bluuebunny/crossref_metadata_2025_split huggingface dataset:
LOPP chemotherapy as a first‐line treatment for dogs with T‐cell lymphoma
Authors: Brown P. M. , Tzannes S. , Nguyen S. , White J. , Langova V. 
Published: May 2017

BackgroundThe aim of this study was to describe the use of a lomustine (CCNU), vincristine, procarbazine and prednisolone (LOPP) protocol used for treatment of chemotherapy naive T‐cell lymphoma patients and to describe the response rate, toxicity and disease‐free interval compared historically to CHOP chemotherapy.Materials and MethodsRetrospective case study of 31 dogs with naïve T‐cell lymphoma treated with a lomustine (CCNU), vincristine, procarbazine and prednisolone (LOPP) protocol.ResultsThirty‐one dogs with T cell lymphoma were treated. The overall response rate was 97%. Of the 30 dogs that had a response to LOPP chemotherapy, the median disease free interval was 176 days (range 0–1745 days). The median overall survival time for this study group was 323 days (range 51–1758 days). All deaths in this study were attributable to lymphoma.Conclusion
LOPP chemotherapy for T cell lymphoma is well tolerated with a low toxicity profile and an excellent overall response rate. This protocol showed minimal toxicity and comparable disease free interval and survival times for canine high grade T cell lymphoma treated with CHOP.
Escalator‐related injuries in 30 dogs (2007–2014)
Authors: Pearson Emma‐Leigh , Whelan Megan , Bracker Kiko 
Published: May 2017

AbstractObjectiveTo describe a population of dogs affected by escalator‐related injuries, and to characterize the types of injuries sustained and describe treatment administered.DesignRetrospective study from March 2007 to November 2014.SettingLarge urban referral and emergency facility.AnimalsThirty client‐owned dogs presenting with injuries acquired while riding an escalator.InterventionsNone.Measurements and Main ResultsAll injuries in this study occurred secondary to entrapment of 1 or more paws in the moving parts of an escalator; 39 paws were injured in total. The median body weight of the patients in this study was 4.25 kg, with 73.3% of the patients weighing less than 10 kg. Fifteen patients (50.0%) were treated surgically, the remainder were managed conservatively. Eight patients (26.7%) underwent digit or partial‐digit amputation. Of the conservatively managed patients, 10 were treated with bandaging of the wounds. Antimicrobials, opiate analgesics, and nonsteroidal anti‐inflammatory drugs were administered in both surgically and conservatively managed patients.ConclusionsWhile uncommon, escalator accidents can result in significant injury to dogs. Measures can be taken to prevent these injuries from occurring, whether through client education, dog training, structural modifications in the escalators themselves, or avoidance of escalators. In the present study, the survival rate of dogs injured on escalators was 100%.
Toxic Electrophiles Induce Expression of the Multidrug Efflux Pump MexEF-OprN in Pseudomonas aeruginosa through a Novel Transcriptional Regulator, CmrA
Authors: Juarez Paulo , Jeannot Katy , Plésiat Patrick , Llanes Catherine 
Published: May 2017

ABSTRACT

The multidrug efflux system MexEF-OprN is produced at low levels in wild-type strains of
Pseudomonas aeruginosa
. However, in so-called
nfxC
mutants, mutational alteration of the gene
mexS
results in constitutive overexpression of the pump, along with increased resistance of the bacterium to chloramphenicol, fluoroquinolones, and trimethoprim. In this study, analysis of
in vitro
-selected chloramphenicol-resistant clones of strain PA14 led to the identification of a new class of MexEF-OprN-overproducing mutants (called
nfxC2
) exhibiting alterations in an as-yet-uncharacterized gene, PA14_38040 (homolog of PA2047 in strain PAO1). This gene is predicted to encode an AraC-like transcriptional regulator and was called
cmrA
(for
c
hlora
m
phenicol
r
esistance
a
ctivator). In
nfxC2
mutants, the mutated CmrA increases its proper gene expression and upregulates the operon
mexEF-oprN
through MexS and MexT, resulting in a multidrug resistance phenotype without significant loss in bacterial virulence. Transcriptomic experiments demonstrated that CmrA positively regulates a small set of 11 genes, including PA14_38020 (homolog of PA2048), which is required for the MexS/T-dependent activation of
mexEF-oprN
. PA2048 codes for a protein sharing conserved domains with the quinol monooxygenase YgiN from
Escherichia coli
. Interestingly, exposure of strain PA14 to toxic electrophilic molecules (glyoxal, methylglyoxal, and cinnamaldehyde) strongly activates the CmrA pathway and upregulates MexEF-OprN and, thus, increases the resistance of
P. aeruginosa
to the pump substrates. A picture emerges in which MexEF-OprN is central in the response of the pathogen to stresses affecting intracellular redox homeostasis.
ERG11
Gene Mutations and
MDR1
Upregulation Confer Pan-Azole Resistance in Candida tropicalis Causing Disseminated Candidiasis in an Acute Lymphoblastic Leukemia Patient on Posaconazole Prophylaxis
Authors: You Liangshun , Qian Wenbin , Yang Qing , Mao Liping , Zhu Li , Huang Xianbo , Jin Jie , Meng Haitao 
Published: May 2017

ABSTRACT

In this study, we present a rare case of fatal breakthrough
Candida tropicalis
infection in a patient with acute lymphoblastic leukemia (ALL) while on posaconazole prophylaxis. Then, we explore the mechanisms underlying azole resistance by focusing on enhanced efflux pumps and changes in the azole target enzyme Erg11p, which was encoded by the ERG11 gene. Our study demonstrates that Y132C substitution of Erg11p combined with MDR1 overexpression may be the pan-azole resistance mechanisms in
Candida tropicalis
.
MCR-1 and OXA-48
In Vivo
Acquisition in KPC-Producing Escherichia coli after Colistin Treatment
Authors: Beyrouthy Racha , Robin Frederic , Lessene Aude , Lacombat Igor , Dortet Laurent , Naas Thierry , Ponties Valérie , Bonnet Richard 
Published: May 2017

ABSTRACT

The spread of
mcr-1
-encoding plasmids into carbapenem-resistant
Enterobacteriaceae
raises concerns about the emergence of untreatable bacteria. We report the acquisition of
mcr-1
in a carbapenem-resistant
Escherichia coli
strain after a 3-week course of colistin in a patient repatriated to France from Portugal. Whole-genome sequencing revealed that the
Klebsiella pneumoniae
carbapenemase-producing
E. coli
strain acquired two plasmids, an IncL OXA-48-encoding plasmid and an IncX4
mcr-1
-encoding plasmid. This is the first report of
mcr-1
in carbapenemase-encoding bacteria in France.
Genome-Wide Survey of Pseudomonas aeruginosa PA14 Reveals a Role for the Glyoxylate Pathway and Extracellular Proteases in the Utilization of Mucin
Authors: Flynn Jeffrey M. , Phan Chi , Hunter Ryan C. 
Published: May 2017

ABSTRACT

Chronic airway infections by the opportunistic pathogen
Pseudomonas aeruginosa
are a major cause of mortality in cystic fibrosis (CF) patients. Although this bacterium has been extensively studied for its virulence determinants, biofilm growth, and immune evasion mechanisms, comparatively little is known about the nutrient sources that sustain its growth
in vivo
. Respiratory mucins represent a potentially abundant bioavailable nutrient source, although we have recently shown that canonical pathogens inefficiently use these host glycoproteins as a growth substrate. However, given that
P. aeruginosa
, particularly in its biofilm mode of growth, is thought to grow slowly
in vivo
, the inefficient use of mucin glycoproteins may be relevant to its persistence within the CF airways. To this end, we used whole-genome fitness analysis, combining transposon mutagenesis with high-throughput sequencing, to identify genetic determinants required for
P. aeruginosa
growth using intact purified mucins as a sole carbon source. Our analysis reveals a biphasic growth phenotype, during which the glyoxylate pathway and amino acid biosynthetic machinery are required for mucin utilization. Secondary analyses confirmed the simultaneous liberation and consumption of acetate during mucin degradation and revealed a central role for the extracellular proteases LasB and AprA. Together, these studies describe a molecular basis for mucin-based nutrient acquisition by
P. aeruginosa
and reveal a host-pathogen dynamic that may contribute to its persistence within the CF airways.
Mutations in the β-Subunit of the RNA Polymerase Impair the Surface-Associated Motility and Virulence of Acinetobacter baumannii
Authors: Pérez-Varela María , Corral Jordi , Vallejo Juan Andrés , Rumbo-Feal Soraya , Bou Germán , Aranda Jesús , Barbé Jordi 
Published: May 2017

ABSTRACT

Acinetobacter baumannii
is a major cause of antibiotic-resistant nosocomial infections worldwide. In this study, several rifampin-resistant spontaneous mutants obtained from the
A. baumannii
ATCC 17978 strain that differed in their point mutations in the
rpoB
gene, encoding the β-subunit of the RNA polymerase, were isolated. All the mutants harboring amino acid substitutions in position 522 or 540 of the RpoB protein were impaired in surface-associated motility and had attenuated virulence in the fertility model of
Caenorhabditis elegans
. The transcriptional profile of these mutants included six downregulated genes encoding proteins homologous to transporters and metabolic enzymes widespread among
A. baumannii
clinical isolates. The construction of knockout mutants in each of the six downregulated genes revealed a significant reduction in the surface-associated motility and virulence of four of them in the
A. baumannii
ATCC 17978 strain, as well as in the virulent clinical isolate MAR002. Taken together, our results provide strong evidence of the connection between motility and virulence in this multiresistant nosocomial pathogen.
An RpoHI-Dependent Response Promotes Outgrowth after Extended Stationary Phase in the Alphaproteobacterium Rhodobacter sphaeroides
Authors: Remes B. , Rische-Grahl T. , Müller K. M. H. , Förstner K. U. , Yu Sung-Huan , Weber L. , Jäger A. , Peuser V. , Klug G. 
Published: May 2017

ABSTRACT

Under unfavorable growth conditions, bacteria enter stationary phase and can maintain cell viability over prolonged periods with no increase in cell number. To obtain insights into the regulatory mechanisms that allow bacteria to resume growth when conditions become favorable again (outgrowth), we performed global transcriptome analyses at different stages of growth for the alphaproteobacterium
Rhodobacter sphaeroides
. The majority of genes were not differentially expressed across growth phases. After a short stationary phase (about 20 h after growth starts to slow down), only 7% of the genes showed altered expression (fold change of >1.6 or less than −1.6, corresponding to a log
2
fold change of >0.65 or less than −0.65, respectively) compared to expression at exponential phase. Outgrowth induced a distinct response in gene expression which was strongly influenced by the length of the preceding stationary phase. After a long stationary phase (about 64 h after growth starts to slow down), a much larger number of genes (15.1%) was induced in outgrowth than after a short stationary phase (1.7%). Many of those genes are known members of the RpoHI/RpoHII regulons and have established functions in stress responses. A main effect of RpoHI on the transcriptome in outgrowth after a long stationary phase was confirmed. Growth experiments with mutant strains further support an important function in outgrowth after prolonged stationary phase for the RpoHI and RpoHII sigma factors.

IMPORTANCE
In natural environments, the growth of bacteria is limited mostly by lack of nutrients or other unfavorable conditions. It is important for bacterial populations to efficiently resume growth after being in stationary phase, which may last for long periods. Most previous studies on growth-phase-dependent gene expression did not address outgrowth after stationary phase. This study on growth-phase-dependent gene regulation in a model alphaproteobacterium reveals, for the first time, that the length of the stationary phase strongly impacts the transcriptome during outgrowth. The alternative sigma factors RpoHI and RpoHII, which are important regulators of stress responses in alphaproteobacteria, play a major role during outgrowth following prolonged stationary phase. These findings provide the first insight into the regulatory mechanisms enabling efficient outgrowth.
Motor and Sensory Cortical Changes after Contralateral Cervical Seventh Nerve Root (CC7) Transfer in Patients with Brachial Plexus Injuries
Authors: Kakinoki Ryosuke , Duncan Scott F.M. , Ikeguchi Ryosuke , Ohta Souichi , Nankaku Manabu , Sakai Hiroshi , Noguchi Takashi , Kaizawa Yukitoshi , Akagi Masao 
Published: May 2017

Background: Previous animal studies demonstrated that the sensory and motor functions in ipsilesional upper limbs that had been reconstructed by CC7 transfer eventually associated with the contralesional brain cortices that had originally mediated the functions of the ipsilesional upper limbs before brachial plexus injury (BPI). Our hypothesis was that the same findings would be seen in humans.Methods: Four patients with total BPI treated with CC7 transfer were included. Changes in the locations of the activated areas in the primary motor (M1) and somatosensory (S1) cortices corresponding to the motor outputs to and sensory inputs from the ipsilesional limbs were investigated using functional near-infrared spectroscopy (fNIRS) 2–3 years and 6–7 years after surgery.Results: One patient was excluded from the evaluation of motor function after CC7 transfer. The motor and sensory functions of the ipsilesional upper limb in all patients were still controlled by the ipsilesional brain hemisphere 2–3 years after CC7 transfer. The reconstructed motions of the ipsilesional upper limbs correlated with the contralesional M1 in one patient and the bilateral M1s in another patient (both of whom demonstrated good motor recovery in the ipsilesional upper limbs) and with the ipsilesional M1 in a third patient with poor motor recovery in the ipsilesional upper limb. Sensory stimulation of the ipsilesional hands 6–7 years after CC7 transfer activated the contralesional S1 in two patients who achieved good sensory recovery in the ipsilesional hands but activated the ipsilesional S1 in the other two patients with poor sensory recovery of the ipsilesional hands.Conclusions: Transhemispheric transposition of the activated brain cortices associated with the recovery of motor and sensory functions of the ipsilesional upper limbs was seen in patients with CC7 transfer as has been reported for animal models of CC7 transfer.
A Protocol for Evaluation and Rehabilitation of Distal Radius Fractures Using Sensorimotor Input: A Case Series
Authors: Wollstein Ronit , Michael Dafna , Harel Hani 
Published: May 2017

Background: Proprioception and sensorimotor input are used to treat neurological and joint injuries. Following distal radius fractures (DRF) there is a temporary loss of proprioception that should be addressed. We created a protocol for evaluation, and a treatment plan following wrist surgery that is based on proprioceptive and sensorimotor input. We describe a series of patients undergoing surgery for DRF that were evaluated and treated with these protocols. Methods: Both evaluation and treatment protocols included comprehensive sensorimotor procedures performed with eyes open and closed. These included Semmes- Weinstein, static and moving 2-point discrimination, vibration, temperature testing, Moberg pick-up- test, stereognosis and proprioception. Results: A series of twelve patients was evaluated and treated with the protocol following surgical treatment for DRF. Patients demonstrated significant sensorimotor deficits, which improved utilizing the comprehensive sensorimotor treatment protocol. Conclusions: Further study is necessary to validate the results of this pilot series. Use of proprioception and sensorimotor input may improve outcomes of rehabilitation following DRF.
Symmetric Peripheral Running Sutures are Superior to Asymmetric Peripheral Running Sutures for Increasing the Tendon Strength in Flexor Tendon Repair
Authors: Takeuchi N. , Okada T. , Kozono N. , Shimoto T. , Higaki H. , Iwamoto Y. 
Published: May 2017

Background: The fatigue strength of three peripheral suture techniques for flexor tendon repair was compared by cyclic loading of the repairs in the porcine flexor digitorum tendon. Methods: Thirty-six tendons were sutured using only peripheral sutures with 6-0 Nylon. An initial cyclic load of 10 N for 500 cycles was applied and increased by 10 N for an additional 500 cycles at each new load until rupture. Results: The fatigue strength of the symmetric running peripheral suture was 85.0% and 144.8% greater than that of the two kinds of the asymmetric running peripheral sutures. Conclusions: Symmetric running sutures can enhance the suture strength and appears to be a useful technique for increasing the strength of the peripheral suture.
Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study)
Authors: Caan Bette J. , Meyerhardt Jeffrey A. , Kroenke Candyce H. , Alexeeff Stacey , Xiao Jingjie , Weltzien Erin , Feliciano Elizabeth Cespedes , Castillo Adrienne L. , Quesenberry Charles P. , Kwan Marilyn L. , Prado Carla M. 
Published: May 2017

Abstract
Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival.
Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan–Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I–III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer–specific mortality (CRCsM).
Results: Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09–1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05–2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and &lt;30 kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of overall mortality due to either low muscle or high adiposity.
Conclusions: Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker.
Impact: Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008–15. ©2017 AACR.
Studying Religion and Trying Theological Applications
Authors: Oviedo Lluis 
Published: May 2017

AbstractJohn Shook’s paperAre People Born to be Believers?raises many questions, for the scientific study of religion and for philosophy and theology. For reasons of convenience this response distinguishes in the target article between three quite different issues and deals with them separately: first issue concerns the supposed innateness of religious beliefs, or some precursor of them; second, the possible theological application that such thesis could entail; and third, a more general and methodological issue, concerns the feasibility of a scientific knowledge about religion that can be disentangled from other sources of religious insight
Lucky Triune Brain
Authors: Pogliano Claudio 
Published: May 2017

The triune brain idea has been rated as the most influential in post-war neuroscience. The first part of this article seeks to retrace its genesis and development through the vicissitudes of the research conducted by Paul D. MacLean (1913–2007). Ten years have passed since his death: despite the loss of scientific credit, the apparent simplicity of his tripartite theory continues to exert a certain popular appeal. In the second part of the article an attempt is made to figure out how the transfer from the laboratory to public fruition could happen. The man initially responsible for the operation was MacLean himself, then aided by a few followers who had the means to spread his message of salvation. Against the background of the Cold War, and while Western culture started to realize the threat posed by overpopulation, pollution, and the exhaustion of critical resources, they deluded themselves that “knowing the brain” might suggest new and more effective approaches to the troubles of the oncoming end of the century. Consulting MacLean’s papers in the archives at the National Library of Medicine (Bethesda, MD) has been essential to this historical reconstruction.
It Blinks, It Thinks?
Authors: Lysen Flora 
Published: May 2017

This article traces attempts in the 1930s to create a spatio-temporal model of the active, living brain. Images and models of electric, illuminated displays – derived from electro-technology and engineering – allowed for a changing imaginary of a brain that was immediately accessible. The example of the Luminous Brain Model, a three-dimensional science education model, demonstrates how the visual language of illumination could serve as a flexible rhetorical tool that offered sensations of liveliness to modern viewers and promised to show a transparent view of a dynamic brain. Alternatively, various scientists in the 1930s used the analogy of the brain as an illuminated electric news ticker to conceptualize temporal patterns of changing brain activity, thus drawing the brain into a new metropolitan sphere of material surfaces with real-time mediation. These two historical imaginaries of blinking brains reveal new trajectories of the ‘metaphorical circuits’ through which technology and cerebral biology are mutually articulated.