bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-referral and associated factors among patients attending adult outpatient departments in Debre tabor general hospital, North West Ethiopia
Authors: Abere Tigist Misganaw , Atnafu Desta Debalkie , Mulu Yaread
Published: June 2021

Background

Self-referral leads to diminished quality of health care service; increase resource depletion and poorer patient outcomes. However, a significant number of patients referred themselves to the higher health care facilities without having referral sheets globally including Ethiopia. Even though the problem is much exacerbated in Ethiopia, there is limited evidence regarding self-referral patients in Ethiopia in particular in the study area.

Objective

To assess the magnitude and associated factors of self-referral among patients at the adult outpatient department in Debre Tabor general hospital, North West Ethiopia.

Method

Institution-based cross-sectional study was conducted from March 11–April 9, 2020 among 693 patients who attended adult outpatient departments. A systematic sampling technique was employed. Structured and pretested interviewer-administered questionnaire was used for data collection. Data were coded, cleaned and entered into Epi Info version 7.1 and exported to SPSS version 23 for further analysis. Binary logistic regression analysis was employed. In bivariable analysis p-value, less than 0.25 was used to select candidate variables for multivariable analysis. P-values less than 0.05 and 95% confidence intervals were used to select significant variables on the outcome of interest.

Result

The proportion of self-referral was 443(63.9%) with 95% CI (60.5; 67.5). Formally educated, (AOR = 1.83; (95% CI: 1.12, 3.01)), enrolled to Community Based Health Insurance (AOR = 1.57; (95% CI: 1.03, 2.39)), poor knowledge about referral system (AOR = 2.07; 95% CI: (1.28, 3.39)), not and partially available medication in the nearby Primary Health Care facilities (AOR = 2.12; (95% CI: 1.82, 6.15)) & (AOR = 3.24; (95% CI: 1.75, 5.97)) respectively and history of visiting general hospital (AOR = 1.52; (95%CI: 1.03, 2.25)) were factors statistically associated with self-referral.

Conclusion and recommendation

The proportion of self-referral was low compared to the Ethiopian health sector transformation plan 2015/16–20. Socio-demographic and institutional factors were associated with self-referral. Therefore, regional health bureau better to work to fulfill the availability of medications in the primary health care facilities. In addition, Community Based Health Insurance (CBHI) agency should work to implement the law of out-of-pocket expenditure which states to pay 50% for self-referred patients who claim utilization of healthcare.
CircRNA_100290 promotes GC cell proliferation and invasion via the miR-29b-3p/ITGA11 axis and is regulated by EIF4A3
Authors: Wang Gang , Sun Dan , Li Wenhui , Xin Yan
Published: June 2021

Background

Circular RNAs (circRNAs) have been reported to be important regulators of the development and progression of various carcinomas. However, the role of circRNA_100290 in gastric cancer (GC) is still unclear. This study aimed to investigate the role of circRNA_100290 in GC invasion and metastasis and the possible underlying mechanism.

Methods

The expression of circRNA_100290 in GC cells and tissues was examined using quantitative real-time polymerase chain reaction (qRT-PCR). The role of circRNA_100290 in cell proliferation, migration, and invasion was evaluated in the AGS and HGC-27 cell lines in vitro. Bioinformatics tools, dual-luciferase reporter assays, Western blot assays and qRT-PCR were used to explore the pathways downstream of circRNA_100290. The mechanism underlying the regulation of circRNA_100290 expression was explored using RNA immunoprecipitation, qRT-PCR, and Western blot assays.

Results

The expression of circRNA_100290 was significantly upregulated in GC cells and 102 GC tissues, and high circRNA_100290 expression in GC was closely related to Borrmann’s type, lymph node metastasis and tumour-node-metastasis stage. In vitro, knockdown of circRNA_100290 in AGS and HGC-27 cells significantly inhibited cell proliferation, migration, and invasion. Mechanistically, a dual-luciferase reporter assay confirmed the direct interaction between circRNA_100290 and miR-29b-3p, which targets ITGA11, an oncogene that is closely related to epithelial–mesenchymal transition (EMT). In addition, EIF4A3, an RNA-binding protein (RBP), could inhibit the formation of circRNA_100290 by binding to the flanking sites of circRNA_100290. Low EIF4A3 expression in GC was related to a poor prognosis.

Conclusions

Elevated circRNA_100290 expression in GC promotes cell proliferation, invasion and EMT via the miR-29b-3p/ITGA11 axis and might be regulated by EIF4A3. CircRNA_100290 might be a promising biomarker and target for GC therapy.

Graphical abstract
Machine learning classification of texture features of MRI breast tumor and peri-tumor of combined pre- and early treatment predicts pathologic complete response
Authors: Hussain Lal , Huang Pauline , Nguyen Tony , Lone Kashif J. , Ali Amjad , Khan Muhammad Salman , Li Haifang , Suh Doug Young , Duong Tim Q.
Published: June 2021

Purpose

This study used machine learning classification of texture features from MRI of breast tumor and peri-tumor at multiple treatment time points in conjunction with molecular subtypes to predict eventual pathological complete response (PCR) to neoadjuvant chemotherapy.

Materials and method

This study employed a subset of patients (N = 166) with PCR data from the I-SPY-1 TRIAL (2002–2006). This cohort consisted of patients with stage 2 or 3 breast cancer that underwent anthracycline–cyclophosphamide and taxane treatment. Magnetic resonance imaging (MRI) was acquired pre-neoadjuvant chemotherapy, early, and mid-treatment. Texture features were extracted from post-contrast-enhanced MRI, pre- and post-contrast subtraction images, and with morphological dilation to include peri-tumoral tissue. Molecular subtypes and Ki67 were also included in the prediction model. Performance of classification models used the receiver operating characteristics curve analysis including area under the curve (AUC). Statistical analysis was done using unpaired two-tailedt-tests.

Results

Molecular subtypes alone yielded moderate prediction performance of PCR (AUC = 0.82,p = 0.07). Pre-, early, and mid-treatment data alone yielded moderate performance (AUC = 0.88, 0.72, and 0.78,p = 0.03, 0.13, 0.44, respectively). The combined pre- and early treatment data markedly improved performance (AUC = 0.96,p = 0.0003). Addition of molecular subtypes improved performance slightly for individual time points but substantially for the combined pre- and early treatment (AUC = 0.98,p = 0.0003). The optimal morphological dilation was 3–5 pixels. Subtraction of post- and pre-contrast MRI further improved performance (AUC = 0.98,p = 0.00003). Finally, among the machine-learning algorithms evaluated, the RUSBoosted Tree machine-learning method yielded the highest performance.

Conclusion

AI-classification of texture features from MRI of breast tumor at multiple treatment time points accurately predicts eventual PCR. Longitudinal changes in texture features and peri-tumoral features further improve PCR prediction performance. Accurate assessment of treatment efficacy early on could minimize unnecessary toxic chemotherapy and enable mid-treatment modification for patients to achieve better clinical outcomes.
Understanding the impact of more realistic low-dose, prolonged engineered nanomaterial exposure on genotoxicity using 3D models of the human liver
Authors: Llewellyn Samantha V. , Conway Gillian E. , Zanoni Ilaria , Jørgensen Amalie Kofoed , Shah Ume-Kulsoom , Seleci Didem Ag , Keller Johannes G. , Kim Jeong Won , Wohlleben Wendel , Jensen Keld Alstrup , Costa Anna , Jenkins Gareth J. S. , Clift Martin J. D. , Doak Shareen H.
Published: June 2021

Background

With the continued integration of engineered nanomaterials (ENMs) into everyday applications, it is important to understand their potential for inducing adverse human health effects. However, standard in vitro hazard characterisation approaches suffer limitations for evaluating ENM and so it is imperative to determine these potential hazards under more physiologically relevant and realistic exposure scenarios in target organ systems, to minimise the necessity for in vivo testing. The aim of this study was to determine if acute (24 h) and prolonged (120 h) exposures to five ENMs (TiO2, ZnO, Ag, BaSO4 and CeO2) would have a significantly different toxicological outcome (cytotoxicity, (pro-)inflammatory and genotoxic response) upon 3D human HepG2 liver spheroids. In addition, this study evaluated whether a more realistic, prolonged fractionated and repeated ENM dosing regime induces a significantly different toxicity outcome in liver spheroids as compared to a single, bolus prolonged exposure.

Results

Whilst it was found that the five ENMs did not impede liver functionality (e.g. albumin and urea production), induce cytotoxicity or an IL-8 (pro-)inflammatory response, all were found to cause significant genotoxicity following acute exposure. Most statistically significant genotoxic responses were not dose-dependent, with the exception of TiO2. Interestingly, the DNA damage effects observed following acute exposures, were not mirrored in the prolonged exposures, where only 0.2–5.0 µg/mL of ZnO ENMs were found to elicit significant (p ≤ 0.05) genotoxicity. When fractionated, repeated exposure regimes were performed with the test ENMs, no significant (p ≥ 0.05) difference was observed when compared to the single, bolus exposure regime. There was < 5.0% cytotoxicity observed across all exposures, and the mean difference in IL-8 cytokine release and genotoxicity between exposure regimes was 3.425 pg/mL and 0.181%, respectively.

Conclusion

In conclusion, whilst there was no difference between a single, bolus or fractionated, repeated ENM prolonged exposure regimes upon the toxicological output of 3D HepG2 liver spheroids, there was a difference between acute and prolonged exposures. This study highlights the importance of evaluating more realistic ENM exposures, thereby providing a future in vitro approach to better support ENM hazard assessment in a routine and easily accessible manner.
Predictive value of computed tomography with coronal reconstruction in right hemicolectomy with complete mesocolic excision for right colon cancers: a retrospective study
Authors: Yu Hui , Zhuang Yong , Jian Jinliang , Yang Chunkang
Published: June 2021

Background

Understanding the vascular anatomy is critical for performing central vascular ligation (CVL) in right hemicolectomy with complete mesocolic excision (CME). This study aimed to investigate the predictive value of multi-slice spiral computed tomography (MSCT) with coronal reconstruction in right hemicolectomy with CME.

Methods

This is a retrospective descriptive study. Eighty patients with right colon cancer who underwent right hemicolectomy from December 2015 to January 2020 were included. The intraoperative reports (including imaging data) and MSCT images with coronal reconstruction were analysed and compared. The detection rates of the ileocolic vein (ICV) and ileocolic artery (ICA) roots and the accuracy in predicting their anatomical relationship were analysed. The detection rate and accuracy in predicting the location of the gastrocolic trunk of Henle (GTH), middle colic artery (MCA) and middle colic vein (MCV) were analysed. The distance from the ICV root to the GTH root (ICV-GTH distance) was measured and analysed. The maximum distance from the left side of the superior mesenteric artery (SMA) to the right side of the superior mesenteric vein (SMV), named the ‘lsSMA-rsSMV distance’, was also measured and analysed.

Results

In seventy-four (92.5%) patients, both the ICV and ICA roots were located; their anatomical relationship was determined by MSCT, and the accuracy of the prediction was 97.2% (72/74). The GTH was located by MSCT in 75 (93.7%) patients, and the accuracy of the prediction was 97.33% (73/75). The MCA was located by MSCT in 47 (58.75%) patients, and the accuracy was 78.72% (37/47). The MCV was located by MSCT in 51 (63.75%) patients, and the accuracy of the prediction was 84.31% (43/51). The ICV-GTH distance was measured in 73 (91.2%) patients, and the mean distance was 4.28 ± 2.5 cm. The lsSMA-rsSMV distance was measured in 76 (95%) patients, and the mean distance was 2.21 ± 0.6 cm.

Conclusions

With its satisfactory accuracy in predicting and visualising the information of key anatomical sites, MSCT with coronary reconstruction has some predictive value in CME with CVL in right hemicolectomy.
Thymosin β4 reverses phenotypic polarization of glial cells and cognitive impairment via negative regulation of NF-κB signaling axis in APP/PS1 mice
Authors: Wang Meng , Feng Li-Rong , Li Zi-Long , Ma Kai-Ge , Chang Ke-Wei , Chen Xin-Lin , Yang Peng-Bo , Ji Sheng-Feng , Ma Yan-Bing , Han Hua , Ruganzua John Bosco , Yang Wei-Na , Qian Yi-Hua
Published: June 2021

Background

Thymosin β4 (Tβ4) is the most abundant member of the β-thymosins and plays an important role in the control of actin polymerization in eukaryotic cells. While its effects in multiple organs and diseases are being widely investigated, the safety profile has been established in animals and humans, currently, little is known about its influence on Alzheimer’s disease (AD) and the possible mechanisms. Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice.

Methods

Behavior tests were conducted to assess the learning and memory, anxiety and depression in APP/PS1 mice. Thioflavin S staining, Nissl staining, immunohistochemistry/immunofluorescence, ELISA, qRT-PCR, and immunoblotting were performed to explore Aβ accumulation, phenotypic polarization of glial cells, neuronal loss and function, and TLR4/NF-κB axis in APP/PS1 mice.

Results

We demonstrated that Tβ4 protein level elevated in all APP/PS1 mice. Over-expression of Tβ4 alone alleviated AD-like phenotypes of APP/PS1 mice, showed less brain Aβ accumulation and more Insulin-degrading enzyme (IDE), reversed phenotypic polarization of microglia and astrocyte to a healthy state, improved neuronal function and cognitive behavior performance, and accidentally displayed antidepressant-like effect. Besides, Tβ4 could downregulate both TLR4/MyD88/NF-κB p65 and p52-dependent inflammatory pathways in the APP/PS1 mice. While combination drug of TLR4 antagonist TAK242 or NF-κB p65 inhibitor PDTC exerted no further effects.

Conclusions

These results suggest that Tβ4 may exert its function by regulating both classical and non-canonical NF-κB signaling and is restoring its function as a potential therapeutic target against AD.
Vitamin D inhibits TNF-α induced apoptosis of human nucleus pulposus cells through regulation of NF-kB signaling pathway
Authors: Zhang Cun , Tong Tong , Miao De-chao , Wang Lin-feng
Published: June 2021

Background

To observe the effects of vitamin D on the apoptotic human nucleus pulposus cells under tumor necrosis factor-α (TNF-α) treatment.

Methods

The gene expression data was downloaded from the NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE34095). Differentially expressed genes between degenerative disc and non-degenerative disc were performed by R software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses were performed using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Then, the human nucleus pulposus tissue was harvested from 12 patients according to the modified Pfirrmann classification and human nucleus pulposus cells were obtained from digestion of herniated nucleus pulposus tissue. The collected nucleus pulposus cells were treated with different concentration of TNF-α, and cellular apoptosis was measured by flow cytometry. Then, human nucleus pulposus cells were divided into following groups: normal culture medium, TNF-α treated, TNF-α, and vitamin D-treated groups. Cellular apoptosis rate was quantified by flow cytometry. Protein expression of p-p65, p65, and IkBa was detected with western blot analysis.

Results

A total of 536 differentially expressed genes were identified through bioinformatic analysis. KEGG pathway revealed that NF-kB signaling pathway was involved in the process of disc degeneration. In the NP cell cultures, vitamin D significantly increased cell proliferation potency. Furthermore, vitamin D inhibited TNF-α induced apoptosis of human nucleus pulposus cells. Vitamin D reduced the phospho-NF-κB/p65 expression in the TNF-α-treated NP cells.

Conclusion

Vitamin D can attenuate TNF-α-induced NP cells apoptosis through interfering with the NF-κB pathway.
The voltage-gated proton channel Hv1 promotes microglia-astrocyte communication and neuropathic pain after peripheral nerve injury
Authors: Peng Jiyun , Yi Min-Hee , Jeong Heejin , McEwan Przemyslaw Peter , Zheng Jiaying , Wu Gongxiong , Ganatra Shashank , Ren Yi , Richardson Jason R. , Oh Seog Bae , Wu Long-Jun
Published: June 2021

Activation of spinal cord microglia contributes to the development of peripheral nerve injury-induced neuropathic pain. However, the molecular mechanisms underlying microglial function in neuropathic pain are not fully understood. We identified that the voltage-gated proton channel Hv1, which is functionally expressed in spinal microglia, was significantly increased after spinal nerve transection (SNT). Hv1 mediated voltage-gated proton currents in spinal microglia and mice lacking Hv1 (Hv1 KO) display attenuated pain hypersensitivities after SNT compared with wildtype (WT) mice. In addition, microglial production of reactive oxygen species (ROS) and subsequent astrocyte activation in the spinal cord was reduced in Hv1 KO mice after SNT. Cytokine screening and immunostaining further revealed that IFN-γ expression was compromised in spinal astrocytes in Hv1 KO mice. These results demonstrate that Hv1 proton channel contributes to microglial ROS production, astrocyte activation, IFN-γ upregulation, and subsequent pain hypersensitivities after SNT. This study suggests Hv1-dependent microglia-astrocyte communication in pain hypersensitivities and identifies Hv1 as a novel therapeutic target for alleviating neuropathic pain.
Role of bulk nanobubbles in removing organic pollutants in wastewater treatment
Authors: Wu Jiajia , Zhang Kejia , Cen Cheng , Wu Xiaogang , Mao Ruyin , Zheng Yingying
Published: June 2021

The occurrence of a variety of organic pollutants has complicated wastewater treatment; thus, the search for sustainable and effective treatment technology has drawn significant attention. In recent years, bulk nanobubbles, which have extraordinary properties differing from those of microbubbles, including high stability and long residence times in water, large specific surface areas, high gas transfer efficiency and interface potential, and the capability to generate free radicals, have shown attractive technological advantages and promising application prospects for wastewater treatment. In this review, the basic characteristics of bulk nanobubbles are summarized in detail, and recent findings related to their implementation pathways and mechanisms in organic wastewater treatment are systematically discussed, which includes improving the air flotation process, increasing water aeration to promote aerobic biological technologies including biological activated carbon, activated sludge, and membrane bioreactors, and generating active free radicals that oxidise organic compounds. Finally, the current technological difficulties of bulk nanobubbles are analysed, and future focus areas for research on bulk nanobubble technology are also proposed.
Cardiac effects and clinical applications of MG53
Authors: Zhong Weina , Benissan-Messan Dathe Z. , Ma Jianjie , Cai Chuanxi , Lee Peter H. U.
Published: June 2021

Heart disease remains the leading cause of mortality globally, so further investigation is required to identify its underlying mechanisms and potential targets for treatment and prevention. Mitsugumin 53 (MG53), also known as TRIM72, is a TRIM family protein that was found to be involved in cell membrane repair and primarily found in striated muscle. Its role in skeletal muscle regeneration and myogenesis has been well documented. However, accumulating evidence suggests that MG53 has a potentially protective role in heart tissue, including in ischemia/reperfusion injury of the heart, cardiomyocyte membrane injury repair, and atrial fibrosis. This review summarizes the regulatory role of MG53 in cardiac tissues, current debates regarding MG53 in diabetes and diabetic cardiomyopathy, as well as highlights potential clinical applications of MG53 in treating cardiac pathologies.
Reconstruction of ocean environment time series since the late nineteenth century using sclerosponge geochemistry in the northwestern subtropical Pacific
Authors: Asami Ryuji , Matsumori Taketo , Shinjo Ryuichi , Uemura Ryu , Miyaoka Yuki , Mizuyama Masaru , Ise Yuji , Sakamaki Takashi
Published: June 2021

The geochemistry of calcifying marine organisms is an excellent proxy for reconstructing paleoceanographic history, but studies of hypercalcified demosponges (sclerosponges) are considerably fewer than those of corals, foraminifers, and bivalves. For this study, we first generated near-annual resolved stable carbon and oxygen isotope (δ13C and δ18O) and element/Ca ratios (Sr/Ca, Ba/Ca, Pb/Ca, U/Ca) time series for 1880–2015 from sclerosponge samples (Acanthochaetetes wellsi) collected at Miyako Island and Okinawa Island in the Ryukyu Islands of southwestern Japan. The δ13C records exhibited a typical variation of anthropogenically derived Suess effects, demonstrating that the rates of decrease of –0.0043‰/year before 1960 and – 0.024‰/year after 1960 in the northwestern subtropical Pacific were respectively similar to and about 1.4 times higher than those of the Caribbean Sea in the tropical Atlantic. Spectral analysis of the δ18O time series revealed significant periodicity of approximately 2, 3, 6.5, 7–10, and 20–30 year/cycle, indicating that sea surface conditions in the southern Ryukyu Islands had been dominated by interannual and decadal variations in temperature and seawater δ18O since the late nineteenth century. The Sr/Ca and U/Ca ratios for the species A. wellsi (high-Mg calcite) might not be a robust proxy for seawater temperatures, unlike Astrosclera willeyana and Ceratoporella nicholsoni sclerosponges (aragonite). An evident increasing Pb/Ca trend after 1950 found in the samples is probably attributable to Pb emissions from industrial activities and atmospheric aerosols in eastern Asian countries. The Ba/Ca variations differ greatly among sampling sites, which might be attributable to the respective local environments. This evidence demonstrates that more high-resolution age determinations and geochemical profilings enable delineation of secular variations in ocean environments on annual and interannual timescales. Results of our study suggest that if sclerosponges living in deeper ocean environments are collected, spatial and vertical oceanographic variations for the last several centuries will be reconstructed along with coral proxy records.
Colorectal cancer in Crohn’s disease: a series of 6 cases
Authors: Ishimaru Kazuhide , Tominaga Tetsuro , Nonaka Takashi , Fukuda Akiko , Moriyama Masaaki , Oyama Shosaburo , Ishii Mitsutoshi , Sawai Terumitu , Nagayasu Takeshi
Published: June 2021

Background

Colorectal cancer (CRC) is the most malignant complication in patients with Crohn’s disease (CD). We report 6 cases of CD-related CRC treated surgically at our hospital.

Case presentation

From 2010 to 2016, six CD patients were diagnosed with CRC. All patients were diagnosed with CD at < 25 years old, and the interval from onset of CD to diagnosis of CRC was > 10 years (range, 15–42 years) in all patients. The histological type of cancer was mucinous carcinoma in two cases, well-differentiated tubular adenocarcinoma in two cases, and moderately differentiated tubular adenocarcinoma in two cases. CRC was detected by screening colonoscopy in three cases (50%), and from clinical symptoms in the remaining three cases (50%). Two cases underwent colonoscopy within 2 months after symptom onset, detecting CRC in the relatively early stage. However, one case was diagnosed with advanced-stage CRC by endoscopy 1 year after symptom onset, and experienced poor prognosis.

Conclusions

Regular surveillance colonoscopy is needed to detect early-stage CRC in CD patients. Clear surveillance methods need to be established based on evidence.
Disparate access to nutritional food; place, race and equity in the United States
Authors: Sansom Garett , Hannibal Bryce
Published: June 2021

Background

Prior research has demonstrated minority communities have fewer options to access healthy foods when compared to their majority counterparts. While much focus has been placed upon community-level resources, little research has been placed on the efforts that minority groups need to undergo to reach well-stocked stores to purchase healthy food options.

Methods

As part of the Water, Energy, Food Nexus Research Group at Texas A&M University, a nationally representative survey (n = 1612) was conducted to acquire self-reported distance, time, and motives that certain populations must travel to purchase food for themselves and their families.

Results

Findings suggest that minority populations consider saving money, driving less, having a better selection of foods, and have the ability to buy organic foods as an important factor when choosing where to buy foods. Further, minority populations across the nation need to drive a significantly greater (p < 0.05) amount of time to reach their destinations than white populations.

Conclusion

This underscores the importance, and scope of the issues, of promoting and implementing more equitably distributed opportunities to purchase healthy food options throughout the United States.
Combined soft measurement on key indicator parameters of new competitive advantages for China's export
Authors: Wang Taosheng , Zuo Hongyan , Wu C. H. , Hu B.
Published: June 2021

The estimation of the difference between the new competitive advantages of China's export and the world’s trading powers have been the key measurement problems in China-related studies. In this work, a comprehensive evaluation index system for new export competitive advantages is developed, a soft-sensing model for China’s new export competitive advantages based on the fuzzy entropy weight analytic hierarchy process is established, and the soft-sensing values of key indexes are derived. The obtained evaluation values of the main measurement index are used as the input variable of the fuzzy least squares support vector machine, and a soft-sensing model of the key index parameters of the new export competitive advantages of China based on the combined soft-sensing model of the fuzzy least squares support vector machine is established. The soft-sensing results of the new export competitive advantage index of China show that the soft measurement model developed herein is of high precision compared with other models, and the technical and brand competitiveness indicators of export products have more significant contributions to the new competitive advantages of China's export, while the service competitiveness indicator of export products has the least contribution to new competitive advantages of China's export.
TAVR and cancer: machine learning-augmented propensity score mortality and cost analysis in over 30 million patients
Authors: Monlezun Dominique J. , Hostetter Logan , Balan Prakash , Palaskas Nicolas , Lopez-Mattei Juan , Cilingiroglu Mehmet , Iakobishvili Zaza , Ewer Michael , Marmagkiolis Konstantinos , Iliescu Cezar
Published: June 2021

Introduction

Cardiovascular disease (CVD) and cancer are the top mortality causes globally, yet little is known about how the diagnosis of cancer affects treatment options in patients with hemodynamically compromising aortic stenosis (AS). Patients with cancer often are excluded from aortic valve replacement (AVR) trials including trials with transcatheter AVR (TAVR) and surgical AVR (SAVR). This study looks at how cancer may influence treatment options and assesses the outcome of patients with cancer who undergo SAVR or TAVR intervention. Additionally, we sought to quantitate and compare both clinical and cost outcomes for patients with and without cancer.

Methods

This population-based case-control study uses the most recent year available National Inpatient Sample (NIS (2016) from the United States Department of Health and Human Services’ Agency for Healthcare Research and Quality (AHRQ). Machine learning augmented propensity score adjusted multivariable regression was conducted based on the likelihood of undergoing TAVR versus medical management (MM) and TAVR versus SAVR with model optimization supported by backward propagation neural network machine learning.

Results

Of the 30,195,722 total hospital admissions, 39,254 (0.13%) TAVRs were performed, with significantly fewer performed in patients with versus without cancer even in those of comparable age and mortality risk (23.82% versus 76.18%, p < 0.001) despite having similar hospital and procedural mortality. Multivariable regression in patients with cancer demonstrated that mortality was similar for TAVR, MM, and SAVR, though LOS and cost was significantly lower for TAVR versus MM and comparable for TAVR versus SAVR. Patients with prostate cancer constituted the largest primary cancer among TAVR patients including those with metastatic disease. There were no significant race or geographic disparities for TAVR mortality.

Discussion

Comparison of aortic valve intervention in patients with and without cancer suggests that interventions are underutilized in the cancer population. This study suggests that patients with cancer including those with metastasis have similar inpatient outcomes to patients without cancer. Further, patients who have symptomatic AS and those with higher risk aortic valve disease should be offered the benefit of intervention. Modern techniques have reduced intervention-related adverse events, provided improved quality of life, and appear to be cost effective; these advantages should not necessarily be denied to patients with co-existing cancer.
Development and implementation of an ultralow-dose CT protocol for the assessment of cerebrospinal shunts in adult hydrocephalus
Authors: Ryan David J. , Kavanagh Richard G. , Joyce Stella , O’Callaghan Maher Mika , Moore Niamh , McMahon Aisling , Hussey Deirdre , O’Sullivan Michael G. J. , Wyse Gerald , Fanning Noel , O’Connor Owen J. , Maher Michael M.
Published: June 2021

Background

Cerebrospinal fluid shunts in the treatment of hydrocephalus, although associated with clinical benefit, have a high failure rate with repeat computed tomography (CT) imaging resulting in a substantial cumulative radiation dose. Therefore, we sought to develop a whole-body ultralow-dose (ULD) CT protocol for the investigation of shunt malfunction and compare it with the reference standard, plain radiographic shunt series (PRSS).

Methods

Following ethical approval, using an anthropomorphic phantom and a human cadaveric ventriculoperitoneal shunt model, a whole-body ULD-CT protocol incorporating two iterative reconstruction (IR) algorithms, pure IR and hybrid IR, including 60% filtered back projection and 40% IR was evaluated in 18 adult patients post new shunt implantation or where shunt malfunction was suspected. Effective dose (ED) and image quality were analysed.

Results

ULD-CT permitted a 36% radiation dose reduction (median ED 0.16 mSv, range 0.07–0.17, versus 0.25 mSv (0.06–1.69 mSv) for PRSS (p = 0.002). Shunt visualisation in the thoracoabdominal cavities was improved with ULD-CT with pure IR (p = 0.004 and p = 0.031, respectively) and, in contrast to PRSS, permitted visualisation of the entire shunt course (p < 0.001), the distal shunt entry point and location of the shunt tip in all cases. For shunt complications, ULD-CT had a perfect specificity. False positives (3/22, 13.6%) were observed with PRSS.

Conclusions

At a significantly reduced radiation dose, whole body ULD-CT with pure IR demonstrated diagnostic superiority over PRSS in the evaluation of cerebrospinal fluid shunt malfunction.
Role of preoperative ultrasound mapping in the surgical management of deep infiltrating endometriosis: a prospective observational study
Authors: El-Maadawy Samar M. , Alaaeldin Nesreen , Nagy Charles B.
Published: June 2021

Background

Endometriosis is a challenging gynecological condition that has a profound influence on the quality of life of affected women. Transvaginal ultrasound is considered the first-line imaging method in preoperative assessment of the extent and severity of endometriosis. Accurate preoperative mapping can aid the surgeon in patient counselling, selection of the most appropriate surgical method that minimizes the operative and post-operative complications. The aim of our study is to evaluate the accuracy of transvaginal sonography (TVS) in precisely assessing the size, location and extent of deep infiltrating endometriosis (DIE) using a new modified endometriosis mapping proforma with histopathological confirmation. Our prospective observational study included 101 women with clinically suspected DIE who underwent TVS followed by laparoscopy from October 2018 to December 2020 with a maximum of 4 weeks interval. Precise mapping of DIE was done during TVS and laparoscopy. Results were correlated with histopathology findings.

Results

DIE was confirmed by histopathology in 88 patients. Sensitivity and specificity for individual DIE locations were rectovaginal septum 67.9% and 98.6%; vagina 52.2% and 98.7%; uterosacral ligaments 82.5% and 96.2%; torus 96.4% and 97.3%; parametrium 68.8% and 96.9%; rectum 100% and 98.8%; bladder 100% and 100%, ureters 63.4% and 99.0%; scar endometriosis 100% and 100%; pouch of Douglas obliteration 97.7% and 100%. No statistically significant difference was detected between ultrasound and histopathology size. Ultrasound tended to underestimate the lesion size; the underestimation was more pronounced for lesions > 3 cm. “Butterfly” and “tram-track” signs are two new sonographic signs related to posterior compartment DIE. No post-operative complications were recorded. There were no cases of DIE recurrence. Eleven out of 22 cases of infertility achieved pregnancy during 18 months follow-up.

Conclusion

TVS provides a thorough and accurate evaluation of the extent of endometriosis. An experienced radiologist can use E-PEP to provide an accurate demonstration of the location and extent of DIE which helps the surgeon select the most appropriate surgical approach ensuring radical treatment of the disease and minimizing short- and long-term complications.
Evaluation of HCV-related liver fibrosis post-successful DAA therapy
Authors: Ehsan Nermine , Sweed Dina , Elsabaawy Maha
Published: June 2021

Background

The rapidly developing era of direct-acting antiviral regimens (DAAs) for more than one hepatitis C virus (HCV) genotype had certainly alleviated HCV burden all over the world. Liver fibrosis is the major dramatic complication of HCV infection, and its progression leads to cirrhosis, liver failure, and hepatocellular carcinoma. The impact of DAAs on liver fibrosis had been debatably evaluated with undetermined resolution.

Main body

The aim of this review is to accurately revise the effects of DAA regimens on liver fibrosis which can either be regression, progression, or non-significant association. Liver fibrosis regression is a genuine fact assured by many retrospective and prospective clinical studies. Evaluation could be concluded early post-therapy reflecting the dynamic nature of the process.

Conclusions

The ideal application of DAA regimens in treating HCV has to be accomplished with efficient non-invasive markers in differentiating proper fibrosis evaluation from necroinflammation consequences. Liver biopsy is the gold standard that visualizes the dynamic of fibrosis regression.
In search of America’s old covered bridges
Authors: Knapp Ronald G.
Published: June 2021

America’s first documented wooden covered bridge was erected at Philadelphia, Pennsylvania in 1805. Hundreds were constructed within two decades and at least 10,000 by the later 1800s. As settlers moved West, broad rivers were crossed with inventive structures incorporating timber trusses ingeniously developed by carpenters. Called covered bridges because of the roof and siding needed to protect the timber trusses, they became ubiquitous features on the American landscape. Over the past two centuries, most covered bridges were lost to flood, ice, arson, lightening, decay, as well as “progress,” replaced by “modern” iron, concrete, and steel spans. Of some 700 covered bridges remaining, many are mere replicas of their original forms no longer supported by timber trusses. Genuine historic bridges remain largely from the last half of the 1800s while civic boosterism has led to claims of earlier dates with often questionable authenticity. This essay presents three wooden covered bridges constructed in the 1820s along a 10-mile stretch of the Wallkill River in New Paltz, New York. Of the three, only Perrine’s Bridge, constructed first in 1821 and covered in 1822, is still standing with intact Burr timber trusses. Perrine’s is an iconic structure with exceptional heritage value because of authentic re-building and restoration in 1834, 1846, 1917, and 1968. Using documentary records, this essay establishes an accurate intertwined chronology for the three bridges, detailing nineteenth century building practices and contentious mid-twentieth century struggles pitting preservationists wanting authentic restoration against those wanting removal.
Fostering Students’ Understanding of Complex Biological Systems
Authors: Gilissen Melde G. R. , Knippels Marie-Christine P. J. , van Joolingen Wouter R.
Published: June 2021

The aim of this study was to investigate how students can be supported to visualize and reason about complex biological problems from a systems thinking perspective. Four design guidelines are presented to foster students’ systems thinking in biology education.
Per- and Polyfluoroalkyl Substances and Hormone Levels During the Menopausal Transition
Authors: Harlow Siobán D , Hood Michelle M , Ding Ning , Mukherjee Bhramar , Calafat Antonia M , Randolph John F , Gold Ellen B , Park Sung Kyun
Published: June 2021

Context

Per- and polyfluoroalkyl substances (PFAS) are widespread chemicals that may affect sex hormones and accelerate reproductive aging in midlife women.

Objective

To examine associations between serum PFAS concentrations at baseline (1999-2000) and longitudinal serum concentrations of follicle-stimulating hormone (FSH), estradiol, testosterone, and sex hormone-binding globulin (SHBG) at baseline and through 2015-2016.

Design

Prospective cohort.

Setting

General community.

Participants

1371 midlife women 45 to 56 years of age at baseline in the Study of Women’s Health Across the Nation (SWAN).

Main Outcome Measure(s)

FSH, estradiol, testosterone, SHBG.

Results

In linear mixed models fitted with log-transformed hormones and log-transformed PFAS adjusting for age, site, race/ethnicity, smoking status, menopausal status, parity, and body mass index, FSH was positively associated with linear perfluorooctanoate [n-PFOA; 3.12% (95% CI 0.37%, 5.95%) increase for a doubling in serum concentration), linear perfluorooctane sulfonate [PFOS; 2.88% (0.21%, 5.63%)], branched perfluorooctane sulfonate [2.25% (0.02%, 4.54%)], total PFOS (3.03% (0.37%, 5.76%)), and 2-(N-ethyl-perfluorooctane sulfonamido) acetate [EtFOSAA; 1.70% (0.01%, 3.42%)]. Estradiol was inversely associated with perfluorononanoate [PFNA; −2.47% (−4.82%, −0.05%)) and n-PFOA (−2.43% (−4.97%, 0.18%)]. Significant linear trends were observed in the associations between PFOS and EtFOSAA with SHBG across parity (Ps trend ≤ 0.01), with generally inverse associations among nulliparous women but positive associations among women with 3+ births. No significant associations were observed between PFAS and testosterone.

Conclusions

This study observed positive associations of PFOA and PFOS with FSH and inverse associations of PFNA and PFOA with estradiol in midlife women during the menopausal transition, consistent with findings that PFAS affect reproductive aging.
The Relation Between Adult Weight Gain, Adipocyte Volume, and the Metabolic Profile at Middle Age
Authors: Verkouter Inge , Noordam Raymond , Loh Nellie Y , van Dijk Ko Willems , Zock Peter L , Mook-Kanamori Dennis O , le Cessie Saskia , Rosendaal Frits R , Karpe Fredrik , Christodoulides Costantinos , de Mutsert Renée
Published: June 2021

Context

Weight gain during adulthood increases cardiometabolic disease risk, possibly through adipocyte hypertrophy.

Objective

We aimed to study the specific metabolomic profile of adult weight gain, and to examine its association with adipocyte volume.

Methods

Nuclear magnetic resonance–based metabolomics were measured in the Netherlands Epidemiology of Obesity (NEO) study (n = 6347, discovery) and Oxford Biobank (n = 6317, replication). Adult weight gain was calculated as the absolute difference between body mass index (BMI) at middle age and recalled BMI at age 20 years. We performed linear regression analyses with both exposures BMI at age 20 years and weight gain, and separately with BMI at middle age in relation to 149 serum metabolomic measures, adjusted for age, sex, and multiple testing. Additionally, subcutaneous abdominal adipocyte biopsies were collected in a subset of the Oxford Biobank (n = 114) to estimate adipocyte volume.

Results

Mean (SD) weight gain was 4.5 (3.7) kg/m2 in the NEO study and 3.6 (3.7) kg/m2 in the Oxford Biobank. Weight gain, and not BMI at age 20 nor middle age, was associated with concentrations of 7 metabolomic measures after successful replication, which included polyunsaturated fatty acids, small to medium low-density lipoproteins, and total intermediate-density lipoprotein. One SD weight gain was associated with 386 μm3 (95% CI, 143-629) higher median adipocyte volume. Adipocyte volume was associated with lipoprotein particles specific for adult weight gain.

Conclusion

Adult weight gain is associated with specific metabolomic alterations of which the higher lipoprotein concentrations were likely contributed by larger adipocyte volumes, presumably linking weight gain to cardiometabolic disease.
Extracellular Vesicles—The Next Frontier in Endocrinology
Authors: Das Gupta Anasuya , Krawczynska Natalia , Nelson Erik R
Published: June 2021

Extracellular vesicles (EVs), including exosomes, are emerging as important carriers of signals in normal and pathological physiology. As EVs are a long-range communication or signaling modality—just like hormones are—the field of endocrinology is uniquely poised to offer insight into their functional biology and regulation. EVs are membrane-bound particles secreted by many different cell types and can have local or systemic effects, being transported in body fluids. They express transmembrane proteins, some of which are shared between EVs and some being specific to the tissue of origin, that can interact with target cells directly (much like hormones can). They also contain cargo within them that includes DNA, RNA, miRNA, and various metabolites. They can fuse with target cells to empty their cargo and alter their target cell physiology in this way also. Similar to the endocrine system, the EV system is likely to be under homeostatic control, making the regulation of their biogenesis and secretion important aspects to study. In this review, we briefly highlight select examples of how EVs are implicated in normal physiology and disease states. We also discuss what is known about their biogenesis and regulation of secretion. We hope that this paper inspires the endocrinology field to use our collective expertise to explore these new multimodal “hormones.”
Hometown Ties and the Quality of Government Monitoring: Evidence from Rotation of Chinese Auditors
Authors: Chu Jian , Fisman Raymond , Tan Songtao , Wang Yongxiang
Published: June 2021

Audits are a standard mechanism for reducing corruption in government investments. The quality of audits themselves, however, may be affected by relationships between auditor and target. We study whether provincial chief auditors in China show greater leniency in evaluating prefecture governments in their hometowns. In city-fixed-effect specifications—in which the role of shared background is identified from auditor turnover—we show that hometown auditors find 38 percent less in questionable monies. This hometown effect is similar throughout the auditor’s tenure and is diminished for audits ordered by the provincial Organization Department as a result of the departure of top city officials. We argue that our findings are most readily explained by leniency toward local officials rather than an endogenous response to concerns of better enforcement by hometown auditors. We complement these city-level findings with firm-level analyses of earnings manipulation by state-owned enterprises (SOE) via real activity manipulation (a standard measure from the accounting literature), which we show is higher under hometown auditors. (JEL D73, H54, H83, L32, M42, O18, P25)
Minority Salience and Political Extremism
Authors: Colussi Tommaso , Isphording Ingo E. , Pestel Nico
Published: June 2021

We investigate how the salience of an ethnic minority affects the majority group’s voting behavior. We use the increased salience of Muslim communities during Ramadan as a natural experiment. Exploiting exogenous variation in the distance of election dates to Ramadan over the 1980–2013 period in Germany, our findings reveal an increased polarization. Vote shares for both right- and left-wing extremist parties increase in municipalities with mosques when an election takes place shortly after Ramadan. We use survey data to provide evidence on mechanisms: Ramadan increases respondents’ perceived share of the foreign-born population and emphasizes cultural dissimilarities, ultimately worsening attitudes toward Muslims. (JEL D72, D91, J15, Z12, Z13)
pyam: Analysis and visualisation of integrated assessment and macro-energy scenarios
Authors: Huppmann Daniel , Gidden Matthew J. , Nicholls Zebedee , Hörsch Jonas , Lamboll Robin , Kishimoto Paul N. , Burandt Thorsten , Fricko Oliver , Byers Edward , Kikstra Jarmo , Brinkerink Maarten , Budzinski Maik , Maczek Florian , Zwickl-Bernhard Sebastian , Welder Lara , Álvarez Quispe Erik Francisco , Smith Christopher J.
Published: June 2021

The open-source Python package pyam provides a suite of features and methods for the analysis, validation and visualization of reference data and scenario results generated by integrated assessment models, macro-energy tools and other frameworks in the domain of energy transition, climate change mitigation and sustainable development. It bridges the gap between scenario processing and visualisation solutions that are "hard-wired" to specific modelling frameworks and generic data analysis or plotting packages.

The package aims to facilitate reproducibility and reliability of scenario processing, validation and analysis by providing well-tested and documented methods for timeseries aggregation, downscaling and unit conversion. It supports various data formats, including sub-annual resolution using continuous time representation and "representative timeslices". The code base is implemented following best practices of collaborative scientific-software development. This manuscript describes the design principles of the package and the types of data which can be handled. The usefulness of pyam is illustrated by highlighting several recent applications.
Afterword
Authors: McGavin John J.
Published: June 2021

This essay reflects on the contents of the Issues in Review section ‘Rethinking Performance in Early Modern England: Sources, Contexts, and Forms’.
Editorial
Authors: Kelly Erin E. , Gough Melinda J.
Published: June 2021

This Editorial summarizes the contents of issue 23.2 while reflecting on the current state of theatre and performance.