bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-25/93 induction by Vpu as a mechanism for counteracting MARCH1-restriction on HIV-1 infectivity in macrophages
Authors: Lodge Robert , Xu Zaikun , Eklund Mckenna , Stürzel Christina , Kirchhoff Frank , Tremblay Michel J. , Hobman Tom C. , Cohen Éric A. 
Published: September 2023

ABSTRACT

The type 1 interferon-regulated E3 ubiquitin ligase MARCH1 reduces surface expression of HIV-1 envelope glycoproteins (Env) and their packaging into nascent virions, a condition that restricts viral infectivity. However, how HIV-1 counters this restriction, notably during infection of macrophages, remains unclear. Here, we show that the HIV-1 accessory protein Vpu increases the levels of microRNAs-25 and -93 to target
MARCH1
mRNA. By recruiting β-TRCP, a component of the SCF
β-TRCP
E3 ligase complex that targets phosphorylated β-catenin for degradation, Vpu increases β-catenin levels, which, in concert with TCF4/LEF, drives transcription of the
MARCH1
-targeting microRNAs. This potentiates HIV-1 infectivity as a result of increased Env incorporation into nascent virions. Pharmacological targeting of the β-catenin pathway inhibits Vpu-mediated upregulation of microRNAs-25 and -93 and restores MARCH1 restriction on HIV-1 infectivity. Overall, our findings highlight a novel mechanism by which HIV-1 counteracts MARCH1 by downregulating its expression via Vpu-mediated induction of microRNAs-25 and -93.

IMPORTANCE

In order to efficiently produce infectious viral particles, HIV must counter several restrictions exerted by host cell antiviral proteins. MARCH1 is a member of the MARCH protein family that restricts HIV infection by limiting the incorporation of viral envelope glycoproteins into nascent virions. Here, we identified two regulatory RNAs, microRNAs-25 and -93, induced by the HIV-1 accessory protein Vpu, that downregulate
MARCH1
mRNA. We also show that Vpu induces these cellular microRNAs in macrophages by hijacking the cellular β-catenin pathway. The notion that HIV-1 has evolved a mechanism to counteract MARCH1 restriction on viral infectivity underlines the importance of MARCH1 in the host antiviral response.
Complete genome sequence of
Kosakonia pseudosacchari
RX.G5M8, a putative methylotroph isolated from Hong Kong soil
Authors: Xu D. Y. , Leung K. M. , Lai G. K. K. , Griffin S. D. J. 
Published: September 2023

ABSTRACT

Kosakonia pseudosacchari
RX.G5M8, a putative methylotroph, was isolated from garden soil in Hong Kong. Its complete genome, a single chromosome of 4,953,935 bp (GC content 53.91%), was established through hybrid assembly.
Draft genome sequences of four
Staphylococcus hyicus
strains, SC302, SC304, SC306, and SC310, isolated from swine from Eastern Canada
Authors: Gagné-Thivierge Cynthia , Vincent Antony T. , Paquet Valérie E. , Gauthier Marie-Lou , Denicourt Martine , Lambert Marie-Ève , Charette Steve J. 
Published: September 2023

ABSTRACT

The bacterium
Staphylococcus hyicus
causes porcine exudative epidermitis in piglets, which represents both health and welfare concerns. Few genome sequences of this pathogen are published. We provide four additional ones to help future genomic analysis of
S. hyicus
. These are genomes of strains isolated from Canadian swine.
Complete genome sequence of
Edwardsiella
sp. NBRC12716 isolated in 1962 from the liver of diseased eel
Authors: Lanza Andre , Mizobata Hideaki , Yonezawa Ryo , Yoshitake Kazutoshi , Shigeharu Kinoshita , Asakawa Shuichi 
Published: September 2023

ABSTRACT

We report the complete genome sequence of
Edwardsiella
sp. NBRC12716 isolated from a diseased eel in 1962. The genome consists of a single, circular chromosome 3,771,060 bp in length with 59.74% GC content and encodes 25 rRNA, 96 tRNA, and 3,182 protein-coding genes.
Emergence of KPC-134, a KPC-2 variant associated with ceftazidime-avibactam resistance in a ST11
Klebsiella pneumoniae
clinical strain
Authors: Huang Xiangning , Shen Siquan , Chang Fan , Liu Xin , Yue Jinxi , Xie Ning , Yin Lin , Hu Fupin , Xiao Daiwen 
Published: September 2023

ABSTRACT

The emergence of various new
Klebsiella pneumoniae
carbapenemase (KPC) variants leading to ceftazidime-avibactam treatment failure is a new challenge in current clinical anti-infection treatment. Here, we report a ceftazidime-avibactam-resistant
K. pneumoniae
1072–2 clinical strain carrying a novel KPC variant, KPC-134, which differs from KPC-2 by both single mutation (D178A) and 8-amino acid insertions (asp-asp-asn-arg-ala-pro-asn-lys). The results of antimicrobial susceptibility testing showed that the isolate was resistant to meropenem (MIC = 4 mg/L), ceftazidime (MIC ≥ 32 mg/L), cefepime (MIC ≥128 mg/L), aztreonam (MIC ≥128 mg/L), and ceftazidime-avibactam (MIC ≥128 mg/L) but sensitive to imipenem (MIC = 0.5 mg/L), imepenem-relebactam (MIC = 0.5 mg/L), meropenem-vaborbactam (MIC = 2 mg/L), and aztreonam-avibactam (MIC = 4 mg/L). The plasmid containing
bla
KPC-134
was isolated from
K. pneumoniae
, and the
bla
KPC-134
gene was cloned into plasmid pHSG398 and transformed into an
Escherichia coli
DH5α to observe changes in antimicrobial resistance. The results indicated that the transformant was positive for
bla
KPC-134
and increased MICs of ceftazidime-avibactam, ceftazidime, cefepime, and aztreonam by 512-fold, 256-fold, 16-fold, and 4-fold, respectively, compared with the recipient. The results of third-generation sequencing showed that the
bla
KPC-134
gene was carried by a 133,789 bp IncFII-IncR plasmid, and many common resistance genes (including
bla
CTX-M-65
,
bla
TEM-1B
,
bla
SHV-12
,
rmtB
, and
catB4
) along with the IS
26
,
tnpR
,
ISkpn8
, IS
kpn6
-like, and Tn
1721
elements were identified.

IMPORTANCE

The emergence of various new KPC variants leading to ceftazidime-avibactam treatment failure is a new challenge for clinical anti-infection treatment. Here, we describe the characterization of a ceftazidime-avibactam-resistant blaKPC-134-positive
Klebsiella pneumoniae
clinical strain for the first time.
K. pneumoniae
bearing with KPC variant often mislead clinical anti-infection treatment because of their unique antimicrobial susceptibility profile and the tendency of conventional carbapenemase assays to give false negative results. Therefore, timely identification of KPC variants and effective anti-infective therapy are key to saving infected patients.
Procedural sedation programme minimising adverse events: a 3-year experience from a tertiary paediatric emergency department
Authors: Erumbala Gokul , Anzar Sabu , Deiratany Samir , Blackie Barbara , Powell Colin , Al Ansari Khalid 
Published: September 2023

IntroductionA well-developed procedural sedation programme in the paediatric emergency department can minimise adverse events. We examined how adherence to current best evidence ensures safe delivery of paediatric sedation in a newly established tertiary paediatric hospital.MethodsOur sedation service uses a robust provider training and privileging system, standardised policy and procedures and rigorous data collection all within an evidence-based clinical governance process. We examined sedation data from the first 3 years of operation.ResultsFrom July 2018 to May 2022, ketamine was used in 3388 of the 3405 sedations. The mean age of sedated children was 5.5 years (range 6 months to 17.8 years) and common indications were closed reduction of fractures and laceration repairs. A total of 148 (4.37%, 95% CI 3.68% to 5.06%) adverse events were documented, including 88 (2.59%, 95% CI 2.06% to 3.13%) cases of vomiting, 50 (1.48%, 95% CI 1.07% to 1.88%) cases related to airway and breathing with 40 (1.18%, 95% CI 0.82% to 1.54%) cases of oxygen desaturation, 6 (0.18%, 95% CI 0.04% to 0.32%) cases of laryngospasm, 4 (0.12%, 95% CI 0% to 0.23%) cases of apnoea.ConclusionThis study presents a large single-centre dataset on the use of intravenous ketamine in paediatric procedural sedation. Adhering to international standards and benchmarks for provider skills and training, drug administration and monitoring facilities, with a strict clinical governance process, optimizes patient safety.
Impact of refresher training on the outcomes of trachomatous trichiasis surgery
Authors: Pak Clara , Hall Nathan , Bekele Demissie Tadesse , Kollmann K H Martin , Tadele Tesfaye , Tekle-Haimanot Redda , Taye Tarik , Qureshi Babar , Yalew Wubante , Gower Emily W , Kempen John H 
Published: September 2023

Background/aims
Trachomatous trichiasis (TT) is a severe consequence of chronic inflammation/conjunctival scarring resulting from trachoma, the leading infectious cause of blindness worldwide. Our prospective cohort study evaluated the effectiveness of refresher training (RT) for experienced surgeons (1–22 years) on the outcomes of upper lid (UL) TT surgery in rural Ethiopia.

Methods
Patients undergoing UL TT surgery in at least one eye by a participating surgeon were included. Patients were split into two cohorts: patients enrolled prior to (C1) and after (C2) RT. RT consisted of a 1-week programme with practice on a HEAD START mannequin and supportive supervision in live surgery by expert trainers. Data were collected at preoperative enrolment, and at 6-month and 12-month follow-up visits. The primary outcome was development of postoperative TT (PTT). A series of multivariate generalised estimating equations were fit to model PTT involving potential covariates of interest.

Results
A total of 261 eyes contributed by 173 patients were studied between 2017 and 2019. By 1-year postoperatively, 37/128 eyes (28.9%) in C1 and 22/133 eyes (16.5%) in C2 had developed PTT (p=0.03). Other than surgeon RT participation, no factors studied were associated with differences in PTT.

Conclusion
Our results indicate a significant reduction in the risk of PTT after experienced surgeons’ participation in RT as compared with eyes receiving surgery before RT. This observation suggests a significant potential benefit of the RT with HEAD START mannequin practice and supportive supervision during surgery, and suggests RT may be a valuable strategy to improve surgical outcomes.
Overall survival benefits of cancer drugs in the WHO Model List of Essential Medicines, 2015–2021
Authors: Zhou Yue , Naci Huseyin , Chen Dingyi , Bai Lin , Shi Luwen , Guan Xiaodong , Wagner Anita Katharina 
Published: September 2023

IntroductionWe examined overall survival (OS) benefits for targeted cancer drugs recommended for List of Essential Medicines (EMLs) since 2015. We assessed consistency of decisions in 2019 and 2021 with more specific criteria: OS benefit >4 months and high scores on European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).MethodsWe identified applications for cancer drug in WHO EMLs from 2015 to 2021. We extracted evidence of OS benefit documented in WHO Technical Report Series (TRS) and compared it to evidence from pivotal trial(s) documented in Food and Drug Administration-approved labels. We retrieved published ESMO-MCBS scores. We summarised availability and magnitude of OS benefit and ESMO-MCBS scores and assessed consistency of inclusion decisions against WHO criteria.Results22/54 targeted cancer drug indications were recommended. Among them, 68.2% and 31.8% had OS benefit evidence documented in WHO-TRS and pivotal trials, respectively. Among those not recommended, 59.4% and 56.3% had OS benefit evidence documented in WHO-TRS and pivotal trials, respectively. Of 11 cancer drug indications recommended in 2019 and 2021, 54.5% and 9.1% had evidence of OS benefit >4 months in WHO-TRS and pivotal trials, respectively; 45.5% met ESMO-MCBS criteria. Ten targeted cancer drugs had more than one application for the same indications. Five of those were eventually recommended, including three without new evidence of OS benefit. Additional factors, such as reduced cost, and increased treatment options, seemed to be important factors in the selection.ConclusionWhile WHO has defined approval criteria for cancer drugs EML, we identified areas where adherence of these criteria and communication of the EML approval decision-making processes can be improved.
Hepatectomy combined with apatinib and camrelizumab for CNLC stage IIIb hepatocellular carcinoma: a phase II trial protocol
Authors: Huang Jun Tao , Zhong Jian-Hong , Zhang Jie , Gong Wen Feng , Ma Liang , Li Le Qun , Xiang Bang-De 
Published: September 2023

IntroductionCurrent clinical guidelines recommend systematic antitumour therapy as the primary treatment option for patients with stage IIIb hepatocellular carcinoma (HCC) based on the China liver cancer (CNLC) staging criteria. Several different targeted therapeutics have been applied in combination with immunotherapeutic regimens to date in patients with advanced HCC. The present study was developed to evaluate the relative safety and efficacy of hepatectomy of HCC in combination with targeted apatinib treatment and immunotherapeutic camrelizumab treatment CNLC-IIIb stage HCC patients with the goal of providing evidence regarding the potential value of this therapeutic regimen in individuals diagnosed with advanced HCC.Methods and analysisThis is a multicentre phase II trial with single-arm in which patients undergo hepatectomy in combination with targeted treatment (apatinib) and immunotherapy (camrelizumab). Patients will undergo follow-up every 2–3 months following treatment initiation to record any evidence of disease progression and adverse event incidence for a minimum of 24 months following the discontinuation of treatment until reaching study endpoint events or trial termination. The primary endpoint for this study is patient mortality.Ethics and disseminationThis study protocol was approved by the Ethics Committee of the Guangxi Medical University Cancer Hospital (KS2022[124]). The results of this study will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT05062837.
Early use of oral semaglutide in the UK: A cost-effectiveness analysis versus continuing metformin and SGLT-2 inhibitor therapy
Authors: Ren Hongye , Berry Sasha , Malkin Samuel Joseph Paul , Hunt Barnaby , Bain Stephen 
Published: September 2023

ObjectivesMany people with type 2 diabetes experience clinical inertia, remaining in poor glycaemic control on oral glucose-lowering medications rather than intensifying treatment with a glucagon-like peptide-1 receptor agonist, despite an efficacious, orally administered option, oral semaglutide, being available. The present study evaluated the long-term cost-effectiveness of initiating oral semaglutide versus continuing metformin plus sodium-glucose cotransporter-2 (SGLT-2) inhibitor therapy in the UK.DesignOutcomes were projected over patients’ lifetimes using the IQVIA Core Diabetes Model (V.9.0). Clinical data were taken from the oral semaglutide and placebo arms of the patient subgroup receiving metformin plus an SGLT-2 inhibitor in PIONEER 4. Costs, expressed in 2021 Pounds sterling (GBP), were accounted from a healthcare payer perspective.InterventionsModelled patients received oral semaglutide immediately (in the first year of the analysis) or after a 2-year delay, after which all physiological parameters were brought to values observed in the immediate therapy arm. During the simulation, patients intensified with the addition of basal insulin and, subsequently, by switching to basal-bolus insulin.ResultsImmediate oral semaglutide therapy was associated with improvements in life expectancy of 0.17 (95% CIs 0.16 to 0.19) years, and quality-adjusted life expectancy of 0.15 (0.14 to 0.16) quality-adjusted life years (QALYs), versus a 2-year delay. Benefits were due to a reduced incidence of diabetes-related complications. Direct costs were estimated to be GBP 1423 (1349 to 1496) higher with immediate oral semaglutide therapy versus a 2-year delay, with higher treatment costs partially offset by cost savings from avoidance of diabetes-related complications. Immediate oral semaglutide therapy was therefore associated with an incremental cost-effectiveness ratio of GBP 9404 (8380 to 10 538) per QALY gained versus a 2-year delay.ConclusionsImmediate oral semaglutide is likely to represent a cost-effective treatment in people with type 2 diabetes with inadequate glycaemic control on metformin plus an SGLT-2 inhibitor in the UK.Trial registration numberNCT02863419.
Shufeng Jiedu capsule for acute exacerbation of chronic obstructive pulmonary disease: a protocol of multicentre, randomised, double-blind, placebo-controlled trial
Authors: Xia Ruyu , Fei Yutong , Zhang Lishan , Jie Zhijun , Fan Xiaoyun , Dai Mengyuan , Moore Michael , Willcox Merlin , Hu Xiaoyang , Francis Nick , Liang Changhao , Fei Guanghe , Liu Jianping 
Published: September 2023

IntroductionChronic obstructive pulmonary disease (COPD) represents one of the leading causes of death worldwide. Published clinical trials suggest that the Chinese patent herbal medicine Shufeng Jiedu capsule (SFJD) is safe and may be effective for treating acute exacerbations of COPD (AECOPD). However, these effects have been reported with low or very low certainty evidence. This trial aims to evaluate the effectiveness and safety of SFJD for AECOPD.Methods and analysisThis study is designed as a multicentre, randomised, double-blind, placebo-controlled trial. Three hundred patients with moderate or severe hospitalised AECOPD will be recruited in Beijing, Shanghai and Hefei. Participants will be randomly assigned to SFJD and usual care or placebo and usual care at a ratio of 1:1. SFJD and placebo will be administered orally four capsules three times daily for 7 consecutive days followed by an 8-week follow-up period. The primary outcome will be COPD symptom severity as measured by the EXAcerbation of Chronic Pulmonary Disease Tool score. Secondary outcomes include clinical symptoms, quality of life, length of hospital stay, a total dose of antibiotics, the frequency of recurrence of AECOPD, haematological biomarkers, death and adverse events. This study will answer the question of whether SFJD was safe to use and will improve symptoms in people with AECOPD, and will therefore reduce the necessity for antibiotics, the risk and duration of admission to hospital, and the risk of recurrence.Ethics and disseminationThe ethics committee of the first affiliated hospital of Anhui Medical University, Beijing University of Chinese Medicine affiliated Dongzhimen hospital and fifth people’s hospital of Shanghai Fudan University approved the study protocol. Informed written consent will be obtained from all the participants. The results of this trial will be disseminated at academic conferences and in peer-reviewed publications.Trial registration numberISRCTN99049821.
Experiences of misuse and symptoms of dependence among people who use gabapentinoids: a qualitative systematic review protocol
Authors: McNeilage Amy Gray , Nielsen Suzanne , Murnion Bridin , Ashton-James Claire 
Published: September 2023

IntroductionGabapentinoids are among the most widely prescribed pain medications. However, there is growing evidence to suggest that gabapentinoids may be associated with dependence and misuse. The aim of this systematic review is to synthesise the qualitative literature on gabapentinoid misuse and symptoms of dependence. The findings of this study will inform efforts to mitigate emerging harms.Methods and analysisA systematic review of qualitative research will explore lived experiences of misuse and symptoms of dependence among people who use gabapentinoids. Six databases (MEDLINE, Scopus, Web of Science, CINAHL, EMBASE and PsycINFO) and grey literature sources will be searched from inception to May 2023. Qualitative studies that include people with lived experiences of gabapentinoid misuse and symptoms of gabapentinoid dependence will be included. Reference lists of included studies will also be screened for additional studies. The methodological quality of included studies will be appraised using the Critical Appraisal Skills Programme qualitative checklist, and higher quality studies will be prioritised in the thematic synthesis. The GRADE-CERQual approach will be used to assess confidence in the overall findings of the review.Ethics and disseminationEthical approval is not required for this systematic review. The findings of this review will be disseminated in peer-reviewed journals, at conferences and on social media.PROSPERO registration numberCRD42023401832.
Goal-directed versus outcome-based financial incentives for smoking cessation among low-income, hospitalised patients: rationale and design of the Financial Incentives for Smoking Treatment II (FIESTA II) randomised controlled trial
Authors: Wali Soma , Gaitonde Anisha , Sherman Scott , Min Noelle , Pesantes Andrea , Bidgoli Ava , Shirley Abraelle , Tseng Chi-Hong , Ladapo Joseph 
Published: September 2023

IntroductionSmoking remains the leading preventable cause of death in the USA. Low utilisation of treatments for smoking cessation remains a major barrier for reducing smoking rates. Financial incentives represent an innovative approach to increasing use of therapies for smoking cessation. This paper will describe the rationale and design of the Financial Incentives for Smoking Treatment II (FIESTA II) study, a randomised controlled trial to evaluate the effectiveness and feasibility of goal-directed and outcome-based financial incentives to promote smoking cessation among hospitalised smokers.Methods and analysisWe are recruiting adult participants who smoked tobacco in the 30 days prior to initial interview and are contemplating quitting smoking. These participants will come from two hospitals in underserved communities in New York City and Los Angeles. They will be randomised into one of three arms. The first arm consists of goal-directed financial incentives plus enhanced usual care, which includes hospital-directed information about quitting smoking, nicotine replacement therapy and referral to a Quitline. The second arm involves outcome-based financial incentives plus enhanced usual care. The third arm consists of enhanced usual care alone. Multiple phone interviews with the participants will be completed after randomisation to assess smoking cessation. Participants will earn $20 for each follow-up interview completed and $30 for each smoking cessation test completed. Those who are randomised to the financial incentive groups can earn an additional $700. The participants in the outcome-based group will receive payments solely for exhibiting cessation, whereas the participants in the goal-based group are also eligible for receiving payments after meeting milestones such as speaking with a helpline coach.EthicsHuman research protection committees at New York University School of Medicine and the University of California Los Angeles (UCLA) David Geffen School of Medicine granted ethics approval.Protocol number:IRB#19-000 084.Trial registration numberNCT03979885.