bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational Analysis Reveals a Key Regulator of Cryptococcal Virulence and Determinant of Host Response
Authors: Gish Stacey R. , Maier Ezekiel J. , Haynes Brian C. , Santiago-Tirado Felipe H. , Srikanta Deepa L. , Ma Cynthia Z. , Li Lucy X. , Williams Matthew , Crouch Erika C. , Khader Shabaana A. , Brent Michael R. , Doering Tamara L. 
Published: April 2016

ABSTRACT

Cryptococcus neoformans
is a ubiquitous, opportunistic fungal pathogen that kills over 600,000 people annually. Here, we report integrated computational and experimental investigations of the role and mechanisms of transcriptional regulation in cryptococcal infection. Major cryptococcal virulence traits include melanin production and the development of a large polysaccharide capsule upon host entry; shed capsule polysaccharides also impair host defenses. We found that both transcription and translation are required for capsule growth and that Usv101 is a master regulator of pathogenesis, regulating melanin production, capsule growth, and capsule shedding. It does this by directly regulating genes encoding glycoactive enzymes and genes encoding three other transcription factors that are essential for capsule growth:
GAT201
,
RIM101
, and
SP1
. Murine infection with cryptococci lacking Usv101 significantly alters the kinetics and pathogenesis of disease, with extended survival and, unexpectedly, death by pneumonia rather than meningitis. Our approaches and findings will inform studies of other pathogenic microbes.

IMPORTANCE
Cryptococcus neoformans
causes fatal meningitis in immunocompromised individuals, mainly HIV positive, killing over 600,000 each year. A unique feature of this yeast, which makes it particularly virulent, is its polysaccharide capsule; this structure impedes host efforts to combat infection. Capsule size and structure respond to environmental conditions, such as those encountered in an infected host. We have combined computational and experimental tools to elucidate capsule regulation, which we show primarily occurs at the transcriptional level. We also demonstrate that loss of a novel transcription factor alters virulence factor expression and host cell interactions, changing the lethal condition from meningitis to pneumonia with an exacerbated host response. We further demonstrate the relevant targets of regulation and kinetically map key regulatory and host interactions. Our work elucidates mechanisms of capsule regulation, provides methods and resources to the research community, and demonstrates an altered pathogenic outcome that resembles some human conditions.
Duplex DNA-Invading γ-Modified Peptide Nucleic Acids Enable Rapid Identification of Bloodstream Infections in Whole Blood
Authors: Nölling Jörk , Rapireddy Srinivas , Amburg Joel I. , Crawford Elizabeth M. , Prakash Ranjit A. , Rabson Arthur R. , Tang Yi-Wei , Singer Alon 
Published: April 2016

ABSTRACT
Bloodstream infections are a leading cause of morbidity and mortality. Early and targeted antimicrobial intervention is lifesaving, yet current diagnostic approaches fail to provide actionable information within a clinically viable time frame due to their reliance on blood culturing. Here, we present a novel pathogen identification (PID) platform that features the use of duplex DNA-invading γ-modified peptide nucleic acids (γPNAs) for the rapid identification of bacterial and fungal pathogens directly from blood, without culturing. The PID platform provides species-level information in under 2.5 hours while reaching single-CFU-per-milliliter sensitivity across the entire 21-pathogen panel. The clinical utility of the PID platform was demonstrated through assessment of 61 clinical specimens, which showed >95% sensitivity and >90% overall correlation to blood culture findings. This rapid γPNA-based platform promises to improve patient care by enabling the administration of a targeted first-line antimicrobial intervention.

IMPORTANCE
Bloodstream infections continue to be a major cause of death for hospitalized patients, despite significant improvements in both the availability of treatment options as well their application. Since early and targeted antimicrobial intervention is one of the prime determinants of patient outcome, the rapid identification of the pathogen can be lifesaving. Unfortunately, current diagnostic approaches for identifying these infections all rely on time-consuming blood culture, which precludes immediate intervention with a targeted antimicrobial. To address this, we have developed and characterized a new and comprehensive methodology, from patient specimen to result, for the rapid identification of both bacterial and fungal pathogens without the need for culturing. We anticipate broad interest in our work, given the novelty of our technical approach combined with an immense unmet need.
Antimicrobial Resistance in Agriculture
Authors: Thanner Sophie , Drissner David , Walsh Fiona 
Published: April 2016

ABSTRACT
In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans.
Aerobic exercise ameliorates cognitive function in older adults with mild cognitive impairment: a systematic review and meta-analysis of randomised controlled trials
Authors: Zheng Guohua , Xia Rui , Zhou Wenji , Tao Jing , Chen Lidian 
Published: April 2016

ObjectiveTo evaluate the effect of aerobic exercise on cognitive function in people with mild cognitive impairment (MCI).DesignSystematic review and meta-analysis of aerobic exercise intervention for cognitive function in older adults with MCI.Data sourcesPubMed, EMBASE, SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang and Chinese Science and Technology Periodical (VIP) databases from their inception to 31 January 2015, the Cochrane Central Register of Controlled Trials (Cochrane Library, 2015, Issue 3) and the reference lists of all retrieved articles.Eligibility criteriaRandomised controlled trials, older adults with MCI, aerobic exercises compared with no specific exercise intervention for global cognitive ability and any specific domains of cognition.Data synthesisMeta-analysis was conducted with RevMan V.5.3 software using the fixed-effect model for the available data without significant heterogeneity, or the random-effect model was used if appropriate.Results11 studies were identified involving 1497 participants. Meta-analysis showed that aerobic exercise significantly improved global cognitive ability (Mini-Mental State Examination (MMSE) scores: MD=0.98, 95% CI 0.5 to 1.45, p<0.0001; Montreal Cognitive Assessment (MoCA) scores: MD=2.7, 95% CI 1.11 to 4.29, p=0.0009); weakly, positively improve memory (immediately recall: SMD=0.29, 95% CI 0.13 to 0.46, p=0.0005; delay recall: SMD=0.22, 95% CI 0.09 to 0.34, p=0.0005). No significant improvement was found in other domains of cognition.ConclusionsAerobic exercise led to an improvement in global cognitive ability and had a positive effect with a small effect size on memory in people with MCI. However, owing to the limitations of the included studies, these findings should be interpreted cautiously.
Pleiotropic effects of sitagliptin versus voglibose in patients with type 2 diabetes inadequately controlled via diet and/or a single oral antihyperglycemic agent: a multicenter, randomized trial
Authors: Matsushima Yukiko , Takeshita Yumie , Kita Yuki , Otoda Toshiki , Kato Ken-ichiro , Toyama-Wakakuri Hitomi , Akahori Hiroshi , Shimizu Akiko , Hamaguchi Erika , Nishimura Yasuyuki , Kanamori Takehiro , Kaneko Shuichi , Takamura Toshinari 
Published: April 2016

PurposeA step-up strategy for diet therapy and/or single oral antihyperglycemic agent (OHA) regimens has not yet been established. The aim of this study was to evaluate hemoglobin A1c (HbA1c) as a primary end point, and the pleiotropic effects on metabolic and cardiovascular parameters as secondary end points, of sitagliptin versus voglibose in patients with type 2 diabetes with inadequate glycemic control while on diet therapy and/or treatment with a single OHA.MethodsIn this multicenter, randomized, open-label, parallel-group trial, a total of 260 patients with inadequately controlled type 2 diabetes (HbA1c levels >6.9%) were randomly assigned to receive either sitagliptin (50 mg, once daily) or voglibose (0.6 mg, thrice daily) for 12 weeks. The primary end point was HbA1c levels.ResultsPatients receiving sitagliptin showed a significantly greater decrease in HbA1c levels (−0.78±0.69%) compared with those receiving voglibose (−0.30±0.78%). Sitagliptin treatment also lowered serum alkaline phosphatase levels and increased serum creatinine, uric acid, cystatin-C and homeostasis model assessment-β values. Voglibose increased low-density lipoprotein-cholesterol levels and altered serum levels of several fatty acids, and increased Δ-5 desaturase activity. Both drugs increased serum adiponectin. The incidence of adverse events (AEs) was significantly lower in the sitagliptin group, due to the decreased incidence of gastrointestinal AEs.ConclusionsSitagliptin shows superior antihyperglycemic effects compared with voglibose as a first-line or second-line therapy. However, both agents possess unique pleiotropic effects that lead to reduced cardiovascular risk in Japanese people with type 2 diabetes.Trial registration numberUMIN 000003503.
Bystander cricothyrotomy with ballpoint pen: a fresh cadaveric feasibility study
Authors: Kisser Ulrich , Braun Christian , Huber Astrid , Stelter Klaus 
Published: April 2016

ObjectiveIn motion pictures and anecdotal reports, ballpoint pens have been used for life-saving cricothyroidotomies. The objective of this study was to examine the widespread belief that ballpoint pens can perforate the skin and cricothyroid ligament and could be used as substitute tracheostomy sets in an emergency setting.MethodsThree different ballpoint pens were examined regarding their inner diameter, their demountability to form a cannula and their airflow properties. Ten medical laypersons were asked to try to puncture the trachea through the skin and the cricothyroid ligament in 10 fresh cadavers just using the ballpoint pens.ResultsTwo of three pens had inner diameters of >3 mm and were both suitable as cannulas in a tracheotomy. All participants could perforate the skin with both ballpoint pens. However, almost no one could penetrate through the cricothyroid ligament or the ventral wall of the trachea, except for one participant. He performed the tracheostomy after three attempts in >5 min with a lot of patience and force.ConclusionsA cricothyroidotomy just with a ballpoint pen is virtually impossible. First, the airflow resistance in commercially available ballpoint pens is too high to produce effective ventilation. Second, the cricothyroid ligament is too strong to be penetrated by ballpoint pens.
The association between visual impairment and the risk of mortality: a meta-analysis of prospective studies
Authors: Zhang Tong , Jiang Wenjie , Song Xinyuan , Zhang Dongfeng 
Published: April 2016

BackgroundThe findings from prospective studies on visual impairment (VI) and the risk of mortality are not consistent.ObjectiveA meta-analysis of prospective studies was conducted to quantitatively summarise the evidence about the association between VI and the risk of mortality.MethodsPertinent studies were identified by a search of PubMed, Web of Science and the Chinese National Knowledge Infrastructure and Wanfang databases up to December 2015. The random-effect model was used to combine study-specific relative risks (RRs) and 95% CIs. Meta-regression and subgroup analysis were conducted to explore potential sources of heterogeneity. Publication bias was estimated by Egger's test and the funnel plot. Dose–response relationship was assessed by restricted cubic spline functions.ResultsThis meta-analysis contained 29 prospective studies including 269 839 participants and 67 061 deaths. Compared to the no VI, the highest VI level was significantly associated with an increased risk of mortality (RR: 1.36, 95% CI 1.25 to 1.46). The association remained significant in participants older than 65 years (RR: 1.28, 95% CI 1.18 to 1.39), and a significant association was also observed in men (RR: 1.29, 95% CI 1.07 to 1.54) and women (RR: 1.39, 95% CI 1.14 to 1.70), respectively. For dose–response analysis, a linear relation was found between visual acuity (VA) and the risk of mortality. For every 0.1 Logarithm of the Minimum Angle of Resolution (LogMAR) increment, the risk of mortality increased by 4% (RR: 1.04, 95% CI 1.01 to 1.06).ConclusionsVI was significantly associated with an increased risk of mortality.
Management and outcome of spontaneous cerebral venous sinus thrombosis in a 5-year consecutive single-institution cohort
Authors: Lee Darrin J , Ahmadpour Arjang , Binyamin Tamar , Dahlin Brian C , Shahlaie Kiarash , Waldau Ben 
Published: April 2016

BackgroundCerebral venous sinus thrombosis (CVST) is an uncommon form of stroke with a variable presentation, ranging from headaches, to coma and death. Although the American Stroke Association has developed guidelines for the treatment of CVST, data are sparse on the outcome after treatment with anticoagulation, thrombolysis, and thrombectomy.MethodsIn this retrospective review, we describe the 5-year UC Davis experience with spontaneous CVST.ResultsForty-one patients (mean age 37.5±23.1, range 0–96 years; 29 female) were identified with CVST. The majority of cases involved the transverse sinus (75.6%), sigmoid sinus (58.5%), and superior sagittal sinus (29.3%). The most common form of treatment was anticoagulation or antiplatelet therapy (n=35), while six patients were managed by observation alone. The overall 1-year modified Rankin score (mRS) was 1.4±1.5. Male patients and patients with a poor admission mRS had a worse outcome. Outcome was unaffected by hypercoagulable state, number of dural sinuses involved, the presence of intracranial hemorrhage, or seizures. Two patients who underwent anticoagulation therapy also required endovascular thrombectomy; both patients had a 1-year mRS of ≤2. Two patients underwent direct open surgical canalization of the superior sagittal sinus with varying outcomes (mRS 2 vs mRS 6).ConclusionsIn our series, the majority (92.9%) of patients with spontaneous dural sinus thrombosis had a favorable clinical outcome as defined by a mRS ≤2. Further prospective studies are needed to study the impact of anticoagulation on the clinical course of the disease.
Cardiac rehabilitation using the Family-Centered Empowerment Model versus home-based cardiac rehabilitation in patients with myocardial infarction: a randomised controlled trial
Authors: Vahedian-Azimi Amir , Miller Andrew C , Hajiesmaieli Mohammadreza , Kangasniemi Mari , Alhani Fatemah , Jelvehmoghaddam Hosseinali , Fathi Mohammad , Farzanegan Behrooz , Ardehali Seyed H , Hatamian Sevak , Gahremani Mehdi , Mosavinasab Seyed M M , Rostami Zohreh , Madani Seyed J , Izadi Morteza 
Published: April 2016

ObjectiveTo determine if a hybrid cardiac rehabilitation (CR) programme using the Family-Centered Empowerment Model (FCEM) as compared with standard CR will improve patient quality of life, perceived stress and state anxiety of patients with myocardial infarction (MI).MethodsWe conducted a randomised controlled trial in which patients received either standard home CR or CR using the FCEM strategy. Patient empowerment was measured with FCEM questionnaires preintervention and postintervention for a total of 9 assessments. Quality of life, perceived stress, and state and trait anxiety were assessed using the 36-Item Short Form Health Survey (SF-36), the 14-item Perceived Stress, and the 20-item State and 20-item Trait Anxiety questionnaires, respectively.Results70 patients were randomised. Baseline characteristics were similar. Ejection fraction was significantly higher in the intervention group at measurements 2 (p=0.01) and 3 (p=0.001). Exercise tolerance measured as walking distance was significantly improved in the intervention group throughout the study. The quality of life results in the FCEM group showed significant improvement both within the group over time (p<0.0001) and when compared with control (p<0.0001). Similarly, the perceived stress and state anxiety results showed significant improvement both within the FCEM group over time (p<0.0001) and when compared with control (p<0.0001). No significant difference was found either within or between groups for trait anxiety.ConclusionsThe family-centred empowerment model may be an effective hybrid cardiac rehabilitation method for improving the physical and mental health of patients post-MI; however, further study is needed to validate these findings. Clinical Trials.gov identifierNCT02402582.Trial registration numberNCT02402582.
Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration
Authors: Schiff Michael , Weinblatt Michael E , Valente Robert , Citera Gustavo , Maldonado Michael , Massarotti Elena , Yazici Yusuf , Fleischmann Roy 
Published: April 2016

ObjectivesTo evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial.MethodsPatients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) ≤2.8, Simplified Disease Activity Index (SDAI) ≤3.3, Routine Assessment of Patient Index Data 3 (RAPID3) ≤3.0, Boolean score ≤1), low disease activity (CDAI <10, SDAI <11, RAPID3 ≤6.0), Health Assessment Questionnaire-Disability Index response and American College of Rheumatology responses were evaluated by baseline disease duration (≤6 vs >6 months). Disease Activity Score 28 (C-reactive protein) <2.6 or ≤3.2 and radiographic non-progression in patients achieving remission were also evaluated.ResultsA total of 646 patients were randomised and treated (abatacept, n=318; adalimumab, n=328). In both treatment groups, comparable responses were achieved in patients with early rheumatoid arthritis (≤6 months) and in those with later disease (>6 months) across multiple clinical measures.ConclusionsAbatacept or adalimumab with background methotrexate were associated with similar onset and sustainability of response over 2 years. Patients treated early or later in the disease course achieved comparable clinical responses.Trial registration numberNCT00929864, Post-results.
The hyperfine excitation of OH radicals by He
Authors: Marinakis Sarantos , Kalugina Yulia , Lique François 
Published: April 2016

Abstract

Hyperfine-resolved collisions between OH radicals and He atoms are investigated using
quantum scattering calculations and the most recent ab initio potential energy surface,
which explicitly takes into account the OH vibrational motion. Such collisions play an
important role in astrophysics, in particular in the modelling of OH masers. The
hyperfine-resolved collision cross sections are calculated for collision energies up to
2500 cm-1 from
the nuclear spin free scattering S-matrices using a recoupling technique. The
collisional hyperfine propensities observed are discussed. As expected, the results from
our work suggest that there is a propensity for collisions with ΔF = Δj.
The new OH−He hyperfine cross
sections are expected to significantly help in the modelling of OH masers from current and
future astronomical observations.

Graphical abstract
Genomic and Immunological Tumor Profiling Identifies Targetable Pathways and Extensive CD8+/PDL1+ Immune Infiltration in Inflammatory Breast Cancer Tumors
Authors: Hamm Christopher A. , Moran Diarmuid , Rao Kakuturu , Trusk Patricia B. , Pry Karen , Sausen Mark , Jones Siân , Velculescu Victor E. , Cristofanilli Massimo , Bacus Sarah 
Published: April 2016

Abstract
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that remains poorly understood at the molecular level. Comprehensive tumor profiling was performed to understand clinically actionable alterations in IBC. Targeted next-generation sequencing (NGS) and IHC were performed to identify activated pathways in IBC tumor tissues. siRNA studies examined the impact of IBC genomic variants in cellular models. IBC tumor tissues were further characterized for immune infiltration and immune checkpoint expression by IHC. Genomic analysis identified recurrent alterations in core biologic pathways, including activating and targetable variants in HER/PI3K/mTOR signaling. High rates of activating HER3 point mutations were discovered in IBC tumors. Cell line studies confirmed a role for mutant HER3 in IBC cell proliferation. Immunologic analysis revealed a subset of IBC tumors associated with high CD8+/PD-L1+ lymphocyte infiltration. Immune infiltration positively correlated with an NGS-based estimate of neoantigen exposure derived from the somatic mutation rate and mutant allele frequency, iScore. Additionally, DNA mismatch repair alterations, which may contribute to higher iScores, occurred at greater frequency in tumors with higher immune infiltration. Our study identifies genomic alterations that mechanistically contribute to oncogenic signaling in IBC and provides a genetic basis for the selection of clinically relevant targeted and combination therapeutic strategies. Furthermore, an NGS-based estimate of neoantigen exposure developed in this study (iScore) may be a useful biomarker to predict immune infiltration in IBC and other cancers. The iScore may be associated with greater levels of response to immunotherapies, such as PD-L1/PD-1–targeted therapies. Mol Cancer Ther; 15(7); 1746–56. ©2016 AACR.
Mechanical Thrombectomy Improves Functional Outcomes Independent of Pretreatment With Intravenous Thrombolysis
Authors: Tsivgoulis Georgios , Katsanos Aristeidis H. , Mavridis Dimitris , Magoufis Georgios , Arthur Adam , Alexandrov Andrei V. 
Published: April 2016

Background and Purpose—
Endovascular intervention for emergent large-vessel occlusion (ELVO) has evolved rapidly during the past decade. The question of whether pretreatment with intravenous thrombolysis (IVT) has a significant impact on the functional outcome of patients with ELVO still remains unanswered.

Methods—
We conducted a systematic review and meta-analysis of all available randomized controlled trials evaluating the efficacy of endovascular therapy (ET) for acute ischemic stroke. We performed a mixed-effects subgroup analysis of the reported odds ratios on the association of ET (versus standard therapy) with 3-month functional outcome, stratified by pretreatment with IVT.

Results—

Six randomized controlled trials were included, comprising 1916 total patients (49.1% receiving ET with IVT pretreatment and 5.6% receiving ET without IVT pretreatment). In the subgroup analysis, ET was associated with a higher likelihood of better 3-month functional outcome in both the subgroup of patients with (odds ratio=1.83; 95% confidence interval, 1.37–2.44;
P
<0.001) and without (odds ratio=2.47; 95% confidence interval, 1.32–4.63;
P
=0.001) pretreatment with IVT. We documented no significant effect of IVT pretreatment on the 3-month functional outcome of patients with ELVO undergoing ET, suggesting that ET is effective in all patients with ELVO. Heterogeneity was documented in the IVT pretreatment subgroup (
I
2
=68.3%;
P
for Cochran
Q
=0.014), but not in the subgroup that did not receive IVT pretreatment (
I
2
=0%,
P
for Cochran
Q
=0.927). The risk of bias was considered to be generally low in the qualitative assessment of the included trials.

Conclusions—
Our observation provides evidence and further reassurance to stroke clinicians regarding the efficacy of ET in ELVO independent of pretreatment with IVT.