bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Cell Death Induction by the Barley NLR Immune Receptor PBR1
Authors: Jaiswal Namrata , Myers Ariana , Weese Terri L. , Carter Morgan E. , Scofield Steven R. , Helm Matthew 
Published: March 2023

The barley ( Hordeum vulgare subsp. vulgare) disease-resistance protein AvrPphB Response 1 (PBR1) mediates recognition of the Pseudomonas syringae effector, AvrPphB. PBR1 belongs to the coiled-coil nucleotide-binding leucine-rich repeat family. However, little is known about the molecular mechanisms that lead to PBR1-dependent cell death (hypersensitive reaction; HR) in response to AvrPphB. Here, we investigated PBR1 immune signaling after Agrobacterium-mediated transient expression in Nicotiana benthamiana. The N-terminal tagging of PBR1 with super yellow fluorescent protein abolished PBR1-mediated cell death, demonstrating that an N-terminal epitope tag disrupts PBR1-mediated immune signaling. Furthermore, none of the individual protein domains (CC, NB-ARC, and LRR) or truncations (CC—NB-ARC and NB-ARC—LRR) of PBR1 induced a HR-like cell death response as strong as full-length PBR1 when coexpressed with AvrPphB, indicating that the individual domains and fragments of PBR1 are insufficient to trigger HR. Intriguingly, introducing the typically autoactivating D496V mutation within NB-ARC-containing fragments of PBR1 does not activate immune signaling, revealing that PBR1-mediated immune signaling requires the cooperation of all domains in cis. Using coimmunoprecipitation and split-luciferase assays, we also show full-length PBR1 self-associates in the absence of AvrPphB, and such self-association is not dependent on a functional P-loop/Walker A motif. Collectively, these findings provide valuable insights into PBR1-mediated disease resistance and extend our understanding of NLR-mediated immune signaling. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Rent-a-MEDEX
Authors: Pedersen Donald , Hooker Roderick S. 
Published: March 2023

ABSTRACT
In the 1970s, busy physicians knew little about the capabilities of a new member of the healthcare team—the physician associate/assistant (PA). Internal studies by the University of Utah and University of Washington educational programs demonstrated that the MEDEX/PA could increase access to care by providing quality, cost-effective care in rural primary care practices. Marketing this concept was essential, and in the early 1970s, the Utah program devised an innovative plan, partially funded through a grant from the federal Bureau of Health Resources Development, called Rent-a-MEDEX. Physicians in the Intermountain West were introduced to graduate MEDEX/PAs in order to gain firsthand experience about how these new clinicians could benefit a busy primary care practice.
Salvage therapies of autoimmune hepatitis limit proinflammatory immune cells while sparing regulatory T cells
Authors: Derben Finn C. , Ytting Henriette , Hartleben Björn , Bantel Heike , Wedemeyer Heiner , Willemoe Gro L. , Jaeckel Elmar , Taubert Richard 
Published: March 2023

Background:
Autoimmune hepatitis (AIH) can be clinically controlled by first-line immunosuppressive therapy in the majority of patients. However, a selective decrease in intrahepatic regulatory T cells (Treg) was observed with immunosuppressive therapy, which was even more pronounced in patients with incomplete responses than in patients who achieved biochemical remission. The effects of salvage therapies on the number of intrahepatic T and B cells, including Treg, are unclear. The hypothesis was that calcineurin inhibitors would further decrease intrahepatic Treg numbers, and the mammalian target of rapamycin inhibitors would increase intrahepatic Treg numbers.

Methods:
In this retrospective study at 2 centers, CD4+, CD8+ and CD4+FOXP3+ T cells, and CD79a+ B cells were quantified in surveillance biopsies under non–standard-of-care treatment [non-SOC: calcineurin inhibitor (n=10), second-line antimetabolites (n=9), mammalian target of rapamycin inhibitors (n=4)] compared with patients under the standard-of-care treatment (SOC).

Results:
Intrahepatic T-cell and B-cell counts were not significantly different between patients with biochemical remission under SOC and non-SOC. However, patients with incomplete response under non-SOC had significantly lower liver infiltration with T and B cells, whereas Treg were not reduced compared with SOC. This resulted in an even higher ratio of Treg to T and B cells in non-SOC compared with SOC when biochemical remission was not achieved. The different non-SOC regimens showed no significant difference in liver infiltration with T cells, including Treg and B cells.

Conclusions:
Non-SOC in AIH partially controls intrahepatic inflammation by limiting the hepatic infiltration of total T and B cells as the main drivers of inflammation without further decreasing intrahepatic Treg. A negative effect of calcineurin inhibitor and a positive effect of mammalian target of rapamycin inhibitors on the number of intrahepatic Treg was not observed.
Long-Term Outcome of Clozapine in Treatment-Resistant Schizophrenia
Authors: Lee Myung A. , Cola Philip , Jayathilake Karu , Meltzer Herbert Y. 
Published: March 2023

AbstractPurpose/BackgroundThe favorable effect of clozapine on psychotic symptoms in patients with treatment-resistant (TR) schizophrenia (SCZ) in short-term studies is well established. However, prospective studies of the long-term outcome of clozapine treatment on psychopathology, cognition, quality of life, and functional outcome in TR-SCZ are limited.Methods/ProceduresHere, we have examined the long-term (mean duration of follow-up 14 years) effects of clozapine on those outcomes in a prospective, open label study in 54 TR-SCZ patients. Assessments were performed at baseline, 6 weeks, 6 months, and at the last follow-up.Findings/ResultsBrief Psychiatric Rating Scale (BPRS) total, positive symptoms, and anxiety/depression at the last follow-up improved significantly from baseline, as well as from the 6-month evaluation (P< 0.0001), with a 70.5% responder rate (≥20% improvement at the last follow-up from baseline). Quality of Life Scale (QLS) total improved by 72% at the last follow-up, with 24% of patients rated as having “good” functioning compared with 0% at baseline. Suicidal thoughts/behavior was significantly reduced at the last follow-up from the baseline. No significant change in negative symptoms was found at the last follow-up in the total sample. Short-term memory function declined at the last follow-up from baseline, but there was no significant change in processing speed. The QLS total showed a significant negative correlation with BPRS positive symptoms but not with cognitive measures, or negative symptoms, at the last follow-up.Implications/ConclusionsFor patients with TR-SCZ, improving psychotic symptoms with clozapine seems to have a more significant impact than negative symptoms or cognition on improving psychosocial function.
Return to Ballet Progression for Dancers After Hip Arthroscopy for Instability or Femoroacetabular Impingement Syndrome
Authors: Curley Andrew J. , Stack Mary Jean , Ruh Ethan , Gibson Brittany , Anderson Kelley A. , Vyas Dharmesh 
Published: March 2023

Abstract:
Ballet dancers may be predisposed to hip injuries because of the unique demands placed on the hips during dance training and performance. Hip arthroscopy can be used to address several of these symptomatic disorders, including hip instability and femoroacetabular impingement syndrome (FAIS). After hip arthroscopy, ballet dancers undergo a rehabilitation program to allow for healing, range of motion restoration, and progressive strengthening. Once patients complete the standard postoperative therapy program, a paucity of information is available to guide dancers back to the advanced hip movements involved in ballet. Therefore, the purpose of this clinical commentary is to present a stepwise rehabilitation protocol with return to ballet progression for dancers undergoing hip arthroscopy for instability or FAIS. Particular emphasis is placed on movement-specific exercises for ballet performers, and objective clinical metrics, to guide return to dance progression.
Update on ladder plates for mandibular angle fractures
Authors: Soliman Luke , King Victor , Yeoh Melvyn S. , Woo Albert S. 
Published: March 2023

Purpose of review
Fractures of the mandibular angle are surgically challenging with high rates of postoperative complications. Among established fixation techniques for these injuries, Champy's tension band approach with miniplate fixation has held prominence. Rigid fixation, using two plates, also remains commonly used. More recently, geometric ladder plates, which confer greater three-dimensional stability have been developed to overcome the shortcomings of conventional fixation approaches. Herein, we aim to summarize the recent evidence surrounding the use of ladder plates and offer our own opinion for optimal treatment of these fractures.

Recent findings
In high-powered studies, the rates of hardware failure, malocclusion, and malunion are lower among cohorts managed with ladder plates relative to miniplate groups. Rates of infection and paresthesia remain similar. Ladder plates have also been shown to decrease operative time in preliminary study.

Summary
Ladder plates show superiority to miniplate approaches across several outcomes. However, the relatively larger strut plate constructs may not be necessary for minor, uncomplicated fractures. It is our belief that reasonable outcomes may be achieved with either approach depending on surgeon experience and comfort with the given fixation technique.
Managing periprosthetic tibia fractures: International perspectives
Authors: Lewis Daniel P. , Tarrant Seth M. , MacKenzie Stuart , Cornford Lachlan , Sato Toru , Shiota Naofumi , Balogh Zsolt J. 
Published: March 2023

Summary:
Knee arthroplasty, both total knee and unicompartmental, has had a significant impact on millions of patients globally. Although satisfaction is usually high, complications such as periprosthetic fracture are increasingly common. Distal femur periprosthetic fractures are relatively well researched and understood in comparison with periprosthetic proximal tibia fractures (PTFs). The management of PTFs is essentially an evidence-free area. This review explores the literature (or lack thereof) and integrates cases from Australia and Japan. As it stands, there is scant literature relating to all facets of PTFs, including, most concerningly, the management of them. Larger studies are required to help further investigate this important interface between arthroplasty and orthopaedic trauma. As a guide, those with loose prostheses will likely benefit most from revision total knee arthroplasty, while those with well-fixed prostheses can be managad according to the fracture with homage paid to the presence of the prosthesis. The use of periarticular locked plates is likely a better option over conventional large or small fragment plates. Nonoperative management is a viable option for selected individuals and can be associated with favorable outcomes.
Exploring Delay to Follow-Up in a Rural Multidisciplinary Cleft Clinic
Authors: Byrnes Yasmeen M. , Miller Stephanie P. , Frank Katie , Hoffman Rebecca L. , Kauffman Christian A. 
Published: March 2023

Background
Oral clefts require longitudinal multidisciplinary care with follow-up visits at regular intervals throughout a patient's childhood, and delayed care can be detrimental. Although loss to follow-up is commonly studied, this metric does not account for patients that do return to care, but months or years later than recommended. The aim of this study was to explore and determine risk factors for delay to follow-up (DTFU) in a cleft clinic at a rural academic center.

Methods
Medical records from the multidisciplinary cleft clinic at a single rural tertiary care institution between January 1, 2010, and December 31, 2019, were reviewed. The primary outcome was DTFU, measured as the difference in days between recommended and actual follow-up dates for a given visit.

Results
A cohort of 282 patients was analyzed, with a total of 953 visits. A total of 71% of patients experienced at least 1 delay in follow-up of 30 days or longer, and 50% had at least 1 delay of 90 days or longer. Out of all visits, the mean DTFU was 73 days (around 2.5 months). For 23% of patients, at least half their visits were delayed by more than 90 days, whereas 11% experienced a delay of more than 90 days with every visit. Patients who failed to show up to at least 1 appointment had significantly higher risk of DTFU (P < 0.0001). Driving distance, driving time, SES, stage of cleft care, and cleft phenotype were not correlated with DTFU. For canceled appointments, 50.5% of recorded cancellation reasons were patient driven.

Conclusions
Delay to follow-up in a multidisciplinary cleft clinic was prevalent in this rural cohort, with half of patients experiencing delays of 3 months or longer, and about 1 in 9 experiencing this delay with every visit. Delay to follow-up identifies patients with consistently high rates of delay in care, which could eventually lead to targeted interventions to increase compliance. Delay to follow-up may be a new and valuable measure of cleft care compliance that can be easily implemented by other institutions. Further investigation is needed to determine the relationship between delay and clinical outcomes in cleft patients.
Augmenting Breast Implant Research
Authors: Shih Sabrina , Salazar Hector F. , Poveromo Luke P. , Askinas Carly , Vernice Nicholas , Corpuz George S. , O'Connell Gillian M. , Dong Xue , Spector Jason 
Published: March 2023

Background
Because of the association of textured breast implants with breast implant–associated anaplastic large cell lymphoma, anatomically shaped breast implants, which rely on a textured surface to maintain rotational stability, have been recalled from the market. The dearth of anatomically shaped implants on the market reflects a need for novel breast implant technology, which has been traditionally developed by commercial breast implant manufacturers due to the complexities of implant manufacturing. To increase the accessibility of preclinical breast implant research, miniature breast implants made from polydimethylsiloxane were designed and fabricated for high throughput and low-cost prototyping and in vivo testing of both smooth and textured implants in a laboratory setting.

Methods
Two-piece negative molds measuring 2 × 1 cm were constructed in Fusion360 and 3D printed in Polysmooth filament. Textured molds were painted with a mixture of an epoxy and fine sugar or granular salt to create textured surfaces, while molds for smooth implants were smoothed using ethanol spray. Molds were injected with polydimethylsiloxane and cured for 12 hours at 37°C. The surface topography of laboratory-made implants and commercial textured and smooth implant shells was analyzed using scanning electron microscopy and implants were evaluated in vivo in an immunocompetent rodent model.

Results
Implants retained the original dome shape of the 3D-printed molds. Qualitative assessment of scanning electron microscopy images demonstrated similar surface topography between laboratory-made and commercial smooth and textured implants. There was no statistical difference in the diameter or density of the surface indentations of the Allergan's textured implant compared with laboratory-made textured implants (P > 0.05). Finally, the surface topography and thickness of laboratory-made implant capsules were similar to previously published data using industry made miniature silicone devices implanted in rats.

Conclusions
This study demonstrates a low-cost, highly customizable approach to fabricate miniature smooth and textured breast implant prototypes for in vivo studies. The accessibility of this implant fabrication strategy allows nonindustry investigators to develop novel implant designs more rapidly for preclinical investigation.
A Critical Analysis of Factors Associated With Anteroposterior Implant Flipping in Immediate Breast Reconstruction
Authors: Leibl Kayla E. , Hwang Lyahn K. , Anderson Cassidy , Weichman Katie E. 
Published: March 2023

Background
Implant-based reconstruction remains the most common form of postmastectomy breast reconstruction. With ever-evolving device characteristics, including the advent of high-profile, cohesive, fifth-generation implants, the incidence of anterior-posterior flipping of implants is presenting a new challenge. Patient and device characteristics associated with this phenomenon have yet to be fully elucidated.

Methods
Patients who underwent nipple- or skin-sparing mastectomy with subsequent 2-stage or direct-to-implant reconstruction with smooth implants between 2015 and 2021 were retrospectively identified and stratified by incidence of implant flipping. Patient, procedural, and device characteristics were evaluated.

Results
Within 165 patients (255 reconstructed breasts), 14 cases of implant flipping were identified (flip rate 5.5%). All flips occurred in patients with cohesive implants (odds ratio [OR], 87.0; P = 0.002). On univariate analysis, extra full implant profile (OR, 11.2; P < 0.001) and use of a smooth tissue expander for 2-stage reconstruction (OR, 4.1; P = 0.03) were associated with flipping. Implants that flipped were larger than those that did not (652.5 ± 117.8 vs 540.1 ± 171.0 mL, P = 0.0004). Prepectoral implant placement (OR, 2.7; P = 0.08) and direct-to-implant method (OR, 3.17; P = 0.07) trended toward association, but this effect was not significant. Patient BMI, weight fluctuation during the reconstructive course, mastectomy weight, AlloDerm use, and history of seroma or periprosthetic infection were not associated with flipping.

Conclusion
Patients who receive a highly cohesive, high profile, larger implant are at increased risk for implant flipping. In addition, patients who receive a smooth tissue expander are more likely to experience flipping of their subsequent implant, compared with those who had textured tissue expanders. These characteristics warrant consideration during device selection to minimize discomfort, aesthetic deformity, and the need for reoperation.
Clinical outcomes after extended 12-month antiretroviral therapy prescriptions in a community-based differentiated HIV service delivery programme in South Africa: a retrospective cohort study
Authors: Lewis Lara , Sookrajh Yukteshwar , van der Molen Johan , Khubone Thokozani , Sosibo Phelelani , Maraj Munthra , van Heerden Rose , Little Francesca , Kassanjee Reshma , Garrett Nigel , Dorward Jienchi 
Published: March 2023

AbstractIntroductionThere is an urgent need for more efficient models of differentiated antiretroviral therapy (ART) delivery for people living with HIV (PLHIV), with the World Health Organization calling for evidence to guide whether annual ART prescriptions and consultations (12M scripts) should be recommended in global guidelines. We assessed the association between 12M scripts (allowed temporarily during the COVID-19 pandemic) versus standard 6-month prescriptions and clinical review (6M scripts) and clinical outcomes.MethodsWe performed a retrospective cohort study using routine, de-identified data from 59 public clinics in KwaZulu-Natal, South Africa. We included PLHIV aged>18 years with a recent suppressed viral load (VL) who had been referred for community ART delivery with 6M or 12M scripts. We used modified Poisson regression to compare 12-month retention-in-care (not >90 days late for any visit) and viral suppression (<50 copies/mL) between prescription groups.ResultsAmong 27,148 PLHIV referred for community ART between Jun-Dec 2020, 42.6% received 6M scripts and 57.4% 12M scripts. The median age was 39 years (interquartile range [IQR] 33-46) and 69.4% were women. Age, gender, prior community ART use and time on ART were similar in the two groups. However, more of the 12M script group had a dolutegravir-based regimen (60.0% versus 46.3%). The median (IQR) number of clinic visits in the 12 months of follow-up was 1(1-1) in the 12M group and 2(2-3) in the 6M group. Retention at 12 months was 94.6% (95% confidence interval [CI] 94.2%-94.9%) among those receiving 12M scripts and 91.8% (95% CI 91.3%-92.3%) among those with 6M scripts. 17.1% and 16.9% of clients in the 12M and 6M groups were missing follow-up VL data, respectively. Among those with VLs, 91.0% (95% CI 90.5%-91.5%) in the 12M group and 89.7% (95% CI 89.0%-90.3%) in the 6M group were suppressed. After adjusting for age, gender, ART regimen, time on ART, prior community ART use and calendar month, retention (adjusted risk ratio [aRR]: 1.03, 95% CI 1.01-1.05) and suppression (aRR: 1.01, 95% CI 1.00-1.02) were similar in the prescription groups.ConclusionsWider use of 12M scripts could reduce clinic visits without impacting short-term clinical outcomes.
Complications Post Endovascular Abdominal Aortic Aneurysm Repair in Patients with Diabetes Mellitus: A Meta-analysis and Systematic Review
Authors: Otify EA , Mekki M , Borucki J , Dhatariya K , Stather P W 
Published: March 2023

AbstractBackgroundPeople with diabetes mellitus (DM) have higher long-term mortality following abdominal aortic aneurysm (AAA) repair than those without DM. However, whether this adverse outcome is directly related to their aneurysm is unclear.AimsTo determine the rates of complications in people with and without DM post endovascular abdominal aortic aneurysm repair. Primary outcome data include AAA sac enlargement, reinterventions, endoleaks, post-operative AAA rupture and conversion to open surgical repair.MethodsPubMed, Embase and Cochrane databases were searched for primary research studies between 2005 and 2023 according to PRISMA guidelines. Those undergoing AAA repair via endovascular aneurysm repair were included.ResultsThirty-five studies were identified totalling 90,347 people in the control group, and 17,660 in the DM group. Those with DM had a lower rate of reintervention compared to controls (9.94% v 11.58%; OR 0.89, 95% CI [0.82-0.97]; P=0.005), however there was no significant difference in the rate of overall, type I or type II endoleaks (P=0.22, P=0.29, P=0.15 respectively).People with DM were also less likely to have sac enlargement post AAA repair (9.66% v 11.27%; OR 0.79, 95% CI [0.68-0.93]; P=0.003). Additionally, people with DM had a significantly reduced rate of conversion to open surgery (2.11 % DM v 3.12% control; OR 0.80, CI [0.66-0.97]: P=0.02).ConclusionReinterventions, sac enlargement post AAA repair, and conversion to open surgical repair were significantly lower in people with DM, however the cause for these differences remains unclear.