold Christian , Wang Evelyn , Aftab Dana T. , Escudier Bernard , George Daniel J. 
Published: August 2021

Abstract
Background
In the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS) and overall survival (OS) versus everolimus in patients with advanced RCC after prior antiangiogenic therapy.

Methods
In this exploratory analysis, plasma biomarkers from baseline and week 4 from 621 of 658 randomized patients were analyzed for CA9, HGF, MET, GAS6, AXL, VEGF, VEGFR2, and IL-8. PFS and OS were analyzed by baseline biomarker levels as both dichotomized and continuous variables using univariate and multivariable methods. For on-treatment changes, PFS and OS were analyzed using fold change in biomarker levels at week 4. Biomarkers were considered prognostic if p < 0.05 and predictive if pinteraction < 0.05 for the interaction between treatment and biomarker.

Results
Hazard ratios for PFS and OS favored cabozantinib versus everolimus for both low and high baseline levels of all biomarkers (hazard ratios ≤0.78). In univariate analyses, low baseline HGF, AXL, and VEGF were prognostic for improvements in both PFS and OS with cabozantinib, and low HGF was prognostic for improvements in both PFS and OS with everolimus. Low AXL was predictive of relative improvement in PFS for cabozantinib versus everolimus. Results were generally consistent when baseline biomarkers were expressed as continuous variables, although none were predictive of benefit with treatment. In multivariable analysis, low baseline HGF was independently prognostic for improved PFS for both cabozantinib and everolimus; low HGF, GAS6, and VEGF were independently prognostic for improved OS with cabozantinib. No biomarkers were independently prognostic for OS with everolimus. On-treatment increases in some biomarkers appeared prognostic for PFS or OS with cabozantinib in univariate analyses; however, none were independently prognostic in multivariable analysis.

Conclusions
PFS and OS were improved with cabozantinib versus everolimus at high and low baseline levels of all biomarkers. Low baseline HGF was consistently identified as a prognostic biomarker for improved PFS or OS with cabozantinib or everolimus, supporting further prospective evaluation of the prognostic significance of HGF in advanced RCC.

Trial registration
ClinicalTrials.gov NCT01865747 (registered on 05/31/2013).
TACR2 is associated with the immune microenvironment and inhibits migration and proliferation via the Wnt/β-catenin signaling pathway in prostate cancer
Authors: Jianfeng Wang , Yutao Wang , Jianbin Bi 
Published: August 2021

Abstract
Background
The tachykinin receptor 2 (TACR2) is encoded by the tachykinin receptor correlation gene. Recent microarray analysis for prostate cancer suggests that TACR2 expression is associated with clinical phenotype and disease-free survival among patients with prostate cancer.

Results
TACR2 protein levels were lower in prostate cancer tissues than in adjacent normal prostate tissue. TACR2 expression significantly correlated with clinical stage, Gleason scores, and survival outcomes. TACR2 expression positively correlated with mast cells and negatively correlated with M2 macrophages. Overexpression of TACR2 promoted the migration and proliferation of prostate cancer cells by regulating the Wnt signaling pathway.

Conclusions
The TACR2-Wnt/β-catenin signaling pathway is critical in prostate cancer. TACR2 may affect tumor cells’ occurrence and development by changing the content of immune cells in the tumor microenvironment. These findings suggest that TACR2 may be a candidate molecular biomarker for prostate cancer therapy.
Development and validation of prognostic nomograms for patients with colon neuroendocrine neoplasms
Authors: Xu Ruitong , Zhou Bingrong , Hu Ping , Xue Bingyan , Gu Danyang , Li Xiaolin , Tang Qiyun 
Published: August 2021

Abstract
Background
Colon neuroendocrine neoplasms (NENs) have one of the poorest median overall survival (OS) rates among all NENs. The American Joint Committee on Cancer (AJCC) tumor–node–metastasis (TNM) staging system—currently the most commonly used prediction model—has limited prediction accuracy because it does not include parameters such as age, sex, and treatment. The aim of this study was to construct nomograms containing various clinically important parameters to predict the prognosis of patients with colon NENs more accurately.

Methods
Using the Surveillance, Epidemiology, and End Results (SEER) database, we performed a retrospective analysis of colon NENs diagnosed from 1975 to 2016. Data were collected from 1196 patients; almost half were female (617/1196, 51.6%), and the average age was 61.94 ± 13.05 years. Based on the age triple cut-off values, there were 396 (33.1%), 408 (34.1%), and 392 (32.8%) patients in age groups 0–55 years, 55–67 years, and ≥ 68 years, respectively. Patients were randomized into training and validation cohorts (3:1). Independent prognostic factors were used for construction of nomograms to precisely predict OS and cancer-specific survival (CSS) in patients with colon NENs.

Results
Multivariate analysis showed that age ≥ 68 years, sex, tumor size, grade, chemotherapy, N stage, and M stage were independent predictors of OS. In the validation cohort, the Concordance index (C-index) values of the OS and CSS nomograms were 0.8345 (95% confidence interval [CI], 0.8044–0.8646) and 0.8209 (95% CI, 0.7808–0.861), respectively. C-index also indicated superior performance of both nomograms (C-index 0.8347 for OS and 0.8668 for CSS) compared with the AJCC TNM classification (C-index 0.7159 for OS and 0.7366 for CSS).

Conclusions
We established and validated new nomograms for more precise prediction of OS and CSS in patients with colon NENs to facilitate individualized clinical decisions.
Role of open cerclage wiring in patients with comminuted fractures of the femoral shaft treated with intramedullary nails
Authors: Wang Tzu-Hao , Chuang Hao-Chun , Kuan Fa-Chuan , Hong Chih-Kai , Yeh Ming-Long , Su Wei-Ren , Hsu Kai-Lan 
Published: August 2021

AbstractIntroductionThe role of open cerclage wiring in comminuted femoral shaft fracture treatment with intramedullary nails remains unclear. Here, we analyzed the effect of open cerclage wiring and the risk factors for nonunion after interlocking nailing in comminuted femoral shaft fracture treatment. We hypothesized that open cerclage wiring can be applied in patients with severe comminuted femoral shaft fractures without affecting bone healing.Patients and methodsThis retrospective cohort study used data from consecutive patients who underwent interlocking nail fixation of a comminuted femoral shaft fracture between January 1, 2009, and December 31, 2016. First, eligible patients were divided into the wire and no wire groups according to the surgical technique used, and their union rate was recorded. The patients were then divided into the union and nonunion groups, and their perioperative data were analyzed.ResultsIn total, 71 comminuted femoral shaft fractures treated with interlocking nail fixation were included: 38 fractures (53.5%) augmented with the open wiring technique and 33 reduced with closed or mini-open techniques without wiring. The wire group demonstrated significant improvements in fracture reduction compared with the no wire group, whereas no significant difference was observed in the union rate between the wire and no wire groups (p= 0.180). Moreover, 46 (65%) of 71 fractures achieved union smoothly, and no significant difference was observed in any perioperative data between the union and nonunion groups.DiscussionAugmentation with open cerclage wiring is indicated for comminuted femoral shaft fractures treated with intramedullary nails, even when the fragments are large or greatly displaced. Thus, open cerclage wiring can be used for fracture treatment without decreasing the union rate.
Septic shock complicated by disseminated herpes simplex virus-1 infection: a case report
Authors: Boquet Amélie , Boulay Guillaume , Hautin Etienne , Mottard Nicolas 
Published: August 2021

Abstract
Background
Herpes virus remains dormant in human cells and could reactivate under immunosuppressed conditions, such as prolonged critical illnesses. The phenomenon of viral replication during intensive care is well known, even in patients without a history of immunosuppression, but it usually does not have a clinical impact. Systemic reactivation leads to viral DNA in blood. It remains unclear whether this replication is a marker of morbimortality or a true pathogenic process. Therefore, it is unclear what medical treatment is most appropriate for simple replication. In organ damage suspected to be induced by herpes virus, there is no consensus on the most appropriate treatment duration. Here, we report a rarely described case of multiorgan failure implicating herpes simplex virus and discuss its treatment.

Case report
A 53-year-old Caucasian immunosuppressed woman was admitted to the intensive care unit for septic shock. She presented pneumonia due to Klebsiella pneumoniae. Two weeks after admission, she showed multiorgan failure with acute respiratory distress syndrome and circulation failure. She had digestive and cutaneous lesions typical of herpes simplex virus 1. Blood and respiratory polymerase chain reaction was strongly herpes simplex virus-1 positive. No other bacteria, fungi, or viruses were found. The evolution was rapidly favorable after the initiation of antiviral treatment. Treatment was stopped after 3 weeks of well-conducted antiviral therapy. Curative-dose treatment was interrupted despite continuous strongly positive blood polymerase chain reaction results. In this context, prophylactic treatment was continued.

Conclusion
We report an exceptional presentation of multiorgan failure in the intensive care unit due to herpes simplex virus-1. The diagnosis was made based on typical herpes simplex virus-1 visceral lesions and the absence of other responsible microorganisms. Intense viral replication is a key diagnostic element. There is no consensus regarding the most appropriate treatment duration, but such decisions should not be based on blood polymerase chain reaction.
Mask decontamination methods (model N95) for respiratory protection: a rapid review
Authors: Probst Livia Fernandes , Guerrero Ana Tereza Gomes , Cardoso Andréia Insabralde de Queiroz , Grande Antonio Jose , Croda Mariana Garcia , Venturini James , Fonseca Maria Cristina de Camargo , Paniago Anamaria Mello Miranda , Barreto Jorge Otávio Maia , de Oliveira Sandra Maria do Vale Leone 
Published: August 2021

Abstract
Background
N95 respiratory protection masks are used by healthcare professionals to prevent contamination from infectious microorganisms transmitted by droplets or aerosols.

Methods
We conducted a rapid review of the literature analyzing the effectiveness of decontamination methods for mask reuse. The database searches were carried out up to September 2020. The systematic review was conducted in a way which simplified the stages of a complete systematic review, due to the worldwide necessity for reliable fast evidences on this matter.

Results
A total of 563 articles were retrieved of which 48 laboratory-based studies were selected. Fifteen decontamination methods were included in the studies. A total of 19 laboratory studies used hydrogen peroxide, 21 studies used ultraviolet germicidal irradiation, 4 studies used ethylene oxide, 11 studies used dry heat, 9 studies used moist heat, 5 studies used ethanol, two studies used isopropanol solution, 11 studies used microwave oven, 10 studies used sodium hypochlorite, 7 studies used autoclave, 3 studies used an electric rice cooker, 1 study used cleaning wipes, 1 study used bar soap, 1 study used water, 1 study used multi-purpose high-level disinfection cabinet, and another 1 study used chlorine dioxide. Five methods that are promising are as follows: hydrogen peroxide vapor, ultraviolet irradiation, dry heat, wet heat/pasteurization, and microwave ovens.

Conclusions
We have presented the best available evidence on mask decontamination; nevertheless, its applicability is limited due to few studies on the topic and the lack of studies on real environments.