bluuebunny/crossref_metadata_2025 huggingface dataset:
Achromobacter spp. healthcare associated infections in the French West Indies: a longitudinal study from 2006 to 2016
Authors: Marion-Sanchez Karine , Pailla Karine , Olive Claude , Le Coutour Xavier , Derancourt Christian
Published: September 2019

Background

Bacteria of the Achromobacter genus, more particularly xylosoxidans species, are responsible for various healthcare associated infections (HAI) which are increasingly described since the last decade. Cystic fibrosis (CF) patients are considered as potential reservoirs in hospitals. We performed a retrospective study to estimate the frequencies of Achromobacter spp. HAI among patients from French West Indies, to determine characteristics of infected patients and establish a possible link between CF and infections.

Methods

All adults with at least one Achromobacter spp. positive sample and infection criteria in accordance with European official definitions of HAI, hospitalized in University Hospital of Martinique from 2006 to 2016 for more than 48 h, were included. Patient clinical features, immune status and underlying diseases were obtained from medical files. A list of CF patients was given by clinicians.

Antibiotic-susceptibility profiles of the strains were determined using an automated method.

Results

Mean incidence density was 0.038/1000 days of hospitalization. Achromobacter spp. HAI evolved as an endemic situation with a low but pretty much stable incidence rate over the 11-year observation period. An epidemic peak was noticed in 2013. Among the 66 included patients, 56.1% were immunocompetent and no one had CF. Pneumonia and bacteraemia were the two main HAI. Among the 79 isolated strains, 92.4% were resistant to at least 1 major antibiotic and 16.4% met the definition of multidrug-resistant bacteria.

Conclusions

This microorganism, little known in our country because of the scarcity of CF patients, represents a threat for both immunosuppressed and immunocompetent patients and a therapeutic challenge because of its high resistance.
Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data
Authors: Schmid Sabine , Klingbiel Dirk , Aebi Stefan , Goldhirsch Aron , Mamot Christoph , Munzone Elisabetta , Nolè Franco , Oehlschlegel Christian , Pagani Olivia , Pestalozzi Bernhard , Rochlitz Christoph , Thürlimann Beat , von Moos Roger , Weder Patrik , Zaman Khalil , Ruhstaller Thomas
Published: September 2019

Background

The impact of HER2-targeted therapy alone followed by the addition of chemotherapy at disease progression (PD) versus upfront combination was investigated by the SAKK 22/99 trial. The aim of this exploratory analysis of the SAKK 22/99 trial was to characterize the specific subset of patients deriving long-term benefit from trastuzumab monotherapy alone and to identify potential predictive factors of long-term response.

Methods

This is an unplanned post-hoc analysis of patients randomized to Arm A (trastuzumab monotherapy). Patients were divided in two groups: patients with durable clinical benefit from trastuzumab monotherapy and short-term responders without durable clinical benefit from trastuzumab monotherapy Univariate and multivariate analyses of clinical characteristics correlating with response duration was performed.

Results

Eighty six patients were randomized in arm A, 24 patients (28%) were long-term responders and 62 (72%) were short-term responders with a 5y-overall survival (OS) of 54% (95% CI 31–72) and of 18% (95%CI 10–30), respectively. Absence of ER expression, absence of PgR expression and presence of visceral disease emerged as possible negative predictive factors for durable clinical benefit.

Conclusion

Durable clinical benefit can be achieved with trastuzumab monotherapy in a subgroup of HER2-positive patients with advanced disease and it is predictive for longer OS. Further investigations of predictive biomarkers are necessary to better characterize this subgroup of patients and develop further de-escalating strategies.

Trial registration

NCT00004935; first posted 27.01.2003, retrospectively registered.
Radioablation +/− hormonotherapy for prostate cancer oligorecurrences (Radiosa trial): potential of imaging and biology (AIRC IG-22159)
Authors: Marvaso Giulia , Ciardo Delia , Corrao Giulia , Gandini Sara , Fodor Cristiana , Zerini Dario , Rojas Damaris Patricia , Augugliaro Matteo , Bonizzi Giuseppina , Pece Salvatore , Cattani Federica , Mazzocco Ketti , Mistretta Francesco Alessandro , Musi Gennaro , Alessi Sarah , Petralia Giuseppe , Pravettoni Gabriella , De Cobelli Ottavio , Di Fiore Pier Paolo , Viale Giuseppe , Orecchia Roberto , Jereczek-Fossa Barbara Alicja
Published: September 2019

Background

Prostate cancer (PCa) is the second most common cancer among men. New imaging-modalities have increased the diagnosed patients with limited number of metastasis after primary curative therapy, introducing so-called oligometastatic state. Stereotactic body radiotherapy (SBRT) is emerging as a low-toxicity treatment to erase PCa localizations and postpone androgen deprivation therapy (ADT). A deeper understanding of the predictive role of biomarkers is desirable for a targeted treatment selection and surveillance programs. The aims of the RADIOSA trial are:

Compare SBRT +/− ADT for oligorecurrent-castration-sensitive PCa (OCS-PCa) in terms of efficacy, toxicity and Quality of Life (QoL).

Develop biology/imaging based prognostic tool that allows identifying OCS-PCa subclasses.

Methods

This is a randomized phase II clinical trial, recruiting 160 OCS-PCa in 3 years, with progression-free survival (PFS) as primary endpoint. Three tasks will be developed:

Randomized clinical study (3 years for accrual and 2 years for follow-up and data analysis);

Imaging study, including imaging registration and METastasis Reporting and Data System (MET-RADS) criteria;

Pre-clinical study, development of a biobank of blood samples for the analysis of neutrophil-to-lymphocyte ratio and preparatory for a subsequent miRNA profiling.

We aim to determine which arm is justified for testing in a subsequent Phase III trial. A decision-tree algorithm, based on prognosis, biological phenotype and imaging profile, will be developed.

Discussion

Recruiting will start in July 2019. SBRT will allow obtaining excellent PFS, local control, QoL and low toxicity. In SBRT arm, ADT deferral will allow for a drug-holiday, delaying the detrimental impact on QoL. A sufficient number of blood samples will be collected to perform biological patient profiling. A stratification tool will be established with an analysis of morphological and functional imaging, based on the use of MET-RADS criteria.

So, in conclusion, RADIOSA aims to define the optimal management of bone/nodal PCa relapses in a SBRT regimen. This study will increase our knowledge on low-burden metastatic PCa in the era of high precision and high technology personalized medicine, offering highly effective therapy in terms of clinical outcome and cost-effectiveness.

Trial registration

The RADIOSA study was prospectively registered at clinicaltrials.gov (NCT03940235, May 2019).
Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol
Authors: Ribera I. , Ruiz A. , Sánchez O. , Eixarch E. , Antolín E. , Gómez-Montes E. , Pérez-Cruz M. , Cruz-Lemini M. , Sanz-Cortés M. , Arévalo S. , Ferrer Q. , Vázquez E. , Vega L. , Dolader P. , Montoliu A. , Boix H. , Simões R. V. , Masoller N. , Sánchez-de-Toledo J. , Comas M. , Bartha J. M. , Galindo A. , Martínez J.M. , Gómez-Roig L. , Crispi F. , Gómez O. , Carreras E. , Cabero L. , Gratacós E. , Llurba E.
Published: September 2019

Background

Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies.

Methods

Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO).

Discussion

The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children’s neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD.

Trial registration

NCT02996630, on 4th December 2016 (retrospectively registered).
Childhood MMR vaccination and the incidence rate of measles infection: a ten year longitudinal cohort study of American children born in the 1990s
Authors: Geier David A. , Kern Janet K. , Geier Mark R.
Published: September 2019

Background

Measles (rubeola) is a highly contagious disease with significant morbidity/mortality. Measles-Mumps-Rubella (MMR) is a live-attenuated vaccine used in the United States (US) since the early 1970s to prevent measles infection. This retrospective longitudinal cohort study examined childhood MMR vaccination effectiveness (VE) on preventing diagnosed measles cases.

Methods

The Independent Healthcare Research Database (IHRD) is composed of non-identifiable linked eligibility and claim healthcare records prospectively generated from the Florida Medicaid system. The SAS system was utilized to examine a cohort of 101,736 persons eligible for Florida Medicaid from 1990 to 2009 and continuously eligible with ≥10 outpatient office visits during the 120-month period following birth. There were 32,870 persons (224,492 person-years) in the cohort receiving a single dose of childhood MMR vaccine (vaccinated) and 43,538 persons (434,637 person-years) in an unvaccinated cohort (no exposures to measles-containing vaccine). The frequency of diagnosed measles (ICD-9 code: 055xxx) was examined. Cox proportional hazards models evaluated MMR vaccination and diagnosed measles over time.

Results

MMR vaccinated cohort members were at significantly reduced risk of measles in the unadjusted (VE = 83.6, 95% CI = 67.2–91.8%) and adjusted (VE = 80.7, 95% CI = 61.5–83.9%) models as compared to the unvaccinated cohort. VE = 80% among younger MMR recipients (12–15 months), whereas VE = 90% among older MMR recipients (16–20 months) as compared to the unvaccinated cohort.

Conclusion

Routine childhood MMR vaccination significantly reduced the incidence rate of childhood measles infections, and the VE was greater in the older recipients (16–20 months) than in the younger recipients (12–15 months).
“I just wish it becomes part of routine care”: healthcare providers’ knowledge, attitudes and perceptions of screening for maternal mental health during and after pregnancy: a qualitative study
Authors: McCauley Mary , Brown Abigail , Ofosu Bernice , van den Broek Nynke
Published: September 2019

Background

Maternal mental health is an international public health concern. Many women experience mental ill-health during and after pregnancy, but assessment is not part of routine maternity care in many low- and middle-income countries. Healthcare providers are in a position to identify and support women who experience mental health disorders during and after pregnancy. We sought to investigate the knowledge, attitudes and perceptions of routine screening for maternal mental health during and after pregnancy among healthcare providers providing routine maternity care in Accra, Ghana. Enabling factors, barriers and potential management options to routinely screen maternal mental health during and after pregnancy were explored.

Methods

Semi-structured key informant interviews (n = 20) and one focus group discussion (n = 4) were conducted with healthcare providers working in one public hospital in Accra, Ghana. Transcribed interviews were coded by topic and then grouped into categories. Thematic framework analysis was undertaken to identify emerging themes.

Results

Most healthcare providers are aware of the importance of maternal mental health and would be keen to help women who experience mental ill-health during and after pregnancy, if resources were available to do so. An enabling factor was the suggestion of introducing a culturally appropriate mental health screening tool. However, compromised mental health was often considered a ‘spiritual issue’ and not routinely screened for by healthcare providers, nor requested by women. Barriers to the provision of quality maternal mental health care included lack of trained staff and lack of time.

Conclusions

Healthcare providers are aware of the problem of the lack of maternal mental health provision during and after pregnancy and are open to developing protocols to improve care. Currently, screening for maternal mental ill-health is not part of routine maternity care. The establishment of such a service requires the reprioritisation of workloads, further training, and a change in the attitudes and practices of healthcare providers. Education to change the attitudes of healthcare providers, women and the wider community towards mental health is needed. The development and implementation of culturally appropriate guidelines would be beneficial and result in better quality of maternity care.
“Who needs secure services for personality disorder?” Results of an expert Delphi study with professional staff
Authors: Foyston Zoe , Taylor Celia , Freestone Mark
Published: September 2019

Background

Personality Disorder (PD) is an enduring, multi-faceted mental disorder, associated with adverse health effects, difficulties with interpersonal relationships and in some cases increased risk to others. A limited number of dedicated forensic mental health services are available for serious offenders with severe personality disorder. The recent Offender Personality Disorder (OPD) strategy aims to ensure that most such offenders are treated in prison rather than secure psychiatric services, except in highly complex cases where this is not possible. While the strategy sets out very broad criteria relating to this, greater clarity is needed to support decisions about appropriate transfer and hence enhance public protection. This study explored which characteristics professional experts associate with appropriate transfer from prison to forensic mental health services for high-risk offenders with PD.

Method

A modified Delphi survey distributed through an online survey system was conducted in two-rounds with a group of professional experts recruited from forensic mental healthcare; criminal justice and specialist commissioning.

Results

Fifty-one (56%) respondents completed stage one of the Delphi and 34 (61%) of these completed stage two. Consensus was reached for a total of 22 items indicating complexity, including co-morbid mental illness, high level of risk, lack of progress in prison and high motivation for treatment. A preliminary checklist for these factors was developed. Panel members consistently emphasised the importance of the individual’s presenting need, the overall clinical picture and formulation in their free text responses.

Conclusions

Professionals face a complex picture when making decisions regarding suitability for hospital admission for high-risk male offenders with PD, with varied opinions amongst professional experts as to priorities for intervention and a focus on individual needs through formulation. It was, nevertheless, possible to condense these views into a set of consistent variables that can be used to highlight the need for transfer into hospital-based treatment services.
Assessing the micro-scale environment using Google Street View: the Virtual Systematic Tool for Evaluating Pedestrian Streetscapes (Virtual-STEPS)
Authors: Steinmetz-Wood Madeleine , Velauthapillai Kabisha , O’Brien Grace , Ross Nancy A.
Published: September 2019

Background

Altering micro-scale features of neighborhood walkability (e.g., benches, sidewalks, and cues of social disorganization or crime) could be a relatively cost-effective method of creating environments that are conducive to active living. Traditionally, measuring the micro-scale environment has required researchers to perform observational audits. Technological advances have led to the development of virtual audits as alternatives to observational field audits with the enviable properties of cost-efficiency from elimination of travel time and increased safety for auditors. This study examined the reliability of the Virtual Systematic Tool for Evaluating Pedestrian Streetscapes (Virtual-STEPS), a Google Street View-based auditing tool specifically designed to remotely assess micro-scale characteristics of the built environment.

Methods

We created Virtual-STEPS, a tool with 40 items categorized into 6 domains (pedestrian infrastructure, traffic calming and streets, building characteristics, bicycling infrastructure, transit, and aesthetics). Items were selected based on their past abilities to predict active living and on their feasibility for a virtual auditing tool. Two raters performed virtual and field audits of street segments in Montreal neighborhoods stratified by the Walkscore that was used to determine the ‘walking-friendliness’ of a neighborhood. The reliability between virtual and field audits (n = 40), as well as inter-rater reliability (n = 60) were assessed using percent agreement, Cohen’s Kappa statistic, and the Intra-class Correlation Coefficient.

Results

Virtual audits and field audits (excluding travel time) took similar amounts of time to perform (9.8 versus 8.2 min). Percentage agreement between virtual and field audits, and for inter-rater agreement was 80% or more for the majority of items included in the Virtual-STEPS tool. There was high reliability between virtual and field audits with Kappa and ICC statistics indicating that 20 out of 40 (50.0%) items had almost perfect agreement and 13 (32.5%) items had substantial agreement. Inter-rater reliability was also high with 17 items (42.5%) with almost perfect agreement and 11 (27.5%) items with substantial agreement.

Conclusions

Virtual-STEPS is a reliable tool. Tools that measure the micro-scale environment are important because changing this environment could be a relatively cost-effective method of creating environments that are conducive to active living.
Readmissions, revisions, and mortality after treatment for proximal humeral fractures in three large states
Authors: Dabija Dominique I. , Guan Hongshu , Neviaser Andrew , Jain Nitin B.
Published: September 2019

Background

Proximal humeral fractures can be treated non-operatively or operatively with open reduction and internal fixation (ORIF) and arthroplasty. Our objective was to assess practice patterns for operative and non-operative treatment of proximal humeral fractures. We also report on complications, readmissions, in-hospital mortality, and need for surgery after initial treatment of proximal humeral fractures in California, Florida, and New York.

Methods

The State Inpatient Databases and State Emergency Department Databases from the Healthcare Cost and Utilization Project, sponsored by the Agency for Healthcare Research and Quality, were used for the states of California (2005–2011), Florida (2005–2014), and New York (2008–2014). Data on patients with proximal humeral fractures was extracted. Patients underwent non-operative or operative (ORIF or arthroplasty) treatment at baseline and were followed for at least 4 years from the index presentation. If the patient needed subsequent surgery, time to event was calculated in days, and Kaplan-Meier survival curves were plotted.

Results

At the index visit, 90.3% of patients with proximal humeral fractures had non-operative treatment, 6.7% had ORIF, and 3.0% had arthroplasty. 7.6% of patients initially treated non-operatively, 6.6% initially treated with ORIF, and 7.2% initially treated with arthroplasty needed surgery during follow-up. Device complications were the primary reason for readmission in 5.3% of ORIF patients and 6.7% of arthroplasty patients (p < 0.0001). All-cause in-hospital mortality was 9.8% for patients managed non-operatively, 8.8% for ORIF, and 10.0% for arthroplasty (p = 0.003).

Conclusions

A majority of patients with proximal humeral fractures underwent non-operative treatment. There was a relatively high all-cause in-hospital mortality irrespective of treatment. Given the recent debate on operative versus non-operative treatment for proximal humeral fractures, our study provides valuable information on the need for revision surgery after initial treatment. The differences in rates of revision surgery between patients treated non-operatively, with ORIF, and with arthroplasty were small in magnitude. At nine years of follow-up, ORIF had the lowest probability of needing follow-up surgery, and arthroplasty had the highest.
Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicine
Authors: Ghaffari Hadi , Tavakoli Ahmad , Moradi Abdolvahab , Tabarraei Alijan , Bokharaei-Salim Farah , Zahmatkeshan Masoumeh , Farahmand Mohammad , Javanmard Davod , Kiani Seyed Jalal , Esghaei Maryam , Pirhajati-Mahabadi Vahid , Monavari Seyed Hamidreza , Ataei-Pirkooh Angila
Published: September 2019

Background

Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus.

Methods

The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed.

Results

Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P < 0.0001). At the highest non-toxic concentrations, the PEGylated and unPEGylated ZnO-NPs led to inhibition rates of 94.6% and 52.2%, respectively, which were calculated based on the viral loads. There was a substantial decrease in fluorescence emission intensity in viral-infected cell treated with PEGylated ZnO-NPs compared to the positive control.

Conclusions

Taken together, our study indicated that PEGylated ZnO-NPs could be a novel, effective, and promising antiviral agent against H1N1 influenza virus infection, and future studies can be designed to explore the exact antiviral mechanism of these nanoparticles.
Adolescent wine consumption is inversely associated with long-term weight gain: results from follow-up of 20 or 22 years
Authors: Poudel Pratiksha , Ismailova Kamila , Andersen Lars Bo , Larsen Sofus C. , Heitmann Berit L.
Published: September 2019

Background

Several studies have suggested a link between the type of alcoholic beverage consumption and body weight. However, results from longitudinal studies have been inconsistent, and the association between adolescent alcohol consumption long-term weight gain has generally not been examined.

Methods

The study was based on data from 720 Danish adolescents aged between 15 to 19 years at baseline from the Danish Youth and Sports Study (YSS). Self-reported alcohol use, height, weight, smoking, social economic status (SES) and physical activity levels were assessed in baseline surveys conducted in 1983 and 1985, and in the follow up survey which was conducted in 2005. Multiple linear regression analyses were used to examine the association between alcohol consumption in adolescence and subsequent weight gain later in midlife.

Results

There was no significant association between total alcohol consumption during adolescence and change in BMI into midlife(P = 0.079) (β − 0.14; 95% CI -0.28, 0.005). Wine consumption was found to be inversely associated to subsequent BMI gain(P = 0.001) (β − 0.46; 95% CI -0.82, − 0.09) while the results were not significant for beer and spirit. The relationship did not differ by gender, but smoking status was found to modify the relationship, and the inverse association between alcohol and BMI gain was seen only among non-smokers (P = 0.01) (β − 0.24; 95% CI -0.41, − 0.06) while no association was found among smokers. Neither adolescent nor attained socioeconomic status in adulthood modified the relationship between alcohol intake and subsequent BMI gain.

Conclusion

Among non-smoking adolescents, consumption of alcohol, and in particular wine, seems to be associated with less weight gain until midlife.

Trial registration

The YSS cohort was retrospectively registered on August 2017. (Study ID number:NCT03244150).
Estimating mean population salt intake in Fiji and Samoa using spot urine samples
Authors: Santos Joseph Alvin , Rosewarne Emalie , Hogendorf Martyna , Trieu Kathy , Pillay Arti , Ieremia Merina , Naseri Leausa Toleafoa Take , Tukana Isimeli , Snowdon Wendy , Petersen Kristina , Webster Jacqui
Published: September 2019

Background

There is an increasing interest in finding less costly and burdensome alternatives to measuring population-level salt intake than 24-h urine collection, such as spot urine samples. However, little is known about their usefulness in developing countries like Fiji and Samoa. The purpose of this study was to evaluate the capacity of spot urine samples to estimate mean population salt intake in Fiji and Samoa.

Methods

The study involved secondary analyses of urine data from cross-sectional surveys conducted in Fiji and Samoa between 2012 and 2016. Mean salt intake was estimated from spot urine samples using six equations, and compared with the measured salt intake from 24-h urine samples. Differences and agreement between the two methods were examined through paired samples t-test, intraclass correlation coefficient analysis, and Bland-Altman plots and analyses.

Results

A total of 414 participants from Fiji and 725 participants from Samoa were included. Unweighted mean salt intake based on 24-h urine collection was 10.58 g/day (95% CI 9.95 to 11.22) in Fiji and 7.09 g/day (95% CI 6.83 to 7.36) in Samoa. In both samples, the INTERSALT equation with potassium produced the closest salt intake estimate to the 24-h urine (difference of − 0.92 g/day, 95% CI − 1.67 to − 0.18 in the Fiji sample and + 1.53 g/day, 95% CI 1.28 to 1.77 in the Samoa sample). The presence of proportional bias was evident for all equations except for the Kawasaki equation.

Conclusion

These data suggest that additional studies where both 24-h urine and spot urine samples are collected are needed to further assess whether methods based on spot urine samples can be confidently used to estimate mean population salt intake in Fiji and Samoa.
A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy
Authors: Niu Shiwei , Williams Gareth R. , Wu Jianrong , Wu Junzi , Zhang Xuejing , Chen Xia , Li Shude , Jiao Jianlin , Zhu Li-Min
Published: September 2019

Background

It is extremely difficult to develop targeted treatments for triple-negative breast (TNB) cancer, because these cells do not express any of the key biomarkers usually exploited for this goal.

Results

In this work, we develop a solution in the form of a cascade responsive nanoplatform based on thermo-sensitive poly(N-vinylcaprolactam) (PNVCL)-chitosan (CS) nanoparticles (NPs). These are further modified with the cell penetrating peptide (CPP) and loaded with the chemotherapeutic drug doxorubicin (DOX). The base copolymer was optimized to undergo a phase change at the elevated temperatures of the tumor microenvironment. The acid-responsive properties of CS provide a second trigger for drug release, and the inclusion of CPP should ensure the formulations accumulate in cancerous tissue. The resultant CPP-CS-co-PNVCL NPs could self-assemble in aqueous media into spherical NPs of size < 200 nm and with low polydispersity. They are able to accommodate a high DOX loading (14.8% w/w). The NPs are found to be selectively taken up by cancerous cells both in vitro and in vivo, and result in less off-target cytotoxicity than treatment with DOX alone. In vivo experiments employing a TNB xenograft mouse model demonstrated a significant reduction in tumor volume and prolonging of life span, with no obvious systemic toxicity.

Conclusions

The system developed in this work has the potential to provide new therapies for hard-to-treat cancers.
Correction to: An isogenic neurovascular unit model comprised of human induced pluripotent stem cell-derived brain microvascular endothelial cells, pericytes, astrocytes, and neurons
Authors: Canfield Scott G. , Stebbins Matthew J. , Faubion Madeline G. , Gastfriend Benjamin D. , Palecek Sean P. , Shusta Eric V.
Published: September 2019

Following publication of the original article [1], the author has reported that in Figure 1 (b and c) the y-axis TEER (© x cm2) should be replaced with TEER (Ω x cm2).
Engineered Thermoanaerobacterium aotearoense with nfnAB knockout for improved hydrogen production from lignocellulose hydrolysates
Authors: Li Yang , Hu Jialei , Qu Chunyun , Chen Lili , Guo Xiaolong , Fu Hongxin , Wang Jufang
Published: September 2019

Background

As a renewable and clean energy carrier, the production of biohydrogen from low-value feedstock such as lignocellulose has increasingly garnered interest. The NADH-dependent reduced ferredoxin:NADP+ oxidoreductase (NfnAB) complex catalyzes electron transfer between reduced ferredoxin and NAD(P)+, which is critical for production of NAD(P)H-dependent products such as hydrogen and ethanol. In this study, the effects on end-product formation of deletion of nfnAB from Thermoanaerobacterium aotearoense SCUT27 were investigated.

Results

Compared with the parental strain, the NADH/NAD+ ratio in the ∆nfnAB mutant was increased. The concentration of hydrogen and ethanol produced increased by (41.1 ± 2.37)% (p < 0.01) and (13.24 ± 1.12)% (p < 0.01), respectively, while the lactic acid concentration decreased by (11.88 ± 0.96)% (p < 0.01) when the ∆nfnAB mutant used glucose as sole carbon source. No obvious inhibition effect was observed for either SCUT27 or SCUT27/∆nfnAB when six types of lignocellulose hydrolysate pretreated with dilute acid were used for hydrogen production. Notably, the SCUT27/∆nfnAB mutant produced 190.63–209.31 mmol/L hydrogen, with a yield of 1.66–1.77 mol/mol and productivity of 12.71–13.95 mmol/L h from nonsterilized rice straw and corn cob hydrolysates pretreated with dilute acid.

Conclusions

The T. aotearoense SCUT27/∆nfnAB mutant showed higher hydrogen yield and productivity compared with those of the parental strain. Hence, we demonstrate that deletion of nfnAB from T. aotearoense SCUT27 is an effective approach to improve hydrogen production by redirecting the electron flux, and SCUT27/∆nfnAB is a promising candidate strain for efficient biohydrogen production from lignocellulosic hydrolysates.
A genetic tool for production of GFP-expressing Rhodopseudomonas palustris for visualization of bacterial colonization
Authors: Zhai Zhongying , Du Jiao , Chen Lijie , Hamid Muhammad Rizwan , Du Xiaohua , Kong Xiaoting , Cheng Jue , Tang Wen , Zhang Deyong , Su Pin , Liu Yong
Published: September 2019

Development of a genetic tool for visualization of photosynthetic bacteria (PSB) is essential for understanding microbial function during their interaction with plant and microflora. In this study, Rhodopseudomonas palustris GJ-22-gfp harboring the vector pBBR1-pckAPT-gfp was constructed using an electroporation transformation method and was used for dynamic tracing of bacteria in plants. The results showed that strain GJ-22-gfp was stable and did not affect the biocontrol function, and the Confocal Laser Scanning Microscopy (CLSM) results indicated it could successfully colonised on the surface of leaf and root of tobacco and rice. In tobacco leaves, cells formed aggregates on the mesophyll epidermal cells. While in rice, no aggregate was found. Instead, the fluorescent cells colonise the longitudinal intercellular spaces between epidermal cells. In addition, the results of strain GJ-22 on the growth promotion and disease resistance of tobacco and rice indicated that the different colonization patterns might be related to the bacteria could induce systemic resistance in tobacco.
Contraindications to immunotherapy: a global approach
Authors: Pitsios C. , Tsoumani M. , Bilò M. B. , Sturm G. J. , Rodríguez del Río P. , Gawlik R. , Ruëff F. , Paraskevopoulos G. , Valovirta E. , Pfaar O. , Calderón M. A. , Demoly P.
Published: September 2019

Background

Recommendations on contraindications to allergen immunotherapy (AIT) have been independently developed by National and International Societies/Academies. AIT contraindications are mainly based on case reports, case-series, or experts’ opinion, while evidence-based information is limited. The aim of the present review was to describe existing guidelines on contraindications to AIT and to highlight differences between them.

Main body

An extended review of the literature regarding contraindications to AIT for respiratory allergy and venom hypersensitivity was performed. Furthermore, Societies and Academies registered in the World Allergy Organization and EAACI databases, were asked for additional information. Only AIT guidelines published under official auspicies were included. A large heterogeneity among the various recommendations on contraindications was registered. Common contraindications to most of the guidelines were: lack of adherence, pregnancy before the start of AIT, the use of beta-blockers, certain age groups, uncontrolled asthma, autoimmune diseases and malignancies.

Conclusion

As new data arise, revisions might soon be needed allowing AIT in the cases of patients treated with ACE inhibitors and beta-blockers, in elderly patients and in patients with concomitant autoimmune diseases and neoplasias in remission. The decision to prescribe AIT is always tailor-made, balancing risk vs benefit. Creating globally accepted guidelines would help Allergologists in their decision making.
Acceptability of innovative biomass heating plants in a German case study—a contribution to cultural landscape management and local energy supply
Authors: Busse Maria , Siebert Rosemarie , Heitepriem Nico
Published: September 2019

Background

To prevent negative effects on the cultural landscape through land abandonment or agricultural intensification, innovative solutions towards more sustainable land use are required. Local bioenergy systems using agricultural co-products are perceived as one solution to threatened cultural landscapes with small-scale meadows. The aim of this paper is to analyse the acceptability of biomass heating plants in the Spreewald region (Germany) and their contribution to cultural landscape management.

Methods

We asked 17 farmers about the likelihood that they would install a biomass plant on their farms and about their reasons for accepting or rejecting it. A fuzzy set qualitative comparative analysis was applied.

Results

The analysis showed that acceptance is relatively low. We identified three types of farmers: proponents and potential adopters, ethically concerned opponents, and open-minded refusers. Biomass plants were likely to be accepted if farmers stated an ethical acceptance of and interest in technology, a need for a new heating system, the availability of sufficient feedstock, and a perceived unproblematic readiness of technology—all these factors had to exist in combination. On the other hand, farmers rejected a biomass plant if one of the following factors existed: ethical concerns about “burning hay”, satisfaction with their current oven, low availability of feedstock, or a perceived low readiness of technology. Other factors were the existence of procedural justice, trust in coordinating actors, and a demonstration plant.

Conclusions

The discussion shows that the specific results have to be contextualised within the innovation process for sustainable landscape management. This may be achieved by integrating the acceptability study into an adaptive landscape design. This relies on mutable acceptability decisions, reflexive learning processes, and iterative feedback loops in innovation processes. Our paper advances knowledge about (1) how to prevent land abandonment and simultaneously promote regional energy and (2) the acceptability in the field of land use and landscape management.

Keywords

Fuzzy set qualitative comparative analysis (fsQCA); Bioenergy; Energy transitions; Co-products; Biomass conversion; Gasification; Land abandonment; Wetlands; Integrative landscape design
Intraoperative MRI-assisted neuro-port surgery for the resection of cerebral intraparenchymal cavernous malformation
Authors: Zhao Min , Lu Changyu , Liang Jianfeng , Zhao Yuanli , Chen Xiaolei
Published: September 2019

Background

Intraparenchymal cerebral cavernous malformation is difficult to localize intraoperatively with conventional frameless navigation due to the “brain shift” effect. We conducted this study to evaluate the efficacy and safety of intraoperative magnetic resonance image (iMRI)-assisted neuro-port surgery for the resection of cerebral intraparenchymal cavernous malformation.

Methods

Between April 2016 and December 2017, 54 consecutive patients with intraparenchymal cerebral cavernous malformation who get surgical treatment in our hospital were enrolled into this study. Twenty-one patients were treated using iMRI-assisted neuro-port surgery (experiment group), and 33 patients underwent treatment by conventional microsurgery (control group). The iMRI was used in all cases for the compensation of the “brain shift” effect and keeping the navigation system up-to-date. The surgical resection rate, the total operation time, and the preoperative and postoperative Karnofsky Performance Status (KPS) scores were determined to evaluate the operative procedures.

Results

There were no significant differences between the two groups in mean age, gender ratio, and volume of lesions (P > 0.05). For the experiment group, the average duration of the procedure was 188.8 min with total resection of the lesions achieved in all 21 cases. For the control group, the average duration of the procedure was 238.2 min with total resection of the lesions achieved in 25 of 33 cases. The differences in the average duration of the procedure and the number of totally resected lesions between the two groups were statistically significant (P < 0.05). Regarding postoperative neurological function, postoperative KPS scores for the experiment group were significantly higher than those of the control group (P = 0.018).

Conclusion

Our results show that iMRI-assisted neuro-port surgery is helpful for intraparenchymal cerebral cavernous malformation surgery. The method provides high accuracy and efficiency for lesion targeting and permits excellent anatomic orientation. With the assistance of iMRI technology, we achieved a higher resection rate and a lower incidence of postoperative neurological deficits. Additionally, iMRI is helpful for the compensation of the “brain shift” effect, and it can update the navigation system.
bicoid RNA localization requires the trans-Golgi network
Authors: Cai Xiaoli , Fahmy Khalid , Baumgartner Stefan
Published: September 2019

Background

The formation of thebicoid(bcd) mRNA gradient is a crucial step for Bcd protein gradient formation inDrosophila. In the past, a microtubule (MT)-based cortical network had been shown to be indispensable forbcdmRNA transport to the posterior.

Results

We report the identification of a MT-binding protein CLASP/Chb as the first component associated with this cortical MT network. Since CLASPs in vertebrates were shown to serve as an acentriolar microtubule organization center (aMTOC) in concert withtrans-Golgi proteins, we examined the effect of theDrosophila trans-Golgins onbcdlocalization and gradient formation. Using a genetic approach, we demonstrate that theDrosophila trans-GolginsdGCC88,dGolgin97anddGCC185indeed affectbcdmRNA localization during oocyte development. Consequently, thebcdmRNA is already mislocalized before the egg is fertilized. The expression domains of genes downstream of the hierarchy ofbcd, e.g. of the gap geneempty spiraclesor of the pair-rule geneeven-skippedare changed, indicating an altered segmental anlagen, due to a faultybcdgradient. Thus, at the end of embryogenesis,trans-Golgin mutants showbcd-like cuticle phenotypes.

Conclusions

Our data provides evidence that the Golgi as a cellular member of the secretory pathway exerts control onbcdlocalization which indicates thatbcdgradient formation is probably more intricate than previously presumed.
Trait emotional experience in individuals with schizophrenia and youth at clinical high risk for psychosis
Authors: Yee Claire I. , Strauss Gregory P. , Allen Daniel N. , Haase Claudia M. , Kimhy David , Mittal Vijay A.
Published: September 2019

Background

Disturbances in trait emotions are a predominant feature in schizophrenia. However, less is known about (a) differences in trait emotion across phases of the illness such as the clinical high-risk (CHR) phase and (b) whether abnormalities in trait emotion that are associated with negative symptoms are driven by primary (i.e. idiopathic) or secondary (e.g. depression, anxiety) factors.

Aims

To examine profiles of trait affective disturbance and their clinical correlates in individuals with schizophrenia and individuals at CHR for psychosis.

Method

In two studies (sample 1: 56 out-patients diagnosed with schizophrenia and 34 demographically matched individuals without schizophrenia (controls); sample 2: 50 individuals at CHR and 56 individuals not at CHR (controls)), participants completed self-report trait positive affect and negative affect questionnaires, clinical symptom interviews (positive, negative, disorganised, depression, anxiety) and community-based functional outcome measures.

Results

Both clinical groups reported lower levels of positive affect (specific to joy among individuals with schizophrenia) and higher levels of negative affect compared with controls. For individuals with schizophrenia, links were found between positive affect and negative symptoms (which remained after controlling for secondary factors) and between negative affect and positive symptoms. For individuals at CHR, links were found between both affect dimensions and both types of symptom (which were largely accounted for by secondary factors).

Conclusions

Both clinical groups showed some evidence of reduced trait positive affect and elevated trait negative affect, suggesting that increasing trait positive affect and reducing trait negative affect is an important treatment goal across both populations. Clinical correlates of these emotional abnormalities were more integrally linked to clinical symptoms in individuals with schizophrenia and more closely linked to secondary influences such as depression and anxiety in individuals at CHR.

Declaration of interest

None.
Broad regulation of gene isoform expression by Wnt signaling in cancer
Authors: Idris Muhammad , Harmston Nathan , Petretto Enrico , Madan Babita , Virshup David M.
Published: September 2019

Differential gene isoform expression is a ubiquitous mechanism to enhance proteome diversity and maintain cell homeostasis. Mechanisms such as splicing that drive gene isoform variability are highly dynamic and responsive to changes in cell signaling pathways. Wnt/β-catenin signaling has profound effects on cell activity and cell fate and is known to modify several splicing events by altering the expression of individual splicing factors. However, a global assessment of how extensively Wnt signaling regulates splicing and other mechanisms that determine mRNA isoform composition in cancer is lacking. We used deep time-resolved RNA-seq in two independent in vivo Wnt-addicted tumor models during treatment with the potent Wnt inhibitor ETC-159 and examined Wnt regulated splicing events and splicing regulators. We found 1025 genes that underwent Wnt regulated variable exon usage leading to isoform expression changes. This was accompanied by extensive Wnt regulated changes in the expression of splicing regulators. Many of these Wnt regulated events were conserved in multiple human cancers, and many were linked to previously defined cancer-associated splicing quantitative trait loci. This suggests that the Wnt regulated splicing events are components of fundamental oncogenic processes. These findings demonstrate the wide-ranging effects of Wnt signaling on the isoform composition of the cell and provides an extensive resource of expression changes of splicing regulators and gene isoforms regulated by Wnt signaling.
Circular code motifs in the ribosome: a missing link in the evolution of translation?
Authors: Dila Gopal , Ripp Raymond , Mayer Claudine , Poch Olivier , Michel Christian J. , Thompson Julie D.
Published: September 2019

The origin of the genetic code remains enigmatic five decades after it was elucidated, although there is growing evidence that the code coevolved progressively with the ribosome. A number of primordial codes were proposed as ancestors of the modern genetic code, including comma-free codes such as the RRY, RNY, or GNC codes (R = G or A, Y = C or T, N = any nucleotide), and the X circular code, an error-correcting code that also allows identification and maintenance of the reading frame. It was demonstrated previously that motifs of the X circular code are significantly enriched in the protein-coding genes of most organisms, from bacteria to eukaryotes. Here, we show that imprints of this code also exist in the ribosomal RNA (rRNA). In a large-scale study involving 133 organisms representative of the three domains of life, we identified 32 universal X motifs that are conserved in the rRNA of >90% of the organisms. Intriguingly, most of the universal X motifs are located in rRNA regions involved in important ribosome functions, notably in the peptidyl transferase center and the decoding center that form the original “proto-ribosome.” Building on the existing accretion models for ribosome evolution, we propose that error-correcting circular codes represented an important step in the emergence of the modern genetic code. Thus, circular codes would have allowed the simultaneous coding of amino acids and synchronization of the reading frame in primitive translation systems, prior to the emergence of more sophisticated start codon recognition and translation initiation mechanisms.