bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergence and Spread of
kelch13
Mutations Associated with Artemisinin Resistance in Plasmodium falciparum Parasites in 12 Thai Provinces from 2007 to 2016
Authors: Kobasa Theerayot , Talundzic Eldin , Sug-aram Rungniran , Boondat Patcharida , Goldman Ira F. , Lucchi Naomi W. , Dharmarak Pratin , Sintasath David , Fukuda Mark , Whistler Toni , MacArthur John , Udhayakumar Venkatachalam , Prempree Preecha , Chinanonwait Nipon 
Published: January 2018

ABSTRACT

Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated
Plasmodium falciparum
malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS) and manifests as slow parasite clearance in patients and reduced ring stage susceptibility to artemisinins in survival assays. The
P. falciparum
kelch13
gene mutations associated with artemisinin-resistant parasites are now widespread in the GMS. We genotyped 277 samples collected during an observational study from 2012 to 2016 from eight provinces in Thailand to identify
P. falciparum kelch13
mutations. The results were combined with previously reported genotyping results from Thailand to construct a map illustrating the evolution of
P. falciparum kelch13
mutations from 2007 to 2016 in that country. Different mutant alleles were found in strains with different geographical origins. The artemisinin resistance-conferring Y493H and R539T mutations were detected mainly in eastern Thailand (bordering Cambodia), while P574L was found only in western Thailand and R561H only in northwestern Thailand. The C580Y mutation was found across the entire country and was nearing fixation along the Thai-Cambodia border. Overall, the prevalence of artemisinin resistance mutations increased over the last 10 years across Thailand, especially along the Thai-Cambodia border. Molecular surveillance and therapeutic efficacy monitoring should be intensified in the region to further assess the extent and spread of artemisinin resistance.
Complete Genome Sequences of the Plant Pathogens
Dickeya solani
RNS 08.23.3.1.A and
Dickeya dianthicola
RNS04.9
Authors: Khayi Slimane , Blin Pauline , Chong Teik Min , Robic Kévin , Chan Kok-Gan , Faure Denis 
Published: January 2018

ABSTRACT

Dickeya
spp. are bacterial pathogens causing soft-rot and blackleg diseases on a wide range of ornamental plants and crops. In this paper, we announce the PacBio complete genome sequences of the plant pathogens
Dickeya solani
RNS 08.23.3.1.A (PRI3337) and
Dickeya dianthicola
RNS04.9.
Timing and mechanism of the rise of the Shillong Plateau in the Himalayan foreland
Authors: Govin G. , Najman Y. , Copley A. , Millar I. , van der Beek P. , Huyghe P. , Grujic D. , Davenport J. 
Published: January 2018

Abstract
The Shillong Plateau (northeastern India) constitutes the only significant topography in the Himalayan foreland. Knowledge of its surface uplift history is key to understanding topographic development and unraveling tectonic–climate–topographic coupling in the eastern Himalaya. We use the sedimentary record of the Himalayan foreland basin north of the Shillong Plateau to show that the paleo-Brahmaputra river was redirected north and west by the rising plateau at 5.2–4.9 Ma. We suggest that onset of plateau uplift is a result of increased fault-slip rates in response to stresses caused by the Indian lithosphere bending beneath the Himalaya.
Primary goals, information-giving and men’s understanding: a qualitative study of Australian and UK doctors’ varied communication about PSA screening
Authors: Pickles Kristen , Carter Stacy M , Rychetnik Lucie , McCaffery Kirsten , Entwistle Vikki A 
Published: January 2018

Objectives(1) To characterise variation in general practitioners’ (GPs’) accounts of communicating with men about prostate cancer screening using the prostate-specific antigen (PSA) test, (2) to characterise GPs’ reasons for communicating as they do and (3) to explain why and under what conditions GP communication approaches vary.Study design and settingA grounded theory study. We interviewed 69 GPs consulting in primary care practices in Australia (n=40) and the UK (n=29).ResultsGPs explained their communication practices in relation to their primary goals. In Australia, three different communication goals were reported: to encourage asymptomatic men to either have a PSA test, or not test, or alternatively, to support men to make their own decision. As well as having different primary goals, GPs aimed to provide different information (from comprehensive to strongly filtered) and to support men to develop different kinds of understanding, from population-level to ‘gist’ understanding. Taking into account these three dimensions (goals, information, understanding) and building on Entwistleet al’s Consider an Offer framework, we derived four overarching approaches to communication:Be screened,Do not be screened,Analyse and choose, andAs you wish. We also describe ways in which situational and relational factors influenced GPs’ preferred communication approach.ConclusionGPs’ reported approach to communicating about prostate cancer screening varies according to three dimensions—their primary goal, information provision preference and understanding sought—and in response to specific practice situations. If GP communication about PSA screening is to become more standardised in Australia, it is likely that each of these dimensions will require attention in policy and practice support interventions.
Timing of probiotic milk consumption during pregnancy and effects on the incidence of preeclampsia and preterm delivery: a prospective observational cohort study in Norway
Authors: Nordqvist Mahsa , Jacobsson Bo , Brantsæter Anne-Lise , Myhre Ronny , Nilsson Staffan , Sengpiel Verena 
Published: January 2018

ObjectivesTo investigate whether the timing of probiotic milk intake before, during early or late pregnancy influences associations with preeclampsia and preterm delivery.DesignPopulation based prospective cohort study.SettingNorway, between 1999 and 2008.Participants70 149 singleton pregnancies resulting in live-born babies from the Norwegian Mother and Child Cohort Study (no chronic disease, answered questionnaires, no placenta previa/cerclage/serious malformation of fetus, first enrolment pregnancy). Only nulliparous women (n=37 050) were included in the preeclampsia analysis. Both iatrogenic and spontaneous preterm delivery (between gestational weeks 22+0 and 36+6) with spontaneous term controls (between gestational weeks 39+0 and 40+6) were included in the preterm delivery analysis resulting in 34 458 cases.Main outcome measuresAdjusted OR for preeclampsia and preterm delivery according to consumption of probiotic milk at three different time periods (before pregnancy, during early and late pregnancy).ResultsProbiotic milk intake in late pregnancy (but not before or in early pregnancy) was significantly associated with lower preeclampsia risk (adjusted OR: 0.80 (95% CI 0.68 to 0.94) p-value: 0.007). Probiotic intake during early (but not before or during late pregnancy) was significantly associated with lower risk of preterm delivery (adjusted OR: 0.79 (0.64 to 0.97) p-value: 0.03).ConclusionsIn this observational study, we found an association between timing of probiotic milk consumption during pregnancy and the incidence of the adverse pregnancy outcomes preeclampsia and preterm delivery. If future randomised controlled trials could establish a causal association between probiotics consumption and reduced risk of preeclampsia and preterm delivery, recommending probiotics would be a promising public health measure to reduce these adverse pregnancy outcomes.
Patient-centred attitudes among medical students in Mali, West Africa: a cross-sectional study
Authors: Hurley Emily A , Doumbia Seydou , Kennedy Caitlin E , Winch Peter J , Roter Debra L , Murray Sarah M , Harvey Steven A 
Published: January 2018

Background/objectivePatient-centred attitudes have been shown to decline during medical training in high-income countries, yet little is known about attitudes among West African medical students. We sought to measure student attitudes towards patient-centredness and examine validity of the 18-item Patient–Practitioner Orientation Scale (PPOS) in this context.Participants/setting430 medical students in years 1, 3, 5 and 6 of a 6-year medical training programme in Bamako, Mali.DesignWe conducted a cross-sectional survey, compared the proportion of students who agreed with each PPOS item by gender and academic year, and calculated composite PPOS scores. To examine psychometrics of the PPOS and its two subscales (‘sharing’ and ‘caring’), we calculated internal consistency (Cronbach’s alpha) and performed confirmatory and exploratory factor analyses (CFA and EFA).ResultsIn seven of the nine ‘sharing’ items, the majority of students held attitudes favouring a provider-dominant style. For five of the nine ‘caring’ items, the majority of student responded consistently with patient-centred attitudes, while in the other four, responses indicated a disease-centred orientation. In eight items, a greater proportion of fifth/sixth year students held patient-centred attitudes as compared with first year students; there were few gender differences. Average PPOS scores indicated students were moderately patient-centred, with more favourable attitudes towards the ‘caring’ aspect than ‘sharing’. Internal consistency of the PPOS was inadequate for the full scale (α=0.58) and subscales (‘sharing’ α=0.37; ‘caring’ α=0.48). CFA did not support the original PPOS factors and EFA did not identify an improved structure.ConclusionsWest African medical students training in Bamako are moderately patient-centred and do not show the same declines in patient-centred attitudes in higher academic years as seen in other settings. Medical students may benefit from training in shared power skills and in attending to patient lifestyle factors. Locally validated tools are needed to guide West African medical schools in fostering patient-centredness among students.
Interdisciplinary collaboration across secondary and primary care to improve medication safety in the elderly (IMMENSE study): study protocol for a randomised controlled trial
Authors: Johansen Jeanette Schultz , Havnes Kjerstin , Halvorsen Kjell H. , Haustreis Stine , Skaue Lillann Wilsgård , Kamycheva Elena , Mathiesen Liv , Viktil Kirsten K. , Granås Anne Gerd , Garcia Beate H. 
Published: January 2018

IntroductionDrug-related problems (DRPs) are common in the elderly, leading to suboptimal therapy, hospitalisations and increased mortality. The integrated medicines management (IMM) model is a multifactorial interdisciplinary methodology aiming to optimise individual medication therapy throughout the hospital stay. IMM has been shown to reduce readmissions and drug-related hospital readmissions. Using the IMM model as a template, we have designed an intervention aiming both to improve medication safety in hospitals, and communication across the secondary and primary care interface. This paper presents the study protocol to explore the effects of the intervention with regard to healthcare use, health-related quality of life (HRQoL) and medication appropriateness in elderly patients.Methods and analysisA total of 500 patients aged ≥70 years will be included and randomised to control (standard care) or intervention group (1:1). The intervention comprises five steps mainly performed by pharmacists: (1) medication reconciliation at admission, (2) medication review during hospital stay, (3) patient counselling about the use of medicines, (4) a comprehensible and patient-friendly medication list with explanations in discharge summary and (5) postdischarge phone calls to the primary care level. The primary outcome is the difference between intervention and control patients in the rate of emergency medical visits (acute readmissions and visits to emergency department) 12 months after discharge. Secondary outcomes include length of index hospital stay, time to first readmission, mortality, hip fractures, strokes, medication changes, HRQoL and medication appropriateness. Patient inclusion started in September 2016.Ethics and disseminationThe trial was approved by the Norwegian Centre for Research Data and the Norwegian Data Protection Authority. We aim to publish the results in international peer-reviewed open access journals, at national and international conferences, and as part of two PhD theses.Trial registration numberNCT02816086.
Association between parent mental health and paediatric TBI: epidemiological observations from the 1987 Finnish Birth Cohort
Authors: Lowery Wilson Michael , Tenovuo Olli , Gissler Mika , Saarijärvi Simo 
Published: January 2018

BackgroundThis study examined whether parental mental illness has implications for child risk for traumatic brain injuries (TBI).MethodData on 60 069 Finnish children born in 1987 and their parents were examined for demographic and mental health-related variables in relationship with paediatric TBI. Altogether, 15 variables were derived from the cohort data with ICD-10 F-codes being available for mental health diagnoses for all parents. Bivariate and multivariate analyses were carried out using inpatient and outpatient diagnoses of child TBI.ResultsPaternal disorders due to psychoactive substance use (F10–F19) was associated with an increased inpatient TBI (OR=1.51; CI=1.07 to 2.14). Mood disorders (F30–F39) were associated with higher rates of outpatient TBI (OR=1.42; CI=1.06 to 1.90). Paternal personality and behavioural disorders (F60–F69) were linked with a twofold increase in risk across both categories of child TBI (OR=2.35; CI=1.41 to 3.90) and (OR=2.29; CI=1.45 to 3.61), respectively. Among the maternal mental health factors associated with child TBI, schizophrenia and other non-mood psychotic disorders (F20–F29) were associated with an increase in inpatient traumatic brain injuries (iTBI) (OR=1.78; 1.22 to 2.59). Mothers having mood disorders (F30–F39) were more likely to have had a child who experienced an iTBI (OR=1.64; CI=1.20 to 2.22). Mothers with personality and behavioural disorders (F60–F69) were also found to have had children with an increased risk for iTBI (OR=2.30; CI=1.14 to 3.65).ConclusionTaken together, these data should call attention to methods and strategies designed to augment and support caregiving environments with modalities that can foster mutually supportive households in cooperation with parents who have been diagnosed with a mental disorder.
Mycobacterial spindle cell pseudotumour: epidemiology and clinical outcomes
Authors: Sfeir Maroun M , Schuetz Audrey , Van Besien Koen , Borczuk Alain C , Soave Rosemary , Jenkins Stephen G , Walsh Thomas J , Small Catherine B 
Published: January 2018

IntroductionMycobacterial spindle cell pseudotumour (MSP) is a rare disease characterised by tumour-like local proliferation of spindle-shaped histiocytes containing acid-fast positive mycobacteria. The aim of this literature review is to describe the clinical parameters and treatment outcomes of patients with MSP.MethodsA literature search was conducted using the search terms related to mycobacteria and spindle cell tumours. A previously unreported stem cell transplant recipient from our institution diagnosed with MSP was also included. Demographics, comorbidities, site of infection, treatment and clinical outcomes were analysed.ResultsFifty-one patients were analysed. Twenty-six (51%) had HIV infection.Mycobacterium aviumcomplex was the most frequent organism isolated in 24 (47.1%) followed byMycobacterium tuberculosiscomplex in eight (16%) cases. Lymph nodes were the most common site of infection (45.1%). Twenty (39.2%) patients received antimycobacterial agents, 12 (23.5%) underwent surgical resection and six (11.8%) received antimycobacterial agents plus surgery. Treatment was successful in 24 (47.1%) patients and failed in 15 (29.4%); 13 of these 15 patients died. Antimycobacterial therapy was significantly associated with successful outcome compared with surgical resection or no treatment (P<0.001).ConclusionMSP is a rare condition associated primarily with immunodeficiencies. Antimycobacterial therapy is significantly associated withsuccessfuloutcome.
Biomarker assessment of tobacco smoking exposure and risk of dementia death: pooling of individual participant data from 14 cohort studies
Authors: Batty G David , Shipley Martin J , Kvaavik Elisabeth , Russ Tom , Hamer Mark , Stamatakis Emmanouil , Kivimaki Mika 
Published: January 2018

BackgroundWhile there is a suggestion that self-reported tobacco smoking may be a risk factor for dementia, to date, it has not been possible to explore the thresholds at which this exposure elevates risk. Accordingly, our aim was to relate cotinine, a biomarker of tobacco smoking, to risk of dementia death.MethodsWe pooled 14 prospective cohort studies that held data on cotinine (plasma or saliva), covariates and death records.ResultsIn the 33 032 study members (17 107 women) with salivary cotinine data, a mean duration of 8.3 years of follow-up gave rise to 135 deaths ascribed to dementia; while in 15 130 study members (7995 women) with plasma cotinine data, there were 119 dementia deaths during 14.3 years of mortality surveillance. After multiple adjustment, both plasma cotinine (per 1 SD higher cotinine; 95% CI 1.29; (1.05 to 1.59)) and salivary cotinine (1.10 (0.89 to 1.36)) were positively related to dementia risk, with stronger effects apparent for plasma.ConclusionOur finding that plasma cotinine was related to an elevated risk of dementia death warrants testing in studies with measures of disease onset as opposed to just mortality.
Flt-3L Expansion of Recipient CD8α+ Dendritic Cells Deletes Alloreactive Donor T Cells and Represents an Alternative to Posttransplant Cyclophosphamide for the Prevention of GVHD
Authors: Markey Kate A. , Kuns Rachel D. , Browne Daniel J. , Gartlan Kate H. , Robb Renee J. , Martins J. Paulo , Henden Andrea S. , Minnie Simone A. , Cheong Melody , Koyama Motoko , Smyth Mark J. , Steptoe Raymond J. , Belz Gabrielle T. , Brocker Thomas , Degli-Esposti Mariapia A. , Lane Steven W. , Hill Geoffrey R. 
Published: January 2018

Abstract
Purpose: Allogeneic bone marrow transplantation (BMT) provides curative therapy for leukemia via immunologic graft-versus-leukemia (GVL) effects. In practice, this must be balanced against life threatening pathology induced by graft-versus-host disease (GVHD). Recipient dendritic cells (DC) are thought to be important in the induction of GVL and GVHD.
Experimental Design: We have utilized preclinical models of allogeneic BMT to dissect the role and modulation of recipient DCs in controlling donor T-cell–mediated GVHD and GVL.
Results: We demonstrate that recipient CD8α+ DCs promote activation-induced clonal deletion of allospecific donor T cells after BMT. We compared pretransplant fms-like tyrosine kinase-3 ligand (Flt-3L) treatment to the current clinical strategy of posttransplant cyclophosphamide (PT-Cy) therapy. Our results demonstrate superior protection from GVHD with the immunomodulatory Flt-3L approach, and similar attenuation of GVL responses with both strategies. Strikingly, Flt-3L treatment permitted maintenance of the donor polyclonal T-cell pool, where PT-Cy did not.
Conclusions: These data highlight pre-transplant Flt-3L therapy as a potent new therapeutic strategy to delete alloreactive T cells and prevent GVHD, which appears particularly well suited to haploidentical BMT where the control of infection and the prevention of GVHD are paramount. Clin Cancer Res; 24(7); 1604–16. ©2018 AACR.
Krüppel-like Factor 4 Suppresses Serine/Threonine Kinase 33 Activation and Metastasis of Gastric Cancer through Reversing Epithelial–Mesenchymal Transition
Authors: Kong Fanyang , Sun Tao , Kong Xiangyu , Xie Dacheng , Li Zhaoshen , Xie Keping 
Published: January 2018

Abstract
Background: Cancers with aberrant expression of Serine/threonine kinase 33 (STK33) has been reported to be particularly aggressive. However, its expression, clinical significance, and biological functions in gastric cancer remain largely unknown. In the present study, we determined the expression and function of STK33 in gastric cancer and delineated the clinical significance of the Krüppel-like factor 4 (KLF4)/STK33 signaling pathway.
Methods: STK33 expression and its association with multiple clinicopathologic characteristics were analyzed immunohistochemically in human gastric cancer specimens. STK33 knockdown and overexpression were used to dissect the underlying mechanism of its functions in gastric cancer cells. Regulation and underlying mechanisms of STK33 expression by KLF4 in gastric cancer cells were studied using cell and molecular biological methods.
Results: Drastically higher expression of STK33 was observed in gastric cancer and gastric intraepithelial neoplasia tissues compared with adjacent normal gastric tissues. Increased STK33 expression correlated directly with tumor size, lymph node, and distant metastasis; and patients with low STK33 expression gastric cancer were predicted to have a favorable prognosis. Enforced expression of STK33 promoted gastric cancer cell proliferation, migration, and invasion in vitro and in vivo, whereas reduced STK33 did the opposite. Moreover, STK33 promoted epithelial–mesenchymal transition (EMT) in vitro. Mechanistically, KLF4 transcriptionally inhibited STK33 expression in gastric cancer cells. KLF4-mediated inhibition of gastric cancer cell invasion was reversed by upregulation of STK33 expression.
Conclusions: STK33 has pro-tumor function and is a critical downstream mediator of KLF4 in gastric cancer. STK33 may serve as a potential prognostic marker and therapeutic target for gastric cancer. Clin Cancer Res; 24(10); 2440–51. ©2018 AACR.
Integration of Oncogenes via Sleeping Beauty as a Mouse Model of HPV16+ Oral Tumors and Immunologic Control
Authors: Lin Yi-Hsin , Yang Ming-Chieh , Tseng Ssu-Hsueh , Jiang Rosie , Yang Andrew , Farmer Emily , Peng Shiwen , Henkle Talia , Chang Yung-Nien , Hung Chien-Fu , Wu T.-C. 
Published: January 2018

Abstract
Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines are available, no effective therapeutic strategies to control active HPV diseases exist. Tumor implantation models are traditionally used to study HPV-associated buccal tumors. However, they fail to address precancerous phases of disease progression and display tumor microenvironments distinct from those observed in patients. Previously, K14-E6/E7 transgenic mouse models have been used to generate spontaneous tumors. However, the rate of tumor formation is inconsistent, and the host often develops immune tolerance to the viral oncoproteins. We developed a preclinical, spontaneous, HPV16+ buccal tumor model using submucosal injection of oncogenic plasmids expressing HPV16-E6/E7, NRasG12V, luciferase, and sleeping beauty (SB) transposase, followed by electroporation in the buccal mucosa. We evaluated responses to immunization with a pNGVL4a-CRT/E7(detox) therapeutic HPV DNA vaccine and tumor cell migration to distant locations. Mice transfected with plasmids encoding HPV16-E6/E7, NRasG12V, luciferase, and SB transposase developed tumors within 3 weeks. We also found transient anti-CD3 administration is required to generate tumors in immunocompetent mice. Bioluminescence signals from luciferase correlated strongly with tumor growth, and tumors expressed HPV16-associated markers. We showed that pNGVL4a-CRT/E7(detox) administration resulted in antitumor immunity in tumor-bearing mice. Lastly, we demonstrated that the generated tumor could migrate to tumor-draining lymph nodes. Our model provides an efficient method to induce spontaneous HPV+ tumor formation, which can be used to identify effective therapeutic interventions, analyze tumor migration, and conduct tumor biology research. Cancer Immunol Res; 6(3); 305–19. ©2018 AACR.