bluuebunny/crossref_metadata_2025 huggingface dataset:
rpoB
Gene Analysis as a Novel Strategy for Identification of Spirochetes from the Genera
Borrelia
,
Treponema
, and
Leptospira
Authors: Renesto Patricia , Lorvellec-Guillon Katell , Drancourt Michel , Raoult Didier
Published: March 2020

Spirochetes are emerging pathogens for which culture and identification are partly unresolved. In fact, 16S rRNA-based sequencing is by far the most widely used PCR methodology that is able to detect such uncultivable pathogens. However, this assay actually has some limitations linked to potential problems of contamination, which hampers diagnosis. To circumvent this, we have devised a simple PCR strategy involving targeting of the gene encoding the RNA polymerase beta subunit (
rpoB
), a highly conserved enzyme. The complete sequence of the
Leptospira biflexa
(serovar patoc)
rpoB
gene was determined and compared with the published sequences for
Borrelia burgdorferi
and
Treponema pallidum
. From the resulting analysis, degenerate nucleotide primers were designed and tested for their ability to amplify a portion of the
rpoB
gene from various spirochetes. Using two different pairs of these primers, we succeeded in obtaining specific
rpoB
-amplified fragments for all members of the genera
Leptospira
,
Treponema
, and
Borrelia
tested and no other bacteria. Our findings may have significant implications for the development of a new tool for the identification of spirochetes, especially if clinical samples are contaminated or when the infecting strain is uncultivable.
Performance of the COBAS AMPLICOR HCV MONITOR Test, Version 2.0, an Automated Reverse Transcription-PCR Quantitative System for Hepatitis C Virus Load Determination
Authors: Gerken G. , Rothaar T. , Rumi M. G. , Soffredini R. , Trippler M. , Blunk M. J. , Butcher A. , Soviero S. , Colucci G.
Published: March 2020

A clinical evaluation of an automated quantitative PCR assay, the COBAS AMPLICOR HCV MONITOR test, version 2.0 (v2.0), was carried out to assess the performance of this test in comparison with that of the previous, manual version, the AMPLICOR HCV MONITOR test, and with that of nested PCR. Serial dilutions of serum samples infected with genotype 1b, 2a, or 3, as well as synthetic RNA transcripts and serum samples derived from 87 patients with chronic hepatitis C and infected with genotype 1a, 1b, 2a, 2b, 3a, 3b, 4, or 5, were analyzed to determine the ability of the system to efficiently quantify various hepatitis C virus (HCV) genotypes. These experiments showed that the COBAS AMPLICOR HCV MONITOR test, v2.0, has mean intra-assay, interassay, and interoperator coefficients of variation that range from 22 to 34.5% and a 3-logarithm dynamic range, which spans from 10
3
to 10
6
copies/ml. Compared to the previous, manual version of the test, the COBAS AMPLICOR HCV MONITOR test, v2.0, showed an improved efficacy for all genotypes, especially genotypes 2, 3, and 4, whose estimated concentrations were on average 1 logarithm higher. When used to monitor patients under treatment, however, both versions showed the same patterns of viremia, indicating that the COBAS AMPLICOR HCV MONITOR test, v2.0, and the AMPLICOR HCV MONITOR test were equally effective at detecting relative viremia changes in serial samples. As expected, the automated test was less sensitive than nested PCR; among specimens from a cohort of patients treated with interferon, nested PCR identified three more viremic specimens, which probably contained very low concentrations of HCV RNA.
Role of
vacA
and
cagA
in
Helicobacter pylori
Inhibition of Mucin Synthesis in Gastric Mucous Cells
Authors: Beil Winfried , Enss Marie Luise , Müller Simone , Obst Barbara , Sewing Karl-Friedrich , Wagner Siegfried
Published: March 2020

The aim of this study was to investigate the effect of
Helicobacter pylori
on the function of gastric mucous cells.
H. pylori
(10
4
to 10
7
CFU/well) was incubated with the mucin-producing gastric cell line HM02 for 12 and 24 h. Mucin synthesis and secretion were determined by the incorporation of
d
-
N
-[
acetyl
-
14
C]glucosamine into intracellular and released high-molecular-weight glycoproteins.
cagA
-positive, cytotoxin-producing and non-cytotoxin-producing
H. pylori
strains impaired the incorporation of
d
-
N
-[
acetyl
-
14
C]glucosamine into intracellular glycoproteins. Significant inhibition of mucin synthesis was noted after 12 and 24 h of cocultivation with a bacterial load of ≥10
5
bacteria (bacterium/cell ratio = 0.25). The
cagA
-positive, cytotoxin-producing strains (HP64, HP57, and HP87) caused significantly stronger inhibition of intracellular mucin synthesis than the
cagA
-positive, non-cytotoxin-producing strains (HP05, HP83, and HP84). The
cagA
-negative, non-cytotoxin-producing strains (HP01, HP04, and HP85) did not affect intracellular mucin synthesis. The results indicate that
H. pylori
directly impairs mucin synthesis in gastric mucous cells and that cytotoxic
cagA
-positive strains cause more profound inhibition of mucin synthesis. We suggest that the increased inhibitory effect of
cagA
-positive, cytotoxin-producing strains on mucin synthesis can be considered one possible factor responsible for the increased risk of developing peptic ulceration with these
H. pylori
strains.
Evaluation of Immunoglobulin M (IgM) and IgG Enzyme Immunoassays in Serologic Diagnosis of West Nile Virus Infection
Authors: Tardei G. , Ruta S. , Chitu V. , Rossi C. , Tsai T. F. , Cernescu C.
Published: March 2020

A unique urban encephalitis epidemic in Romania signaled the emergence of neurological infection due to West Nile (WN) virus as a novel public health threat in Eastern Europe and provided an opportunity to evaluate patterns of immunoglobulin G (IgG) and IgM reactivity in IgM capture and IgG enzyme-linked immunosorbent assays (ELISAs). WN virus infection was diagnosed serologically in 236 of 290 patients from whom acute serum or cerebrospinal fluid (CSF) samples were available. In 37% of serum samples and in 25% of CSF samples collected in the first week of illness, anti-WN virus IgM antibody was detected in the absence of virus-specific IgG. The switch to an IgG antibody response occurred after 4 to 5 days of illness and earlier in CSF than in serum. A specific humoral immune response was detected in the CSF before the serum in some patients for whom paired CSF and serum samples from the same day were available. IgM antibody in convalescent serum samples persisted beyond 2 months after the onset of illness in more than 50% of patients. ELISA optical density values and antibody concentrations were well correlated for both IgM and IgG immunoassays. Anti-WN virus IgM antibody in acute-phase samples did not cross-react significantly with flaviviruses in other antigenic groups.
Molecular Characterization of
Campylobacter jejuni
from Patients with Guillain-Barré and Miller Fisher Syndromes
Authors: Endtz Hubert P. , Ang C. Wim , van den Braak Nicole , Duim Birgitta , Rigter Alan , Price Lawrence J. , Woodward David L. , Rodgers Frank G. , Johnson Wendy M. , Wagenaar Jaap A. , Jacobs Bart C. , Verbrugh Henri A. , van Belkum Alex
Published: March 2020

Campylobacter jejuni
has been identified as the predominant cause of antecedent infection in Guillain-Barrésyndrome (GBS) and Miller Fisher syndrome (MFS). The risk of developing GBS or MFS may be higher after infection with specific
C. jejuni
types. To investigate the putative clonality, 18 GBS- or MFS-related
C. jejuni
strains from The Netherlands and Belgium and 17 control strains were analyzed by serotyping (Penner and Lior), restriction fragment length polymorphism analysis of PCR products of the
flaA
gene, amplified fragment length polymorphism analysis, pulsed-field gel electrophoresis, and randomly amplified polymorphic DNA analysis. Serotyping revealed 10 different O serotypes and 7 different Lior serotypes, thereby indicating a lack of serotype clustering. Two new O serotypes, O:35 and O:13/65, not previously associated with GBS or MFS were found. Serotype O:19 was encountered in 2 of 18 strains, and none was of serotype O:41. The results of all genotypic methods also demonstrated substantial heterogeneity. No clustering of GBS- or MFS-related strains occurred and no molecular marker capable of separating pathogenic GBS or MFS from non-GBS- or non-MFS-related enteritis strains could be identified in this study. Sialic-acid-containing lipopolysaccharides (LPS) are thought to be involved in the triggering of GBS or MFS through molecular mimicry with gangliosides in human peripheral nerves. Therefore, further characterization of GBS- or MFS-related
C. jejuni
should target the genes involved in the synthesis of LPS and the incorporation of sialic acid.
Dynamics of Meningococcal Long-Term Carriage among University Students and Their Implications for Mass Vaccination
Authors: Ala'Aldeen D. A. A. , Neal K. R. , Ait-Tahar K. , Nguyen-Van-Tam J. S. , English A. , Falla T. J. , Hawkey P. M. , Slack R. C. B.
Published: March 2020

In the 1997-98 academic year, we conducted a longitudinal study of meningococcal carriage and acquisition among first-year students at Nottingham University, Nottingham, United Kingdom. We examined the dynamics of long-term meningococcal carriage with detailed characterization of the isolates. Pharyngeal swabs were obtained from 2,453 first-year students at the start of the academic year (October), later on during the autumn term, and again in March. Swabs were immediately cultured on selective media, and meningococci were identified and serologically characterized. Nongroupable strains were genetically grouped using a PCR-based assay. Pulsed-field gel electrophoresis was used to determine the link between sequential isolates. Of the carriers initially identified in October, 44.1% (98 of 222) were still positive later on in the autumn (November or December); 57.1% of these remained persistent carriers at 6 months. Of the index carriers who lost carriage during the autumn, 16% were recolonized at 6 months. Of 344 index noncarriers followed up, 22.1% acquired carriage during the autumn term and another 13.7% acquired carriage by March. Overall, 43.9% (397 of 904) of the isolates were noncapsulated (serologically nongroupable); by PCR-based genogrouping, a quarter of these belonged to the capsular groups B and C. The ratio of capsulated to noncapsulated forms for group B and C strains was 2.9 and 0.95, respectively. Sequential isolates of persistent carriers revealed that individuals may carry the same or entirely different organisms at different times. We identified three strains that clearly switched their capsular expression on and off at different times in vivo. One student developed invasive meningococcal disease after carrying the same organism for over 7 weeks. The study revealed a high rate of turnover of meningococcal carriage among students. Noncapsulated organisms are capable of switching their capsular expression on and off (both ways) in the nasopharynx, and group C strains are more likely to be noncapsulated than group B strains. Carriage of a particular meningococcal strain does not necessarily protect against colonization or invasion by a homologous or heterologous strain.
Intervening Transcribed Spacer Region 1 Variability in
Cyclospora cayetanensis
Authors: Adam Rodney D. , Ortega Ynes R. , Gilman Robert H. , Sterling Charles R.
Published: March 2020

Cyclospora cayetanensis
is an apicomplexan protozoan parasite which has emerged as an important cause of epidemic and endemic diarrhea. Water-borne as well as food-borne outbreaks have occurred, including a large number of U.S. cases associated with raspberries imported from Guatemala. Molecular markers exist for tracing the epidemiology of many of the bacterial pathogens associated with water-borne or food-borne diarrhea, such as serotyping and pulsed-field electrophoresis. However, there are currently no molecular markers available for
C. cayetanensis
. The intervening transcribed spacer (ITS) regions between the small- and large-subunit rRNA genes demonstrate much greater sequence variability than the small-subunit rRNA sequence itself and have been useful for the molecular typing of other organisms. Thus, ITS1 variability might allow the identification of different genotypes of
C. cayetanensis
. In order to determine the degree of ITS1 variability among
C. cayetanensis
isolates, the ITS1 sequences of
C. cayetanensis
isolates from a variety of sources, including raspberry-associated cases, cases from Guatemala, and pooled and individual isolates from Peru, were obtained. The ITS1 sequences of all five raspberry-associated isolates were identical, consistent with their origin from a single source. In contrast, one of the two Guatemala isolates and two Peruvian isolates contained multiple ITS1 sequences. These multiple sequences could represent multiple clones from a single clinical source or, more likely, variability of the ITS1 region within the genome of a single clone.
New Chromogenic Identification and Detection of
Staphylococcus aureus
and Methicillin-Resistant
S. aureus
Authors: Merlino John , Leroi Marcel , Bradbury Ross , Veal Duncan , Harbour Colin
Published: March 2020

This paper describes a new chromogenic plate medium, CHROMagar Staph aureus (CHROMagar, Paris, France), for the identification of
Staphylococcus aureus
on the basis of colony pigmentation. The abilities of CHROMagar Staph aureus, thermostable nuclease (DNase), and mannitol salt agar (MSA) to identify
S. aureus
isolates (
n
= 114) and discriminate between
S. aureus
and coagulase-negative staphylococci (CoNS;
n
= 22) were compared. CHROMagar Staph aureus proved to be more sensitive and specific than DNase and MSA, allowing a reliable, simple, and rapid method for the identification of
S. aureus
isolates. All CoNS encountered in this study with the exception of
S. chromogenes
could be easily differentiated from
S. aureus
on this medium. The supplementation with 4 μg of oxacillin or methicillin per ml allowed simple identification of methicillin resistance in hospital-acquired
S. aureus
strains which show multiple-drug resistance profiles. Community-acquired methicillin-resistant
S. aureus
strains showing non-multi-drug resistance profiles require further evaluation on this new chromogenic medium. Methicillin or oxacillin resistance of all
S. aureus
isolates was confirmed by the detection of penicillin-binding protein 2a, encoded by the
mecA
gene, using the latex slide agglutination MRSA-Screen test (PBP 2′ Test, DR900M; Oxoid).
Direct Evidence by DNA Fingerprinting that Endoscopic Cross-Infection of
Helicobacter pylori
Is a Cause of Postendoscopic Acute Gastritis
Authors: Sugiyama Toshiro , Naka Hiroji , Yachi Akira , Asaka Masahiro
Published: March 2020

The DNA fingerprinting of
Helicobacter pylori
strains in two cases of acute gastritis that occurred after endoscopy was examined.
H. pylori
was isolated from the stomachs of two patients with acute gastritis and from the stomachs of the patients in whom the same gastrofiberscope had previously been used. The genomic DNA digested with
Hae
III was subjected to pulsed-field gel electrophoresis. The corresponding paired electrophoretic patterns were completely identical. These findings provide direct evidence that postendoscopic acute gastritis can be caused by cross-infection with
H. pylori
via endoscopy.
Reproducibility Problems with the Abbott Laboratories LCx Assay for
Chlamydia trachomatis
and
Neisseria gonorrhoeae
Authors: Gronowski Ann M. , Copper Susan , Baorto David , Murray Patrick R.
Published: March 2020

This study demonstrates that significant reproducibility problems can occur during routine use of the Abbott Laboratories LCx assay for
Chlamydia trachomatis
and
Neisseria gonorrhoeae
. These problems can go undetected by the quality control procedures outlined in the manufacturer's package insert. We outline here procedures for detecting and preventing contamination and reproducibility problems.
Culture of
Helicobacter pylori
from a Gastric String May Be an Alternative to Endoscopic Biopsy
Authors: Samuels Amy L. , Windsor Helen M. , Ho Grace Y. , Goodwin Luke D. , Marshall Barry J.
Published: March 2020

Helicobacter pylori
was isolated from a swallowed string from 32 of 33 adult subjects (97%) with selective culture media. With this method, antibiotic susceptibility testing and molecular epidemiology studies of
H. pylori
can be carried out without the need for the collection of specimens by endoscopic biopsy.
More than Simple Parasites: the Sociobiology of Bacteriophages and Their Bacterial Hosts
Authors: Secor Patrick R. , Dandekar Ajai A.
Published: March 2020

Bacteria harbor viruses called bacteriophages that, like all viruses, co-opt the host cellular machinery to replicate. Although this relationship is at first glance parasitic, there are social interactions among and between bacteriophages and their bacterial hosts. These social interactions can take on many forms, including cooperation, altruism, and cheating. Such behaviors among individuals in groups of bacteria have been well described. However, the social nature of some interactions between phages or phages and bacteria is only now becoming clear.
In Vitro
Characterization of Protein Effector Export in the Bradyzoite Stage of Toxoplasma gondii
Authors: Mayoral Joshua , Shamamian Peter , Weiss Louis M.
Published: March 2020

Toxoplasma
bradyzoites persist within tissue cysts and are refractory to current treatments, serving as a reservoir for acute complications in settings of compromised immunity. Much remains to be understood regarding how this life stage successfully establishes and maintains persistent infection. In this study, we investigated whether the export of parasite effector proteins into the host cell occurs during the development of
in vitro
tissue cysts. We quantified the presence of four previously described effectors in host cell nuclei at different time points after bradyzoite differentiation and found that they accumulated largely during the early stages of infection. Despite a decline in nuclear accumulation, we found that one of these effectors still mediated its function after prolonged infection with bradyzoites, and we provide evidence that this effector is exported beyond early infection stages. These findings suggest that effector export from within developing tissue cysts provides one potential mechanism by which this parasite achieves chronic infection.
In Vivo
Assay Reveals Microbial OleA Thiolases Initiating Hydrocarbon and β-Lactone Biosynthesis
Authors: Smith Megan D. , Robinson Serina L. , Molomjamts Mandkhai , Wackett Lawrence P.
Published: March 2020

Microbially produced β-lactones are found in antibiotic, antitumor, and antiobesity drugs. Long-chain olefinic membrane hydrocarbons have potential utility as fuels and specialty chemicals. The metabolic pathway to both end products share bacterial enzymes denoted as OleA, OleC, and OleD that transform acyl-CoA cellular intermediates into β-lactones. Bacteria producing membrane hydrocarbons via the Ole pathway additionally express a β-lactone decarboxylase, OleB. Both β-lactone and olefin biosynthesis pathways are initiated by OleA enzymes that define the overall structure of the final product. There is currently very limited information on OleA enzymes apart from the single representative from
Xanthomonas campestris
. In this study, bioinformatic analysis identified hundreds of new, putative OleA proteins, 74 proteins were screened via a rapid whole-cell method, leading to the identification of 25 stably expressed OleA proteins representing seven bacteria phyla.
Complementary Metagenomic Approaches Improve Reconstruction of Microbial Diversity in a Forest Soil
Authors: Alteio L. V. , Schulz F. , Seshadri R. , Varghese N. , Rodriguez-Reillo W. , Ryan E. , Goudeau D. , Eichorst S. A. , Malmstrom R. R. , Bowers R. M. , Katz L. A. , Blanchard J. L. , Woyke T.
Published: March 2020

Microbial ecologists have historically used cultivation-based approaches as well as amplicon sequencing and shotgun metagenomics to characterize microbial diversity in soil. However, challenges persist in the study of microbial diversity, including the recalcitrance of the majority of microorganisms to laboratory cultivation and limited sequence assembly from highly complex samples. The uncultivated majority thus remains a reservoir of untapped genetic diversity. To address some of the challenges associated with bulk metagenomics as well as low throughput of single-cell genomics, we applied flow cytometry-enabled mini-metagenomics to capture expanded microbial diversity from forest soil and compare it to soil bulk metagenomics. Our resulting data from this pooled-cell sorting approach combined with bulk metagenomics revealed increased phylogenetic diversity through novel soil taxa and rare biosphere members. In-depth analysis of genomes within the highly represented
Bacteroidetes
phylum provided insights into conserved and clade-specific patterns of carbon metabolism.
Initiation of modern-style subduction in the Neoarchean: From plume to subduction with frequent slab break-off
Authors: Li Dapeng , Chen Yuelong , Xue Guoliang , Kang Huan , Yu Yang , Geng Jianzhen , Zhang Yulong , Li Ting
Published: March 2020

Fundamental geodynamic changes from vertical tectonics to lateral subduction occurred during the Neoarchean, yet detailed processes related to this transition and initiation of modern-style subduction remain enigmatic. Successive Neoarchean magmatic rocks including both plume-derived komatiites and subduction-related supracrustal and intrusive rocks appeared and preserved key information on the late Archean geodynamic changes in the Western Shandong Province granite-greenstone belt (WSP), North China Craton. In this study, whole-rock geochemical and Sm-Nd isotopic data and zircon U-Pb and Lu-Hf isotopes are reported for early Neoarchean supracrustal and intrusive rocks for the WSP. Temporally, the early Neoarchean magmatic movements in the WSP can be subdivided into two stages, including the early stage (2.77–2.69 Ga) and the late stage (2.69–2.60 Ga). Spatially, from southwest to northeast, intrusive rocks with similar ages define three belts (A, B, and C). Early stage tholeiitic and enriched meta-basalts were plume-related, representing oceanic crust opening from a pre-early Neoarchean continent. Slab subduction at least initiated at ca. 2.74 Ga and generated various Neoarchean tonalite-trondhjemite-granodiorites, quartz diorites, and arc-related volcanic rocks and mafic intrusions. Episodic emergence of meta-basaltic rocks and/or mafic intrusions with depleted εHf(t) values and low (La/Yb)N ratios indicates frequent slab break-offs during ca. 2.70–2.68 Ga, 2.66–2.64 Ga, and 2.62–2.60 Ga due to a relatively hotter mantle and regional heating by mantle plume. Secular geochemical changes of mafic and felsic rocks in this study outline roles of slab subduction in contributions of cooling the mantle, secular mantle refertilization, and crustal growth.
Splenectomy for isolated splenic metastasis from primary lung adenocarcinoma
Authors: Grant-Freemantle Marc C , Bass Gary A , Butt Waqas T , Gillis Amy E
Published: March 2020

A 73-year-old woman was referred to a tertiary centre with isolated splenic metastasis from previous pT1aNo stage 1a lung adenocarcinoma. The patient underwent a right lower lobe lobectomy and mediastinal lymph node dissection 2 years ago for invasive adenocarcinoma with no adjuvant therapy. An incidental finding of new splenic cyst was noted on surveillance imaging, which was fluorodeoxyglucose positive on positron emission tomography, and confirmed on cytology to be metastatic lung adenocarcinoma. After multi-disciplinary team’s review, the patient underwent splenectomy, with partial excision of diaphragm due to local infiltration. Her postoperative course was eventful, and was complicated by a simple fluid collection in the surgical bed (amylase negative), a left sided pneumonia and atelectasis and left sided pleural effusion, requiring antibiotics and radiological drainage of the abdominal and pleural collection. The patient recovered well and is currently doing well 9 months postoperatively with no evidence of recurrence or metastatic disease.
Use of the Aptima mRNA high-risk human papillomavirus (HR-HPV) assay compared to a DNA HR-HPV assay in the English cervical screening programme: a decision tree model based economic evaluation
Authors: Weston Georgie , Dombrowski Caroline , Harvey Michael J , Iftner Thomas , Kyrgiou Maria , Founta Christina , Adams Elisabeth J
Published: March 2020

Objective

To estimate the impact of using the Aptima messenger RNA (mRNA) high-risk human papilloma virus (HR-HPV) assay versus a DNA HR-HPV assay in a primary HPV cervical screening programme.

Design

One hypothetical cohort followed for 3 years through HPV primary cervical screening.

Setting

England.

Participants

A hypothetical cohort of women aged 25–65 years tested in the National Health Service (NHS) Cervical Screening Programme (CSP) for first call or routine recall testing.

Methods

A decision tree parameterised with data from the CSP (2017/18) and the HORIZON study. Uncertainty analyses were conducted using data from the FOCAL and GAST studies, other DNA HPV tests in addition to one-way and probabilistic sensitivity and scenarios analyses, to test the robustness of results.

Interventions

Aptima mRNA HR-HPV assay and a DNA HR-HPV assay (cobas 4800 HPV assay).

Main outcome measures

Primary: total colposcopies and total costs for the cohort. Secondary: total HPV and cytology tests, number lost to follow-up.

Results

At baseline for a population of 2.25 million women, an estimated £15.4 million (95% credibility intervals (CI) £6.5 to 24.1 million) could be saved and 28 009 (95% CI 27 499 to 28 527) unnecessary colposcopies averted if Aptima mRNA assays are used instead of a DNA assay, with 90 605 fewer unnecessary HR-HPV and 253 477 cytology tests performed. These savings are due to a lower number of HPV positive samples in the mRNA arm. When data from other primary HPV screening trials were compared, results indicated that using the Aptima mRNA assay generated cost savings and reduced testing in every scenario.

Conclusion

Using the Aptima mRNA assay versus a DNA assay would almost certainly yield cost savings and reduce unnecessary testing and procedures, benefiting the NHS and women in the CSP.
Safetxt: a safer sex intervention delivered by mobile phone messaging on sexually transmitted infections (STI) among young people in the UK - protocol for a randomised controlled trial
Authors: Free Caroline , McCarthy Ona L , Palmer Melissa J , Knight Rosemary , Edwards Phil , French Rebecca , Baraitser Paula , Hickson Ford Colin Ian , Wellings Kaye , Roberts Ian , Bailey Julia V , Hart Graham , Michie Susan , Clayton Tim , Ploubidis George B , Carpenter James R , Turner Katy M E , Devries Karen , Potter Kimberley
Published: March 2020

Introduction

Young people aged 16 to 24 have the highest prevalence of genital chlamydia and gonorrhoea compared with other age groups and re-infection rates following treatment are high. Long-term adverse health effects include subfertility and ectopic pregnancy, particularly among those with repeated infections. We developed the safetxt intervention delivered by text message to reduce sexually transmitted infection (STI) by increasing partner notification, condom use and (STI) testing among young people in the UK.

Methods and analysis

A single-blind randomised trial to reliably establish the effect of the safetxt intervention on chlamydia and gonorrhoea infection at 1 year. We will recruit 6250 people aged 16 to 24 years who have recently been diagnosed with chlamydia, gonorrhoea or non-specific urethritis from health services in the UK. Participants will be allocated to receive the safetxt intervention (text messages designed to promote safer sexual health behaviours) or to receive the control text messages (monthly messages asking participants about changes in contact details) by an automated remote online randomisation system. The primary outcome will be the cumulative incidence of chlamydia and gonorrhoea infection at 1 year assessed by nucleic acid amplification tests. Secondary outcomes include partner notification, correct treatment of infection, condom use and STI testing prior to sex with new partners.

Ethics and dissemination

Ethics approval was obtained from NHS Health Research Authority - London – Riverside Research Ethics Committee (REC reference: 15/LO/1665) and the London School of Hygiene & Tropical Medicine. We will submit the results of the trial for publication in peer-reviewed journals.

Trial registration number

International Standard Randomised Controlled Trials Number:ISRCTN64390461. Registered on 17thMarch 2016.WHO trial registration data setavailable at:http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN64390461.

Trial protocol version

12, 19thJuly 2018.
Arthroscopic meniscectomy versus non-surgical or sham treatment in patients with MRI confirmed degenerative meniscus lesions: a protocol for an individual participant data meta-analysis
Authors: Wijn Stan R W , Rovers Maroeska M , Rongen Jan J , Østerås Håvard , Risberg May A , Roos Ewa M , Hare Kristoffer B , van de Graaf Victor A , Poolman Rudolf W , Englund Martin , Hannink Gerjon
Published: March 2020

Introduction

Arthroscopic partial meniscectomy (APM) after degenerative meniscus tears is one of the most frequently performed surgeries in orthopaedics. Although several randomised controlled trials (RCTs) have been published that showed no clear benefit compared with sham treatment or non-surgical treatment, the incidence of APM remains high. The common perception by most orthopaedic surgeons is that there are subgroups of patients thatdoneed APM to improve, and they argue that each study sample of the existing trials is not representative for the day-to-day patients in the clinic. Therefore, the objective of this individual participant data meta-analysis (IPDMA) is to assess whether there are subgroups of patients with degenerative meniscus lesions who benefit from APM in comparison with non-surgical or sham treatment.

Methods and analysis

An existing systematic review will be updated to identify all RCTs worldwide that evaluated APM compared with sham treatment or non-surgical treatment in patients with knee symptoms and degenerative meniscus tears. Time and effort will be spent in contacting principal investigators of the original trials and encourage them to collaborate in this project by sharing their trial data. All individual participant data will be validated for missing data, internal data consistency, randomisation integrity and censoring patterns. After validation, all datasets will be combined and analysed using a one-staged and two-staged approach. The RCTs’ characteristics will be used for the assessment of clinical homogeneity and generalisability of the findings. The most important outcome will be the difference between APM and control groups in knee pain, function and quality of life 2 years after the intervention. Other outcomes of interest will include the difference in adverse events and mental health.

Ethics and dissemination

All trial data will be anonymised before it is shared with the authors. The data will be encrypted and stored on a secure server located in the Netherlands. No major ethical concerns remain. This IPDMA will provide the evidence base to update and tailor diagnostic and treatment protocols as well as (international) guidelines for patients for whom orthopaedic surgeons consider APM. The results will be submitted for publication in a peer-reviewed journal.

PROSPERO registration number

CRD42017067240.
Out of sight, out of mind: a prospective observational study to estimate the duration of the Hawthorne effect on hand hygiene events
Authors: Vaisman Alon , Bannerman Grace , Matelski John , Tinckam Kathryn , Hota Susy S
Published: March 2020

Background

Human auditing has been the gold standard for evaluating hand hygiene (HH) compliance but is subject to the Hawthorne effect (HE), the change in subjects’ behaviour due to their awareness of being observed. For the first time, we used electronic HH monitoring to characterise the duration of the HE on HH events after human auditors have left the ward.

Methods

Observations were prospectively conducted on two transplant wards at a tertiary centre between May 2018 and January 2019. HH events were measured using the electronic GOJO Smartlink Activity Monitoring System located throughout the ward. Non-covert human auditing was conducted in 1-hour intervals at random locations on both wards on varying days of the week. Two adjusted negative binomial regression models were fit in order to estimate an overall auditor effect and a graded auditor effect.

Results

In total, 365 674 HH dispensing events were observed out of a possible 911 791 opportunities. In the adjusted model, the presence of an auditor increased electronic HH events by approximately 2.5-fold in the room closest to where the auditor was standing (9.86 events per hour/3.98 events per hour; p<0.01), an effect sustained across only the partial hour before and after the auditor was present but not beyond the first hour after the auditor left. This effect persisted but was attenuated in areas distal from the auditor (total ward events of 6.91*6.32–7.55, p<0.01). Additionally, there was significant variability in the magnitude of the HE based on temporal and geographic distribution of audits.

Conclusion

The HE on HH events appears to last for a limited time on inpatient wards and is highly dynamic across time and auditor location. These findings further challenge the validity and value of human auditing and support the need for alternative and complementary monitoring methods.
Appropriateness of peripherally inserted central catheter use among general medical inpatients: an observational study using routinely collected data
Authors: Verma Amol A , Kumachev Alexander , Shah Sonam , Guo Yishan , Jung Hae Young , Rawal Shail , Lapointe-Shaw Lauren , Kwan Janice L , Weinerman Adina , Tang Terence , Razak Fahad
Published: March 2020

Background

Peripherally inserted central catheters (PICC) are among the most commonly used medical devices in hospital. This study sought to determine the appropriateness of inpatient PICC use in general medicine at five academic hospitals in Toronto, Ontario, Canada, based on the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC).

Methods

This was a retrospective, cross-sectional study of general internal medicine patients discharged between 1 April 2010 and 31 March 2015 who received a PICC during hospitalisation. The primary outcomes were the proportions of appropriate and inappropriate inpatient PICC use based on MAGIC recommendations. Hospital administrative data and electronic clinical data were used to determine appropriateness of each PICC placement. Multivariable regression models were fit to explore patient predictors of inappropriate use.

Results

Among 3479 PICC placements, 1848 (53%, 95% CI 51% to 55%) were appropriate, 573 (16%, 95% CI 15% to 18%) were inappropriate and 1058 (30%, 95% CI 29% to 32%) were of uncertain appropriateness. The proportion of appropriate and inappropriate PICCs ranged from 44% to 61% (p<0.001) and 13% to 21% (p<0.001) across hospitals, respectively. The most common reasons for inappropriate PICC use were placement in patients with advanced chronic kidney disease (n=500, 14%) and use for fewer than 15 days in patients who are critically ill (n=53), which represented 14% of all PICC placements in the intensive care unit. Patients who were older, female, had a Charlson Comorbidity Index score greater than 0 and more severe illness based on the Laboratory-based Acute Physiology Score were more likely to receive an inappropriate PICC.

Conclusions

Clinical practice recommendations can be operationalised into measurable domains to estimate the appropriateness of PICC insertions using routinely collected hospital data. Inappropriate PICC use was common and varied substantially across hospitals in this study, suggesting that there are important opportunities to improve care.
Impact of the distance from the chest wall to the heart on surface ECG voltage in athletes
Authors: Hedman Kristofer , Patti Alessandro , Moneghetti Kegan J , Hsu David , Christle Jeffrey W , Ashley Euan , Hadley David , Haddad Francois , Froelicher Victor
Published: March 2020

Objective

Available ECG criteria for detection of left ventricular (LV) hypertrophy have been reported to have limited diagnostic capability. Our goal was to describe how the distance between the chest wall and the left ventricle determined by echocardiography affected the relationship between ECG voltage and LV mass (LVM) in athletes.

Methods

We retrospectively evaluated digitised ECG data from college athletes undergoing routine echocardiography as part of their preparticipation evaluation. Along with LV mass and volume, we determined the chest wall–LV distance in the parasternal short-axis and long-axis views from two-dimensional transthoracic echocardiographic images and explored the relation with ECG QRS voltages in all leads, as well as summed voltages as included in six major ECG-LVH criteria.

Results

239 athletes (43 women) were included (age 19±1 years). In men, greater LV–chest wall distance was associated with higher R-wave amplitudes in leads aVL and I (R=0.20 and R=0.25, both p<0.01), while in women greater distance was associated with higher R-amplitudes in V5 and V6 (R=0.42 and R=0.34, both p<0.01). In women, the chest wall–LV distance was the only variable independently (and positively) associated with R V5 voltage, while LVM, height and weight contributed to the relationship in men.

Conclusions

The chest wall–LV distance was weakly associated with ECG voltage in athletes. Inconsistent associations in men and women imply different intrathoracic factors affecting impedance and conductance between sexes. This may help explain the poor relationship between QRS voltage and LVM in athletes.
Downregulation of RIG-I mediated by ITGB3/c-SRC/STAT3 signaling confers resistance to interferon-α-induced apoptosis in tumor-repopulating cells of melanoma
Authors: Li Yong , Song Yingqiu , Li Pindong , Li Mingxing , Wang Haizhou , Xu Tao , Yu Xiongjie , Yu Yuandong , Tai YunYan , Chen Ping , Cai Xiaojun , Wang Xianhe , Xiang Longchao , Deng Rui , Zhang Xiufang , Gao Liping , Wang Xuanbin , Liu Jing , Cao Fengjun
Published: March 2020

Background

Interferon-α (IFN-α) plays a pivotal role in host antitumor immunity, and the evasion of IFN-α signaling pathway can lead to IFN-α resistance during the treatment of cancer. Although the interplay between IFN-α and tumor cells has been extensively investigated in differentiated tumor cells, much less attention has been directed to tumor-repopulating cells (TRCs).

Methods

Three-dimentional soft fibrin matrix was used to select and grow highly malignant and tumorigenic melanoma TRCs. The regulation of integrin β3 (ITGB3)-c-SRC-STAT signaling pathway in melanoma TRCs was investigated both in vitro and in vivo. The relevant mRNA and protein expression levels were analyzed by qRT-PCR and western blot analysis. Immunoprecipitation and chromatin immunoprecipitation (ChIP) followed by qPCR (ChIP-qPCR) assays were performed to detect protein-protein and protein-DNA interactions. The clinical impacts of retinoic acid inducible gene-I (RIG-I) were assessed in melanoma datasets obtained from The Cancer Genome Atlas and Gene Expression Omnibus profiles.

Results

IFN-α-induced apoptosis was decreased in melanoma TRCs. Compared with conventional flask-cultured cells, IFN-α-mediated STAT1 activation was diminished in melanoma TRCs. Decreased expression of RIG-I in melanoma TRCs led to diminished activation of STAT1 via enhancing the interaction between Src homology region 2 domain-containing phosphatase-1 and STAT1. In addition, low expression levels of RIG-I correlated with poor prognosis in patients with melanoma. STAT3 was highly phosphorylated in TRCs and knockdown of STAT3 reversed the downregulation of RIG-I in TRCs. Knockdown of STAT3 resulted in STAT1 activation and increased expression of the pro-apoptosis genes in IFN-α-treated TRCs. Combined treatment of STAT3 inhibitor and IFN-α increased the apoptosis rate of TRCs. Disruption of ITGB3/c-SRC/STAT3 signaling pathway significantly elevated the efficiency of IFN-α-induced apoptosis of TRCs.

Conclusions

In melanoma TRCs, ITGB3-c-SRC-STAT3 pathway caused RIG-I repression and then affect STAT1 activation to cause resistance to IFN-α-induced apoptosis. RIG-I is a prognostic marker in patients with melanoma. Combination of STAT3 inhibitor and IFN-α could enhance the efficacy of melanoma treatment. Our findings may provide a new concept of combinatorial treatment for future immunotherapy.
Association of smoking and right ventricular function in middle age: CARDIA study
Authors: Moreira Henrique T , Armstrong Anderson C , Nwabuo Chike C , Vasconcellos Henrique D , Schmidt Andre , Sharma Ravi K , Ambale-Venkatesh Bharath , Ostovaneh Mohammad R , Kiefe Catarina I , Lewis Cora E , Schreiner Pamela J , Sidney Stephen , Ogunyankin Kofo O , Gidding Samuel S , Lima Joao A C
Published: March 2020

Objective

To evaluate the association of cigarette smoking and right ventricular (RV) systolic and diastolic functions in a population-based cohort of individuals at middle age.

Methods

This cross-sectional study included participants who answered the smoking questionnaire and underwent echocardiography at the Coronary Artery Risk Development in Young Adulthood year 25 examination. RV systolic function was assessed by echocardiographic-derived tricuspid annular plane systolic excursion (TAPSE) and by right ventricular peak systolic velocity (RVS’), while RV diastolic function was evaluated by early right ventricular tissue velocity (RVE’). Multivariable linear regression models assessed the relationship of smoking with RV function, adjusting for age, sex, race, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, diabetes mellitus, alcohol consumption, pulmonary function, left ventricular systolic and diastolic function and coronary artery calcium score.

Results

A total of 3424 participants were included. The mean age was 50±4 years; 57% were female; and 53% were black. There were 2106 (61%) never smokers, 750 (22%) former smokers and 589 (17%) current smokers. In the multivariable analysis, current smokers had significantly lower TAPSE (β=−0.082, SE=0.031, p=0.008), RVS’ (β=−0.343, SE=0.156, p=0.028) and RVE’ (β=−0.715, SE=0.195, p<0.001) compared with never smokers. Former smokers had a significantly lower RVE’ compared with never smokers (β=−0.414, SE=0.162, p=0.011), whereas no significant difference in RV systolic function was found between former smokers and never smokers.

Conclusions

In a large multicenter community-based biracial cohort of middle-aged individuals, smoking was independently related to both worse RV systolic and diastolic functions.
miR‐106B‐25 Cluster expression: a comparative human and canine osteosarcoma study
Authors: Leonardi Leonardo , Benassi Maria Serena , Pollino Serena , Locaputo Carmen , Pazzaglia Laura
Published: March 2020

Background

Osteosarcoma (OS) is the most common primary malignant bone tumour in dogs and human beings, characterised by similar genetic and clinical features. With the aim to define similarities and differences in the biological aspects involved in OS progression, a comparative study was performed to create a model to improve patient outcome.

Methods

First, the expression of microRNAs (miRNAs) belonging to the cluster miR‐106b‐25 (miR‐106b, miR‐25 and miR‐93‐5p) in human and canine OS tissue was compared.

Results

miR‐25 and miR‐106b presented a variable expression not significantly different from the corresponding normal bone, while miR‐93‐5p expression was increased in all OS specimens, with higher levels in the canine subset compared with human. Accordingly, its target p21 presented a weaker and less homogeneous immunostaining distribution in the canine group. Given the high expression of miR‐93‐5p in all OS specimens, the functional response of human 143B and canine DAN OS cells to miRNA inhibition was evaluated. Although p21 expression increased after miR‐93‐5p inhibition both at mRNA and protein level, a more significant cell response in terms of proliferation and apoptosis was seen in canine OS cells.

Conclusions

In conclusion, canine OS tissue and cell line presented higher expression levels of miR‐93‐5p than human OS. In addition, the introduction of miR‐93‐5p inhibitor caused a cell response in 143B and DAN that differed for the more intense functional impact in the canine OS cell line.
Towards Round-Optimal Secure Multiparty Computations: Multikey FHE Without a CRS
Authors: Kim Eunkyung , Lee Hyang-Sook , Park Jeongeun
Published: March 2020

Multikey fully homomorphic encryption (MFHE) allows homomorphic operations between ciphertexts encrypted under different keys. In applications for secure multiparty computation (MPC) protocols, MFHE can be more advantageous than usual fully homomorphic encryption (FHE) since users do not need to agree with a common public key before the computation when using MFHE. In EUROCRYPT 2016, Mukherjee and Wichs constructed a secure MPC protocol in only two rounds via MFHE which deals with a common random/reference string (CRS) in key generation. After then, Brakerski et al. replaced the role of CRS with the distributed setup for CRS calculation to form a four round secure MPC protocol. Thus, recent improvements in round complexity of MPC protocols have been made using MFHE.

In this paper, we go further to obtain round-efficient and secure MPC protocols. The underlying MFHE schemes in previous works still involve the common value, CRS, it seems to weaken the power of using MFHE to allow users to independently generate their own keys. Therefore, we resolve the issue by constructing an MFHE scheme without CRS based on LWE assumption, and then we obtain a secure MPC protocol against semi-malicious security in three rounds. We also define a new security notion “multikey-CPA security” to prove that a multikey ciphertext cannot be decrypted unless all the secret keys are gathered and our scheme is multikey-CPA secure.
Numerical Analysis of Wind-Induced Response of a Wrinkled Membrane
Authors: Wang Xiaofeng , Chu Haoyue , Yang Qingshan
Published: March 2020

Membranes have been popularly used in the fields of civil engineering and aerospace engineering. When wrinkled, a membrane loses its stiffness in the direction perpendicular to wrinkles and is more sensitive to wind loads. This paper numerically studied the wind-induced responses of a wrinkled membrane and their variations with respect to wind speed, wind direction and wrinkling deformation. Based on the stability theory of plates and shells, the wrinkling deformation of a rectangular membrane under shear was obtained by post-buckling analysis. Then, by using the wind load derived from a wind tunnel test, the dynamic responses of the wrinkled membrane were numerically analyzed for different wind speeds, wind directions and wrinkling deformations. The results indicate the following: (1) the displacement and extreme stresses of a membrane are gradually intensified with an increase in the wind speed; (2) the wind direction plays an important role in the displacement, but it has little effect on the stresses and (3) the displacement increases with the wrinkling deformation, and the extreme stresses are intensified with an increase in the pre-tension. This study on the wind-induced responses of a wrinkled membrane is helpful to the understanding of the complex behavior of a wrinkled membrane under wind loads while reducing the adverse effects of wrinkling deformation and ensuring the dynamic stability of membrane structures.
Quasi-order Γ-semihypergroups: Fundamental relations and complete parts
Authors: Ostadhadi-Dehkordi S. , Shum K. P.
Published: March 2020

The main purpose of this paper is to introduce and study quasi-order [Formula: see text]-semihypergroups that is a generalization of quasi-order semihypergroups. Also, we introduce quasi-order semihypergroups associated with quasi-order [Formula: see text]-semihypergroups and some important results obtained. Moreover, we study complete parts and fundamental relation on quasi-order [Formula: see text]-semihypergroups and prove that the fundamental relation is transitive.