bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the Key Sequence in the FliK C-Terminal Domain for Substrate Specificity Switching in the Flagellar Protein Secretion
Authors: Uchida Kaoru , Dono Kohei , Aizawa Shin-Ichi 
Published: November 2015

ABSTRACT

The flagellar hook is a short tubular structure located between the external filament and the membrane-bound basal body. The average hook length is 55 nm and is determined by the soluble protein FliK and the integral membrane protein FlhB. Hook elongation is terminated by FliK-mediated cessation of hook protein secretion, followed by the secretion of filamentous proteins. This process is referred to as the substrate specificity switch. Switching of the secretion modes results from a direct interaction between the FliK C-terminal domain (FliK
C
) and the secretion gate in FlhB. FliK
C
consists of two α-helices and four β-strands. Loop 2 connects the first two β-sheets and contains a conserved sequence of 9 residues. Genetic and physiological analyses of various
fliK
partial deletion mutants pointed to loop 2 as essential for induction of a conformational change in the FlhB gate. We constructed single-amino-acid substitutions in the conserved region of loop 2 of FliK and discovered that the loop sequence LRL is essential for the timely switching of secretion modes.

IMPORTANCE
Flagellar protein secretion is controlled by the soluble protein FliK. We discovered that the loop 2 sequence LRL in the FliK C terminus was essential for timely switching of secretion modes. This mechanism is applicable to type three secretions systems that secrete virulence factors in bacterial pathogens.
Mutation of the Thiol-Disulfide Oxidoreductase SdbA Activates the CiaRH Two-Component System, Leading to Bacteriocin Expression Shutdown in Streptococcus gordonii
Authors: Davey Lauren , Halperin Scott A. , Lee Song F. 
Published: November 2015

ABSTRACT

Streptococcus gordonii
is a commensal inhabitant of the human oral cavity. To maintain its presence as a major component of oral biofilms,
S. gordonii
secretes inhibitory molecules such as hydrogen peroxide and bacteriocins to inhibit competitors.
S. gordonii
produces two nonmodified bacteriocins (i.e., Sth
1
and Sth
2
) that are regulated by the Com two-component regulatory system, which also regulates genetic competence. Previously we found that the thiol-disulfide oxidoreductase SdbA was required for bacteriocin activity; however, the role of SdbA in Com signaling was not clear. Here we demonstrate that Δ
sdbA
mutants lacked bacteriocin activity because the bacteriocin gene
sthA
was strongly repressed and the peptides were not secreted. Addition of synthetic competence-stimulating peptide to the medium reversed the phenotype, indicating that the Com pathway was functional but was not activated in the Δ
sdbA
mutant. Repression of bacteriocin production was mediated by the CiaRH two-component system, which was strongly upregulated in the Δ
sdbA
mutant, and inactivation of CiaRH restored bacteriocin production. The CiaRH-induced protease DegP was also upregulated in the Δ
sdbA
mutant, although it was not required for inhibition of bacteriocin production. This establishes CiaRH as a regulator of Sth bacteriocin activity and links the CiaRH and Com systems in
S. gordonii
. It also suggests that either SdbA or one of its substrates is an important factor in regulating activation of the CiaRH system.

IMPORTANCE
Streptococcus gordonii
is a noncariogenic colonizer of the human oral cavity. To be competitive in the oral biofilm,
S. gordonii
secretes antimicrobial peptides called bacteriocins, which inhibit closely related species. Our previous data showed that mutation of the disulfide oxidoreductase SdbA abolished bacteriocin production. In this study, we show that mutation of SdbA generates a signal that upregulates the CiaRH two-component system, which in turn downregulates a second two-component system, Com, which regulates bacteriocin expression. Our data show that these systems are also linked in
S. gordonii
, and the data reveal that the cell's ability to form disulfide bonds is sensed by the CiaRH system.
Cost-effectiveness of integrated COPD care: the RECODE cluster randomised trial
Authors: Boland Melinde R S , Kruis Annemarije L , Tsiachristas Apostolos , Assendelft Willem J J , Gussekloo Jacobijn , Blom Coert M G , Chavannes Niels H , Rutten-van Mölken Maureen P M H 
Published: November 2015

ObjectivesTo investigate the cost-effectiveness of a chronic obstructive pulmonary disease (COPD) disease management (COPD-DM) programme in primary care, called RECODE, compared to usual care.DesignA 2-year cluster-randomised controlled trial.Setting40 general practices in the western part of the Netherlands.Participants1086 patients with COPD according to GOLD (Global Initiative for COPD) criteria. Exclusion criteria were terminal illness, cognitive impairment, alcohol or drug misuse and inability to fill in Dutch questionnaires. Practices were included if they were willing to create a multidisciplinary COPD team.InterventionsA multidisciplinary team of caregivers was trained in motivational interviewing, setting up individual care plans, exacerbation management, implementing clinical guidelines and redesigning the care process. In addition, clinical decision-making was supported by feedback reports provided by an ICT programme.Main outcome measuresWe investigated the impact on health outcomes (quality-adjusted life years (QALYs), Clinical COPD Questionnaire, St. George's Respiratory Questionnaire and exacerbations) and costs (healthcare and societal perspective).ResultsThe intervention costs were €324 per patient. Excluding these costs, the intervention group had €584 (95% CI €86 to €1046) higher healthcare costs than did the usual care group and €645 (95% CI €28 to €1190) higher costs from the societal perspective. Health outcomes were similar in both groups, except for 0.04 (95% CI −0.07 to −0.01) less QALYs in the intervention group.ConclusionsThis integrated care programme for patients with COPD that mainly included professionally directed interventions was not cost-effective in primary care.Trial registration numberNetherlands Trial Register NTR2268.
‘The phone reminder is important, but will others get to know about my illness?’ Patient perceptions of an mHealth antiretroviral treatment support intervention in the HIVIND trial in South India
Authors: Rodrigues Rashmi , Poongulali S , Balaji Kavitha , Atkins Salla , Ashorn Per , De Costa Ayesha 
Published: November 2015

ObjectivesThe recent explosion of mHealth applications in the area of HIV care has led to the development of mHealth interventions to support antiretroviral treatment adherence. Several of these interventions have been tested for effectiveness, but few studies have explored patient perspectives of such interventions. Exploring patient perspectives enhances the understanding of how an intervention works or why it does not. We therefore studied perceptions regarding an mHealth adherence intervention within the HIVIND trial in South India.MethodsThe study was conducted at three clinics in South India. The intervention comprised an automated interactive voice response (IVR) call and a pictorial short messaging service (SMS), each delivered weekly. Sixteen purposively selected participants from the intervention arm in the HIVIND trial were interviewed. All participants had completed at least 84 weeks since enrollment in the trial. Perceptions on the usefulness and perceived benefits and risks of receiving the intervention were sought. The interviews were transcribed and analysed using the framework approach to qualitative data analysis.ResultsDespite varying perceptions of the intervention, most participants found it useful. The intervention was perceived as a sign of ‘care’ from the clinic. The IVR call was preferred to the SMS reminder. Two-way communication was preferred to automated calls. Participants also perceived a risk of unintentional disclosure of their HIV status and stigma thereof via the intervention and took initiatives to mitigate this risk. Targeting reminders at those with poor adherence and those in need of social support was suggested.ConclusionsmHealth adherence interventions go beyond their intended role to provide a sense of care and support to the recipient. Although automated interventions are impersonal, they could be a solution for scale up. Interventions that engage both the recipient and the healthcare provider have greater potential for success. Personalising mHealth interventions could mitigate the risk of stigma and promote their uptake.Trial registration numberISRCTN79261738.
Is it possible to predict improved diabetes outcomes following diabetes self-management education: a mixed-methods longitudinal design
Authors: Huxley Caroline , Sturt Jackie , Dale Jeremy , Walker Rosie , Caramlau Isabela , O'Hare Joseph P , Griffiths Frances 
Published: November 2015

ObjectiveTo predict the diabetes-related outcomes of people undertaking a type 2 Diabetes Self-Management Education (DSME) programme from their baseline data.DesignA mixed-methods longitudinal experimental study. 6 practice nurses and 2 clinical academics undertook blind assessments of all baseline and process data to predict clinical, behavioural and psychological outcomes at 6 months post-DSME programme.SettingPrimary care.Participants–31 people with type 2 diabetes who had not previously undertaken DSME.InterventionAll participants undertook the Diabetes Manual 1:1 self-directed learning 12-week DSME programme supported by practice nurses trained as Diabetes Manual facilitators.Outcome variablesGlycated haemoglobin (HbA1c), diabetes knowledge, physical activity, waist circumference, self-efficacy, diabetes distress, anxiety, depression, demographics, change talk and treatment satisfaction. These variables were chosen because they are known to influence self-management behaviour or to have been influenced by a DSME programme in empirical evidence.ResultsBaseline and 6-month follow-up data were available for 27 participants of which 13 (48%) were male, 22 (82%) white British, mean age 59 years and mean duration of type 2 diabetes 9.1 years. Significant reductions were found in HbA1c t(26)=2.35, p=0.03, and diabetes distress t(26)=2.30, p=0.03, and a significant increase in knowledge t(26)=−2.06, p=0.05 between baseline and 6 months. No significant changes were found in waist circumference, physical activity, anxiety, depression or self-efficacy. Accuracy of predictions varied little between clinical academics and practice nurses but greatly between outcome (0–100%). The median and mode accuracy of predicted outcome was 66.67%. Accuracy of prediction for the key outcome of HbA1c was 44.44%. Diabetes distress had the highest prediction accuracy (81.48%).ConclusionsClinicians in this small study were unable to identify individuals likely to achieve improvement in outcomes from DSME. DSME should be promoted to all patients with diabetes according to guidelines.
Can clinical features be used to differentiate type 1 from type 2 diabetes? A systematic review of the literature
Authors: Shields Beverley M , Peters Jaime L , Cooper Chris , Lowe Jenny , Knight Bridget A , Powell Roy J , Jones Angus , Hyde Christopher J , Hattersley Andrew T 
Published: November 2015

ObjectiveClinicians predominantly use clinical features to differentiate type 1 from type 2 diabetes yet there are no evidence-based clinical criteria to aid classification of patients. Misclassification of diabetes is widespread (7–15% of cases), resulting in patients receiving inappropriate treatment. We sought to identify which clinical criteria could be used to discriminate type 1 and type 2 diabetes.DesignSystematic review of all diagnostic accuracy studies published since 1979 using clinical criteria to predict insulin deficiency (measured by C-peptide).Data sources14 databases including: MEDLINE, MEDLINE in Process and EMBASE. The search strategy took the form of: (terms for diabetes) AND (terms for C-Peptide).Eligibility criteriaDiagnostic accuracy studies of any routinely available clinical predictors against a reference standard of insulin deficiency defined by cut-offs of C-peptide concentrations. No restrictions on race, age, language or country of origin.Results10 917 abstracts were screened, and 231 full texts reviewed. 11 studies met inclusion criteria, but varied by age, race, year and proportion of participants who were C-peptide negative. Age at diagnosis was the most discriminatory feature in 7/9 studies where it was assessed, with optimal cut-offs (>70% mean sensitivity and specificity) across studies being <30 years or <40 years. Use of/time to insulin treatment and body mass index (BMI) were also discriminatory. When combining features, BMI added little over age at diagnosis and/or time to insulin (<1% improvement in classification).ConclusionsDespite finding only 11 studies, and considerable heterogeneity between studies, age at diagnosis and time to insulin were consistently the most discriminatory criteria. BMI, despite being widely used in clinical practice, adds little to these two criteria. The criteria identified are similar to the Royal College of General Practitioners National Health Service (RCGP/NHS) Diabetes classification guidelines, which use age at diagnosis <35 years and time to insulin <6 m. Until further studies are carried out, these guidelines represent a suitable classification scheme.Systematic review registrationPROSPERO reference CRD42012001736.
Predicting physical activity energy expenditure in wheelchair users with a multisensor device
Authors: Nightingale T E , Walhin J P , Thompson D , Bilzon J L J 
Published: November 2015

AimTo assess the error in predicting physical activity energy expenditure (PAEE), using a multisensor device in wheelchair users, and to examine the efficacy of using an individual heart rate calibration (IC) method.Methods15 manual wheelchair users (36±10 years, 72±11 kg) completed 10 activities: resting, folding clothes, wheelchair propulsion on a 1% gradient (3456 and 7 km/h) and propulsion at 4 km/h (with an additional 8% of body mass, 2% and 3% gradient) on a motorised wheelchair treadmill. Criterion PAEE was measured using a computerised indirect calorimetry system. Participants wore a combined accelerometer and heart rate monitor (Actiheart). They also performed an incremental arm crank ergometry test to exhaustion which permitted retrospective individual calibration of the Actiheart for the activity protocol. Linear regression analysis was conducted between criterion (indirect calorimetry) and estimated PAEE from the Actiheart using the manufacturer's proprietary algorithms (group calibration, GC) or IC. Bland-Altman plots were used and mean absolute error was calculated to assess the agreement between criterion values and estimated PAEE.ResultsPredicted PAEE was significantly (p<0.01) correlated with criterion PAEE (GC, r=0.76 and IC, r=0.95). The absolute bias ±95% limits of agreement were 0.51±3.75 and −0.22±0.96 kcal/min for GC and IC, respectively. Mean absolute errors across the activity protocol were 51.4±38.9% using GC and 16.8±15.8% using IC.SummaryPAEE can be accurately and precisely estimated using a combined accelerometer and heart rate monitor device, with integration of an IC. Interindividual variance in cardiovascular function and response to exercise is high in this population. Therefore, in manual wheelchair users, we advocate the use of an IC when using the Actiheart to predict PAEE.
Validity of theFitbitactivity tracker for measuring steps in community-dwelling older adults
Authors: Paul Serene S , Tiedemann Anne , Hassett Leanne M , Ramsay Elisabeth , Kirkham Catherine , Chagpar Sakina , Sherrington Catherine 
Published: November 2015

BackgroundCommercially available activity monitors, such as theFitbit, may encourage physical activity. However, the accuracy of theFitbitin older adults remains unknown. This study aimed to determine (1) the criterion validity ofFitbitstep counts compared to visual count andActiGraphaccelerometer step counts and (2) the accuracy ofActiGraphstep counts compared to visual count in community-dwelling older people.MethodsThirty-two community-dwelling adults aged over 60 woreFitbitandActiGraphdevices simultaneously during a 2 min walk test (2MWT) and then during waking hours over a 7-day period. A physiotherapist counted the steps taken during the 2MWT.ResultsThere was excellent agreement betweenFitbitand visually counted steps (intraclass correlation coefficient (ICC2,1)=0.88, 95% CI 0.76 to 0.94) from the 2MWT, and good agreement betweenFitbitandActiGraph(ICC2,1=0.66, 95% CI 0.41 to 0.82), and betweenActiGraphand visually counted steps (ICC2,1=0.60, 95% CI 0.33 to 0.79). There was excellent agreement between theFitbitandActiGraphin average steps/day over 7 days (ICC2,1=0.94, 95% CI 0.88 to 0.97). Percentage agreement was closest forFitbitsteps compared to visual count (mean 0%, SD 4%) and least forFitbitaverage steps/day compared to theActiGraph(mean 13%, SD 25%).ConclusionsTheFitbitaccurately tracked steps during the 2MWT, but theActiGraphappeared to underestimate steps. There was strong agreement betweenFitbitandActiGraphcounted steps. TheFitbittracker is sufficiently accurate to be used among community-dwelling older adults to monitor and give feedback on step counts.
Force and acceleration characteristics of military foot drill: implications for injury risk in recruits
Authors: Carden Patrick P J , Izard Rachel M , Greeves Julie P , Lake Jason P , Myers Stephen D 
Published: November 2015

BackgroundFoot drill involving marching and drill manoeuvres is conducted regularly during basic military recruit training. Characterising the biomechanical loading of foot drill will improve our understanding of the contributory factors to lower limb overuse injuries in recruits.AimQuantify and compare forces, loading rates and accelerations of British Army foot drill, within and between trained and untrained personnel.Methods24 trained soldiers (12 men and 12 women; TRAINED) and 12 civilian men (UNTRAINED) performed marching and five drill manoeuvres on force platforms; motion capture recorded tibial position. Peak vertical impact force (PF), peak vertical loading rate (PLR), expressed as multiples of body weight (BW) and peak tibial impact acceleration (PTA) were recorded.ResultsDrill manoeuvre PF, PLR and PTA were similar, but higher in TRAINED men (PF, PLR: p<0.01; PTA: p<0.05). Peak values in TRAINED men were shown for the halt (mean (SD); PF: 6.5 (1.5) BW; PLR: 983 (333) BW/s PTA; PTA: 207 (57) m/s2) and left turn (PF: 6.6 (1.7) BW; PLR: 928 (300) BW/s; 184 (62) m/s2). Marching PF, PLR, PTA were similar between groups and lower than all drill manoeuvres (PF: 1.1–1.3 BW; PLR: 42–70 BW/s; p<0.01; PTA: 23–38 m/s2; p<0.05).ConclusionsArmy foot drill generates higher forces, loading rates and accelerations than activities such as running and load carriage, while marching is comparable to moderate running (10.8 km/h). The large biomechanical loading of foot drill may contribute to the high rate of overuse injuries during initial military training, and strategies to regulate/reduce this loading should be explored.
Elevated Coexpression of KITENIN and the ErbB4 CYT-2 Isoform Promotes the Transition from Colon Adenoma to Carcinoma Following APC loss
Authors: Bae Jeong A , Kho Dhong Hyo , Sun Eun Gene , Ko Yoo-Seung , Yoon Somy , Lee Kyung Hwa , Ahn Kyu Youn , Lee Jae Hyuk , Joo Young Eun , Chung Ik Joo , Lee Sug Hyung , Kim Hangun , Kim Kyung Keun 
Published: November 2015

Abstract
Purpose and Experimental Design: The molecular events in the malignant progression of colon adenoma after loss of adenomatous polyposis coli (APC) are not fully understood. KITENIN (KAI1 C-terminal interacting tetraspanin) increases the invasiveness of colorectal cancer cells, and we identified a novel EGFR-independent oncogenic signal of EGF that works under coexpressed KITENIN and ErbB4. Here we tested whether elevated KITENIN and ErbB4 contribute to further progression of intestinal adenoma following APC loss.
Results: The intestinal tissues of villin-KITENIN transgenic mice in which villin-driven KITENIN expression induces increased c-Jun expression exhibit mild epithelial cell proliferation but no epithelial lineage changes compared with those of nontransgenic mice. Among the four ErbB4 isoforms, JM-a/CYT-2 and JM-b/CYT-2 exhibited the highest AP-1 activity when cells coexpressing KITENIN and each isoform were stimulated by EGF. Interestingly, predominant overexpression of the ErB4-CYT-2 mRNA as well as increased EGFR expression were observed in intestinal adenoma of APCmin/+ mice, which makes the microenvironment of activated EGF signaling. When we crossed villin-KITENIN mice with APCmin/+ mice, intestinal tumor tissues in the crossed mice showed the characteristics of early-stage invading adenocarcinoma. In patients with colorectal cancer, ErbB4-CYT-2 mRNA expression was significantly greater in tumor tissues than in normal adjacent tissues, but no significant differences in tumor tissue expression were found between different colorectal cancer stages. Furthermore, the mRNA expression of KITENIN and that of ErbB4-CYT-2 were positively correlated in human colorectal cancer tissue.
Conclusions: Elevated coexpression of KITENIN and ErbB4-CYT-2 promotes the transition of colon adenoma to adenocarcinoma within an APC loss–associated tumor microenvironment. Clin Cancer Res; 22(5); 1284–94. ©2015 AACR.
A Presurgical Study of Oral Silybin-Phosphatidylcholine in Patients with Early Breast Cancer
Authors: Lazzeroni Matteo , Guerrieri-Gonzaga Aliana , Gandini Sara , Johansson Harriet , Serrano Davide , Cazzaniga Massimiliano , Aristarco Valentina , Puccio Antonella , Mora Serena , Caldarella Pietro , Pagani Gianmatteo , Pruneri Giancarlo , Riva Antonella , Petrangolini Giovanna , Morazzoni Paolo , DeCensi Andrea , Bonanni Bernardo 
Published: November 2015

Abstract
Silybin-phosphatidylcholine is an orally bioavailable complex of silybin, a polyphenolic flavonolignan derived from milk thistle, endowed with potential anticancer activity in preclinical models. The purpose of this window of opportunity trial was to determine, for the first time in early breast cancer patients, the breast tissue distribution of silybin. Twelve breast cancer patients received silybin-phosphatidylcholine, 2.8 g daily for 4 weeks prior to surgery. Silybin levels were measured before (SIL) and after (TOT-SIL) enzymatic hydrolysis by high-performance liquid chromatography (HPLC)-MS/MS in biologic samples (plasma, urine, breast cancer, and surrounding normal tissue). Fasting blood samples were taken at baseline, before the last administration, and 2 hours later. All patients were fully compliant and completed the treatment program. No toxicity was observed. SIL and TOT-SIL were undetectable in baseline samples. Despite a high between-subject variability, repeated administration of Siliphos achieved levels of TOT-SIL of 31,121 to 7,654 ng/mL in the plasma and up to 1,375 ng/g in breast cancer tissue. SIL concentrations ranged from 10,861 to 1,818 ng/mL in plasma and up to 177 ng/g in breast cancer tissue. Median TOT-SIL concentration was higher in the tumor as compared with the adjacent normal tissue (P = 0.018). No significant change in either blood levels of IGF-I and nitric oxide or Ki-67 in tumors was noted. Silybin-phosphatidylcholine, taken orally, can deliver high blood concentrations of silybin, which selectively accumulates in breast tumor tissue. These findings provide the basis for a future phase II biomarker trial in breast cancer prevention. Cancer Prev Res; 9(1); 89–95. ©2015 AACR.