bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early enterovirus translation deficits extend viral RNA replication and elicit sustained MDA5-directed innate signaling
Authors: Dobrikov Mikhail I. , Dobrikova Elena Y. , Nardone-White Dasean T. , McKay Zachary P. , Brown Michael C. , Gromeier Matthias 
Published: November 2023

ABSTRACT

Enteroviruses (EVs)—positive-sense single-strand RNA viruses of
Picornaviridae
—are among the most common human viral pathogens. Unlike other cytoplasmic viral RNAs (vRNAs), which are detected by RIG-I, sensing of EV RNAs is mediated primarily by MDA5. EVs evolved with rapid, cytotoxic life cycles as a means of host cell interference, ostensibly to suppress MDA5-orchestrated antiviral type-I interferon (IFN) responses. At the core of this strategy are viral 2A protease (2A
pro
)-directed cleavage of the eukaryotic initiation factor (eIF)4G—the central translation initiation scaffold and ribosome adaptor—and degradation of nuclear pores. EV MDA5 agonism has an intriguing innate footprint, characterized by polar TBK1-IFN regulatory factor 3 (IRF3) signaling, which fuels sustained type-I IFN release to provide context for antitumor CD8
+
T-cell priming after
in situ
cancer vaccination. Here we compared EV-host interactions between wild-type EVs and the highly attenuated recombinant polio:rhinovirus chimera and cancer immunotherapy agent (PVSRIPO) to test how targeted inhibition of discrete steps in the viral life cycle affects the innate antiviral response. Our investigations demonstrate that sustained MDA5-TBK1-IRF3 signaling elicited by PVSRIPO is the result of inefficient immediate 2A
pro
-directed eIF4G degradation, while wild-type EVs counter host innate type-I IFN defenses via rapid eIF4G cleavage. The MDA5-directed innate signature of profoundly attenuated EVs may provide efficient innate immune-stimulatory assets, for example, in
in situ
cancer vaccination strategies.

IMPORTANCE

Multiple pattern recognition receptors sense vRNAs and initiate downstream innate signaling: endosomal Toll-like receptors (TLRs) 3, 7, and 8 and cytoplasmic RIG-I-like receptors (RLRs) RIG-I, and MDA5. They engage distinct signaling scaffolds: mitochondrial antiviral signaling protein (RLR), MyD88, and TLR-adaptor interacting with SLC15A4 on the lysosome (TLR7 and TLR8) and toll/IL-1R domain-containing adaptor inducing IFN (TLR3). By virtue of their unusual vRNA structure and direct host cell entry path, the innate response to EVs uniquely is orchestrated by MDA5. We reported that PVSRIPO’s profound attenuation and loss of cytopathogenicity triggers MDA5-directed polar TBK1-IRF3 signaling that generates priming of polyfunctional antitumor CD8
+
T-cell responses and durable antitumor surveillance
in vivo
. Here we unraveled EV-host relations that control suppression of host type-I IFN responses and show that PVSRIPO’s deficient immediate host eIF4G cleavage generates unopposed MDA5-directed downstream signaling cascades resulting in sustained type-I IFN release.
Lung transplant in chronic HIV infection
Authors: Yarlagadda Keerthi , Werne Rachel , Sinha Neeraj 
Published: November 2023

Lung transplantation is the treatment of choice for many end-stage chronic lung conditions. Chronic Human Immunodeficiency Virus (HIV) infection is considered a relative contraindication for lung transplantation. In the era of Highly Active Antiretroviral Therapy (HAART), there has been an increase in the number of HIV-positive patients living with chronic lung conditions. In this paper, we aim to summarise the available literature in the field of lung transplantation in HIV-positive patients. We also present our experience of an HIV-positive woman who underwent lung transplantation for chronic interstitial lung disease from an HIV-negative donor.Careful candidate selection, along with management focused on closer monitoring, may result in favourable outcomes, including improved longevity among HIV-positive patients with chronic lung disease.
COVID-19 severity is associated with the risk of gastrointestinal bleeding
Authors: Hibiya Shuji , Fujii Takashi , Fujii Toshimitsu , Suzuki Shinji , Kondo Mayumi , Ooka Shinya , Furumoto Yohei , Azuma Seishin , Tanaka Kei , Kurata Hitoshi , Tanaka Shohei , Kurosaki Masayuki , Nagayama Kazuyoshi , Kusano Fumihiko , Iizuka Yasuhiro , Kawamura Takahiro , Ikemiyagi Hidekazu , Sakita Shinya , Yauchi Tsunehito , Watanabe Hideki , Kawamoto Ami , Matsuyama Yusuke , Ohtsuka Kazuo , Okamoto Ryuichi 
Published: November 2023

ObjectiveThe association between the severity of COVID-19 and gastrointestinal (GI) bleeding is unknown. This study aimed to determine whether the severity of COVID-19 is a risk factor for GI bleeding.DesignA multicentre, retrospective cohort study was conducted on hospitalised patients with COVID-19 between January 2020 and December 2021. The severity of COVID-19 was classified according to the National Institute of Health severity classification. The primary outcome was the occurrence of GI bleeding during hospitalisation. The main analysis compared the relationship between the severity of COVID-19 and the occurrence of GI bleeding. Multivariable logistic regression analysis was performed to evaluate the association between the severity of COVID-19 and the occurrence of GI bleeding.Results12 044 patients were included. 4165 (34.6%) and 1257 (10.4%) patients had severe and critical COVID-19, respectively, and 55 (0.5%) experienced GI bleeding. Multivariable analysis showed that patients with severe COVID-19 had a significantly higher risk of GI bleeding than patients with non-severe COVID-19 (OR: 3.013, 95% CI: 1.222 to 7.427). Patients with critical COVID-19 also had a significantly higher risk of GI bleeding (OR: 15.632, 95% CI: 6.581 to 37.130). Patients with severe COVID-19 had a significantly increased risk of lower GI bleeding (OR: 10.349, 95% CI: 1.253 to 85.463), but the risk of upper GI bleeding was unchanged (OR: 1.875, 95% CI: 0.658 to 5.342).ConclusionThe severity of COVID-19 is associated with GI bleeding, and especially lower GI bleeding was associated with the severity of COVID-19. Patients with severe or critical COVID-19 should be treated with caution as they are at higher risk for GI bleeding.
Baduanjin exercise for chronic non-specific low back pain: protocol for a series of N-of-1 trials
Authors: Zhai Jingbo , Liu Ai Feng , Yu Weijie , Guo Tianci 
Published: November 2023

IntroductionChronic non-specific low back pain (CNLBP) is one of the most common health problems worldwide. According to the clinical guideline released by the American College of Physicians, exercise has been recommended for the treatment of chronic LBP. In recent years, traditional Chinese medicine (TCM) is becoming increasingly popular for the management of chronic LBP. Baduanjin exercise is one of the exercise therapies in TCM. N-of-1 trial is a randomised cross-over self-controlled trial suitable for patients with this chronic disease. A series of similar N-of-1 trials can be pooled to estimate the overall and individual therapeutic effects synchronously by hierarchical Bayesian analysis. And N-of-1 trials are considered as a good tool for evaluating the therapeutic effect of TCM. Therefore, this study aims to conduct a series of N-of-1 trials with hierarchical Bayesian analysis for assessing whether Baduanjin exercise is effective and safe for CNLBP.Methods and analysisThis study conducts a series of N-of-1 trials on Baduanjin exercise for the management of CNLBP. Fifty participants will receive 1–3 treatment cycles. They will be randomised into a Baduanjin exercise or waiting list group for a week during the two periods of each treatment cycle. The primary outcome is the 10-point Visual Analogue Scale. The secondary outcomes include the Oswestry Disability Index, the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and the Short Form Health Survey 12. Statistical analysis will be conducted with WinBUGS V.1.4.3 software. Overall and individual therapeutic effects will be estimated synchronously by hierarchical Bayesian analysis.Ethics and disseminationThis study is approved by the Medical Ethics Committee of Tianjin University of TCM (reference number TJUTCM-EC20220005). Our findings will be published in a peer-reviewed journal or international conference.Trial registration numberChiCTR2200063307.
Needle-tip electrocautery versus steel scalpel incision in neurosurgery: study protocol for a prospective single-centre randomised controlled double-blind trial
Authors: Xu Wei , Fang Mei , Wang Zexu , Wang Jiayan , Tao Chuanyuan , Ma Lu , Li Li , Hu Xin 
Published: November 2023

IntroductionElectrocautery is used widely in surgical procedures, but making skin incision has routinely been performed with scalpel rather than electrocautery, for fear that electrocautery may cause poor incision healing, excessive scarring and increased wound complication rates. More and more studies on general surgery support the use of electrocautery for skin incision, but research comparing the two modalities for scalp incision in neurosurgery remains inadequate. This trial aims to evaluate the safety and efficacy of needle-tip monopolar for scalp incision in supratentorial neurosurgery compared with steel scalpel.Methods and analysisIn this prospective, randomised, double-blind trial, 120 eligible patients who are planned to undergo supratentorial neurosurgery will be enrolled. Patients will be randomly assigned to two groups. In controlled group scalp incision will be made with a scalpel from the epidermis to the galea aponeurotica, while in intervention group scalp will be first incised with a steel scalpel from the epidermis to the dermis, and then the subcutaneous tissue and galea aponeurotica will be incised with needle-tip monopolar on cutting mode. The primary outcomes are scar score (at 90 days). The secondary outcomes include incision pain (at 1 day, on discharge, at 90 days) and alopecia around the incision (at 90 days), incision blood loss and incision-related operation time (during operation), incision infection and incision healing (on discharge, at 2 weeks, 90 days).Ethics and disseminationThis trial will be performed according to the principles of Declaration of Helsinki and good clinical practice guidelines. This study has been validated by the ethics committee of West China Hospital. Informed consent will be obtained from each included patient and/or their designated representative. Final results from this trial will be promulgated through publications.Trial registration numberChiCTR2200063243.
Time trends and patterns in opioid prescription use following orthopaedic surgery in Ontario, Canada, from 2004/2005 to 2017/2018: a population-based study
Authors: Canizares Mayilee , Power J Denise , Perruccio Anthony V , Veillette Christian , Mahomed Nizar , Rampersaud Y Raja 
Published: November 2023

ObjectivesIncreased use of opioids and their associated harms have raised concerns around prescription opioid use for pain management following surgery. We examined trends and patterns of opioid prescribing following elective orthopaedic surgery.DesignPopulation-based study.SettingOntario, Canada.ParticipantsOntario residents aged 66+ years who had elective orthopaedic surgery from April 2004 to March 2018.Primary and secondary outcome measuresPostoperative opioid use (short term: within 90 days of surgery, prolonged: within 180 days and chronic: within 1 year), specific opioids prescribed, average duration (days) and amount (morphine milligram equivalents) of the initial prescription by year of surgery.ResultsWe included 464 460 elective orthopaedic surgeries in 2004/2005–2017/2018: 80% of patients used opioids within 1 year of surgery—25.1% were chronic users. There was an 8% increase in opioid use within 1 year of surgery, from 75.1% in 2004/2005 to 80.9% in 2017/2018: a 29% increase in short-term use and a decline in prolonged (9%) and chronic (22%) use. After 2014/2015, prescribed opioid amounts initially declined sharply, while the duration of the initial prescription increased substantially. Across categories of use, there was a steady decline in coprescription of benzodiazepines and opioids.ConclusionsMost patients filled opioid prescriptions after surgery, and many continued filling prescriptions after 3 months. During a period of general increase in awareness of opioid harms and dissemination of guidelines/policies aimed at opioid prescribing for chronic pain, we found changes in prescribing practices following elective orthopaedic surgery. Findings illustrate the potential impact of guidelines/policies on shaping prescription patterns in the surgical population, even in the absence of specific guidelines for surgical prescribing.
Investigating the associations of age of initiation and other psychosocial factors of singular alcohol, tobacco and marijuana usage on polysubstance use: analysis of a population-based survey in Jamaica
Authors: Lalwani Kunal , Whitehorne-Smith Patrice , McLeary Joni-Gaye , Albarus Neena , Abel Wendel 
Published: November 2023

ObjectivesThis study aimed to examine concurrent polysubstance use of alcohol, tobacco and marijuana and determine correlations with access to marijuana, friend and familial drug use habits, risk perception and the age of initiation associated with the singular use of these substances.DesignA secondary data analysis.SettingUsed the Jamaica National Drug Prevalence Survey 2016 dataset.ParticipantsInvolved the entire dataset comprising 4623 randomly selected respondents between 12 and 65 years old.Outcome measuresPrimary outcome: concurrent polysubstance use recorded as using two or more of alcohol, tobacco and marijuana. Predictor variables include risk perception and age of initiation of singular alcohol, tobacco and marijuana use, ease of marijuana access and family and friend alcohol and illegal drug use.ResultsApproximately 58%–66% of respondents commenced singular alcohol, tobacco or marijuana use under 17. Participants commencing marijuana use at 11 years and under and between 12 and 17 were 3.346 and 4.560 times more likely to report past month concurrent polysubstance use (p=0.030 and p<0.001). Respondents who did not believe that smoking tobacco sometimes (p=0.049), and smoking marijuana sometimes and often was harmful, had increased odds of concurrent polysubstance use (p=0.047 and p<0.001, respectively). Respondents who indicated access to marijuana as easy were significantly more likely to report past month concurrent polysubstance use compared with those who reported access as difficult (p=0.002). Participants who indicated that friends or family members get drunk and take illegal drugs were associated with 1.722 and 1.864 increased odds of reporting past month concurrent polysubstance use (p=0.004 and p=0.017, respectively).ConclusionsDecreased perceived risk, childhood and adolescent age of initiation and easy access to marijuana were significantly associated with polysubstance use among Jamaicans. The influence of friends and family members’ drug and alcohol use behaviours on individuals developing polysubstance use habits further endorses the need for interventions.
Gender and racialisation of pharmaceutical sector leaders in Canada: a cross-sectional study
Authors: Satgunanathan Kasthuri , Workentin Aine , Woods Hannah , Sabir Areesha , Persaud Nav 
Published: November 2023

Objective/designLacking diversity in pharmaceutical leadership positions could contribute to inequities in medicine access. The objective of this cross-sectional study was to determine the gender and racial identities of individuals who hold leadership positions in the Canadian pharmaceutical sector.ParticipantsWe compiled a list of all Canadian governmental bodies, pharmaceutical companies and insurance providers. We identified individuals who were part of the leadership team, including executives and members of the board of directors.Primary outcome measuresThe main outcomes of the study were the racialisation and gender of the individuals in leadership positions. The gender and racialisation of an individual were determined by reviewing their name, pronouns and institutional profile through internet searches. Two members of the research team performed the assessment and a third reviewer resolved disagreements.ResultsWe identified 957 individuals holding leadership positions within the pharmaceutical sector, including 280 drug evaluation committee members, 12 governmental executive officers, 273 insurance company executive and board members and 392 executive and board members. Reviewers identified a total of 375 (39.2% of 957) women holding leadership roles, with most of these positions being held by governmental leaders (52.4% of 292) and a minority by insurance (37.0% of 273) and pharmaceutical (30.9% of 392) leaders. There were a total of 157 (16.4% of 957) racialised leaders, with most of these positions being held by governmental (18.5% of 292) and pharmaceutical (18.1% of 392) leaders, and a minority in insurance companies (11.7% of 273). Across the pharmaceutical sector, there were a total of 48 (5.0% of 957) racialised women and 327 (34.2% of 957) white women.ConclusionsLeaders within the Canadian pharmaceutical sector are mostly white men, and racialised women hold few leadership roles. Public policy should recognise that these institutions are mostly led by white men and reasons for this disparity could be explored.
Evaluating the balance of benefits and harms in chronic pain clinical trials: prioritizing individual participants over individual outcomes
Authors: Nishtar Mahd , Mark Remington , Langford Dale J , McDermott Michael P , Markman John D , Evans Scott R , France Fallon O , Park Meghan , Sharma Sonia , Turk Dennis C , Dworkin Robert H , Gewandter Jennifer S 
Published: November 2023

BackgroundRandomized clinical trials (RCTs) generally assess efficacy and safety separately, with the conclusion of whether a treatment is beneficial based solely on the efficacy endpoint. However, assessing and combining efficacy and safety domains, using a single composite outcome measure, can provide a more comprehensive assessment of the overall effect of a treatment. Furthermore, composite outcomes can incorporate information regarding the relationship between the individual outcomes. In fact, such outcomes have been suggested in the clinical trials literature for at least 15 years.ObjectivesTo (1) identify whether recent primary publications of chronic pain RCTs from major pain journals included a composite outcome measure of benefits and harms and (2) discuss the potential benefits of such outcomes in various stages of treatment development, including as outcome measures in RCTs, and to support decisions of Data and Safety Monitoring Boards and ordering of treatments in the context of treatment guidelines.Evidence reviewRCTs published in 6 major pain journals published between 2016 and 2021 that investigated interventions for chronic pain were reviewed.FindingsOf 73 RCTs identified, only 2 included a composite outcome measure of benefits and harms. Both of these articles compared 2 active treatments.ConclusionsComposite outcomes of benefits and harms are underutilized in chronic pain RCTs. The advantages and challenges of using such outcomes are discussed.
The Early Jurassic sequence of Lyme Regis, Dorset, England and its place in the history of geology and palaeontology
Authors: Sharpe Tom 
Published: November 2023

Abstract

The cliffs and foreshore at Lyme Regis on the Dorset coast expose a sequence of Early Jurassic marine limestones and mudstones of the Blue Lias Formation and the overlying Charmouth Mudstone Formation, the lowest units of the Hettangian–Aalenian Lias Group. Known for its fossils since at least the mid-seventeenth century, this coastal section became famous in the early nineteenth century for the bones of ‘fossil crocodiles’. Many of the most significant discoveries were made by a family of fossil dealers whose best-known member was Mary Anning (1799–1847). Anning and her family recovered the first scientifically described ichthyosaurs, the first complete plesiosaur and the first British pterosaur to be identified. Anning's finds from Lyme Regis formed the basis of the pioneering palaeoenvironmental reconstruction
Duria antiquior
. Her geologist friends, some with close personal associations to the town, did much to publicize her discoveries and contribute to both her fame and that of the locality. This famous coastal section, with its important historical associations with a key period in the development of geology and the source of so many significant discoveries in the early nineteenth century, now lies within the Jurassic Coast UNESCO World Heritage Site.
The Timurid Regions and Moghulistan through the Eyes of a Ming Diplomat: An Annotated Translation of the Xiyu fanguo zhi and Selected Poems by Chen Cheng (1415)
Authors: Fan Carol 
Published: November 2023

Abstract
The article investigates the fifteenth-century Ming diplomat Chen Cheng’s travel accounts by situating them against the backdrop of Islamic and Mongol history. The first part of the article presents Chen Cheng’s travels and his reports in the context of Ming-Timurid relations and comprehensively studies the existing editions of Chen’s writings. The second part of the article provides a complete, critical, and annotated translation of Chen’s travel narrative, the Xiyu fanguo zhi, and a selection of his poems that describe the Timurid and eastern Chaghatayid regions through which the ambassador traveled. The translation is based on the text from Chen’s personal literary collection, the Chen Zhushan wenji, which has not yet been adequately utilized in English scholarship. Incorporating information from contemporary sources, the annotated translation contextualizes Chen’s accounts in Islamic history of Western and Central Asia. Finally, the article supplements the translation with a biography of Chen Cheng and information extracted from his itinerary.