bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant endocrine therapy in locally advanced estrogen or progesterone receptor-positive breast cancer: determining the optimal endocrine agent and treatment duration in postmenopausal women—a literature review and proposed guidelines
Authors: Madigan Lauren I. , Dinh Phuong , Graham J. Dinny 
Published: July 2020

Abstract
Introduction
For patients with locally advanced estrogen receptor or progesterone receptor-positive breast cancer, neoadjuvant endocrine therapy (NET) facilitates down-staging of the tumor and increased rates of breast-conserving surgery. However, NET remains under-utilized, and there are very limited clinical guidelines governing which therapeutic agent to use, or the optimal duration of treatment in postmenopausal women. This literature review aims to discuss the evidence surrounding (1) biomarkers for patient selection for NET, (2) the optimal neoadjuvant endocrine agent for postmenopausal women with locally advanced breast cancer, and (3) the optimal duration of NET. In addition, we make initial recommendations towards developing a clinical guideline for the prescribing of NET.

Method
A wide-ranging search of online electronic databases was conducted using a truncated PIC search strategy to identify articles that were relevant to these aims and revealed a number of key findings.

Results
Randomized trials have consistently demonstrated that aromatase inhibitors are more effective than tamoxifen, in terms of objective response rate and rate of BCS, and should be used as first-line NET. The three available aromatase inhibitors have so far been demonstrated to be biologically equivalent, with the choice of aromatase inhibitor not having been shown to affect clinical outcomes. There is increasing evidence for extending the duration of NET beyond 3 to 4 months, to at least 6 months or until maximal clinical response is achieved. While on-treatment levels of the proliferation marker Ki67 are predictive of long-term outcome, the choice of adjuvant therapy in patients who have received NET and then surgery is best guided by the preoperative endocrine prognostic index, or PEPI, which incorporates Ki67 with other clinical parameters.

Conclusion
This study reveals that in appropriately selected patients, NET can provide equivalent clinical benefit to neoadjuvant chemotherapy in the same cohort, if suitable treatments and durations are chosen. Our findings highlight the need for better defined biomarkers both for guiding patient selection and for measuring outcomes. Development of standard guidelines for the prescribing of NET has the potential to improve both clinical outcomes and quality of life in this patient cohort.
Use of olanzapine to treat agitation in traumatic brain injury: study protocol for a randomised controlled trial
Authors: Phyland Ruby K , McKay Adam , Olver John , Walterfang Mark , Hopwood Malcolm , Hicks Amelia J , Mortimer Duncan , Ponsford Jennie L 
Published: July 2020

AbstractBackgroundAgitation is common in the early stages of recovery from traumatic brain injury (TBI), when patients are in post-traumatic amnesia (PTA). Agitation is associated with risk of harm to patients and caregivers. Recent guidelines recommend that agitation during PTA is managed using environmental modifications. Agitation is also frequently treated pharmacologically, with the use of atypical antipsychotics such as olanzapine among the most common. This is despite a lack of well-designed studies to support the use of antipsychotics within this context. This study will be a double-blind, placebo-controlled randomised controlled trial. We will examine the efficacy, safety, cost-effectiveness and outcomes associated with the use of olanzapine for reducing agitation in patients in PTA following TBI over and above recommended environmental management.MethodsFifty-eight TBI rehabilitation inpatients who are in PTA and are agitated will receive olanzapine or placebo for the duration of PTA. All participants will additionally receive optimal environmental management for agitation. Measures of agitation, PTA and health will be undertaken at baseline. Treatment administration will begin at a dose of 5 mg daily and may be escalated to a maximum dose of 20 mg per day. Throughout the treatment period, agitation and PTA will be measured daily, and adverse events monitored weekly. Efficacy will be assessed by treatment group comparison of average Agitated Behaviour Scale scores during PTA. Participants will cease treatment upon emergence from PTA. Agitation levels will continue to be monitored for a further 2 weeks, post-treatment measures of health will be undertaken and cognitive and functional status will be assessed. Level of agitation and functional health will be assessed at hospital discharge. At 3 months post-discharge, functional outcomes and health service utilisation will be measured.DiscussionThis trial will provide crucial evidence to inform the management of agitation in patients in PTA following TBI. It will provide guidance as to whether olanzapine reduces agitation over and above recommended environmental management or conversely whether it increases or prolongs agitation and PTA, increases length of inpatient hospitalisation and impacts longer term cognitive and functional outcomes. It will also speak to the safety and cost-effectiveness of olanzapine use in this population.Trial registrationANZCTRACTRN12619000284167. Registered on 25 February 2019
Infection patterns of dengue, Zika and endosymbiont Wolbachia in the mosquito Aedes albopictus in Hong Kong
Authors: Huang Elaine Y. Y. , Wong Annette Y. P. , Lee Ivy H. T. , Qu Zhe , Yip Ho Yin , Leung Chi-wah , Yin Shuk-may , Hui Jerome H. L. 
Published: July 2020

AbstractBackgroundThe mosquitoAedes albopictusis a vector of dengue and Zika viruses. Insecticide-resistant mosquito populations have evolved in recent decades, suggesting that new control strategies are needed. Hong Kong has a monsoon-influenced humid subtropical climate, which favours the spread of mosquitoes. However, baseline information on the composition and dynamics of the occurrence of endosymbiontWolbachiain localAe. albopictusis lacking, hindering the development of scientifically-informed control measures. This study identifies the presence and absence of dengue and Zika viruses, andWolbachiainfection inAedes albopictusin Hong Kong.MethodsOviposition traps were set at 57 areas in Hong Kong, and both immature and adult mosquitoes were collected on a monthly basis between April 2018 and April 2019 as the study sample. Each individual mosquito in this sample was processed and screened for the presence of the dengue and Zika viruses and the endosymbiontsWolbachia wAlbA andwAlbB with PCR.ResultsTotals of 967 and 984 mosquitoes were tested respectively for the presence of dengue and Zika viruses, and no trace of either infection was found in these samples. The presence ofwAlbA andwAlbB was also tested in 1582 individuals. Over 80% of these individuals were found to be stably infected withWolbachiathroughout the thirteen-month collection period (~ 47% singly-infected; ~ 36.8% doubly infected with bothwAlbA andwAlbB).ConclusionsThe high degree ofWolbachia wAlbA andwAlbB infection inAe. albopictusmosquitoes in Hong Kong, coupled with the absence of any signs of infection by dengue and Zika viruses, contrasts significantly with the pattern of mosquito infection in other parts of Asia. Further studies of the infection pattern in local mosquitoes are warranted before mosquito control strategies used in other regions are implemented in Hong Kong.
Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo
Authors: Carvalho Leonardo J. M. , Tuvshintulga Bunduurem , Nugraha Arifin B. , Sivakumar Thillaiampalam , Yokoyama Naoaki 
Published: July 2020

Abstract
Background
Babesiosis represents a veterinary and medical threat, with a need for novel drugs. Artemisinin-based combination therapies (ACT) have been successfully implemented for malaria, a human disease caused by related parasites, Plasmodium spp. The aim of this study was to investigate whether ACT is active against Babesia in vitro and in vivo.

Methods
Mefloquine, tafenoquine, primaquine, methylene blue and lumefantrine, alone or in combination with artesunate, were tested in vitro against Babesia bovis. Parasite growth was verified using a SYBR green I-based fluorescence assay. Mice infected with Babesia microti were treated with mefloquine or tafenoquine, alone or in combination with artesunate, and parasitemia was verified by microscopy and PCR.

Results
All drugs, except lumefantrine, showed in vitro activity against B. bovis, with methylene blue showing the most potent activity (concentration 0.2 μM). Combination with artesunate led to improved activity, with mefloquine showing a striking 20-fold increase in activity. Tafenoquine (10 mg/kg, base), combined or not with artesunate, but not mefloquine, induced rapid clearance of B. microti in vivo by microscopy, but mice remained PCR-positive. Blood from mice treated with tafenoquine alone, but not with tafenoquine-artesunate, was infective for naive mice upon sub-inoculation.

Conclusions
Tafenoquine, and most likely other 8-aminoquinoline compounds, are promising compounds for the development of ACT for babesiosis.
Evaluation and utility of mitochondrial ribosomal genes for molecular systematics of parasitic nematodes
Authors: Chan Abigail Hui En , Chaisiri Kittipong , Morand Serge , Saralamba Naowarat , Thaenkham Urusa 
Published: July 2020

AbstractBackgroundMolecular advances have accelerated our understanding of nematode systematics and taxonomy. However, comparative analyzes between various genetic markers have led to discrepancies in nematode phylogenies. This study aimed to evaluate the suitability of using mitochondrial12Sand16Sribosomal RNA genes for nematode molecular systematics.MethodsTo study the suitability of mitochondrial12Sand16Sribosomal RNA genes as genetic markers for nematode molecular systematics, we compared them with the other commonly used genetic markers, nuclear internal transcribed spacer 1 and 2 regions, nuclear18Sand28Sribosomal RNA genes, and mitochondrial cytochromecoxidase subunit 1 gene. After that, phylum-wide primers for mitochondrial12Sand16Sribosomal RNA genes were designed, and parasitic nematodes of humans and animals from 75 taxa with 21 representative species were inferred through phylogenetic analyzes. Phylogenetic analyzes were carried out using maximum likelihood and Bayesian inference algorithms.ResultsThe phylogenetic relationships of nematodes based on the mitochondrial12SrRNA gene supported the monophyly of nematodes in clades I, IV, and V, reinforcing the potential of this gene as a genetic marker for nematode systematics. In contrast, the mitochondrial16SrRNA gene only supported the monophyly of clades I and V, providing evidence that the12SrRNA gene is more suitable for nematode molecular systematics. In this study, subclades of clade III containing various nematode families were not monophyletic when the16Sor12SrRNA gene was used as the genetic marker. This is similar to the phylogenetic relationship revealed by previous studies using whole mitochondrial genomes as genetic markers.ConclusionsThis study supports the use of the12SrRNA gene as a genetic marker for studying the molecular systematics of nematodes to understand intra-phyla relationships. Phylum-wide primers for nematodes using mitochondrial ribosomal genes were prepared, which may enhance future studies. Furthermore, sufficient genetic variation in the mitochondrial12Sand16SrRNA genes between species also allowed for accurate taxonomy to species level, revealing the potential of these two genes as genetic markers for DNA barcoding.
Cytokine-induced molecular responses in airway smooth muscle cells inform genome-wide association studies of asthma
Authors: Thompson Emma E. , Dang Quynh , Mitchell-Handley Blair , Rajendran Kavitha , Ram-Mohan Sumati , Solway Julian , Ober Carole , Krishnan Ramaswamy 
Published: July 2020

AbstractBackgroundA challenge in the post-GWAS era is to assign function to disease-associated variants. However, available resources do not include all tissues or environmental exposures that are relevant to all diseases. For example, exaggerated bronchoconstriction of airway smooth muscle cells (ASMCs) defines airway hyperresponsiveness (AHR), a cardinal feature of asthma. However, the contribution of ASMC to genetic and genomic studies has largely been overlooked. Our study aimed to address the gap in data availability from a critical tissue in genomic studies of asthma.MethodsWe developed a cell model of AHR to discover variants associated with transcriptional, epigenetic, and cellular responses to two AHR promoting cytokines, IL-13 and IL-17A, and performed a GWAS of bronchial responsiveness (BRI) in humans.ResultsOur study revealed significant response differences between ASMCs from asthma cases and controls, including genes implicated in asthma susceptibility. We defined molecular quantitative trait loci (QTLs) for expression (eQTLs) and methylation (meQTLs), and cellular QTLs for contractility (coQTLs) and performed a GWAS of BRI in human subjects. Variants in asthma GWAS were significantly enriched for ASM QTLs and BRI-associated SNPs, and near genes enriched for ASM function, many with smallPvalues that did not reach stringent thresholds of significance in GWAS.ConclusionsOur study identified significant differences between ASMCs from asthma cases and controls, potentially reflecting trained tolerance in these cells, as well as a set of variants, overlooked in previous GWAS, which reflect the AHR component of asthma.
Multiple brain abscesses with good prognosis in an infant with cyanotic congenital heart disease: a case report
Authors: Kudo-Kubo Atsuko , Shimakawa Shuichi , Odanaka Yutaka , Ikeda Naokado , Kitahara Hikaru , Toshikawa Hiromitsu , Ashida Atsuko , Fukui Miho , Ozaki Noriyasu , Kishi Kanta , Wanibuchi Masahiko , Ashida Akira 
Published: July 2020

Abstract
Background
Brain abscesses are relatively rare, but they are a potentially life-threatening condition. Predictive factors for poor outcome are a young age and the presence of multiple abscesses. We report a case of a 15-month-old girl with cyanotic congenital heart disease who developed multiple brain abscesses caused by Streptococcus intermedius. The patient was treated with a combination of surgical aspiration and antimicrobial therapy without apparent neurological sequelae. To the best of our knowledge, this is the youngest such patient to have been reported in the literature. We explore the possible causes of her good outcome.

Case presentation
At the age of 15 months, the Japanese patient initially was presented to our hospital with transient eye deviation to the left and vomiting. In a blood examination, her white blood cell count (12,720 per mm3 with a left shift) and C-reactive protein level (1.23 mg/ml) were slightly elevated. Magnetic resonance imaging of the brain showed three mass lesions. These were 1.5-cm, 1.9-cm, and 1.2-cm rim-enhancing lesions with extensive surrounding edema. Brain abscesses were diagnosed, and vancomycin (50 mg every 12 hours) and meropenem (40 mg every 8 hours) were started empirically. However, because each brain abscess was enlarged at 8 days after admission, surgical aspiration was performed at 10 days after admission, and cultures of the aspirated pus grew S. intermedius. Penicillin G (0.7 million units every 4 hours) and ceftriaxone (280 mg every 12 hours), to which this isolate is susceptible, were then administered, and the brain abscesses reduced in size. After 1 month of ceftriaxone and 3 months of penicillin G treatment, all of the brain abscesses disappeared. Apparent neurological sequelae were not observed at 6 months after onset.

Conclusions
A good outcome can be obtained if multiple brain abscesses develop in infancy or early childhood in cases without unconsciousness at admission, meningitis, or sepsis. Appropriate antimicrobial therapy should be started immediately after diagnosis, with surgical aspiration performed to identify the causative pathogen and avoid intraventricular rupture of the brain abscesses.
An interaction between fetal sex and placental weight and efficiency predicts intrauterine growth in response to maternal protein insufficiency and gestational exposure window in a mouse model of FASD
Authors: Kwan Sze Ting Cecilia , Presswood Brandon H. , Helfrich Kaylee K. , Baulch Joshua W. , Mooney Sandra M. , Smith Susan M. 
Published: July 2020

AbstractBackgroundIndividuals exposed to gestational stressors such as alcohol exhibit a spectrum of growth patterns, suggesting individualized responses to the stressors. We hypothesized that intrauterine growth responses to gestational alcohol are modified not only by the stressor’s severity but by fetal sex and the placenta’s adaptive capacity.MethodsPregnant C57BL/6J mice were assigned to one of three groups. Group 1 consumed a normal protein diet (18% protein by weight) and received 4.5 g alcohol/kg body weight (NP-Alc-8) or isocaloric maltodextrin (NP-MD-8) daily from embryonic day (E) 8.5–E17.5. Group 2 consumed the same diet but received alcohol (NP-Alc-13) or maltodextrin (NP-MD-13) daily from E13.5–E17.5. Group 3 consumed the same diet but containing a lower protein content (12% protein by weight) from E0.5 and also received alcohol (LP-Alc-8) or maltodextrin (LP-MD-8) daily from E8.5–E17.5. Maternal, placental, and fetal outcomes were assessed on E17.5 using 2-way ANOVA or mixed linear model.ResultsWe found that intrauterine growth differed in the alcohol-exposed fetuses depending on sex and insult severity. Both NP-Alc-8 (vs. NP-MD-8) males and females had lower body weight and asymmetrical growth, but only NP-Alc-8 females had lower placental weight (P< 0.05). NP-Alc-13 (vs. NP-MD-13) females, but not their male littermates, had lower body weight (P= 0.019). Alcohol exposure beginning from E8.5 (vs. E13.5) decreased the ratio of fetal liver-to-body weight and increased the ratio of fetal brain-to-liver weight in both sexes (P< 0.05). LP-Alc-8 (vs. NP-MD-8) group had smaller litter size (P= 0.048), but the survivors had normal placental and body weight at E17.5. Nevertheless, LP-Alc-8 fetuses still showed asymmetrical growth. Correlation analyses reveal a relationship between litter size and placental outcomes, which were related to fetal outcomes in a sex-dependent manner, suggesting that the placenta may mediate the consequence of LP-Alc-altered litter size on fetal development.ConclusionsOur data indicate that the placenta is strongly involved in the fetal stress response and adapts in a sex-dependent fashion to support fetal development under the alcohol stressor. These variables may further influence the spectrum of intrauterine growth outcomes observed in those diagnosed with fetal alcohol spectrum disorder.
Environmental and landscape influences on the spatial and temporal distribution of a cattle herd in a South Texas rangeland
Authors: Cheleuitte-Nieves Christopher , Perotto-Baldivieso Humberto L. , Wu X. Ben , Cooper Susan M. 
Published: July 2020

AbstractThe multiple spatial and temporal parameters affecting cattle herd distribution and activity dynamics can significantly affect resource utilization but are not fully understood. The aim of this study was to determine whether current animal tracking technology and spatio-temporal analysis tools can be used to integrate multi-scale information on herd distribution patterns as a function of seasonal forage production, periods of the day, animal activity, and landscape features. Positional and activity information of 11 free-ranging cows within a 31-member herd was obtained at 5-min intervals by using GPS collars for 1 year within a 457-ha ranch in the semi-arid rangelands of South Texas. Forage biomass was calculated with satellite imagery. Spatial analysis of cattle distribution and landscape features was conducted with GIS.Herd spread was greatest during the growing season. Throughout the year, during midday, the herd showed smaller spread and greater use of shade patches than any other time of day. Cattle also aggregated under trees in winter, particularly during the night. There was no statistically significant overall pattern of seasonal changes in the use of water and supplemental feeding areas, but a trend toward highest use during the winter. However, significantly different diurnal patterns in the use of supplemental feed and water were observed within each season.This study found a strong influence of shade patches relative to the influence of water and supplemental feeding areas on the diurnal and seasonal movement patterns of cattle in shrub-dominated rangeland. Although this study used only 11 tracked cows in a 31-member herd, the results indicated that techniques such as seasonal and diurnal GPS tracking, GIS, and remote sensing data enable evaluation of multiple spatial and temporal dynamics of cattle distribution and activity patterns. The smaller spread during the dry winter season associated with the observed aggregation of individuals in water and supplemental feeding areas, may aid in determining the most critical times for providing supplemental resources and guide the allocation of those resources to areas not frequently used by cattle, thus stimulating the animals to visit unused sites during the non-growing season.
Relative contributions of large-scale and wedgelet currents in the substorm current wedge
Authors: Nishimura Y. , Lyons L. R. , Gabrielse C. , Weygand J. M. , Donovan E. F. , Angelopoulos V. 
Published: July 2020

AbstractWe examined how much large-scale and localized upward and downward currents contribute to the substorm current wedge (SCW), and how they evolve over time, using the THEMIS all-sky imagers (ASIs) and ground magnetometers. One type of events is dominated by a single large-scale wedge, with upward currents over the surge and broad downward currents poleward-eastward of the surge. The other type of events is a composite of large-scale wedge and wedgelets associated with streamers, with each wedgelet having comparable intensity to the large-scale wedge currents. Among 17 auroral substorms with wide ASI coverage, the composite current type is more frequent than the single large-scale wedge type. The dawn–dusk size of each wedgelet is ~ 600 km in the ionosphere (~ 3.2 RE in the magnetotail, comparable to the flow channel size). We suggest that substorms have more than one type of SCW, and the composite current type is more frequent.
Solving the k-dominating set problem on very large-scale networks
Authors: Nguyen Minh Hai , Hà Minh Hoàng , Nguyen Diep N. , Tran The Trung 
Published: July 2020

AbstractThe well-known minimum dominating set problem (MDSP) aims to construct the minimum-size subset of vertices in a graph such that every other vertex has at least one neighbor in the subset. In this article, we study a general version of the problem that extends the neighborhood relationship: two vertices are called neighbors of each other if there exists a path through no more thankedges between them. The problem called “minimumk-dominating set problem” (MkDSP) becomes the classical dominating set problem ifkis 1 and has important applications in monitoring large-scale social networks. We propose an efficient heuristic algorithm that can handle real-world instances with up to 17 million vertices and 33 million edges. This is the first time such large graphs are solved for the minimumk-dominating set problem.