bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents
Authors: Bengtsson-Palme Johan , Angelin Martin , Huss Mikael , Kjellqvist Sanela , Kristiansson Erik , Palmgren Helena , Larsson D. G. Joakim , Johansson Anders 
Published: August 2015

ABSTRACTPrevious studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance ofProteobacteriain 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producingEscherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.
RapidIn VitroEvolution of Human Cytomegalovirus UL56 Mutations That Confer Letermovir Resistance
Authors: Chou Sunwen 
Published: August 2015

ABSTRACTLetermovir (LMV) is an experimental cytomegalovirus terminase inhibitor undergoing phase 3 clinical trials. Viral mutations have been described at UL56 codons 231 to 369 that confer widely variable levels of LMV resistance. In this study, 15 independent experiments propagating an exonuclease mutant viral strain in escalating LMV concentrations replicated 6 of the 7 published UL56 mutations and commonly elicited additional resistance-conferring mutations at UL56 codons 231, 236, 237, 244, 257, 261, 325, and 329. Mutations were first detected earlier in LMV (median, 3 passages) than in 8 parallel experiments with foscarnet (median, 15 passages). As LMV concentrations increased, the typical initial UL56 change F261L, which confers low-grade resistance, combined or was replaced with mutations conferring higher-grade resistance, eventually enabling normal viral growth in 30 μM LMV (>5,000-fold the 50% effective concentration [EC50] for the wild type). At high LMV concentrations, the UL56 changes C325F/R were commonly detected, as well as a combination of changes at codons 236, 257, 329, and/or 369. Recombinant viruses containing individual UL56 mutations and combinations were constructed to confirm their resistance phenotypes and normal growth in cell culture. Several double and triple mutants showed much higher LMV resistance than the respective single mutants, particularly those including changes at both codons 236 and 257. The multiplicity of pathways to high-grade LMV resistance with minimal viral growth impact suggests a low viral genetic barrier and the need for close monitoring during treatment of active infection.
Comparative Genomic Analysis of Meningitis- and Bacteremia-Causing Pneumococci Identifies a Common Core Genome
Authors: Kulohoma Benard W. , Cornick Jennifer E. , Chaguza Chrispin , Yalcin Feyruz , Harris Simon R. , Gray Katherine J. , Kiran Anmol M. , Molyneux Elizabeth , French Neil , Parkhill Julian , Faragher Brian E. , Everett Dean B. , Bentley Stephen D. , Heyderman Robert S. 
Published: August 2015

ABSTRACT

Streptococcus pneumoniae
is a nasopharyngeal commensal that occasionally invades normally sterile sites to cause bloodstream infection and meningitis. Although the pneumococcal population structure and evolutionary genetics are well defined, it is not clear whether pneumococci that cause meningitis are genetically distinct from those that do not. Here, we used whole-genome sequencing of 140 isolates of
S. pneumoniae
recovered from bloodstream infection (
n
= 70) and meningitis (
n
= 70) to compare their genetic contents. By fitting a double-exponential decaying-function model, we show that these isolates share a core of 1,427 genes (95% confidence interval [CI], 1,425 to 1,435 genes) and that there is no difference in the core genome or accessory gene content from these disease manifestations. Gene presence/absence alone therefore does not explain the virulence behavior of pneumococci that reach the meninges. Our analysis, however, supports the requirement of a range of previously described virulence factors and vaccine candidates for both meningitis- and bacteremia-causing pneumococci. This high-resolution view suggests that, despite considerable competency for genetic exchange, all pneumococci are under considerable pressure to retain key components advantageous for colonization and transmission and that these components are essential for access to and survival in sterile sites.
NanI Sialidase, CcpA, and CodY Work Together To Regulate Epsilon Toxin Production by Clostridium perfringens Type D Strain CN3718
Authors: Li Jihong , Freedman John C. , McClane Bruce A. 
Published: August 2015

ABSTRACT

Clostridium perfringens
type D strains are usually associated with diseases of livestock, and their virulence requires the production of epsilon toxin (ETX). We previously showed (J. Li, S. Sayeed, S. Robertson, J. Chen, and B. A. McClane, PLoS Pathog 7:e1002429, 2011,
http://dx.doi.org/10.1371/journal.ppat.1002429
) that BMC202, a
nanI
null mutant of type D strain CN3718, produces less ETX than wild-type CN3718 does. The current study proved that the lower ETX production by strain BMC202 is due to
nanI
gene disruption, since both genetic and physical (NanI or sialic acid) complementation increased ETX production by BMC202. Furthermore, a sialidase inhibitor that interfered with NanI activity also reduced ETX production by wild-type CN3718. The NanI effect on ETX production was shown to involve reductions in
codY
and
ccpA
gene transcription levels in BMC202 versus wild-type CN3718. Similar to CodY, CcpA was found to positively control ETX production. A double
codY
ccpA
null mutant produced even less ETX than a
codY
or
ccpA
single null mutant. CcpA bound directly to sequences upstream of the
etx
or
codY
start codon, and bioinformatics identified putative CcpA-binding
cre
sites immediately upstream of both the
codY
and
etx
start codons, suggesting possible direct CcpA regulatory effects. A
ccpA
mutation also decreased
codY
transcription, suggesting that CcpA effects on ETX production can be both direct and indirect, including effects on
codY
transcription. Collectively, these results suggest that NanI, CcpA, and CodY work together to regulate ETX production, with NanI-generated sialic acid from the intestines possibly signaling type D strains to upregulate their ETX production and induce disease.

IMPORTANCE
Clostridium perfringens
NanI was previously shown to increase ETX binding to, and cytotoxicity for, MDCK host cells. The current study demonstrates that NanI also regulates ETX production via increased transcription of genes encoding the CodY and CcpA global regulators. Results obtained using single
ccpA
or
codY
null mutants and a
ccpA
codY
double null mutant showed that
codY
and
ccpA
regulate ETX production independently of one another but that
ccpA
also affects
codY
transcription. Electrophoretic mobility shift assays and bioinformatic analyses suggest that both CodY and CcpA may directly regulate
etx
transcription. Collectively, results of this study suggest that sialic acid generated by NanI from intestinal sources signals ETX-producing
C. perfringens
strains, via CcpA and CodY, to upregulate ETX production and cause disease.
Current pain education within undergraduate medical studies across Europe: Advancing the Provision of Pain Education and Learning (APPEAL) study
Authors: Briggs Emma V , Battelli Daniele , Gordon David , Kopf Andreas , Ribeiro Sofia , Puig Margarita M , Kress Hans G 
Published: August 2015

ObjectivesUnrelieved pain is a substantial public health concern necessitating improvements in medical education. The Advancing the Provision of Pain Education and Learning (APPEAL) study aimed to determine current levels and methods of undergraduate pain medicine education in Europe.Design and methodsUsing a cross-sectional design, publicly available curriculum information was sought from all medical schools in 15 representative European countries in 2012–2013. Descriptive analyses were performed on: the provision of pain teaching in dedicated pain modules, other modules or within the broader curriculum; whether pain teaching was compulsory or elective; the number of hours/credits spent teaching pain; pain topics; and teaching and assessment methods.ResultsCurriculum elements were publicly available from 242 of 249 identified schools (97%). In 55% (133/242) of schools, pain was taught only within compulsory non-pain-specific modules. The next most common approaches were for pain teaching to be provided wholly or in part via a dedicated pain module (74/242; 31%) or via a vertical or integrated approach to teaching through the broader curriculum, rather than within any specific module (17/242; 7%). The curricula of 17/242 schools (7%) showed no evidence of any pain teaching. Dedicated pain modules were most common in France (27/31 schools; 87%). Excluding France, only 22% (47/211 schools) provided a dedicated pain module and in only 9% (18/211) was this compulsory. Overall, the median number of hours spent teaching pain was 12.0 (range 4–56.0 h; IQR: 12.0) for compulsory dedicated pain modules and 9.0 (range 1.0–60.0 h; IQR: 10.5) for other compulsory (non-pain specific) modules. Pain medicine was principally taught in classrooms and assessed by conventional examinations. There was substantial international variation throughout.ConclusionsDocumented pain teaching in many European medical schools falls far short of what might be expected given the prevalence and public health burden of pain.
IQ and alcohol-related morbidity and mortality among Swedish men and women: the importance of socioeconomic position
Authors: Sjölund Sara , Hemmingsson Tomas , Gustafsson Jan-Eric , Allebeck Peter 
Published: August 2015

AimsTo investigate the association between intelligence in childhood and later risk of alcohol-related disease and death by examining (1) the mediating effect of social position as an adult and (2) gender as a possible moderator.DesignCohort study.Setting and participants21 809 Swedish men and women, born in 1948 and 1953, from the Swedish “Evaluation Through Follow-up” database were followed until 2006/2007.MeasurementsIQ was measured in school at the age of 13 and alcohol-related disease and death (International Classification of Disease codes) were followed from 1971 and onwards.FindingsWe found an increased crude HR of 1.23 (95% CI 1.18 to 1.29) for every decrease in group of IQ test results for alcohol-related admissions and 1.14 (95% CI 1.04 to 1.24) for alcohol-related death. Social position as an adult was found to mediate both outcomes. Gender was not found to moderate the association. However, adjusting for socioeconomic position lowered the risk more among men than among women.ConclusionsThere was an inverse, graded association between IQ and alcohol-related disease and death, which at least partially was mediated by social position as an adult. For alcohol-related death, complete mediation by socioeconomic position as an adult was found. Gender does not moderate this association. The role of socioeconomic position may differ between the genders.
Inequity of access to ACE inhibitors in Swedish heart failure patients: a register-based study
Authors: Ohlsson Anna , Lindahl Bertil , Hanning Marianne , Westerling Ragnar 
Published: August 2015

BackgroundSeveral international studies suggest inequity in access to evidence-based heart failure (HF) care. Specifically, studies of ACE inhibitors (ACEIs) point to reduced ACEI access related to female sex, old age and socioeconomic position. Thus far, most studies have either been rather small, lacking diagnostic data, or lacking the possibility to account for several individual-based sociodemographic factors. Our aim was to investigate differences, which could reflect inequity in access to ACEIs based on sex, age, socioeconomic status or immigration status in Swedish patients with HF.MethodsIndividually linked register data for all Swedish adults hospitalised for HF in 2005–2010 (n=93 258) were analysed by multivariate regression models to assess the independent risk of female sex, high age, low employment status, low income level, low educational level or foreign country of birth, associated with lack of an ACEI dispensation within 1 year of hospitalisation. Adjustment for possible confounding was made for age, comorbidity, Angiotensin receptor blocker therapy, period and follow-up time.ResultsAnalysis revealed an adjusted OR for no ACEI dispensation for women of 1.31 (95% CI 1.27 to 1.35); for the oldest patients of 2.71 (95% CI 2.53 to 2.91); and for unemployed patients of 1.59 (95% CI 1.46 to 1.73).ConclusionsAccess to ACEI treatment was reduced in women, older patients and unemployed patients. We conclude that access to ACEIs is inequitable among Swedish patients with HF. Future studies should include clinical data, as well as mortality outcomes in different groups.
Hypocalcaemia in a six‐month‐old hand‐reared female giraffe (Giraffa camelopardalis)
Authors: Stegmann George Frik , Buck Roxanne , O'Dell Jaques 
Published: August 2015

Radiological examination and surgical biopsy were required of a swelling in the cervical region in a healthy 200 kg, six‐month‐old hand‐reared female giraffe (Giraffa camelopardalis). Induction was with intramuscular administration of medetomidine, butorphanol and ketamine and maintained with 1.5 per cent isoflurane‐in‐oxygen on a circle anaesthetic machine. Induction and maintenance were uneventful but recovery delayed and characterised by hindlimb weakness, opistotonus and torticollis of the head and neck. Atipamezole and naltrexone were administered to facilitate recovery but with minimal clinical improvement. Venous blood gas analysis indicated moderate metabolic acidosis, hypochloraemia, increased anion gap and marked hypocalcaemia (0.64 mmol/l). Intravenous administration of 60 ml calcium borogluconate resulted in a rapid improvement in muscle tone and the ability to stand. Hypocalcaemia was diagnosed in a juvenile giraffe after anaesthesia characterised by delayed recovery. Intravenous administration of calcium borogluconate resulted in rapid recovery of muscle strength and ambulance.
Left Ventricular Myocardial Function in Children With Pulmonary Hypertension
Authors: Burkett Dale A. , Slorach Cameron , Patel Sonali S. , Redington Andrew N. , Ivy D. Dunbar , Mertens Luc , Younoszai Adel K. , Friedberg Mark K. 
Published: August 2015

Background—
Through ventricular interdependence, pulmonary hypertension (PH) induces left ventricular (LV) dysfunction. We hypothesized that LV strain/strain rate, surrogate measures of myocardial contractility, are reduced in pediatric PH and relate to invasive hemodynamics, right ventricular strain, and functional measures of PH.

Methods and Results—

At 2 institutions, echocardiography was prospectively performed in 54 pediatric PH patients during cardiac catheterization, and in 54 matched controls. Patients with PH had reduced LV global longitudinal strain (LS; −18.8 [−17.3 to −20.4]% versus −20.2 [−19.0 to −20.9]%;
P
=0.0046) predominantly because of reduced basal (−12.9 [−10.8 to −16.3]% versus −17.9 [−14.5 to −20.7]%;
P
<0.0001) and mid (−17.5 [−15.5 to −19.0]% versus −21.1 [−19.1 to −23.0]%;
P
<0.0001) septal strain. Basal global circumferential strain was reduced (−18.7 [−15.7 to −22.1]% versus −20.6 [−19.0 to −22.5]%;
P
=0.0098), as were septal and free-wall segments. Mid circumferential strain was reduced within the free-wall. Strain rates were reduced in similar patterns. Basal septum LS, the combined average LS of basal and mid interventricular septal segments, correlated strongly with degree of PH (
r
=0.66;
P
<0.0001), pulmonary vascular resistance (
r
=0.60;
P
<0.0001), and right ventricular free-wall LS (
r
=0.64;
P
<0.0001). Brain natriuretic peptide levels correlated moderately with septal LS (
r
=0.48;
P
=0.0038). PH functional class correlated moderately with LV free-wall LS (
r
=−0.48;
P
=0.0051). The septum, shared between ventricles and affected by septal shift, was the most affected LV region in PH.

Conclusions—
Pediatric PH patients demonstrate reduced LV strain/strain rate, predominantly within the septum, with relationships to invasive hemodynamics, right ventricular strain, and functional PH measures.
Iron-Sensitive Cardiac Magnetic Resonance Imaging for Prediction of Ventricular Arrhythmia Risk in Patients With Chronic Myocardial Infarction
Authors: Cokic Ivan , Kali Avinash , Yang Hsin-Jung , Yee Raymond , Tang Richard , Tighiouart Mourad , Wang Xunzhang , Jackman Warren S. , Chugh Sumeet S. , White James A. , Dharmakumar Rohan 
Published: August 2015

Background—
Recent canines studies have shown that iron deposition within chronic myocardial infarction (CMI) influences the electric behavior of the heart. To date, the link between the iron deposition and malignant ventricular arrhythmias in humans with CMI is unknown.

Methods and Results—
Patients with CMI (n=94) who underwent late-gadolinium-enhanced cardiac magnetic resonance imaging before implantable cardioverter-defibrillator implantation for primary and secondary preventions were retrospectively analyzed. The predictive values of hypointense cores (HIC) in balanced steady-state free precession images and conventional cardiac magnetic resonance imaging and ECG malignant ventricular arrhythmia parameters for the prediction of primary combined outcome (appropriate implantable cardioverter-defibrillator therapy, survived cardiac arrest, or sudden cardiac death) were studied. The use of HIC within CMI on balanced steady-state free precession as a marker of iron deposition was validated in a canine MI model (n=18). Nineteen patients met the study criteria with events occurring at a median of 249 (interquartile range of 540) days after implantable cardioverter-defibrillator placement. Of the 19 patients meeting the primary end point, 18 were classified as HIC+, whereas only 1 was HIC−. Among the cohort in whom the primary end point was not met, there were 28 HIC+ and 47 HIC− patients. Receiver operating characteristic curve analysis demonstrated an additive predictive value of HIC for malignant ventricular arrhythmias with an increased area under the curve of 0.87 when added to left ventricular ejection fraction (left ventricular ejection fraction alone, 0.68). Both cardiac magnetic resonance imaging and histological validation studies performed in canines demonstrated that HIC regions in balanced steady-state free precession images within CMI likely result from iron depositions.

Conclusions—
Hypointense cores within CMI on balanced steady-state free precession cardiac magnetic resonance imaging can be used as a marker of iron deposition and yields incremental information toward improved prediction of malignant ventricular arrhythmias.
A new species of Lamiogethes and a new species of Meligethes from China (Coleoptera: Nitidulidae: Meligethinae)
Authors: CHEN YING , LIN XIAOLI , HUANG MIN , YANG XING KE 
Published: August 2015

A new species of Lamiogethes Audisio & Cline, 2009, L. nyingchiensis sp. nov., and a new species of Meligethes Stephens, 1830, M. (Odontogethes) scrobescens sp. nov. are described and illustrated from China. The differences between these new species and closely related species are discussed. The materials examined are deposited in the Institute of Zoology, Chinese Academy of Sciences, Beijing, China (IZAS).
What is dignity in prehospital emergency care?
Authors: Abelsson Anna , Lindwall Lillemor 
Published: August 2015

Background: Ethics and dignity in prehospital emergency care are important due to vulnerability and suffering. Patients can lose control of their body and encounter unfamiliar faces in an emergency situation. Objective: To describe what specialist ambulance nurse students experienced as preserved and humiliated dignity in prehospital emergency care. Research design: The study had a qualitative approach. Method: Data were collected by Flanagan’s critical incident technique. The participants were 26 specialist ambulance nurse students who described two critical incidents of preserved and humiliated dignity, from prehospital emergency care. Data consist of 52 critical incidents and were analyzed with interpretive content analysis. Ethical considerations: The study followed the ethical principles in accordance with the Declaration of Helsinki. Findings: The result showed how human dignity in prehospital emergency care can be preserved by the ambulance nurse being there for the patient. The ambulance nurses meet the patient in the patient’s world and make professional decisions. The ambulance nurse respects the patient’s will and protects the patient’s body from the gaze of others. Humiliated dignity was described through the ambulance nurse abandoning the patient and by healthcare professionals failing, disrespecting, and ignoring the patient. Discussion: It is a unique situation when a nurse meets a patient face to face in a critical life or death moment. The discussion describes courage and the ethical vision to see another human. Conclusion: Dignity was preserved when the ambulance nurse showed respect and protected the patient in prehospital emergency care. The ambulance nurse students’ ethical obligation results in the courage to see when a patient’s dignity is in jeopardy of being humiliated. Humiliated dignity occurs when patients are ignored and left unprotected. This ethical dilemma affects the ambulance nurse students badly due to the fact that the morals and attitudes of ambulance nurses are reflected in their actions toward the patient.