bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lyme Disease Surveillance in New York State: an Assessment of Case Underreporting
Authors: White J. , Noonan‐Toly C. , Lukacik G. , Thomas N. , Hinckley A. , Hook S. , Backenson P. B. 
Published: September 2016

SummaryDespite the mandatory nature of Lyme disease (LD) reporting in New York State (NYS), it is believed that only a fraction of the LD cases diagnosed annually are reported to public health authorities. Lack of complete LD case reporting generally stems from (i) lack of report of provider‐diagnosed cases where supportive laboratory testing is not ordered or results are negative (i.e. provider underreporting) and (ii) incomplete case information (clinical laboratory reporting only with no accompanying clinical information) such that cases are considered ‘suspect’ and not included in national and statewide case counts (i.e. case misclassification). In an attempt to better understand LD underreporting in NYS, a two‐part study was conducted in 2011 using surveillance data from three counties. Case misclassification was assessed by obtaining medical records on suspect cases and reclassifying according to the surveillance case definition. To assess provider underreporting, lists of patients for whom ICD‐9‐CM code 088.81 (LD) had been used were reported to NYS Department of Health (NYSDOH). These lists were matched to the NYSDOH case reporting system, and medical records were requested on patients not previously reported; cases were then classified according to the case definition. When including both provider underreporting and case misclassification, approximately 20% (range 18.4–24.6%) more LD cases were identified in the three‐county study area than were originally reported through standard surveillance. The additional cases represent a minimum percentage of unreported cases; the true percentage of unreported cases is likely higher. Unreported cases were more likely to have a history of erythema migrans (EM) rash and were more likely to be young paediatric cases. Results of the study support the assertion that LD cases are underreported in NYS. Initiatives to increase reporting should highlight the importance of reporting clinically diagnosed EM and be targeted to those providers most likely to diagnose LD, specifically providers treating paediatric patients.
Synaptic transmission at the endbulb of Held deteriorates during age‐related hearing loss
Authors: Xie Ruili , Manis Paul B. 
Published: September 2016

Key points
Synaptic transmission at the endbulb of Held was assessed by whole‐cell patch clamp recordings from auditory neurons in mature (2–4 months) and aged (20–26 months) mice.
Synaptic transmission is degraded in aged mice, which may contribute to the decline in neural processing of the central auditory system during age‐related hearing loss.
The changes in synaptic transmission in aged mice can be partially rescued by improving calcium buffering, or decreasing action potential‐evoked calcium influx.
These experiments suggest potential mechanisms, such as regulating intraterminal calcium, that could be manipulated to improve the fidelity of transmission at the aged endbulb of Held.
AbstractAge‐related hearing loss (ARHL) is associated with changes to the auditory periphery that raise sensory thresholds and alter coding, and is accompanied by alterations in excitatory and inhibitory synaptic transmission, and intrinsic excitability in the circuits of the central auditory system. However, it remains unclear how synaptic transmission changes at the first central auditory synapses during ARHL. Using mature (2–4 months) and old (20–26 months) CBA/CaJ mice, we studied synaptic transmission at the endbulb of Held. Mature and old mice showed no difference in either spontaneous quantal synaptic transmission or low frequency evoked synaptic transmission at the endbulb of Held. However, when challenged with sustained high frequency stimulation, synapses in old mice exhibited increased asynchronous transmitter release and reduced synchronous release. This suggests that the transmission of temporally precise information is degraded at the endbulb during ARHL. Increasing intraterminal calcium buffering with EGTA‐AM or decreasing calcium influx with ω‐agatoxin IVA decreased the amount of asynchronous release and restored synchronous release in old mice. In addition, recovery from depression following high frequency trains was faster in old mice, but was restored to a normal time course by EGTA‐AM treatment. These results suggest that intraterminal calcium in old endbulbs may rise to abnormally high levels during high rates of auditory nerve firing, or that calcium‐dependent processes involved in release are altered with age. These observations suggest that ARHL is associated with a decrease in temporal precision of synaptic release at the first central auditory synapse, which may contribute to perceptual deficits in hearing.
Improving hyperthermia treatment planning for the pelvis by accurate fluid modeling
Authors: Schooneveldt G. , Kok H. P. , Balidemaj E. , Geijsen E. D. , van Ommen F. , Sijbrands J. , Bakker A. , de la Rosette J. J. M. C. H. , Hulshof M. C. C. M. , de Reijke T. M. , Crezee J. 
Published: September 2016

PurposeHyperthermia is an established (neo)adjuvant treatment modality for a number of pelvic malignancies. Optimal treatment of these tumors requires robust treatment planning, but up until now, the urinary bladder was not modeled accurately, making current simulations less reliable. The authors improved the dielectric and thermophysical model of the urinary bladder in their treatment planning system, and showed the improvements using phantom experiments.MethodsThe authors suspended a porcine bladder in muscle tissue equivalent gel and filled it with 120 ml 0.9% saline. The authors heated the phantom during 15 min with their deep hyperthermia device, using clinical settings, and measured the temperature both inside and outside the bladder. The authors simulated the experiment, both using the clinically used treatment planning system, and using the improved model featuring correct dielectric properties for the bladder content and an enhanced thermophysical model, enabling the simulation of convection.ResultsAlthough the dielectric changes have an impact throughout the phantom, the dominant effect is a higher net heat absorption in the bladder. The effects of changing the thermophysical model are limited to the bladder and its surroundings, but result in a very different temperature profile. The temperatures predicted by the simulations using the new bladder model were in much better agreement with the measurements than those predicted by currently used treatment planning system.ConclusionsModeling convection in the urinary bladder is very important for accurate hyperthermia treatment planning in the pelvic area.
Computer aided diagnosis of prostate cancer: A texton based approach
Authors: Rampun Andrik , Tiddeman Bernie , Zwiggelaar Reyer , Malcolm Paul 
Published: September 2016

PurposeIn this paper the authors propose a texton based prostate computer aided diagnosis approach which bypasses the typical feature extraction process such as filtering and convolution which can be computationally expensive. The study focuses the peripheral zone because 75% of prostate cancers start within this region and the majority of prostate cancers arising within this region are more aggressive than those arising in the transitional zone.MethodsFor the model development, square patches were extracted at random locations from malignant and benign regions. Subsequently, extracted patches were aggregated and clustered using k‐means clustering to generate textons that represent both regions. All textons together form a texton dictionary, which was used to construct a texton map for every peripheral zone in the training images. Based on the texton map, histogram models for each malignant and benign tissue samples were constructed and used as a feature vector to train our classifiers. In the testing phase, four machine learning algorithms were employed to classify each unknown sample tissue based on its corresponding feature vector.ResultsThe proposed method was tested on 418 T2‐W MR images taken from 45 patients. Evaluation results show that the best three classifiers were Bayesian network (Az = 92.8% ± 5.9%), random forest (89.5% ± 7.1%), and k‐NN (86.9% ± 7.5%). These results are comparable to the state‐of‐the‐art in the literature.ConclusionsThe authors have developed a prostate computer aided diagnosis method based on textons using a single modality of T2‐W MRI without the need for the typical feature extraction methods, such as filtering and convolution. The proposed method could form a solid basis for a multimodality magnetic resonance imaging based systems.
Re‐examining TG‐142 recommendations in light of modern techniques for linear accelerator based radiosurgery
Authors: Faught Austin M. , Trager Michael , Yin Fang‐Fang , Kirkpatrick John , Adamson Justus 
Published: September 2016

PurposeThe recent development of multifocal stereotactic radiosurgery (SRS) using a single isocenter volumetric modulated arc theory (VMAT) technique warrants a re‐examination of the quality assurance (QA) tolerances for routine mechanical QA recommended by the American Association of Physicists in Medicine Task Group Report Number 142. Multifocal SRS can result in targets with small volumes being at a large off‐axis distance from the treatment isocenter. Consequently, angular errors in the collimator, patient support assembly (PSA), or gantry could have an increased impact on target coverage.MethodsThe authors performed a retrospective analysis of dose deviations caused by systematic errors in PSA, collimator, and gantry angle at the tolerance level for routine linear accelerator QA as recommended by TG‐142. Dosimetric deviations from multifocal SRS plans (N = 10) were compared to traditional single target SRS using dynamic conformal arcs (N = 10). The chief dosimetric quantities used in determining clinical impact were V100% and D99% of the individual planning target volumes and V12Gy of the healthy brain.ResultsInduced errors at tolerance levels showed the greatest change in multifocal SRS target coverage for collimator rotations (±1.0°) with the average changes to V100% and D99% being 5% and 6%, respectively, with maximum changes of 33% and 20%. A reduction in the induced error to half the TG‐142 tolerance (±0.5°) demonstrated similar changes in coverage loss to traditional single target SRS assessed at the recommended tolerance level. The observed change in coverage for multifocal SRS was reduced for gantry errors (±1.0°) at 2% and 4.5% for V100% and D99%, respectively, with maximum changes of 18% and 12%. Minimal change in coverage was noted for errors in PSA rotation.ConclusionsThis study indicates that institutions utilizing a single isocenter VMAT technique for multifocal disease should pay careful attention to the angular mechanical tolerances in designing a robust and complete QA program.
A Model for Transposition of the Colistin Resistance Gene
mcr-1
by IS
Apl1
Authors: Snesrud Erik , He Susu , Chandler Michael , Dekker John P. , Hickman Alison B. , McGann Patrick , Dyda Fred 
Published: September 2016

ABSTRACT

Analysis of
mcr-1
-containing sequences identified a common ∼2,607-bp DNA segment that in many cases is flanked on one or both ends by IS
Apl1
. We present evidence that
mcr-1
is mobilized by an IS
Apl1
composite transposon which has, in some cases, subsequently lost one or both copies of IS
Apl1
. We also show that
mcr-1
can be mobilized in some circumstances by a single upstream copy of IS
Apl1
in conjunction with the remnants of a downstream IS
Apl1
.
Facilitating the Evolution of Esterase Activity from a Promiscuous Enzyme (Mhg) with Catalytic Functions of Amide Hydrolysis and Carboxylic Acid Perhydrolysis by Engineering the Substrate Entrance Tunnel
Authors: Yan Xiaodan , Wang Jianjun , Sun Yu , Zhu Junge , Wu Sheng 
Published: September 2016

ABSTRACT

Promiscuous enzymes are generally considered to be starting points in the evolution of offspring enzymes with more specific or even novel catalytic activities, which is the molecular basis of producing new biological functions. Mhg, a typical α/β fold hydrolase, was previously reported to have both γ-lactamase and perhydrolase activities. However, despite having high structural similarity to and sharing an identical catalytic triad with an extensively studied esterase from
Pseudomonas fluorescens
, this enzyme did not show any esterase activity. Molecular docking and sequence analysis suggested a possible role for the entry of the binding pocket in blocking the entrance tunnel, preventing the ester compounds from entering into the pocket. By engineering the entrance tunnel with only one or two amino acid substitutions, we successfully obtained five esterase variants of Mhg. The variants exhibited a very broad substrate acceptance, hydrolyzing not only the classical
p
-nitrophenol esters but also various types of chiral esters, which are widely used as drug intermediates. Site 233 at the entrance tunnel of Mhg was found to play a pivotal role in modulating the three catalytic activities by adjusting the size and shape of the tunnel, with different amino acid substitutions at this site facilitating different activities. Remarkably, the variant with the L233G mutation was a very specific esterase without any γ-lactamase and perhydrolase activities. Considering the amino acid conservation and differentiation, this site could be a key target for future protein engineering. In addition, we demonstrate that engineering the entrance tunnel is an efficient strategy to regulate enzyme catalytic capabilities.

IMPORTANCE
Promiscuous enzymes can act as starting points in the evolution of novel catalytic activities, thus providing a molecular basis for the production of new biological functions. In this study, we identified a critical amino acid residue (Leu233) at the entry of the substrate tunnel of a promiscuous enzyme, Mhg. We found that substitution of this residue with smaller amino acids such as Gly, Ala, Ser, or Pro endowed the enzyme with novel esterase activity. Different amino acids at this site can facilitate different catalytic activities. These findings exhibited universal significance in this subset of α/β fold hydrolases, including Mhg. Furthermore, we demonstrate that engineering the entrance tunnel is an efficient strategy to evolve new enzyme catalytic capabilities. Our study has important implications for the regulation of enzyme catalytic promiscuity and development of protein engineering methodologies.
The Escherichia coli
rhaSR-PrhaBAD
Inducible Promoter System Allows Tightly Controlled Gene Expression over a Wide Range in Pseudomonas aeruginosa
Authors: Meisner Jeffrey , Goldberg Joanna B. 
Published: September 2016

ABSTRACT

The
araC-ParaBAD
inducible promoter system is tightly controlled and allows gene expression to be modulated over a wide range in
Escherichia coli
, which has led to its widespread use in other bacteria. Although anecdotal evidence suggests that
araC-ParaBAD
is leaky in
Pseudomonas aeruginosa
, neither a thorough analysis of this inducible promoter system in
P. aeruginosa
nor a concerted effort to identify alternatives with improved functionality has been reported. Here, we evaluated the functionality of the
araC-ParaBAD
system in
P. aeruginosa
. Using transcriptional fusions to a
lacZ
reporter gene, we determined that the noninduced expression from
araC-ParaBAD
is high and cannot be reduced by carbon catabolite repression as it can in
E. coli
. Modulating translational initiation by altering ribosome-binding site strength reduced the noninduced activity but also decreased the maximal induced activity and narrowed the induction range. Integrating the inducible promoter system into the posttranscriptional regulatory network that controls catabolite repression in
P. aeruginosa
significantly decreased the noninduced activity and increased the induction range. In addition to these improvements in the functionality of the
araC-ParaBAD
system, we found that the
lacI
q
-
Ptac
and
rhaSR-PrhaBAD
inducible promoter systems had significantly lower noninduced expression and were inducible over a broader range than
araC-ParaBAD
. We demonstrated that noninduced expression from the
araC-ParaBAD
system supported the function of genes involved in antibiotic resistance and tryptophan biosynthesis in
P. aeruginosa
, problems that were avoided with
rhaSR-PrhaBAD. rhaSR-PrhaBAD
is tightly controlled, allows gene expression over a wide range, and represents a significant improvement over
araC-ParaBAD
in
P. aeruginosa
.

IMPORTANCE
We report the shortcomings of the commonly used
Escherichia coli araC-ParaBAD
inducible promoter system in
Pseudomonas aeruginosa
, successfully reengineered it to improve its functionality, and show that the
E. coli
rhaSR-PrhaBAD
system is tightly controlled and allows inducible gene expression over a wide range in
P. aeruginosa
.
Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene (
nkd
) Improves Host Immune Function and Reduces Nosema ceranae Infections
Authors: Li Wenfeng , Evans Jay D. , Huang Qiang , Rodríguez-García Cristina , Liu Jie , Hamilton Michele , Grozinger Christina M. , Webster Thomas C. , Su Songkun , Chen Yan Ping 
Published: September 2016

ABSTRACT

Nosema ceranae
is a new and emerging microsporidian parasite of European honey bees,
Apis mellifera
, that has been implicated in colony losses worldwide. RNA interference (RNAi), a posttranscriptional gene silencing mechanism, has emerged as a potent and specific strategy for controlling infections of parasites and pathogens in honey bees. While previous studies have focused on the silencing of parasite/pathogen virulence factors, we explore here the possibility of silencing a host factor as a mechanism for reducing parasite load. Specifically, we used an RNAi strategy to reduce the expression of a honey bee gene,
naked cuticle
(
nkd
), which is a negative regulator of host immune function. Our studies found that
nkd
mRNA levels in adult bees were upregulated by
N. ceranae
infection (and thus, the parasite may use this mechanism to suppress host immune function) and that ingestion of double-stranded RNA (dsRNA) specific to
nkd
efficiently silenced its expression. Furthermore, we found that RNAi-mediated knockdown of
nkd
transcripts in
Nosema
-infected bees resulted in upregulation of the expression of several immune genes (
Abaecin
,
Apidaecin
,
Defensin-1
, and
PGRP-S2
), reduction of
Nosema
spore loads, and extension of honey bee life span. The results of our studies clearly indicate that silencing the host
nkd
gene can activate honey bee immune responses, suppress the reproduction of
N. ceranae
, and improve the overall health of honey bees. This study represents a novel host-derived therapeutic for honey bee disease treatment that merits further exploration.

IMPORTANCE
Given the critical role of honey bees in the pollination of agricultural crops, it is urgent to develop strategies to prevent the colony decline induced by the infection of parasites/pathogens. Targeting parasites and pathogens directly by RNAi has been proven to be useful for controlling infections in honey bees, but little is known about the disease impacts of RNAi silencing of host factors. Here, we demonstrate that knocking down the honey bee immune repressor-encoding
nkd
gene can suppress the reproduction of
N. ceranae
and improve the overall health of honey bees, which highlights the potential role of host-derived and RNAi-based therapeutics in controlling the infections in honey bees. The information obtained from this study will have positive implications for honey bee disease management practices.
Process quality of diabetes care under favorable access to healthcare: a 2-year longitudinal study using claims data in Japan
Authors: Tanaka Hirokazu , Tomio Jun , Sugiyama Takehiro , Kobayashi Yasuki 
Published: September 2016

ObjectiveTo investigate the process quality of diabetes care provided to patients under universal health insurance coverage.Research design and methodsUsing claim data for 570 363 beneficiaries aged 20–69 years who were covered by Health Insurance Societies between April 2010 and March 2012, we identified patients with type 2 diabetes who made follow-up visits at least every 3 months in the first year (subject-identification year). We assessed patient adherence to follow-up visits in the second year (quality-reporting year), calculated the proportion of patients that completed routine examinations for glycemic control and complications, and evaluated associations between characteristics of patients and quality indicators using multivariable logistic regression models.ResultsWe identified 12 909 patients with diabetes; in the subject-identification year, 1415 (11.0%) had prescriptions for insulin injections, 6049 (46.9%) had prescriptions for oral antihyperglycemic agents, and 5445 (42.2%) had no diabetes-related prescriptions. Among patients using medication, 474 (6.4%) dropped out in the quality-reporting year. The adjusted percentages of quality indicators among patients using oral antihyperglycemic agents were 95.8% for glycated hemoglobin, 35.6% for eye examinations, 15.4% for urine microalbumin excretion, and 90.6% for serum lipids; the percentages among patients taking insulin were the same or higher. Annual testing for glycated hemoglobin was less frequent in patients aged 40–49 years than in patients aged 60–69 years (OR 0.77; 95% CI 0.66 to 0.91). Fewer men than women (OR 0.59; 95% CI 0.54 to 0.64), and fewer patients aged 40–49 years than those aged 60–69 years (OR 0.56; 95% CI 0.50 to 0.63) tended to complete routine eye examinations.ConclusionsScreening for retinopathy and nephropathy was less frequent than required despite favorable conditions for access to healthcare in Japan. Suboptimal quality of care appeared to depend on provider factors as well as patient factors, such as limited access to retinopathy prevention among working-age men with diabetes.
Diagnostic accuracy of the APPY1 Test in patients aged 2–20 years with suspected acute appendicitis presenting to emergency departments
Authors: González del Castillo Juan , Ayuso Francisco Javier , Trenchs Victoria , Martinez Ortiz de Zarate Mikel , Navarro Carmen , Altali Kinda , Fernandez Cristina , Huckins David , Martín-Sánchez Francisco Javier ,   representing INFURG-SEMES group
Published: September 2016

ObjectiveEvaluate the diagnostic accuracy of the APPY1 Test alone and in combination with the Alvarado score (AS) to rule out acute appendicitis (AA) in patients presenting to EDs with abdominal pain suspicious for AA.MethodologyObservational study in a prospective consecutive cohort including all patients from 2 to 20 years with abdominal pain suggestive of AA in four EDs. The APPY1 Test was performed and AS was calculated to determine risk stratification for each patient.Results321 patients enrolled (mean age 11.8 (SD 3.8) years, 52.0% male), with 32.4% low risk, 23.7% intermediate risk and 43.9% high risk according to the AS. 111 (34.6%) had AA, of whom 1 (0.9%) had a false-negative APPY1 Test result. The APPY1 Test had a sensitivity (Se) of 99.1% (95% CI 94.4% to 99.9%), specificity (Sp) of 32.9% (95% CI 26.6% to 39.7%), negative predictive value (NPV) of 98.6% (95% CI 91.2% to 99.9%) and negative likelihood ratio (LHR−) of 0.03 (0.00 to 0.19) in this population. For patients at low risk by AS, the APPY1 Test had a Se of 100% (95% CI 62.9% to 100%), NPV of 100% (95% CI 91.1% to 100%) and LHR− of 0.0 (not calculable), and for patients at intermediate risk by AS, the APPY1 Test had a Se of 94.4% (95% CI 70.6% to 99.7%), NPV of 94.7% (95% CI 71.9% to 99.7%) and LHR− of 0.18 (0.0 to 1.2), respectively.ConclusionsAPPY1 Test is a potentially useful diagnostic tool to rule out AA in this population, with clinical utility primarily in those patients classified as having low clinical risk of appendicitis according to the AS.