bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring Rates and Heterogeneity of High-Pressure Germination of Bacillus Spores by Phase-Contrast Microscopy of Individual Spores
Authors: Kong Lingbo , Doona Christopher J. , Setlow Peter , Li Yong-qing 
Published: October 2013

ABSTRACT

Germination of
Bacillus
spores with a high pressure (HP) of ∼150 MPa is via activation of spores' germinant receptors (GRs). The HP germination of multiple individual
Bacillus subtilis
spores in a diamond anvil cell (DAC) was monitored with phase-contrast microscopy. Major conclusions were that (i) >95% of wild-type spores germinated in 40 min in a DAC at ∼150 MPa and 37°C but individual spores' germination kinetics were heterogeneous; (ii) individual spores' HP germination kinetic parameters were similar to those of nutrient-triggered germination with a variable lag time (
T
lag
) prior to a period of the rapid release (Δ
T
release
) of the spores' dipicolinic acid in a 1:1 chelate with Ca
2+
(CaDPA); (iii) spore germination at 50 MPa had longer average
T
lag
values than that at ∼150 MPa, but the Δ
T
release
values at the two pressures were identical and HPs of <10 MPa did not induce germination; (iv)
B. subtilis
spores that lacked the cortex-lytic enzyme CwlJ and that were germinated with an HP of 150 MPa exhibited average Δ
T
release
values ∼15-fold longer than those for wild-type spores, but the two types of spores exhibited similar average
T
lag
values; and (v) the germination of wild-type spores given a ≥30-s 140-MPa HP pulse followed by a constant pressure of 1 MPa was the same as that of spores exposed to a constant pressure of 140 MPa that was continued for ≥35 min; (vi) however, after short 150-MPa HP pulses and incubation at 0.1 MPa (ambient pressure), spore germination stopped 5 to 10 min after the HP was released. These results suggest that an HP of ∼150 MPa for ≤30 s is sufficient to fully activate spores' GRs, which remain activated at 1 MPa but can deactivate at ambient pressure.
Glycine Betaine as a Direct Substrate for Methanogens (Methanococcoides spp.)
Authors: Watkins Andrew J. , Roussel Erwan G. , Parkes R. John , Sass Henrik 
Published: October 2013

ABSTRACT

Nine marine methanogenic
Methanococcoides
strains, including the type strains of
Methanococcoides methylutens
,
M. burtonii
, and
M. alaskense
, were tested for the utilization of
N
-methylated glycines. Three strains (NM1, PM2, and MKM1) used glycine betaine (
N
,
N
,
N
-trimethylglycine) as a substrate for methanogenesis, partially demethylating it to
N
,
N
-dimethylglycine, whereas none of the strains used
N
,
N
-dimethylglycine or sarcosine (
N
-methylglycine). Growth rates and growth yields per mole of substrate with glycine betaine (3.96 g [dry weight] per mol) were similar to those with trimethylamine (4.11 g [dry weight] per mol). However, as glycine betaine is only partially demethylated, the yield per methyl group was significantly higher than with trimethylamine. If glycine betaine and trimethylamine are provided together, trimethylamine is demethylated to dimethyl- and methylamine with limited glycine betaine utilization. After trimethylamine is depleted, dimethylamine and glycine betaine are consumed rapidly, before methylamine. Glycine betaine extends the range of substrates that can be directly utilized by some methanogens, allowing them to gain energy from the substrate without the need for syntrophic partners.
The Cold-Induced Two-Component System CBO0366/CBO0365 Regulates Metabolic Pathways with Novel Roles in Group I Clostridium botulinum ATCC 3502 Cold Tolerance
Authors: Dahlsten Elias , Zhang Zhen , Somervuo Panu , Minton Nigel P. , Lindström Miia , Korkeala Hannu 
Published: October 2013

ABSTRACTThe two-component system CBO0366/CBO0365 was recently demonstrated to have a role in cold tolerance of group IClostridium botulinumATCC 3502. The mechanisms under its control, ultimately resulting in increased sensitivity to low temperature, are unknown. A transcriptomic analysis with DNA microarrays was performed to identify the differences in global gene expression patterns of the wild-type ATCC 3502 and a derivative mutant with insertionally inactivatedcbo0365at 37 and 15°C. Altogether, 150 or 141 chromosomal coding sequences (CDSs) were found to be differently expressed in thecbo0365mutant at 37 or 15°C, respectively, and thus considered to be under the direct or indirect transcriptional control of the response regulator CBO0365. Of the differentially expressed CDSs, expression of 141 CDSs was similarly affected at both temperatures investigated, suggesting that the putative CBO0365 regulon was practically not affected by temperature. The regulon involved genes related to acetone-butanol-ethanol (ABE) fermentation, motility, arsenic resistance, and phosphate uptake and transport. Deteriorated growth at 17°C was observed for mutants with disrupted ABE fermentation pathway components (crt,bcd,bdh, andctfA), arsenic detoxifying machinery components (arsCandarsR), or phosphate uptake mechanism components (phoT), suggesting roles for these mechanisms in cold tolerance of group IC. botulinum. Electrophoretic mobility shift assays showed recombinant CBO0365 to bind to the promoter regions ofcrt,arsR, andphoT, as well as to the promoter region of its own operon, suggesting direct DNA-binding transcriptional activation or repression as a means for CBO0365 in regulating these operons. The results provide insight to the mechanisms group IC. botulinumutilizes in coping with cold.
Effects of Electroacupuncture on Bone Mineral Density, Oestradiol Level and Osteoprotegerin Ligand Expression in Ovariectomised Rabbits
Authors: He Jing , Yang Lin , Qing Yuxi , He Chengqi 
Published: October 2013

Objectives To investigate the effects of electroacupuncture (EA) on the oestradiol level, bone mineral density and osteoprotegerin ligand (OPGL) expression, and to explore whether EA might be a complementary method to prevent and treat osteoporosis. Methods A total of 21 New Zealand rabbits were randomly divided into three groups: a normal control (NC) group undergoing no surgery or EA; an ovariectomised (OVX) group, in which rabbits were ovariectomised but did not receive EA; an EA group, in which rabbits were ovariectomised and treated with EA. Acupuncture was applied at ST35, BL20 and BL23 points bilaterally. EA (10 Hz, 2 mA) was applied bilaterally at BL20 and BL23 for 30 min a day for 14 days. After 14 days, all animals were killed. OPGL expression level was determined by immunohistochemistry. Blood serum levels of oestradiol were measured by ELISA and bone mineral density was detected by dual-energy x-ray absorptiometry. Results After ovariectomy, the bone mineral density and oestradiol level decreased significantly in the OVX group compared with the NC group (p=0.001), whereas the OPGL expression level increased. After EA, the bone mineral density and oestradiol level increased compared with the OVX group (p=0.049 and p=0.012, respectively). The OPGL level OPGL level in the EA group was lower than that in the OVX group (p=0.022). Conclusions EA restored bone mineral density towards normal and was associated with increased plasma oestradiol level and reduced OPGL expression in an ovariectomised rabbit model of osteoporosis.
Do variations in hospital mortality patterns after weekend admission reflect reduced quality of care or different patient cohorts? A population-based study
Authors: Concha Oscar Perez , Gallego Blanca , Hillman Ken , Delaney Geoff P , Coiera Enrico 
Published: October 2013

BackgroundProposed causes for increased mortality following weekend admission (the ‘weekend effect’) include poorer quality of care and sicker patients. The aim of this study was to analyse the 7 days post-admission time patterns of excess mortality following weekend admission to identify whether distinct patterns exist for patients depending upon the relative contribution of poorer quality of care (care effect) or a case selection bias for patients presenting on weekends (patient effect).MethodsEmergency department admissions to all 501 hospitals in New South Wales, Australia, between 2000 and 2007 were linked to the Death Registry and analysed. There were a total of 3 381 962 admissions for 539 122 patients and 64 789 deaths at 1 week after admission. We computed excess mortality risk curves for weekend over weekday admissions, adjusting for age, sex, comorbidity (Charlson index) and diagnostic group.ResultsWeekends accounted for 27% of all admissions (917 257/3 381 962) and 28% of deaths (18 282/64 789). Sixteen of 430 diagnosis groups had a significantly increased risk of death following weekend admission. They accounted for 40% of all deaths, and demonstrated different temporal excess mortality risk patterns: early care effect (cardiac arrest); care effect washout (eg, pulmonary embolism); patient effect (eg, cancer admissions) and mixed (eg, stroke).ConclusionsThe excess mortality patterns of the weekend effect vary widely for different diagnostic groups. Recognising these different patterns should help identify at-risk diagnoses where quality of care can be improved in order to minimise the excess mortality associated with weekend admission.
Improving management of patients with hyperemesis
Authors: Lloyd Jilly , Ramskill Nikki , Sharma Bhavna 
Published: October 2013

AbstractHyperemesis gravidarum (HG), defined as severe nausea and vomiting resulting in dehydration, is a common reason for emergency admission in gynaecology (1). The management of HG is supportive, including the correction of dehydration and electrolyte disturbances and use of antiemetics.An audit in our unit identified that women with HG were not receiving appropriate fluid resuscitation and in particular inadequate potassium replacement. A proforma was developed by a multidiscplinary team to prompt appropriate investigations, medications, and fluid resuscitation. The proforma was introduced in paper format and electronically, accompanied by an education programme for junior doctors.This intervention has improved prescribing practice and fluid resuscitation for these patients. Length of admission has reduced. Efforts have been made to ensure this change is sustainable in the long term, through involvement of the junior doctors using the proforma at all stages of the project.
Improving the inpatient oncology experience through a new consultant ward round
Authors: Navani Vishal 
Published: October 2013

AbstractRegular consultant ward rounds have been shown to reduce the length of stay and improve the discharge planning for patients (1). To balance the competing demands of outpatient activity and inpatient oncology, it has been difficult to provide specialist care in our hospital. Previously, inpatients were managed primarily by the oncology specialist trainees, who are qualified in internal medicine, with an ad-hoc review by their named consultant. A regular consultant ward round was introduced for the first time on the 7/1/13. Each consultant was timetabled to give a twice weekly morning ward round on a rolling rota.To evaluate this intervention, a retrospective case note analysis was undertaken. This included all patients admitted under oncology for the two months preceding and succeeding the new ward round. For each patient the admission date, time to first consultant review, number of consultant reviews, time to discharge after consultant review, and discharge date was identified. A staff survey also took place. Statistical analysis was performed using Mann-Whitney U or Chi-Squared tests.85 patient episodes met the inclusion criteria. Case notes were available for 63 episodes (74%). The average length of stay significantly decreased from 11 days to three and half days (p<0.05). The time to discharge after first consultant review also significantly decreased from six days to two days (p<0.05). The number of consultant reviews and time to first consultant review remained unchanged (p>0.05). The percentage of patients receiving a consultant review increased, from 54.3% to 71.4%, though this was not statistically significant. However it is likely such a large increase is clinically significant. Medical and nursing staff satisfaction also improved.This study suggests that a regular consultant ward round improves length of stay for patients. This is possibly because an increase in patients received a consultant review and that the treatment and discharge decisions were expedited after such a review.
The term ‘Anthropocene’ in the context of formal geological classification
Authors: Gibbard P. L. , Walker M. J. C. 
Published: October 2013

Abstract
In recent years, ‘Anthropocene’ has been proposed as an informal stratigraphic term to denote the current interval of anthropogenic global environmental change. A case has also been made to formalize it as a series/epoch, based on the recognition of a suitable marker event, such as the start of the Industrial Revolution in northern Europe. For the Anthropocene to merit formal definition, a global signature distinct from that of the Holocene is required that is marked by novel biotic, sedimentary and geochemical change. Although there is clear evidence of anthropogenic effects in geological sequences, it is uncertain whether these trends are sufficiently distinct, consistent and dated for the proposal for a Holocene/Anthropocene boundary to be substantiated. The current view of the Earth-Science community is that it should remain informal. For formal definition a Global Stratigraphic Section and Point (GSSP) is required. Adoption of the term ‘Anthropocene’ will ultimately depend on recognition of a global event horizon. Without this, there is no justification for decoupling the Anthropocene from the Holocene. If the Anthropocene is deemed to have utility, it should be as an informal historical designation rather than a formally defined stratigraphic unit (of whatever status) within the geological timescale.
The Role of Cell Density and Intratumoral Heterogeneity in Multidrug Resistance
Authors: Lavi Orit , Greene James M. , Levy Doron , Gottesman Michael M. 
Published: October 2013

Abstract
Recent data have demonstrated that cancer drug resistance reflects complex biologic factors, including tumor heterogeneity, varying growth, differentiation, apoptosis pathways, and cell density. As a result, there is a need to find new ways to incorporate these complexities in the mathematical modeling of multidrug resistance. Here, we derive a novel structured population model that describes the behavior of cancer cells under selection with cytotoxic drugs. Our model is designed to estimate intratumoral heterogeneity as a function of the resistance level and time. This updated model of the multidrug resistance problem integrates both genetic and epigenetic changes, density dependence, and intratumoral heterogeneity. Our results suggest that treatment acts as a selection process, whereas genetic/epigenetic alteration rates act as a diffusion process. Application of our model to cancer treatment suggests that reducing alteration rates as a first step in treatment causes a reduction in tumor heterogeneity and may improve targeted therapy. The new insight provided by this model could help to dramatically change the ability of clinical oncologists to design new treatment protocols and analyze the response of patients to therapy. Cancer Res; 73(24); 7168–75. ©2013 AACR.
mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1
Authors: Faber Anthony C. , Coffee Erin M. , Costa Carlotta , Dastur Anahita , Ebi Hiromichi , Hata Aaron N. , Yeo Alan T. , Edelman Elena J. , Song Youngchul , Tam Ah Ting , Boisvert Jessica L. , Milano Randy J. , Roper Jatin , Kodack David P. , Jain Rakesh K. , Corcoran Ryan B. , Rivera Miguel N. , Ramaswamy Sridhar , Hung Kenneth E. , Benes Cyril H. , Engelman Jeffrey A. 
Published: October 2013

Abstract
Colorectal cancers harboring KRAS or BRAF mutations are refractory to current targeted therapies. Using data from a high-throughput drug screen, we have developed a novel therapeutic strategy that targets the apoptotic machinery using the BCL-2 family inhibitor ABT-263 (navitoclax) in combination with a TORC1/2 inhibitor, AZD8055. This combination leads to efficient apoptosis specifically in KRAS- and BRAF-mutant but not wild-type (WT) colorectal cancer cells. This specific susceptibility results from TORC1/2 inhibition leading to suppression of MCL-1 expression in mutant, but not WT, colorectal cancers, leading to abrogation of BIM/MCL-1 complexes. This combination strategy leads to tumor regressions in both KRAS-mutant colorectal cancer xenograft and genetically engineered mouse models of colorectal cancer, but not in the corresponding KRAS-WT colorectal cancer models. These data suggest that the combination of BCL-2/BCL-XL inhibitors with TORC1/2 inhibitors constitutes a promising targeted therapy strategy to treat these recalcitrant cancers.
Significance: Effective targeted therapies directed against colorectal cancer with activating mutations in KRAS remain elusive. We have leveraged drug-screen data from a large panel of human colorectal cancers to uncover an effective, rational targeted therapy strategy that has preferential activity in colorectal cancers with KRAS or BRAF mutations. This combination may be developed for clinical testing. Cancer Discov; 4(1); 42–52. ©2013 AACR.
See related commentary by Russo et al., p. 19
This article is highlighted in the In This Issue feature, p. 1
Impact of Local Ablation on Interconnected Channels Within Ventricular Scar
Authors: Tung Roderick , Mathuria Nilesh S. , Nagel Rich , Mandapati Ravi , Buch Eric F. , Bradfield Jason S. , Vaseghi Marmar , Boyle Noel G. , Shivkumar Kalyanam 
Published: October 2013

Background—
The extent to which channels within scar are interconnected is not known. The objective of the study was to evaluate the impact of local ablation of late potentials (LPs) on adjacent and remote areas of slow conduction with simultaneous multipolar mapping.

Methods and Results—
Analysis was performed on consecutive patients referred for ablation of scar-mediated ventricular tachycardia with double ventricular access. Ablation was performed targeting the earliest of LPs visualized on the multipolar catheter, and the impact on later LPs was recorded. In 21 patients, a multipolar catheter placed within scar visualized spatially distinct LPs. Among 39 radiofrequency applications, ablation at earlier LPs had an effect on neighboring and remote LPs in 31 (80%), with delay in 8 (21%), partial elimination in 9 (23%), and complete elimination in 14 (36%). The mean distance where an ablation impact was detected was 17.6±14.7 mm (range, 2–50 mm). Among all patients, 9.7±7.8 radiofrequency applications were delivered to homogenize the targeted scar region with a mean number of 23±12 LPs targeted.

Conclusions—
Ablation can eliminate neighboring and remote areas of slow conduction, suggesting that channels within scar are frequently interconnected. This is the first mechanistic demonstration to show that ablation can modify electrical activity in regions of scar outside of the known radius of an radiofrequency lesion. The targeting of relatively earlier LPs can expedite scar homogenization without the need for extensive ablation of all LPs.
Impact of Atrial Fibrillation on Exercise Capacity in Heart Failure With Preserved Ejection Fraction
Authors: Zakeri Rosita , Borlaug Barry A. , McNulty Steven E. , Mohammed Selma F. , Lewis Gregory D. , Semigran Marc J. , Deswal Anita , LeWinter Martin , Hernandez Adrian F. , Braunwald Eugene , Redfield Margaret M. 
Published: October 2013

Background—

Atrial fibrillation (AF) is common among patients with heart failure and preserved ejection fraction (HFpEF), but its clinical profile and impact on exercise capacity remain unclear. RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF) was a multicenter randomized trial testing the impact of sildenafil on peak V
O
2
in stable outpatients with chronic HFpEF. We sought to compare clinical features and exercise capacity among patients with HFpEF who were in sinus rhythm (SR) or AF.

Methods and Results—

RELAX enrolled 216 patients with HFpEF, of whom 79 (37%) were in AF, 124 (57%) in SR, and 13 in other rhythms. Participants underwent baseline cardiopulmonary exercise testing, echocardiogram, biomarker assessment, and rhythm status assessment before randomization. Patients with AF were older than those in SR but had similar symptom severity, comorbidities, and renal function. β-blocker use and chronotropic indices were also similar. Despite comparable left ventricular size and mass, AF was associated with worse systolic (lower EF, stroke volume, and cardiac index) and diastolic (shorter deceleration time and larger left atria) function compared with SR. Pulmonary artery systolic pressure was higher in AF. Patients with AF had higher N-terminal pro-B-type natriuretic peptide, aldosterone, endothelin-1, troponin I, and C-telopeptide for type I collagen levels, suggesting more severe neurohumoral activation, myocyte necrosis, and fibrosis. Peak V
O
2
was lower in AF, even after adjustment for age, sex, and chronotropic response, and V
E
/V
CO
2
was higher.

Conclusions—
AF identifies an HFpEF cohort with more advanced disease and significantly reduced exercise capacity. These data suggest that evaluation of the impact of different rate or rhythm control strategies on exercise tolerance in patients with HFpEF and AF is warranted.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00763867.
Derivation and Validation of a Risk Standardization Model for Benchmarking Hospital Performance for Health-Related Quality of Life Outcomes After Acute Myocardial Infarction
Authors: Arnold Suzanne V. , Masoudi Frederick A. , Rumsfeld John S. , Li Yan , Jones Philip G. , Spertus John A. 
Published: October 2013

Background—
Before outcomes-based measures of quality can be used to compare and improve care, they must be risk-standardized to account for variations in patient characteristics. Despite the importance of health-related quality of life (HRQL) outcomes among patients with acute myocardial infarction (AMI), no risk-standardized models have been developed.

Methods and Results—

We assessed disease-specific HRQL using the Seattle Angina Questionnaire at baseline and 1 year later in 2693 unselected AMI patients from 24 hospitals enrolled in the Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients’ Health status (TRIUMPH) registry. Using 57 candidate sociodemographic, economic, and clinical variables present on admission, we developed a parsimonious, hierarchical linear regression model to predict HRQL. Eleven variables were independently associated with poor HRQL after AMI, including younger age, previous coronary artery bypass graft surgery, depressive symptoms, and financial difficulties (R
2
=20%). The model demonstrated excellent internal calibration and reasonable calibration in an independent sample of 1890 AMI patients in a separate registry, although the model slightly overpredicted HRQL scores in the higher deciles. Among the 24 TRIUMPH hospitals, 1-year unadjusted HRQL scores ranged from 67–89. After risk-standardization, HRQL score variability narrowed substantially (range=79–83), and the group of hospital performance (bottom 20%/middle 60%/top 20%) changed in 14 of the 24 hospitals (58% reclassification with risk-standardization).

Conclusions—
In this predictive model for HRQL after AMI, we identified risk factors, including economic and psychological characteristics, associated with HRQL outcomes. Adjusting for these factors substantially altered the rankings of hospitals as compared with unadjusted comparisons. Using this model to compare risk-standardized HRQL outcomes across hospitals may identify processes of care that maximize this important patient-centered outcome.