bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimated Organ Doses to Patients from Diagnostic Nuclear Medicine Examinations over Five Decades
Authors: Villoing Daphnée , Drozdovitch Vladimir , Simon Steven L. , Kitahara Cari M. , Linet Martha S. , Melo Dunstana R.
Published: September 2017

Ionizing radiation exposure to the general U.S. population nearly doubled between 1980 and 2006, due almost entirely to the significant increase in the number of radiologic and nuclear medicine procedures performed. Significant changes in the types of procedures and radionuclides used in nuclear medicine, as well as in detection technology, have led to notable changes over time in absorbed doses to specific organs. This study is the first to estimate per-procedure organ doses to nuclear medicine patients and trends in doses over five decades. Weighted average organ doses per examination to 14 organs of interest were calculated for 17 examination types over 10 5‐y time periods (1960–2010) as the product of the percentage of use of each radiopharmaceutical in those diagnostic procedures based on comprehensive literature review, the administered activity, and ICRP dose coefficients; doses per radiopharmaceutical were also provided for each organ, procedure, and time period. The weighted doses to adult nuclear medicine patients from cardiac procedures increased to all organs of interest between 1960 and 2010 except for the urinary bladder wall. From high radiation doses for most other procedures in the 1960s, with up to 0.7 Gy in the specific case of radioiodinated thyroid scans, organ-absorbed doses generally decreased from 1960 to 1990. In contrast, during the 1990s and 2000s, the weighted doses were gradually increased for some procedures, such as brain and skeleton scans. The increasing number of nuclear medicine procedures, specifically cardiac scans and changes in weighted doses, underscore the need to monitor exposure levels and radiation-related disease risks in nuclear medicine patients.
Contact Lens Compliance With Ophthalmologists and Other Health Professionals
Authors: Taslipinar Uzel Ayse Guzin , Uzel Mehmet Murat , Yuksel Nilay , Akcay Emine Kalkan
Published: September 2017

Purpose:

To assess the compliance with contact lens (CL) use among ophthalmologists and other health professionals, and to identify the main noncompliant behaviors.

Methods:

A cross-sectional, comparative study was designed for soft CL wearers. Twenty-five ophthalmologists, 24 medical doctors other than ophthalmologists, 20 nurses (health professionals), and 52 lay people (members of the public) subjects were included in the interview. The compliance rate for each behavior were determined and compared. Users were asked to rate their subjective use to calculate self-evaluation scores.

Results:

The compliance rate was found to be the highest among ophthalmologists; however, the difference was not significant (P=0.083). Although the level of compliance was not associated with the subjects' age, duration of lens wear, or wearing days per week (P>0.05), an association was found with the number of wearing hours per day (P=0.010). Increased wearing hours per day was found to increase the rate of poor compliance (P=0.010). Significant differences were found between the groups in storing lenses in fresh solution, lens wearing time according to the ophthalmologist recommendation, and follow-up visits according to ophthalmologist recommendation (P<0.001, P=0.036, P=0.001, respectively). Self-evaluation scores among ophthalmologists, health professionals, and the lay people were 7.56±0.86, 7.59±1.29, and 7.67±1.60, respectively, and no significant differences existed between the groups (P=0.930).

Conclusion:

No differences were evident between the groups in terms of good compliance with CL wear and care practices. As this result shows that compliance with CL wear and care practices is not only related to the level of knowledge, different methods should be developed to increase compliance.
Examining Variation in Mental Models of Influence and Leadership Among Nursing Leaders and Direct Care Nurses
Authors: Weaver Sallie J. , Mossburg Sarah E. , Pillari MarieSarah , Kent Paula S. , Daugherty Biddison Elizabeth Lee
Published: September 2017

This study explored similarities and differences in the views on team membership and leadership held by nurses in formal unit leadership positions and direct care nurses. We used a mixed-methods approach and a maximum variance sampling strategy, sampling from units with both high and low safety behaviors and safety culture scores. We identified several key differences in mental models of care team membership and leadership between formal leaders and direct care nurses that warrant further exploration.
Immature Terminal Deoxynucleotidyl Transferase Positive B Cells are Detected in a Subset of Adult and Pediatric Liver Biopsies
Authors: Wen Kwun Wah , Gill Ryan M.
Published: September 2017

Terminal deoxynucleotidyl transferase (TdT) is a nuclear enzyme restricted to precursor lymphoid cells and their malignant counterparts; immunohistochemical TdT labeling is helpful in recognition of lymphoblasts, which can resemble mature lymphocytes. The diagnosis of B-lymphoblastic leukemia/lymphoma (B-ALL) is occasionally first encountered on liver core biopsy, but TdT immunostain specificity for B-ALL is not clearly established in this setting, which can be problematic when only a few TdT-positive cells are identified. In this study, we evaluated the incidence and distribution of immature B lymphocytes coexpressing TdT and PAX-5, in pediatric and adult liver biopsies, to determine whether a normal complement of hepatic immature B cells can be detected, which must be recognized in a workup to exclude B-ALL. We selected 41 pediatric and adult liver biopsies with a significant portal and/or sinusoidal hematolymphoid infiltrate and performed immunohistochemical stains for TdT and PAX-5 to identify and categorize distribution of immature B cells. TdT-positive cells were detected in 40% of pediatric liver biopsies with a significant hematolymphoid infiltrate (4/10), which included all biopsies from neonates (and infants under 9 wk of age). In adults, immature B-cell infiltrates were less common (6%, 2/31). Dual immunostaining was performed on 2 cases of neonatal hepatitis, which documented B-cell lineage in at least a subset of TdT-positive cells and there was no colabeling with CD3. Immature B cells can be detected in liver biopsies in a variety of clinical settings, most commonly in children, and presence of a few TdT-positive cells cannot be considered entirely specific for involvement by B-ALL. Further workup for B-ALL can be warranted if there is more extensive multifocal portal and/or sinusoidal involvement by blasts with TdT labeling.
Reconstruction of Peripelvic Oncologic Defects
Authors: Weichman Katie E. , Matros Evan , Disa Joseph J.
Published: September 2017

Learning Objectives:

After studying this article, the participant should be able to: 1. Understand the anatomy of the peripelvic area. 2. Understand the advantages and disadvantages of performing peripelvic reconstruction in patients undergoing oncologic resection. 3. Select the appropriate local, pedicled, or free-flap reconstruction based on the location of the defect and donor-site characteristics.

Peripelvic reconstruction most commonly occurs in the setting of oncologic ablative surgery. The peripelvic area contains several distinct reconstructive regions, including vagina, vulva, penis, and scrotum. Each area provides unique reconstructive considerations. In addition, prior or future radiation therapy or chemotherapy along with cancer cachexia can increase the complexity of reconstruction.
Five-Year Safety Data for More than 55,000 Subjects following Breast Implantation: Comparison of Rare Adverse Event Rates with Silicone Implants versus National Norms and Saline Implants
Authors: Singh Navin , Picha George J. , Hardas Bhushan , Schumacher Andrew , Murphy Diane K.
Published: September 2017

Background:

The U.S. Food and Drug Administration has required postapproval studies of silicone breast implants to evaluate the incidence of rare adverse events over 10 years after implantation.

Methods:

The Breast Implant Follow-Up Study is a large 10-year study (>1000 U.S. sites) evaluating long-term safety following primary augmentation, revision-augmentation, primary reconstruction, or revision-reconstruction with Natrelle round silicone breast implants compared with national norms and outcomes with saline implants. Targeted adverse events in subjects followed for 5 to 8 years included connective tissue diseases, neurologic diseases, cancer, and suicide.

Results:

The safety population comprised 55,279 women (primary augmentation, n = 42,873; revision-augmentation, n = 6837; primary reconstruction, n = 4828; and revision-reconstruction, n = 741). No targeted adverse events occurred at significantly greater rates in silicone implant groups versus national norms across all indications. The standardized incidence rate (observed/national norm) for all indications combined was 1.4 for cervical/vulvar cancer, 0.8 for brain cancer, 0.3 for multiple sclerosis, and 0.1 for lupus/lupus-like syndrome. Silicone implants did not significantly increase the risk for any targeted adverse events compared with saline implants. The risk of death was similar with silicone versus saline implants across all indications. The suicide rate (10.6 events per 100,000 person-years) was not significantly higher than the national norm. No implant-related deaths occurred.

Conclusions:

Results from 5 to 8 years of follow-up for a large number of subjects confirmed the safety of Natrelle round silicone implants, with no increased risk of systemic disease or suicide versus national norms or saline implants.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Extended Alar Contour Grafts: An Evolution of the Lateral Crural Strut Graft Technique in Rhinoplasty
Authors: Cochran C. Spencer , Sieber David A.
Published: September 2017

Modification of the lower lateral cartilage complex is the sine qua non of modern rhinoplasty, and the open approach to rhinoplasty has expanded the number of techniques available to help achieve an aesthetically pleasing tip. The ideal tip has been described as having a diamond-shaped configuration, with the lateral points formed by the tip-defining points, the superior point by the supratip, and the inferior point by the columellar break point. Over the years, various techniques have been described to minimize isolation of the tip and to help achieve the ideal tip configuration: lateral crural strut grafts, alar contour grafts (i.e., rim grafts), alar strut grafts, subdomal grafts, and suturing techniques such as alar flaring sutures. The authors present their technique of the extended alar contour graft, which represents an evolution of the lateral crural strut graft and its marriage with the alar contour graft. Lateral crural abnormalities do not usually occur singularly, but rather are the result of an interplay of several factors. Nevertheless, the recurring theme of orientation and alar support to prevent isolation of the tip by extended alar grooves remains. Extended alar contour grafts are a versatile technique to optimize tip shape and orientation by combining the many positive attributes of lateral crural strut grafts and alar contour grafts.
What Is the Best Lens Angle for Rigid Diagnostic Cystoscopy? A Comparison of 30-Degree and 70-Degree Lenses
Authors: Ragsdale Cassandra , Hreha Holly , Hardesty Jeffrey S. , Yune Junchan J. , Chan Philip J. , Siddighi Sam
Published: September 2017

Objectives

The optimal degree of cystoscope to perform diagnostic cystoscopy is dependent on the surgeon’s discretion because there are no studies addressing the superiority of one degree of cystoscope over another. The objective was to determine which lens, 70-degree versus 30-degree lens, was better in identifying lesions scattered throughout the bladder.

Methods

A simulation was created using 3 different artificial bladder models complete with sutures representing lesions placed at different locations in each bladder. Gynecologists and urologists performed cystoscopy using both the 30- and 70-degree lenses on the bladder models in a randomized and single-blinded fashion. The physicians performed routine diagnostic cystoscopy and noted the number of lesions throughout the bladder. The number of lesions each physician identified and the time to complete cystoscopy were noted. A total of 16 physicians participated, and there were a total of 18 lesions among the 3 different bladder models.

Results

A total of 86 cystoscopy trials were obtained from all physicians and bladder models attempted. The odds of detecting a lesion with the 70-degree lens cystoscope was 1.77 times greater than the 30-degree lens cystoscope (95% confidence interval, 1.24–2.53; P = 0.002). There was also difference in the average number of lesions found between the 30- and 70-degree cystoscopes with 2.6 ± 2.7 more lesions identified using the 70-degree cystoscope compared with the 30-degree cystoscope. In terms of specific location, 2.6 ± 1.7 more lesions were found at the bladder neck using the 70-degree lens scope versus the 30-degree lens scope (95% confidence interval, 1.37–3.83; P = 0.013).

Conclusions

The results suggested that the 70-degree lens was the better choice for the identification of bladder lesions when compared with the 30-degree lens in rigid diagnostic cystoscopy.
Is There a Relationship Between Patient-Reported Satisfaction and Persistence on Overactive Bladder Syndrome Pharmacotherapy?
Authors: Tran Alexis M. , Reis Renata , Iyer Shilpa , Botros Carolyn , Goldberg Roger P. , Sand Peter K. , Botros Sylvia M.
Published: September 2017

Objectives

This study aimed to determine the relationship between patient satisfaction with overactive bladder syndrome (OAB) pharmacotherapy and persistence rates. We compared persistence rates between satisfied and dissatisfied patients at designated study intervals.

Methods

This was a retrospective cohort study of new patients who initiated OAB medication. Patients were classified as either satisfied or dissatisfied on the basis of a single-item treatment satisfaction question. Persistence was defined as continuous days on therapy. The measured rate of persistence was determined as the ratio of patients who persisted on medication at 4, 12, and 24 weeks. Data collection included demographic and prescription information; urinary symptom parameters, symptom and quality-of-life scales, and patient-reported outcomes. Two-sample t test or Wilcoxon rank sum test was used to compare continuous outcomes between both groups (satisfied vs not satisfied). χ2 Test or Fisher exact test was used to compare categorical outcomes between groups.

Results

We analyzed the first 116 charts that met our inclusion criteria. Satisfied and dissatisfied patients did not differ in demographic variables. Satisfied patients had a median of 461 vs 254 persistent days (P = 0.0001). Satisfied patients (12.5% vs 40%) were less likely to discontinue medication (P = 0.0068). The discontinuation-free distribution was significantly different between satisfied and dissatisfied cohorts, favoring those who reported satisfaction with OAB medication at all time points (P < 0.0001). Patients who totally discontinued pharmacotherapy were 7 times more likely to be dissatisfied (odds ratio, 7.0; P = 0.002).

Conclusions

Our study helps clarify the relationship between persistence on OAB medication and treatment satisfaction. We found that persistence could serve as a surrogate marker for patient satisfaction because those who reported being satisfied were more likely to persist on therapy at all study intervals.
Age-related decline in behavioral discrimination of amplitude modulation frequencies compared to envelope-following responses
Authors: Lai Jesyin , Bartlett Edward L.
Published: September 2017

The ability to discriminate modulation frequencies is important for speech intelligibility because speech has amplitude and frequency modulations. Neurophysiological responses assessed by envelope following responses (EFRs) significantly decline at faster amplitude modulation frequencies (AMF) in older subjects. A typical assumption is that a decline in EFRs will necessarily result in corresponding perceptual deficits. To test this assumption, we investigated young and aged Fischer-344 rats’ behavioral AMF discrimination abilities and compared to their EFRs. A modified version of prepulse inhibition (PPI) of acoustic startle reflex (ASR) was used to obtain behavioral performance. A PPI trial contains pulses of sinusoidal AM (SAM) at 128 Hz presented sequentially, a SAM prepulse with different AMF and a startle-eliciting-stimulus. To account for hearing threshold shift or age-related synaptopathy, stimulus levels were presented at 10-dB lower or match to the aged peripheral neural activation (using auditory brainstem response wave I amplitude). When AMF differences and modulation depths were large, young and aged animals’ behavioral performances were comparable. Aged animals’ AMF discrimination abilities declined as the AMF difference or the modulation depth reduced, even compared to the young with peripheral matching. Young animals showed smaller relative decreases in EFRs with reduced modulation depths. The correlation of EFRs and AM perception was identified to be more consistent in young animals. The overall results revealed larger age-related deficits in behavioral perception compared to EFRs, suggesting additional factors that affect perception despite smaller degradation in neural responses. Hence, behavioral and physiological measurements are critical in unveiling a more complete picture on the auditory function.
Quantifying ethical tradeoffs for vaccine efficacy trials during severe epidemics
Authors: Bellan Steven E. , Pulliam Juliet R.C. , van der Graaf Rieke , Fox Spencer J. , Dushoff Jonathan , Meyers Lauren Ancel
Published: September 2017

Background

During emerging epidemics of highly fatal diseases, rapid development and testing of new vaccines may be critical to curbing transmission and saving lives. However, the design of vaccine efficacy trials in such contexts may face considerable logistical, epidemiological, or ethical impediments. Three different vaccine efficacy trials were conducted during the 2014-2016 Ebola virus epidemic in West Africa, each with different designs. At the time, there was vigorous debate on the tradeoff between a trial’s ability to yield information of scientific and societal value versus the perceived ethical dilemma of withholding potentially life-saving vaccines from control participants. Whereas the scientific value of a trial is often estimated in terms of statistical power, speed, and rigor, we lack similar metrics for the ethical costs of withholding interventions.

Methods and Findings

Here, we introduce a conceptual framework that fills this gap and allows quantitative assessment of both the scientific value of a study and the risks incurred by trial participants. We show that even untested vaccines against severe diseases may be probabilistically beneficial—i.e. after accounting for realistic uncertainty in their safety and efficacy, trial participants are expected to be better off vaccinated than not. While accounting for this uncertainty, we estimate trial participant risk under a hypothetical, idealized vaccine rollout scenario and compare it to risk under various candidate trial designs, in order to elucidate specific quantitative tradeoffs between cumulative risk to trial participants and information gained. Through an illustrative simulation example, we highlight specific trial-design modifications that allow for conscientious balance between minimizing participant risk and acquiring information of societal value. These include modifications that affect the speed with which a trial would detect an efficacious vaccine (greater sample size or enrollment rate, interim analyses, or risk-prioritized vaccine rollout), which leads to earlier vaccination of control participants should the vaccine be efficacious, and those that systematically limit the risk “spent” by unvaccinated individuals (e.g., providing vaccination to controls after a delay, or presumptive vaccination of subjects above a risk threshold).

Conclusion

We advocate this conceptual approach as a means of clarifying the tensions between opposing viewpoints and facilitating transparent discussion to aid ethical and efficient responses to future emerging epidemics.
The GENIUS Approach to Robust Mendelian Randomization Inference
Authors: Tchetgen Eric J. Tchetgen , Sun BaoLuo , Walter Stefan
Published: September 2017

Mendelian randomization (MR) is a popular instrumental variable (IV) approach, in which one or several genetic markers serve as IVs that can be leveraged to recover under certain conditions, valid inferences about a given exposure-outcome causal association subject to unmeasured confounding. A key IV identification condition known as the exclusion restriction states that the IV has no direct effect on the outcome that is not mediated by the exposure in view. In MR studies, such an assumption requires an unrealistic level of knowledge and understanding of the mechanism by which the genetic markers causally affect the outcome, particularly when a large number of genetic variants are considered as IVs. As a result, possible violation of the exclusion restriction can seldom be ruled out in such MR studies, and if present, such violation can invalidate IVbased inferences even if unbeknownst to the analyst, confounding is either negligible or absent. To address this concern, we introduce a new class of IV estimators which are robust to violation of the exclusion restriction under a large collection of data generating mechanisms consistent with parametric models commonly assumed in the MR literature. Our approach which we have named “MR G-Estimation under No Interaction with Unmeasured Selection” (MR GENIUS) may in fact be viewed as a modification to Robins’ G-estimation approach that is robust to both additive unmeasured confounding and violation of the exclusion restriction assumption. We also establish that estimation with MR GENIUS may also be viewed as a robust generalization of the well-known Lewbel estimator for a triangular system of structural equations with endogeneity. Specifically, we show that unlike Lewbel estimation, MR GENIUS is under fairly weak conditions also robust to unmeasured confounding of the effects of the genetic IVs on both the exposure and the outcome, another possible violation of a key IV Identification condition. Furthermore, while Lewbel estimation involves specification of linear models both for the outcome and the exposure, MR GENIUS generally does not require specification of a structural model for the direct effect of invalid IVs on the outcome, therefore allowing the latter model to be unrestricted. Finally, unlike Lewbel estimation, MR GENIUS is shown to equally apply for binary, discrete or continuous exposure and outcome variables and can be used under prospective sampling, or retrospective sampling such as in a case-control study, as well as for right censored time-to-event outcomes under an additive hazards model.
Neonatal Zika virus infection causes epileptic seizures, viral persistence and long-term behavioral impairment
Authors: Souza Isis N. O. , Frost Paula S. , França Julia V. , Nascimento-Viana Jéssica , Neris Rômulo L. S. , Freitas Leandro , Pinheiro Daniel J. L. L. , Neves Gilda , Chimelli Leila , De Felice Fernanda G. , Cavalheiro Ésper A. , Ferreira Sergio T. , Da Poian Andrea T. , Assunção-Miranda Iranaia , Figueiredo Claudia P. , Clarke Julia R.
Published: September 2017

A causal relationship between congenital Zika virus (ZIKV) exposure and microcephaly and other neurological disorders have been established, but long-term consequences of infection are still unknown. We evaluated acute and late neuropathological and behavioral consequences of ZIKV infection in a neonatal immunocompetent mouse model. ZIKV showed brain tropism, causing post-natal microcephaly and several behavioral dysfunctions. During the acute phase of infection, mice developed very frequent epileptic seizures, which are consistently reduced by TNF-α neutralization. Although adult animals recover from seizures, they become more susceptible to chemically-induced crises. Intriguingly, the virus remained actively replicating in adult animals, which show persistent necrosis and calcifications in the mice brain. Altogether the results reveal late consequences of neonatal ZIKV exposure and suggest the early inhibition of neuroinflammation as a potential treatment.
Integrative pipeline for profiling DNA copy number and inferring tumor phylogeny
Authors: Urrutia Eugene , Chen Hao , Zhou Zilu , Zhang Nancy R , Jiang Yuchao
Published: September 2017

Copy number variation is an important and abundant source of variation in the human genome, which has been associated with a number of diseases, especially cancer. Massively parallel next-generation sequencing allows copy number profiling with fine resolution. Such efforts, however, have met with mixed successes, with setbacks arising partly from the lack of reliable analytical methods to meet the diverse and unique challenges arising from the myriad experimental designs and study goals in genetic studies. In cancer genomics, detection of somatic copy number changes and profiling of allele-specific copy number (ASCN) are complicated by experimental biases and artifacts as well as normal cell contamination and cancer subclone admixture. Furthermore, careful statistical modeling is warranted to reconstruct tumor phylogeny by both somatic ASCN changes and single nucleotide variants. Here we describe a flexible computational pipeline, MARATHON, which integrates multiple related statistical software for copy number profiling and downstream analyses in disease genetic studies.

Availability and implementation

MARATHON is publicly available athttps://github.com/yuchaojiang/MARATHON.

Contact

yuchaoj@email.unc.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.
Mutational signatures reveal the role of RAD52 in p53-independent p21 driven genomic instability
Authors: Galanos Panagiotis , Pappas George , Polyzos Alexander , Kotsinas Athanassios , Svolaki Ioanna , Giakoumakis Nikos N , Glytsou Christina , Pateras Ioannis S , Swain Umakanta , Souliotis Vassilis , Georgakilas Alexander , Geacintov Nicholas , Scorrano Luca , Lukas Claudia , Lukas Jiri , Livneh Zvi , Lygerou Zoi , Sørensen Claus Storgaard , Bartek Jiri , Gorgoulis Vassilis G.
Published: September 2017

Background

Genomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential to design appropriate therapeutic strategies. In a recent study we reported an unexpected oncogenic property of p21WAF1/Cip1showing that its chronic expression, in a p53-deficient environment, causes genomic instability by deregulating the replication licensing machinery.

Results

Extending on this work we now demonstrate that p21WAF1/Cip1can further fuel genomic instability by suppressing the repair capacity of low and high fidelity pathways that deal with nucleotide abnormalities. Consequently, fewer single nucleotide substitutions (SNSs) occur, while formation of highly deleterious DNA double-strand breaks (DSBs) is enhanced, crafting a characteristic mutational signature landscape. Guided by the mutational signatures formed, we found at the mechanistic level that the DSBs were repaired by Rad52-dependent Break-Induced Replication (BIR) and Single-Strand Annealing (SSA). Conversely, the error-free synthesis-dependent strand annealing (SDSA) repair route was deficient. Surprisingly, Rad52 was activated transcriptionally in an E2F1-dependent manner, rather than post-translationally as is common for DNA repair factor activation.

Conclusions

Our results signify the importance of mutational signatures as guides to disclose the “repair history” leading to genomic instability. In this vein, following this approach we unveiled how chronic p21WAF1/Cip1expression rewires the repair process, identifying Rad52 as a source of genomic instability and a candidate therapeutic target.
Impact of spatial organization on a novel auxotrophic interaction among soil microbes
Authors: Jiang Xue , Zerfaß Christian , Eichmann Ruth , Asally Munehiro , Schäfer Patrick , Soyer Orkun S
Published: September 2017

A key prerequisite to achieve a deeper understanding of microbial communities and to engineer synthetic ones is to identify the individual metabolic interactions among key species and how these interactions are affected by different environmental factors. Deciphering the physiological basis of species-species and species-environment interactions in spatially organized environment requires reductionist approaches using ecologically and functionally relevant species. To this end, we focus here on a specific defined system to study the metabolic interactions in a spatial context among a plant-beneficial endophytic fungusSerendipita indica,and the soil-dwelling model bacteriumBacillus subtilis. Focusing on the growth dynamics ofS. indicaunder defined conditions, we identified an auxotrophy in this organism for thiamine, which is a key co-factor for essential reactions in the central carbon metabolism. We found thatS. indicagrowth is restored in thiamine-free media, when co-cultured withB. subtilis. The success of this auxotrophic interaction, however, was dependent on the spatial and temporal organization of the system; the beneficial impact ofB. subtiliswas only visible when its inoculation was separated from that ofS. indicaeither in time or space. These findings describe a key auxotrophic interaction in the soil among organisms that are shown to be important for plant ecosystem functioning, and point to the potential importance of spatial and temporal organization for the success of auxotrophic interactions. These points can be particularly important for engineering of minimal functional synthetic communities as plant-seed treatments and for vertical farming under defined conditions.
Force dependence of filopodia adhesion: involvement of myosin II and formins
Authors: Alieva N. O. , Efremov A. K. , Hu S. , Oh D. , Chen Z. , Natarajan M. , Ong H. T. , Jégou A. , Romet-Lemonne G. , Groves J. T. , Sheetz M. P. , Yan J. , Bershadsky A. D.
Published: September 2017

Filopodia are dynamic membrane protrusions driven by polymerization of an actin filament core, mediated by formin molecules at the filopodia tips. Filopodia can adhere to the extracellular matrix and experience both external and cell generated pulling forces. The role of such forces in filopodia adhesion is however insufficiently understood. Here, we induced sustained growth of filopodia by applying pulling force to their tips via attached fibronectin-coated beads trapped by optical tweezers. Strikingly, pharmacological inhibition or knockdown of myosin IIA, which localized to the base of filopodia, resulted in weakening of filopodia adherence strength. Inhibition of formins, which caused detachment of actin filaments from formin molecules, produced similar effect. Thus, myosin IIA-generated centripetal force transmitted to the filopodia tips through interactions between formins and actin filaments are required for filopodia adhesion. Force-dependent adhesion led to preferential attachment of filopodia to rigid versus fluid substrates, which may underlie cell orientation and polarization.
Acute condensin depletion causes genome decompaction without altering the level of global gene expression inSaccharomyces cerevisiae
Authors: Paul Matthew Robert , Markowitz Tovah Elise , Hochwagen Andreas , Ercan Sevinç
Published: September 2017

Condensins are broadly conserved chromosome organizers that function in chromatin compaction and transcriptional regulation, but to what extent these two functions are linked has remained unclear. Here, we analyzed the effect of condensin inactivation on genome compaction and global gene expression in the yeastSaccharomyces cerevisiae. Spike-in-controlled 3C-seq analysis revealed that acute condensin inactivation leads to a global decrease in close-range chromosomal interactions as well as more specific losses of homotypic tRNA gene clustering. In addition, a condensin-rich topologically associated domain between the ribosomal DNA and the centromere on chromosome XII is lost upon condensin inactivation. Unexpectedly, these large-scale changes in chromosome architecture are not associated with global changes in transcript levels as determined by spike-in-controlled mRNA-seq analysis. Our data suggest that the global transcriptional program ofS. cerevisiaeis resistant to condensin inactivation and the associated profound changes in genome organization.

Significance Statement

Gene expression occurs in the context of higher-order chromatin organization, which helps compact the genome within the spatial constraints of the nucleus. To what extent higher-order chromatin compaction affects gene expression remains unknown. Here, we show that gene expression and genome compaction can be uncoupled in the single-celled model eukaryoteSaccharomyces cerevisiae. Inactivation of the conserved condensin complex, which also organizes the human genome, leads to broad genome decompaction in this organism. Unexpectedly, this reorganization has no immediate effect on the transcriptome. These findings indicate that the global gene expression program is robust to large-scale changes in genome architecture in yeast, shedding important new light on the evolution and function of genome organization in gene regulation.
Development of an Intrinsic Skin Sensor for Blood Glucose Level with CRISPR-mediated Genome Editing in Epidermal Stem Cells
Authors: Yue Jiping , Li Yuanyuan , Gou Xuewen , Wu Xiaoyang
Published: September 2017

Biointegrated sensors can address various challenges in medicine by transmitting a wide variety of biological signals. A tempting possibility that has not been explored before is whether we can take advantage of genome editing technology to transform a small portion of endogenous tissue into an intrinsic and long-lasting sensor of physiological signals. The human skin and epidermal stem cells have several unique advantages, making them particularly suitable for genetic engineering and applications
in vivo
. In this report, we took advantage of a novel platform for manipulation and transplantation of epidermal stem cells, and presented the key evidence that genome-edited skin stem cells can be exploited for continuous monitoring of blood glucose level
in vivo
. Additionally, by advanced design of genome editing, we developed an autologous skin graft that can sense glucose level and deliver therapeutic proteins for diabetes treatment. Our results revealed the clinical potential for skin somatic gene therapy.
Integrating phylogenetic and network approaches to study gene family evolution: the case of the AGAMOUS family of floral genes
Authors: Carvalho Daniel S. , Schnable James C. , Almeida Ana Maria R.
Published: September 2017

The study of gene family evolution has benefited from the use of phylogenetic tools, which can greatly inform studies of both relationships within gene families and functional divergence. Here, we propose the use of a network-based approach that in combination with phylogenetic methods can provide additional support for models of gene family evolution. We dissect the contributions of each method to the improved understanding of relationships and functions within the well-characterized family of AGAMOUS floral development genes. The results obtained with the two methods largely agreed with one another. In particular, we show how network approaches can provide improved interpretations of branches with low support in a conventional gene tree. The network approach used here may also better reflect known and suspected patterns of functional divergence relative to phylogenetic methods. Overall, we believe that the combined use of phylogenetic and network tools provide more robust assessments of gene family evolution.
EWS-FLI-1 creates a cell surface microenvironment conducive to IGF signaling by inducing pappalysin-1
Authors: Jayabal Panneerselvam , Houghton Peter J. , Shiio Yuzuru
Published: September 2017

Ewing sarcoma is an aggressive cancer of bone and soft tissue in children with poor prognosis. It is characterized by the chromosomal translocation between EWS and an Ets family transcription factor, most commonly FLI-1. EWS-FLI-1 fusion accounts for 85% of Ewing sarcoma cases. EWS-FLI-1 regulates the expression of a number of genes important for sarcomagenesis, can transform NIH3T3 and C3H10T1/2 cells, and is necessary for proliferation and tumorigenicity of Ewing sarcoma cells, suggesting that EWS-FLI-1 is the causative oncoprotein.

Here we report that EWS-FLI-1 induces the expression of pappalysin-1 (PAPPA), a cell surface protease that degrades IGF binding proteins (IGFBPs) and increases the bioavailability of IGF. EWS-FLI-1 binds to the pappalysin-1 gene promoter and stimulates the expression of pappalysin-1, leading to degradation of IGFBPs and enhanced IGF signaling. Silencing of pappalysin-1 strongly inhibited anchorage-dependent and anchorage-independent growth as well as xenograft tumorigenicity of Ewing sarcoma cells. These results suggest that EWS-FLI-1 creates a cell surface microenvironment conducive to IGF signaling by inducing pappalysin-1, which emerged as a novel target to inhibit IGF signaling in Ewing sarcoma.
First-line antituberculosis drug, pyrazinamide, its pharmaceutically relevant cocrystals and a salt
Authors: Sarmah Kashyap Kumar , Rajbongshi Trishna , Bhowmick Sourav , Thakuria Ranjit
Published: September 2017

A few pyrazinamide (Pyz) cocrystals involving hydroxybenzoic/cinnamic acid derivatives [2,4-dihydroxybenzoic acid (24DHBA); 2,6-dihydroxybenzoic acid (26DHBA); 3,5-dihydroxybenzoic acid (35DHBA) and nutraceutical molecule ferulic acid (FRA)] and the first example of a molecular salt withp-toluenesulfonic acid (pTSA) have been prepared and characterized using various solid-state techniques. A high-temperature cocrystal polymorph of Pyz·FRA has been characterized from the endothermic peaks observed using differential scanning calorimetry. The presence of substituent groups carrying hydrogen bond donors or acceptors and their influence on supramolecular synthon formation has been investigated using a Cambridge Structural Database search. Equilibrium solubility of all the binary complexes of Pyz follows the order of their coformer solubility,i.e.Pyz+·pTSA−> Pyz·35DHBA > Pyz > Pyz·26DHBA > Pyz·24DHBA > Pyz·FRA. A twofold enhancement in solubility of Pyz+·pTSA−molecular salt compared with the parent drug suggests a potential drug formulation for the treatment of tuberculosis.
A new two-dimensional CdIIcoordination polymer based on 2-(1H-imidazol-1-ylmethyl)-6-methyl-1H-benzimidazole and benzene-1,2-dicarboxylate: synthesis, crystal structure and characterization
Authors: Yang Huai-Xia , Yang Yan-Qiu , Cheng Di , Li Ya-Xue , Meng Xiang-Ru
Published: September 2017

In the construction of coordination polymers, many factors can influence the formation of the final architectures, such as the nature of the metal centres, the organic ligands and the counter-anions. In the coordination polymer poly[aqua(μ-benzene-1,2-dicarboxylato-κ4O1,O1′:O2,O2′)[μ-2-(1H-imidazol-1-ylmethyl)-6-methyl-1H-benzimidazole-κ2N2:N3]cadmium(II)], [Cd(C12H12N4)(C8H4O4)(H2O)]nor [Cd(immb)(1,2-bdic)(H2O)]n, each CdIIion is seven-coordinated by two N atoms from two symmetry-related 2-(1H-imidazol-1-ylmethyl)-6-methyl-1H-benzimidazole (immb) ligands, by four O atoms from two symmetry-related benzene-1,2-dicarboxylate (1,2-bdic2−) ligands and by one water molecule, leading to a CdN2O5distorted pentagonal bipyramidal coordination environment. The immb and 1,2-bdic2−ligands bridge CdIIions and form a two-dimensional network structure. O—H...O and N—H...O hydrogen bonds stabilize the structure. In addition, the IR spectroscopic properties, PXRD patterns, thermogravimetric behaviour and fluorescence properties of the title polymer have been investigated.
Crystal structures of 1-benzenesulfonyl-2-methyl-3-(4-nitrobenzoyl)-2,3-dihydro-1H-indole and 1-benzenesulfonyl-2-methyl-3-[(thiophen-2-yl)carbonyl]-2,3-dihydro-1H-indole
Authors: Dhanalakshmi G. , Saravanan Velu , Mohanakrishnan Arasambattu K. , Aravindhan S.
Published: September 2017

In the title indole derivatives, C22H16N2O5S, (I) and C20H15NO3S2, (II), the sulfonyl-bound phenyl rings are almost orthogonal to the indole ring system, subtending dihedral angles of 88.33 (10) and 87.58 (16)°, respectively. In both compounds, the sulfonyl S atom has a distorted tetrahedral geometry [O—S—O = 119.98 (9) and N—S—C = 104.01 (8)° for compound (I) and O—S—O = 120.08 (18) and N—S—C = 104.91 (14)° for compound (II)] and the sum of the bond angles at N indicatessp2hybridization. The molecules of both (I) and (II) feature intramolecular C—H...O hydrogen bonds that generateS(6) ring motifs with the sulfone O atom. In the crystals, molecules of (I) are linked by C—H—O hydrogen bonds, formingR44(18) ring motifs while molecules of (II) are linked by C—H—O and C—H—S hydrogen bonds, formingR22(12) ring motifs. Compound (II) was refined as an inversion twin.
X-ray and EM structures of a natively glycosylated HIV-1 envelope trimer
Authors: Gristick Harry B. , Wang Haoqing , Bjorkman Pamela J.
Published: September 2017

The structural and biochemical characterization of broadly neutralizing anti-HIV-1 antibodies (bNAbs) has been essential in guiding the design of potential vaccines to prevent infection by HIV-1. While these studies have revealed critical mechanisms by which bNAbs recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env), they have been limited to the visualization of high-mannose glycan forms only, since heterogeneity introduced from the presence of complex glycans makes it difficult to obtain high-resolution structures. 3.5 and 3.9 Å resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation were solved, revealing a glycan shield of high-mannose and complex-type N-glycans that were used to define the complete epitopes of two bNAbs. Here, the refinement of the N-glycans in the crystal structures is discussed and comparisons are made with glycan densities in glycosylated Env structures derived by single-particle cryo-electron microscopy.
Travelers’ preferences for peer-to-peer (P2P) accommodations and hotels
Authors: Young Cheri A. , Corsun David L. , Xie Karen L.
Published: September 2017

Purpose

The purpose of this study was to investigate travelers’ preferences for peer-to-peer (P2P) accommodations or hotels when traveling for leisure or business purposes given the rise of P2P accommodations in the form of Airbnb, Vacation Rentals by Owners (VRBO) One Fine Stay, etc.

Design/methodology/approach

VRBO hosts in Denver, Colorado, USA provided contact information for 788 travelers who stayed with them over the prior three years. These travelers received an email survey and the opportunity to be entered in a drawing for one of three US$250 gift cards.

Findings

P2P usage was driven by leisure travel. The most influential factors in the choice of P2P over hotel were price, location, party size, dwelling size and trip length. When choosing a hotel for business travel, the influential factors were location, safety and security, price and knowing what one will receive in the way of facility and services.

Research limitations/implications

The external validity of the findings is limited as the study was conducted in one US city using travelers of only one P2P accommodations platform.

Practical implications

Hotels may want to leverage their loyalty programs and stress the importance of safety and security when traveling as a means of competing with P2P accommodations.

Originality/value

Given limited empirical research on P2P accommodations, this study provides an informative first look at the preferences and behaviors of travelers using P2P accommodations and points to a growing loyalty to P2P accommodations versus hotels in the leisure segment.
Patients’ perspectives of emergency care quality and priorities for care improvement
Authors: Yarney Lily , Atinga Roger Ayimbillah
Published: September 2017

Purpose

Studies have examined strategies implemented to strengthen quality of emergency care in healthcare provider institutions in Ghana. But few studies have focused on what determines quality of emergency care from the patient’s perspective. The purpose of this paper is to fill that gap by examining factors salient to gauging quality of emergency care and priority areas for care improvement.

Design/methodology/approach

Cross-sectional data were collected from patients admitted in emergency units of public hospitals in two regions: Greater Accra and Central Regions. A structured questionnaire designed with inputs from emergency medicine physicians and patients was used to collect data from 381 patients. Principal component analysis (PCA) and logistic regression models were computed to respectively determine salient measures of emergency care quality and their association with patient overall perceived quality of emergency care.

Findings

Using the PCA, four factors (social and relational care, attentive prehospitalised care, ward quality and privacy and medical supplies) were derived as salient measures of emergency care quality. All the factors derived had statistically significant association with patient overall perception of quality.

Originality/value

Emergency care quality improvement strategies that incorporate the dimensions identified can produce effective therapeutic outcomes.
Internal coordination to enable high load factor
Authors: Rogerson Sara , Sallnäs Uni
Published: September 2017

Purpose

The purpose of this paper is to clarify how activities may be coordinated within shippers’ organisations to enable high load factor (a key aspect of transport efficiency).

Design/methodology/approach

A multiple-case study involving three shippers was conducted, in which the logistics or transport managers of each company were interviewed. The cases were analysed according to which activities were coordinated to achieve high load factor, interdependencies between the activities, and the coordination mechanisms that shippers adopted.

Findings

A matrix is developed to show the differences in applying various coordination mechanisms in eight categories, according to intrafunctional or interfunctional coordination, sequential or reciprocal interdependencies, and the number of activities (dyadic or multiple). For example, coordination mechanisms aimed at exerting control are more suitable for intrafunctional than interfunctional interaction; interfunctional coordination relies more on mechanisms that aim to increase the understanding of transport-related issues among non-logistics activities.

Research limitations/implications

The study is based on data from three Swedish companies.

Practical implications

Managers are provided with suggestions for coordinating activities when their goal is to improve load factor. These findings are of interest for reducing costs and emissions.

Originality/value

In response to suggestions in the earlier literature that shippers could improve their internal coordination to improve their load factor, this paper articulates several mechanisms for performing such coordination in eight situations.