bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laparoscopic Evaluation of the Epiploic Foramen after Celiotomy for Epiploic Foramen Entrapment in the Horse
Authors: van Bergen Thomas , Wiemer Peter , Schauvliege Stijn , Paulussen Ellen , Ugahary Franz , Martens Ann 
Published: June 2016

ObjectivesTo evaluate the epiploic foramen using laparoscopy in horses previously treated for epiploic foramen entrapment to determine if spontaneous epiploic foramen closure had occurred.Study DesignNon‐consecutive case series.AnimalsSeven horses.MethodsThe epiploic foramen was inspected by right flank laparoscopy between 35 and 71 days after successful surgical treatment for epiploic foramen entrapment. Data were collected on the presence of behavior vices, details of surgery for epiploic foramen entrapment (time from colic onset to surgery, site and length of entrapped intestine, direction of entrapment, compromise of the intestine, intestine resected), the time between surgery for epiploic foramen entrapment and laparoscopy, and the laparoscopic appearance of the epiploic foramen. If the epiploic foramen was open, a mesh was introduced to obliterate the epiploic foramen (Foramen Epiploicum Mesh Closure [FEMC]). Clinical progress of the horses was followed by owner telephone interview at 1 and 4 months after laparoscopy, and a final interview between 135 and 282 days after laparoscopy. Owners were questioned on specific postoperative complications and the exercise level of the horse.ResultsAt laparoscopy, 3/7 horses had complete closure of the epiploic foramen by dense fibrous tissue. The FEMC was performed in 4 horses without major complications. Postoperative colic episodes were recorded in 3 horses, all of them displaying windsucking/cribbing behavior.ConclusionLaparoscopic evaluation after celiotomy for epiploic foramen entrapment revealed spontaneous closure of the epiploic foramen in 3/7 horses. This finding could explain the reported low recurrence rate after surgical treatment for epiploic foramen entrapment.
Recombination in liquid‐filled ionization chambers beyond the Boag limit
Authors: Brualla‐González L. , Aguiar P. , González‐Castaño D. M. , Gómez F. , Roselló J. , Pombar M. , Pardo‐Montero J. 
Published: June 2016

Purpose:The high mass density and low mobilities of charge carriers can cause important recombination in liquid‐filled ionization chambers (LICs). Saturation correction methods have been proposed for LICs. Correction methods for pulsed irradiation are based on Boag equation. However, Boag equation assumes that the charge ionized by one pulse is fully collected before the arrival of the next pulse. This condition does not hold in many clinical beams where the pulse repetition period may be shorter than the charge collection time, causing overlapping between charge carriers ionized by different pulses, and Boag equation is not applicable there. In this work, the authors present an experimental and numerical characterization of collection efficiencies in LICs beyond the Boag limit, with overlapping between charge carriers ionized by different pulses.Methods:The authors have studied recombination in a LIC array for different dose‐per‐pulse, pulse repetition frequency, and polarization voltage values. Measurements were performed in a Truebeam Linac using FF and FFF modalities. Dose‐per‐pulse and pulse repetition frequency have been obtained by monitoring the target current with an oscilloscope. Experimental collection efficiencies have been obtained by using a combination of the two‐dose‐rate method and ratios to the readout of a reference chamber (CC13, IBA). The authors have also used numerical simulation to complement the experimental data.Results:The authors have found that overlap significantly increases recombination in LICs, as expected. However, the functional dependence of collection efficiencies on the dose‐per‐pulse does not change (a linear dependence has been observed in the near‐saturation region for different degrees of overlapping, the same dependence observed in the nonoverlapping scenario). On the other hand, the dependence of collection efficiencies on the polarization voltage changes in the overlapping scenario and does not follow that of Boag equation, the reason being that changing the polarization voltage also affects the charge collection time, thus changing the amount of overlapping.Conclusions:These results have important consequences for saturation correction methods for LICs. On one hand, the two‐dose‐rate method, which relies on the functional dependence of the collection efficiencies on dose‐per‐pulse, can also be used in the overlapping situation, provided that the two measurements needed to feed the method are performed at the same pulse repetition frequency (monitor unit rate). This result opens the door to computing collection efficiencies in LICs in many clinical setups where charge overlap in the LIC exists. On the other hand, correction methods based on the voltage‐dependence of Boag equation like the three‐voltage method or the modified two‐voltage method will not work in the overlapping scenario due to the different functional dependence of collection efficiencies on the polarization voltage.
Investigation of practical initial attenuation image estimates in TOF‐MLAA reconstruction for PET/MR
Authors: Cheng Ju‐Chieh (Kevin) , Salomon Andre , Yaqub Maqsood , Boellaard Ronald 
Published: June 2016

Purpose:Time‐of‐flight joint attenuation and activity positron emission tomography reconstruction requires additional calibration (scale factors) or constraints during or post‐reconstruction to produce a quantitative μ‐map. In this work, the impact of various initializations of the joint reconstruction was investigated, and the initial average mu‐value (IAM) method was introduced such that the forward‐projection of the initial μ‐map is already very close to that of the reference μ‐map, thus reducing/minimizing the offset (scale factor) during the early iterations of the joint reconstruction. Consequently, the accuracy and efficiency of unconstrained joint reconstruction such as time‐of‐flight maximum likelihood estimation of attenuation and activity (TOF‐MLAA) can be improved by the proposed IAM method.Methods:2D simulations of brain and chest were used to evaluate TOF‐MLAA with various initial estimates which include the object filled with water uniformly (conventional initial estimate), bone uniformly, the average μ‐value uniformly (IAM magnitude initialization method), and the perfect spatial μ‐distribution but with a wrong magnitude (initialization in terms of distribution). 3D gate simulation was also performed for the chest phantom under a typical clinical scanning condition, and the simulated data were reconstructed with a fully corrected list‐mode TOF‐MLAA algorithm with various initial estimates. The accuracy of the average μ‐values within the brain, chest, and abdomen regions obtained from the MR derived μ‐maps was also evaluated using computed tomography μ‐maps as the gold‐standard.Results:The estimated μ‐map with the initialization in terms of magnitude (i.e., average μ‐value) was observed to reach the reference more quickly and naturally as compared to all other cases. Both 2D and 3D gate simulations produced similar results, and it was observed that the proposed IAM approach can produce quantitative μ‐map/emission when the corrections for physical effects such as scatter and randoms were included. The average μ‐value obtained from MR derived μ‐map was accurate within 5% with corrections for bone, fat, and uniform lungs.Conclusions:The proposed IAM‐TOF‐MLAA can produce quantitative μ‐map without any calibration provided that there are sufficient counts in the measured data. For low count data, noise reduction and additional regularization/rescaling techniques need to be applied and investigated. The average μ‐value within the object is prior information which can be extracted from MR and patient database, and it is feasible to obtain accurate average μ‐value using MR derived μ‐map with corrections as demonstrated in this work.
Changes in Passive Properties of the Gastrocnemius Muscle–Tendon Unit During a 4-Week Routine Static-Stretching Program
Authors: Nakamura Masatoshi , Ikezoe Tome , Umegaki Hiroki , Kobayashi Takuya , Nishishita Satoru , Ichihashi Noriaki 
Published: June 2016

Context:Static stretching (SS) is commonly performed in a warm-up routine to increase joint range of motion (ROM) and to decrease muscle stiffness. However, the time course of changes in ankle-dorsiflexion (DF) ROM and muscle stiffness during a routine SS program is unclear.Objective:To investigate changes in ankle-DF ROM, passive torque at DF ROM, and muscle stiffness during a routine SS program performed 3 times weekly for 4 wk.Design:A quasi-randomized controlled-trial design.Participants:The subjects comprised 24 male volunteers (age 23.8 ± 2.3 y, height 172.0 ± 4.3 cm, body mass 63.1 ± 4.5 kg) randomly assigned to either a group performing a 4-wk stretching program (SS group) or a control group.Main Outcome Measures:DF ROM, passive torque, and muscle stiffness were measured during passive ankle dorsiflexion in both groups using a dynamometer and ultrasonography once weekly during the 4-wk intervention period.Results:In the SS group, DF ROM and passive torque at DF ROM significantly increased after 2, 3, and 4 wk compared with the initial measurements. Muscle stiffness also decreased significantly after 3 and 4 wk in the SS group. However, there were no significant changes in the control group.Conclusions:Based on these results, the SS program effectively increased DF ROM and decreased muscle stiffness. Furthermore, an SS program of more than 2 wk duration effectively increased DF ROM and changed the stretch tolerance, and an SS program more than 3 wk in duration effectively decreased muscle stiffness.
Efficacy of the Novel Antibiotic POL7001 in Preclinical Models of Pseudomonas aeruginosa Pneumonia
Authors: Cigana Cristina , Bernardini Francesca , Facchini Marcella , Alcalá-Franco Beatriz , Riva Camilla , De Fino Ida , Rossi Alice , Ranucci Serena , Misson Pauline , Chevalier Eric , Brodmann Maj , Schmitt Michel , Wach Achim , Dale Glenn E. , Obrecht Daniel , Bragonzi Alessandra 
Published: June 2016

ABSTRACT

The clinical development of antibiotics with a new mode of action combined with efficient pulmonary drug delivery is a priority against untreatable
Pseudomonas aeruginosa
lung infections. POL7001 is a macrocycle antibiotic belonging to the novel class of protein epitope mimetic (PEM) molecules with selective and potent activity against
P. aeruginosa
. We investigated ventilator-associated pneumonia (VAP) and cystic fibrosis (CF) as indications of the clinical potential of POL7001 to treat
P. aeruginosa
pulmonary infections. MICs of POL7001 and comparators were measured for reference and clinical
P. aeruginosa
strains. The therapeutic efficacy of POL7001 given by pulmonary administration was evaluated in murine models of
P. aeruginosa
acute and chronic pneumonia. POL7001 showed potent
in vitro
activity against a large panel of
P. aeruginosa
isolates from CF patients, including multidrug-resistant (MDR) isolates with adaptive phenotypes such as mucoid or hypermutable phenotypes. The efficacy of POL7001 was demonstrated in both wild-type and CF mice. In addition to a reduced bacterial burden in the lung, POL7001-treated mice showed progressive body weight recovery and reduced levels of inflammatory markers, indicating an improvement in general condition. Pharmacokinetic studies indicated that POL7001 reached significant concentrations in the lung after pulmonary administration, with low systemic exposure. These results support the further evaluation of POL7001 as a novel therapeutic agent for the treatment of
P. aeruginosa
pulmonary infections.
Role of
gyrB
Mutations in Pre-extensively and Extensively Drug-Resistant Tuberculosis in Thai Clinical Isolates
Authors: Disratthakit Areeya , Prammananan Therdsak , Tribuddharat Chanwit , Thaipisuttikul Iyarit , Doi Norio , Leechawengwongs Manoon , Chaiprasert Angkana 
Published: June 2016

ABSTRACT

DNA gyrase mutations are a major cause of quinolone resistance in
Mycobacterium tuberculosis
. We therefore conducted the first comprehensive study to determine the diversity of gyrase mutations in pre-extensively drug-resistant (pre-XDR) (
n
= 71) and extensively drug-resistant (XDR) (
n
= 30) Thai clinical tuberculosis (TB) isolates. All pre-XDR-TB and XDR-TB isolates carried at least one mutation within the quinolone resistance-determining region of GyrA (G88A [1.1%], A90V [17.4%], S91P [1.1%], or D94A/G/H/N/V/Y [72.7%]) or GyrB (D533A [1.1%], N538D [1.1%], or E540D [2.2%]). MIC and DNA gyrase supercoiling inhibition assays were performed to determine the role of gyrase mutations in quinolone resistance. Compared to the MICs against
M. tuberculosis
H37Rv, the levels of resistance to all quinolones tested in the isolates that carried GyrA-D94G or GyrB-N538D (8- to 32-fold increase) were significantly higher than those in isolates bearing GyrA-D94A or GyrA-A90V (2- to 8-fold increase) (
P
< 0.01). Intriguingly, GyrB-E540D led to a dramatic resistance to later-generation quinolones, including moxifloxacin, gatifloxacin, and sparfloxacin (8- to 16-fold increases in MICs and 8.3- to 11.2-fold increases in 50% inhibitory concentrations [IC
50
s]). However, GyrB-E540D caused low-level resistance to early-generation quinolones, including ofloxacin, levofloxacin, and ciprofloxacin (2- to 4-fold increases in MICs and 1.5- to 2.0-fold increases in IC
50
s). In the present study, DC-159a was the most active antituberculosis agent and was little affected by the gyrase mutations described above. Our findings suggest that although they are rare,
gyrB
mutations have a notable role in quinolone resistance, which may provide clues to the molecular basis of estimating quinolone resistance levels for drug and dose selection.
The Redox Cycler Plasmodione Is a Fast-Acting Antimalarial Lead Compound with Pronounced Activity against Sexual and Early Asexual Blood-Stage Parasites
Authors: Ehrhardt Katharina , Deregnaucourt Christiane , Goetz Alice-Anne , Tzanova Tzvetomira , Gallo Valentina , Arese Paolo , Pradines Bruno , Adjalley Sophie H. , Bagrel Denyse , Blandin Stephanie , Lanzer Michael , Davioud-Charvet Elisabeth 
Published: June 2016

ABSTRACT

Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent
in vitro
and
in vivo
activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox cyclers—a strategy that is broadly recognized for the development of new antimalarial agents. Here we report a detailed parasitological characterization of the
in vitro
activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intraerythrocytic stages of the human malaria parasite
Plasmodium falciparum
. We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intraerythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common mechanisms of resistance to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a high killing speed, as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that plasmodione is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents.
Latency-Associated Nuclear Antigen E3 Ubiquitin Ligase Activity Impacts Gammaherpesvirus-Driven Germinal Center B Cell Proliferation
Authors: Cerqueira Sofia A. , Tan Min , Li Shijun , Juillard Franceline , McVey Colin E. , Kaye Kenneth M. , Simas J. Pedro 
Published: June 2016

ABSTRACTViruses have evolved mechanisms to hijack components of cellular E3 ubiquitin ligases, thus modulating the ubiquitination pathway. However, the biological relevance of such mechanisms for viral pathogenesisin vivoremains largely unknown. Here, we utilized murid herpesvirus 4 (MuHV-4) infection of mice as a model system to address the role of MuHV-4 latency-associated nuclear antigen (mLANA) E3 ligase activity in gammaherpesvirus latent infection. We show that specific mutations in the mLANA SOCS box (V199A, V199A/L202A, or P203A/P206A) disrupted mLANA's ability to recruit Elongin C and Cullin 5, thereby impairing the formation of the Elongin BC/Cullin 5/SOCS (EC5SmLANA) complex and mLANA's E3 ligase activity on host NF-κB and Myc. Although these mutations resulted in considerably reduced mLANA binding to viral terminal repeat DNA as assessed by electrophoretic mobility shift assay (EMSA), the mutations did not disrupt mLANA's ability to mediate episome persistence.In vivo, MuHV-4 recombinant viruses bearing these mLANA SOCS box mutations exhibited a deficit in latency amplification in germinal center (GC) B cells. These findings demonstrate that the E3 ligase activity of mLANA contributes to gammaherpesvirus-driven GC B cell proliferation. Hence, pharmacological inhibition of viral E3 ligase activity through targeting SOCS box motifs is a putative strategy to control gammaherpesvirus-driven lymphoproliferation and associated disease.IMPORTANCEThe gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause lifelong persistent infection and play causative roles in several human malignancies. Colonization of B cells is crucial for virus persistence, and access to the B cell compartment is gained by virus-driven proliferation in germinal center (GC) B cells. Infection of B cells is predominantly latent, with the viral genome persisting as a multicopy episome and expressing only a small subset of viral genes. Here, we focused on latency-associated nuclear antigen (mLANA) encoded by murid herpesvirus-4 (MuHV-4), which exhibits homology in sequence, structure, and function to KSHV LANA (kLANA), thereby allowing the study of LANA-mediated pathogenesis in mice. Our experiments show that mLANA's E3 ubiquitin ligase activity is necessary for efficient expansion of latency in GC B cells, suggesting that the development of pharmacological inhibitors of LANA E3 ubiquitin ligase activity may allow strategies to interfere with gammaherpesvirus-driven lymphoproliferation and associated disease.
Bordetella pertussis
Authors: Nieves Delma J. , Heininger Ulrich 
Published: June 2016

ABSTRACT

Pertussis is a highly infectious vaccine-preventable cough illness that continues to be a significant source of morbidity and mortality around the world. The majority of human illness is caused by
Bordetella pertussis
, and some is caused by
Bordetella parapertussis
.
Bordetella
is a Gram-negative, pleomorphic, aerobic coccobacillus. In the past several years, even countries with high immunization rates in early childhood have experienced rises in pertussis cases. Reasons for the resurgence of reported pertussis may include molecular changes in the organism and increased awareness and diagnostic capabilities, as well as lessened vaccine efficacy and waning immunity. The most morbidity and mortality with pertussis infection is seen in infants too young to benefit from immunization. Severe infection requiring hospitalization, including in an intensive care setting, is mostly seen in those under 3 months of age. As a result, research and public health actions have been aimed at better understanding and reducing the spread of
Bordetella pertussis
. Studies comparing the cost benefit of cocooning strategies versus immunization of pregnant women have been favorable towards immunizing pregnant women. This strategy is expected to prevent a larger number of pertussis cases, hospitalizations, and deaths in infants <1 year old while also being cost-effective. Studies have demonstrated that the source of infection in infants usually is a family member. Efforts to immunize children and adults, in particular pregnant women, need to remain strong.
Artemisinin-Resistant
Plasmodium falciparum
Malaria
Authors: Fairhurst Rick M. , Dondorp Arjen M. 
Published: June 2016

ABSTRACT

For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant
Plasmodium falciparum
malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins, the world’s most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs)—the first-line treatments for malaria—are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical,
in vitro
, genomics, and transcriptomics studies in SEA have defined
in vivo
and
in vitro
phenotypes of artemisinin resistance, identified its causal genetic determinant, explored its molecular mechanism, and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early-ring-stage parasites
in vitro
; is caused by single nucleotide polymorphisms in the parasite’s
K13
gene, is associated with an upregulated “unfolded protein response” pathway that may antagonize the pro-oxidant activity of artemisinins, and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where
K13
mutations are prevalent, test whether new combinations of currently available drugs cure ACT failures, and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to sub-Saharan Africa, where the world’s malaria transmission, morbidity, and mortality rates are highest.