bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors related balance disorder for patients with dizziness/vertigo
Authors: Cao Zhentang , Zhu Cuiting , Zhou Yanan , Wang Yan , Chen Meimei , Ju Yi , Zhao Xingquan
Published: May 2021

Background

When dizziness/vertigo patients presented with balance disorder, it will bring severe morbidity. There is currently lack of research to explore risk factor related balance disorder in dizziness patients, especially in those who walk independently.

Aim

To investigate risk factors related balance disorder in dizziness/vertigo patients who walk independently.

Methods

Medical data of 1002 dizziness/vertigo patients registered in vertigo/balance disorder registration database were reviewed. The demographic data, medical history, and risk factors for atherosclerosis (AS) were collected. Enrolled dizziness/vertigo patients could walk independently, completed Romberg test, videonystagmography (VNG), and limits of stability (LOS). The subjective imbalance was patient complained of postural symptom when performing Romberg test. Multivariable logistic regression analyzed risk factors related balance disorder. The receiver operating characteristic (ROC) curve evaluated the utility of regression model.

Results

Five hundred fifty-three dizziness/vertigo patients who walk independently were included in the final analysis. According to LOS, patients were divided into 334 (60%) normal balance and 219 (40%) balance disorder. Compared with normal balance, patients with balance disorder were older (P = 0.045) and had more risk factors for AS (P<0.0001). The regression showed that risk factors for AS (OR 1.494, 95% CI 1.198–1.863), subjective imbalance (OR 4.835, 95% CI 3.047–7.673), and abnormality of optokinetic nystagmus (OR 8.308, 95% CI 1.576–43.789) were related to balance disorder. The sensitivity and specificity of model were 71 and 63% (P<0.0001). The area under the curve (AUC) was 0.721.

Conclusions

Risk factors for AS, subjective imbalance, and abnormality of optokinetic nystagmus were predictors for balance disorder in patients with dizziness/vertigo who walk independently.
Fetal weight estimation by automated three-dimensional limb volume model in late third trimester compared to two-dimensional model: a cross-sectional prospective observational study
Authors: Wu Xining , Niu Zihan , Xu Zhonghui , Jiang Yuxin , Zhang Yixiu , Meng Hua , Ouyang Yunshu
Published: May 2021

Background

Accurate estimation of fetal weight is important for prenatal care and for detection of fetal growth abnormalities. Prediction of fetal weight entails the indirect measurement of fetal biometry by ultrasound that is then introduced into formulae to calculate the estimated fetal weight. The aim of our study was to evaluate the accuracy of fetal weight estimation of Chinese fetuses in the third trimester using an automated three-dimensional (3D) fractional limb volume model, and to compare this model with the traditional two-dimensional (2D) model.

Methods

Prospective 2D and 3D ultrasonography were performed among women with singleton pregnancies 7 days before delivery to obtain 2D data, including fetal biparietal diameter, abdominal circumference and femur length, as well as 3D data, including the fractional arm volume (AVol) and fractional thigh volume (TVol). The fetal weight was estimated using the 2D model and the 3D fractional limb volume model respectively. Percentage error was defined as (estimated fetal weight - actual birth weight) divided by actual birth weight and multiplied by 100. Systematic errors (accuracy) were evaluated as the mean percentage error (MPE). Random errors (precision) were calculated as ±1 SD of percentage error. The intraclass correlation coefficient (ICC) was used to analyze the inter-observer reliability of the 3D ultrasound measurements of fractional limb volume.

Results

Ultrasound examination was performed on 56 fetuses at 39.6 ± 1.4 weeks’ gestation. The average birth weight of the newborns was 3393 ± 530 g. The average fetal weight estimated by the 2D model was 3478 ± 467 g, and the MPE was 3.2 ± 8.9. The average fetal weights estimated by AVol and TVol of the 3D model were 3268 ± 467 g and 3250 ± 485 g, respectively, and the MPEs were − 3.3 ± 6.6 and − 3.9 ± 6.1, respectively. For the 3D TVol model, the proportion of fetuses with estimated error ≤ 5% was significantly higher than that of the 2D model (55.4% vs. 33.9%, p < 0.05). For fetuses with a birth weight < 3500 g, the accuracy of the AVol and TVol models were better than the 2D model (− 0.8 vs. 7.0 and − 2.8 vs. 7.0, both p < 0.05). Moreover, for these fetuses, the proportions of estimated error ≤ 5% of the AVol and TVol models were 58.1 and 64.5%, respectively, significantly higher than that of the 2D model (19.4%) (both p < 0.05). The inter-observer reliability of measuring fetal AVol and TVol were high, with the ICCs of 0.921 and 0.963, respectively.

Conclusion

In this cohort, the automated 3D fractional limb volume model improves the accuracy of weight estimation in most third-trimester fetuses. Prediction accuracy of the 3D model for neonatal BW, particularly < 3500 g was higher than that of the traditional 2D model.
A nomogram predicting overall survival in patients with non-metastatic pancreatic head adenocarcinoma after surgery: a population-based study
Authors: Zou Wenbo , Wang Zizheng , Wang Fei , Zhang Gong , Liu Rong
Published: May 2021

Background

Pancreatic head adenocarcinoma (PHAC), a malignant tumour, has a very poor prognosis, and the existing prognostic tools lack good predictive power. This study aimed to develop a better nomogram to predict overall survival after resection of non-metastatic PHAC.

Methods

Patients with non-metastatic PHAC were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided randomly into training and validation cohorts at a ratio of 7:3. Cox regression analysis was used to screen prognostic factors and construct the nomogram. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the performance of the model. The predictive accuracy and clinical benefits of the nomogram were validated using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA).

Results

From 2010 to 2016, 6419 patients with non-metastatic PHAC who underwent surgery were collected from the SEER database. A model including T stage, N stage, grade, radiotherapy, and chemotherapy was constructed. The concordance index of the nomogram was 0.676, and the AUCs of the model assessing survival at multiple timepoints within 60 months were significantly higher than those of the American Joint Committee on Cancer (AJCC) 8th staging system in the training cohort. Calibration curves showed that the nomogram had ability to predict the actual survival. The NRI, IDI, and DCA curves also indicated that our nomogram had higher predictive capability and clinical utility than the AJCC staging system.

Conclusions

Our nomogram has an ability to predict overall survival after resection of non-metastatic PHAC and includes prognostic factors that are easy to obtain in clinical practice. It would help assist clinicians to conduct personalized medicine.
Poor prognosis of male triple-positive breast Cancer patients: a propensity score matched SEER analysis and molecular portraits
Authors: Wang Biyuan , Wang Hui , Zhao Andi , Zhang Mi , Yang Jin
Published: May 2021

Background

The purpose of this study was to explore clinicalpathology features, molecular features and outcome of male breast cancer patients who expressed ER, PR as well as HER-2, namely triple-positive male breast cancer (TP-MBC), and compared them with triple-positive female breast cancer patients (TP-FBC).

Methods

TP-MBC and TP-FBC from 2010 to 2017 were selected from the Surveillance, Epidemiology, and End Results database (SEER). Kaplan-Meier plotter and multivariable Cox regression model were applied to analyse the difference between TP-MBC and TP-FBC on cancer-specific survival (CSS) and overall survival (OS). Propensity score matched (PSM) analysis was used to ensure well-balanced characteristics. 7 cases TP-MBC and 174 cases TP-FBC patients with the genomic and clinical information were identified from the cohort of The Cancer Genome Atlas (TCGA) and the Memorial Sloan Kettering (MSK).

Result

336 TP-MBC and 33,339 TP-FBC patients were taken into the study. The percentages of TP-MBC in MBC patients were higher than the rates of TP-FBC in FBC patients from 2010 to 2017 except 2012. Compared with TP-FBC, more TP-MBC were staged III (17.9% vs. 13.5%) or stage IV (11.0% vs. 6.9%). TP-MBC were more frequently to be older than 65-years-old (47.0% vs. 29.3%), Balck (15.2% vs. 10.8%), ductal carcinoma (91.7% vs. 84.4%) and metastases to lung (4.5% vs. 2.1%) or bone (8.6% vs. 4.7%). TP-MBC had worse OS and CSS than TP-FBC in all stages (P < 0.001). In multivariable prediction model of TPBC, male patients had a higher risk than female. Lastly, the worse OS (P < 0.001) and CSS (P = 0.013) were seen in the 1:3 PSM analysis between TP-MBC and TP-FBC. Genomic analysis revealed that TP-MBCs have some notable rare mutations, like ERBB2, ERBB3, RB1, CDK12, FGFR2, IDH1, AGO2, GATA3, and some of them are not discovered in TP-FBC.

Conclusion

TP-MBC had a worse survival than TP-FBC, and there were different genomic features between two groups. Current knowledge and treatment to TP-MBC maybe inadequate and remain to be explored.
Efficacy of positron emission tomography in diagnosis of lateral lymph node metastases in patients with rectal Cancer: a retrospective study
Authors: Yukimoto Ryohei , Uemura Mamoru , Tsuboyama Takahiro , Hata Tsuyoshi , Fujino Shiki , Ogino Takayuki , Miyoshi Norikatsu , Takahashi Hidekazu , Hata Taishi , Yamamoto Hirofumi , Mizushima Tsunekazu , Kida Akira , Furuyashiki Mamoru , Doki Yuichiro , Eguchi Hidetoshi
Published: May 2021

Background

The presence of lateral pelvic lymph node (LLN) metastasis is an essential prognostic factor in rectal cancer patients. Thus, preoperative diagnosis of LLN metastasis is clinically important to determine the therapeutic strategy. The aim of this study was to evaluate the efficacy of preoperative positron emission tomography/computed tomography (PET/CT) in the diagnosis of LLN metastasis.

Methods

Eighty-four patients with rectal cancer who underwent LLN dissection at Osaka University were included in this study. The maximum standardized uptake value (SUVmax) of the primary tumor and LLN were preoperatively calculated using PET/CT. Simultaneously, the short axis of the lymph node was measured using multi-detector row computed tomography (MDCT). The presence of metastases was evaluated by postoperative pathological examination.

Results

Of the 84 patients, LLN metastases developed in the left, right, and both LLN regions in 6, 7, and 2 patients, respectively. The diagnosis of the metastases was predicted with a sensitivity of 82%, specificity of 93%, positive predictive value of 58%, negative predictive value of 98%, false positive value of 7%, and false negative value of 18% when the cutoff value of the LLN SUVmax was set at 1.5. The cutoff value of the short axis set at 7 mm on MDCT was most useful in diagnosing LLN metastases, but SUVmax was even more useful in terms of specificity.

Conclusions

The cutoff value of 1.5 for lymph node SUVmax in PET is a reasonable measure to predict the risk of preoperative LLN metastases in rectal cancer patients.
Prognostic value of different maternal obesity phenotypes in predicting offspring obesity in a family-based cohort study
Authors: Jalali-Farahani Sara , Amiri Parisa , Lashkari Bita , Cheraghi Leila , Hosseinpanah Farhad , Azizi Fereidoun
Published: May 2021

Background

Parental weight is studied as an important determinant of childhood obesity; however, obesity-related metabolic abnormalities have been less considered as determinants of childhood obesity. This study aimed to investigate the association between maternal obesity phenotypes and incidence of obesity in their offspring.

Methods

This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study. A total of 2151 non-obese children who had complete parental information were followed for incidence of obesity over a mean of 148.7 ± 34.7 months. Obesity in children was defined using the World Health Organization criteria. Maternal body mass index (BMI) was classified into three categories: normal weight, overweight and obese. Dysmetabolic status was considered as having metabolic syndrome or diabetes. Metabolic syndrome and diabetes were defined according to the Joint Interim Statement and American diabetes association criteria, respectively. Considering maternal BMI categories and metabolic status, six obesity phenotypes were defined as followed: 1) normal weight and normal metabolic status, 2) overweight and normal metabolic status, 3) obese and normal metabolic status, 4) normal weight and dysmetabolic status, 5) overweight and dysmetabolic status, and 6) obese and dysmetabolic status. The association between maternal obesity phenotypes and incidence of obesity in children was studied using Cox proportional regression hazard model.

Results

In male offspring, the risk of incidence of obesity significantly increased in those with maternal obesity phenotypes including overweight/normal metabolic: 1.75(95% CI: 1.10–2.79), obese/normal metabolic: 2.60(95%CI: 1.51–4.48), overweight/dysmetabolic: 2.34(95%CI: 1.35–4.03) and obese/dysmetabolic: 3.21(95%CI: 1.94–5.03) compared to the normal weight/normal metabolic phenotype. Similarly, in girls, the risk of incidence of obesity significantly increased in offspring with maternal obesity phenotypes including overweight/normal metabolic: 2.39(95%CI: 1.46–3.90), obese/normal metabolic: 3.55(95%CI: 1.94–6.46), overweight/dysmetabolic: 1.92(95%CI: 1.04–3.52) and obese/dysmetabolic: 3.89(95%CI: 2.28–6.64) compared to normal weight/normal metabolic phenotype. However, maternal normal weight/dysmetabolic phenotype did not significantly change the risk of obesity in both male and female offspring.

Conclusion

Except for normal weight/dysmetabolic phenotype, all maternal obesity phenotypes had significant prognostic values for incidence of offspring obesity with the highest risk for obese/dysmetabolic phenotype. This study provides valuable findings for identifying the first line target groups for planning interventions to prevent childhood obesity.
Lefamulin efficacy and safety in a pooled phase 3 clinical trial population with community-acquired bacterial pneumonia and common clinical comorbidities
Authors: File Thomas M. , Alexander Elizabeth , Goldberg Lisa , Das Anita F. , Sandrock Christian , Paukner Susanne , Moran Gregory J.
Published: May 2021

Background

Lefamulin, a first-in-class pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia (CABP), was noninferior to moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) 1 intravenous-to-oral switch study and the LEAP 2 oral-only study. Using pooled LEAP 1/2 data, we examined lefamulin efficacy/safety overall and within subgroups of patients presenting with comorbidities typical in CABP management.

Methods

In LEAP 1, adults with CABP were randomized to receive intravenous lefamulin (150 mg every 12 h) for 5‒7 days or moxifloxacin (400 mg every 24 h) for 7 days, with optional intravenous-to-oral switch if predefined improvement criteria were met. In LEAP 2, adults with CABP were randomized to receive oral lefamulin (600 mg every 12 h) for 5 days or moxifloxacin (400 mg every 24 h) for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 h after first study drug dose and investigator assessment of clinical response (IACR) at test-of-cure (5‒10 days after last dose). Pooled analyses of the overall population used a 10% noninferiority margin.

Results

Lefamulin (n = 646) was noninferior to moxifloxacin (n = 643) for ECR (89.3% vs 90.5%, respectively; difference  − 1.1%; 95% CI  − 4.4 to 2.2); IACR success rates at test-of-cure were similarly high (≥ 85.0%). High efficacy with both lefamulin and moxifloxacin was also demonstrated across all well-represented patient subgroups, including those with advanced age, diabetes mellitus, a history of cardiovascular diseases (e.g., hypertension, congestive heart failure, or arrhythmia) or chronic lung diseases (e.g., asthma or chronic obstructive pulmonary disease), elevated liver enzymes, or mild-to-moderate renal dysfunction. No new safety signals were identified.

Conclusions

Lefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities.

Trial registration

ClinicalTrials.gov LEAP 1 (NCT02559310; Registration Date: 24/09/2015) and LEAP 2 (NCT02813694; Registration Date: 27/06/2016).
Comparison of anterior and posterior trabecular bone microstructure of human mandible using cone-beam CT and micro CT
Authors: Ibrahim Norliza , Parsa Azin , Hassan Bassam , van der Stelt Paul , Rahmat Rabiah A. , Ismail Siti M. , Aartman Irene H. A.
Published: May 2021

Background

The aim of this study was to compare the trabecular bone microstructures of anterior and posterior edentulous regions of human mandible using cone-beam computed tomography (CBCT) and micro computed tomography (µCT).

Methods

Twenty volumes of interests consisting of six anterior and fourteen posterior edentulous regions were obtained from human mandibular cadavers. A CBCT system with a resolution of 80 µm (3D Accuitomo 170, J. Morita, Kyoto, Japan) and a µCT system with a resolution of 35 µm (SkyScan 1173, Kontich, Belgium) were used to scan the mandibles. Three structural parameters namely, trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were analysed using CTAn software (v 1.11, SkyScan, Kontich, Belgium). For each system, the measurements obtained from anterior and posterior regions were tested using independent samplet-test. Subsequently, all measurements between systems were tested using pairedt-test.

Results

In CBCT, all parameters of the anterior and posterior mandible showed no significant differences (p > 0.05). However, µCT showed a significant different of Tb.Th (p = 0.023) between anterior and posterior region. Regardless of regions, the measurements obtained using both imaging systems were significantly different (p ≤ 0.021) for Tb.Th and Tb.N.

Conclusions

The current study demonstrated that only the variation of Tb.Th between anterior and posterior edentulous region of mandible can be detected using µCT. In addition, CBCT is less feasible than µCT in assessing trabecular bone microstructures at both regions.
Primary ovarian serous carcinomas with extensive squamous differentiation: a case report and literature review
Authors: Sun Yao , Chen Yuezhou , Zhang Xiaofei , Chen Hao , Zhou Feng
Published: May 2021

Background

Primary ovarian serous carcinomas (OSC) with extensive squamous differentiation is a rare, and histological diagnostic criteria and biological behavior have not been fully established. We present an extremely rare case of primary OSC of the ovary with squamous differentiation.

Case presentation

A 58-year-old (gravidity 3, parity 2) female was admitted complaining of abdominal distention for 6 months. No apparent tumor in the cervix was found by a physical examination. Serum levels of cancer antigen 125 (CA125) was elevated (2723.0 IU/L). Macroscopically, a 7 cm tumor of the left uterine adnexa, a 5 cm tumor of the right adnexa, and a 3 cm tumor of the omentum were found. Histological and immunochemical tests confirmed a diagnosis of OSC with squamous differentiation. Debulking surgery with tumor resection was performed. The patient was subsequently received postoperative chemotherapy.

Conclusions

In summary, OSC with extensive squamous differentiation is a rare, and the inter- and intratumor heterogeneity may be the reason for this phenomenon. Histological diagnostic criteria and biological behavior have not been fully established because of the limited data.
The association between variants in PLA2R and HLA-DQA1 and renal outcomes in patients with primary membranous nephropathy in Western China
Authors: Fan Shulei , Wang Qiuxia , Wang Amanda Y. , Zhang Ping , Zhong Xiang , Chen Shasha , Li Guisen , Wang Li , Wang Wei
Published: May 2021

Background

Both Genome-wide associations and our previous study have shown that single nucleotide polymorphisms (SNPs) of M-type phospholipase A2 receptor (PLA2R) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) gene were identified to be associated with primary membranous nephropathy (PMN). However, whether these SNPs affect clinical manifestation and renal outcome for PMN patients is poorly defined. Here, we evaluated whether there is an association between these SNPs and clinical manifestations and renal outcomes of PMN in a western Chinese cohort.

Methods

Seven SNPs within PLA2R and one SNP in HLA-DQA1 were selected in our study. Clinical data from 314 patients with PMN were collected and the relationship between the genotype and phenotype was evaluated. A total of 186 patients had follow-up data. We assessed the treatment responses and renal outcomes between patients with these gene polymorphisms after a median follow-up of 18.6 months.

Results

Eight SNPs were not associated with clinical manifestations of PMN patients (Pc < 0.05). rs3828323 T allele was marginally significantly associated with hypertension (P = 0.008, Pc = 0.064, OR = 1.821). After treatment for PMN, the SR group (including CR and PR) had lower serum creatinine level (68.4 ± 18.8 μmol/L vs. 122.8 ± 126.6 μmol/L, P < 0.001), urea (5.5 ± 1.9 mmol/L vs. 8.0 ± 4.0 mmol/L, P < 0.001), uric acid (358.5 ± 95.1 μmol/L vs. 392.8 ± 118.1 μmol/L, P = 0.037) and urinary protein (0.23 (0.76,1.05) g/d vs. 3.01 (2.06,7.95) g/d, P < 0.001), higher eGFR (100.0 ± 20.1 ml/min/1.73m2 vs. 77.1 ± 35.3 ml/min/1.73m2, P < 0.001) and albumin (41.1 ± 5.1 g/L vs.30.4 ± 8.2 g/L, P < 0.001). We also identified that PMN patients with CT/TT genotype for rs3828323 achieved higher cumulative survival rate than patients with CC genotype.

Conclusions

Rs3828323 may influence hypertension and renal outcome in patients with PMN. Further research is needed to explore the mechanism for this genotype-disease phenotype association.
A five metastasis-related long noncoding RNA risk signature for osteosarcoma survival prediction
Authors: Yu SiYuan , Shao FengLing , Liu HuiJun , Liu QingQing
Published: May 2021

Background

Osteosarcoma is a highly malignant and common bone tumour with an aggressive disease course and a poor prognosis. Previous studies have demonstrated the relationship between long noncoding RNAs (lncRNAs) and tumorigenesis, metastasis, and progression.

Methods

We utilized a large cohort from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database osteosarcoma project to identify potential lncRNAs related to the overall survival of patients with osteosarcoma by using univariate and multivariate Cox proportional hazards regression analyses. Kaplan–Meier curves were generated to evaluate the overall survival difference between patients in the high-risk group and the low-risk group. A time-dependent receiver operating characteristic curve (ROC) was employed, and the area under the curve (AUC) of ROC was measured to assess the sensitivity and specificity of the multi-lncRNA signature.

Results

Five lncRNAs (RP11-128N14.5, RP11-231|13.2, RP5-894D12.4, LAMA5-AS1, RP11-346L1.2) were identified, and a five-lncRNA signature was constructed. The AUC for predicting 5-year survival was 0.745, which suggested good performance of the five-lncRNA signature. In addition, functional enrichment analysis of the five-lncRNA-correlated protein-coding genes (PCGs) was performed to show the biological function of the five lncRNAs. Additionally, PPI network suggested RTP1 is a potential biomarker that regulates the prognosis of osteosarcoma.

Conclusions

We developed a five-lncRNA signature as a potential prognostic indicator for osteosarcoma.
Genetic engineering of the precursor supply pathway for the overproduction of the nC14-surfactin isoform with promising MEOR applications
Authors: Hu Fangxiang , Cai Weijie , Lin Junzhang , Wang Weidong , Li Shuang
Published: May 2021

Background

Surfactin, a representative biosurfactant of lipopeptide mainly produced byBacillus subtilis,consists of a cyclic heptapeptide linked to a β-hydroxy fatty acid chain. The functional activity of surfactin is closely related to the length and isomerism of the fatty acid chain.

Results

In this study, the fatty acid precursor supply pathway inBacillus subtilis168 for surfactin production was strengthened through two steps. Firstly, pathways competing for the precursors were eliminated with inactivation ofppsandpks. Secondly, the plant medium-chain acyl-carrier protein (ACP) thioesterase (BTE) fromUmbellularia californicawas overexpressed. As a result, the surfactin titer after 24 h of cultivation improved by 34%, and the production rate increased from 0.112 to 0.177 g/L/h. The isoforms identified by RP-HPLC and GC–MS showed that the proportion ofnC14-surfactin increased 6.4 times compared to the control strain. A comparison of further properties revealed that the product with morenC14-surfactin had higher surface activity and better performance in oil-washing. Finally, the product with morenC14-surfactin isoform had a higher hydrocarbon-emulsification index, and it increased the water-wettability of the oil-saturated silicate surface.

Conclusion

The obtained results identified that enhancing the supply of fatty acid precursor is very essential for the synthesis of surfactin. At the same time, this study also proved that thioesterase BTE can promote the production ofnC14-surfactin and experimentally demonstrated its higher surface activity and better performance in oil-washing. These results are of great significance for the MEOR application of surfactin.

Graphic abstract
RFX1: a promising therapeutic arsenal against cancer
Authors: Issac Joby , Raveendran Pooja S. , Das Ani V.
Published: May 2021

Regulatory factor X1 (RFX1) is an evolutionary conserved transcriptional factor that influences a wide range of cellular processes such as cell cycle, cell proliferation, differentiation, and apoptosis, by regulating a number of target genes that are involved in such processes. On a closer look, these target genes also play a key role in tumorigenesis and associated events. Such observations paved the way for further studies evaluating the role of RFX1 in cancer. These studies were indispensable due to the failure of conventional chemotherapeutic drugs to target key cellular hallmarks such as cancer stemness, cellular plasticity, enhanced drug efflux, de-regulated DNA repair machinery, and altered pathways evading apoptosis. In this review, we compile significant evidence for the tumor-suppressive activities of RFX1 while also analyzing its oncogenic potential in some cancers. RFX1 induction decreased cellular proliferation, modulated the immune system, induced apoptosis, reduced chemoresistance, and sensitized cancer stem cells for chemotherapy. Thus, our review discusses the pleiotropic function of RFX1 in multitudinous gene regulations, decisive protein–protein interactions, and also its role in regulating key cell signaling events in cancer. Elucidation of these regulatory mechanisms can be further utilized for RFX1 targeted therapy.
Longitudinal study based on a safety registry for malaria patients treated with artenimol–piperaquine in six European countries
Authors: Vignier Nicolas , Bouchaud Olivier , Angheben Andrea , Bottieau Emmanuel , Calleri Guido , Salas-Coronas Joaquín , Martin Charlotte , Ramos José Manuel , Mechain Matthieu , Rapp Christophe , Nothdurft Hans-Dieter , Velasco Maria , Bardají Azucena , Rojo-Marcos Gerardo , Visser Leo G. , Hatz Christoph , Bisoffi Zeno , Jelinek Tomas , Duparc Stephan , Bourhis Yann , Tommasini Silva , Iannucelli Maurizio , Bacchieri Antonella , Mattera Giovan Giuseppe , Merlo Pich Emilio , Behrens Ronald H.
Published: May 2021

Background

European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)–piperaquine (APQ) Eurartesim® during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap.

Methods

Participants were recruited through Health Care Provider’s safety registry in 15 centres across 6 European countries in the period 2013–2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett’s (QTcB) or Fridericia’s (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females.

Results

Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m2 (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p < 0.05) more AEs. Among AEs, 21 were due to cardiotoxicity (7.1%), mostly QT prolongation, while 6 were due to neurotoxicity (2.0%), mostly dizziness. Using QTcF correction, QT prolongation was observed in 17/143 participants (11.9%), only 2 of them reporting QTcF > 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%).

Conclusions

APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries.

Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942
The effect of different methods to identify, and scenarios used to address energy intake misestimation on dietary patterns derived by cluster analysis
Authors: Lo Siou Geraldine , Akawung Alianu K. , Solbak Nathan M. , McDonald Kathryn L. , Al Rajabi Ala , Whelan Heather K. , Kirkpatrick Sharon I.
Published: May 2021

Background

All self-reported dietary intake data are characterized by measurement error, and validation studies indicate that the estimation of energy intake (EI) is particularly affected.

Methods

Using self-reported food frequency and physical activity data from Alberta’s Tomorrow Project participants (n = 9847 men 16,241 women), we compared the revised-Goldberg and the predicted total energy expenditure methods in their ability to identify misreporters of EI. We also compared dietary patterns derived by k-means clustering under different scenarios where misreporters are included in the cluster analysis (Inclusion); excluded prior to completing the cluster analysis (ExBefore); excluded after completing the cluster analysis (ExAfter); and finally, excluded before the cluster analysis but added to the ExBefore cluster solution using the nearest neighbor method (InclusionNN).

Results

The predicted total energy expenditure method identified a significantly higher proportion of participants as EI misreporters compared to the revised-Goldberg method (50% vs. 47%, p < 0.0001). k-means cluster analysis identified 3 dietary patterns: Healthy, Meats/Pizza and Sweets/Dairy. Among both men and women, participants assigned to dietary patterns changed substantially between ExBefore and ExAfter and also between the Inclusion and InclusionNN scenarios (Hubert and Arabie’s adjusted Rand Index, Kappa and Cramer’s V statistics < 0.8).

Conclusions

Different scenarios used to account for EI misreporters influenced cluster analysis and hence the composition of the dietary patterns. Continued efforts are needed to explore and validate methods and their ability to identify and mitigate the impact of EI misestimation in nutritional epidemiology.
Critical evaluation of stents in coronary angioplasty: a systematic review
Authors: Stevens Joseph Robert , Zamani Ava , Osborne James Ian Atkins , Zamani Reza , Akrami Mohammad
Published: May 2021

Background

Coronary stents are routinely placed in the treatment and prophylaxis of coronary artery disease (CAD). Current coronary stent designs are prone to developing blockages: in-stent thrombosis (IST) and in-stent re-stenosis (ISR). This is a systematic review of the design of current coronary stent models, their structural properties and their modes of application, with a focus on their associated risks of IST and ISR. The primary aim of this review is to identify the best stent design features for reducing the risk of IST and ISR. To review the three major types of stents used in clinical settings today, determining best and relevant clinical practice by exploring which types and features of offer improved patient outcomes regarding coronary angioplasty. This information can potentially be used to increase the success rate of coronary angioplasty and stent technology in the future taking into account costs and benefits.

Methods

Scientific databases were searched to find studies concerning stents. After the exclusion criteria were applied, 19 of the 3192 searched literature were included in this review. Studies investigating three major types of stent design were found: bare-metal stents (BMS), drug-eluting stents (DES) and bioresorbable stents (BRS). The number of participants varied between 14 and 1264. On average 77.4% were male, with a mean age of 64 years.

Results

From the findings of these studies, it is clear that DES are superior in reducing the risk of ISR when compared to BMS. Conflicting results do not clarify whether BRS are superior to DES at reducing IST occurrence, although studies into newer BRS technologies show reducing events of IST to 0, creating a promising future for BRS showing them to be non-inferior. Thinner stents were shown to reduce IST rates, due to better re-endothelialisation. Scaffold material has also been shown to play a role with cobalt alloy stents reducing the risk of IST. This study found that thinner stents that release drugs were better at preventing re-blockages. Some dissolvable stents might be better at stopping blood clots blocking the arteries when compared to metal stents. The method and procedure of implanting the stent during coronary angioplasty influences success rate of these stents, meaning stent design is not the only significant factor to consider.

Conclusions

Positive developments in coronary angioplasty could be made by designing new stents that encompass all the most desirable properties of existing stent technology. Further work is needed to investigate the benefits of BRS in reducing the risk of IST compared to DES, as well as to investigate the effects of different scaffold materials on IST and ISR outcomes.
Psychometric properties of the Persian translation of maternal postpartum quality of life questionnaire (MAPP-QOL)
Authors: Mokhtaryan-Gilani Tahereh , Ozgoli Giti , Kariman Nourossadat , Sharif Nia Hamid , Ahmadi Doulabi Mahbobeh , Nasiri Malihe
Published: May 2021

Background and objective

Many studies have been conducted in Iran on the postpartum quality of life, and the majority have used the general quality of life questionnaire. With a specific tool in this context, the dimensions of maternal postpartum quality of life can be more accurately determined. The present study was conducted to determine psychometric properties and validate the Persian version of the Maternal Postpartum Quality of Life Questionnaire (MAPP-QOL).

Materials and methods

The present methodological study was conducted in 2018. The original version of MAPP-QOL was translated into Persian by both forward and backward translation. In a cross-sectional study, the Persian version was completed by 407 eligible postpartum women aged 18 to 47 and living in Tehran. Reliability of the questionnaire was assessed using Cronbach's alpha coefficient and test–retest. For construct validity, exploratory and confirmatory factor analyses were used.

Results

The MAPP-QOL showed good content validity; content validity ratio (CVR) ranged from 0.6 to 1.00, and content validity index (CVI) ranged from 0.7 to 1.00. Using exploratory factor analysis, five factors, including Socioeconomic; Relational/Family-Friends; Psychological/Baby; Health & functioning; and Relational/Spouse-Partner, were extracted, which together explained 78.84% of the total variance. After modifications of CFA, the confirmatory factor analysis showed an acceptable goodness-of-fit. AVE value Above 0.5 exhibited appropriate convergent validity, and AVE greater than MSV confirmed divergent validity. The Cronbach's alpha, McDonald's Omega, Composite reliability and maximum reliability H of the five extracted factors were excellent (> 0.9). Also, the AIC values of the factors were good (between 0.721 to 0.859).

Conclusion

The 38-item Persian version of the postpartum quality of life questionnaire is adequately reliable for postpartum women in Iran. Given its appropriate psychometric properties, this scale is fit to be used in future studies on postpartum women.
Predictive value of pretreatment PD-L1 expression in EGFR-mutant non-small cell lung cancer: a meta-analysis
Authors: Peng Zhiyu , Lin Huahang , Zhou Ke , Deng Senyi , Mei Jiandong
Published: May 2021

Objective

To investigate the predictive value of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).

Methods

We conducted a systemic search of PubMed, EMBASE, and the Cochrane Library from 1 January 2000 to 30 August 2020, to identify related studies. We combined the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of PD-L1 expression with progression-free survival (PFS) and overall survival (OS). We assessed the quality of the included studies by the Newcastle–Ottawa Scale (NOS). We performed subgroup analyses based on immunohistochemistry (IHC) scoring system, IHC antibodies, sample size, countries, and survival analysis mode. Sensitivity analysis and evaluation of publication bias were also performed.

Results

Twelve studies including 991 patients met the criteria. The mean NOS score was 7.42 ± 1.19. Patients with high PD-L1 expression was associated with poorer PFS (HR = 1.90; 95% CI = 1.16–3.10; P = 0.011), while there was no association between PD-L1 expression and OS (HR = 1.19; 95% CI = 0.99–1.43; P = 0.070). Subgroup analysis prompted IHC scoring systems, IHC antibodies, and sample size have important effects on heterogeneity. The pooled results were robust according to the sensitivity analysis.

Conclusions

The result of this meta-analysis suggested that PD-L1 expression might be a predictive biomarker for EGFR-mutant non-small cell lung cancer treated with EGFR-TKIs.
Application of stem cell-derived exosomes in ischemic diseases: opportunity and limitations
Authors: Babaei Majid , Rezaie Jafar
Published: May 2021

Ischemic diseases characterized by an insufficient blood flow that leads to a decrease in oxygen and nutrient uptake by cells have emerged as an important contributor to both disability and death worldwide. Up-regulation of angiogenesis may be a key factor for the improvement of ischemic diseases. This article searched articles in PubMed with the following keywords: stem cells, exosomes, angiogenesis, ischemic diseases either alone or in grouping form. The most relevant selected items were stem cell-derived exosomes and ischemic diseases. A growing body of evidence indicates that stem cells produce exosomes, which is the novel emerging approach to cell-to-cell communication and offers a new standpoint on known therapeutic strategies of ischemic diseases. Exosomes transport biological molecules such as many types of proteins, RNAs, DNA fragments, signaling molecules, and lipids between cells. Different stem cells release exosomes representing beneficial effects on ischemic diseases as they promote angiogenesis both in vitro and in vivo experiments. Application of exosomes for therapeutic angiogenesis opened new opportunities in the regenerative medicine, however, some limitations regarding exosomes isolation and application remain concerned. In addition, most of the experiments were conducted in preclinical and therefore translation of these results from bench to bed requires more effort in this field. Exosomes from stem cells are a promising tool for the treatment of ischemic diseases. In addition, translation of pre-clinic results into clinic needs further studies in this field.
Cost-effectiveness analysis of a quality improvement program to reduce caesarean sections in Brazilian private hospitals: a case study
Authors: Domingues Rosa Maria Soares Madeira , Luz Paula Mendes , da Silva Ayres Barbara Vasques , Torres Jacqueline Alves , do Carmo Leal Maria
Published: May 2021

Background

In 2015, a quality improvement project of childbirth care called Adequate Childbirth Project (“Projeto Parto Adequado”- PPA) was implemented in Brazilian public and private hospitals, aiming to improve the quality of childbirth care and to reduce caesarean sections without clinical indications. The objective of this study is to conduct an economic analysis of two models of care existing in a private Brazilian hospital—the model following the recommendations of the PPA and the standard of care model—in reducing the proportion of caesarean sections.

Methods

We conducted a cost-effectiveness analysis using data from one of the private hospitals included in the PPA project. The main outcome was the proportion of caesarean section. We used total cost of hospitalization for women and newborns, from the health care sector perspective, during the length of the observed hospital stay. We did not apply discount rates and inflation rate adjustments due to the short time horizon. We conducted univariate sensitivity analysis using the minimum and maximum costs observed in hospitalizations and variation in the probabilities of caesarean section and of maternal and neonatal complications.

Results

238 puerperal women were included in this analysis. The PPA model of care resulted in a 56.9 percentage point reduction in the caesarean section probability (88.6% vs 31.7%, p < 0.001) with an incremental cost-effectiveness ratio of US$1,237.40 per avoided caesarean section. Women in the PPA model of care also had a higher proportion of spontaneous and induced labor and a lower proportion of early term births. There were no maternal, fetal or neonatal deaths and no significant differences in cases of maternal and neonatal near miss. The cost of uncomplicated vaginal births and caesarean sections was the parameter with the greatest impact on the cost-effectiveness ratio of the PPA model of care.

Conclusion

The PPA model of care was cost-effective in reducing caesarean sections in women assisted in a Brazilian private hospital. Moreover, it reduced the frequency of early term births and did not increase the occurrence of severe negative maternal and neonatal outcomes.
CircASH2L facilitates tumor-like biologic behaviours and inflammation of fibroblast-like synoviocytes via miR-129-5p/HIPK2 axis in rheumatoid arthritis
Authors: Li Xia , Qu Meiting , Zhang Jie , Chen Kuanyin , Ma Xianghui
Published: May 2021

Background

Previous study showed that circular RNA Absent-Small-Homeotic-2--Like protein (circASH2L) was higher in rheumatoid arthritis (RA) patients. However, the roles and mechanisms of circASH2L in RA progression remain unclear.

Methods

Levels analysis was conducted using western blot and qRT-PCR. The proliferation, apoptosis, cell cycle progression, migration, invasiveness, and inflammation of RA fibroblast-like synoviocytes (RA-FLSs) were determined via MTT, flow cytometry, western blot, transwell, and ELISA assays.

Results

CircASH2L knockdown in RA-FLSs suppressed cell proliferative, migratory, and invasive capacities, triggered cell cycle arrest, promoted apoptosis, and inhibited inflammation. Mechanistically, circASH2L targeted miR-129-5p, and repression of miR-129-5p abolished the functions of circASH2L silencing on the growth, motility, and inflammation of RA-FLSs. Besides, miR-129-5p was found to directly target HIPK2, and suppressed the tumor-like biologic behaviors and inflammation of RA-FLSs via regulating HIPK2. Importantly, we proved that circASH2L could modulate HIPK2 expression via miR-129-5p.

Conclusion

CircASH2L promoted RA-FLS growth, motility, and inflammation through miR-129-5p/HIPK2 axis.
Comparison of two methods in the treatment of congenital pseudarthrosis of clavicle: multicenter experience
Authors:   Chinese Multi-center Pediatric Orthopedic Study Group (CMPOS), Li Jin , Tang Sheng Ping , Mei Hai Bo , Shao Jing Fan , Shi Bao Jie , Wang Hai Qiang , Tang Xin
Published: May 2021

Background

Congenital pseudoarthrosis of the clavicle (CPC) is an uncommon entity. Owing to its scarce presentation, treatment of this disorder has not been well established. This study aimed (1) to compare surgical treatment methods that included excision of pseudoarthrosis and iliac crest bone graft and fixate with either the elastic stable intramedullary nail (ESIN) or K-wires or plate and screws, and (2) to assess the clinical outcomes of two different surgical methods.

Methods

A multi-central retrospective study was performed between 2013 and 2017 in four tertiary teaching hospitals. Fifteen clavicles of 11 children were identified as CPC. All patients underwent pseudarthrosis resection and iliac crest bone autograft. They were divided into two groups as per the surgical treatment they underwent—plate stabilization as group A and elastic stable intramedullary nailing (ESIN) or K-wires as group B. Nine clavicles in 6 patients in group A and 6 clavicles in 5 patients in group B, were included. The Quick Disabilities of the Arm and Shoulder (QuickDASH) score was used to assess patients’ satisfaction and function following treatment at each follow-up.

Results

There were eight boys and three girls, with an average age of 4.7 years. All patients, except one with intellectual impairments, had radiological healing. Implant removal time was significantly shorter in group B compared to group A. No statistically significant differences existed in terms of age at surgery, time of radiological healing, complication, and clinical outcome between different groups.

Conclusion

Surgical resection of pseudoarthrosis with an iliac crest bone graft was an effective means of surgical treatment in CPC. However, ESIN or K-wires can achieve shorter union time compared to the plate. Hence, surgical treatment is recommended for congenital pseudarthrosis of clavicular in pediatric patients.

Level of evidence

Retrospective comparative study; Level III