bluuebunny/crossref_metadata_2025_split huggingface dataset:
A
Coccidioides posadasii CPS1
Deletion Mutant Is Avirulent and Protects Mice from Lethal Infection
Authors: Narra Hema P. , Shubitz Lisa F. , Mandel M. Alejandra , Trinh Hien T. , Griffin Kurt , Buntzman Adam S. , Frelinger Jeffrey A. , Galgiani John N. , Orbach Marc J. 
Published: August 2016

ABSTRACT

The
CPS1
gene was identified as a virulence factor in the maize pathogen
Cochliobolus heterostrophus
. Hypothesizing that the homologous gene in
Coccidioides posadasii
could be important for virulence, we created a Δ
cps1
deletion mutant which was unable to cause disease in three strains of mice (C57BL/6, BALB/c, or the severely immunodeficient NOD-
scid
,γ
c

null

[NSG]). Only a single colony was recovered from 1 of 60 C57BL/6 mice following intranasal infections of up to 4,400 spores. Following administration of very high doses (10,000 to 2.5 × 10
7
spores) to NSG and BALB/c mice, spherules were observed in lung sections at time points from day 3 to day 10 postinfection, but nearly all appeared degraded with infrequent endosporulation. Although the role of
CPS1
in virulence is not understood, phenotypic alterations and transcription differences of at least 33 genes in the Δ
cps1
strain versus
C. posadasii
is consistent with both metabolic and regulatory functions for the gene. The
in vitro
phenotype of the Δ
cps1
strain showed slower growth of mycelia with delayed and lower spore production than
C. posadasii
, and
in vitro
spherules were smaller. Vaccination of C57BL/6 or BALB/c mice with live Δ
cps1
spores either intranasally, intraperitoneally, or subcutaneously resulted in over 95% survival with mean residual lung fungal burdens of <1,000 CFU from an otherwise lethal
C. posadasii
intranasal infection. Considering its apparently complete attenuation of virulence and the high degree of resistance to
C. posadasii
infection when used as a vaccine, the Δ
cps1
strain is a promising vaccine candidate for preventing coccidioidomycosis in humans or other animals.
Interaction of Erp Protein of Mycobacterium tuberculosis with Rv2212 Enhances Intracellular Survival of Mycobacterium smegmatis
Authors: Ganaie Arsheed Ahmad , Trivedi Garima , Kaur Amanpreet , Jha Sidharth Shankar , Anand Shashi , Rana Vibhuti , Singh Amit , Kumar Shekhar , Sharma Charu 
Published: August 2016

ABSTRACT

The
Mycobacterium tuberculosis
e
xported
r
epetitive
p
rotein (RvErp) is a crucial virulence-associated factor as determined by its role in the survival and multiplication of mycobacteria in cultured macrophages and
in vivo
. Although attempts have been made to understand the function of Erp protein, its exact role in
Mycobacterium
pathogenesis is still elusive. One way to determine this is by searching for novel interactions of RvErp. Using a yeast two-hybrid assay, an adenylyl cyclase (AC), Rv2212, was found to interact with RvErp. The interaction between RvErp and Rv2212 is direct and occurs at the endogenous level. The Erp protein of
Mycobacterium smegmatis
(MSMEG_6405, or MsErp) interacts neither with Rv2212 nor with Ms_4279, the
M. smegmatis
homologue of Rv2212. Deletion mutants of Rv2212 revealed its adenylyl cyclase domain to be responsible for the interaction. RvErp enhances Rv2212-mediated cyclic AMP (cAMP) production. Also, the biological significance of the interaction between RvErp and Rv2212 was demonstrated by the enhanced survival of
M. smegmatis
within THP-1 macrophages. Taken together, these studies address a novel mechanism by which Erp executes its function.

IMPORTANCE
RvErp is one of the important virulence factors of
M. tuberculosis
. This study describes a novel function of RvErp protein of
M. tuberculosis
by identifying Rv2212 as its interacting protein. Rv2212 is an adenylyl cyclase (AC) and produces cAMP, one of the prime second messengers that regulate the intracellular survival of mycobacteria. Therefore, the significance of investigating novel interactions of RvErp is paramount in unraveling the mechanisms governing the intracellular survival of mycobacteria.
Effects of
tcpB
Mutations on Biogenesis and Function of the Toxin-Coregulated Pilus, the Type IVb Pilus of Vibrio cholerae
Authors: Gao Yang , Hauke Caitlyn A. , Marles Jarrad M. , Taylor Ronald K. 
Published: August 2016

ABSTRACT

Vibrio cholerae
is the etiological agent of the acute intestinal disorder cholera. The toxin-coregulated pilus (TCP), a type IVb pilus, is an essential virulence factor of
V. cholerae
. Recent work has shown that TcpB is a large minor pilin encoded within the
tcp
operon. TcpB contributes to efficient pilus formation and is essential for all TCP functions. Here, we have initiated a detailed targeted mutagenesis approach to further characterize this salient TCP component. We have identified (thus far) 20 residues of TcpB which affect either the steady-state level of TcpB or alter one or more TCP functions. This study provides a solid framework for further understanding of the complex role of TcpB and will be of use upon determination of the crystal structure of TcpB or related minor pilin orthologs of type IVb pilus systems.

IMPORTANCE
Type IV pili, such as the toxin-coregulated pilus (TCP) in
V. cholerae
, are bacterial appendages that often act as essential virulence factors. Minor pilins, like TcpB, of these pili systems often play integral roles in pilus assembly and function. In this study, we have generated mutations in
tcpB
to determine residues of importance for TCP stability and function. Combined with a predicted tertiary structure, characterization of these mutants allows us to better understand critical residues in TcpB and the role they may play in the mechanisms underlying minor pilin functions.
Genomic Amplifications Cause False Positives in CRISPR Screens
Authors: Sheel Ankur , Xue Wen 
Published: August 2016

Abstract
Summary: In CRISPR-based screens for essential genes, Munoz and colleagues and Aguirre and colleagues show that gene-independent targeting of genomic amplifications in human cancer cell lines reduces proliferation or survival. The correlation between CRISPR target site copy number and lethality demonstrates the need for scrutiny and complementary approaches to rule out off-target effects and false positives in CRISPR screens. Cancer Discov; 6(8); 824–6. ©2016 AACR.
See related article by Munoz et al., p. 900.
See related article by Aguirre et al., p. 914.
Consistent Reduction in Periprocedural Myocardial Infarction With Cangrelor as Assessed by Multiple Definitions
Authors: Cavender Matthew A. , Bhatt Deepak L. , Stone Gregg W. , White Harvey D. , Steg Ph. Gabriel , Gibson C. Michael , Hamm Christian W. , Price Matthew J. , Leonardi Sergio , Prats Jayne , Deliargyris Efthymios N. , Mahaffey Kenneth W. , Harrington Robert A. 
Published: August 2016

BACKGROUND:

Cangrelor is an intravenous P2Y
12
inhibitor approved to reduce periprocedural ischemic events in patients undergoing percutaneous coronary intervention not pretreated with a P2Y
12
inhibitor.

METHODS:
A total of 11 145 patients were randomized to cangrelor or clopidogrel in the CHAMPION PHOENIX trial (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition). We explored the effects of cangrelor on myocardial infarction (MI) using different definitions and performed sensitivity analyses on the primary end point of the trial.

RESULTS:

A total of 462 patients (4.2%) undergoing percutaneous coronary intervention had an MI as defined by the second universal definition. The majority of these MIs (n=433, 93.7%) were type 4a. Treatment with cangrelor reduced the incidence of MI at 48 hours (3.8% versus 4.7%; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.67–0.97;
P
=0.02). When the Society of Coronary Angiography and Intervention definition of periprocedural MI was applied to potential ischemic events, there were fewer total MIs (n=134); however, the effects of cangrelor on MI remained significant (OR, 0.65; 95% CI, 0.46–0.92;
P
=0.01). Similar effects were seen in the evaluation of the effects of cangrelor on MIs with peak creatinine kinase-MB ≥10 times the upper limit of normal (OR, 0.64; 95% CI, 0.45–0.91) and those with peak creatinine kinase-MB ≥10 times the upper limit of normal, ischemic symptoms, or ECG changes (OR, 0.63; 95% CI, 0.48–0.84). MIs defined by any of these definitions were associated with increased risk of death at 30 days. Treatment with cangrelor reduced the composite end point of death, MI (Society of Coronary Angiography and Intervention definition), ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis (1.4% versus 2.1%; OR, 0.69; 95% CI, 0.51–0.92).

CONCLUSIONS:
MI in patients undergoing percutaneous coronary intervention, regardless of definition, remains associated with increased risk of death in the current era. Cangrelor compared with clopidogrel significantly reduces MI regardless of the definition.

CLINICAL TRIAL REGISTRATION:

URL:
http://clinicaltrials.gov
. Unique identifier: NCT01156571.
A Study of the Impacts of Climate Change Scenarios on the Plant Hardiness Zones of Albania
Authors: Teqja Zydi , Kopali Albert , Libohova Zamir , Owens Phillip R. 
Published: August 2016

AbstractMaps of plant hardiness zones are useful tools for determining the extreme limits for the survival of plants. Exploration of projected climate change effects on hardiness zones can help identify areas most affected by climate change. Such studies are important in areas with high risks related to climate change, such as the Mediterranean Sea region. The objectives of this study were to (i) map plant hardiness zones for Albania and (ii) assess the projected effects of climate scenarios on the distribution of hardiness zones. Hardiness zones were affected by IPCC AR5 climate scenarios. The most extreme hardiness zone (6a) disappeared while a new, warmer zone (10b) appeared, reflecting rising temperature trends during the cold season. The shifts in spatial distribution of hardiness zones may represent opportunities for introducing new species to Albanian agriculture and forestry; however, the introduction of new species would require further studies on the variability of plant hardiness zones at local scales.
Enhancing Access to Diabetes Self-management Education in Primary Care
Authors: Chomko Maureen E. , Odegard Peggy S. , Evert Alison B. 
Published: August 2016

Purpose The purpose of this continuous quality improvement project was to improve access to diabetes self-management education (DSME) and to evaluate the impact on glycemic and weight control by translating an academic medical center’s DSME program, accredited per the Education Recognition Program (ERP) of the American Diabetes Association, into a program offered at primary care clinics (PCCs). Methods Certified diabetes educators from the medical center trained PCC registered dietitian nutritionists, registered nurses, and social workers to provide DSME in their community-based clinic. Main outcomes of this retrospective, pretest/posttest, observational project were to evaluate enrollment in DSME classes and change in A1C and weight as patients underwent a combined intervention of diabetes education classes with or without consultation and support from a PCC registered dietitian nutritionist or registered nurse. Results PCC DSME was associated with increased enrollment in DSME classes and a significant reduction of A1C and weight at 3 and 6 months post-DSME. Greatest A1C and weight reductions were observed in patients with newly diagnosed diabetes. Reductions were also seen in patients with diabetes duration ≥10 years, participants taking insulin, and those with depression. Conclusions PCC DSME availability increased access to group diabetes education and resulted in reduced A1C and weight for participants. This model was successful in translating an established academic accredited DSME-ERP into a PCC. Results have implications for increasing access to diabetes education programs and improving diabetes control for patients not located near major hospital-based DSME programs.
What Is the Critical Value of Glenoid Bone Loss at Which Soft Tissue Bankart Repair Does Not Restore Glenohumeral Translation, Restricts Range of Motion, and Leads to Abnormal Humeral Head Position?
Authors: Shin Sang-Jin , Koh Yong Won , Bui Christopher , Jeong Woong Kyo , Akeda Masaki , Cho Nam Su , McGarry Michelle H. , Lee Thay Q. 
Published: August 2016

Background: A general consensus has been formed that glenoid bone loss greater than 20% to 25% is the critical amount at which bony augmentation procedures are needed; however, recent clinical results suggest that the critical levels must be reconsidered to lower values. Purpose: This study aimed to find the critical value of anterior glenoid bone loss when a soft tissue repair is not adequate to restore anterior-inferior glenohumeral translation, rotational range of motion, or humeral head position using a biomechanical anterior shoulder instability model. Study Design: Controlled laboratory study. Methods: Eight cadaveric shoulders were tested with a customized shoulder testing system. Range of motion, translation, and humeral head position were measured at 60° of glenohumeral abduction in the scapular plane under a total of 40-N rotator cuff muscle loading in the following 11 conditions: intact; soft tissue Bankart lesion and repair; Bankart lesion with 10%, 15%, 20%, and 25% glenoid bone defects based on the largest anteroposterior width of the glenoid; and soft tissue Bankart repair for each respective glenoid defect. Serial osteotomies for each percentage of bone loss were made parallel to the long axis of the glenoid. Results: There was significantly decreased external rotation (121.2° ± 2.8° to 113.5° ± 3.3°; P = .004), increased anteroinferior translation with an externally applied load (3.0 ± 1.2 mm to 7.5 ± 1.1 mm at 20 N; P = .008), and increased posterior (0.2 ± 0.6 mm to 2.7 ± 0.8 mm; P = .049) and inferior shift (2.9 ± 0.7 mm to 6.6 ± 1.1 mm; P = .018) of the humeral head apex in the position of maximum external rotation after soft tissue Bankart repair of a 15% glenoid defect compared with the repair of a Bankart lesion without a glenoid defect, respectively. Conclusion: Glenoid defects of 15% or more of the largest anteroposterior glenoid width should be considered the critical bone loss amount at which soft tissue repair cannot restore glenohumeral translation, restricts rotational range of motion, and leads to abnormal humeral head position. Clinical Relevance: The critical level of anterior glenoid bone loss at which bony restorations should be considered is closer to 15% of the largest anteroposterior width of glenoid for defects perpendicular to the superoinferior glenoid axis, which is lower than the commonly accepted threshold of 20% to 25%.
Asenapine for the Treatment of Psychotic Disorders
Authors: Orr Catherine , Deshpande Santosh , Sawh Sonja , Jones Philip M. , Vasudev Kamini 
Published: August 2016

Objective: A systematic review was conducted to examine the efficacy, tolerability, and acceptability of asenapine compared with other antipsychotics in the treatment of psychotic disorders. Methods: Four databases, 8 trial registries, and conference presentations were searched for randomized clinical trials of asenapine versus any comparator for the treatment of any psychotic illness. Primary outcome measures were changes in the Positive and Negative Syndrome Scale (PANSS) total score and the incidence of withdrawal due to adverse effects. Results: Eight randomized clinical trials, encompassing 3765 patients, that compared asenapine with placebo ( n = 5) and olanzapine ( n = 3) were included. No differences were found between asenapine and olanzapine in terms of changes to PANSS total or PANSS negative subscale scores. Patients taking asenapine were more likely to experience worsening schizophrenia and/or psychosis than were those taking olanzapine. No differences were found between asenapine and olanzapine in rates of discontinuation due to adverse drug reactions or lack of efficacy, but those taking asenapine had higher rates of withdrawal for any reason than those taking olanzapine. Asenapine caused less clinically significant weight gain or increases in triglycerides than olanzapine and was more likely to cause extrapyramidal symptoms than olanzapine. In comparison to placebo, either no difference or superiority was demonstrated in favour of asenapine on all efficacy measures. Conclusion: The current evidence is limited, as asenapine has been compared only with placebo or olanzapine. In the randomized clinical trials analysed, asenapine was similar or superior to placebo and similar or inferior to olanzapine on most efficacy outcomes. While asenapine demonstrated fewer adverse metabolic outcomes than olanzapine, rates of extrapyramidal symptom–related adverse effects were higher.
A Pharmacist–Physician Collaboration to Optimize Benzodiazepine Use for Anxiety and Sleep Symptom Control in Primary Care
Authors: Furbish Shannon M. L. , Kroehl Miranda E. , Loeb Danielle F. , Lam Huong Mindy , Lewis Carmen L. , Nelson Jennifer , Chow Zeta , Trinkley Katy E. 
Published: August 2016

Introduction: Benzodiazepines are prescribed inappropriately in up to 40% of outpatients. The purpose of this study is to describe a collaborative team-based care model in which clinical pharmacists work with primary care providers (PCPs) to improve the safe use of benzodiazepines for anxiety and sleep disorders and to assess the preliminary results of the impact of the clinical service on patient outcomes. Methods: Adult patients were eligible if they received care from the academic primary care clinic, were prescribed a benzodiazepine chronically, and were not pregnant or managed by psychiatry. Outcomes included baseline PCP confidence and knowledge of appropriate benzodiazepine use, patient symptom severity, and medication changes. Results: Twenty-five of 57 PCPs responded to the survey. PCPs reported greater confidence in diagnosing and treating generalized anxiety and panic disorders than sleep disorder and had variable knowledge of appropriate benzodiazepine prescribing. Twenty-nine patients had at least 1 visit. Over 44 total patient visits, 59% resulted in the addition or optimization of a nonbenzodiazepine medication and 46% resulted in the discontinuation or optimization of a benzodiazepine. Generalized anxiety symptom severity scores significantly improved (−2.0; 95% confidence interval (CI): −3.57 to −0.43). Conclusion: Collaborative team-based models that include clinical pharmacists in primary care can assist in optimizing high-risk benzodiazepine use. Although these findings suggest improvements in safe medication use and symptoms, additional studies are needed to confirm these preliminary results.
The International Translations Centre (ITC): An International Network Facilitating Access to Scientific and Technical Translations
Authors: Risseeuw Mickey 
Published: August 2016

One of the barriers to the transfer of scientific and technical information is that of language. Access to information is frequently denied or hampered on the basis of the source language. While English-language publications are in the majority, this is no excuse to neglect documents published in other languages. Researchers may often find themselves confronted with documents or references to material published in a language they do not read. If the article has ever been translated, they can turn to the International Translations Centre. ITC neither prepares nor commissions translations itself; its primary function is that of a clearinghouse for translations already in existence. The results of the Centre's activities are made available through various printed outlets and databases such as World Transindex. ITC's Information Department can be contacted for further assistance if necessary. The largest number of requests nowadays is for translation from Japanese.
Endothelin-1 Gene Polymorphism and Its Level Predict the Risk of Venous Thromboembolism in Male Indian Population
Authors: Kumari Babita , Prabhakar Amit , Sahu Anita , Chatterjee Tathagata , Tyagi Tarun , Gupta Neha , Nair Velu , Ashraf Mohammad Zahid 
Published: August 2016

Objectives: Genes related to endothelial function are responsible for the regulation of vascular functions. Aim: The aim of this study is to investigate whether endothelial gene-associated polymorphism and their plasma levels can be used to predict the risk for venous thromboembolism (VTE). Methods: We studied 133 patients with VTE and 164 healthy controls. Endothelin (EDN) G8002A, EDN T1370G, EDN 3A/4A, eNOSG894T, angiotensin-converting enzyme I/D, vascular endothelial growth factor C936T, and endothelial cell protein C receptor A6936G polymorphism was genotyped by restriction fragment length polymorphism. Plasma levels of endothelin 1 (EDN1), endothelial nitric oxide synthase, and angiotensin-converting enzyme were measured by enzyme-linked immunoassay kit. Results: The genotype and allele frequency between control and patients with VTE were significantly altered only for EDN T1370G polymorphism. The plasma EDN1 concentration was relatively higher in patients with VTE ( P = .0017) compared to healthy controls and showed an association with the EDN1 gene polymorphism in male Indian population. Logistic regression model analysis for EDN T1370G indicated a significant association between EDN G allele and occurrence of VTE. Conclusion: The EDN1 gene polymorphism may play a significant role in predicting individual’s susceptibility toward VTE and its clinical progression.
Biomechanical Profiles When Towing a Sled and Wearing a Weighted Vest Once Cleared for Sports Post–ACL Reconstruction
Authors: Hartigan Erin , Lawrence Michael , Murray Thomas , Shaw Bernadette , Collins Erin , Powers Kaitlin , Townsend James 
Published: August 2016

Background: Though rehabilitation attempts to correct “stiff knee gait” and control for dynamic limb valgus after anterior cruciate ligament reconstruction (ACLR), impaired biomechanics often persist when an individual is cleared to return to sport (RTS). Reduced knee extension moments (KEMs) and knee flexion angles (KFAs) often continue. While at the hip, increased hip adduction angles (HADDAs) and hip internal rotation angles (HIRAs) often persist in spite of dynamic hip stabilization exercises. Sled towing and weighted vest tasks increase KEM and hip extension moments (HEMs) in healthy individuals, yet biomechanical profiles during these tasks after ACLR are unknown. Hypothesis: Weighted gait will increase KEM, HEM, hip abduction moments (HABDMs), and hip external rotation moments (HERMs) and will not increase unwanted biomechanics (limb asymmetries, HIRA, HADDA) compared with normal gait. Study Design: Controlled laboratory study. Level of Evidence: Level 4. Methods: Fourteen men and 24 women who were 5 to 12 months after ACLR, had no concomitant ligament injuries, and were cleared to RTS were recruited. Sexes were evaluated independently given the sex-specific incidence to ACL injury, reinjury, and gait responses to certain interventions. Joint moment impulses and peak angles over the first 25% of stance were compared between limbs and across tasks (eg, unweighted gait, sled 50% body weight [BW], and vest 50% BW). Results: Men showed that weighted gait increased KEM, HEM, HERM, HADBM (vest only), HADDA, HIRA (sled only), and KFA. Asymmetrical KEM and KFA existed across tasks. Women showed that weighted gait increased KEM, HEM, HERM, HADBM (vest only), HFA (sled only), HADDA, and KFA. Asymmetrical KEM, HEM, HIRA, and KFA (sled only) existed across tasks. Conclusion: Weighted gait generally increased joint moments. Unwanted biomechanics were unique for each weighted gait task. Clinical Relevance: Though joint moments increased, both tasks created unwanted biomechanics after ACLR. Persistent hip (women only) and KEM asymmetries across tasks when cleared to RTS are concerning given the relationship among these biomechanics and decreased functional performance.