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Article: Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4

Itell, Hannah L / Humes, Daryl / Overbaugh, Julie

bioRxiv : the preprint server for biology

2023

Abstract: Type I interferon (IFN) upregulates proteins that inhibit HIV within infected cells. Prior studies have identified IFN-stimulated genes (ISGs) that impede lab-adapted HIV in cell lines, yet the ISG(s) that mediate IFN restriction in HIV target cells, ... ...

Abstract	Type I interferon (IFN) upregulates proteins that inhibit HIV within infected cells. Prior studies have identified IFN-stimulated genes (ISGs) that impede lab-adapted HIV in cell lines, yet the ISG(s) that mediate IFN restriction in HIV target cells, primary CD4
Language	English
Publishing date	2023-02-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.07.527545
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Article ; Online: Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4

Itell, Hannah L / Humes, Daryl / Overbaugh, Julie

Cell reports

2023 Volume 42, Issue 6, Page(s) 112556

Abstract	Type I interferon (IFN) upregulates proteins that inhibit HIV within infected cells. Prior studies have identified IFN-stimulated genes (ISGs) that impede lab-adapted HIV in cell lines, yet the ISG(s) that mediate IFN restriction in HIV target cells, primary CD4
MeSH term(s)	Humans ; Interferon Type I ; HIV-1/genetics ; HIV Infections/metabolism ; Cell Line ; HIV Seropositivity ; CD4-Positive T-Lymphocytes/metabolism
Chemical Substances	Interferon Type I
Language	English
Publishing date	2023-05-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112556
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Article ; Online: Regional variations and deprivation are linked to poorer access to laparoscopic and robotic colorectal surgery: a national study in England.

Morton, A J / Simpson, A / Humes, D J

Techniques in coloproctology

2023 Volume 28, Issue 1, Page(s) 9

Abstract: Background: Laparoscopic and now robotic colorectal surgery has rapidly increased in prevalence; however, little is known about how uptake varies by region and sociodemographics. The aim of this study was to quantify the uptake of minimally invasive ... ...

Abstract	Background: Laparoscopic and now robotic colorectal surgery has rapidly increased in prevalence; however, little is known about how uptake varies by region and sociodemographics. The aim of this study was to quantify the uptake of minimally invasive colorectal surgery (MIS) over time and variations by region, sociodemographics and ethnicity. Methods: Retrospective analysis of routinely collected healthcare data (Clinical Practice Research Datalink linked to Hospital Episode Statistics) for all adults having elective colorectal resectional surgery in England from 1 January 2006 to 31 March 2020. Sociodemographics between modalities were compared and the association between sociodemographic factors, region and year on MIS was compared in multivariate logistic regression analysis. Results: A total of 93,735 patients were included: 52,098 open, 40,622 laparoscopic and 1015 robotic cases. Laparoscopic surgery surpassed open in 2015 but has plateaued; robotic surgery has rapidly increased since 2017, representing 3.2% of cases in 2019. Absolute differences up to 20% in MIS exist between regions, OR 1.77 (95% CI 1.68-1.86) in South Central and OR 0.75 (95% CI 0.72-0.79) in the North West compared to the largest region (West Midlands). MIS was less common in the most compared to least deprived (14.6% of MIS in the most deprived, 24.8% in the least, OR 0.85 95% CI 0.81-0.89), with a greater difference in robotic surgery (13.4% vs 30.5% respectively). Female gender, younger age, less comorbidity, Asian or 'Other/Mixed' ethnicity and cancer indication were all associated with increased MIS. Conclusions: MIS has increased over time, with significant regional and socioeconomic variations. With rapid increases in robotic surgery, national strategies for procurement, implementation, equitable distribution and training must be created to avoid worsening health inequalities.
MeSH term(s)	Adult ; Humans ; Female ; Robotic Surgical Procedures ; Colorectal Surgery ; Retrospective Studies ; Digestive System Surgical Procedures ; Laparoscopy
Language	English
Publishing date	2023-12-11
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2083309-X
ISSN	1128-045X ; 1123-6337
ISSN (online)	1128-045X
ISSN	1123-6337
DOI	10.1007/s10151-023-02874-3
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Article: Host cell glycosylation selects for infection with CCR5- versus CXCR4-tropic HIV-1.

Itell, Hannah L / Humes, Daryl / Baumgarten, Nell E / Overbaugh, Julie

bioRxiv : the preprint server for biology

2023

Abstract: HIV-1 infection involves a selection bottleneck that leads to transmission of one or a few HIV variants, which nearly always use CCR5 as the coreceptor (R5 viruses) for viral entry as opposed to CXCR4 (X4 viruses). The host properties that drive this ... ...

Abstract	HIV-1 infection involves a selection bottleneck that leads to transmission of one or a few HIV variants, which nearly always use CCR5 as the coreceptor (R5 viruses) for viral entry as opposed to CXCR4 (X4 viruses). The host properties that drive this selection are not well understood and may hold keys to factors that govern HIV susceptibility. In this report, we identified SLC35A2, a transporter of UDP-galactose, as a candidate X4-specific restriction factor in CRISPR-knockout screens in primary target CD4
Language	English
Publishing date	2023-09-05
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.05.556399
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Article ; Online: Differences in progression by surgical specialty: a national cohort study.

Hope, Carla / Lund, Jonathan / Griffiths, Gareth / Humes, David

BMJ open

2022 Volume 12, Issue 2, Page(s) e053391

Abstract: The aim of surgical training across the 10 surgical specialties is to produce competent day 1 consultants. Progression through training in the UK is assessed by the Annual Review of Competency Progression (ARCP).: Objective: This study aimed to ... ...

Abstract	The aim of surgical training across the 10 surgical specialties is to produce competent day 1 consultants. Progression through training in the UK is assessed by the Annual Review of Competency Progression (ARCP). Objective: This study aimed to examine variation in ARCP outcomes within surgical training and identify differences in outcomes between specialties. Design: A national cohort study using data from the UK Medical Education Database was performed. ARCP outcome was the primary outcome measure. Multilevel ordinal regression analyses were performed, with ARCP outcomes nested within trainees. Participants: Higher surgical trainees (ST3-ST8) from nine UK surgical specialties were included (vascular surgery was excluded due to insufficient data). All surgical trainees across the UK with an ARCP outcome between 2010 and 2017 were included. Results: Eight thousand two hundred and twenty trainees with an ARCP outcome awarded between 2010 and 2017 were included, comprising 31 788 ARCP outcomes. There was substantial variation in the proportion of non-standard outcomes recorded across specialties with general surgery trainees having the highest proportion of non-standard outcomes (22.5%) and urology trainees the fewest (12.4%). After adjustment, general surgery trainees were 1.3 times more likely to receive a non-standard ARCP outcome compared with trainees in trauma and orthopaedics (T&O) (OR 1.33, 95% CI 1.21 to 1.45, p=0.001). Urology trainees were 36% less likely to receive a non-standard outcome compared with T&O trainees (OR 0.64, 95% CI 0.54 to 0.75, p<0.001). Female trainees and older age were associated with non-standard outcomes (OR 1.11, 95% CI 1.02 to 1.22, p=0.020; OR 1.04, 95% CI 1.03 to 1.05, p<0.001). Conclusion: There is wide variation in the training outcome assessments across surgical specialties. General surgery has higher rates of non-standard outcomes compared with other surgical specialties. Across all specialties, female sex and older age were associated with non-standard outcomes.
MeSH term(s)	Clinical Competence ; Cohort Studies ; Education, Medical ; Education, Medical, Graduate ; Educational Measurement ; Female ; Humans ; Specialties, Surgical/education ; United Kingdom
Language	English
Publishing date	2022-02-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2021-053391
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Article ; Online: Correction to: The impact of COVID-19 on surgical training: a systematic review.

Hope, C / Reilly, J-J / Griffiths, G / Lund, J / Humes, D

Techniques in coloproctology

2021 Volume 25, Issue 11, Page(s) 1267–1268

Language	English
Publishing date	2021-09-21
Publishing country	Italy
Document type	Published Erratum
ZDB-ID	2083309-X
ISSN	1128-045X ; 1123-6337
ISSN (online)	1128-045X
ISSN	1123-6337
DOI	10.1007/s10151-021-02520-w
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Article ; Online: The impact of COVID-19 on surgical training: a systematic review.

Hope, C / Reilly, J-J / Griffiths, G / Lund, J / Humes, D

Techniques in coloproctology

2021 Volume 25, Issue 5, Page(s) 505–520

Abstract: Background: Coronavirus disease (COVID-19) has caused global disruption to health care. Non-urgent elective surgical cases have been cancelled, outpatient clinics have reduced and there has been a reduction in the number of patients presenting as an ... ...

Abstract	Background: Coronavirus disease (COVID-19) has caused global disruption to health care. Non-urgent elective surgical cases have been cancelled, outpatient clinics have reduced and there has been a reduction in the number of patients presenting as an emergency. These factors will drastically affect the training opportunities of surgical trainees. The aim of this systematic review is to describe the impact of COVID-19 on surgical training globally. Methods: The review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with the Open Science Framework (OSF). Medline, EMBASE, PubMed and the Cochrane Central Register of Controlled Trials were searched. Results: The searches identified 499 articles, 29 of which were included in the review. This contained data from more than 20 countries with 5260 trainees and 339 programme directors. Redeployment to non-surgical roles varied across studies from 6% to 35.1%. According to all of the studies, operative experience has been reduced. Knowledge learning had been switched to online platforms across 17 of the studies and 7 reported trainees had increased time to devote to educational/academic activities. All of the studies reporting on mental health report negative associations with increased stress, ranging from 54.9% to 91.6% of trainees. Conclusions: The impact of COVID-19 on surgical trainees has been experienced globally and across all specialities. Negative effects are not limited to operative and clinical experience, but also the mental health and wellbeing of trainees. Delivery of surgical training will need to move away from traditional models of learning to ensure trainees are competent and well supported.
MeSH term(s)	COVID-19 ; Humans ; SARS-CoV-2
Language	English
Publishing date	2021-01-28
Publishing country	Italy
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	2083309-X
ISSN	1128-045X ; 1123-6337
ISSN (online)	1128-045X
ISSN	1123-6337
DOI	10.1007/s10151-020-02404-5
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Article ; Online: Personal Characteristics Associated with Progression in Trauma and Orthopaedic Specialty Training: A Longitudinal Cohort Study.

Hope, Carla / Humes, David / Griffiths, Gareth / Lund, Jonathan

Journal of surgical education

2021 Volume 79, Issue 1, Page(s) 253–259

Abstract: Aim: To identify demographic factors, including protected characteristics, and training specific factors which predict a nonstandard Annual Review of Competency Progression (ARCP) outcome during Trauma and Orthopedic Specialty training in the United ... ...

Abstract	Aim: To identify demographic factors, including protected characteristics, and training specific factors which predict a nonstandard Annual Review of Competency Progression (ARCP) outcome during Trauma and Orthopedic Specialty training in the United Kingdom (UK). Method: A longitudinal cohort study using data from UKMED was performed. ARCP outcome was the primary outcome measure. Multilevel univariate and multiple ordinal regression analyses were performed using STATA v 15. Results: Two thousand five hundred and ten Trauma and Orthopedic surgery trainees (ST3-ST8) with an ARCP outcome between 2010 and 2017 were included, comprising 11,011 ARCP outcomes. Eighty five percent (2130/2510) of trainees were male. Eighty two percent of outcomes were satisfactory. Female trainees had a 26% increased risk of nonstandard outcome (OR 1.26 95% CI 1.10-1.44) after adjusting for other factors. Older age at ARCP was associated with an increased risk of nonstandard ARCP outcome (OR 1.04 95% CI 1.03-1.06). International medical graduates had a 34% decreased risk of nonstandard outcome compared to UK graduates (OR 0.66 95% CI 0.54-0.81). Less than full time training was not associated with risk of a nonstandard ARCP outcome (OR 0.92 95% CI 0.76-1.12). Conclusion: Female sex and older age at ARCP were significantly associated with nonstandard ARCP outcomes in Trauma and Orthopedic surgery, while international medical graduation was protective.
MeSH term(s)	Clinical Competence ; Cohort Studies ; Education, Medical, Graduate ; Educational Measurement ; Female ; Humans ; Longitudinal Studies ; Male ; Orthopedics ; United Kingdom
Language	English
Publishing date	2021-07-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2277538-9
ISSN	1878-7452 ; 1931-7204
ISSN (online)	1878-7452
ISSN	1931-7204
DOI	10.1016/j.jsurg.2021.06.027
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Article ; Online: Predictors of persistent postoperative opioid use following colectomy: a population-based cohort study from England.

Baamer, R M / Humes, D J / Toh, L S / Knaggs, R D / Lobo, D N

Anaesthesia

2023 Volume 78, Issue 9, Page(s) 1081–1092

Abstract: This retrospective cohort study on adults undergoing colectomy from 2010 to 2019 used linked primary (Clinical Practice Research Datalink), and secondary (Hospital Episode Statistics) care data to determine the prevalence of persistent postoperative ... ...

Abstract	This retrospective cohort study on adults undergoing colectomy from 2010 to 2019 used linked primary (Clinical Practice Research Datalink), and secondary (Hospital Episode Statistics) care data to determine the prevalence of persistent postoperative opioid use following colectomy, stratified by pre-admission opioid exposure, and identify associated predictors. Based on pre-admission opioid exposure, patients were categorised as opioid-naïve, currently exposed (opioid prescription 0-6 months before admission) and previously exposed (opioid prescription within 7-12 months before admission). Persistent postoperative opioid use was defined as requiring an opioid prescription within 90 days of discharge, along with one or more opioid prescriptions 91-180 days after hospital discharge. Multivariable logistic regression analyses were conducted to obtain odds ratios for predictors of persistent postoperative opioid use. Among the 93,262 patients, 15,081 (16.2%) were issued at least one opioid prescription within 90 days of discharge. Of these, 6791 (45.0%) were opioid-naïve, 7528 (49.9%) were currently exposed and 762 (5.0%) were previously exposed. From the whole cohort, 7540 (8.1%) developed persistent postoperative opioid use. Patients with pre-operative opioid exposure had the highest persistent use: 5317 (40.4%) from the currently exposed group; 305 (9.8%) from the previously exposed group; and 1918 (2.5%) from the opioid-naïve group. The odds of developing persistent opioid use were higher among individuals who used long-acting opioid formulations in the 180 days before colectomy than those who used short-acting formulations (odds ratio 3.41 (95%CI 3.07-3.77)). Predictors of persistent opioid use included: previous opioid exposure; high deprivation index; multiple comorbidities; use of long-acting opioids; white race; and open surgery. Minimally invasive surgical approaches were associated with lower odds of persistent opioid use and may represent a modifiable risk factor.
MeSH term(s)	Adult ; Humans ; Analgesics, Opioid/therapeutic use ; Retrospective Studies ; Cohort Studies ; Pain, Postoperative/drug therapy ; Pain, Postoperative/epidemiology ; Opioid-Related Disorders/epidemiology ; Opioid-Related Disorders/etiology ; Drug Prescriptions ; Colectomy/adverse effects
Chemical Substances	Analgesics, Opioid
Language	English
Publishing date	2023-06-02
Publishing country	England
Document type	Journal Article
ZDB-ID	80033-8
ISSN	1365-2044 ; 0003-2409
ISSN (online)	1365-2044
ISSN	0003-2409
DOI	10.1111/anae.16055
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Article: The TOP vector: a new high-titer lentiviral construct for delivery of sgRNAs and transgenes to primary T cells.

Humes, Daryl / Rainwater, Stephanie / Overbaugh, Julie

Molecular therapy. Methods & clinical development

2020 Volume 20, Page(s) 30–38

Abstract: Efficient delivery of nucleic acids for the engineering of primary T cells is central to the study of the basic biology of these key immune effector cells and has clinical implications. To date, lentiviral vectors delivering guide RNAs for CRISPR-Cas9 ... ...

Abstract	Efficient delivery of nucleic acids for the engineering of primary T cells is central to the study of the basic biology of these key immune effector cells and has clinical implications. To date, lentiviral vectors delivering guide RNAs for CRISPR-Cas9 editing are not optimal for use in primary cells. Herein, we describe the T cell optimized for packaging (TOP) vector for delivering guide RNAs and transgenes into primary T cells. The TOP vector produces high-titer virus compared to a routinely used guide RNA vector, resulting in a ~10-fold increase in transduction in T cells. Moreover, a TOP vector expressing a chimeric antigen receptor and a guide RNA targeting the T cell receptor showed an ~5- to 9-fold increased transduction efficiency with ~2- to 3-fold higher expression compared to the commonly used epHIV7 vector and was simultaneously able to mediate efficient knockout of the endogenous T cell receptor in >71% of transduced cells upon Cas9 electroporation. The increased packaging of the TOP vector genome into viral particles appears to contribute to its higher transduction efficiency. The TOP vector represents an optimal tool for tandem delivery of transgenes and guide RNAs to primary T cells for use in functional screens and immunotherapy applications.
Language	English
Publishing date	2020-10-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2020.10.020
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