bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spot 42 Small RNA Regulates Arabinose-Inducible
araBAD
Promoter Activity by Repressing Synthesis of the High-Affinity Low-Capacity Arabinose Transporter
Authors: Chen Jiandong , Gottesman Susan 
Published: November 2016

ABSTRACT

The
l
-arabinose-inducible
araBAD
promoter (P
BAD
) enables tightly controlled and tunable expression of genes of interest in a broad range of bacterial species. It has been used successfully to study bacterial sRNA regulation, where P
BAD
drives expression of target mRNA translational fusions. Here we report that in
Escherichia coli
, Spot 42 sRNA regulates P
BAD
promoter activity by affecting arabinose uptake. We demonstrate that Spot 42 sRNA represses
araF
, a gene encoding the AraF subunit of the high-affinity low-capacity arabinose transporter AraFGH, through direct base-pairing interactions. We further show that endogenous Spot 42 sRNA is sufficient to repress
araF
expression under various growth conditions. Finally, we demonstrate this posttranscriptional repression has a biological consequence, decreasing the induction of P
BAD
at low levels of arabinose. This problem can be circumvented using strategies reported previously for avoiding all-or-none induction behavior, such as through constitutive expression of the low-affinity high-capacity arabinose transporter AraE or induction with a higher concentration of inducers. This work adds
araF
to the set of Spot 42-regulated genes, in agreement with previous studies suggesting that Spot 42, itself negatively regulated by the cyclic AMP (cAMP) receptor protein-cAMP complex, reinforces the catabolite repression network.

IMPORTANCE
The bacterial arabinose-inducible system is widely used for titratable control of gene expression. We demonstrate here that a posttranscriptional mechanism mediated by Spot 42 sRNA contributes to the functionality of the P
BAD
system at subsaturating inducer concentrations by affecting inducer uptake. Our finding extends the inputs into the known transcriptional control for the P
BAD
system and has implications for improving its usage for tunable gene expression.
Effect of type and amount of dietary carbohydrate on biomarkers of glucose homeostasis and C reactive protein in overweight or obese adults: results from the OmniCarb trial
Authors: Juraschek Stephen P , Miller Edgar R , Selvin Elizabeth , Carey Vincent J , Appel Lawrence J , Christenson Robert H , Sacks Frank M 
Published: November 2016

ObjectiveThe glycemic index (GI) of dietary carbohydrate is thought to affect glucose homeostasis. Recently, the Effect of Amount and Type of Dietary Carbohydrates on Risk for Cardiovascular Heart Disease and Diabetes Study (OmniCarb) trial reported that a low-GI diet did not improve insulin sensitivity. We conducted this ancillary study of the OmniCarb trial to determine the effects of GI and carbohydrate content on glucose homeostasis and inflammation.Research design and methodsOmniCarb was a randomized cross-over feeding study conducted in overweight or obese adults without diabetes (N=163). Participants were fed each of 4 diets for 5 weeks with 2-week washout periods. Weight was held constant. Diets were: high GI (GI≥65) with high carbohydrate (58% kcal), low GI (GI≤45) with low carbohydrate (40% kcal), low GI with high carbohydrate, and high GI with low carbohydrate. We measured glycated albumin (GA), fructosamine, and high sensitivity C reactive protein (CRP) at baseline and following each dietary period. These biomarkers were compared within-person between diets.ResultsThe study population was 52% female and 50% black. Mean age was 53 (SD, 11) years; mean body mass index was 32 (SD 6) kg/m2. Reducing GI had no effect on GA or fructosamine, but increased fasting glucose in the setting of a high-carbohydrate diet (+2.2 mg/dL; p=0.02). Reducing carbohydrate content decreased GA in the setting of a high-GI diet (−0.2%; p=0.03) and decreased fructosamine in the setting of a low-GI diet (−4 µmol/L; p=0.003). Reducing carbohydrate while simultaneously increasing GI significantly reduced both GA (−0.2%; p=0.04) and fructosamine (−4 µmol/L; p=0.009). Neither reducing GI nor amount of carbohydrate affected insulin or CRP.ConclusionsReducing carbohydrate, regardless of high or low GI, decreased GA and fructosamine. This suggests that reducing carbohydrate content, rather than GI, is a better strategy for lowering glycemia in adults at risk for diabetes.Trial registration numberNCT00608049.
A critical appraisal of the methodology and quality of evidence of systematic reviews and meta-analyses of traditional Chinese medical nursing interventions: a systematic review of reviews
Authors: Jin Ying-Hui , Wang Guo-Hao , Sun Yi-Rong , Li Qi , Zhao Chen , Li Ge , Si Jin-Hua , Li Yan , Lu Cui , Shang Hong-Cai 
Published: November 2016

ObjectiveTo assess the methodology and quality of evidence of systematic reviews and meta-analyses of traditional Chinese medical nursing (TCMN) interventions in Chinese journals. These interventions include acupressure, massage, Tai Chi, Qi Gong, electroacupuncture and use of Chinese herbal medicines—for example, in enemas, foot massage and compressing the umbilicus.DesignA systematic literature search for systematic reviews and meta-analyses of TCMN interventions was performed. Review characteristics were extracted. The methodological quality and the quality of the evidence were evaluated using the Assessment of Multiple Systematic Reviews (AMSTAR) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) approaches.ResultWe included 20 systematic reviews and meta-analyses, and a total of 11 TCMN interventions were assessed in the 20 reviews. The compliance with AMSTAR checklist items ranged from 4.5 to 8 and systematic reviews/meta-analyses were, on average, of medium methodological quality. The quality of the evidence we assessed ranged from very low to moderate; no high-quality evidence was found. The top two causes for downrating confidence in effect estimates among the 31 bodies of evidence assessed were the risk of bias and inconsistency.ConclusionsThere is room for improvement in the methodological quality of systematic reviews/meta-analyses of TCMN interventions published in Chinese journals. Greater efforts should be devoted to ensuring a more comprehensive search strategy, clearer specification of the interventions of interest in the eligibility criteria and identification of meaningful outcomes for clinicians and patients (consumers). The overall quality of evidence among reviews remains suboptimal, which raise concerns about their roles in influencing clinical practice. Thus, the conclusions in reviews we assessed must be treated with caution and their roles in influencing clinical practice should be limited. A critical appraisal of systematic reviews/meta-analyses of TCMN interventions is particularly important to provide sound guidance for TCMN.
Use of the Diabetes Medication Choice Decision Aid in patients with type 2 diabetes in Greece: a cluster randomised trial
Authors: Karagiannis Thomas , Liakos Aris , Branda Megan E , Athanasiadou Eleni , Mainou Maria , Boura Panagiota , Goulis Dimitrios G , LeBlanc Annie , Montori Victor M , Tsapas Apostolos 
Published: November 2016

ObjectiveTo assess the efficacy of the Diabetes Medication Choice Decision Aid among patients with type 2 diabetes in Greece.DesignOpen-label cluster randomised controlled trial.SettingPrimary and secondary care practices across Greece.Participants5 sites allocated to the decision aid (n=101 patients) and 4 sites to control (n=103 patients).InterventionClinicians and patients in the intervention arm used a decision aid, based on outcomes that both consider important when choosing among antihyperglycaemic medications. Patients in the control arm received usual care.Outcome measuresThe primary outcome was patient's level of decisional comfort after the initial clinical encounter. Secondary outcomes included patient's knowledge about type 2 diabetes and medications, and patient's and clinician's satisfaction. Adherence to prescribed antihyperglycaemic medication and change in glycated haemoglobin were assessed at 24 weeks.ResultsPatients in both arms had similar scores in overall decisional comfort (mean difference between the usual care and decision aid arms −6.9, 95% CI −21.5 to 7.7) and its subscales. Patients' knowledge was high in both arms (mean difference 2.3%, 95% CI −15.7% to 20.4%). Patients and clinicians in both groups were equally satisfied with the decision-making. No significant difference in medication adherence and glycaemic control was found across arms. Clinicians found the decision aid useful and reported that its integration in their daily routine was easy.ConclusionsThe decision aid was implemented and positively received in the clinical setting in Greece, in line with the patient-centred approach endorsed by current guidelines. However, this trial yielded imprecise results in terms of patient outcomes. Further research is needed to investigate the interaction between the patient and the clinician in order to clarify the association between the use of decision aids and implementation of shared decision-making.Trial registration numberNCT01861756. Pre-results.
Impact of scheduled appointments on cervical screening participation in Norway: a randomised intervention
Authors: Lönnberg Stefan , Andreassen Trude , Engesæter Birgit , Lilleng Rune , Kleven Cecilia , Skare Annelie , Johansson Karin , Fredheim Christina Stangeland , Tropé Ameli 
Published: November 2016

BackgroundThe main barrier to optimal effect in many established population-based screening programmes against cervical cancer is low participation. In Norway, a routine health service integrated population-based screening programme has been running since 1995, using open invitations and reminders. The aim of this randomised health service study was to pilot scheduled appointments and assess their potential for increased participation.MethodsWithin the national screening programme, we randomised 1087 women overdue for screening to receive invitations with scheduled appointments (intervention) or the standard open reminders (control). Letters were sent 2–4 weeks before the scheduled appointments at three centres: a midwife clinic, a public healthcare centre and a general practitioner centre. The primary outcome was participation at 6 months of follow-up. Secondary outcomes were participation at 1 and 3 months. Risk ratios (RRs) overall, and stratified by screening centre, age group and previous participation, were calculated using log-binomial regression.ResultsAt 6 months, 20% of the 510 women in the control group and 37% of the 526 women in the intervention group had participated in screening, excluding 51 women in total from analysis due to participation just before invitation and therefore not yet visible in the central records. The RR for participation at 6 months was 1.9 (95% CI 1.5 to 2.3). There was no significant heterogeneity between centres or age groups. Participation increased among women both with (RR 1.7; 95% CI 1.4 to 2.1) and without (RR 3.5; 95% CI 1.3 to 9.2) previous participation. The RRs for participation at 1 and 3 months were 4.0 (95% CI 2.6 to 6.2) and 2.7 (95% CI 2.1 to 3.5), respectively.ConclusionsScheduled appointments increased screening participation consistently across all target ages and screening centres among women overdue for screening. Participation increased also among women with no previous records of cervical screening.
Molecular characterisation of acute intermittent porphyria in a cohort of South African patients and kinetic analysis of two expressed mutants
Authors: Fortgens Philip , Pienaar Elaine , Corrigall Anne , Sonderup Mark , Spearman C Wendy , Meissner Peter 
Published: November 2016

AimsAcute intermittent porphyria (AIP) is a disorder of the haem biosynthetic pathway caused by mutations in the hydroxymethylbilane synthase (HMBS) gene. Knowledge of the spectrum of mutations present in South Africa is limited. This study presents the molecular profile of 20 South African patients with AIP, and the kinetic analysis of one novel expressed mutated HMBS enzyme and a previously identified mutation at the same position.MethodsGenomic DNA was isolated from affected probands and selected family members, theHMBSgene amplified and mutations characterised by direct sequencing and restriction enzyme analysis. One of the novel mutations (p.Lys98Glu), a previously characterised mutation at the same position (p.Lys98Arg), and the wild-type enzyme were expressed, purified and subjected to partial kinetic characterisation.ResultsFour new mutations, p.Lys98Glu, p.Asp230Aspfs*20, c.161-1G>A and c.422+3_6delAAGT, are described. Seven previously described mutations were found, while four patients revealed no mutations. Mutation analysis of five offspring of one of the probands carrying the p.Trp283X mutation revealed two asymptomatic carriers. Kinetic analysis showed that the p.Lys98Glu mutation results in loss of substrate affinity, whereas the previously described p.Lys98Arg mutation causes the loss of binding between the enzyme and its dipyrromethane cofactor, rendering the enzyme inactive.ConclusionsThis study comprises the most comprehensive characterisation ofHMBSgene mutations in patients with AIP in South Africa. The biochemical characterisation of expressedHMBSmutants reveals insight into the mechanism of catalytic activity loss, which may inspire investigation into individualised therapy based on the molecular lesion identified.
Single-stage endovascular treatment of multiple intracranial aneurysms with combined endovascular techniques: is it safe to treat all at once?
Authors: Andic Cagatay , Aydemir Fatih , Kardes Ozgur , Gedikoglu Murat , Akin Sule 
Published: November 2016

Background and purposeMultiple aneurysms have a high reported incidence, but the optimal treatment strategy is not clear. The aim of this study was to evaluate the safety and effectiveness of single-stage endovascular treatment of multiple aneurysms with a combination of various endovascular techniques.Materials and methodsFifty-three consecutive patients with multiple intracranial aneurysms who underwent single-stage endovascular treatment for ≥2 aneurysms from June 2011 to May 2016 were included in the study. Patient and aneurysm characteristics, treatment technique, complications, clinical and angiographic outcomes were retrospectively evaluated.Results125 of 128 aneurysms (97.6%) were treated by the following endovascular techniques: simple coiling in 19, balloon-assisted coiling in 27, stent-assisted coiling in 33, flow diverters in 43, intrasaccular flow modifiers in 2, and a neck-bridging device in 1. Overall mortality and mortality directly related to the single-stage treatment was 15% (8/53) and 3.7% (2/53), respectively. Clinical and angiographic follow-up was available in 44 (83%) patients for 104 (83.2%) aneurysms for a mean duration of 16.2 months (range 3–51 months). According to the last angiographic follow-up, overall occlusion rates were complete in 85 (81.7%), near complete in 8 (7.6%), and incomplete in 11 (10.5%) aneurysms.ConclusionsSingle-stage endovascular treatment of multiple aneurysms with combined endovascular techniques is technically feasible and increases the treatment possibility of all detected aneurysms. However, the safety of the procedure is controversial due to relatively high complication rates. In particular, in patients with bilateral internal carotid artery aneurysms, staged therapy may be used instead of simultaneous treatment with flow diverters to avoid thromboembolic events.
New Developments in Diagnosis, Prognosis, and Assessment of Response in Multiple Myeloma
Authors: Landgren Ola , Rajkumar S. Vincent 
Published: November 2016

Abstract
Over the past few years, the management of multiple myeloma has changed. We have new guidelines regarding how to set the diagnosis, when to initiate therapy, and how to monitor treatment response. In 2014, the updated International Myeloma Working Group (IMWG) diagnostic criteria changed the definition of multiple myeloma from being a disease defined by symptoms to a disease defined by biomarkers. Today, modern combination therapies have reported up to 60% to 80% of patients reaching a complete response. As a logical and necessary step forward, investigators have explored strategies to detect minimal residual disease (MRD) and its correlation with clinical outcomes. Recent meta-analysis data show that MRD negativity is associated with longer progression-free survival and overall survival. In 2016, the updated IMWG response criteria include MRD as the deepest level of treatment response in multiple myeloma. Simultaneously, we are still quite behind in our understanding of the heterogeneous biology of multiple myeloma and its implications for therapy. Emerging DNA sequencing data show that newly diagnosed multiple myeloma patients have a broad range of mutations, which are distributed unevenly in multiple parallel subclones already present at diagnosis. To move beyond the ill-defined category of “high-risk multiple myeloma,” which confers to approximately 25% of all newly diagnosed patients, prospective studies are needed to dissect tumor biology and define multiple myeloma subtypes, and, based on biology, seek to define rational therapies for individual subtypes. This article discusses novel insights and gives perspectives on diagnosis and MRD monitoring and future directions for prognosis and clinical management of multiple myeloma. Clin Cancer Res; 22(22); 5428–33. ©2016 AACR.
See all articles in this CCR Focus section, “Multiple Myeloma: Multiplying Therapies.”
Honokiol Decreases Lung Cancer Metastasis through Inhibition of the STAT3 Signaling Pathway
Authors: Pan Jing , Lee Yongik , Zhang Qi , Xiong Donghai , Wan Tina C. , Wang Yian , You Ming 
Published: November 2016

Abstract
Lung cancer is the leading cause of cancer death in the United States. Metastasis to lymph nodes and distal organs, especially brain, leads to severe complications and death. Preventing lung cancer development and metastases is an important strategy to reduce lung cancer mortality. Honokiol (HNK), a natural compound present in the extracts of magnolia bark, has a favorable bioavailability profile and recently has been shown to readily cross the blood–brain barrier. In the current study, we evaluated the antimetastatic effects of HNK in both the lymph node and brain mouse models of lung tumor metastasis. We tested the efficacy of HNK in preventing 18 H2030-BrM3 cell (brain-seeking human lung tumor cells) migration to lymph node or brain. In an orthotopic mouse model, HNK significantly decreased lung tumor growth compared with the vehicle control group. HNK also significantly reduced the incidence of lymph node metastasis and the weight of mediastinal lymph nodes. In a brain metastasis model, HNK inhibits metastasis of lung cancer cells to the brain to approximately one third of that observed in control mice. We analyzed HNK's mechanism of action, which indicated that its effect is mediated primarily by inhibiting the STAT3 pathway. HNK specifically inhibits STAT3 phosphorylation irrespective of the mutation status of EGFR, and knockdown of STAT3 abrogated both the antiproliferative and the antimetastatic effects of HNK. These observations suggest that HNK could provide novel chemopreventive or therapeutic options for preventing both lung tumor progression and lung cancer metastasis. Cancer Prev Res; 10(2); 133–41. ©2016 AACR.
Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive Disease
Authors: Taqueti Viviany R. , Shaw Leslee J. , Cook Nancy R. , Murthy Venkatesh L. , Shah Nishant R. , Foster Courtney R. , Hainer Jon , Blankstein Ron , Dorbala Sharmila , Di Carli Marcelo F. 
Published: November 2016

Background:
Cardiovascular disease (CVD) fatality rates are higher for women than for men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Coronary flow reserve (CFR), an integrated measure of large- and small-vessel CAD and myocardial ischemia, identifies patients at risk for CVD death, but is not routinely measured in clinical practice. We sought to investigate the impact of sex, CFR, and angiographic CAD severity on adverse cardiovascular events.

Methods:
Consecutive patients (n=329, 43% women) referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography and with left ventricular ejection fraction >40% were followed (median, 3.0 years) for a composite end point of major adverse cardiovascular events, including cardiovascular death and hospitalization for nonfatal myocardial infarction or heart failure. The extent and severity of angiographic CAD were estimated by using the CAD prognostic index, and CFR was quantified by using positron emission tomography.

Results:

Although women in comparison with men had lower pretest clinical scores, rates of prior myocardial infarction, and burden of angiographic CAD (
P
<0.001), they demonstrated greater risk of CVD events, even after adjustment for traditional risk factors, imaging findings, and early revascularization (adjusted hazard ratio, 2.05; 95% confidence interval, 1.05–4.02;
P
=0.03). Impaired CFR was similarly present among women and men, but in patients with low CFR (<1.6, n=163), women showed a higher frequency of nonobstructive CAD, whereas men showed a higher frequency of severely obstructive CAD (
P
=0.002). After also adjusting for CFR, the effect of sex on outcomes was no longer significant. When stratified by sex and CFR, only women with severely impaired CFR demonstrated significantly increased adjusted risk of CVD events (
P
<0.0001,
P
for interaction=0.04).

Conclusions:
Women referred for coronary angiography had a significantly lower burden of obstructive CAD in comparison with men but were not protected from CVD events. Excess cardiovascular risk in women was independently associated with impaired CFR, representing a hidden biological risk, and a phenotype less amenable to revascularization. Impaired CFR, particularly absent severely obstructive CAD, may represent a novel target for CVD risk reduction.