bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knowledge, attitudes and practices concerning visceral leishmaniasis among residents of a sporadic transmission area in southeast Brazil
Authors: Limongi Jean E , Costa Luiz C G P , Perissato Izabela L , Giorgiani Mariana , Rocha Máyra B , Faria Larissa F D , Valente Hiléia C O , Oliveira Stefan V 
Published: September 2020

Abstract

Background
In the last four decades, visceral leishmaniasis (VL) has undergone an urbanization process in Brazil. This research aimed to assess the knowledge, attitudes and practices concerning VL among residents of a sporadic transmission urban area in southeast Brazil.

Methods
A community-based, cross-sectional quantitative study was conducted. Scores for knowledge, attitudes and practices concerning VL were evaluated and the bivariate analysis was performed.

Results
The analysis indicated that 29.9% had good knowledge, 5.2% had appropriate attitudes and 62.1% had appropriate practices. Notwithstanding that, pivotal practices for controlling VL had unsatisfactory individual frequencies. Good knowledge on VL was related to women, a higher level of education, a higher income, the place of residence and having pets. Appropriate attitudes were related to the place of residence. The practices had no significant associations with the sociodemographic and epidemiological variables.

Conclusion
This study demonstrated that even in the area of disease transmission, knowledge on VL is very limited, including at the most basic level. In order to achieve effectiveness in actions against VL in Brazil, the participation of the affected communities is imperative, therefore popular health education interventions are necessary to improve the population's understanding of the disease and to avoid inappropriate attitudes and practices.
Validation and Precision of Mixed Reality Technology in Baha Attract Implant Surgery
Authors: Tian Xu , Gao Zhi-qiang , Zhang Zhu-hua , Chen Yu , Zhao Yang , Feng Guo-dong 
Published: September 2020

Objective:
To test the feasibility of image-guided Baha Attract implant surgery with mixed reality (MR) in the form of the HoloLens to visualize critical structures and facilitate precise Baha implant placement.

Methods:
A cadaveric case study of bilateral Baha Attract implant approaches was conducted using Star Atlas MR three-dimensional (3D) medical interaction system guidance at the Otolaryngology Department of PUMCH, Beijing, China. The accuracy of visual surface registration was determined by the target registration error (TRE) between the predefined points on the preoperative 3D holographic Baha Attract implant model and the postoperatively reconstructed 3D model.

Results:
Bilateral Baha Attract implantation was completed successfully for all four cadaveric heads using the Star Atlas MR 3D medical interaction system with the HoloLens. The preoperative 3D digital model characteristics (including bone quality and thickness and avoidance of cranial vessels, air cells, and cranial sutures) corresponded well with the 3D model of the actual implantation reconstructed postoperatively. The median TRE of our system was 2.97 mm (ranging from 1.98 to 4.58 mm) in terms of distance and 2.76 degrees (ranging from 0.59 to 6.4 degrees) in terms of angle.

Conclusions:
Applying MR technology in the form of the HoloLens in Baha Attract implant surgery is feasible and could improve the accuracy of the surgery. The described MR system for Baha Attract implantation has the potential to improve the surgeon's confidence, as well as the surgical safety, efficiency, and precision.
Diurnal Variation in Medical Emergency Team Calls at a Tertiary Care Children’s Hospital
Authors: Conway Susan R. , Tegtmeyer Ken , Wheeler Derek S. , Loechtenfeldt Allison , Stalets Erika L. , Brady Patrick W. 
Published: September 2020

Introduction:
Medical emergency teams (METs) bring critical care expertise to the bedsides of hospital ward patients who may be deteriorating. Diurnal variation in MET activation rates may identify inconsistencies in the detection of patients needing intervention. We aimed to determine whether such variation exists at our tertiary care children’s hospital.

Methods:
In this retrospective cohort study, we collected data including date and time of MET and disposition following MET for all inpatients at Cincinnati Children’s Hospital Medical Center with a MET call between January 2008 and May 2014. The analysis compared the MET rate between days and nights, weekdays and weekends, and before and after nursing shift change.

Results:
The number of METs per hour varied throughout the day. More METs were called during the day than at night (0.7 calls/shift ± 0.95 vs 0.6 ± 0.9, P < 0.001). There were also more METs per day on weekdays than weekends (1.4 ± 1 calls/d vs 1.2 ± 1, P < 0.001). Daytime METs were more likely to lead to transfer to the intensive care unit or operating room than those called at night (61.9% vs. 52.9%, P < 0.001). MET activation rates did not differ significantly in the 2 hours before nursing shift change compared to the 2 hours after.

Conclusions:
At our large tertiary care children’s hospital, there are both diurnal variations and variations across weekdays versus weekends in the MET activation rate. This difference may indicate variations in our ability to detect deteriorating patients on the wards and be further studied.
Comparing geographic information system–based estimates with trauma center registry data to assess the effects of additional trauma centers on system access
Authors: Winchell Robert J. , Broecker Justine , Kerwin Andrew J. , Eastridge Brian , Crandall Marie 
Published: September 2020

BACKGROUND
Geographic information systems (GISs) are often used to analyze trauma systems. Geographic information system–based approaches can model access to a trauma center (TC), including estimates of transport time and population coverage, when accurate trauma registry and emergency medical systems (EMS) data are not available. We hypothesized that estimates of trauma system performance calculated using a standard GIS method with public data would be comparable with trauma registry data.

METHODS
A standardized GIS-based method was used to estimate metrics of TC access in a regional trauma system in which the number of TCs increased from one to three during a 3-year period. Registry data from the index TC in the system were evaluated for different periods during this evolution. The number of admissions to the TC in different periods was compared with changes predicted by the GIS-based model, and the distribution of observed ground-based transportation times was compared with the predicted distribution.

RESULTS
With the addition of two TCs to the system, the volume of patients transported by ground to the index TC decreased by 30%. However, the model predicted a 68% decrease in population having the shortest predicted transport time to the index TC. The model predicted the geographic trend seen in the registry data, but many patients were transported to the index TC even though it was not the closest center. Observed transport times were uniformly shorter than predicted times.

CONCLUSION
The GIS-based model qualitatively predicted changes in distribution of trauma patients, but registry data highlight that field triage decisions are more complex than model assumptions. Similarly, transport times were systematically overestimated. This suggests that model assumptions, such as vehicle speed, based on normal traffic may not fully reflect emergency medical systems (EMS) operations. There remains great need for metrics to guide policy based on widely available data.

LEVEL OF EVIDENCE
Epidemiological, level III.
Fluviibacter phosphoraccumulans gen. nov., sp. nov., a polyphosphate-accumulating bacterium of Fluviibacteraceae fam. nov., isolated from surface river water
Authors: Watanabe Keiji , Morohoshi Sho , Kunihiro Tadao , Ishii Yuichi , Takayasu Lena , Ogata Yusuke , Shindo Chie , Suda Wataru 
Published: September 2020

Three aerobic, Gram-stain-negative, non-motile, rod-shaped bacteria, designated as strains SHINM1T, ICHIJ1 and ICHIAU1, were isolated from surface river water (Saitama Prefecture, Japan). Phylogenetic analyses based on 16S rRNA and 40 marker gene sequences revealed that the strains formed a distinct phylogenetic lineage within the order

Rhodocyclales

. The three strains shared 100 % 16S rRNA gene similarity. Growth occurred at 15–30 °C and pH 6.0–9.5, but not in the presence of ≥1.0 % (w/v) NaCl. The isolates stained positive for intracellular polyphosphate granules. The major cellular fatty acids were C16 : 0, summed feature 2 (C12 : 1 aldehyde and/or iso-C16 : 1 I and/or C14 : 0 3-OH), summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c) and summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c). The major polar lipids were phosphatidylethanolamine and an unidentified phospholipid. The predominant quinone system of strain SHINM1T was ubiquinone-8 and its DNA G+C content was 56.7 mol%. Genome sequencing of the three isolates revealed a genome size of 2.29–2.43 Mbp and average nucleotide identity by orthology values of ≥98.9 %. Based on the results of phenotypic and phylogenetic analyses, strains SHINM1T, ICHIJ1 and ICHIAU1 represent a novel species of a new genus, for which the name Fluviibacter phosphoraccumulans gen. nov., sp. nov. is proposed, within a new family, Fluviibacteraceae fam. nov. of the order

Rhodocyclales

. The type strain is SHINM1T (=JCM 32071T=NCIMB 15105T).
Antisense oligonucleotide therapy for SCN2A gain-of-function epilepsy
Authors: Li Melody , Jancovski Nikola , Jafar-Nejad Paymaan , Burbano Lisseth Estefania , Rollo Ben , Richards Kay , Drew Lisa , Sedo Alicia , Pachernegg Svenja , Soriano Armand , Jia Linghan , Blackburn Todd , Roberts Blaine , Nemiroff Alex , Dalby Kelley , Maljevic Snezana , Reid Christopher , Rigo Frank , Petrou Steven 
Published: September 2020

AbstractThe clinical spectrum associated with SCN2Ade novomutations (DNMs) continues to expand and includes autism spectrum disorder with or without seizures, in addition to early and late seizure onset developmental and epileptic encephalopathies (DEEs). Recent biophysical studies on SCN2A variants suggest that the majority of early seizure onset DEE DNMs cause gain of function. Gain of function in SCN2A, the principal sodium channel of excitatory pyramidal neurons, would result in heightened neuronal activity and is likely to underlie the pathology seen in early seizure onset DEE patients. Supratherapeutic dosing of the non-selective sodium channel blocker phenytoin, is effective in controlling seizures in these patients but does not impact neurodevelopment, raising the idea that more profound and specific reduction in SCN2A function could significantly improve clinical outcome. To test the potential therapeutic benefit of reducing SCN2A in early seizure onset DEE we centrally administered an antisense oligonucleotide (ASO) targeting mouse Scn2a (Scn2a ASO) to a mouse model of human SCN2A early seizure onset DEE. Mice were genetically engineered to harbour the human equivalent SCN2A p.R1882Q mutation (Q/+), one of the most recurrent mutations in early seizure onset DEE. Q/+ mice presented with spontaneous seizures at postnatal day (P) 1 and did not survive beyond P30. Intracerebroventricular Scn2a ASO administration into Q/+ mice between P1-2 (that reduced Scn2a mRNA levels by 50%) significantly extended lifespan and markedly reduced spontaneous seizures occurrence. Across a range of cognitive and motor behavioural tests, Scn2a ASO treated Q/+ mice were largely indistinguishable from wildtype (+/+) mice. Further improvements in survival and behaviour were seen by adjustment of dosing regimens during development. Scn2a ASO efficacy was also evident at the cellular level. Whole cell patch clamp recording showed that Scn2a ASO administration reversed changes in neuronal excitability in layer 2/3 pyramidal neurons of Q/+ mice to levels seen in +/+ mice. Safety was assessed in +/+ mice and showed a developmental stage dependent tolerability and a favourable therapeutic index. This study suggests that a human SCN2A gapmer ASO could profoundly and safely impact early seizure onset DEE patients and heralds a new era of precision therapy in neurodevelopmental disorders.
c-Myb expression is critical to maintain proliferation and glucose metabolism of large pre-B cells
Authors: Daamen Andrea R. , Crittenden Rowena B. , Bender Timothy P. 
Published: September 2020

AbstractThe c-Myb transcription factor is required for the differentiation of CD19+B-lineage cells and plays significant roles from the specification of the B cell lineage to the survival of pro-B cells. c-Myb coordinates the survival of pro-B cells with the expression of genes required for transition to the large pre-B cell stage of differentiation. However, it is not known if c-Myb is important for the proliferative expansion or subsequent differentiation into small pre-B cells. Here we demonstrate that c-Myb expression is important for large pre-B cell survival, proliferation, and differentiation into small pre-B cells. Utilizing genome-wide analysis, we found that c-Myb was important for maintaining glucose uptake and utilization and exogenous expression of Glut1 and Hk1 rescued large pre-B cell recovery and survival. Furthermore, we found that c-Myb is important for repression of Ikaros and Aiolos and our c-Myb-dependent gene signature was enriched in an Ikaros footprint of genes that drive cell cycle exit and the large to small pre-B cell transition. However, upon loss of c-Myb expression, inhibition of Ikaros activity was able to restore certain Ikaros-mediated gene expression changes but was insufficient to rescue recovery of large pre-B cell numbers. We found that c-Myb regulates glucose utilization and glucose-dependent survival through Hk1 in an Ikaros-independent manner. Thus, c-Myb regulation of glucose metabolism is critical to maintain large pre-B cell survival while repression of the Ikaros-mediated gene expression program is critical to prevent premature cell cycle exit and premature differentiation into small pre-B cells.
Nanoparticle-mediated microRNA-145 Delivery for Vascular Smooth Muscle Cell Phenotype Modulation and Atherosclerosis Treatment
Authors: Chin Deborah D. , Poon Christopher , Wang Jonathan , Joo Johan , Ong Victor , Jiang Zhangjingyi , Cheng Kayley , Plotkin Anastasia , Magee Gregory A. , Chung Eun Ji 
Published: September 2020

AbstractVascular smooth muscle cells (VSMCs) change from contractile to the synthetic phenotype during atherogenesis and 30-70% of cells that make up plaques have been elucidated to be of VSMC origin. MicroRNA-145 (miR-145) is responsible for regulating VSMC phenotypic switching, and low miR-145 levels in circulation have been linked with atherosclerosis. Hence, we developed nanoparticles for targeted delivery of miR-145 by synthesizing micelles co-assembled with miR-145 and the CCR2-binding peptides for plaque targeting. The miR cargo was protected in micelles from premature endosomal degradation and rescued contractile markers in synthetic VSMCs and SMCs isolated from patient arteriesin vitro. In ApoE-/- mid-stage atherosclerotic mice, miR-145 micelles halted plaque growth and maintained contractile phenotypes similar to baseline levels. In early-stage atherosclerosis, a single dose of miR-145 micelles prevented lesion growth by 49%. We present the potential of miR-145 micelles as a therapeutic that can be applied longitudinally and intervene throughout atherosclerosis pathogenesis.
R-spondins are BMP receptor antagonists in early embryonic development
Authors: Lee Hyeyoon , Seidl Carina , Sun Rui , Glinka Andrei , Niehrs Christof 
Published: September 2020

ABSTRACTBMP signalling plays key roles in development, stem cells, adult tissue homeostasis, and disease. How BMP receptors are extracellularly modulated and in which physiological context, is therefore of prime importance. R-spondins (RSPOs) are a small family of secreted proteins that co-activate WNT signalling and function as potent stem cell effectors and oncogenes. Evidence is mounting that RSPOs act WNT-independently but how and in which physiological processes remains enigmatic. Here we show that RSPO2 and RSPO3 also act as BMP antagonists. RSPO2 is a high affinity ligand for the type I BMP receptor BMPR1A/ALK3, and it engages ZNRF3 to trigger internalization and degradation of BMPR1A. In earlyXenopusembryos, Rspo2 is a negative feedback inhibitor in the BMP4 synexpression group and regulates dorsoventral axis formation. We conclude that R-Spondins are bifunctional ligands, which activate WNT- and inhibit BMP signalling via ZNRF3, with implications for development and cancer.
Carry on caring: infected females maintain their level of parental care despite suffering high mortality
Authors: Ratz Tom , Monteith Katy M. , Vale Pedro F. , Smiseth Per T. 
Published: September 2020

AbstractParental care is a key component of an organism’s reproductive strategy that is thought to trade-off with allocation towards immunity. Yet it is unclear how caring parents respond to pathogens: do infected parents reduce their amount of care as a sickness behaviour or simply from being ill, or do they prioritise their offspring by maintaining high levels of care? Here we explored the consequences of infection by the pathogenSerratia marcescenson mortality, time spent providing care, reproductive output, and expression of immune genes of female parents in the burying beetleNicrophorus vespilloides. We compared untreated control females with infected females that were inoculated with live bacteria, immune-challenged females that were inoculated with heat-killed bacteria, and injured females that were injected with buffer. We found that infected and immune-challenged females mounted an immune response and that infected females suffered increased mortality. Nevertheless, infected and immune-challenged females maintained their normal level of care and reproductive output. There was thus no evidence that infection led to either a decrease or an increase in parental care or reproductive output. Our results show that parental care, which is generally highly flexible, can remain remarkably robust and consistent despite the elevated mortality caused by infection by pathogens. Overall, these findings suggest that infected females maintain a high level of parental care; a strategy that may ensure that offspring receive the necessary amount of care but that might be detrimental to the parents’ own survival or that may even facilitate disease transmission to offspring.
Visual perceptual learning generalizes to untrained effectors
Authors: Awada Asmara , Bakhtiari Shahab , Pack Christopher C. 
Published: September 2020

AbstractVisual perceptual learning (VPL) is an improvement in visual function following training. Although the practical utility of VPL was once thought to be limited by its specificity to the precise stimuli used during training, more recent work has shown that such specificity can be overcome with appropriate training protocols. In contrast, relatively little is known about the extent to which VPL exhibits motor specificity. Indeed, previous studies have shown that training paradigms that require one type of response (e.g., a button press) do not necessarily transfer to those that require a different response (e.g., a mouse movement). In this work, we have examined the effector specificity of VPL by training observers on tasks that maintain the same visual stimuli and task structure, but that require different effectors to indicate the response. We find that, in these conditions, VPL transfers fully between manual and oculomotor responses. These results are consistent with the idea that VPL entails the learning of a decision rule that can generalize across effectors.
Fine-tuning of Epithelial EGFR signals Supports Coordinated Mammary Gland Development
Authors: Samocha Alexandr , Doh Hanna M. , Sitarama Vaishnavi , Nguyen Quy H. , Gbenedio Oghenekevwe , Rudolf Joshua D. , Eckalbar Walter L. , Barczak Andrea J. , Miao Yi , Garcia K. Christopher , Lawson Devon , Werb Zena , Kessenbrock Kai , Depeille Philippe , Roose Jeroen P. 
Published: September 2020

SummaryDuring puberty, robust morphogenesis occurs in the mammary gland; stem- and progenitor-cells develop into mature basal- and luminal-cells to form the ductal tree. The receptor signals that govern this process in mammary epithelial cells (MECs) are incompletely understood. The EGFR has been implicated and here we focused on EGFR’s downstream pathway component Rasgrp1. We find that Rasgrp1 dampens EGF-triggered signals in MECs. Biochemically andin vitro,Rasgrp1perturbation results in increased EGFR-Ras-PI3K-AKT and mTORC1-S6 kinase signals, increased EGF-induced proliferation, and aberrant branching-capacity in 3D cultures. However,in vivo, Rasgrp1perturbation results in delayed ductal tree maturation with shortened branches and reduced cellularity.Rasgrp1-deficient MEC organoids revealed lower frequencies of basal cells, the compartment that incorporates stem cells. Molecularly, EGF effectively counteracts Wnt signal-driven stem cell gene signature in organoids. Collectively, these studies demonstrate the need for fine-tuning of EGFR signals to properly instruct mammary epithelium during puberty.
Recursive splicing is a rare event in the mouse brain
Authors: Moon Sohyun , Zhao Ying-Tao 
Published: September 2020

AbstractRecursive splicing (RS) is a splicing mechanism to remove long introns from messenger RNA precursors of long genes. Compared to the hundreds of RS events identified in humans and drosophila, only ten RS events have been reported in mice. To further investigate RS in mice, we analyzed RS in the mouse brain, a tissue that is enriched in the expression of long genes. We found that nuclear total RNA sequencing is an efficient approach to investigate RS events. We analyzed 1.15 billion uniquely mapped reads from the nuclear total RNA sequencing data in the mouse cerebral cortex. Unexpectedly, we only identified 20 RS sites, suggesting that RS is a rare event in the mouse brain. We also identified that RS is constitutive between excitatory and inhibitory neurons and between sexes in the mouse cerebral cortex. In addition, we found that the primary sequence context is associated with RS splicing intermediates and distinguishes RS AGGT site from non-RS AGGT sites, indicating the importance of the primary sequence context in RS sites. Moreover, we discovered that cryptic exons may use an RS-like mechanism for splicing. Overall, our findings provide novel insights into RS in long genes.
TTAPE-Me dye is not selective to cardiolipin and responds to main anionic phospholipids unspecifically
Authors: Pyrshev Kyrylo , Yesylevskyy Semen , Bogdanov Mikhail 
Published: September 2020

AbstractIdentification, visualization and quantitation of cardiolipin (CL) in biological membranes is of great interest due to important structural and physiological roles of this lipid. Selective fluorescent detection of CL using non-covalently bound fluorophore TTAPE-Me (1,1,2,2-tetrakis[4-(2-trimethylammonioethoxy)-phenylethene) has been recently proposed. However, this dye was only tested on wild-type mitochondria or liposomes containing neglegible amounts of other anionic lipids, such as PG and PS. No clear preference of TTAPE-Me for binding to CL compared to PG and PS was found in our experiments. The shapes of the emission spectra for these anionic phospholipids were also found to be indistinguishable. Our experiments and complementary molecular dynamics simulations suggest that fluorescence intensity of TTAPE-Me is regulated by dynamic equilibrium between emitting dye, bound to anionic lipids by means of unspecific electrostatic attraction, and non-emitting dye aggregates in aqueous solution. Therefore, TTAPE-Me is not suitable for detection, visualization and localization of CL in the presence of PS and PG present in physiological amounts in the membranes of eukaryotic and prokaryotic cells, respectively.