bluuebunny/crossref_metadata_2025 huggingface dataset:
The safety and efficiency of retroperitoneal laparoscopic adrenalectomy via extra and intra perinephric fat approaches: a retrospective clinical study
Authors: Wang Xuejian , Liu Junqiang , Ji Aozhang , Liu Changli , Nahayo Sony , Wang Lina , Zhu Xinqing , Fan Weiwei , Song Xishuang , Wang Jianbo , Yang Deyong
Published: December 2019

Background

This retrospective clinical study is to evaluate the safety and efficiency of two different approaches in retroperitoneal laparoscopic adrenalectomy and provide experience and basis for the treatment of adrenal tumors through retroperitoneal approach.

Methods

From July 2015 to February 2018, 112 patients with adrenal lesions underwent retroperitoneal laparoscopic adrenalectomy (RLA) using a 3-port method. Among them, 56 patients underwent RLA via the extra perinephric fat approach (EPFA), 56 patients underwent RLA via the intra perinephric fat approach (IPFA). Clinical data, including preoperative, operative and postoperative management were recorded.

Results

All surgeries were successfully completed, and there was no single patient who died during these surgeries. There was no statistically significant difference between the two groups in blood loss, postoperative complications, vena cava injury, renal cortex injury, peripheral organ injury, and post operation hospital stay. Peritoneum injury occurred more frequently in the EPFA group when compared with the IPEA group (p = 0.042). The average surgery time of the IPEA group is significantly shorter when compared with that of the EPEA group (p < 0.001). Due to serious saponification of the perinephric fat and heavy adhesion to renal fascia, three cases in IPFA group were converted to the EPFA surgery.

Conclusion

RLA is a safe and effective procedure both via extra perinephric fat and intra perinephric fat approaches. IPEA is superior to EPEA in terms of peritoneal injury and duration. The choice may mainly depend on the experience of the surgeon, the characteristics of the adrenal tumor and the nature of the perinephric fat.
The next generation of biopanning: next gen sequencing improves analysis of bacterial display libraries
Authors: Stellwagen Sarah D. , Sarkes Deborah A. , Adams Bryn L. , Hunt Mia A. , Renberg Rebecca L. , Hurley Margaret M. , Stratis-Cullum Dimitra N.
Published: December 2019

Background

Bacterial surface display libraries are a popular tool for novel ligand discovery due to their ease of manipulation and rapid growth rates. These libraries typically express a scaffold protein embedded within the outer membrane with a short, surface-exposed peptide that is either terminal or is incorporated into an outer loop, and can therefore interact with and bind to substrates of interest.

Results

In this study, we employed a novel bacterial peptide display library which incorporates short 15-mer peptides on the surface ofE. coli, co-expressed with the inducible red fluorescent protein DsRed in the cytosol, to investigate population diversity over two rounds of biopanning. The naive library was used in panning trials to select for binding affinity against 3D printing plastic coupons made from polylactic acid (PLA). Resulting libraries were then deep-sequenced using next generation sequencing (NGS) to investigate selection and diversity.

Conclusions

We demonstrated enrichment for PLA binding versus a sapphire control surface, analyzed population composition, and compared sorting rounds using a binding assay and fluorescence microscopy. The capability to produce and describe display libraries through NGS across rounds of selection allows a deeper understanding of population dynamics that can be better directed towards peptide discovery.
Optimized production of a biologically active Clostridium perfringens glycosyl hydrolase phage endolysin PlyCP41 in plants using virus-based systemic expression
Authors: Hammond Rosemarie W. , Swift Steven M. , Foster-Frey Juli A. , Kovalskaya Natalia Y. , Donovan David M.
Published: December 2019

Background

Clostridium perfringens, a gram-positive, anaerobic, rod-shaped bacterium, is the third leading cause of human foodborne bacterial disease and a cause of necrotic enteritis in poultry. It is controlled using antibiotics, widespread use of which may lead to development of drug-resistant bacteria. Bacteriophage-encoded endolysins that degrade peptidoglycans in the bacterial cell wall are potential replacements for antibiotics. Phage endolysins have been identified that exhibit antibacterial activities against several Clostridium strains.

Results

AnEscherichia colicodon-optimized gene encoding the glycosyl hydrolase endolysin (PlyCP41) containing a polyhistidine tag was expressed inE. coli. In addition, TheE. colioptimized endolysin gene was engineered for expression in plants (PlyCP41p) and a plant codon-optimized gene (PlyCP41pc), both containing a polyhistidine tag, were expressed inNicotiana benthamianaplants using a potato virus X (PVX)-based transient expression vector. PlyCP41p accumulated to ~ 1% total soluble protein (100μg/gm f. wt. leaf tissue) without any obvious toxic effects on plant cells, and both the purified protein and plant sap containing the protein lysedC. perfringensstrain Cp39 in a plate lysis assay. Optimal systemic expression of PlyCP41p was achieved at 2 weeks-post-infection. PlyCP41pc did not accumulate to higher levels than PlyCP41p in infected tissue.

Conclusion

We demonstrated that functionally active bacteriophage PlyCP41 endolysin can be produced in systemically infected plant tissue with potential for use of crude plant sap as an effective antimicrobial agent againstC. perfringens.
Salivary gland function in nasopharyngeal carcinoma before and late after intensity-modulated radiotherapy evaluated by dynamic diffusion-weighted MR imaging with gustatory stimulation
Authors: Shi Dai , Qian Jian-Jun , Fan Guo-Hua , Shen Jun-Kang , Tian Ye , Xu Liang
Published: December 2019

Background

Xerostomia caused by radiation-induced salivary glands injury has a considerable impact on patients’ quality of life. Nowadays, the existed different methods of evaluating xerostomia in clinical practice there are still some disadvantages and limitations. This study used diffusion-weighted magnetic resonance imaging (DW-MRI) with gustatory stimulation to assess salivary glands function after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC).

Methods

DW-MRI was performed in 30 NPC patients and swab method was used to calculate rest and stimulated salivary flow rates (SFR). DW sequence at rest and then repeated ten times during stimulation were obtained. Apparent diffusion coefficients (ADCs) maps of three glands were calculated. Patients before and after RT were recorded as xerostomia and non-xerostomia groups separately. Rest and stimulated ADCs, ADCs increase rates (IRs), time to maximum ADCs (Tmax), ADCs change rates (CRs), rest and stimulated SFR, SFR increase rates (IRs) and SFR change rates (CRs) before and after RT were assessed.

Results

The rest and stimulated ADCs of three glands after RT were higher than those before RT (p < 0.001). The rest and stimulated SFR of all salivary glands after RT were lower than those before RT (p < 0.001). A correlation existed between rest ADCs of submandibular glands and rest SFR of submandibular mixed with sublingual glands and full three glands before RT (p = 0.019,p = 0.009), stimulated ADCs and stimulated SFR in parotid glands before RT (p = 0.047). The rest ADCs of parotid glands after RT correlated to XQ scores (p = 0.037).

Conclusions

The salivary glands’ ADCs increased after RT both in rest and stimulated state due to the radiation injury and the ADCs correlated with SFR and XQ scores of evaluating the xerostomia in clinical practice.
Oral health related quality of life of patients with class III skeletal malocclusion before and after orthognathic surgery
Authors: Rezaei Farzad , Masalehi Hiwa , Golshah Amin , Imani Mohammad Moslem
Published: December 2019

Background

Orthognathic surgery includes improvement of morphology and function of occlusion as well as psychological perception and oral health-related quality of life (OHRQoL) of patients. The aim of this study was to determine the OHRQoL of patients with class III skeletal malocclusion before and after orthognathic surgery.

Materials and methods

A total of 112 skeletal class III patients including 39 (34.8%) males and 73 (65.2%) females participated in this descriptive quasi-experimental study in three groups: “prior to orthodontic treatment” (n = 25); “under orthodontic treatment and prior to surgery” (n = 65), and “after surgery” (n = 25). All patients filled out a demographic information questionnaire, the oral health impact profile-14 (OHIP-14), and the orthognathic quality of life questionnaire (OQLQ) under the supervision of the examiner. Data were analyzed using ANOVA, independent samples t-test, Mann Whitney test, and Kruskal-Wallis test.

Results

OHRQoL summary score changed from 14.5 prior to orthodontic treatment to 23.4 prior to surgery and during orthodontic treatment to 5.4 after surgery. These OHRQoL changes were statistically significant (P < 0.001).

Conclusions

Orthognathic surgery matters to patients with class III skeletal malocclusion and significantly improves their OHRQoL.
The psychometric properties of the Barkin index of maternal functioning (BIMF) for the Iranian population
Authors: Mirghafourvand Mojgan , Barkin Jennifer L. , Jafarabadi Mohammad Asghari , Karami Fatemeh , Ghanbari-Homayi Solmaz
Published: December 2019

Background

Mothers’ capability for childcare and compatibility with the maternal role represent important challenges in postpartum care. Given the significance of evaluating maternal functioning, and the lack of adequate standard instruments in Iran for this purpose, the present study was aimed at translating and conducting a psychometric assessment of the Barkin Index of Maternal Functioning (BIMF) for Iranian women.

Methods

The instrument was translated into Persian using the Backward Forward method. The study included 530 women in the postpartum period admitted to healthcare centers in Tabriz, Iran; they were selected through the cluster sampling method. Face, content, and construct (through exploratory and confirmatory analyses) validity were presently examined. Reliability of the questionnaire was determined using the internal consistency and test-retest reliability methods.

Results

Two factors (mom’s needs and competency), emerged based on exploratory factor analysis. The x2/df ratio was less than 5, and the values of the Root Mean Square Error of Approximation (RMSEA) and the Root Mean Square Residual (RMR) were less than 0.08 and 0.1, respectively, verifying the model validity. Cronbach’s alpha coefficient and Intra-class Correlation Coefficient (ICC) were calculated as 0.88 and 0.85, respectively, indicating reliability.

Conclusion

The Persian version of the BIMF is a valid and reliable instrument for measuring the postpartum functioning of Iranian mothers.
Health numeracy skills of medical students:cross-sectional and controlled before-and-after study
Authors: Buljan Ivan , Tokalić Ružica , Marušić Matko , Marušić Ana
Published: December 2019

Background

Although numeracy, defined as understanding and handling numbers, is an important skill for the medical profession, it is not clear whether it changes during graduate medical education and whether it can be improved by specific interventions. The objective of this study was to assess objective and subjective numeracy levels at different stages of medical education and explore whether a research methodology/statistics course improves numeracy levels in a longer period.

Methods

We performed cross-sectional and controlled before-and-after studies. First-year sociology students and first- to sixth-year medical students from the in the cross sectional study and two groups of first-year medical students in a controlled before-and-after study. The intervention was a course on biostatistics and research methodology using blended approach. Numeracy was measured using Subjective Numeracy Scale (Cronbach α = 0.70) and Numeracy Understanding in Medicine instrument (Cronbach α = 0.75).

Results

Whereas first-year medical students did not differ from first-year sociology students in objective numeracy, medicine students had higher results on subjective numeracy. Students from higher years of medical school had generally higher subjective and objective numeracy scores. In the controlled before-and-after study, the intervention group improved more in subjective numeracy (median difference on a 0–8 scale = 0.5, 95% CI 0.3 to 0.7 vs − 0.4, 95% CI − 0.4 to − 0.1, P < 0.001) but not in objective numeracy.

Conclusions

Although the numeracy levels at the beginning of the medical school are within the range of non-medical population, both objective and subjective numeracy improve during the higher years of medical school. Curriculum during medical school may help in numeracy increase, while research methodology training may help to increase subjective but not objective numeracy skills.
Research approvals iceberg: helping it melt away
Authors: Kolstoe Simon E. , Carpenter David
Published: December 2019

Background

In their paper “Research approvals iceberg: how a ‘low-key’ study in England needed 89 professionals to approve it and how we can do better” Petrova and Barclay highlight concerns with the health research regulatory environment in the UK.

Discussion

As long-standing chairs of NHS research ethics committees, researchers, and also academics in research ethics, we are also often frustrated with the regulatory process in the UK. However, we think that Petrova and Barclay’s analysis is misleading because it conflates research ethics with governance and funding processes, thus failing to adequately distinguish between the national coordinating function of the Health Research Authority, local research governance processes, and interactions with research sponsors and/or the Clinical Research Network.
A national intervention to reduce imaging for low back pain by general practitioners: a retrospective economic program evaluation using Medicare Benefits Schedule data
Authors: Morgan Tessa , Wu Jianyun , Ovchinikova Ludmila , Lindner Robyn , Blogg Suzanne , Moorin Rachael
Published: December 2019

Background

The overuse of diagnostic imaging for low back pain (LBP) in Australia results in unnecessary cost to the health system and, for patients, avoidable exposure to radiation. The 2013 NPS MedicineWise LBP program aimed to reduce unnecessary diagnostic imaging for non-specific acute LBP in the Australian primary care setting. The LBP program delivered referral pattern feedback, a decision support tool and patient information to 19,997 (60%) of registered Australian general practitioners (GPs). This study describes the findings from evaluation of the effectiveness of the 2013 LBP program at reducing X-ray and computed tomography (CT) scans of the lower back, and the financial costs and benefits of the program to the government funder.

Methods

The effectiveness of the 2013 LBP program was evaluated using population-based time-series analysis of administrative claims data of Medicare Benefits Schedule (MBS) funded X-ray and CT scan services of the lower back. The CT scan referral trend of non-GP health professionals was used as an observational control group in a Bayesian structural time-series model. A retrospective cost–benefit analysis and cost-effectiveness analysis was conducted using program costs from organisational records and reimbursement data from the MBS.

Results

The 2013 NPS MedicineWise LBP program was associated with a statistically significant 10.85% relative reduction in the volume of CT scans of the lumbosacral region, equating to a cost reduction to the MBS of AUD$11,600,898. The best available estimate of program costs was AUD$141,154. Every dollar of funding spent on the 2013 LBP program saved AUD$82 of funding to the MBS for CT scan reimbursements. Therefore, from the perspective of the Australian Government Department of Health, the 2013 LBP program was cost saving. The program cost AUD$2.82 per CT scan averted in comparison to the scenario of no program. No association between the 2013 NPS MedicineWise LBP program and the volume of X-ray items on the MBS was observed.

Conclusions

The 2013 NPS MedicineWise LBP program reduced CT scan referral by GPs, in line with the program’s messages and clinical guidelines. Reducing this low-value care produced savings to the health system that exceeded the costs of program implementation.
Why does the NHS struggle to adopt eHealth innovations? A review of macro, meso and micro factors
Authors: Asthana Sheena , Jones Ray , Sheaff Rod
Published: December 2019

Background

Having a tax-funded and supposedly ‘National’ Health Service (NHS), one might assume that the UK is well-positioned to roll out eHealth innovations at scale. Yet, despite a strong policy push, the English NHS has been limited in the extent to which it has exploited the potential of eHealth.

Main body

This paper considers a range of macro, meso and micro factors influencing eHealth innovation in the English NHS.

Conclusions

While barriers to eHealth innovation exist at all scales, the fragmentation of the NHS is the most significant factor limiting adoption and diffusion. Rather than addressing problems of fragmentation, national policy seems to have intensified the digital divide. As the recently published NHS Long Term Plan places great emphasis on the role of digital transformation in helping health and care professionals communicate better and enabling people to access the care they need quickly and easily, the implications for the digital divide are likely to be significant for effectiveness, efficiency and equity.
Ultrasonic liver steatosis quantification by a learning-based acoustic model from a novel shear wave sequence
Authors: Shi Xiudong , Ye Wen , Liu Fengjun , Zhang Rengyin , Hou Qinguo , Shi Chunzi , Yu Jinhua , Shi Yuxin
Published: December 2019

Background

An efficient and accurate approach to quantify the steatosis extent of liver is important for clinical practice. For the purpose, we propose a specific designed ultrasound shear wave sequence to estimate ultrasonic and shear wave physical parameters. The utilization of the estimated quantitative parameters is then studied.

Results

Shear wave attenuation, shear wave absorption, elasticity, dispersion slope and echo attenuation were simultaneously estimated and quantified from the proposed novel shear wave sequence. Then, a regression tree model was utilized to learn the connection between the space represented by all the physical parameters and the liver fat proportion. MR mDIXON quantification was used as the ground truth for liver fat quantification. Our study included a total of 60 patients. Correlation coefficient (CC) with the ground truth were applied to mainly evaluate different methods for which the corresponding values were − 0.25, − 0.26, 0.028, 0.045, 0.46 and 0.83 for shear wave attenuation, shear wave absorption, elasticity, dispersion slope, echo attenuation and the learning-based model, respectively. The original parameters were extremely outperformed by the learning-based model for which the root mean square error for liver steatosis quantification is only 4.5% that is also state-of-the-art for ultrasound application in the related field.

Conclusions

Although individual ultrasonic and shear wave parameters were not perfectly adequate for liver steatosis quantification, a promising result can be achieved by the proposed learning-based acoustic model based on them.
Thoracic tumor resection combined with SVC replacement using autologous pericardium
Authors: Jiang Sicong , Hu Hao , Guo Changying , Jiang Feng , Liu Xi , Tang Lang , Tang Jianjun , Cheng Xiaoliang
Published: December 2019

Background

Invasion of the superior vena cava (SVC) by thoracic tumors and occurrence of SVC syndrome are often encountered in clinical practice; but the prognosis in these cases is poor. Replacement of the SVC with autologous pericardial tissue is rarely performed. In this study, we sought to investigate the postoperative outcomes of this rare procedure.

Methods

We performed a retrospective analysis of six patients who underwent SVC replacement using autologous pericardial tissue between October 2010 and November 2016. We collected data on the patients’ pathological features, operative characteristics, postoperative outcomes, and survival.

Results

All six patients were male with an average age of 52 years (range, 18–62 years). Three of the patients had lung cancer, one had stage III thymoma, and two had germinoma. Four of the six patients had mild or moderate superior vena cava compression and no corresponding clinical symptoms. The other two patients had severe compression and obvious symptoms of SVC syndrome, with the typical swelling of the face, eyelids, and upper extremities. All six patients underwent complete tumor resection, with two of the lung cancer patients undergoing right lobectomy and one undergoing right pneumonectomy. With respect to the postoperative outcomes, one patient died, whereas the others did not develop any major complications. At the end of the follow-up period, five of the patients were alive and none of the patients had developed thrombosis in the grafts.

Conclusions

Our findings indicated that SVC replacement with autologous pericardium is technically feasible and safe, with few postoperative complications and favorable long-term effects. Although it has some limitations, this method appears to be useful in achieving SVC reconstruction of moderate size. SVC replacement with autologous pericardium appears to have the potential for widespread clinical use.
Gender and active travel: a qualitative data synthesis informed by machine learning
Authors: Haynes Emily , Green Judith , Garside Ruth , Kelly Michael P. , Guell Cornelia
Published: December 2019

Background

Innovative approaches are required to move beyond individual approaches to behaviour change and develop more appropriate insights for the complex challenge of increasing population levels of activity. Recent research has drawn on social practice theory to describe the recursive and relational character of active living but to date most evidence is limited to small-scale qualitative research studies. To ‘upscale’ insights from individual contexts, we pooled data from five qualitative studies and used machine learning software to explore gendered patterns in the context of active travel.

Methods

We drew on 280 transcripts from five research projects conducted in the UK, including studies of a range of populations, travel modes and settings, to conduct unsupervised ‘topic modelling analysis’. Text analytics software, Leximancer, was used in the first phase of the analysis to produce inter-topic distance maps to illustrate inter-related ‘concepts’. The outputs from this first phase guided a second researcher-led interpretive analysis of text excerpts to infer meaning from the computer-generated outputs.

Results

Guided by social practice theory, we identified ‘interrelated’ and ‘relating’ practices across the pooled datasets. For this study we particularly focused on respondents’ commutes, travelling to and from work, and on differentiated experiences by gender. Women largely described their commute as multifunctional journeys that included the school run or shopping, whereas men described relatively linear journeys from A to B but highlighted ‘relating’ practices resulting from or due to their choice of commute mode or journey such as showering or relaxing. Secondly, we identify a difference in discourses about practices across the included datasets. Women spoke more about ‘subjective’, internal feelings of safety (‘I feel unsafe’), whereas men spoke more about external conditions (‘it is a dangerous road’).

Conclusion

This rare application of machine learning to qualitative social science research has helped to identify potentially important differences in co-occurrence of practices and discourses about practice between men’s and women’s accounts of travel across diverse contexts. These findings can inform future research and policy decisions for promoting travel-related social practices associated with increased physical activity that are appropriate across genders.
HTLV-1 CTCF-binding site is dispensable for in vitro immortalization and persistent infection in vivo
Authors: Martinez Michael P. , Cheng Xiaogang , Joseph Ancy , Al-Saleem Jacob , Panfil Amanda R. , Palettas Marilly , Dirksen Wessel P. , Ratner Lee , Green Patrick L.
Published: December 2019

Background

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL) and the neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The exact mechanism(s) through which latency and disease progression are regulated are not fully understood. CCCTC-binding factor (CTCF) is an 11-zinc finger, sequence-specific, DNA-binding protein with thousands of binding sites throughout mammalian genomes. CTCF has been shown to play a role in organization of higher-order chromatin structure, gene expression, genomic imprinting, and serve as a barrier to epigenetic modification. A viral CTCF-binding site (vCTCF-BS) was previously identified within the overlapping p12 (sense) and Hbz (antisense) genes of the HTLV-1 genome. Thus, upon integration, HTLV-1 randomly inserts a vCTCF-BS into the host genome. vCTCF-BS studies to date have focused primarily on HTLV-1 chronically infected or tumor-derived cell lines. In these studies, HTLV-1 was shown to alter the structure and transcription of the surrounding host chromatin through the newly inserted vCTCF-BS. However, the effects of CTCF binding in the early stages of HTLV-1 infection remains unexplored. This study examines the effects of the vCTCF-BS on HTLV-1-induced in vitro immortalization and in vivo viral persistence in infected rabbits.

Results

HTLV-1 and HTLV-1∆CTCF LTR-transactivation, viral particle production, and immortalization capacity were comparable in vitro. The total lymphocyte count, proviral load, and Hbz gene expression were not significantly different between HTLV-1 and HTLV-1∆CTCF-infected rabbits throughout a 12 week study. However, HTLV-1∆CTCF-infected rabbits displayed a significantly decreased HTLV-1-specific antibody response compared to HTLV-1-infected rabbits.

Conclusions

Mutation of the HTLV-1 vCTCF-BS does not significantly alter T-lymphocyte transformation capacity or early in vivo virus persistence, but results in a decreased HTLV-1-specific antibody response during early infection in rabbits. Ultimately, understanding epigenetic regulation of HTLV-1 gene expression and pathogenesis could provide meaningful insights into mechanisms of immune evasion and novel therapeutic targets.
Combination of the natural compound Periplocin and TRAIL induce esophageal squamous cell carcinoma apoptosis in vitro and in vivo: Implication in anticancer therapy
Authors: Han Lujuan , Dai Suli , Li Zhirong , Zhang Cong , Wei Sisi , Zhao Ruinian , Zhang Hongtao , Zhao Lianmei , Shan Baoen
Published: December 2019

Background

Esophageal cancer is one of the most common malignant tumors in the world. With currently available therapies, only 20% ~ 30% patients can survive this disease for more than 5 years. TRAIL, a natural ligand for death receptors that can induce the apoptosis of cancer cells, has been explored as a therapeutic agent for cancers, but it has been reported that many cancer cells are resistant to TRAIL, limiting the potential clinical use of TRAIL as a cancer therapy. Meanwhile, Periplocin (CPP), a natural compound from dry root of Periploca sepium Bge, has been studied for its anti-cancer activity in a variety of cancers. It is not clear whether CPP and TRAIL can have activity on esophageal squamous cell carcinoma (ESCC) cells, or whether the combination of these two agents can have synergistic activity.

Methods

We used MTS assay, flow cytometry and TUNEL assay to detect the effects of CPP alone or in combination with TRAIL on ESCC cells. The mechanism of CPP enhances the activity of TRAIL was analyzed by western blot, dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay. The anti-tumor effects and the potential toxic side effects of CPP alone or in combination with TRAIL were also evaluated in vivo.

Results

In our studies, we found that CPP alone or in combination with TRAIL could inhibit the proliferation of ESCC cells and induce apoptosis, and we certificated that combination of two agents exert synergized functions. For the first time, we identified FoxP3 as a key transcriptional repressor for both DR4 and DR5. By down-regulating FoxP3, CPP increases the expression of DR4/DR5 and renders ESCC cells much more sensitive to TRAIL. We also showed that CPP reduced the expression of Survivin by inhibiting the activity of Wnt/β-catenin pathway. All these contributed to synergistic activity of CPP and TRAIL on ESCC cells in vitro and in vivo.

Conclusion

Our data suggest that CPP and TRAIL could be further explored as potential therapeutic approach for esophageal cancer.
The somatic mutation landscape of the human body
Authors: García-Nieto Pablo E. , Morrison Ashby J. , Fraser Hunter B.
Published: December 2019

Background

Somatic mutations in healthy tissues contribute to aging, neurodegeneration, and cancer initiation, yet they remain largely uncharacterized.

Results

To gain a better understanding of the genome-wide distribution and functional impact of somatic mutations, we leverage the genomic information contained in the transcriptome to uniformly call somatic mutations from over 7500 tissue samples, representing 36 distinct tissues. This catalog, containing over 280,000 mutations, reveals a wide diversity of tissue-specific mutation profiles associated with gene expression levels and chromatin states. For example, lung samples with low expression of the mismatch-repair geneMLH1show a mutation signature of deficient mismatch repair. In addition, we find pervasive negative selection acting on missense and nonsense mutations, except for mutations previously observed in cancer samples, which are under positive selection and are highly enriched in many healthy tissues.

Conclusions

These findings reveal fundamental patterns of tissue-specific somatic evolution and shed light on aging and the earliest stages of tumorigenesis.
The effect of an educational program for pregnant women to prevent allergic diseases in infants: study protocol for a randomized controlled trial
Authors: Nakamura Rie , Ishiguro Nao , Naru Eiji , Ishitsuka Yukiko , Nakade Masato , Nezu Yoko
Published: December 2019

Background

Allergic diseases in infants have dramatically increased in developed countries during the past few decades. To date, extensive research has been done on risk factors for allergies in infancy, and preventive measures against them. However, the effect of the primary approach to preventing infantile allergy is still limited.

The aim of this trial is to evaluate whether prenatal education interventions, including the latest public research results on allergic diseases, prevent the onset of infant allergies.

Methods/design

We designed a randomized controlled, two-arm (standard prenatal education vs our education), parallel-group, assessor-blind trial. A sample of 120 pregnant women will be recruited at Chiba Aiyu-kai Kinen Hospital and allocation is by computer-generated randomization.

Pregnant women in the intervention arm participate in the childbirth education program established by the specialist and a pediatric allergy educator. The program was developed based on evidences supporting interventions on primary prevention, which are suggested to be beneficial to infantile allergies in recent studies.

The primary objective of the study is to determine whether it is possible to establish effective behaviors for allergy prevention in early infancy in the children of pregnant women who participate in an educational program developed by pediatric allergy specialists. Four months after birth, their behaviors will be compared against those of pregnant women who did not participate in the program.

Discussion

Allergies are common in many individuals worldwide, and can be present from babyhood through the person’s lifetime. One of the strong points of this study is that it should provide pregnant women with accumulated information on preventive knowledge against allergy, that can be effective in some cases, and that women can apply a combination of these behaviors before and after pregnancy. The results of our program will be publicized to help change the behaviors of mothers, and, if the program is effective, for preventing allergies in infants, it will be disclosed worldwide as a new preventive strategy for allergy in infants.

Trial registration

UMIN-CTR, ID: UMIN000034730 Retrospectively registered on 1 December 2018.
A review on the eco-epidemiology and clinical management of human granulocytic anaplasmosis and its agent in Europe
Authors: Matei Ioana A. , Estrada-Peña Agustín , Cutler Sally J. , Vayssier-Taussat Muriel , Varela-Castro Lucía , Potkonjak Aleksandar , Zeller Herve , Mihalca Andrei D.
Published: December 2019

Anaplasma phagocytophilum is the agent of tick-borne fever, equine, canine and human granulocytic anaplasmosis. The common route of A. phagocytophilum transmission is through a tick bite, the main vector in Europe being Ixodes ricinus. Despite the apparently ubiquitous presence of the pathogen A. phagocytophilum in ticks and various wild and domestic animals from Europe, up to date published clinical cases of human granulocytic anaplasmosis (HGA) remain rare compared to the worldwide status. It is unclear if this reflects the epidemiological dynamics of the human infection in Europe or if the disease is underdiagnosed or underreported. Epidemiologic studies in Europe have suggested an increased occupational risk of infection for forestry workers, hunters, veterinarians, and farmers with a tick-bite history and living in endemic areas. Although the overall genetic diversity of A. phagocytophilum in Europe is higher than in the USA, the strains responsible for the human infections are related on both continents. However, the study of the genetic variability and assessment of the difference of pathogenicity and infectivity between strains to various hosts has been insufficiently explored to date. Most of the European HGA cases presented as a mild infection, common clinical signs being pyrexia, headache, myalgia and arthralgia. The diagnosis of HGA in the USA was recommended to be based on clinical signs and the patient’s history and later confirmed using specialized laboratory tests. However, in Europe since the majority of cases are presenting as mild infection, laboratory tests may be performed before the treatment in order to avoid antibiotic overuse. The drug of choice for HGA is doxycycline and because of potential for serious complication the treatment should be instituted on clinical suspicion alone.
Factors affecting perception of the normal pediatric appendix on sonography
Authors: Castro Denise , Yang Joseph , Patel Prasan , Sauerbrei Eric , Hopman Wilma , Kolar Mila , Soboleski Don
Published: December 2019

Background

To determine if an inherent perception skill along with sonographer experience, knowledge base, scanning time play a role in the identification of the normal appendix in the pediatric population. This is a retrospective review of pediatric (< 18 years old) patients with a clinical suspicion of acute appendicitis presenting to the emergency department of two affiliated academic tertiary care hospitals over a 1-year time span. All patients had a sonogram performed by 1/15 sonographers or by 1/8 on-call radiology residents. Those with a normal or non-visualized appendix with subsequent discharge from ER were included in the study. Patient demographics, minutes spent scanning, and sonographer years of experience in general abdominal scanning and residents level of training were recorded.

Results

Of the 127 patients included in the study, 51 (40%) were male and 76 (60%) were female, with a mean age of 11.8 ± 4.2 years. Sonographers who failed to see a normal appendix had less experience (median 8 years) than those who did visualize the appendix (median 15 years), p ≤ 0.001. Longer time spent scanning was also associated with visualizing a normal appendix (20.4 versus 29.1 min, p = 0.001). In multivariable logistic regression, more time spent scanning (OR 1.04, 95% CI 1.01, 1.07, p = 0.012) and increased sonographer experience (OR 1.07, 95% CI 1.02, 1.13, p = 0.012) resulted in greater odds of perceiving the appendix. The top 4 were significantly more likely to visualize the appendix (88.0%) than all of the other combined (20.8%, p < 0.001), and they also had substantially more experience (median 15 years versus 8 years, p < 0.001). Overall, sonographers were more likely to see a normal appendix (61%) than the residents (14%), p < 0.001.

Conclusion

Sonography to rule out appendicitis in the pediatric patient is in general most successful when performed by experienced sonographers with adequate time to perform the scan. Triaging patients to those sonographers who have displayed optimal perceptual ability of the normal appendix may help optimize patient care and hospital resources. Having experienced sonographers available after hours would allow for optimal care in the setting of ‘query’ appendicitis.
Comparison of methylation patterns generated from genomic and cell-line derived DNA using the Illumina Infinium MethylationEPIC BeadChip array
Authors: Smyth L. J. , Kilner J. , Maxwell A. P. , McKnight A. J.
Published: December 2019

Objectives

Genomic DNA (gDNA) is the optimal source of DNA for methylation analysis. This study compared methylation patterns in gDNA derived from blood with cell-line derived DNA (clDNA) from the same individuals. The clDNA had been generated via an Epstein-Barr virus transformation of the participant’s lymphocytes. This analysis sought to determine whether clDNA has the potential to be utilised in lieu of finite/unavailable gDNA in methylation analyses using Illumina Infinium MethylationEPIC BeadChip arrays that assess 862,927 CpG sites.

Results

DNA samples were divided into two groups with eight gDNA and eight matched clDNA samples compared in each group (n = 16 individuals with 32 samples in total). Methylation patterns for gDNA samples generated for both groups were compared to the clDNA equivalent samples using Partek® Genomics Suite® to assess whether the significantly different CpG sites were consistent between both groups. In total, 28,632 CpG sites with significantly different levels of methylation (p < ×10−8) were common to both groups while 828,072 CpG sites assessed by the MethylationEPIC array were not significantly different in either group. This indicates that there is potential for clDNA to be used as a replacement for finite gDNA samples when absolutely necessary in DNA methylation studies.
Crowdsourced dataset to study the generation and impact of text highlighting in classification tasks
Authors: Ramírez Jorge , Baez Marcos , Casati Fabio , Benatallah Boualem
Published: December 2019

Objectives

Text classification is a recurrent goal in machine learning projects and a typical task in crowdsourcing platforms. Hybrid approaches, leveraging crowdsourcing and machine learning, work better than either in isolation and help to reduce crowdsourcing costs. One way to mix crowd and machine efforts is to have algorithms highlight passages from texts and feed these to the crowd for classification. In this paper, we present a dataset to study text highlighting generation and its impact on document classification.

Data description

The dataset was created through two series of experiments where we first asked workers to (i) classify documents according to a relevance question and to highlight parts of the text that supported their decision, and on a second phase, (ii) to assess document relevance but supported by text highlighting of varying quality (six human-generated and six machine-generated highlighting conditions). The dataset features documents from two application domains: systematic literature reviews and product reviews, three document sizes, and three relevance questions of different levels of difficulty. We expect this dataset of 27,711 individual judgments from 1851 workers to benefit not only this specific problem domain, but the larger class of classification problems where crowdsourced datasets with individual judgments are scarce.
Gender discrepancy in research activities during radiology residency
Authors: Vernuccio Federica , Arzanauskaite Monika , Turk Sevcan , Torres Estefania Terrazas , Choa Joanna Marie D. , Udare Ashlesha Satish , Haroun Dina , Serra Maria Mercedes , Shelmerdine Susan , Bold Bayarbaatar , Bae Jae Seok , Romero Eduardo Estades , Vilgrain Valérie
Published: December 2019

Objective

To investigate the presence of gender disparity in academic involvement during radiology residency and to identify and characterize any gender differences in perceived barriers for conducting research.

Methods

An international call for participation in an online survey was promoted via social media and through multiple international and national radiological societies. A 35-question survey invited radiology trainees worldwide to answer questions regarding exposure and barriers to academic radiology during their training. Gender differences in response proportions were analyzed using either Fisher’s exact or chi-squared tests.

Results

Eight hundred fifty-eight participants (438 men, 420 women) from Europe (432), Asia (241), North and South America (144), Africa (37), and Oceania (4) completed the survey. Fewer women radiology residents were involved in research during residency (44.3%, 186/420 vs 59.4%, 260/438; p ≤ 0.0001) and had fewer published original articles (27.9%, 117/420 vs. 40.2%, 176/438; p = 0.001).

Women were more likely to declare gender as a barrier to research (24.3%, 102/420 vs. 6.8%, 30/438; p < 0.0001) and lacked mentorship/support from faculty (65%, 273/420 vs. 55.7%, 244/438; p = 0.0055). Men were more likely to declare a lack of time (60.3%, 264/438 vs. 50.7%, 213/420; p = 0.0049) and lack of personal interest (21%, 92/438 vs. 13.6%, 57/420, p = 0.0041) in conducting research.

Conclusion

Fewer women were involved in academic activities during radiology residency, resulting in fewer original published studies compared to their men counterparts. This is indicative of an inherent gender imbalance. Lack of mentorship reported by women radiologists was a main barrier to research.
Menstrual blood-derived stem cells: toward therapeutic mechanisms, novel strategies, and future perspectives in the treatment of diseases
Authors: Chen Lijun , Qu Jingjing , Cheng Tianli , Chen Xin , Xiang Charlie
Published: December 2019

Menstrual blood-derived stem cells (MenSCs) have great potential in the treatment of various diseases. As a novel type of mesenchymal stem cells (MSCs), MenSCs have attracted more interest due to their therapeutic effects in both animal models and clinical trials. Here, we described the differentiation, immunomodulation, paracrine, homing, and engraftment mechanisms of MenSCs. These include differentiation into targeting cells, immunomodulation with various immune cells, the paracrine effect on secreting cytokines, and homing and engraftment into injured sites. To better conduct MenSC-based therapy, some novel hotspots were proposed such as CRISPR (clustered regularly interspaced short palindromic repeats)/cas9-mediated gene modification, exosomes for cell-free therapy, single-cell RNA sequence for precision medicine, engineered MenSC-based therapy for the delivery platform, and stem cell niches for improving microenvironment. Subsequently, current challenges were elaborated on, with regard to age of donor, dose of MenSCs, transplantation route, and monitoring time. The management of clinical research with respect to MenSC-based therapy in diseases will become more normative and strict. Thus, a more comprehensive horizon should be considered that includes a combination of traditional solutions and novel strategies. In summary, MenSC-based treatment has a great potential in treating diseases through diverse strategies, and more therapeutic mechanisms and novel strategies need to be elucidated for future regenerative medicine and clinical applications.
Comparative prebiotic activity of mixtures of cereal grain polysaccharides
Authors: Harris Suzanne , Monteagudo-Mera Andrea , Kosik Ondrej , Charalampopoulos Dimitris , Shewry Peter , Lovegrove Alison
Published: December 2019

The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan. These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats. Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity. AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios. Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH). Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8–24 h of fermentation, however β-glucan alone did not show prebiotic activity. The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet. This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential.
Microbial inoculants: reviewing the past, discussing the present and previewing an outstanding future for the use of beneficial bacteria in agriculture
Authors: Santos Mariana Sanches , Nogueira Marco Antonio , Hungria Mariangela
Published: December 2019

More than one hundred years have passed since the development of the first microbial inoculant for plants. Nowadays, the use of microbial inoculants in agriculture is spread worldwide for different crops and carrying different microorganisms. In the last decades, impressive progress has been achieved in the production, commercialization and use of inoculants. Nowadays, farmers are more receptive to the use of inoculants mainly because high-quality products and multi-purpose elite strains are available at the market, improving yields at low cost in comparison to chemical fertilizers. In the context of a more sustainable agriculture, microbial inoculants also help to mitigate environmental impacts caused by agrochemicals. Challenges rely on the production of microbial inoculants for a broader range of crops, and the expansion of the inoculated area worldwide, in addition to the search for innovative microbial solutions in areas subjected to increasing episodes of environmental stresses. In this review, we explore the world market for inoculants, showing which bacteria are prominent as inoculants in different countries, and we discuss the main research strategies that might contribute to improve the use of microbial inoculants in agriculture.