bluuebunny/crossref_metadata_2025 huggingface dataset:
New Strategies in Clinical Guideline Delivery: Randomized Trial of Online, Interactive Decision Support Versus Guidelines for Human Immunodeficiency Virus Treatment Selection by Trainees
Authors: Ramirez Jesus A , Maddali Manoj V , Nematollahi Saman , Li Jonathan Z , Shah Maunank
Published: March 2020

Background

Support for clinicians in human immunodeficiency virus (HIV) medicine is critical given national HIV-provider shortages. The US Department of Health and Human Services (DHHS) guidelines are comprehensive but complex to apply for antiretroviral therapy (ART) selection. Human immunodeficiency virus antiretroviral selection support and interactive search tool (HIV-ASSIST) (www.hivassist.com) is a free tool providing ART decision support that could augment implementation of clinical practice guidelines.

Methods

We conducted a randomized study of medical trainees at Johns Hopkins University, in which participants were asked to select an ART regimen for 10 HIV case scenarios through an electronic survey. Participants were randomized to receive either DHHS guidelines alone, or DHHS guidelines and HIV-ASSIST to support their decision making. ART selections were graded “appropriate” if consistent with DHHS guidelines, or concordant with regimens selected by HIV experts at 4 academic institutions.

Results

Among 118 trainees, participants randomized to receive HIV-ASSIST had a significantly higher percentage of appropriate ART selections compared to those receiving DHHS guidelines alone (percentage of appropriate responses in DHHS vs HIV-ASSIST arms: median [Q1, Q3], 40% [30%, 50%] vs 90% [80%, 100%]; P < .001). The effect was seen for all case types, but most pronounced for complex cases involving ART-experienced patients with ongoing viremia (DHHS vs HIV-ASSIST: median [Q1, Q3], 0% [0%, 33%] vs 100% [66%, 100%]).

Conclusions

Trainees using HIV-ASSIST were significantly more likely to choose appropriate ART regimens compared to those using guidelines alone. Interactive decision support tools may be important to ensure appropriate implementation of HIV guidelines.

Clinical Trials Registration

NCT04080765.
Dantrolene reduces CaMKIIδC-mediated atrial arrhythmias
Authors: Pabel Steffen , Mustroph Julian , Stehle Thea , Lebek Simon , Dybkova Nataliya , Keyser Andreas , Rupprecht Leopold , Wagner Stefan , Neef Stefan , Maier Lars S , Sossalla Samuel
Published: March 2020

Aims

In atrial fibrillation (AF), an increased diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) mediated by calcium/calmodulin-dependent-protein-kinaseIIδC (CaMKII) can serve as a substrate for arrhythmia induction and persistence. Dantrolene has been shown to stabilize the cardiac ryanodine-receptor. This study investigated the effects of dantrolene on arrhythmogenesis in human and mouse atria with enhanced CaMKII activity.

Methods and results

Human atrial cardiomyocytes (CMs) were isolated from patients with AF. To investigate CaMKII-mediated arrhythmogenesis, atrial CMs from mice overexpressing CaMKIIδC (TG) and the respective wildtype (WT) were studied using confocal microscopy (Fluo-4), patch-clamp technique, and in vivo atrial catheter-based burst stimulations. Dantrolene potently reduced Ca2+ spark frequency (CaSpF) and diastolic SR Ca2+ leak in AF CMs. Additional CaMKII inhibition did not further reduce CaSpF or leak compared to dantrolene alone. While the increased SR CaSpF and leak in TG mice were reduced by dantrolene, no effects could be detected in WT. Dantrolene also potently reduced the pathologically enhanced frequency of diastolic SR Ca2+ waves in TG without having effects in WT. As an increased diastolic SR Ca2+ release can induce a depolarizing transient inward current, we could demonstrate that the incidence of afterdepolarizations in TG, but not in WT, mice was significantly diminished in the presence of dantrolene. To translate these findings into an in vivo situation we could show that dantrolene strongly suppressed the inducibility of AF in vivo in TG mice.

Conclusion

Dantrolene reduces CaMKII-mediated atrial arrhythmogenesis and may therefore constitute an interesting antiarrhythmic drug for treating patients with atrial arrhythmias driven by an enhanced CaMKII activity, such as AF.
Safety and quality of bacterially fermented functional foods and beverages: a mini review
Authors: Ashaolu Tolulope Joshua
Published: March 2020

Bacteria have been employed widely in the food and beverage industry, with evolving dimensions in recent years. Proteases derived from lactic acid bacteria (LAB) are useful in the production of fermented functional beverages and are of particular use in conditioning their shelf life, nutritional content, flavour, and texture quality, thus making fermented foods and beverages functional and therapeutic. This review focuses on bacteria, especially protease-producing LAB used in food processing, and their usefulness in the production of functional foods and beverages. A case study of oat beverages was briefly explored due to its popularity. The safety and quality importance of the food products were also considered with a few recommendations.
Relocated aftershocks and background seismicity in eastern Indonesia shed light on the 2018 Lombok and Palu earthquake sequences
Authors: Supendi P , Nugraha A D , Widiyantoro S , Pesicek J D , Thurber C H , Abdullah C I , Daryono D , Wiyono S H , Shiddiqi H A , Rosalia S
Published: March 2020

High seismicity rates in eastern Indonesia occur due to the complex interaction of several tectonic plates which resulted in two deadly, destructive earthquake sequences that occurred in Lombok Island and the city of Palu, Sulawesi in 2018. The first sequence began in July with an Mw 6.4 event near Lombok, culminating in an Mw 7.0 event 8 d later. This was then followed by a nearby Mw 6.9 event 12 d later. Approximately 1000 km to the northeast, a separate sequence began several weeks later near Palu where an Mw 7.5 event occurred that triggered a tsunami. In this study, we present hypocentre relocations for both earthquake sequences as well as all other regional earthquakes in eastern Indonesia. The relocations were performed using a teleseismic double-difference relocation method and arrival times for P and S waves from stations at local, regional, and teleseismic distances. The catalogue and phase data were taken from the Agency for Meteorology, Climatology and Geophysics (BMKG) of Indonesia and the International Seismological Centre (ISC) for the period of April 2009 through November 2018. The relocated catalogue provides an improved view of seismicity in eastern Indonesia over the study period, sharpening locations and interpretations of seismogenic features throughout the region. In the Lombok area, the relocated earthquakes clearly show a backarc thrust to the north of the Sunda-Banda Arc transition zone. The relocated aftershocks show that the destructive Mw 7.0 and Mw 6.9 earthquakes of the Lombok sequence ruptured two different regions: The Mw 7.0 earthquake propagated westward, whereas the Mw 6.9 earthquake propagated eastward. The entire sequence of Lombok earthquakes was most likely started by the Mw 6.4 event as the initial event or foreshock, which then triggered backarc thrusts on both sides. Several weeks later and far to the northeast, the Mw 7.5 Palu earthquake occurred along the Palu-Koro Fault, filling a seismic gap that had not ruptured in an Mw 6.0 event or larger since at least 1900. The distribution of aftershocks indicates that the northern part of the Palu-Koro Fault has lower relative seismicity rates than the southern part at shallow depths, and that off fault aftershocks are mostly located to the east of the Palu-Koro Fault.
Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome
Authors: Alharatani Reham , Ververi Athina , Beleza-Meireles Ana , Ji Weizhen , Mis Emily , Patterson Quinten T , Griffin John N , Bhujel Nabina , Chang Caitlin A , Dixit Abhijit , Konstantino Monica , Healy Christopher , Hannan Sumayyah , Neo Natsuko , Cash Alex , Li Dong , Bhoj Elizabeth , Zackai Elaine H , Cleaver Ruth , Baralle Diana , McEntagart Meriel , Newbury-Ecob Ruth , Scott Richard , Hurst Jane A , Au Ping Yee Billie , Hosey Marie Therese , Khokha Mustafa , Marciano Denise K , Lakhani Saquib A , Liu Karen J
Published: March 2020

CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell–cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signalling. Due to advances in next-generation sequencing, CTNND1 has been implicated in human diseases including cleft palate and blepharocheilodontic (BCD) syndrome albeit only recently. In this study, we identify eight novel protein-truncating variants, six de novo, in 13 participants from nine families presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders. Using conditional deletions in mice as well as CRISPR/Cas9 approaches to target CTNND1 in Xenopus, we identified a subset of phenotypes that can be linked to p120-catenin in epithelial integrity and turnover, and additional phenotypes that suggest mesenchymal roles of CTNND1. We propose that CTNND1 variants have a wider developmental role than previously described and that variations in this gene underlie not only cleft palate and BCD but may be expanded to a broader velocardiofacial-like syndrome.
Population dynamics of three brachyuran crab species (Decapoda) in Icelandic waters: impact of recent colonization of the Atlantic rock crab (Cancer irroratus)
Authors: Gíslason Sindri , Pálsson Snæbjörn , Jónasson Jónas P , Guls Hermann Dreki , Svavarsson Jörundur , Halldórsson Halldór P
Published: March 2020

The Atlantic rock crab (Cancer irroratus) was first found in Icelandic waters in 2006. Since then, the species has dispersed rapidly and is currently found clockwise from the southwest coast of Iceland to the east, corresponding to >70% of the coastline. Here, we present a monitoring study on this non-indigenous crab species in Iceland from 2007 to 2019. The study shows that the rock crab is now the most abundant brachyuran crab species on soft substrate bottoms in Southwest Iceland, both as adults and planktonic larvae, indicating that it is outcompeting its rival native species, the European green crab (Carcinus maenas) and the spider crab (Hyas araneus). The average size of the rock crab was similar over time (2007–2019), although it fluctuated between years in a pattern similar to that for the green crab, while significant reduction in size was observed for male spider crabs. The rock crab population is still in a growth phase in Icelandic waters, as seen in increasing distributional range, and can be found in densities comparable to the highest reported for the species in its native range in North America.
Tumour necrosis factor receptor-associated factors: interacting protein with forkhead-associated domain inhibition decreases inflammatory cell infiltration and cardiac remodelling after acute myocardial infarction
Authors: Jiang Yicheng , Li Xue , Xu Hai , Gu Yang , Shi Feiya , Wang Fang , Zhang Xiwen
Published: March 2020

OBJECTIVES

Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Post-AMI cardiac remodelling is closely related to the prognosis of AMI. The excess inflammatory responses could promote cardiac remodelling. Tumour necrosis factor receptor-associated factor-interacting protein with forkhead-associated domain (TIFA) has been identified as a nuclear factor (NF)-κB activator, which plays a key role in the activation of the NF-κB signalling pathway. The goal of this research was to investigate the expression and the underlying mechanism of TIFA in an AMI mouse model.

METHODS

The AMI mouse model was induced by ligation of the left coronary artery. TIFA and NF-κB knockdown were established by lentivirus transduction. The expression levels of associated proteins were analysed by a western blot or an enzyme-linked immunosorbent assay. Histological characteristics were evaluated by haematoxylin–eosin staining.

RESULTS

The TIFA level was elevated in our AMI mouse model. The production of interleukin-1β and tumour necrosis factor-α increased markedly in the mice with AMI. TIFA knockdown inhibited the infiltration of inflammatory cells, production of pro-inflammatory mediators (interleukin-1β and tumour necrosis factor-α), NF-κB activation and cardiac remodelling (matrix metallopeptidase 9) post-AMI. In addition, NF-κB knockdown could also alleviate cardiac remodelling after AMI.

CONCLUSIONS

The preceding results indicated that TIFA inhibition could ameliorate cardiac remodelling after AMI partly through inactivation of NF-κB. This study provides insights into further research of cardiac remodelling and AMI from bench to clinic.
Burden of Adults Hospitalized With Group B Streptococcal Infection
Authors: McLaughlin John M , Peyrani Paula , Furmanek Stephen , Khan Farid L , Quinn Angela , Jodar Luis , Ramirez Julio , Swerdlow David L
Published: March 2020

Background

The burden of noninvasive group B Streptococcus (GBS) infections in adults is unknown. We determined population-based rates of hospitalization where invasive or noninvasive GBS infections were identified among US adults in a defined catchment area.

Methods

We identified adults with clinical and laboratory-confirmed evidence of GBS infection from January 2014 through December 2016 from 6 hospitals in Louisville, Kentucky. Invasive disease was defined as GBS isolated from a normally sterile site.

Results

Among 1076 adults with GBS infection, the median age was 52 years, 51% were male, and 89% had ≥1 chronic medical condition. The most prevalent infection sites were skin and soft tissue (39%), urinary tract (23%), bone and joint (16%), and bloodstream (11%). Forty percent of infections were polymicrobial. The annual incidence of GBS-associated hospitalization was 73 per 100 000 adults and 68 and 100 per 100 000 for patients aged 18–64 and ≥ 65 years, respectively. For every invasive GBS infection, 3.7 noninvasive infections occurred.

Conclusions

Our population-based study outlines the full burden of GBS-associated hospitalization in adults and found incidence rates comparable to those of pneumococcal disease, where vaccines are recommended. Noninvasive disease was 3–4 times more common than invasive disease, suggesting that the GBS burden among adults is considerably greater than previously recognized.
Prospectively identifying adults with serious mental illness at risk for poor physical health: The role of person reported outcomes
Authors: Hochman Limor , Moran Galia S , Gelkopf Marc , Roe David , Shadmi Efrat
Published: March 2020

Objective

Persons with serious mental illnesses are at increased risk for co-occurring physical comorbidities. Patient-reported outcome measures are increasingly used in routine assessments of persons with serious mental illnesses, yet the relation of patient-reported outcome measures to physical health outcomes has not been comprehensively investigated. We examined the association between patient-reported outcome measures and self-reported physical health at 1-year follow-up.

Design

A retrospective cohort study.

Setting

Data were collected as part of the Israeli Psychiatric Rehabilitation Patient-Reported Outcome Measurement program in Israel.

Participants

A total of 2581 psychiatric rehabilitation service users assessed between April 2013 and January 2016.

Main Outcome Measures

Self-reports on two consecutive years of physical health dichotomized as poor versus good.

Results

More than one-third of participants reported having poor physical health. Multivariate regression analysis showed that quality of life (odds ratio [OR] = 0.71; 95% confidence interval [CI]: 0.60–0.84) and lack of effect of symptoms on functioning (OR = 0.81; 95%CI: 0.74–0.89) predict subsequent physical health, controlling for all other factors. Compared to a multivariate model with personal characteristics and self-reports on physical health at baseline (Model A), the model which also included patient-reported outcome measures (Model B) showed slightly better discrimination (c-statistic: 0.74 vs. 0.76, respectively).

Conclusions

These results suggest that patient-reported outcome measures contribute to the prediction of poor physical health and thus can be useful as an early screening tool for people with serious mental illnesses living in the community, who are at risk of physical health problems.
Contribution of hypermutation to fosfomycin heteroresistance in Escherichia coli
Authors: Portillo-Calderón Inés , Ortiz-Padilla Miriam , Rodríguez-Martínez Jose Manuel , de Gregorio-Iaria Belen , Blázquez Jesús , Rodríguez-Baño Jesús , Pascual Alvaro , Docobo-Pérez Fernando
Published: March 2020

Objectives

To explore the effect of combining defects in DNA repair systems with the presence of fosfomycin-resistant mechanisms to explain the mechanisms underlying fosfomycin heteroresistance phenotypes in Enterobacteriaceae.

Materials and methods

We used 11 clinical Escherichia coli isolates together with isogenic single-gene deletion mutants in the E. coli DNA repair system or associated with fosfomycin resistance, combined with double-gene deletion mutants. Fosfomycin MICs were determined by gradient strip assay (GSA) and broth microdilution (BMD). Mutant frequencies for rifampicin (100 mg/L) and fosfomycin (50 and 200 mg/L) were determined. Using two starting inocula, in vitro fosfomycin activity was assessed over 24 h in growth (0.5–512 mg/L) and time–kill assays (64 and 307 mg/L).

Results

Strong and weak mutator clinical isolates and single-gene deletion mutants, except for ΔuhpT and ΔdnaQ, were susceptible by GSA. By BMD, the percentage of resistant clinical isolates reached 36%. Single-gene deletion mutants showed BMD MICs similar to those for subpopulations by GSA. Strong mutators showed a higher probability of selecting fosfomycin mutants at higher concentrations. By combining the two mechanisms of mutation, MICs and ranges of resistant subpopulations increased, enabling strains to survive at higher fosfomycin concentrations in growth monitoring assays. In time–kill assays, high inocula increased survival by 37.5% at 64 mg/L fosfomycin, compared with low starting inocula.

Conclusions

The origin and variability of the fosfomycin heteroresistance phenotype can be partially explained by high mutation frequencies together with mechanisms of fosfomycin resistance. Subpopulations should be considered until clinical meaning is established.
Strategies for Successful Recruitment and Retention of Parents in Pediatric Psychosocial eHealth Interventions: A Qualitative Study in Pediatric Oncology
Authors: Canter Kimberly S , Vega Gabriela , Ramirez Alejandra Perez , Deatrick Janet A , Kazak Anne E
Published: March 2020

Objective

Psychosocial intervention studies with parents often have difficulty with regard to participant recruitment, retention, and engagement. Prior to conducting a pilot test of the Electronic Surviving Cancer Competently Intervention Program (eSCCIP), a psychosocial eHealth intervention for parents of children with cancer, a qualitative study was designed to preemptively generate strategies to address potential difficulties in these domains.

Methods

Two focus groups and three semi-structured interviews were conducted with parents of children with cancer. Qualitative data were analyzed using the principles of thematic and content analysis. Themes were generated to describe results and inform the development of concrete recruitment, retention, and engagement strategies to be utilized in future intervention trials.

Results

Five themes emerged specific to recruitment, and three themes emerged related to retention and engagement. Parents highlighted a number of important potential recruitment, retention, and engagement strategies, including the importance of flexibility, ease of access and use, intervention timing, and pathways to follow-up care. Themes were linked to actionable recruitment, retention, and engagement strategies which can be utilized in future studies.

Conclusion

Results from the current study will be utilized when designing future eSCCIP intervention trials and will also be of use to the broader field of psychosocial eHealth intervention research in pediatric psychology. This study also underscores the importance of working with parent stakeholders at all phases of study design and implementation.
Viewing Participation in Censuses and Surveys through the Lens of Lifestyle Segments
Authors: Mulry Mary H , Bates Nancy , Virgile Matthew
Published: March 2020

As the 2020 US Census approaches, the preparations include tests of new methodologies for enumeration that have the potential to reduce cost and improve quality. The 2015 Census Test in Savannah, GA, included tests of Internet and mail response modes and of online delivery of social marketing communications focused on persuading the public to respond by Internet and mail. Merging data from the 2015 Census Test with external third-party lifestyle segments and the Census Bureau’s new Low Response Score (LRS) produces a dataset suitable for studying relationships between census response, LRSs, and lifestyle segments. This paper uses the merged dataset to examine whether lifestyle segments can provide insight to hard-to-survey populations, their response behavior, and interactions with social marketing communications. The article also includes analyses with nationwide data that support the broader application of using segmentation variables in self-response propensity models and a discussion of potential applications of segment lifestyle information in tailored and targeted survey designs for hard-to-survey populations.
Dynamical and physical features of Perseid meteoroids from Tajikistan fireball network observations
Authors: Kokhirova G I , Babadzhanov P B , Khamroev U H , Latipov M N , Faizov Sh B
Published: March 2020

We present the results of a study of the dynamical and physical properties of large-sized Perseid meteoroids based on optical observations. Photographic observations of the Perseid meteor shower were carried out during the maximum of its activity in 2007–2011 using the Tajikistan fireball network. Multistation images of 29 Perseids recorded during this period were processed. The atmospheric trajectories, velocities, radiants, orbits, photometric masses and densities of the meteoroids were determined using the astrometric and photometric reduction of fireball images. The initial masses of meteoroids that produced fireballs range from several to 20 g. The observed light-curves of the Perseids and the mean bulk density of most meteoroids of ~0.4 g cm−3 are typical for cometary matter. According to the radiants, velocities and orbits, the captured Perseids are related both to the annual component of the stream and to the dust trail ejected by the parent comet 109P/Swift–Tuttle during its last perihelion passage in 1992.
Spatial correlations of extended cosmological structures
Authors: Santucho V , Luparello H E , Lares M , Lambas D G , Ruiz A N , Sgró M A
Published: March 2020

Studies of large-scale structures in the Universe, such as superstructures or cosmic voids, have been widely used to characterize the properties of the cosmic web through statistical analyses. On the other hand, the two-point correlation function of large-scale tracers such as galaxies or haloes provides a reliable statistical measure. However, this function applies to the spatial distribution of point-like objects, and therefore it is not appropriate for extended large structures that strongly depart from spherical symmetry. Here we present an analysis based on the standard correlation function formalism that can be applied to extended objects exhibiting arbitrary shapes. Following this approach, we compute the probability excess Ξ of having spheres sharing parts of cosmic structures with respect to a realization corresponding to a distribution of the same structures in random positions. For this aim, we identify superstructures defined as future virialized structures (FVSs) in semi-analytic galaxies in the MPDL2 MultiDark simulation. We have also identified cosmic voids to provide a joint study of their relative distribution with respect to the superstructures. Our analysis suggests that Ξ provides useful characterizations of the large-scale distribution, as suggested from an analysis of subsets of the simulation. Even when superstructure properties may exhibit negligible variations across the subsets, Ξ has the sensitivity to statistically distinguish sub-boxes that depart from the mean at larger scales. Thus, our methods can be applied in analysis of future surveys to provide characterizations of large-scale structure suitable to distinguish different theoretical scenarios.
On the nature of the soft γ-ray emission in the hard state of the black hole transient GRS 1716−249
Authors: Bassi T , Malzac J , Del Santo M , Jourdain E , Roques J-P , D’Aì A , Miller-Jones J C A , Belmont R , Motta S E , Segreto A , Testa V , Casella P
Published: March 2020

The black hole transient GRS 1716−249 was monitored from the radio to the γ-ray band during its 2016–2017 outburst. This paper focuses on the spectral energy distribution (SED) obtained in 2017 February–March, when GRS 1716−249 was in a bright hard spectral state. The soft γ-ray data collected with the INTEGRAL/SPI telescope show the presence of a spectral component that is in excess of the thermal Comptonization emission. This component is usually interpreted as inverse Compton emission from a tiny fraction of non-thermal electrons in the X-ray corona. We find that hybrid thermal/non-thermal Comptonization models provide a good fit to the X-/γ-ray spectrum of GRS 1716−249. The best-fitting parameters are typical of the bright hard state spectra observed in other black hole X-ray binaries. Moreover, the magnetized hybrid Comptonization model belm provides an upper limit on the intensity of the coronal magnetic field of about 106 G. Alternatively, this soft γ-ray emission could originate from synchrotron emission in the radio jet. In order to test this hypothesis, we fit the SED with the irradiated disc plus Comptonization model combined with the jet internal shock emission model ishem. We found that a jet with an electron distribution of p ≃ 2.1 can reproduce the soft γ-ray emission of GRS 1716−249. However, if we introduce the expected cooling break around 10 keV, the jet model can no longer explain the observed soft γ-ray emission, unless the index of the electron energy distribution is significantly harder (p < 2).
Proton and carbon ion radiotherapy in skull base chordomas: a prospective study based on a dual particle and a patient-customized treatment strategy
Authors: Iannalfi Alberto , D’Ippolito Emma , Riva Giulia , Molinelli Silvia , Gandini Sara , Viselner Gisela , Fiore Maria Rosaria , Vischioni Barbara , Vitolo Viviana , Bonora Maria , Ronchi Sara , Petrucci Rachele , Barcellini Amelia , Mirandola Alfredo , Russo Stefania , Vai Alessandro , Mastella Edoardo , Magro Giuseppe , Maestri Davide , Ciocca Mario , Preda Lorenzo , Valvo Francesca , Orecchia Roberto
Published: March 2020

Background

The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS), and toxicity profile and to better identify factors influencing clinical outcome of skull base chordoma treated with proton therapy (PT) and carbon ion radiotherapy (CIRT).

Methods

We prospectively collected and analyzed data of 135 patients treated between November 2011 and December 2018. Total prescription dose in the PT group (70 patients) and CIRT group (65 patients) was 74 Gy relative biological effectiveness (RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan–Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes.

Results

After a median follow-up of 49 (range, 6–87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. Five-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in the CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, gross tumor volume (GTV), optic pathways, and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity grade ≥3 was reported in 11% of patients.

Conclusions

Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways, and/or brainstem compression and target coverage were independent prognostic factors for LC.

Key Points

• Proton and carbon ion therapy are effective and safe in skull base chordoma.

• Prognostic factors are GTV, organs at risk compression, and dose coverage.

• Dual particle therapy and customized strategy was adopted.
Statistical double Λ hypernuclear formation from Ξ− absorption at rest in light nuclei
Authors: Ohnishi Akira , Ishizuka Chikako , Tsubakihara Kohsuke , Hirata Yuichi
Published: March 2020

We investigate double $\Lambda$ hyperfragment formation from the statistical decay of double $\Lambda$ compound nuclei produced in the $\Xi^-$ absorption at rest in the light nuclei $^{12}\mathrm{C}$, $^{14}\mathrm{N}$, and $^{16}\mathrm{O}$. We examine the target and the $\Lambda\Lambda$ bond energy dependence of the double $\Lambda$ hyperfragment formation probabilities, especially of those double hypernuclei observed in experiments. For the $^{12}\mathrm{C}$ ($^{14}\mathrm{N}$) target, the formation probabilities of $^{\,\;\;6}_{\Lambda\Lambda}\mathrm{He}$ and $^{\;10}_{\Lambda\Lambda}\mathrm{Be}$ ($^{\;13}_{\Lambda\Lambda}\mathrm{B}$) are found to be reasonably large as they are observed in the KEK-E373 (KEK-E176) experiment. By comparison, for the $^{16}\mathrm{O}$ target, the formation probability of $^{\;11}_{\Lambda\Lambda}\mathrm{Be}$ is calculated to be small with $\Delta B_{\Lambda\Lambda}$ consistent with the Nagara event. We also evaluate the formation probability of ${}^{\,\;\;5}_{\Lambda\Lambda}\mathrm{H}$ from a $\Xi^-$–${}^{6}\mathrm{He}$ bound state, ${}^{7}_{\Xi}\mathrm{H}$.
Association of fine-particulate and acidic-gas air pollution with premenstrual syndrome risk
Authors: Lin S-Y , Yang Y-C , Chang C Y-Y , Hsu W-H , Lin C-C , Jiang C-C , Wang I-K , Lin C-D , Hsu C-Y , Kao C-H
Published: March 2020

Objective

Air pollution had been reported to be associated with the reproductive health of women. However, the association of particulate matter (PM) and acid gases air pollution with premenstrual syndrome (PMS) warrants investigation. This study investigated the effects of air pollution on PMS risk.

Population

We combined data from the Taiwan Air Quality-Monitoring Database and the Longitudinal Health Insurance Database. In total, an observational cohort of 85 078 Taiwanese women not diagnosed as having PMS.

Methods

Air pollutant concentrations were grouped into four levels based on the concentration quartiles of several types of air pollutants.

Main outcome measures

We then applied univariable and multivariable Cox proportional hazard regression models to assess PMS risk in association with each pollutant type.

Results

Women exposed to Q4-level SO2 exhibited a 7.77 times higher PMS risk compared with those to Q1-level SO2 (95% confidence interval [CI] = 6.22–9.71). Women exposed to Q4-level NOx exhibited a 2.86 times higher PMS risk compared with those exposed to Q1-level NOx (95% CI = 2.39–3.43). Women exposed to Q4-level NO exhibited a 3.17 times higher PMS risk compared with women exposed to Q1-level NO (95% CI = 2.68–3.75). Finally, women exposed to Q4-level PM with a ≤2.5-µm diameter (PM2.5) exhibited a 3.41 times higher PMS risk compared with those exposed to Q1-level PM2.5 (95% CI = 2.88–4.04).

Conclusions

High incidences of PMS were noted in women who lived in areas with higher concentrations of SO2, NOx, NO, NO2 and PM2.5.
Child-Related Transfers, Household Labour Supply, and Welfare
Authors: Guner Nezih , Kaygusuz Remzi , Ventura Gustavo
Published: March 2020

What are the macroeconomic effects of transfers to households with children? How do alternative policies fare in welfare terms? We answer these questions in an equilibrium life-cycle model with household labour supply decisions, skill losses of females associated to non-participation, and heterogeneity in terms of fertility, childcare expenditures, and access to informal care. Calibrating our model to the U.S. economy, we first provide a roadmap for policy evaluation by contrasting transfers that are conditional on market work (childcare subsidies and childcare credits) with those that are not (child credits), when both types can be means tested or universal. We then evaluate expansions of current arrangements for the U.S. and find that expansions of conditional transfers have substantial positive effects on female labour supply, that are largest at the bottom of the skill distribution. Expanding childcare credits leads to long-run increases in the participation of married females of 10.6%, while an equivalent expansion of child credits leads to the opposite ($-$2.4%). Expanding existing programs generates substantial welfare gains for newborn households, which are largest for less-skilled households. Expanding childcare credits leads to the largest welfare gains for newborns and achieves majority support.
Exploring the influence of silver and lead on structure and function of xylanase: spectroscopic and calorimetric methods
Authors: Jing Mingyang , Tang Rui , Han Guangye , Zhang Shansheng , Liu Rutao
Published: March 2020

Soil contamination with heavy metal could induce the alteration of soil ecological environments, and soil enzyme activities are sensitive indicators for the soil toxicology. Xylanase is one of predominant soil enzymes related to carbon nitrogen cycle. In this work, we explored the underlying mechanisms for conformational and enzymatic activity alterations of xylanase after silver and lead exposure at molecular level with systematical measurements including multiple spectroscopic methods, isothermal titration calorimetry, and enzymatic activity. Both silver and lead could loosen and unfold the skeleton of xylanase with the quenching of endogenous fluorescence. Silver interacted with xylanase forming larger-size aggregations through Van der Waals forces and hydrogen bonding, while lead interacted with xylanase forming larger-size aggregations through hydrophobic force. Silver and lead induced an obvious loss (67.1 and 56.31%) of the xylanase enzymatic activity, but silver has a greater impact on xylanase than that of lead. The xylanase enzymatic activity significantly decreased due to the conformational alterations. The negative effect of silver exposure on xylanase structure and function was more prominent than that of lead.
Frequent unregulated use of antibiotics in rural Cambodian infants
Authors: Miyazaki Asuka , Tung Rathavy , Taing Bunsreng , Matsui Mitsuaki , Iwamoto Azusa , Cox Sharon E
Published: March 2020

Background

Despite a high prevalence of antibiotic resistance in Cambodia, few studies have assessed health-seeking behaviour and the use of antibiotics by caregivers of young children in Cambodia.

Methods

We conducted a cross-sectional survey of infants <12 months of age and their caregivers, assessing the frequency of reported illness, common symptoms and associated health-seeking behaviour through structured questionnaires administered by trained fieldworkers at a home visit. In a subset of these participants, ages 4–8 months with no acute malnutrition, we conducted a 3-month surveillance with fortnightly home visits.

Results

Of 149 infants (ages 1–11 months, 54.4% male) enrolled in the cross-sectional study, 76 (51.4%) reported symptoms of diarrhoea, fever or cough in the previous 14 d, with associated use of antibiotics reported in 22 (14.8%) infants. In 47 infants enrolled in the longitudinal surveillance, there were 141 reported episodes of illness in 44 (94%) infants with 21 infants (45%) reported to have received antibiotics in 32/141 (22.7%) episodes. Amoxicillin was the most commonly reported antibiotic in both surveys (68% [40/59 episodes reporting the use of antibiotics]).

Conclusions

Antibiotic usage is high in this population and appears to be occurring largely outside of the formal healthcare system.
How unique is unique? Quantifying geometric differences in stripe patterns of Cape mountain zebra,Equus zebra zebra(Perissodactyla: Equidae)
Authors: Prinsloo Nicolas D , Postma Martin , de Bruyn P J Nico
Published: March 2020

Quantified coat pattern dissimilarity provides a visible surface for individual animal traceability to populations. We determined the feasibility in quantifying uniqueness of stripe patterns of Cape mountain zebra (CMZ; Equus zebra zebra) using geometric morphometrics. We photogrammetrically created dense surface models of CMZ (N = 56). Stripe edges were landmarked, superimposed and compared for shape variation across replicates and the population. Significant allometry in stripe patterns prompted allometric correction to remove increased curvature of stripes at the rump, belly and back with larger adult individuals, to facilitate equilibrated comparison between individuals. Re-landmarked replicates showed lower dissimilarity (Di) than non-replicates (Dp), representing minimal landmarking error. Individuals were 78.07 ± 1.79% unique (U=1−DiDp×100%) relative to the study population. Size, the number of torso stripes and degree of branching in four rear torso stripes described the most shape variation (36.79%) but a significant portion could only be distinguished with geometric morphometrics (41.82%). This is the first known use of geometric morphometrics to quantify coat pattern uniqueness, using a model species to provide baseline individual morphological variation. Measures of coat pattern similarity have a place in phenotypic monitoring and identification.
Deep Learning-based Detection for COVID-19 from Chest CT using Weak Label
Authors: Zheng Chuansheng , Deng Xianbo , Fu Qiang , Zhou Qiang , Feng Jiapei , Ma Hui , Liu Wenyu , Wang Xinggang
Published: March 2020

Accurate and rapid diagnosis of COVID-19 suspected cases plays a crucial role in timely quarantine and medical treatment. Developing a deep learning-based model for automatic COVID-19 detection on chest CT is helpful to counter the outbreak of SARS-CoV-2. A weakly-supervised deep learning-based software system was developed using 3D CT volumes to detect COVID-19. For each patient, the lung region was segmented using a pre-trained UNet; then the segmented 3D lung region was fed into a 3D deep neural network to predict the probability of COVID-19 infectious. 499 CT volumes collected from Dec. 13, 2019, to Jan. 23, 2020, were used for training and 131 CT volumes collected from Jan 24, 2020, to Feb 6, 2020, were used for testing. The deep learning algorithm obtained 0.959 ROC AUC and 0.976 PR AUC. There was an operating point with 0.907 sensitivity and 0.911 specificity in the ROC curve. When using a probability threshold of 0.5 to classify COVID-positive and COVID-negative, the algorithm obtained an accuracy of 0.901, a positive predictive value of 0.840 and a very high negative predictive value of 0.982. The algorithm took only 1.93 seconds to process a single patient’s CT volume using a dedicated GPU. Our weakly-supervised deep learning model can accurately predict the COVID-19 infectious probability in chest CT volumes without the need for annotating the lesions for training. The easily-trained and highperformance deep learning algorithm provides a fast way to identify COVID-19 patients, which is beneficial to control the outbreak of SARS-CoV-2. The developed deep learning software is available athttps://github.com/sydney0zq/covid-19-detection.
Purging of deleterious mutations during domestication in the predominant selfing crop soybean
Authors: Kim Myung-Shin , Lozano Roberto , Kim Ji Hong , Bae Dong Nyuk , Kim Sang-Tae , Park Jung-Ho , Choi Man Soo , Kim Jaehyun , Ok Hyun Choong , Park Soo-Kwon , Gore Michael A. , Moon Jung-Kyung , Jeong Soon-Chun
Published: March 2020

As a predominant plant protein and oil source for both food and feed, soybean is unique in that both domesticated and wild types are predominantly selfing. Here we present a genome-wide variation map of 781 soybean accessions that include 418 domesticated (Glycine max) and 345 wild (Glycine soja) accessions and 18 of their natural hybrids. We identified 10.5 million single nucleotide polymorphisms and 5.7 million small indels that contribute to within- and between-population variations. We describe improved detection of domestication-selective sweeps and drastic reduction of overall deleterious alleles in domesticated soybean relative to wild soybean in contrast to the cost of domestication hypothesis. This resource enables the marker density of existing data sets to be increased to improve the resolution of association studies.
Mental health status among family members of health care workers in Ningbo, China during the Coronavirus Disease 2019 (COVID-19) outbreak: a Cross-sectional Study
Authors: Ying Yuchen , Kong Fanqian , Zhu Binbin , Ji Yunxin , Lou Zhongze , Ruan Liemin
Published: March 2020

Background

So far, the psychological impact of COVID-19 epidemic among family members of Health care workers (HCWs) in China has been neglected. The present cross-sectional study aimed to investigate the mental health status and related factors of families of HCWs in Designated Hospitals in Ningbo, China.

Method

Family members of HCWs working in five designated hospitals in Ningbo, China were recruited between February 10th and 20th, 2020. Information on demographic variables, the COVID-19-related events in the lives, knowledge of COVID-19 and the working status of family members (that is, HCWs) was collected using online self-administered questionnaires. The mental health status were assessed using the Chinese version of Patient Health Questionnare-9 (PHQ-9) and Chinese version of Generalized Anxiety Disorder-7 (GAD-7). Multivariable logistic regression analyses were conducted to identify the main factors associated with the mental health conditions.

Results

A total of 822 participants completed questionnaires correctly. (response rate of 95.80%). The overall prevalence of GAD and depressive symptoms were 33.73%, and 29.35%, respectively. More times (hours) to focus on the COVID-19 (Odd ratio (OR)=1.215, 95% confidence interval (CI):1.061-1.391), family members (that is, HCWs) directly contact with confirmed or suspected COVID-19 patients (OR=1.477, 95%CI:1.069-2.040) were risk factors for GAD, while higher participants self-reported safety score for protective equipment of HCWs (OR=0.807, 95%CI:0.700-0.930) was a protective factor. More times (hours) to focus on the COVID-19 (OR=1.215, 95%CI:1.061-1.391), longer average working times per week for family members (that is, HCWs) (OR=1.017, 95%CI:1.005-1.029), being parents and other next of kin of HCWs were risk factors for depressive symptoms (OR=3.526, 95%CI:1.609-7.728 and OR=1.639, 95%CI:1.096-2.451, respectively). In addition, compared with participants who were HCWs, participants who were enterprise workers and were more likely to develop depressive symptoms(OR=1.750, 95%CI:1.104-2.776), while who were government employees or institutions employees were less likely to suffer depressive symptoms (OR=0.529, 95%CI:0.286-0.977).

Conclusions

Psychological responses to COVID-19 have been dramatic among family members of HCWs during the rising phase of the outbreak. Our findings provide strong evidence to pay more attention on the mental health status of this vulnerable but often unseen populations during COVID-19 epidemic.
A Cybernetics-based Dynamic Infection Model for Analyzing SARS-COV-2 Infection Stability and Predicting Uncontrollable Risks
Authors: Xiao Wenlei , Liu Qiang , Huan Ji , Sun Pengpeng , Wang Liuquan , Zang Chenxin , Zhu Sanying , Gao Liansheng
Published: March 2020

Since December 2019, COVID-19 has raged in Wuhan and subsequently all over China and the world. We propose a Cybernetics-based Dynamic Infection Model (CDIM) to the dynamic infection process with a probability distributed incubation delay and feedback principle. Reproductive trends and the stability of the SARS-COV-2 infection in a city can then be analyzed, and the uncontrollable risks can be forecasted before they really happen. The infection mechanism of a city is depicted using the philosophy of cybernetics and approaches of the control engineering. Distinguished with other epidemiological models, such as SIR, SEIR, etc., that compute the theoretical number of infected people in a closed population, CDIM considers the immigration and emigration population as system inputs, and administrative and medical resources as dynamic control variables. The epidemic regulation can be simulated in the model to support the decision-making for containing the outbreak. City case studies are demonstrated for verification and validation.
Wuhan and Hubei COVID-19 mortality analysis reveals the critical role of timely supply of medical resources
Authors: Zhang Zuqin , Yao Wei , Wang Yan , Long Cheng , Fu Xinmiao
Published: March 2020

We report that COVID-19 mortality and recovery rates in Hubei Province, China exponentially decays (R2>0.93) and grows (R2>0.95), respectively. A great number of newly supplied medical resources, including more than 42000 aided health workers, over 26000 makeshift beds and 23000 acute care beds, enabled overwhelming patients to be treated effectively in hospitals. This may inform other countries to deal with the coming COVID-19 pandemic when patients are overwhelming the local health care system.
The breadth-depth dilemma in a finite capacity model of decision-making
Authors: Moreno-Bote Rubén , Ramírez-Ruiz Jorge , Drugowitsch Jan , Hayden Benjamin Y.
Published: March 2020

Decision-makers are often faced with limited information about the outcomes of their choices. Current formalizations of uncertain choice, such as the explore-exploit dilemma, do not apply well to decisions in which search capacity can be allocated to each option in variable amounts. Such choices confront decision-makers with the need to tradeoff betweenbreadth- allocating a small amount of capacity to each of many options – anddepth- focusing capacity on a few options. We formalize the breadth-depth dilemma through a finite sample capacity model. We find that, if capacity is smaller than 4-7 samples, it is optimal to draw one sample per alternative, favoring breadth. However, for larger capacities, a sharp transition is observed, and it becomes best to deeply sample a very small fraction of alternatives, that decreases with the square root of capacity. Thus, ignoring most options, even when capacity is large enough to shallowly sample all of them, reflects a signature of optimal behavior. Our results also provide a rich casuistic for metareasoning in multi-alternative decisions with bounded capacity.