bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the causal effects of blood lipid levels on gout with summary level GWAS data: two-sample Mendelian randomization and mediation analysis
Authors: Yu Xinghao , Wang Ting , Huang Shuiping , Zeng Ping
Published: March 2020

Background: Observational studies have identified gout patients are often comorbid with dyslipidemia, which is characterized by a decrease in high-density lipoprotein cholesterol (HDL) and an increase in triglycerides (TG). However, the relationship between dyslipidemia and gout is still unclear. Methods: We first performed Mendelian randomization (MR) to evaluate the causal effect of four lipid traits on gout and serum urate based on publicly available GWAS summary statistics ( n ~100,000 for lipid, 69,374 for gout and 110,347 for serum urate). We then employed multivariable MR to estimate the independent causal effect for lipid on gout via serum urate with mediation analysis. Results: MR showed each standard deviation (SD) (~12.26 mg/dL) increase in HDL resulted in about 25% (95% CI 9.0% ~ 38%, p = 3.31E-3) reduction of gout risk, with 0.09 mg/dL (95% CI: -0.12 ~ -0.05, p = 7.00E-04) decrease in serum urate, and each SD (~112.33 mg/dL) increase of TG was associated with 0.10 mg/dL (95% CI: 0.06 ~ 0.14, p = 9.87E-05) increase in serum urate. Those results were robust against various sensitive analyses. Additionally, independent effects of HDL and TG on gout/serum urate were confirmed. Finally, mediation analysis demonstrated HDL or TG could also indirectly affect gout via the pathway of serum urate. Conclusion: Our study confirmed the causal associations between HDL (and TG) and gout, and further revealed the effect of HDL or TG on gout could also be mediated via serum urate.
A multicenter study assessing the prevalence of germline genetic alterations in Chinese gastric cancer patients
Authors: Zhang Yinjie , Yang Yang , Wei Qing , Xu Ting , Zhang Xiaotian , Gao Jing , Zhu Changbin , Shao Di , Ke Yang , Tan Siyi , Liu Baorui , Zhang Jingdong , Chen Xiaobing , Wang Zhaojie , Qiu Meng , Wang Xin , Shen Lin , Wang Xicheng
Published: March 2020

Background: Approximately 10% of patients with gastric cancer (GC) have a genetic predisposition for the disease. To date, knowledge regarding germline mutations in predisposing genes in the Chinese GC population is scarce. The aim of this study was to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer. Methods: Forty patients from among ten families were recruited from seven medical institutions in China. Next-generation sequencing was performed on 171 genes associated with cancer predisposition. For probands with pathogenic/likely pathogenic germline variants, Sanger sequencing was used to validate the variants in the probands and their relatives. Results: Sequencing indicated that 25% (10/40) of the patients carried a combined total of ten pathogenic or likely pathogenic germline variants involving nine different genes: CDH1 (n = 1), MLH1 (n = 1), MSH2 (n = 1), CHEK2 (n = 1), BLM (n = 1), EXT2 (n = 1), PALB2 (n = 1), ERCC2 (n = 1), and SPINK1 (n = 2). Five of these variants have not previously been reported. In addition, a total of 129 variants of uncertain significance were identified in 27 patients. Conclusions: This study found that 25% of Chinese GC patients with hereditary high-risk factors have deleterious germline alterations. This result may indicate a unique genetic background of GC among Chinese patients.
Presence of additional P. vivax malaria in Duffy negative individuals from Southwestern Nigeria: Short Report
Authors: OBOH MARY Aigbiremo , Singh Upasana Shyamsunder , Ndiaye Daouda , Badiane Aida Sadikh , Ali Nazia Anwar , Bharti Praveen Kumar , Das Aparup
Published: March 2020

Background Malaria in sub-Saharan Africa (sSA) is thought to be hugely caused by Plasmodium falciparum . Recently, growing reports of cases due to P. ovale , P. malariae , and P. vivax have been significantly reported to play a role in malaria epidemiology in sSA. This in fact is due to the usage of very sensitive diagnostic tools (e.g. PCR) which have highlighted the underestimation of non-falciparum malaria in this sub-region. P. vivax was historically thought to be absent in sSA due to the high prevalence of the Duffy null antigen in individuals residing in this sub-continent. For example, recent studies reporting the detection of vivax malaria in Duffy-negative individuals from Mali, Mauritania, Cameroon to mention a few challenges this notion.Methods Following our earlier report of P. vivax in Duffy-negative individuals, we have collected and assessed RDT and/or microscope malaria positive samples following the conventional PCR method and DNA sequencing to confirm both single/mixed infections as well as the Duffy status of the individuals.Results Amplification of Plasmodium gDNA was possible in 59.9% (145/242) of the evaluated isolates and as expected P. falciparum was the most predominant (91.7%) species identified. Interestingly, four P. vivax isolates were identified either as single (3) or mixed (1 – P. falciparum / P. vivax ) infection. Sequencing results confirmed, all vivax isolates as truly vivax malaria and their Duffy status to be that of the Duffy-negative genotype.Conclusion Identification of more vivax isolates among these Duffy-negative individuals from Nigeria, substantiate the expanding body of evidence on the ability of P. vivax to infect RBCs that do not express the DARC gene. Hence, such genetic-epidemiological study should be conducted at the national level in order to evaluate the actual burden of P. vivax in the country.
Moral Competence, Moral Teamwork and Moral Action – The European Moral Case Deliberation Outcomes (Euro-MCD) Instrument 2.0 and its revision process
Authors: de Snoo-Trimp Janine , de Vet Riekie , Widdershoven Guy , Molewijk Bert , Svantesson Mia
Published: March 2020

Background Clinical Ethics Support (CES) services are offered to support healthcare professionals in dealing with ethically difficult situations. Evaluation of CES is important to understand if it is indeed a supportive service in order to inform and improve future implementation of CES. Yet, methods to measure outcomes of CES are scarce. In 2014, the European Moral Case Deliberation Outcomes Instrument (Euro-MCD) was developed to measure outcomes of Moral Case Deliberation (MCD). To further validate the instrument, we tested it in field studies and revised it. This paper presents the Euro-MCD 2.0 and describes the revision process.Methods The revision process comprised an iterative dialogue among the authors as Euro-MCD-project team, including empirical findings from six Euro-MCD field-studies and input from European experts in CES and theory. Empirical findings contained perceptions and experiences of MCD outcomes among healthcare professionals who participated in MCDs in various settings in Norway, Sweden and the Netherlands. Theoretical viewpoints on CES, literature on goals of CES and MCD and ethics theory guided the interpretation of the empirical findings and final selection of MCD outcomes.Results The Euro-MCD 2.0 Instrument includes three domains: Moral Competence, Moral Teamwork and Moral Action. Moral Competence consists of items about moral sensitivity, analytical skills and virtuous attitude. Moral Teamwork includes open dialogue and supportive relationships and Moral Action refers to moral decision-making and responsible care. During the revision process, we made decisions about adding and reformulating items as well as decreasing the number from 26 to 15 items. We also altered the sentence structure of items to assess the current status of outcomes (e.g. ‘now’) instead of an assumed improvement over time (e.g. ‘better’) and we omitted the question about perceived importance.Conclusions : The Euro-MCD 2.0 is shorter, less complex and more strongly substantiated by an integration of empirical findings, theoretical reflections and dialogues with participants and experts. Use of the Euro-MCD 2.0 will facilitate evaluation of MCD and can thereby monitor and foster implementation and quality of MCD. The Euro-MCD 2.0 will strengthen future research on evaluation of outcomes of MCD.
Multiple factors involved in T cell depletion in AIDS patients with immune non-responder to cART
Authors: Qian Feng , Hu Song , Zhu Yueping , Wang Yinling , Liu Jin , Qiao Jialu , Shu Xiji , Gao Yong , Sun Binlian , Zhu Chuanwu
Published: March 2020

Background: The replication of HIV-1 can be effectively controlled by combination antiretroviral therapy (cART) at present. However, in approximately 20% of AIDS patients with undetectable viral load under effective cART, the amount of CD4+ T cells continues to be lower than normal, showing poor immune reconstitution, which is called immune non-responder (INR). The mechanism of immune reconstitution in AIDS patients is still unclear, and thus far there is no effective improvement strategy. Aim: To investigate what factors involved in T lymphocyte depletion in INR patients.Methods: A retrospective analysis of a cohort from Suzhou Infectious Disease Hospital was performed. From October 2015 to April 2019, 29 AIDS patients, whose CD4+ T cells were less than 100/ul before treatment, were included in this study. Laboratory results were obtained from the medical records, including basic clinical information, and the results of Flow cytometer detection for CD4 T cells and ELISA for T cell-related cytokines.Results: According to the number of CD4+ T cells after 24 months of treatment, the 29 patients were divided into two groups: 15 patients with CD4+ T cells <200/ul were INR, and 14 patients with CD4+ T cells >200/ul were immune responder (IR). When Compared with IR patients, the total number of red blood cells and white blood cells, especially T lymphocytes in INR patients, was significantly lower, while programmed cell death protein 1（PD-1）on CD4+T and CD8+ T lymphocyte surface were significantly higher in INR group, which implies that the probability of T cell apoptosis was greatly increased (p<0.05). ELISA results showed that the overall production of T cell-related cytokines were lower in INR group, but the amount of cytokine secreted from each T cell was higher in INR group than that in IR group due to the significant decrease of T cell in this group. Furthermore, the proportion and the killing efficiency of CD56dim subgroup of NK cells were significantly higher in INR group. Conclusion: Multiple factors are involved in the immune reconstitution in AIDS patients, including myelosuppression, T cell destruction enhanced through PD-1 pathway, over-activation of T lymphocyte, and higher killing efficiency of CD56dim subgroup of NK cells.
The Use Of The Hungarian Test Your Memory (Tym-hun), Mmse And Adas-cog Tests For Patients With Mild Cognitive Impairment (Mci) In A Hungarian Population: A Cross-sectional Study
Authors: Garbóczy Szabolcs , Magócs Éva , Szőllősi Gergő , Harsányi Szilvia , Anikó Égerházi , Kolozsvári László
Published: March 2020

BACKGROUNDAlzheimer's Disease (AD) is a growing disease process with aging. If we could recognize the disease at an early stage and increase the number of years spent in a better condition through preventive and treatment measures, we could reduce the pressure both directly on families and indirectly on society. There is a need for testing methods that are easy to perform even in general practitioner’s office, inexpensive and non-invasive, which could help early recognition of mental decline. We have selected Test Your Memory (TYM), which has proven to be reliable for detecting AD and mild cognitive impairment (MCI) in several countries. Our study was designed to test the usability of the TYM-HUN comparing with the ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale) in MCI recognition in the Hungarian population.METHODSTYM test was translated and validated into Hungarian (TYM-HUN). The TYM-HUN test was used in conjunction with and compared with the Mini-Mental State Examination (MMSE) and the ADAS-Cog. For our study, 50 subjects were selected, 25 MCI patients and 25 healthy controls. Spearman’s rank correlation was used to analyze the correlation between the scores of MMSE and ADAS-Cog with TYM-HUN.RESULTSMCI can be distinguished from AD and normal aging using ADAS-Cog and MMSE is a useful tool to detect dementia. We established a 'cut-off' point of TYM-HUN (44/45points) where optimal sensitivity and specificity values were obtained to screen MCI. The total TYM-HUN scores significantly correlated with the MMSE scores (ρ=0.626; p<0.001) and ADAS-Cog scores (ρ=-0.723; p<0.001).CONCLUSIONSOur results showed that the Hungarian version of TYM (TYM-HUN) is an easy, fast, self-administered questionnaire with the right low threshold regarding MCI and can be used for the early diagnosis of cognitive impairment.
The Role of Physical Activity in Cancer Survivors’ Quality of Life
Authors: Liska Tayah M. , Kolen Angie
Published: March 2020

Purpose: As a result of a cancer diagnosis and treatment, many cancer survivors experience persistent physical, mental, and emotional symptoms that affect their quality of life. Physical activity has been identified as an intervention that may help to manage the side effects of a cancer diagnosis and its treatment. The purpose of this study was to investigate the role of physical activity on overall quality of life in adult cancer survivors. Methods: One-on-one semi structured interviews were conducted in person or via telephone with 13 adult (≥18 yrs) cancer survivors who had completed cancer treatment. Results: These cancer survivors described their physical activity as improving their physical functioning and mental health, as a means of positive social engagement, and adding positivity to their daily life. Conclusion: These results support the role of physical activity to enhance cancer survivors’ quality of life regardless of the individuals’ treatment(s) type, duration, or time since the end of active cancer treatment. Further research is warranted to (a) expand this research with a larger sample, (b) examine healthcare providers’ knowledge and application of exercise guidelines to cancer survivors in cancer care, and (c) explore implementation strategies for greater advocacy for healthcare providers to share the exercise recommendations with cancer survivors.
An objective system for appraising clear aligner treatment difficulty: clear aligner treatment complexity assessment tool
Authors: Long Hu , Wu Zhouqiang , Wang Qingxuan , Liu Lu , Wang Yan , Jian Fan , Liao Lina , Li Xiaolong , Lai Wenli
Published: March 2020

Background : Recent years has witnessed a remarkable evolution of clear aligner technology and clear aligners are becoming more and more versatile in managing orthodontic patents. The aim of this study was to develop an objective evaluation system for assessing clear-aligner treatment difficulty. Methods : A total of 100 eligible patients were recruited in this study. Based on clinical data (dental models, radiographs and photographs), difficulty levels were evaluated by two experts and regarded as the gold standard. Difficulty scores were determined through an evaluation system encompassing three domains (dental model analysis, radiographic examinations and clinical examinations). The reliability of the evaluation system was examined through analyzing the agreement between difficulty levels and difficulty scores. Moreover, multivariate linear regression test was used to examine the independent effect of each variable (e.g. overbite and crowding) on difficulty level. Results : The results revealed that the assessment of treatment complexity by this objective evaluation system matched perfectly with the gold standard (kappa=0.80). The multivariate regression test revealed that difficulty level was significantly associated with difficulty score (β=0.13, p<0.001), age (β=-0.04, p=0.015<0.01), tooth extraction (β=1.14, p<0.001) and number of difficult tooth movement (β=0.09, p=0.005<0.05). This objective evaluation system elaborated in this study is viable and reliable in appraising clear-aligner treatment difficulty in clinical practice. Conclusions : We suggest practitioners, especially general practitioners, use this evaluation system for appropriate clear-aligner patient selections.
The most stable pinning configurations in transverse supracondylar humerus fracture fixation in children: A novel three-dimensional finite element analysis of a pediatric bone model
Authors: Kamara Allieu , Ji Xianglu , Liu Chuang , Liu Tianjing , Wang Enbo
Published: March 2020

Background : This study aimed at finding out the effect of exit height of pins, pin trajectory and pin number on the stability of crossed and lateral pinning configurations used in the fixation of extension-type supracondylar humerus fracture (SHF) in children, through finite element analysis of a novel pediatric humerus bone model. Method : Distal humerus model consisting of the ossific nucleus of the capitellum (ONC) and distal cartilage of a 6-year-old boy was developed computationally. Various crossed and lateral pinning fixation models with either two or three pins were simulated on an extension-type, transverse SHF and tested in six loading directions. Results : Two-crossed pins and 2-lateral pins were respectively more stable in rotation and compression loadings, while 3-crossed pins were the most stable in all loading directions. The crossed pins exiting at the upper border of the distal metaphyseal-diaphyseal junction (MDJ) had the best stiffness among the 2-crossed pins, while the lateral pins with a mid-ONC distal pin provided the best stiffness among the 2-lateral pins. A third pin however, going through the olecranon fossa led to improved stability of the 2-lateral pins in flexion, extension, internal and external rotations. Conclusion : In the fixation of extension-type, transverse supracondylar humerus fractures, 2-crossed pins are only superior to 2-divergent lateral pins in rotational loadings. Two-crossed pins exiting at the upper border of the MDJ provides the best stability, whereas 2-lateral pins with a distal pin going through the middle third of the ONC provides the best stability against compression forces for these fractures. Three-crossed pins however offer the best stability against both compression and rotation forces.This study offers important clues in the preoperative evaluation and management of extension-type supracondylar fractures in children.
Salt tolerance involved candidate genes in rice: an integrative meta-analysis approach
Authors: Mansuri Raheleh Mirdar , Shobbar Zahra-Sadat , Jelodar Nadali Babaeian , Ghaffari Mohammadreza , Mohammadi Seyed Mahdi , Daryani Parisa
Published: March 2020

Background: Salinity, as one of the main abiotic stresses, critically threatens growth and fertility of main food crops including rice in the world. To get insight into the molecular mechanisms by which tolerant genotypes responds to the salinity stress, we propose an integrative meta-analysis approach to find the key genes involved in salinity tolerance. Herein, a genome-wide meta-analysis, using microarray and RNA-seq data was conducted which resulted in the identification of differentially expressed genes (DEGs) under salinity stress at tolerant rice genotypes. DEGs were then confirmed by meta-QTL analysis and literature review.Results: A total of 3449 DEGs were detected in 46 meta-QTL positions, while 1286, 86, 1729 and 348 DEGs were observed respectively in root, shoot, seedling and leaves tissues. Moreover, functional annotation of DEGs located in meta-QTLs suggested some involved biological processes (e.g. ion transport, regulation of transcription, cell wall organization and modification as well as response to stress) and molecular function terms (e.g. transporter activity, transcription factor activity and oxidoreductase activity). Remarkably, 20 potential candidate genes were detected in Saltol and hotspot-regions overlying original QTLs for both yield components and ion homeostasis traits; among which, there were many unreported salinity-responsive genes. Some promising candidate genes were detected as pectinesterase, peroxidase, transcription regulator, high-affinity potassium transporter, cell wall organization, protein serine/threonine phosphatase, and CBS domain cotaining protein.Conclusions: The obtained results indicate that, the salt tolerant genotypes use qualified mechanisms particularly in sensing and signalling of the salt stress, regulation of transcription, ionic homeostasis, and ROS scavenging in response to the salt stress.
Oncological outcome of patients with salivary gland cancer treated with surgery and postoperative intensity-modulated radiotherapy: a retrospective study
Authors: Zang Shoumei , Huang Huijie , Zhu Xinli , Chen Meiqin , Yan Danfang , Yan Senxiang
Published: March 2020

Background To investigate the outcomes, prognostic factors, patterns of failure, and adverse events in patients with salivary gland cancer (SGC) treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). Methods We identified 60 patients with major SGC treated with surgery followed by postoperative IMRT. Data for overall survival (OS),progression-free survival (PFS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), prognostic factors, and treatment-related toxicities were analyzed. Survival was calculated with the Kaplan–Meier method. Multivariable analysis (MVA) was used to identify prognostic factors for OS, PFS, LRRFS and DMFS. Results Adenoid cystic carcinoma (ACC) was the most common histology ( n =21; 35%). With a median follow-up of 55.5 months, OS and PFS were 90.7%, 85.1%, and 85.1%; and 80.1%, 72.7%, and 63.1%, at 3, 5, and 10 years, respectively. LRRFS and DMFS at 3, 5, and 10 years were 87.4%, 82.1%, and 82.1%; and 85.3%, 78.4%, and 66.1%, respectively. Five-year OS, PFS, LRRFS, and DMFS for ACC was 100%, 67.7%, 76.2%, and 90.2%, respectively. In MVA, N stage was an independent predictor of PFS ( p =0.047). Positive margin was a significant prognostic factor for PFS, LRRFS, and DMFS ( p =0.036, 0.026, and 0.011, respectively). Major nerve involvement was significantly correlated with PFS and DMFS ( p =0.034 and 0.008, respectively). Interval from surgery to radiotherapy (RT) predicted PFS and DMFS ( p =0.036 and 0.012, respectively). The most common acute toxicities were mucositis and dermatitis, and xerostomia was the most common late adverse event. Lung metastasis was the most common pattern of distant failure. Conclusion Postoperative IMRT leads to improved survival for SGC patients with acceptable toxicities.
Robustness of single-isocenter multiple-metastasis stereotactic radiosurgery end-to-end testing across institutions
Authors: Saenz Daniel L , Papanikolaou Niko , Zoros Emmanouil , Pappas Evangelos , Reiner Michael , Chew Lip Teck , Lim Hooi Yin , Hancock Sam , Nevelsky Alex , Njeh Christopher , Anagnostopoulos Georgios
Published: March 2020

Background The accuracy of stereotactic radiosurgery to multiple brain metastases with a single isocenter using high definition dynamic radiosurgery (HDRS) was evaluated to assess robustness, repeatability, and possibility of inter-institutional quality assurance amongst multiple institutions. Methods A CT simulation scan obtained from a previously treated patient was used as the data set for targeting seven brain lesions. A VMAT treatment plan was generated using Monaco and was replicated at six HDRS-capable institutions using a plan template. All institutions subsequently irradiated 3D-printed head anthropomorphic phantoms mimicking the patient’s anatomy. Three different phantoms with a point dosimeter insert, film insert, and a gel dosimeter were used. Absolute dosimetry end-to-end dosimetric accuracy as well as gamma analysis for relative dose distribution agreement analysis was used to evaluate measurement agreement with calculation. Results Point measurements averaged across all institutions using six-degree-of-freedom treatment positioning correction were within 1.2±0.5%. The average gamma passing rate in the film plane using 3D global 3D gamma analysis was 96.6±2.2% (3%/2 mm). For all targets within 4 cm of the isocenter, the 3D dosimetric gel gamma passing rate averaged across institutions was >90% (3%/2 mm). 88.0% average gamma passing rate was found for targets beyond 4 cm. The targeting accuracy of high definition dynamic radiosurgery assessed by geometrical offset of the center of dose distributions was established across multiple institutions in this study to be within 1 mm for targets within 4 cm of isocenter. Conclusions Across variations in clinical practice, comparable dosimetry and localization is possible with this treatment planning and delivery technique.
Nanodelivery of Triamcinolone Acetonide using PLGA-Chitosan Nanoparticles for the Treatment of Inflammation-related Ocular Cataract
Authors: Xing Yi , Zhu Lijuan , Zhang Ke , Li Teng , Huang Shaohua
Published: March 2020

This preprint has been removed from Research Square.
Cost-effectiveness analysis of fruquintinib for metastatic colorectal cancer third-line treatment in China
Authors: Peng Zhi , Hou Xingduo , Huang Yangmu , Xie Tong , Hua Xinyang
Published: March 2020

Background : In this study, we analyze the cost-effectiveness of fruquintinib as third-line treatment for patients with metastatic colorectal cancer in China, especially after a recent price drop suggested by the National Healthcare Security Administration. Methods : A Markov model was developed to investigate the cost-effectiveness of fruquintinib compared to placebo among patients with metastatic colorectal cancer. Effectiveness was measured in quality-adjusted life year (QALY). The Chinese healthcare payer’s perspective was considered with a lifetime horizon, including direct medical cost (2019 US dollars [USD]). A willing‐to‐pay threshold was set USD 27,130/QALY, which is 3 times gross domestic product (GDP) per capita. We examined the robustness of the model in one-way and probabilistic sensitivity analysis. Results : Fruquintinib was associated with better health outcomes than placebo (0.640 vs 0.478 QALYs) with a higher cost (USD 20750.9 vs USD 12042.2), resulting an incremental results effectiveness ratio (ICER) of USD 53508.7 per QALY. This ICER is 25% lower than the one calculated before the price drop (USD 70952.6 per QALY). Conclusion : After the price negotiation, the drug becomes cheaper and the ICER is lower, but the drug is still not cost effective under the standard of 3 times GDP willing‐to‐pay threshold. For patients with metastatic colorectal cancer in China, fruquintinib is not a cost-effective option under the current circumstances in China.
Engagement of private healthcare providers for case finding of Tuberculosis and Diabetes Mellitus in Pakistan
Authors: Habib Shifa Salman , Rafiq Sana , Jamal Wafa Zehra , Ayub Shaikh Mohammad , Ferrand Rashida Abbas , Khan Aamir , Zaidi Syed Mohammad Asad
Published: March 2020

Background: The rising co-epidemic of tuberculosis (TB) and diabetes mellitus (DM) is a challenge for constrained health systems in low and middle-income countries. Diabetes is a known risk factor for tuberculosis and associated with poor tuberculosis treatment outcomes, while tuberculosis is associated with worsening glycemic control. We investigated the performance of bi-directional TB and DM case finding approaches through a private-sector engagement model in Karachi, Pakistan.Methods: Between July 2016 and July 2018, private health care providers were engaged to generate referrals for bi-directional TB and DM screening at private diagnostic and treatment centers in Karachi, Pakistan. Individuals diagnosed with TB underwent glycated hemoglobin (HbA1c) testing at the time of anti-tuberculous treatment initiation and at three -month follow up stage. All individuals with a history of diabetes or random blood sugar of greater than 200 mg/dl were screened for TB using a chest X-ray and Xpert MTB/RIF. Results: A total of 6,312 persons with tuberculosis were tested on HbA1c at treatment initiation, of whom 1,516 (24%) were newly diagnosed with DM. About one third of those with HbA1c in the diabetic range (≥ 6.5%) at baseline were found to have a normal HbA1c (<5.7%) result at 3-month follow-up. A total of 3,824 individuals with DM, of whom 2,396 (63%) were known cases and 1,428 (37%) were newly identified with random blood sugar >200mg/dl, underwent chest x-ray and Xpert MTB/RIF testing, with 321 (13.4%) known and 54 (3.8%) new diabetics respectively identified with tuberculosis.Conclusion: This study demonstrates a high yield of TB and DM through bidirectional screening and the feasibility of engagement of private sector in finding missing cases of tuberculosis and diabetes. Given the high prevalence of undiagnosed DM in individuals with TB tuberculosis patients, there is a need to scale-up DM screening within TB programmes. Increased awareness of the high risk of TB among individuals with DM is needed among private health providers and screening for TB among diabetics should be strongly considered.
Raman and FT-IR Spectroscopy investigation the cellulose structural differences from bacteria Gluconacetobacter sucrofermentans during the different regimes of cultivation on a molasses media
Authors: Atykyan Nelli , Revin Victor , Shutova Vitalina
Published: March 2020

Raman and Fourier Transform Infrared (FT-IR) spectroscopy was used for investigation of structural differences of bacterial celluloses (BC), obtained by cultivation native and immobilized cells of Gluconacetobacter sucrofermentans during static and dynamic regimes of cultivation on a molasses media. It was found that the Raman and FT-IR spectra could characterized the groups of the cellulose molecules. The culturing bacterial cellulose in the presence of results in an increase of crystalline and it increased during cultivated on a molasses media with the addition of 1.5% ethanol - 75.62%. The degree of BC crystallinity increased during dynamic regime of cultivation is higher than under static regime one. The maximal BC content was observed when 0.5% ascorbic acid was added to the cultivation medium with molasses and native cells. It was found, the degree of BC crystallinity during static regime cultivation on a molasses medium with ethanol, increased significantly to 73.5%, and during dynamic regime - 75.6%. So, in this study, the changes of the bacterial cellulose conformation of were revealed during bacterial cultivation in a medium containing molasses in various cultivation modes.
Trans-Aortic or Pulmonary Artery-Based Drainage for Left Ventricular Unloading and Veno-Arterial Extracorporeal Life Support Management in a Porcine Cardiogenic Shock Model.
Authors: Meani Paolo , Mlcek Mikulas , Kowalewski Mariusz , Raffa Giuseppe Maria , Jiritano Federica , Matteucci Matteo , Fina Dario , Martucci Gennaro , Sels Jan Willem , Delnoij Thijs , Popkova Michaela , Pilato Michele , Arcadipane Antonio , Belohlavek Jan , Lorusso Roberto
Published: March 2020

Background The use of peripheral veno-arterial extracorporeal life support (V-A ECLS) as a mechanical circulatory support in cardiogenic shock has increased dramatically over the last years. However, increased afterload may jeopardize left ventricle (LV) recovery and cause blood stasis and pulmonary edema. Therefore, several LV unloading techniques have been developed and used with limited understanding of the actual difference among them. The aim of the present study was to compare a trans-aortic suction device (Impella) and pulmonary artery (PA) drainage, for LV unloading and V-A ECLS management as well as efficacy in a porcine cardiogenic shock (CS) model Methods A dedicated CS model compared included twelve female swine (21± 1,8-weeks old and weighing 54,3 ± 4,6 kg) supported with V-A ECLS and randomized to Impella or PA-related LV drainage. LV unloading and end-organ perfusion were evaluated through the pulmonary artery catheter and the LV pressure/volume analysis. All the variables were collected at baseline, profound CS, V-A ECLS support with maximum flow and when Impella or PA cannula run on top. Results CS was successfully induced in all twelve animals. Impella resulted in a marked drop of LVEDV compared to a slight decrease in the PA cannula group, resulting in an overall stroke work (SW) and Pressure-Volume Area (PVA) reductions with both techniques. However, SW reduction was significant in the Impella CP group (VA ECMO 3998.82027.6 mmHg x mL vs VAECMO + Impella 1796.9±1033.9 mmHg x ml, p value 0,016), leading to a more consistent PVA reduction (Impella reduction 34,7% vs PA cannula reduction 9,7%) In terms of end organ perfusion, central and mixed O 2 saturation improved with V-A ECLS, and subsequently, remaining unchanged with either Impella or PA cannula as unloading strategy Conclusions Trans-aortic suction and PA drainage provided effective LV unloading during V-A ECLS while maintaining adequate end-organ perfusion. Trans-aortic suction device provides a greater LV unloading effect and reduces more effectively the total LV stroke work.
The Therapeutic Efficacy of Adjunct Therapeutic Plasma Exchange for Septic Shock with Multiple Organ Failure: A Single Center Retrospective Review
Authors: Keith Philip , Wells Adam H , Hodges Jeremy , Fast Stephen H , Adams Amber , Scott L Keith
Published: March 2020

Background: Sepsis remains a common condition with high mortality when multiple organ failure develops. The evidence behind therapeutic plasma exchange in this setting is promising but inconclusive. Our study aims to evaluate the efficacy of adjunct therapeutic plasma exchange for septic shock with multiple organ failure compared to standard therapy alone. Methods: A retrospective, observational chart review was performed, evaluating outcomes of patients with catecholamine resistant septic shock and multiple organ failure in Intensive care units at a tertiary care hospital in Winston Salem, North Carolina from August 2015- March 2019. Adult patients with catecholamine resistant septic shock (≥ 2 vasopressors) and evidence of multiple organ failure (lactic acid >2, platelets < 200, and pH < 7.3) were included. Patients who received adjunct TPE were identified and compared to patients who received standard care alone. A propensity score using APACHE II score, SOFA score, and age was used to match patients, resulting in 40 patients in each arm. Results: Mean baseline APACHE II and SOFA scores were 32.5 and 14.3 in TPE patients versus 32.7 and 13.8 in control patients. The 28-day mortality rate was 40% in the TPE group versus 62.5% in the standard care group (p=0.07). The subgroup of patients with pneumonia as the primary diagnosis had a 28-day mortality rate of 47.8% with adjunct TPE compared 81.3% with standard care alone (p = 0.05). Improvements in baseline SOFA scores at 48 hours were greater in the TPE group compared to standard care alone (p= 0.001). Patients receiving adjunct TPE had longer ICU and hospital lengths of stay. Conclusions: Our retrospective, observational study in adult patients with septic shock and multiple organ failure did not show improvement with adjunct TPE except in patients with pneumonia as the primary source of sepsis. Hemodynamics and organ dysfunction did improve with TPE regardless of source. A prospective, randomized clinical trial is needed to investigate TPE in adult sepsis and to identify subgroups that are most likely to benefit.
Mitochondrial DNA drives noncanonical inflammation activation via cGAS–STING signaling pathway in retinal microvascular endothelial cells
Authors: Guo Yue , Gu Ruiping , Gan Dekang , Hu Fangyuan , Li Gang , Xu Gezhi
Published: March 2020

Background Pathological stimuli cause mitochondrial damage and leakage of mitochondrial DNA (mtDNA) into the cytosol, as demonstrated in many cell types. The cytosolic mtDNA then drives the activation of noninfectious inflammation. Retinal microvascular endothelial cells (RMECs) play an important role in the inner endothelial blood–retinal barrier (BRB). RMEC dysfunction frequently occurs in posterior-segment eye diseases, causing loss of vision. In this study, we investigated the involvement of cytosolic mtDNA in noninfectious immune inflammation in RMECs under pathological stimuli.Methods RMECs were stimulated with 100 ng/ml lipopolysaccharide (LPS), 200 μM hydrogen peroxide (H 2 O 2 ), or 25 mM d -glucose. After 24 h, immunofluorescent staining was used to detect the opening of the mitochondrial permeability transition pore (MPTP). Cytosolic mtDNA was detected with immunofluorescent staining and PCR after stimulation. mtDNA was then isolated and used to transfect RMECs in vitro, and the protein levels of cGAS were evaluated with western blotting. Real-time PCR was used to examine cGAS mRNA expression levels at different time points after mtDNA stimulation. The activation of STING was detected with immunofluorescent staining 6 h after mtDNA stimulation. Western blotting was used to determine the phosphorylation status of TBK1, IRF3, and nuclear factor-κB (NF-κB) P65, and the nuclear translocation of IRF3 and NF-κB P65 at 0, 3, 6, 12, and 24 h. The mRNA expression of proinflammatory cytokines CCL4, CXCL10, IRF1, and IFNB1 was determined with real-time PCR, together with the concentrations of intercellular adhesion molecule 1 (ICAM-1) mRNA.Results Pathological stimuli caused mtDNA to leak into the cytosol by opening the MPTP in RMECs after 24 h. Cytosolic mtDNA regulated the expression of cGAS and the distribution of STING in RMECs. It promoted TBK1, IRF3, and NF-κB phosphorylation and the nuclear translocation in RMECs at 12 and 24 h after its transfection. The mRNAs of proinflammatory cytokines CCL4, CXCL10, IRF1, and IFNB1 were significantly elevated at 12 and 24 h after mtDNA stimulation.Conclusions Pathological stimulation induces mtDNA escape into the cytosol of RMECs. This cytoplasmic mtDNA is recognized by the DNA sensor cGAS, increasing the expression of inflammatory cytokines through the STING–TBK1 signaling pathway.
Intraoperative hypotension is associated with shortened overall survival after lung cancer surgery
Authors: Huang Wen-Wen , Zhu Wen-Zhi , Mu Dong-Liang , Ji Xin-Qiang , Li Xue-Ying , Ma Daqing , Wang Dong-Xin
Published: March 2020

Background: Intraoperative hypotension is associated with worse perioperative outcomes, but evidence is lacking regarding long-term survival after cancer surgery. Herein, we analyzed the association between intraoperative blood pressure fluctuation and overall survival after lung cancer surgery. Methods: In this retrospective cohort study, 676 patients who received lung cancer surgery between January 1, 2006 and December 31, 2009 were reviewed. Intraoperative hyper- and hypotension were defined according to their correlation with long-term survival. The primary endpoint was overall survival. The association between intraoperative blood pressure fluctuation and overall survival was analyzed with multivariable Cox proportional hazard models. Results: Long-term follow-ups were completed in 515 patients with a median duration of 5.2 years. The estimated 5-year survival rates were 66.5%, 61.3%, 56.5%, and 41.2% in patients with only hypertension (systolic blood pressure >140 mmHg for ³5 minutes), with both hyper- and hypotension (systolic blood pressure <100 mmHg for ³5 minutes), with neither hyper- nor hypotension, and with only hypotension during surgery, respectively. After adjusting confounding factors, intraoperative hypotension was significantly associated with shortened overall survival (compared with patients with only intraoperative hypertension, those with both hyper- and hypotension: hazard ratio [HR]1.033, 95% confidence interval [CI] 0.709 to 1.507, p=0.864; those with neither hyper- nor hypotension: HR 0.952, 95% CI 0.608 to 1.489, p=0.829; those with only hypotension: HR 1.736, 95% CI 1.218 to 2.475, p=0.002). Conclusions: For patients undergoing lung cancer surgery, intraoperative hypotension, but not hypertension, was associated with shortened overall survival.
Comparison of a flexible versus rigid bone cement injection system in unilateral percutaneous vertebroplasty.
Authors: li yuwei , cui wei , zhou peng , li cheng , wen yan , xiao wei
Published: March 2020

Background: Percutaneous vertebroplasty (PVP) has been demonstrated to be effective in the treatment of acute osteoporotic vertebral fracture (AOVF). However, bilateral puncture takes more time to accept more X-ray irradiation; some scholars apply unilateral puncture PVP, but the cement cannot be symmetrically distributed in the vertebral body, so we use a flexible cement injector that undergoes PVP through the unilateral pedicle puncture. This research aims to compare the clinical results of PVP for AOVF with unilateral pedicle puncture using a straight bone cement injector and a bendable cement injector, determine the value of a bendable cement injector.Methods: We undertook a retrospective analysis of patients with thoracic and lumbar compression fracture treated with unilateral pedicle puncture Percutaneous vertebroplasty from our institution from June 2013 to July 2015. Operation time, radiation exposure, bone cement injection amount, and the incidence of bone cement leakage were recorded on presentation, the cement leakage was measured by x-ray and computed tomography scan. The patients were followed up postoperatively and were assessed mainly with regard to clinical and radiological outcomes.Results: There was no significant difference in the operation time, radiation exposure time and incidence of bone cement leakage between the two groups. There was significant difference in the amount of bone cement injection and the difference between the two groups. there were no significant differences in VAS and the relative height of the vertebral body and local Cobb angle and QUALEFFO between 2 groups at 1 week after PVP, only significant difference was observed between 12 months after operation.Conclusions: Application of flexible cement injector is safe and feasible,Compared with the application of straight bone cement injector, without prolonging the operative time, radiation exposure time and the incidence of bone cement leakage, it has the advantages of good long-term effect and low incidence of vertebral fracture recurrence.
Investigating Research Hotspots and Publication Trends of Spinal Stenosis: A Bibliometric Analysis during 2000-2018
Authors: Yang Keda , Pei Lei , Wen Kaicheng , Zhou Siming , Tao Lin
Published: March 2020

Background: Spinal stenosis is a common elderly disease, present in a variety of forms. High incidence forces researchers to pay more attention and give countermeasures. Our study aimed to conclude the knowledge hierarchy and research anticipation of spinal stenosis according to bibliometric analysis.Methods: Admitted published papers were obtained from Web of Science Core collection and PubMed database. Bibliometric analysis was conducted by using online analysis software CiteSpace and Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). Exported major MeSH terms were further biclustered with gCLUTO according to co-word analysis. Then the research hotspots and publication trends were identified based on the high-frequency MeSH terms.Results: 5606 scientific literatures were retrieved about spinal stenosis and the number maintained a roughly increasing trend from 108 in 2000 to 512 in 2018, only declining in 2011. The United States is the country keeping an academic leadership in this field. And the journal SPINE was the most authoritative with total 695 articles and average 12.73 citations. There were 17 major and 18 expanded MeSH terms extracted after bibliometric analysis. Co-word and biclustering analysis revealed seven research hotspots involved in etiology, pathogenesis, clinical manifestation, conservative treatment, operative indication, internal implantation and postoperative complications. Conclusions: In this study, we revealed the research hotspots in spinal stenosis focusing on the pathogenesis and surgical treatment. Narrowing caused by the pathological change of flavum ligamentum hypertrophy and posterior longitudinal ligament ossification attracts more attention in recent years. Besides, minimally invasive surgery and internal implantation fixation are more valid in clinical. Refining pathological classification, optimizing surgical method and instrument property will be an expectable direction of spinal stenosis.
Pigmented Villonodular Synovitis does not Influence the Outcome Following Cruciate-retaining Total Knee Arthroplasty: A Case- Control Study with Middle-term Follow-up Minimum 5-Year Follow-up
Authors: Lin Wei , Dai Yike , Niu Jinghui , Yang Guangmin , Li Ming , Wang Fei
Published: March 2020

Background: Pigmented villonodular synovitis (PVNS) is a rare synovial disease with benign hyperplasia, which has been successfully treated with total knee arthroplasty (TKA). The purpose of this study was to investigate the middle-term follow-up results of cruciate-retaining (CR) total knee arthroplasty (TKA) in PVNS patients.Methods: 17 patients with PVNS were treated with CR TKA between 2012 and 2014. 68 patients with osteoarthritis (OA) who received CR TKA as control group. The two groups matched in a 4:1 ratio based on age,gender, body mass index (BMI) and follow-up time. In the two groups, the range of motion (ROM), Knee Society Score (KSS), revision rate, disease recurrence, complications and the survivorship curve of Kaplan-Meier implant were compared. Results: All patients were followed up at least 7 years. At the last follow-up, no patients with recurrence of PVNS were found. There was no difference in KSS between the two groups, and no patients experienced infection and death. In the PVNS group, 3 patients had stiffness complications but did not need revision. 1 patient underwent revision surgery due to periprosthetic fracture. At 7 years,the implant survivorship was 90.0% in the PVNS group and 96.6% in the control group (p = 0.54).Conclusions: This study demonstrates that the function of PVNS patients who received CR TKA has been significantly improved. The survival rate of implants in PVNS patients is similar to that of OA patients. Consequently, PVNS patients who treated with CR TKA may be an achievable option. However, patients with PVNS should pay more attention to the occurrence of postoperative stiffness complications.
Inability to Obtain Sperm for Fresh IVF Cycles: Analysis and Incidence of Outcomes Using a National Database
Authors: Berger Alexandra Joice , Raup Valary , Ghayda Ramy Abou , Lanes Andrea , Kathrins Martin N
Published: March 2020

Background: Azoospermia is present in 10% of men presenting with infertility and surgical sperm retrieval rates for men with azoospermia due to spermatogenic dysfunction remain low. We investigated the incidence of failed fresh IVF cycles due to inability to obtain sperm and describe predictors for subsequent IVF. Methods: A national IVF database was used to identify fresh IVF cycles in which there was failure to obtain sperm. Patient linkage was utilized to determine outcomes of subsequent IVF. Results: 243,291 fresh IVF cycles were identified; 719 (0.3%) listed "inability to obtain sperm" as reason for embryo non-transfer. Male infertility was a factor in 537 (75%) and ejaculation was the most common anticipated sperm source (414, 57%). 713 (99.2%) cycles resulted in retrieved oocytes, but only 627 (87.2%) cryopreserved. 265 (37%) of couples underwent subsequent IVF. On multivariable analysis, lack of initial oocyte cryopreservation (OR 0.34, p=0.01) and male infertility (OR 0.14, p=0.01) were associated with having no subsequent cycles. Partner sperm was used in 213 (80%) second cycles and sperm retrieval method was largely conserved (181/213, 85%). Embryos were transferred in 186 (70%) second cycles. Failed embryo transfers were due to repeat inability to obtain sperm in 5 (6%) cycles. Conclusions: Failure to obtain sperm during fresh IVF is rare, but fresh IVF cycles should be undertaken with caution.