bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutting back malaria: CRISPR/Cas9 genome editing of Plasmodium
Authors: Lee Marcus C S , Lindner Scott E , Lopez-Rubio Jose-Juan , Llinás Manuel 
Published: June 2019

Abstract
CRISPR/Cas9 approaches are revolutionizing our ability to perform functional genomics across a wide range of organisms, including the Plasmodium parasites that cause malaria. The ability to deliver single point mutations, epitope tags and gene deletions at increased speed and scale is enabling our understanding of the biology of these complex parasites, and pointing to potential new therapeutic targets. In this review, we describe some of the biological and technical considerations for designing CRISPR-based experiments, and discuss potential future developments that broaden the applications for CRISPR/Cas9 interrogation of the malaria parasite genome.
A Novel Approach to Evaluate Antibiotic Utilization Across the Spectrum of Inpatient and Ambulatory Care and Implications for Prioritization of Antibiotic Stewardship Efforts
Authors: Frost Holly M , Knepper Bryan C , Shihadeh Katherine C , Jenkins Timothy C 
Published: June 2019

Abstract

Background
Antibiotic overuse remains a significant problem. The objective of this study was to develop a methodology to evaluate antibiotic use across inpatient and ambulatory care sites in an integrated healthcare system to prioritize antibiotic stewardship efforts.

Methods
We conducted an epidemiologic study of antibiotic use across an integrated healthcare system on 12 randomly selected days from 2017 to 2018. For inpatients and perioperative patients, administrations of antibiotics were recorded, whereas prescriptions were recorded for outpatients.

Results
On the study days, 10.9% (95% confidence interval [CI], 10.6%–11.3%) of patients received antibiotics. Of all antibiotics, 54.1% were from ambulatory care (95% CI, 52.6%–55.7%), 38.0% were from the hospital (95% CI, 36.6%–39.5%), and 7.8% (95% CI, 7.1%–8.7%) were perioperative. The emergency department/urgent care centers, adult outpatient clinics, and adult non–critical care inpatient wards accounted for 26.4% (95% CI, 25.0%–27.7%), 23.8% (95% CI, 22.6%–25.2%), and 23.9% (95% CI, 22.7%–25.3%) of antibiotic use, respectively. Only 9.2% (95% CI, 8.3%–10.1%) of all antibiotics were administered in critical care units. Antibiotics with a broad spectrum of gram-negative activity accounted for 30.4% (95% CI, 29.0%–31.9%) of antibiotics. Infections of the respiratory tract were the leading indication for antibiotics.

Conclusions
In an integrated healthcare system, more than half of antibiotic use occurred in the emergency department/urgent care centers and outpatient clinics. Antibiotics with a broad spectrum of gram-negative activity accounted for a large portion of antibiotic use. Analysis of antibiotic utilization across the spectrum of inpatient and ambulatory care is useful to prioritize antibiotic stewardship efforts.
Life-History Traits of a Subtropical Cerambycid Beetle, Ropica honesta (Coleoptera: Cerambycidae)
Authors: Nagamine Keisuke , Kusakabe Yoshiyasu , Tsuchida Takashi , Horiuchi Yuya , Nemoto Yuya , Sato Yoshiki , Shintani Yoshinori 
Published: June 2019

AbstractRopica honesta Pascoe is a small-sized cerambycid that has been recorded in tropical to subtropical Asia. In this study, life-history traits were examined for a local population collected from Iriomote Island (24.3°N, 123.8°E), Okinawa, Japan, by rearing insects on artificial diet as larval food. The egg period was 5.9 ± 0.3 d at 25°C. There was no significant difference in the duration of the larval, pupal, and adult preoviposition periods between long-day (14:10 [L:D]) and short-day (12:12 [L:D]) photoperiods at both 20 and 25°C. These periods at 25°C (14:10 [L:D]) were 28.5 ± 1.4, 8.4 ± 0.5, and 9.6 ± 1.9 d (mean ± SD), respectively. The relationship between the developmental rate and temperature followed the law of total effective temperature; thus, the developmental threshold temperature and thermal constant were estimated based on these data. Together with the finding that R. honesta may not have diapause in the egg stage, it is suggested that this beetle does not have diapause in the life cycle. Furthermore, when larvae were reared on natural food (dead twigs of hardwoods) adults emerged from the twigs 47.6 ± 2.9 d after oviposition, and this value was close to the total duration of the egg to pupal periods. Together with the data for annual temperature of the habitat and the fact that food resources for the species (dead twigs and leaves of hardwoods) are available throughout the year, we conclude that R. honesta develops and reproduces all year round, with five generations at maximum.
Multicentre reference values for cardiac magnetic resonance imaging derived ventricular size and function for children aged 0–18 years
Authors: van der Ven J P G , Sadighy Z , Valsangiacomo Buechel E R , Sarikouch S , Robbers-Visser D , Kellenberger C J , Kaiser T , Beerbaum P , Boersma E , Helbing W A 
Published: June 2019

Abstract

Aims
Cardiovascular magnetic resonance (CMR) imaging is an important tool in the assessment of paediatric cardiac disease. Reported reference values of ventricular volumes and masses in the paediatric population are based on small cohorts and several methodologic differences between studies exist. We sought to create steady-state free precession (SSFP) CMR reference values for biventricular volumes and mass by combining data of previously published studies and re-analysing these data in a standardized manner.

Methods and results
A total of 141 healthy children (68 boys) from three European centres underwent cine-SSFP CMR imaging. Cardiac structures were manually contoured for end-diastolic and end-systolic phases in the short-axis orientation according to current standardized CMR post-processing guidelines. Volumes and masses were derived from these contours. Age-related reference curves were constructed using the lambda mu sigma method. Median age was 12.7 years (range 0.6–18.5). We report biventricular volumes and masses, unindexed and indexed for body surface area, stratified by age groups. In general, boys had approximately 15% higher biventricular volumes and masses compared with girls. Only in children aged &lt;6 years old no gender differences could be observed. Left ventricle ejection fraction was slightly higher in boys in this study population (median 67% vs. 65%, P = 0.016). Age-related reference curves showed non-linear relations between age and cardiac parameters.

Conclusion
We report volumetric SSFP CMR imaging reference values for children aged 0–18 years old in a relatively large multi-centre cohort. These references can be used in the follow-up of paediatric cardiac disease and for research purposes.
Problems in Online Dictionary Use for Advanced Slovenian Learners of English
Authors: Farina Donna M T Cr , Vrbinc Marjeta , Vrbinc Alenka 
Published: June 2019

AbstractThis article reports on findings from interviews with students from the University of Ljubljana. The study is based on fourteen questions about participants’ habits of dictionary use, their look-up abilities, and their perceptions of the utility and quality of definitions and illustrative examples. Students were given nine contexts containing a clearly-marked common word used in an infrequent sense; they had to locate the relevant sense in the online Merriam–Webster Learner’s Dictionary (MWLD). A think-aloud method enabled the researchers to follow the students’ look-up process and record their problems as well as their suggestions on how to improve the content and presentation of information in the dictionary. Recommendations are provided on: the improvement of drop-down menus; the inclusion of the form(s) of a target word; illustrative examples; the use of italics, boldface, and colors as well as what types of information should be displayed or available if needed.
Equivalence of Sobolev Norms Involving Generalized Hardy Operators
Authors: Frank Rupert L , Merz Konstantin , Siedentop Heinz 
Published: June 2019

Abstract
We consider the fractional Schrödinger operator with Hardy potential and critical or subcritical coupling constant. This operator generates a natural scale of homogeneous Sobolev spaces, which we compare with the ordinary homogeneous Sobolev spaces. As a byproduct, we obtain generalized and reversed Hardy inequalities for this operator. Our results extend those obtained recently for ordinary (non-fractional) Schrödinger operators and have an important application in the treatment of large relativistic atoms.
Evaluation of HIV-1 reservoir levels as possible markers for virological failure during boosted darunavir monotherapy
Authors: Rutsaert Sofie , De Spiegelaere Ward , De Clercq Laura , Vandekerckhove Linos 
Published: June 2019

AbstractBackgroundThe gold standard for HIV-1 treatment is to administer triple antiretroviral therapy, but a shift to simplified regimens is being explored. Boosted darunavir monotherapy can be considered for patients who are for specific reasons not good candidates for dual or triple therapy. Still, a number of patients fail virologically or need to switch treatment.ObjectivesTo identify predictive markers for those patients that are more likely to sustain virological control under monotherapy, virological and immunological markers were explored in HIV-1-positive patients that experienced virological failure on ritonavir-boosted darunavir monotherapy in the PROTEA trial.MethodsAs a retrospective nested study of the PROTEA study (NCT01448707), we analysed 77 HIV-1-infected patients who were on darunavir/ritonavir 800/100 mg monotherapy up to 96 weeks. Patients were appointed to three distinct cohorts based on viral loads (VLs): (i) undetectable VL after 96 weeks; (ii) very-low-level viraemia (5–39 copies/mL); and (iii) failing treatment. Total HIV-1 DNA, integrated HIV-1 DNA and 2-long terminal repeat circular HIV-1 DNA (2LTR circles) were measured in PBMCs at baseline, week 48 and week 96.ResultsTotal HIV-1 DNA and integrated HIV-1 DNA at baseline differed significantly between patients who experienced virological failure on monotherapy (P < 0.01 and P < 0.001). Although a higher level of HIV-1 DNA was measured in failures, this marker by itself does not provide enough predictive value to prospectively predict virological failure in patients on monotherapy.ConclusionsHIV-1 reservoir markers correlate with therapy failure in ritonavir-boosted darunavir monotherapy. However, their role as a predictive marker combined with other markers in a routine clinical setting should be further explored.
Changing Pedagogy to Improve Skills in Preschools: Experimental Evidence from Peru
Authors: Gallego Francisco A , Näslund-Hadley Emma , Alfonso Mariana 
Published: June 2019

Abstract
Changing pedagogical practices is a promising, cost-effective avenue for improving education in developing countries, especially when done without changing current inputs such as teachers and instruction time. This article presents the results of a randomized evaluation of a program that aimed at changing the pedagogical approach used to teach the existing national mathematics curriculum. The program provides tools to regular preschool teachers to use an inquiry- and problem-based learning approach to tailor instruction to preschoolers in Peru. The results show an improvement of overall mathematics outcomes, which persist for some content areas even one year after the program ended. In contrast to results from previous research that suggest mathematics programs are biased along gender and socioeconomic lines, there is no evidence of differential effects by gender, language spoken at home, or proxies for socioeconomic status. Results also imply persistent stronger impacts on students whose teachers have university degrees.
Carbon Dioxide Embolism Associated With Total Mesorectal Excision Surgery: A Report From the International Registries
Authors: Dickson Edward A. , Penna Marta , Cunningham Chris , Ratcliffe Fiona M. , Chantler Jonathan , Crabtree Nicholas A. , Tuynman Jurriaan B. , Albert Matthew R. , Monson John R.T. , Hompes Roel 
Published: June 2019

BACKGROUND:
Carbon dioxide embolus has been reported as a rare but clinically important risk associated with transanal total mesorectal excision surgery. To date, there exists limited data describing the incidence, risk factors, and management of carbon dioxide embolus in transanal total mesorectal excision.

OBJECTIVE:
This study aimed to obtain data from the transanal total mesorectal excision registries to identify trends and potential risk factors for carbon dioxide embolus specific to this surgical technique.

DESIGN:
Contributors to both the LOREC and OSTRiCh transanal total mesorectal excision registries were invited to report their incidence of carbon dioxide embolus. Case report forms were collected detailing the patient-specific and technical factors of each event.

SETTINGS:
The study was conducted at the collaborating centers from the international transanal total mesorectal excision registries.

MAIN OUTCOME MEASURES:
Characteristics and outcomes of patients with carbon dioxide embolus associated with transanal mesorectal excision were measured.

RESULTS:
Twenty-five cases were reported. The incidence of carbon dioxide embolus during transanal total mesorectal excision is estimated to be ≈0.4% (25/6375 cases). A fall in end tidal carbon dioxide was noted as the initial feature in 22 cases, with 13 (52%) developing signs of hemodynamic compromise. All of the events occurred in the transanal component of dissection, with mean (range) insufflation pressures of 15 mm Hg (12–20 mm Hg). Patients were predominantly (68%) in a Trendelenburg position, between 30° and 45°. Venous bleeding was reported in 20 cases at the time of carbon dioxide embolus, with periprostatic veins documented as the most common site (40%). After carbon dioxide embolus, 84% of cases were completed after hemodynamic stabilization. Two patients required cardiopulmonary resuscitation because of cardiovascular collapse. There were no deaths.

LIMITATIONS:
This is a retrospective study surveying reported outcomes by surgeons and anesthetists.

CONCLUSIONS:
Surgeons undertaking transanal total mesorectal excision must be aware of the possibility of carbon dioxide embolus and its potential risk factors, including venous bleeding (wrong plane surgery), high insufflation pressures, and patient positioning. Prompt recognition and management can limit the clinical impact of such events. See Video Abstract at http://links.lww.com/DCR/A961.
Raoultella planticola, an Emerging Pathogen
Authors: Olivier Maxim , Madruga Mario , Carlan Stephen 
Published: June 2019

Abstract

Raoultella planticola is an aerobic gram-negative bacillus closely related to bacteria in the genus Klebsiella. It typically resides in the environment and human gut and is only noted as an opportunistic pathogen creating clinical infection in compromised individuals. A 56-year-old previously healthy individual developed acute prostatitis confirmed by examination and computed tomography, and R. planticola was cultured. He was placed on oral ciprofloxin for 6 weeks, and as of 6 months, he has had no recurrence. R. planticola can infect the prostate of healthy individuals, and when it does, the condition presents clinically no different from acute prostatitis caused by other pathogens. In addition, most clinical microbiological laboratories are capable of accurate identification of R. planticola. Antibiotic sensitivity studies are critical for treatment, as the organism reportedly has developed patterns of resistance.
Incidental Detection of Splenic Hemangioma on 68Ga-PSMA PET/CT
Authors: Sheng Kevin , Le Ken , Bui Chuong , Mansberg Robert 
Published: June 2019

Abstract
A 73-year-old man underwent a 68Ga-PSMA-HBED-CC 11 PET/CT for evaluation of rising PSA in the context of previous radical retropubic prostatectomy and salvage radiotherapy for prostatic adenocarcinoma. There was no definite PSMA avid recurrence in the prostatic bed. Intense PSMA avid uptake was seen in the anterior aspect of the spleen. Further characterization with multiplanar multisequence pre- and post-IV contrast MRI of the upper abdomen with arterial, portal venous, and delayed phase acquisitions revealed a lesion with appearances consistent with a splenic hemangioma.
Local ancestry analysis reveals genomic convergence in extremophile fishes
Authors: Brown Anthony P. , McGowan Kerry L. , Schwarzkopf Enrique J. , Greenway Ryan , Rodriguez Lenin Arias , Tobler Michael , Kelley Joanna L. 
Published: June 2019

The molecular basis of convergent phenotypes is often unknown. However, convergence at a genomic level is predicted when there are large population sizes, gene flow among diverging lineages or strong genetic constraints. We used whole-genome resequencing to investigate genomic convergence in fishes (Poeciliaspp.) that have repeatedly colonized hydrogen sulfide (H2S)-rich environments in Mexico. We identified genomic similarities in both single nucleotide polymorphisms (SNPs) and structural variants (SVs) among independently derived sulfide spring populations, with approximately 1.2% of the genome being shared among sulfidic ecotypes. We compared these convergent genomic regions to candidate genes for H2S adaptation identified from transcriptomic analyses and found that a significant proportion of these candidate genes (8%) were also in regions where sulfidic individuals had similar SNPs, while only 1.7% were in regions where sulfidic individuals had similar SVs. Those candidate genes included genes involved in sulfide detoxification, the electron transport chain (the main toxicity target of H2S) and other processes putatively important for adaptation to sulfidic environments. Regional genomic similarity across independent populations exposed to the same source of selection is consistent with selection on standing variation or introgression of adaptive alleles across divergent lineages. However, combined with previous analyses, our data also support that adaptive changes in mitochondrially encoded subunits arose independently via selection on de novo mutations. Pressing questions remain on what conditions ultimately facilitate the independent rise of adaptive alleles at the same loci in separate populations, and thus, the degree to which evolution is repeatable or predictable.This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions'.
The conical shape of DIM lipids promotes Mycobacterium tuberculosis infection of macrophages
Authors: Augenstreich Jacques , Haanappel Evert , Ferré Guillaume , Czaplicki George , Jolibois Franck , Destainville Nicolas , Guilhot Christophe , Milon Alain , Astarie-Dequeker Catherine , Chavent Matthieu 
Published: June 2019

AbstractPhthiocerol dimycocerosate (DIM) is a major virulence factor of the pathogen Mycobacterium tuberculosis (Mtb). While this lipid promotes the entry of Mtb into macrophages, which occurs via phagocytosis, its molecular mechanism of action is unknown. Here, we combined biophysical, cell biology, and modelling approaches to reveal the molecular mechanism of DIM action on macrophage membranes leading to the first step of Mtb infection. MALDI-TOF mass spectrometry showed that DIM molecules are transferred from the Mtb envelope to macrophage membranes during infection. Multi-scale molecular modeling and 31P-NMR experiments revealed that DIM adopts a conical shape in membranes and aggregate in the stalks formed between two opposing lipid bilayers. Infection of macrophages pre-treated with lipids of various shapes uncovered a general role for conical lipids in promoting phagocytosis. Taken together, these results reveal how the molecular shape of a mycobacterial lipid can modulate the biological function of macrophages.
LST-1 acts in trans with a conserved RNA-binding protein to maintain stem cells
Authors: Haupt Kimberly A. , Enright Amy L. , Ferdous Ahlan S. , Kershner Aaron M. , Shin Heaji , Wickens Marvin , Kimble Judith 
Published: June 2019

ABSTRACTStem cell self-renewal is essential to development and tissue repair. The C. elegans LST-1 protein is a pivotal regulator of self-renewal and oncogenic when misexpessed. Here we define regions within the LST-1 protein that provide molecular insights into both its function and regulation. LST-1 self-renewal activity resides within a predicted disordered region that harbors two KXXL motifs. These KXXL motifs mediate LST-1 binding to FBF, a broadly conserved Pumilio/PUF RNA-binding protein that represses differentiation. Point mutations of the KXXL motifs abrogate LST-1 self-renewal activity. Therefore, FBF binding is essential to LST-1 function. A second distinct region regulates LST-1 spatial expression and primarily affects LST-1 protein turnover. Upon loss of this regulatory region, LST-1 protein distribution expands and drives formation of a larger than normal GSC pool. Thus, LST-1 promotes self-renewal as a key FBF partner, and its spatial regulation helps determine size of the GSC pool.IMPACT STATEMENTA key stem cell regulator partners with a broadly conserved PUF RNA-binding protein to drive self-renewal and maintain a stem cell pool.
Sox2 is an oncogenic driver of small cell lung cancer
Authors: Voigt Ellen , Wollenzien Hannah , Feiner Josh , Thompson Ethan , Vande Kamp Madeline , Kareta Michael S. 
Published: June 2019

AbstractAlthough many cancer prognoses have improved in the past fifty years due to advancements in treatments, there has been little to no improvement in therapies for small cell lung cancer (SCLC) which currently has a five-year survival rate of less than 7%. One promising avenue to improve treatment for SCLC is to understand its underlying genetic alterations that drive its formation and growth. One such mutation in SCLC, which appears in many cancers, is of the Rb gene. When mutated, Rb causes hyperproliferation and loss of cellular identity. Normally Rb promotes differentiation by regulating lineage specific transcription factors including regulation of pluripotency factors such as Sox2. However, there is evidence that when certain tissues lose Rb, Sox2 becomes upregulated and promotes oncogenesis. To better understand the relationship between Rb and Sox2 and to uncover new treatments for SCLC we have studied the role of Sox2 in Rb loss initiated tumors by investigating both the tumor initiation in SCLC genetically engineered mouse models, as well as tumor maintenance in SCLC cell lines.