bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction therapy with mesenchymal stromal cells in kidney transplantation: A meta-analysis
Authors: Zhao Lingfei , Hu Chenxia , Han Fei , Chen Dajin , Cheng Jun , Wu Jianyong , Peng Wenhan , Chen Jianghua
Published: January 2021

Objective The aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) versus traditional regimens for induction therapy in kidney transplantation (KT), especially the safety of MSC infusion, practicability of MSCs as induction therapy agents and posttransplant complications. Methods PubMed, Embase, EBSCO, Ovid and the Cochrane Library were searched for prospective clinical trials that compared MSCs with traditional regimens for induction therapy in KT. Results Four trials were included, including a total of 197 patients. The pooled results revealed that MSC therapy had a lower 1-year infection rate than did the traditional therapies (RR=0.65, 95% CI: 0.46-0.9, P=0.01). There were no significant differences between the two protocols regarding the 1-year acute rejection (AR) rate (RR=0.77, 95% CI: 0.41–1.45, P=0.42), 1-year graft survival rate (RR=0.99, 95% CI: 0.95–1.03, P=0.74), delayed graft function (DGF) rate (RR=0.54, 95% CI: 0.21–1.38, P=0.2) and renal graft function at 1 month (MD=-1.56, 95% CI: -14.2– 11.08, p=0.81), 3 months (MD=0.15, 95% CI: -5.63– 5.93, p=0.96), 6 months (MD=-1.95, 95% CI: -9.87– 5.97, p=0.63), and 12 months (MD=-1.13, 95% CI: -7.16– 4.89, p=0.71) postsurgery. Subgroup analysis demonstrated that the 1-year AR rate, 1-year graft survival rate, DGF rate and renal graft function at 12 months postsurgery did not significantly differ between the low-dose calcineurin inhibitor (CNI) group and the standard-dose CNI group, indicating the potential benefits of successful CNI sparing in combination with MSC treatment. Moreover, when MSCs were applied as an alternative therapy rather than an additional therapy or allogeneic MSCs were utilized instead of autologous MSCs, all of the outcomes mentioned above were comparable. Conclusion Induction therapy with MSCs is safe and has immune response modulation effects to those of traditional regimens in the short term in KT recipients. However, regarding the long-term effects, as suggested by the 1-year infection rate and the potential of CNI sparing, MSC therapy has significant advantages. However, these advantages should be further verified in more well-designed, multicenter RCTs with large sample sizes and long follow-up periods.
Talking the talk in junior interprofessional education: Is healthcare terminology a barrier or facilitator?
Authors: Nadarajah Shamara , Azim Arden , Yılmaz Derya Uzelli , Sibbald Matthew
Published: January 2021

Background: Use of healthcare terminology is a potential barrier to interprofessional education (IPE). This study describes how junior learners perceive and classify healthcare terminology in IPE settings.Methods: We conducted a mixed methods study involving 29 medical, 14 nursing, and 2 physician assistant students who had previously attended or were registered to participate in educational activities at McMaster University’s Centre for Simulation-Based Learning. 23 participants identified “inclusive” or “exclusive” terminology in a series of scenarios used for IPE workshops using an online survey. We collated lists of “inclusive” and “exclusive” terminology from survey responses, and characterized the frequencies of included words. 22 students participated in focus group discussions on attitudes and perceptions around healthcare terminology after attending IPE workshops. We identified themes through an iterative direct content analysis of verbatim transcripts.Results: Students analyzed 14 cases, identifying on average 21 terms per case as healthcare terminology (29% of overall word count). Of the 290 terms identified, 113 terms were classified as healthcare terminology, 46 as inclusive and 17 as exclusive by >50% of participants. Analysis of focus group transcripts revealed 4 themes: abbreviations were commonly perceived as complex terminology, lack of familiarity with terminology was often attributed to inexperience, simulation was considered a safe space for learning terminology, and learning terminology was a valued IPE objective.Conclusions: While students perceive a lot of healthcare terminology in IPE learning materials, categorization of terminology as “inclusive” or “exclusive” is inconsistent. Moreover, healthcare terminology is perceived as a desirable difficulty among junior learners, and should not be avoided in IPE.
Predictors of the Length of Stay of Psychiatric Inpatients: Protocol for a Systematic Review and Meta-Analysis
Authors: Carranza Farid , Álvarez Neri Alejandro , Contreras Andrea Muriel , Guerrero Andrea Fernanda , Tamayo Natalia Sofía , Saucedo Erasmo
Published: January 2021

Background: Length of stay (LOS) for inpatient psychiatric services is an important factor with serious drawbacks when it is extended more than needed. Impacts on economy, social functioning and stigma can hamper improvement and affect the patients’ experiences on future mental healthcare. Predictions of which patients have a higher chance for prolonged LOS have been extensively researched. Previous systematic reviews found consistent predictors of both longer and shorter LOS. However, they do not provide an estimate from the pooled effect sizes. Furthermore, to our knowledge, there are no meta-analysis on the influence of these factors. The primary objective of this study will be to provide point estimates on the effect sizes of all studied predictors of the LOS of psychiatric inpatients.Methods: We will conduct a systematic search in PubMed, MEDLINE, EMBASE and PsycINFO for observational studies evaluating the effect size of independent factors on the length of stay of psychiatric inpatients. Prospective and retrospective cohorts that assess the influence of predictors through the reporting of standardized regression coefficients will be included. We will provide a qualitative synthesis of the findings from each study and perform a meta-analysis from pooled regression coefficients that were adjusted for other variables or confounders in order to obtain a point estimate and confidence interval for all factors extracted from the included studies.Discussion: The results from this study may provide more accurate predictions for mental health institutions, psychiatrists, mental health service providers, patients, and families on the prognosis regarding the length of stay for needed inpatient care. This information may be used to anticipate individuals with a higher chance for prolonged hospitalization to plan the necessary interventions for these specific situations. Considering both the benefits and disadvantages of longer and shorter stays, the pooled estimates for independent factors may be used by mental healthcare providers and patients for informed decision-making. The results from this study will also update results presented in previous studies and identify the strengths and limitations from the current available evidence. Systematic Review Registration: PROSPERO ID CRD42020172840
Mini-invasive surgical instruments in transaortic myectomy for hypertrophic obstructive cardiomyopathy: A single-center experience with 168 cases
Authors: Ji Qiang , Wang YuLin , Yang Ye , Lai Hao , Ding WenJun , Xia LiMin , Wang Chun Sheng
Published: January 2021

Background: Although septal myectomy is a standard strategy for managing patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug-refractory symptoms, so far, only a few experienced myectomy centers exist globally. Mainly, this can be explained by the many technical challenges presented by myectomy. From our clinical experience, applying the mini-invasive surgical instruments during myectomy potentially reduces the technical difficulty. This study reports the preliminary experience regarding transaortic septal myectomy using mini-invasive surgical instruments for managing patients with HOCM and drug-refractory symptoms; also, we evaluate the early results following myectomy.Methods Between March 2016 and March 2019, consecutive HOCM patients who underwent isolated transaortic septal myectomy using the mini-invasive surgical instruments were enrolled in this analysis. Intraoperative, in-hospital and follow-up results were analyzed.Results We included 168 eligible patients (83 males, mean 56.8±12.3 years). The midventricular obstruction was recorded in 7 (4.2%) patients. All patients underwent transaortic septal myectomy with a mean aortic cross-clamping time of 36.0±8.1 minutes. During myectomy, 9 (5.4%) patients received repeat aortic cross-clamping. Surgical mortality was 0.6%. Notably, 5 (3.0%) patients developed complete atrioventricular block, they needed permanent pacemaker implantation. The median follow-up time was 6 months; however, no follow-up deaths occurred with a significant improvement in New York Heart Association functional status. We reported a sharp decrease in the maximum gradients from the preoperative value (11.6±7.4 mmHg vs. 94.4±22.6 mmHg, p<0.001). The median degree of mitral regurgitation fell to 1.0 (vs. 3.0 preoperatively, p<0.001) with a significant reduction in the proportion of moderate or more regurgitation (1.2% vs. 57.7%, p<0.001).Conclusions Mini-invasive surgical instruments may be beneficial in reducing the technical challenges of transaortic septal myectomy procedure. Of note, transaortic septal myectomy using the mini-invasive surgical instruments may present with favorable results.
Comparative Cost Analysis Of Cervical Cancer Screening Programme Based On Molecular Detection Of HPV In Spain
Authors: Ibáñez Raquel , Mareque María , Granados Rosario , Andía Daniel , García-Rojo Marcial , Quílez Jose C , Oyagüez Itziar
Published: January 2021

Background: HPV cervical cancer screening (CCS) must use validated HPV tests based on the molecular detection of either viral mRNA (Aptima HPV Assay – AHPV) or DNA. AHPV has demonstrated the same cross-sectional and longitudinal sensitivity for the detection of HSIL/CIN2+ lesions but with greater specificity than HPV-DNA tests. The study aimed to estimate the total costs of a CCS with a primary HPV test based on the detection of mRNA compared to DNA in women aged 35-65 years for the National Health System.Methods: A decision-tree-based model to estimate the cost of the CCS until the first colposcopy was designed based on Spanish CCS guidelines. The total cost (€,2019) for CCS with AHPV or DNA tests (HC2 and Cobas) was calculated, including HPV test, liquid-based cytology (LBC) and colposcopy, for a population of 7,263,529 women aged 35-65 years (assuming 70% coverage). Clinical inputs derived from a literature review were validated by a multidisciplinary expert panel. Data from head-to-head studies between different HPV tests were selected. Results: The use of AHPV showed reduction of 290,541 (-35%) and 355,913 (-40%) LBC compared to HC2 or Cobas, respectively. Furthermore, AHPV avoided 151,699 (-47%) colposcopies vs HC2 and 151,165 (-47%) vs Cobas. The total cost of CCS was €282,747,877 with AHPV, €322,587,588 with HC2 and €324,614,490 with Cobas. Therefore, AHPV savings €-39,839,711 vs HC2 and €-41,866,613 vs Cobas.Conclusions: Assuming that 70% of women from 35-65 years attend the CCS programme, the cost of screening up to the first colposcopy using AHPV would provide cost savings of up to €41.9 million vs DNA tests in Spain.
Comparative genomics and transcriptomics analyses provide insights into the high yield and regulatory mechanism of Norvancomycin biosynthesis in Amycolatopsis orientalis NCPC 2-48
Authors: Li Xingxing , Zhang Cong , Zhao Ying , Lei Xuan , Jiang Zhibo , Zhang Xuexia , Zheng Zhihui , Si Shuyi , Wang Lifei , Hong Bin
Published: January 2021

Background Norvancomycin has been widely used in clinic to treat against MRSA (Methicillin-resistant Staphylococcus aureus) and MRSE (Methicillin-resistant Staphylococcus epidermidis) infections in China. Amycolatopsis orientalis NCPC 2-48, a high yield strain derived from A. orientalis CPCC 200066, has been applied in industrial large-scale production of norvancomycin by North China Pharmaceutical Group. However, the potential high-yield and regulatory mechanism involved in norvancomycin biosynthetic pathway has not yet been addressed.Results Here we sequenced and compared the genomes and transcriptomes of A. orientalis CPCC 200066 and NCPC 2-48. These two genomes are extremely similar with an identity of more than 99.9%, and no duplication and structural variation was found in the norvancomycin biosynthetic gene cluster. Comparative transcriptomic analysis indicated that biosynthetic genes of norvancomycin, as well as some primary metabolite pathways for the biosynthetic precursors of norvancomycin were generally upregulated. AoStrR1 and AoLuxR1, two cluster-situated regulatory genes in norvancomycin cluster, were 23.3-fold and 5.8-fold upregulated in the high yield strain at 48 h, respectively. Over-expression of AoStrR1 and AoLuxR1 in CPCC 200066 resulted in an increase of norvancomycin production, indicating their positive roles in norvancomycin biosynthesis. Furthermore, AoStrR1 can regulate the production of norvancomycin by directly interacting with at least 8 promoters of norvancomycin biosynthetic genes or operons.Conclusion Our results suggested that the high yield of NCPC 2-48 can be ascribed to increased expression level of norvancomycin biosynthetic genes in its cluster as well as the genes responsible for the supply of its precursors. The norvancomycin biosynthetic genes are presumably regulated by AoStrR1 and AoLuxR1, of them AoStrR1 is possibly the ultimate pathway-specific regulator for the norvancomycin production. These results are helpful for further clarification of the holistic and pathway-specific regulatory mechanism of norvancomycin biosynthesis in the industrial production strain.
Prevalence of neonatal near miss and associated factors in Nepal: a cross-sectional study
Authors: Rajbanshi Sushma , Noor Norhayati Mohd , Hussain Nik Hazlina Nik
Published: January 2021

Background: Unlike the infant mortality rate, the rate of neonatal mortality has not significantly declined and remains a major health challenge in the low- and middle-income countries. There is an urgent need to focus on newborn care, especially during the first 24 hours after birth and the early neonatal period. Neonatal near miss (NNM) is an emerging concept similar to that of maternal near miss. NNM events occur three to eight times more often than neonatal deaths. The objective of this study was to establish the prevalence of NNM and identify its associated factors. Methods: A hospital-based cross-sectional study was conducted in Koshi Hospital, Morang district, Nepal. Neonates and their mothers of unspecified maternal age and number of gestational weeks were enrolled. The key inclusion criterion was the pragmatic and management markers of NNM, and admission of newborn infants to the neonatal intensive care unit (NICU) in Koshi Hospital. Non-Nepali citizens were excluded. Consecutive sampling was used until the required sample size of 1,000 newborn infants was reached. Simple and multiple logistic regression was performed using SPSS® version 24.0.Results: One thousand respondents were recruited. Prevalence of NNM was 79 per 1,000 live births. Severe maternal morbidity (adjusted odds ratio (aOR) 4.52; 95% confidence interval (CI): 2.07–9.84), no education (aOR 2.16; 95% CI 1.12–4.14), multiparity (aOR 0.52; 95% CI 0.32–0.86), and caesarean section (aOR 0.44: 95% CI 0.19–0.99) were associated with NNM. Conclusions: Prevalence of NNM in Nepal was 7.9%. Mothers’ obstetric factors, maternal complications and education were associated with NNM. Women in referral hospitals should have safer access to caesarean section and be prepared for NICU intervention to save mothers and their newborns.
When to resume bariatric surgery after COVID-19 pandemic? – results of patients’ and surgeons’ survey.
Authors: Dudek Alicja , Wysocki Michał , Walędziak Maciej , Szeliga Jacek , Proczko-Stepaniak Monika , Pedziwiatr Michał , Major Piotr
Published: January 2021

BackgroundCoronavirus Disease 2019 is affecting most countries around the world, including Poland. In response, all elective surgeries have been postponed. We asked patients and surgeons when they want bariatric surgery to resume after pandemic. The main aim of the study was to determine patients’ and surgeons’ expectations about when to resume bariatric surgery regarding COVID-19 pandemic state.MethodsThe study was conducted in two groups: Group 1 – bariatric patients; Group 2 – bariatric surgeons. Two online surveys were distributed.ResultsA total of 895 patients, 299 before, 596 after surgery and 32 surgeons took part in survey. All patients and surgeons declared willingness to resume bariatric surgeries after pandemic and responded that they should be resumed immediately the World Health Organization announces end of pandemic (42%). The majority of patients before surgery answered that bariatric procedures should be resumed immediately the number of daily incidents begins to decrease (53%). In the patient group, current body mass index (p<0.001) and contact with COVID+/quarantined persons (p<0.001) had impact on the response to resumption of bariatric procedures.ConclusionsPatients opted to wait for bariatric surgery until the oncological queue has become shorter. Surgeons presented a readiness to resume both procedures in parallel.Trial registration: 1072.6120.103.2020
Shaping Code in Conjunction with DCT for PAPR Reduction in Multicarrier System
Authors: Aimer Younes , Bouazza Boubakar Seddik , Bachir Smail , Duvanaud Claude
Published: January 2021

Nonlinear behavior and power efficiency of the Power Amplifier (PA) contradictorily depend on the input signal amplitude distribution. The transmitted signal in multi-carrier modulation exhibits high Peak-to-Average Power Ratio (PAPR) and large bandwidths, leading to the degradation of the radio link and additional generation out-of-band interferences, which degrade the quality of the transmission. Practical solutions exist, like a power back-off, but with unacceptable efficiency performances of the transmitter.
This paper deals with efficiency and linearity improvement using a new PAPR reduction method based on the combination of Discrete Cosine Transform (DCT) and shaping technique. The main principle is to determine an optimal coding scheme according to a trade-off between coding complexity and performance benefits in the presence of PA non-linearities.
Simulation and experimental results in the context of OFDM signal and using a 20W - 3.7GHz Radio-Frequency Power Amplifier (RF-PA) show an improvement on PAPR reduction of about 3.25dB. Also, the communication criteria like BER (Bit Error Rate) and EVM (Error Vector Magnitude) are improved by about one decade and a half and 8%, respectively.
“I have SMA, SMA doesn’t have me”- A Qualitative Snapshot into the Challenges, Successes, and Quality of Life of Adolescents and Young Adults with SMA
Authors: Mazzella Allison Joy , Curry Mary , Belter Lisa , Cruz Rosangel , Jarecki Jill
Published: January 2021

Background: With the approval of three treatments for spinal muscular atrophy (SMA) and several promising therapies on the horizon, the SMA adolescent and young adult populations are expected to evolve in the coming years. It is imperative to understand this cohort as it exists today to provide optimal care and resources, as well as to assess possible treatment effects over time. In 2018, Cure SMA launched two initiatives geared towards understanding adolescents and young adults with SMA, ages 12-25. First, Cure SMA launched a Quality of Life (QoL) survey to capture quantitative and qualitative information on this specific age demographic. Concurrently, Cure SMA invited SMA-affected individuals, ages 12-25, to create a three-minute video on their everyday experiences living with SMA. An inductive thematic analysis of the free-text survey questions along with the video contest findings are reported here. Results: Eighty-five individuals — 6 type Is, 58 type IIs, and 21 type IIIs — completed the Quality of Life free-response, while six individuals participated in the SMA awareness video contest. In both settings, individuals detailed a variety of challenges, including but not limited to forming or maintaining close relationships, experiencing feelings of isolation, challenges with accessibility, independence, and dealing with the stigma of being perceived as mentally disabled. Individuals also discussed their successes, including but not limited to higher education enrollment and attendance, development of quality friendships, and perseverance through obstacles. Additionally, notably in the survey, 39% of respondents requested the creation of an SMA peer support group in efforts to connect with each other as well as collectively navigate the aforementioned challenges they face. Conclusion: Together, these findings provide a rare glimpse into the unique mindsets, challenges and motivations of SMA adolescents and young adults, via patient-reported measures instead of caregiver proxy. The adolescent and young adult age demographics assessed represent a critical transition period in life and in SMA care. No one understands the needs of an adolescent or young adult with SMA better than the individuals themselves, and it is critical to encapsulate their insights to affect change.
Estimation of Energy Expenditure of Nordic Walking: A Crossover Trial
Authors: Baek Sora , Ha Yuncheol
Published: January 2021

Background: Nordic walking (NW) requires more energy compared with conventional walking (W). However, the metabolic equation for NW has not been reported. Therefore, this study aimed to characterize responses in oxygen uptake, minute ventilation, heart rate, systolic blood pressure, and surface electromyography of the upper and lower limb muscles during NW and W and develop a metabolic equation for energy expenditure (E, mL·kg-1·min-1) of NW.Methods: This study was performed in a randomized, controlled, crossover design to test the energy expenditure during NW and W. Fifteen healthy young men were enrolled (aged 23.7 ± 3.0 years). All participants performed two randomly ordered walking tests (NW and W) on a treadmill at a predetermined stepwise incremental walking speed (3–5 km·h-1) and grade (0%–7%). The oxygen uptake, minute ventilation, heart rate, systolic blood pressure, and surface electromyography signals of the three upper limb muscles and three lower limb muscles in their right body were recorded and compared between NW and W using paired-t test. Multiple linear regression analysis was used to draw estimation of E during W and NW.Results: Oxygen uptake (+15.8%), minute ventilation (+17.0%), heart rate (+8.4%), and systolic blood pressure (+7.7%) were higher in NW than in W (P<.05). NW resulted in increased muscle activity in all of the upper limb muscles (P<.05). In the lower limb, surface electromyography activities in two of the three lower limb muscles were increased in NW than in W only during level walking (P<.05). Energy expenditure during W and NW was estimated as follows: ENW = 6.1 + 0.09 × speed + 1.19 × speed × grade and EW = 4.4 + 0.09 × speed + 1.20 × speed × grade.Conclusion: NW showed higher work intensity than W, with an oxygen consumption difference of 1.7 mL·kg-1·min-1. The coefficients were not different between the two walking methods. NW involved more muscles of the upper body than W.
Characteristics of human papillomavirus infection among women with cervical cytological abnormalities in the Zhoupu District, Shanghai City, China, 2014–2019
Authors: Li Ping , Liu Qing , Li Wei , Liu Zhou , Xing Baoling , Wu Suqin , Zhou Zhaoli , Sun Liping , Ren He , Li Hengfeng , Li Huaping
Published: January 2021

Background: Human papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in female patients. By analyzing 6-year patient data from Shanghai Zhoupu Hospital in China, we retrospectively analyzed the epidemiological characteristics of women to determine the relationship between HPV genotype and cytological test results.Methods: From 2014 to 2019, 23,724 cases of cervical shedding were collected from Zhoupu Hospital in Shanghai, China. By comparing the results of HPV and ThinPrep cytology test (TCT), the HPV infection rate of patients was retrospectively analyzed. HPV genotyping using commercial kits can detect 21 HPV subtypes (15 high-risk and 6 low-risk). According to the definition of the Bethesda system, seven types of cervical cytology results were involved.Results: 3,816 among 23,724 women, nearly 16.08%, were infected with HPV. The top three highest HPV prevalence rates were high-risk type infection, including HPV52 (3.19%), 58 (2.47%) and 16 (2.34%). The number of single-type HPV infections (3,480 (91.20%)) was much larger than the number of multi-type ones (336 (8.8%)). Single-type infections were mainly in women aged 50-60 (16.63%) and women under 30 (15.37%), while multi-type infections were more common in women over 60 (2.67%). By analyzing the long-term trends, between 2014 and 2019, HPV52, 58, and 16 subtypes changed significantly, and the HPV positive rate also changed significantly during this period.Among 4,502 TCT positive women, 15 (4.04%), 125 (2.64%) ,159 (1.54%), 4,202(17.71%) and 1(0.004%) had atypical glandular cells (AGC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), atypical squamous cells (ASC)and cervical adenocarcinoma, respectively. The HPV infection rates were 66.08%, 63.99%, 115.20%, 119.50%, and 31.72% for NILM, AGCs, HSILs LSILs and ASCs, respectively.Conclusions: HPV and TCT screening were very important steps in the secondary prevention of cervical cancer. Through the tracking and analysis of HPV and TCT results in this study, it can provide valuable information for Shanghai's HPV screening and prevention strategies, and provide references for clinical decision-making in the treatment of cervical cancer and precancerous lesions.
Insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptides.
Authors: Carratalá Jose Vicente , Cisneros Andrés , Hellman Elijah , Villaverde Antonio , Ferrer-Miralles Neus
Published: January 2021

Background

Protein aggregation is a biological event observed in expression systems in which the recombinant protein is produced under stressful conditions surpassing the homeostasis of the protein quality control system. In addition, protein aggregation is related to conformational diseases in animals as transmissible prion diseases, and non-transmissible neurodegenerative diseases including Alzheimer, Parkinson's disease, amyloidosis and multiple system atrophy among others. At the molecular level, the presence of aggregating-prone domains in protein molecules act as seeding igniters to induce the accumulation of protein molecules in protease-resistant clusters by intermolecular interactions.

Results

In this work the aggregating-prone performance of a small peptide (L6K2) with additional antimicrobial activity was studied and the relevance of the accompanying scaffold protein to enhance the aggregating profile of the fusion protein has been elucidated. Furthermore, it was demonstrated that the fusion of L6K2 to highly soluble recombinant proteins directs the protein to inclusion bodies (IBs) in E. coli through stereospecific interactions in the presence of an insoluble protein displaying the same aggregating-prone peptide (APP).

Conclusions

These data suggest that the molecular bases of protein aggregation are related not only to the presence of aggregation-prone stretches, but to the net balance of protein aggregation potential. and not only to the presence of aggregation-prone stretches. This is ultimately presented as a generic platform to generate hybrid protein aggregates in microbial cell factories for biopharmaceutical and biotechnological applications.
Differential mitochondrial proteomic analysis of A549 cells infected with avian influenza virus subtypes H5 and H9
Authors: Yang Yuting , Zhang Yun , Yang Changcheng , Fang Fang , Wang Ying , Chang Haiyan , Chen Ze , Chen Ping
Published: January 2021

Background: Both the highly pathogenic avian influenza (HPAI) H5N1 and low pathogenic avian influenza (LPAI) H9N2 viruses have been reported to cross species barriers to infect humans. H5N1 viruses can cause severe damage and are associated with a high mortality rate, but H9N2 viruses do not cause such outcomes. Our purpose was to use proteomics technology to study the differential expression of mitochondrial-related proteins related to H5N1 and H9N2 virus infections.Methods: According to the determined viral infection titer, A549 cells were infected with 1 multiplicity of infection (MOI) virus, and the mitochondria were extracted after 24 h of incubation. The protein from lysed mitochondria was analyzed by the BCA method to determine the protein concentration, as well as SDS-PAGE (preliminary analysis), two-dimensional gel electrophoresis, and mass spectrometry. Differential protein spots were selected, and Western blotting was performed to verify the proteomics results. The identified proteins were subjected to GO analysis for subcellular localization, KEGG analysis for functional classification and signaling pathways assessment, and STRING analysis for functional protein association network construction.Results: In the 2-D gel electrophoresis analysis, 227 protein spots were detected in the H5N1-infected group, and 169 protein spots were detected in the H9N2-infected group. Protein spots were further subjected to mass spectrometry identification and removal of redundancy, and 32 differentially expressed proteins were identified. Compared with the H9N2 group, the H5N1-infected group had 16 upregulated mitochondrial proteins and 16 downregulated proteins. The differential expression of 70-kDa heat shock protein analogs, short-chain enoyl-CoA hydratase, malate dehydrogenase, and ATP synthase was verified by Western blot, and the results were consistent with the proteomics findings. Functional analysis indicated that these differentially expressed proteins were primarily involved in apoptosis and metabolism.Conclusions: Compared with their expression in the H9N2 group, the differential expression of eight mitochondrial proteins in the H5N1 group led to host T cell activation, antigen presentation, stress response, ATP synthesis and cell apoptosis reduction, leading to higher pathogenicity of H5N1 than H9N2.
Efficiency of Non-invasive Prenatal Screening in Pregnant Women at Advanced Maternal Age
Authors: Zhu Hui , Jin Xiaoxiao , Xu Yuqing , Zhang Weihua , Liu Xiaodan , Jin Jinglei , Qian Yeqing , Dong Minyue
Published: January 2021

Background: Non-invasive prenatal screening (NIPS) is widely used as the alternative choice for pregnant women at high-risk of fetal aneuploidy. However, whether NIPS has a good detective efficiency for pregnant women at advanced maternal age (AMA) has not been fully studied especially in Chinese women. Methods: 29,343 pregnant women at AMA with singleton pregnancy who received NIPS and followed-up were recruited. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), receiver operating characteristic (ROC) curves and the Youden Index for detecting fetal chromosomal aneuploidies were analyzed. The relationship between maternal age and common fetal chromosomal aneuploidy was observed. Results: The sensitivity, specificity, PPV, NPV of NIPS for detecting fetal trisomy 21 were 99.11%, 99.96%, 90.98%, and 100%, respectively. These same parameters for detecting fetal trisomy 18 were 100%, 99.94%, 67.92%, and 100%, respectively. Finally, these parameters for detecting trisomy 13 were 100%, 99.96%, 27.78%, and 100%, respectively. The prevalence of fetal trisomy 21 increased exponentially with maternal age. The high-risk percentage incidence rate of fetal trisomy 21 was significantly higher in the pregnant women at 37 years old or above than that in pregnant women at 35 to 37 years old. (Youden index=37). Conclusion: It is indicated that NIPS is an effective prenatal screening method for pregnant women at AMA.
Successful live birth in a Chinese woman with P450 oxidoreductase deficiency through frozen-thawed embryo transfer: a case report with review of the literature
Authors: Pan Ping , Zheng Lingyan , Chen Xiaoli , Huang Jia , Yang Dongzi , Li Yu
Published: January 2021

Background: Congenital adrenal hyperplasia (CAH) caused by P450 oxidoreductase deficiency (PORD) in 46,XX patients is characterized by genital ambiguity, primary amenorrhea, absent or incomplete sexual maturation, infertility, skeletal malformations and so on. But few pregnancies have been reported from these female patients with PORD. Case Description: A 29-year-old Chinese woman with PORD due to the compound heterozygous mutation (c.1370G>A/c.1196_1204del) in the P450 oxidoreductase(POR) gene had suffered from primary amenorrhea and infertility. She had one cancelled cycle of ovulation induction due to low serum estradiol(E2), high progesterone(P) levels and thin endometrium，then in vitro fertilization (IVF) was recommended. At the first IVF cycle, 4 oocytes were retrieved and 4 viable embryos were cryopreserved due to thin endometrium associated with low E2 and prematurely elevated P after ovarian stimulation, even though oral dexamethasone were used to control adrenal P overproduction at the same time. When basal P fell to <1.5ng/ml after the therapy of oral dexamethasone, artificial endometrial preparation and frozen embryo transfer were performed, resulting in a twin pregnancy. She delivered a healthy boy and a healthy girl by caesarean section at 37 weeks and 2 days of gestation. After the literature search in PORD women, no spontaneous pregnancy has been reported and only two previous case reports of 3 successful pregnancies through IVF were summarized.Conclusions: It is the third report that successful pregnancy was achieved in a CAH woman caused by a compound heterozygous POR mutation, with primary amenorrhea and disorders of steroidogenesis. It seemed that disorders of steroidogenesis caused by PORD didn’t impair the developmental potential of oocytes. IVF and frozen embryo transfer after adequate hormonal control and endometrial preparation should be an effective infertility treatment for PORD women.
Loco-regional recurrence trend and prognosis in young women with breast cancer according to molecular subtypes ： analysis of 1099 cases
Authors: Li Yang , Lu Su , Zhang Yuhan , Wang Shuaibing , Liu Hong
Published: January 2021

BackgroundThe number of young patients diagnosed with breast cancer is on the rise. We studied the rate trend of local recurrence (LR) and regional recurrence (RR) in young breast cancer (YBC) patients and outcomes among these patients based on molecular subtypes. Methods A retrospective cohort study was conducted based on data from Tianjin Medical University Cancer Institute and Hospital for patients ≤35 years of age with pathologically-confirmed primary invasive breast cancer surgically treated between 2006 and 2014. Patients were categorized according to molecular subtypes on the basis of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The 5-year rates for LR, RR, and distant metastases (DM) were estimated by Kaplan-Meir statistics. Nelson-Aalen cumulative-hazard plots were used to describe local recurrence- and distant metastases-free intervals. ResultsWe identified 25,284 patients with a median follow-up of 82 months, of whom 1099 (4.3%) were YBC patients ≤35 years of age. The overall 5-year LR, RR and DM rates in YBC patients were 6.7%, 5.1%, and 16.6%, respectively. The LR and RR rates demonstrated a decreasing trend over time (P=0.028 and P=0.015, respectively). We found that early-stage breast cancer and less lymph node metastases increased over time (P=0.004 and P=0.007, respectively). Patients with HR-/HER2+ status had a significantly higher LR (HR 20.4; 95% CI,11.8-35.4) and DM (HR 37.2; 95% CI, 24.6-56.3) at 10 years. Breast conserving surgery (BCS) or mastectomy did not influence rates of LR and RR. In the overall population, the 5-year survival of YBC patients exceeded 90%. ConclusionsThe rates of LR and RR with YBC patients demonstrated a downward trend and the proportion of early-stage breast cancer increased between 2006 and 2014. We report the highest LR rates in this young population were associated with HR-/HER2+ tumors in absence of standard treatment.
External Stenting of Vein Grafts in Coronary Artery Bypass Grating: Interim Results from a Two Centers Prospective Study
Authors: Weltert Luca , Audisio Katia , Bellisaro Alessandro , Bardi Gianluca , Flocco Roberto , De Paulis Ruggero , Centofanti Paolo
Published: January 2021

Background – previous studies evaluating external stents for saphenous vein grafts (SVG) in CABG were limited to on-pump isolated CABG and single grafting technique with one external stent per patient. The objective of this prospective study was to evaluate the safety and the short-term performance of external stents in heterogeneous group of patients which underwent on and off-pump CABG, single and sequential grafting.Methods - 102 patients undergoing CABG were enrolled in two centers. All patients received internal mammary artery to the left anterior descending artery and additional arterial and/or venous grafts. In each patient, at least one SVG was supported with an external stent. Grafts’ patency and SVG lumen uniformity were assessed using CT angiography at a pre-defined time window of 6-12 months post procedure. All patients were prospectively followed-up via phone call and/or visit every 6 months for Major Adverse Cardiac and Cerebrovascular Events.Results - 51 patients (50%) underwent off-pump CABG and 23 patients (23%) were grafted with bilateral internal mammary arteries. Each patient received one or more SVG grafted in a sequential technique (44%) or as single graft (56%). All SVG were externally stented in 84% of patients and in 16% (n=16) one SVG was stented and one remained unsupported. At 6-12 months, patency rates of LIMA, RIMA, externally stented SVG and none-stented SVG were 100%, 100%, 98% and 87.5% respectively. 90% of the externally stented SVG had uniform lumen compared to 37% of the non-stented SVG. Clinical follow-up was completed for all patients with a mean duration of 20 months (range 6-54 months). During follow up period, one patient experienced myocardial infarction due to occlusion of the LIMA-LAD graft and one patient experienced transient ischemic attack. Conclusions - External stenting of SVG is feasible and safe in CABG setting which includes off pump CABG and sequential SVG grafting and associated with acceptable early patency rates.Study registration- Study was registered at ClinicalTrials.gov. NCT01860274 (initial release 20.05.2013)
Strategies for involving patients and the public in scaling-up initiatives in health and social services: study protocol for a scoping review and Delphi survey
Authors: Charif Ali Ben , Plourde Karine V. , Guay-Belanger Sabrina , Zomahoun Hervé Tchala Vignon , Gogovor Amédé , Straus Sharon , Beleno Ron , Kastner Kathy , McLean Robert K.D. , Milat Andrew J. , Wolfenden Luke , Paquette Jean-Sébastien , Geiger Friedemann , Légaré France , Network The RePOS
Published: January 2021

Background: The scale-up of evidence-based innovations is required to reduce waste and inequities in health and social services (HSS). However, it often tends to be a top-down process initiated by policy-makers, and the values of the intended beneficiaries are forgotten. Involving multiple stakeholders including patients and the public in the scaling-up process is thus essential but highly complex. We propose to identify relevant strategies for meaningfully and equitably involving patients and the public in the science and practice of scaling up in HSS.Methods: We will adapt our overall method from the RAND/UCLA Appropriateness Method. Following this, we will perform a two-prong study design (knowledge synthesis and Delphi study) grounded in an integrated knowledge translation approach. This approach involves extensive participation of a network of stakeholders interested in patient and public involvement (PPI) in scaling up and a multidisciplinary steering committee. We will conduct a systematic scoping review following the methodology recommended in the Joanna Briggs Institute Reviewers Manual. We will use the following eligibility criteria: 1) Participants – any stakeholder involved in creating or testing a strategy for PPI; 2) Intervention – any PPI strategy proposed for scaling-up initiatives; 3) Comparator – no restriction; 4) Outcomes: any process or outcome metrics related to PPI; and 5) Setting – HSS. We will search electronic databases (e.g., Medline, Web of Science, Sociological Abstract) from inception onwards, hand searching relevant websites, screen the reference lists of included records, and consult experts in the field. Two reviewers will independently select and extract eligible studies. We will summarize data quantitatively and qualitatively and report results using the PRISMA extension for Scoping Reviews (PRISMA-ScR) checklist. We will conduct an online Delphi survey to achieve consensus on the relevant strategies for PPI in scaling-up initiatives in HSS. Participants will include stakeholders from low-, middle-, and high-income countries. We anticipate that three rounds will allow an acceptable degree of agreement on research priorities. Discussion: Our findings will advance understanding of how to meaningfully and equitably involve patients and the public in scaling-up initiatives for sustainable HSS.Registration: We registered this protocol with the Open Science Framework on August 19, 2020 (https://osf.io/zqpx7/).
A Novel Experimental Porcine Model to Assess the Impact of Differential Pulmonary Blood Flow on Ischemia-reperfusion Injury After Unilateral Lung Transplantation
Authors: Frick Anna Elisabeth , Orlitová Michaela , Vanstapel Arno , Ordies Sofie , Claes Sandra , Schols Dominique , Heigl Tobias , Kaes Janne , Saez-Gimenez Berta , Vos Robin , Verleden Geert M. , Vanaudenaerde Bart , Verleden Stijn E. , Raemdonck Dirk E. Van , Neyrinck Arne P.
Published: January 2021

Background Primary graft dysfunction (PGD) remains a major obstacle after lung transplantation. Ischemia-reperfusion injury is a known contributor to the development of PGD following lung transplantation. We developed a novel approach to assess the impact of increased pulmonary blood flow in a large porcine single-left lung transplantation model.Materials Twelve porcine left lung transplants were divided in two groups (n = 6, in low (LF) and high flow (HF) group). Donor lungs were stored for 24 hours on ice, followed by left lung transplantation. In the HF group, recipient animals were observed for 6h after reperfusion with partially clamping right pulmonary artery to achieve a higher flow (target flow 40 – 60% of total cardiac output) to the transplanted lung compared to the LF group, where the right pulmonary artery was not clamped.Results Survival at 6 hours was 100% in both groups. Histological, functional and biological assessment did not significantly differ between both groups during the first 6 hours of reperfusion. injury was also present in the right native lung and showed signs compatible with the pathophysiological hallmarks of ischemia-reperfusion injury.Conclusions Partial Clamping native pulmonary artery in large animal lung transplantation setting to study the impact of low versus high pulmonary flow on the development of ischemia reperfusion is feasible. In our study, differential blood flow had no effect on IRI. However, our findings might impact future studies with extra-corporeal devices and represents a specific intra-operative problem during bilateral sequential single lung transplantation.
Role of human Pegivirus infections in whole Plasmodium falciparum sporozoite vaccination and controlled human malaria infection in African volunteers
Authors: Tumbo Anneth-Mwasi , Schindler Tobias , Dangy Jean-Pierre , Orlova-Fink Nina , Bieri Jose Raso , Mpina Maximillian , Milando Florence A. , Juma Omar , Hamad Ali , Nyakarungu Elizabeth , Chemba Mwajuma , Mtoro Ali , Ramadhan Kamaka , Olotu Ally , Makweba Damas , Mgaya Stephen , Stuart Kenneth , Perreau Matthieu , Stapleton Jack T. , Jongo Said , Hoffman Stephen L. , Tanner Marcel , Abdulla Salim , Daubenberger Claudia
Published: January 2021

Background: Diverse vaccination outcomes and protection levels among different populations pose a serious challenge to the development of an effective malaria vaccine. Co-infections are among many factors associated with immune dysfunction and sub-optimal vaccination outcomes. Chronic, asymptomatic viral infections can contribute to the modulation of vaccine efficacy through various mechanisms. Human Pegivirus-1 (HPgV-1) persists in immune cells thereby potentially modulating immune responses. We investigated whether Pegivirus infection influences vaccine-induced responses and protection in African volunteers undergoing whole P. falciparum sporozoites-based malaria vaccination and controlled human malaria infections (CHMI). Methods: HPgV-1 prevalence was quantified by RT-qPCR in plasma samples of 96 individuals before, post vaccination with PfSPZ Vaccine and after CHMI in cohorts from Tanzania and Equatorial Guinea. The impact of HPgV-1 infection was evaluated on (1) systemic cytokine and chemokine levels measured by Luminex, (2) PfCSP-specific antibody titers quantified by ELISA, (3) asexual blood-stage parasitemia pre-patent periods and parasite multiplication rates, (4) HPgV-1 RNA levels upon asexual blood-stage parasitemia induced by CHMI.Results: The prevalence of HPgV-1 was 29.2% (28/96) and sequence analysis of the 5' UTRand E2 regions revealed the predominance of genotypes 1, 2 and 5. HPgV-1 infection was associated with elevated systemic levels of IL-2 and IL-17A. Comparable vaccine-induced anti-PfCSP antibody titers, asexual blood-stage multiplication rates and pre-patent periods were observed in HPgV-1 positive and negative individuals. However, a tendency for higher protection levels was detected in the HPgV-1 positive group (62.5%) compared to the negative one (51.6%) following CHMI. HPgV-1 viremia levels were not significantly altered after CHMI. Conclusions: HPgV-1 infection did not alter PfSPZ Vaccine elicited levels of PfCSP-specific antibody responses and parasite multiplication rates. Ongoing HPgV-1 infection appears to improve to some degree protection against CHMI in PfSPZ-vaccinated individuals. This is likely through modulation of immune system activation and systemic cytokines as higher levels of IL-2 and IL17A were observed in HPgV-1 infected individuals. CHMI is safe and well tolerated in HPgV-1 infected individuals. Identification of cell types and mechanisms of both silent and productive infection in individuals will help to unravel the biology of this widely present but largely under-researched virus.