bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of a capsule endoscope delivery device in children
Authors: Iwama Itaru , Shimizu Hirotaka , Nambu Ryusuke , Okuhira Takeru , Kakuta Fumihiko , Tachibana Nao , Abe Naoki , Honma Hitoshi , Kudo Takahiro , Nakayama Yoshiko
Published: August 2019

Objectives

This multicenter, cross-sectional study aimed to elucidate the efficacy and safety of the AdvanCE capsule endoscope delivery device for children in Japan.

Methods

The present study analyzed 183 cases of small bowel capsule endoscope (SBCE) insertion performed using the AdvanCE in 154 patients aged less than 18 years at participating institutions between 2013 and 2017. Statistical analyses were conducted to identify factors contributing to the completion rate for the entire small intestine examination, small intestine transit time, adverse events and technical issues.

Results

The commonest reason for using the AdvanCE was the patient’s inability to swallow the SBCE, which was attributed to young age. SBCE was successfully delivered into the stomach or duodenum in 180 cases and was placed in the duodenum in 90% patients. In 89% patients, the entire small intestine was completely examined, and in 63% patients, findings leading to a new diagnosis or involving changing or maintaining the treatment strategy were obtained. No severe adverse events were observed; however, mild adverse events were observed in 35% patients. No factors considerably contributed to the completion rate for the entire small intestine examination or small intestine transit time and onset of technical issues. The factors that contributed to mild adverse events included intravenous anesthesia, technical issue, and absence of prior insertion of a patency capsule using the AdvanCE.

Conclusion

The AdvanCE is well tolerated and effective for children.
Criteria for difficult biliary cannulation: start to count
Authors: Ismail Shamel , Udd Marianne , Lindström Outi , Rainio Mia , Halttunen Jorma , Kylänpää Leena
Published: August 2019

Objective

In European Society of Gastrointestinal Endoscopy guidelines, biliary cannulation of native papilla is defined as difficult in the presence of >5 papilla contacts, >5 min cannulation time or >1 unintended pancreatic duct cannulation (5-5-2). The aim is to test 5-5-2-criteria in a single-center practice predicting the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), and to study the efficacy of transpancreatic biliary sphincterotomy (TPBS) as an advanced method for biliary cannulation.

Methods

Prospectively collected data of 821 patients with native papilla were analyzed. Primary cannulation was the first method chosen for cannulation (sphincterotome and a guidewire). Advanced cannulation method was endoscopist-chosen cannulation method after failed primary cannulation.

Results

Primary cannulation succeeded in 599 (73%) patients in a median of 2 min. TPBS ± needle knife resulted in a 90% success rate. The final cannulation success was 814 (99.1%) cases in a median of 5.3 min. PEP risk was 4.0%. When primary cannulation succeeded, the PEP rate was 2.3%. When advanced methods were needed, the PEP rate increased to 13.5%. Altogether 311 (37.9%) patients fulfilled at least one 5-5-2-criterion. In patients without 5-5-2-criteria, the primary cannulation succeeded in 79.6% (n = 477), compared to 20.4% (n = 122) with the criteria, P < 0.001, indicating the need to exchange the cannulation method instead of persistence. If all the 5-5-2-criteria were present, the risk of PEP was 12.7%.

Conclusion

The results support the use of the 5-5-2-criteria for difficult cannulation. TPBS is an effective advanced cannulation method with an acceptable complication rate.
Wire-guided biliary cannulation: a comprehensive approach to a set of techniques
Authors: Cennamo Vincenzo , Bassi Marco , Landi Stefano , Binda Cecilia , Fabbri Carlo , Ghersi Stefania , Gasbarrini Antonio
Published: August 2019

Biliary cannulation represent a challenge for the endoscopists that approach to endoscopic retrograde cholangiopancreatography, with non-negligible rate of failure even in expert hands. In order to achieve the biliary tree, two main technique are nowadays mainly used, namely the contrast-assisted cannulation and the wire-guided cannulation (WGC) techniques. The WGC technique is widely used because it seems to be related to higher success rate of cannulation of the common bile duct and, at the same time, to lower rates of complications. Particularly, this approach is associated with lower risk of post endoscopic retrograde cholangiopancreatography pancreatitis, although the pathogenesis of this adverse event is still not completely understood. The outspread of this technique among endoscopists promoted the development of different methods of performing WGC-assisted endoscopic retrograde cholangiopancreatography, such as the touch technique, the no-touch technique and the double guide-wire cannulation. Furthermore, the variety of guide wires and accessories, with their different characteristics, contribute to make the scenario extremely heterogeneous. To date, the published studies did not highlight which is the best strategy that maximizes the rate of success and minimizes the percentage of complications, even because the experience of the operator represents an important variable that conditions the outcomes. The aim of this review is to define state of the art in WGC technique, in order to better understand the possible advantages in using this approach and to bring to light the possible area that may be object of further studies.
The Impact of Rhode Island’s Multipayer Patient-centered Medical Home Program on Utilization and Cost of Care
Authors: Cole Megan B. , Galárraga Omar , Wilson Ira B.
Published: August 2019

Objective:

To estimate the effect of patient-centered medical home (PCMH) participation on cost and utilization of care for patients in Rhode Island’s statewide, multipayer PCMH program, which serves over one-third of the state population.

Data Sources/Study Setting:

2009–2014 claims data from all payers in Rhode Island, representing >743,000 unique patients.

Study Design:

A propensity score–matched difference-in-differences framework was used to separately estimate the effect of the PCMH on 3 patient cohorts, which were defined by their intervention start dates and amounts of implementation time. Outcomes included patient costs (total, inpatient, outpatient, professional, pharmacy) and utilization [emergency department (ED) visits, preventable ED visits, inpatient admissions, preventable inpatient admissions, all-cause 30-day readmissions]. Interaction effects were estimated to assess heterogeneity among clinical risk groups and payers.

Principal Findings:

There was no evidence of a PCMH effect on total costs, though we observed evidence of an increase in the odds of PCMH patients having outpatient and professional costs, and in one cohort, a decrease in inpatient costs for those with an inpatient visit. We also observed evidence of reduced ED visits, preventable ED visits, and inpatient admissions for PCMH patients. While subgroup effects varied by cohort and measure, high-risk patients often experienced the largest reductions in ED visits.

Conclusions:

All PCMH cohorts experienced statistically significant reductions in some types of utilization in as little as 1.25 years. Reductions were greatest for measures included in the PCMH contractual agreement. While PCMH programs may not expect cost savings in the short-term, costs could potentially be reduced in the longer-term through avoided ED and inpatient expenses.
Effects of adjuvant mental practice using inverse video of the unaffected upper limb in subacute stroke: a pilot randomized controlled study
Authors: Nam Je Shik , Yi Tae Im , Moon Hyun Im
Published: August 2019

Mental practice has shown some positive effects on arm and hand ability and mobility after stroke. This study’s objective was to investigate the adjuvant effects of mental practice using an inverse video of the unaffected limb in subacute stroke patients with severe motor impairment on motor improvement, functional outcomes, and activities of daily living. Participants (n = 20) with severe hemiplegia after a unilateral first-ever stroke within 6 months were divided into two groups. The intervention group performed additional mental practice using an inverse video of the unaffected limb for 20 minutes before every session of their rehabilitation program. The primary outcomes were the Fugl-Meyer assessment for the upper extremity (FMA-UE) and manual function test (MFT). Assessments were performed at baseline and after 4 weeks of rehabilitation intervention. Significant differences were found from baseline to postintervention assessments within both groups on FMA-UE and FIM scores, whereas there were no statistically significant differences in mean FMA-UE, MFT, and FIM scores between groups. We cannot draw conclusions about the superiority of adjuvant mental practice training using inverse video compared with conventional occupation therapy alone in subacute poststroke patients.
Using telerehabilitation to improve cognitive function in post-stroke survivors: is this the time for the continuity of care?
Authors: Torrisi Michele , Maresca Giuseppa , De Cola Maria Cristina , Cannavò Antonio , Sciarrone Francesca , Silvestri Giuseppe , Bramanti Alessia , De Luca Rosaria , Calabrò Rocco Salvatore
Published: August 2019

Post-stroke cognitive disorders can affect different domains, depending on typology of stroke and lesion localization, onset time, age and diagnostic tools used. In recent years, telerehabilitation using virtual reality has been used to reduce the healthcare costs encouraging continuity of care. The aim of our study is to evaluate the efficacy of a virtual reality rehabilitation system in improving cognitive function in stroke survivors. Forty patients affected by stroke were enrolled in this study and randomized into either the control or the experimental groups in order of recruitment. The study lasted 6 months, and included two phases: (1) during the first phase the experimental group underwent cognitive rehabilitation training using the Virtual Reality Rehabilitation System-Evo, whereas the control group was submitted to standard cognitive training; (2) in the second phase (after discharge), the experimental group was treated by means of virtual reality rehabilitation system Home Tablet (three sessions a week, each session lasting about 50 minutes), and the control group continued the traditional training, with the same amount of treatment. The patients underwent a neuropsychological evaluation before and at the end of the treatment. Linear mixed-effects analysis results showed that the scores of Montreal overall cognitive assessment, attentive matrices, Trail Making Test B, Phonemic Fluency, Semantic Fluency, Rey Auditory Verbal Learning Test I, Hamilton Rating Scale-Anxiety and Hamilton Rating Scale-Depression were affected by the type of the rehabilitative treatment. Our data show the effectiveness of telerehabilitation for the treatment of cognitive disorders following stroke.
Nurses' Attitudes Toward Electronic Clinical Quality Measures
Authors: Lin Feng-Lien , Huang Szu-Fen , Hou I-Ching
Published: August 2019

Background:

Electronic clinical quality measures (eCQMs) are a method that automatically extract data from electronic health records (EHRs) and compute and generate the results to report and track the quality of care and patient outcomes.

Purpose:

The purpose of this study was to explore nurses' attitudes toward eCQMs and the factors influencing this attitude.

Methods:

A descriptive cross-sectional study was conducted using a closed-ended questions survey of 92 nurses in a teaching hospital.

Results:

The average score for nurses' attitudes toward eCQMs was 3.47 out of 4. Participants with a master's degree had more positive attitudes than those with a baccalaureate degree. Head nurses had more positive attitudes than staff nurses.

Conclusions:

The nurses in the study hospital have a positive attitude toward eCQMs. Health care organizations should strengthen the attitudes of nurses toward eCQMs.
Neurasthenia
Authors: Overholser James C. , Beale Eleanor E.
Published: August 2019

Neurasthenia was a popular diagnosis from 1869 through 1930. Despite being discarded, the core symptoms of neurasthenia can still be found throughout modern society. The present article reviews the symptoms, common course, proposed causes, and common treatments for neurasthenia. Similarities are seen in several familiar diagnoses, including depression, chronic fatigue syndrome, and fibromyalgia. Through reviewing the trends of neurasthenia, modern doctors may learn more about the subtleties of the diagnostic process, as well as the patient-physician relationship. The goal is to learn from the past as it relates to current problems that may be related to the stress of modern living. The history of neurasthenia is presented as it relates to problems that may remain today.
Madness and Crime
Authors: Haldipur C.V.
Published: August 2019

It is generally acknowledged that the insanity defense has its roots in ancient Greek philosophy. There are references to the insanity defense in the works of Plato and Homer. Little, though, is known about how non-Western cultures dealt with the insane who commit crimes. This article focuses on one non-Western culture: ancient India. The author refers to extant medical texts and Sanskrit literature to argue that the notion that the insane are not responsible for criminal acts was current during that epoch.
Use of the Electrodiagnostic Entrustable Professional Activity for Competency Assessment in Physical Medicine and Rehabilitation Training Programs
Authors: Baer Heather R. , Gilbert Aaron R. , Forster Jeri E. , Ketchum Nicholas C. , Mallow Michael , Nguyen Vu Q. C.
Published: August 2019

Entrustable professional activities have emerged as a means for the evaluation of resident competency that is expressed in terms of the assessed need for supervision. Recently, 19 physical medicine and rehabilitation–specific entrustable professional activities were published (Am J Phys Med Rehabil. 2017;96:762–764). The electrodiagnostic entrustable professional activity and six new electrodiagnostic entrustable professional activities subcategories (observable practice activities) were piloted as an entrustable professional activities/observable practice activities set within five residency programs. Survey-based (quantitative) and open-ended (qualitative) feedback was collected from participants. Participating attendings found this method feasible and generally reported satisfaction with the entrustable professional activities/observable practice activities as a means of providing feedback to residents. Residents were less clear on the added value of this approach. Qualitative data supported the need for adjustments to the entrustment scale to allow for more gradations within supervisory levels, a standardized orientation of residents to the use of observable practice activities and an increased quantity of assessments for each observable practice activities category to allow for demonstration of resident progress toward independence. Use of the electrodiagnostic entrustable professional activity/observable practice activities set shows promise as a means for observational competency assessment in the outpatient setting. However, feedback acquired through this pilot study suggests changes that could be made to improve future implementation.
Technical Strategy of Bone Graft Augmentation in the Anterior Maxilla
Authors: Ribeiro Jonathan , Pereira Rodrigo dos Santos , Marin Charles , Granato Rodrigo , Fernandes Breno dos Reis , Mulinari-Santos Gabriel , Mendes Bruno Coelho , Hochuli Eduardo
Published: August 2019

Bone graft augmentation in the anterior maxilla has a high successful rate. However, suture dehiscence and consequent bone graft exposure can compromise and fail this procedure. Therefore, this article presents a new strategy of closure technique to guarantee the bone graft augmentation. The sutures occur in muscular and mucous planes to avoid suture tension, thus decreasing complications of bone graft augmentation in the anterior maxilla.
Surgical Management of the Palatal Pleomorphic Adenoma
Authors: Moon Seong-Yong
Published: August 2019

Introduction:

Surgical excision is the basic treatment option of the palatal pleomorphic adenoma (PA), it is generally accepted to prevent for recurrence. The purpose of this study was to determine the decision criteria for the management of the palatal PA through evaluating the postoperative results of palatal PA correlation with the clinical appearance.

Materials and Methods:

All of patients were evaluated the mucosal ulceration, palatal erosion, and size with CT images in all 18 palatal PAs. The clinical features, surgical methods, and surgical results of these 18 PAs were reviewed.

Results:

The most common age was 51 to 70 years. One patient was in pediatric age (14 years). Females were involved more commonly than males (F:M ratio was 5:1) Mucosa was normal in 16 patients. Ulcerations of the overlying mucosa were seen in 2 cases. On the coronal CT images, hard palate was erosion in 14 patients who had involved hard palate. The size of tumors was from 7 mm to 33 mm in CT scans. Two patients were ruptured the tumor during the operation, and 1 out of 2 patients was recurred.

Conclusions:

For the definitive diagnosis is necessary to perform the preoperative core biopsy for the histopathological examination, and CT is necessary for evaluating the erosion of the hard palate and severity of the erosion. Hard palatal PA can be managed by surgical enucleation and removal of the periosteum or involved bone. Soft palatal PA can be managed by surgical enucleation without mucosal resection. Rupture of the tumor is related to the recurrence.
Life-saving interventions in pediatric trauma: A National Trauma Data Bank experience
Authors: Swendiman Robert A. , Sharoky Catherine E. , Russell Katie W. , Goldshore Matthew A. , Blinman Thane A. , Nance Michael L.
Published: August 2019

BACKGROUND

Emergent procedures are infrequent in pediatric trauma. We sought to determine the frequency and efficacy of life-saving interventions (LSI) performed for pediatric trauma patients within the first hour of care at a trauma center.

METHODS

The National Trauma Data Bank (2010–2014) was queried for patients 19 years or younger who underwent LSIs within 1 hour of arrival to the emergency department. Life-saving interventions included emergency department thoracotomy (EDT) and emergent airway procedures (EAP). Multivariable logistic regression was used to evaluate the influence of patient and hospital characteristics on mortality.

RESULTS

Of 725,284 recorded traumatic encounters, only 1,488 (0.2%) pediatric patients underwent at least one of the defined LSI during the 5-year study period (EDT, 1,323; EAP, 187). Most patients (85.6%) were 15 years or older. Mortality was high but varied by procedure type (EDT, 64.3%; EAP, 28.3%). Mortality for patients younger than 1 year undergoing EDT was 100%, decreasing to 62.6% in patients aged 15 years to 19 years. For EAP, mortality ranged from 66.7% for infants to 27.2% in 15-year-old to 19-year-old patients. Lower Glasgow Coma Scale score, higher Injury Severity Score, presence of shock, and a blunt mechanism of injury were independently associated with mortality in the EDT cohort. On average, trauma centers in this study performed approximately one LSI per year, with only 13.8% of cases occurring at a verified pediatric trauma center.

CONCLUSION

Life-saving interventions in the pediatric trauma population are uncommon and outcomes variable. Novel solutions to keep proficient at such interventions should be sought, especially for younger children. Guidelines to improve identification of appropriate candidates for LSI are critical given their rare occurrence.

LEVEL OF EVIDENCE

Retrospective cohort study, III.
Immunosuppression and Graft Rejection in Living-related HLA-identical Renal Transplantation: The RADOVFULL Study
Authors: Ossman Rim , Jamme Matthieu , Moulin Bruno , Legendre Christophe , Morelon Emmanuel , Frimat Luc , Hourmant Maryvonne , Durrbach Antoine , Malvezzi Paolo , Rostaing Lionel , Luc Taupin Jean , Mesnard Laurent , Rondeau Eric
Published: August 2019

Background.

We aimed to describe the immunosuppressive regimens and graft rejection rates in living-related HLA-identical (LR HLAid) renal transplantation.

Methods.

We performed a retrospective multicenter analysis of the French national database for LR HLAid renal transplantations performed between 2002 and 2012. Univariate and multivariate analysis were performed to determine risk factors for graft rejection in LR HLAid recipients.

Results.

A total of 27 218 renal transplantations were performed, of whom 163 had a LR HLAid donor. About immunosuppressive treatment, <60% of the cohort had induction therapy with polyclonal or monoclonal antibodies, 28% did not receive calcineurin inhibitors, and 36% did not receive steroids in maintenance. Biopsy-proven acute rejection was diagnosed in 21 patients (12.9%). Rejection occurred on an average of 24 months after transplantation, in 28.5% of the cases after minimization of immunosuppression. Factors associated with rejection were age of recipient (OR, 0.91 [0.84–0.96]; P = 0.003), the body mass index of donors (odds ratio [OR], 1.22 [1.04–1.46]; P = 0.01), and minimization of immunosuppression (OR, 26.2 [5.48–166.6]; P < 0.001). Overall and graft survival rates were not statistically different according to rejection at 1, 5, and 10 years posttransplantation.

Conclusions.

Minimization of immunosuppression should be done with caution in LR HLAid renal transplantations.
Spontaneous Venous Pulsations Detected With Infrared Videography
Authors: McHugh James A. , D'Antona Linda , Toma Ahmed K. , Bremner Fion D.
Published: August 2019

Background:

Assessment of spontaneous venous pulsation (SVP) is commonly undertaken to help determine whether intracranial pressure (ICP) is elevated. Previous studies using direct ophthalmoscopy or slit-lamp assessments have found that SVP is not observed in 67%–81% of subjects with normal ICP, and that interobserver agreement when grading SVP is poor.

Methods:

Patients (n = 105) undergoing clinically indicated retinal OCT scans, who were all believed to have normal ICP, had 10-second infrared video recordings performed with the Heidelberg Spectralis OCT system (Heidelberg Engineering GmbH, Heidelberg, Germany). The presence and amplitude of SVP in each video was independently graded by 2 neuro-ophthalmologists.

Results:

The 2 observers found SVP present in 97% and 98% of right eyes and in one or both eyes in 99% and 100% of subjects. Interobserver agreement was high (Cohen's kappa 0.82 for right eyes). Optic discs with a smaller cup had a significantly lower SVP amplitude (Spearman's rho = 0.22, P = 0.02).

Conclusions:

Infrared video is widely available in eye clinics by the use of OCT imaging systems and is substantially more sensitive in detecting SVP than traditional assessments using ophthalmoscopy. SVP is absent in as few as 1% of people with presumed normal ICP.
In silicoand empirical evaluation of twelve COI & 16S metabarcoding primer sets for insectivorous diet analyses
Authors: Tournayre Orianne , Leuchtmann Maxime , Filippi-Codaccioni Ondine , Trillat Marine , Piry Sylvain , Pontier Dominique , Charbonnel Nathalie , Galan Maxime
Published: August 2019

This last decade, environmental DNA metabarcoding approaches have been developed and improved to minimize biological and technical biases; some challenges, however, remain, as the design of primers. Here we have performed a comprehensive assessment of ten COI and two 16S primer sets. We have combinedin silico, in vivo-mock community of 33 arthropod taxa from 16 orders and guano analyses to identify primer sets that should maximize arthropod detection and taxonomic identification, whilst identifying bat species and minimizing labour time and cost. We have focused on two insectivorous bat species living in mixed-colonies, the greater horseshoe bat (Rhinolophus ferrumequinum) and Geoffroy’s bat (Myotis emarginatus). We have found that the level of primer degeneracy is the main factor influencing arthropod detection forin silicoand mock community analyses, while the amplicon length is critical for the detection of arthropods from degraded DNA samples. Our results confirm the importance of performing predator detection and taxonomic identification, simultaneously with arthropod sequencing, as faeces samples can be contaminated by different insectivorous species. Moreover, amplifying bat DNA does not affect the primers’ capacity to detect arthropods. We therefore recommend the systematic simultaneous identification of predator and prey. Finally, we evidenced that one third of the prey occurrences are unreliable and probably not of primary interest in diet studies, which might decrease the relevance of combining several primer sets instead of using one efficient primer set. In conclusion, this study provides general criteria enabling the selection of primers whilst considering different scientific and methodological constraints.
Electrophysiological evidence for impaired auditory sensory memory in Cystinosis despite typical sensory processing: An MMN investigation
Authors: Francisco Ana A. , Foxe John J. , Horsthuis Douwe J. , Molholm Sophie
Published: August 2019

Cystinosis, a genetic rare disease characterized by cystine accumulation and crystallization, results in significant damage in a multitude of tissues and organs, such as the kidney, thyroid, eye, and brain. While Cystinosis’ impact on brain function is relatively mild compared to its effects on other organs, the increased lifespan of this population and thus potential for productive societal contributions have led to increased interest on the effects on brain function. Nevertheless, and despite some evidence of structural brain differences, the neural impact of the mutation is still not well characterized.

Here, using a passive duration oddball paradigm (with different stimulus onset asynchronies (SOAs), representing different levels of demand on memory) and high-density electrophysiology, we tested basic auditory processing in a group of 22 children and adolescents diagnosed with Cystinosis (age range: 6-17 years old) and in neurotypical age-matched controls (N=24). We examined whether the N1 and mismatch negativity (MMN) significantly differed between the groups and if those neural measures correlated with verbal and non-verbal IQ. Individuals diagnosed with Cystinosis presentedsimilarN1 responses to their age-matched peers, indicating typical basic auditory processing in this population. However, whereas both groups showed similar MMN responses for the shortest (450ms) SOA, suggesting intact change detection and sensory memory, individuals diagnosed with Cystinosis presented clearly reduced responses for the longer (900ms and 1800ms) SOAs. This could indicate reduced duration auditory sensory memory traces, and thus sensory memory impairment, in children and adolescents diagnosed with Cystinosis. Future work addressing other aspects of sensory and working memory is needed to understand the underlying bases of the differences described here, and their implication for higher order processing.
Impact of ultrasonography on identifying noninvasive prenatal screening false-negative aneuploidy
Authors: Li Wei , Zeng Fanwei , Fan Baitong , Yu Nan , Wu Jing , Yang Yun , Huang Hui , Li Sheng-li , Peng Zhiyu
Published: August 2019

Purpose

To evaluate the impact of ultrasonography (US) on identifying noninvasive prenatal screening (NIPS) false-negative aneuploidy.

Methods

Analysis of large population-based NIPS false-negative aneuploidy data comprising karyotypes, clinical outcomes, and US results.

Results

From December 2010 to July 2018, a total of 3,320,457 pregnancies were screened by NIPS performed in BGI; among them, 69 NIPS false-negative aneuploidy cases with informed consent were confirmed, and US examination data for 48 cases were not available. Of the 21 cases with US results, 19 (90.5%) had various abnormalities on ultrasound, and 2 (9.5%) cases were shown to be normal on ultrasound. Additionally, 6 out of 7 live born fetuses (approximately 85.7%) were found to have abnormalities on ultrasound. Ventricular septal defects constituted the most frequently observed ultrasound abnormality type among the 21 NIPS false-negative aneuploidy cases.

Conclusion

NIPS has expanded rapidly worldwide and now accounts for a large proportion of prenatal screening tests in China. This study suggests that abnormal US findings should not be neglected, even when NIPS produces a negative result. Combining NIPS with an US examination can further reduce the incidence of livebirths with aneuploidy.
From intent to implementation: Factors affecting public involvement in life science research
Authors: Burns John. A. , Korzec Kora , Dorris Emma R.
Published: August 2019

Public involvement is key to closing the gap between research production and research use, and the only way to achieving ultimate transparency in science. The majority of life science research is not public-facing, but is funded by the public and impacts the community. We undertook a survey of researchers within the life sciences to better understand their views and perceived challenges to involving the public in their research. We had a valid response cohort of n=110 researchers, of whom 90% were primarily laboratory based. Using a mixed methods approach, we demonstrate that a top-down approach is key to motivate progression of life scientists from feeling positive towards public involvement to actually engaging in it. Researchers who viewed public involvement as beneficial to their research were more likely to have direct experience of doing it. We demonstrate that the systemic flaws in the way life sciences research enterprise is organised, including the promotion system, hypercompetition, and time pressures are major barriers to involving the public in the scientific process. Scientists are also apprehensive of being involuntarily involved in the current politicized climate, misinformation and publicity hype surrounding science nowadays makes them hesitant to share their early and in-progress research. The time required to deliberate study design and relevance, plan and build relationships for sustained involvement, provide and undertake training, and improve communication in the current research environment is often considered nonpragmatic, particularly for early career researchers. In conclusion, a top-down approach involving institutional incentives and infrastructure appears most effective at transitioning researchers from feeling positive towards public involvement to actually implementing it.
Dysbiosis personalizes fitness effect of antibiotic resistance in the mammalian gut
Authors: Cardoso Luís Leónidas , Durão Paulo , Amicone Massimo , Gordo Isabel
Published: August 2019

The fitness cost of antibiotic resistance in the absence of antibiotics is crucial to the success of suspending antibiotics as a strategy to lower resistance. Here we show that after antibiotic treatment the cost of resistance within the complex ecosystem of the mammalian gut is personalized. Using mice as anin vivomodel, we find that the fitness effect of the same resistant mutation can be deleterious in a host, but neutral or even beneficial in other hosts. Such antagonistic pleiotropy is shaped by the microbiota, as in germ-free mice resistance is consistently costly across all hosts. An eco-evolutionary model of competition for resources identifies a general mechanism underlying between host variation and predicts that the dynamics of compensatory evolution of resistant bacteria should be host specific, a prediction that was supported by experimental evolutionin vivo. The microbiome of each human is close to unique and our results suggest that the short-term costs of resistance and its long-term within-host evolution will also be highly personalized, a finding that may contribute to the observed variable outcome of control therapies.

One Sentence Summary

Personalized Fitness of Resistance Mutations.
Structural elements that modulate the substrate specificity of plant purple acid phosphatases: avenues for improved phosphorus acquisition in crops
Authors: Feder Daniel , McGeary Ross P. , Mitić Natasa , Lonhienne Thierry , Furtado Agnelo , Schulz Benjamin L. , Henry Robert J. , Schmidt Susanne , Guddat Luke W. , Schenk Gerhard
Published: August 2019

Phosphate acquisition by plants is an essential process that is directly implicated in the optimization of crop yields. Purple acid phosphatases (PAPs) are ubiquitous metalloenzymes, which catalyze the hydrolysis of a wide range of phosphate esters and anhydrides. While some plant PAPs display a preference for ATP as the substrate, others are efficient in hydrolyzing phytate or 2-phosphoenolpyruvate (PEP). PAP from red kidney bean (rkbPAP) is an efficient ATP- and ADPase, but has no activity towards phytate. The crystal structure of this enzyme in complex with an ATP analogue (to 2.20 Å resolution) provides insight into the amino acid residues that play an essential role in binding this substrate. Homology modelling was used to generate three-dimensional structures for the active sites of PAPs from tobacco (NtPAP) andArabidopsis thaliana(AtPAP12 and AtPAP26) that are efficient in hydrolyzing phytate and PEP as substrates, respectively. In combination with substrate docking simulations and a phylogenetic analysis of 49 plant PAP sequences (including the first PAP sequences reported fromEucalyptus), several active site residues were identified that are important in defining the substrate specificities of plant PAPs. These results may inform bioengineering studies aimed at identifying and incorporating suitable plant PAP genes into crops to improve phosphorus use efficiency. Organic phosphorus sources increasingly supplement or replace inorganic fertilizer, and efficient phosphorus use of crops will lower the environmental footprint of agriculture while enhancing food production.
Segregation of Familial Risk of Obesity in NHANES Cohort Supports a Major Role for Large Genetic Effects in the Current Obesity Epidemic
Authors: Jenkins Arthur B. , Batterham Marijka , Campbell Lesley V.
Published: August 2019

The continuing increase in many countries in adult body mass index (BMI kg/m2) and its dispersion is contributed to by interaction between genetic susceptibilities and an increasingly obesogenic environment (OE). The determinants of OE-susceptibility are unresolved, due to uncertainty around relevant genetic and environmental architecture. We aimed to test the multi-modal distributional predictions of a Mendelian genetic architecture based on collectively common, but individually rare, large-effect variants and their ability to account for current trends in a large population-based sample. We studied publicly available adult BMI data (n = 9102) from 3 cycles of NHANES (1999, 2005, 2013). A first degree family history of diabetes served as a binary marker (FH0/FH1) of genetic obesity susceptibility. We tested for multi-modal BMI distributions non-parametrically using kernel-smoothing and conditional quantile regression (CQR), obtained parametric fits to a Mendelian model in FH1, and estimated FH x OE interactions in CQR models and ANCOVA models incorporating secular time. Non-parametric distributional analyses were consistent with multi-modality and fits to a Mendelian model in FH1reliably identified 3 modes. Mode separation accounted for ~40% of BMI variance in FH1providing a lower bound for the contribution of large effects. CQR identified strong FH x OE interactions and FH1accounted for ~60% of the secular trends in BMI and its SD in ANCOVA models. Multimodality in the FH effect is inconsistent with a predominantly polygenic, small effect architecture and we conclude that large genetic effects interacting with OE provide a better quantitative explanation for current trends in BMI.
Experimental evolution reveals the genetic basis and systems biology of superoxide stress tolerance
Authors: Tan Justin , Olson Connor A. , Park Joon Ho , Sastry Anand V. , Phaneuf Patrick V. , Yang Laurence , Szubin Richard , Hefner Ying , Feist Adam M. , Palsson Bernhard O.
Published: August 2019

Bacterial response to oxidative stress is of fundamental importance. Oxidative stresses are endogenous, such as reactive oxidative species (ROS) production during respiration, or exogenous in industrial biotechnology, due to culture conditions or product toxicity. The immune system inflicts strong ROS stress on invading pathogens. In this study we make use of Adaptive Laboratory Evolution (ALE) to generate two independent lineages ofEscherichia coliwith increased tolerance to superoxide stress by up to 500% compared to wild type. We found: 1) that the use of ALE reveals the genetic basis for and systems biology of ROS tolerance, 2) that there are only 6 and 7 mutations, respectively, in each lineage, five of which reproducibly occurred in the same genes (iron-sulfur cluster regulatoriscR, putative iron-sulfur repair proteinygfZ, pyruvate dehydrogenase subunit EaceE, succinate dehydrogenasesucA, and glutamine tRNAglnX), and 3) that the transcriptome of the strain lineages exhibits two different routes of tolerance: the direct mitigation and repair of ROS damage and the up-regulation of cell motility and swarming genes mediated through phosphate starvation, which has been linked to biofilm formation and aggregation. These two transcriptomic responses can be interpreted as ‘flight’ and ‘fight’ phenotypes.

Importance

Bacteria encounter oxidative stress from multiple sources. During pathogenic infections, our body’s immune system releases ROS as a form of antimicrobial defense whilst bacteria used in industrial biotechnology are frequently exposed to genetic modifications and culture conditions which induce oxidative stress. In order to get around the body’s defences, pathogens have developed various adaptations to tolerate high levels of ROS, and these adaptive mechanisms are not always well understood. At the same time, there is a need to improve oxidative stress tolerance for industrially relevant strains in order to increase robustness and productivity. In this study we generate two strains of superoxide tolerantEscherichia coliand identify several adaptive mechanisms. These findings can be directly applied to improve production strain fitness in an industrial setting. They also provide insight into potential virulence factors in other pathogens, highlighting potential targets for antimicrobial compounds.
Retention and predictors of attrition among patients who started antiretroviral therapy in Zimbabwe’s National Antiretroviral Therapy Programme between 2012 and 2015
Authors: Makurumidze Richard , Mutasa-Apollo Tsitsi , Decroo Tom , Choto Regis C. , Takarinda Kudakwashe C. , Dzangare Janet , Lynen Lutgarde , Van Damme Wim , Hakim James , Magure Tapuwa , Mugurungi Owen , Rusakaniko Simbarashe
Published: August 2019

Background

The last evaluation to assess outcomes for patients receiving antiretroviral therapy (ART) through the Zimbabwe public sector was conducted in 2011, covering the 2007-2010 cohorts. The reported retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. We report findings of a follow up evaluation for the 2012-2015 cohorts to assess the implementation & impact of recommendations from this prior evaluation.

Methods

A nationwide retrospective study was conducted in 2016. Multi-stage proportional sampling was used to select health facilities and study participants records. The data extracted from patient manual records included demographic, baseline clinical characteristics and patient outcomes (active on treatment, died, transferred out, stopped ART and lost to follow-up (LFTU)) at 6, 12, 24 and 36 months. The data were analysed using Stata/IC 14.2. Retention was estimated using survival analysis. The predictors associated with attrition were determined using a multivariate Cox regression model.

Results

A total of 3,810 participants were recruited in the study. The median age in years was 35 (IQR: 28-42). Overall, retention increased to 92.4%, 86.5%, 79.2% and 74.4% at 6, 12, 24 and 36 months respectively. LFTU accounted for 98% of attrition. Being an adolescent or a young adult (aHR 1.41; 95%CI:1.14-1.74), receiving care at primary health care facility (aHR 1.23; 95%CI:1.01-1.49), having initiated ART between 2014-2015 (aHR 1.45; 95%CI:1.24-1.69), having WHO Stage 4 (aHR 2.06; 95%CI:1.51-2.81) and impaired functional status (aHR 1.24; 95%CI:1.04-1.49) predicted attrition.

Conclusion

The overall retention was higher in comparison to the previous 2007–-2010 evaluation. Further studies to understand why attrition was found to be higher at primary health care facilities are warranted. Implementation of strategies for managing patients with advanced HIV disease, differentiated care for adolescents and young adults and tracking of LFTU should be prioritised to further improve retention.
The effect of APOBEC3B deaminase on double-stranded DNA
Authors: Chapman Joseph , Custance Michael , Shen Birong , Furano Anthony V.
Published: August 2019

Mutations mediated by the APOBEC3 (A3) family of single-strand specific cytosine deaminases can accumulate in various cancers, as strand-coordinated clusters and isolated lesions. A3-mediated mutations also occur during normal development, accounting for ~20% of heritable mutations. A3B is an archetypical member of this family and is thought to contribute to both cancer initiation and progression. A3B has a strong preference for C in a TC context and catalyzes hydrolysis of the primary amine of un-paired C to generate U. Subsequent repair generates a distinctive pattern of C-substitutions, which along with their context signify their A3B origin. Although single-stranded DNA is the preferred A3B substrate, we report here that in some instances A3B can deaminate the C of TC in a double-stranded DNA context in vitro. These include C paired to O6-methylguanine (O6meG), to an abasic (AP) site, or to a G adjacent to an AP site. AP sites are the most common lesion in DNA, and O6meG levels increase under alkylating conditions caused by environmental nitrosamines and some chemotherapeutic agents. We also show that elevated expression of A3B can enhance double-stranded breaks induced by the alkylating agent MNNG in mammalian cells, but this effect does not require A3B deaminase activity.
An improved auxin-inducible degron system preserves native protein levels and enables rapid and specific protein depletion
Authors: Sathyan Kizhakke Mattada , McKenna Brian D. , Anderson Warren D. , Duarte Fabiana M. , Core Leighton , Guertin Michael J.
Published: August 2019

Rapid perturbation of protein function permits the ability to define primary molecular responses while avoiding downstream cumulative effects of protein dysregulation. The auxin-inducible degron (AID) system was developed as a tool to achieve rapid and inducible protein degradation in nonplant systems. However, tagging proteins at their endogenous loci results in chronic auxin-independent degradation by the proteasome. To correct this deficiency, we expressed the auxin response transcription factor (ARF) in an improved inducible degron system. ARF is absent from previously engineered AID systems but is a critical component of native auxin signaling. In plants, ARF directly interacts with AID in the absence of auxin, and we found that expression of the ARF PB1 (Phox and Bem1) domain suppresses constitutive degradation of AID-tagged proteins. Moreover, the rate of auxin-induced AID degradation is substantially faster in the ARF-AID system. To test the ARF-AID system in a quantitative and sensitive manner, we measured genome-wide changes in nascent transcription after rapidly depleting the ZNF143 transcription factor. Transcriptional profiling indicates that ZNF143 activates transcription incisand regulates promoter-proximal paused RNA polymerase density. Rapidly inducible degradation systems that preserve the target protein's native expression levels and patterns will revolutionize the study of biological systems by enabling specific and temporally defined protein dysregulation.
Unique genetic basis of the distinct antibiotic potency of high acetic acid production in the probiotic yeast Saccharomyces cerevisiae var. boulardii
Authors: Offei Benjamin , Vandecruys Paul , De Graeve Stijn , Foulquié-Moreno María R. , Thevelein Johan M.
Published: August 2019

The yeast Saccharomyces boulardii has been used worldwide as a popular, commercial probiotic, but the basis of its probiotic action remains obscure. It is considered conspecific with budding yeast Saccharomyces cerevisiae, which is generally used in classical food applications. They have an almost identical genome sequence, making the genetic basis of probiotic potency in S. boulardii puzzling. We now show that S. boulardii produces at 37°C unusually high levels of acetic acid, which is strongly inhibitory to bacterial growth in agar-well diffusion assays and could be vital for its unique application as a probiotic among yeasts. Using pooled-segregant whole-genome sequence analysis with S. boulardii and S. cerevisiae parent strains, we succeeded in mapping the underlying QTLs and identified mutant alleles of SDH1 and WHI2 as the causative alleles. Both genes contain a SNP unique to S. boulardii (sdh1F317Y and whi2S287*) and are fully responsible for its high acetic acid production. S. boulardii strains show different levels of acetic acid production, depending on the copy number of the whi2S287* allele. Our results offer the first molecular explanation as to why S. boulardii could exert probiotic action as opposed to S. cerevisiae. They reveal for the first time the molecular-genetic basis of a probiotic action-related trait in S. boulardii and show that antibacterial potency of a probiotic microorganism can be due to strain-specific mutations within the same species. We suggest that acquisition of antibacterial activity through medium acidification offered a selective advantage to S. boulardii in its ecological niche and for its application as a probiotic.
Targeted delivery of CRISPR interference system against Fabp4 to white adipocytes ameliorates obesity, inflammation, hepatic steatosis, and insulin resistance
Authors: Chung Jee Young , Ain Qurrat Ul , Song Yoonsung , Yong Seok-Beom , Kim Yong-Hee
Published: August 2019

Obesity is an increasing pathophysiological problem in developed societies. Despite all major progress in understanding molecular mechanisms of obesity, currently available anti-obesity drugs have shown limited efficacy with severe side effects. CRISPR interference (CRISPRi) mechanism based on catalytically dead Cas9 (dCas9) and single guide RNA (sgRNA) was combined with a targeted nonviral gene delivery system to treat obesity and obesity-induced type 2 diabetes. A fusion peptide targeting a vascular and cellular marker of adipose tissue, prohibitin, was developed by conjugation of adipocyte targeting sequence (CKGGRAKDC) to 9-mer arginine (ATS-9R). (dCas9/sgFabp4) + ATS-9R oligoplexes showed effective condensation and selective delivery into mature adipocytes. Targeted delivery of the CRISPRi system against Fabp4 to white adipocytes by ATS-9R induced effective silencing of Fabp4, resulting in reduction of body weight and inflammation and restoration of hepatic steatosis in obese mice. This RNA-guided DNA recognition platform provides a simple and safe approach to regress and treat obesity and obesity-induced metabolic syndromes.