bluuebunny/crossref_metadata_2025_split huggingface dataset:
GLABRA3-mediated trichome branching requires transcriptional repression of MICROTUBULE-DESTABILIZING PROTEIN25
Authors: Xie Wenfei , Zhao Yuang , Deng Xianwang , Chen Ruixin , Qiang Zhiquan , García-Caparros Pedro , Mao Tonglin , Qin Tao 
Published: October 2024

Abstract
Microtubules play pivotal roles in establishing trichome branching patterns, which is a model system for studying cell-shape control in Arabidopsis (Arabidopsis thaliana). However, the signaling pathway that regulates microtubule reorganization during trichome branching remains poorly understood. In this study, we report that MICROTUBULE-DESTABILIZING PROTEIN25 (MDP25) is involved in GLABRA3 (GL3)-mediated trichome branching by regulating microtubule stability. Loss of MDP25 function led to excessive trichome branching, and this phenotype in mdp25 could not be rescued by the MDP25 K7A or MDP25 K18A mutated variants. Pharmacological treatment and live-cell imaging revealed increased microtubule stability in the mdp25 mutant. Furthermore, the microtubule collar observed during trichome branching remained more intact in mdp25 compared to the WT under oryzalin treatment. Results of genetic assays further demonstrated that knocking out MDP25 rescued the reduced branching phenotype of gl3 trichomes. In gl3 trichomes, normal microtubule organization was disrupted, and microtubule stability was significantly compromised. Moreover, GL3 physically bound to the MDP25 promoter, thereby inhibiting its expression. Overexpression of GL3 negated the effects of PMDP25-driven MDP25 or its mutant proteins on trichome branching and microtubules in the mdp25 background. Overall, our study uncovers a mechanism by which GL3 inhibits MDP25 transcription, thereby influencing microtubule stability and regulating trichome branching. This mechanism provides a connection between early regulatory components and microtubules during trichome development.
Infliximab vs interferon-α in the treatment of Behçet’s syndrome: clinical data from the BIO-BEHÇET’S randomized controlled trial
Authors: Moots Robert J , Fortune Farida , Jackson Richard , Thornburn Tony , Morgan Ann , Carr Daniel F , Murray Philip I , Wallace Graham R , Situnayake Deva 
Published: October 2024

Abstract

Objectives
Whilst biologic therapy is used for Behçet’s syndrome of all subtypes refractory to first-line immunomodulation, there has been an absence of high-quality evidence and no predictive biomarkers to optimally inform choice. BIO-BEHÇET’S was a randomized, controlled, head-to-head clinical trial comparing the two most frequently used biologics in active refractory Behçet’s.

Methods
This was a Bayesian-designed, pragmatic, standard of care, two-arm, parallel head-to-head trial at four UK centres. Patients with active disease were randomized to infliximab or IFN-α2a, and received follow-up with symptom-directed examination at weeks 12 and 24. The primary outcome was the Behçet’s Disease Activity Index (BDAI) at 12 weeks. Secondary outcomes included BDAI at 24 weeks and significant improvement in individual organ systems, including ocular symptoms, oral and genital ulcers, arthritis pain, quality of life, disease activity and steroid use. Biomarkers were also investigated but are reported elsewhere.

Results
Seventy-nine patients were recruited. Both treatments were equally effective, with a mean difference of 0.13 in BDAI (80% confidence interval: –0.19, 0.46). No significant differences were observed for secondary outcomes, though there were clinically significant within-group reductions for each over time. A modest steroid-sparing effect was observed, with complete cessation of steroids in 20% and 44% of those randomized to infliximab and IFN-α2a, respectively. There was a trend for minor benefit in favour of infliximab in terms of tolerability and persistence.

Conclusion
In this first reported, high-quality, head-to-head trial of two biologics in Behçet’s, both infliximab and IFN-α2a showed comparable short-term clinical efficacy and safety in refractory active disease of all subtypes.

Trial registration
EudraCT: 2014–005390-36; ISRCTN: ISRCTN49793874
Serological and molecular analysis of Leishmania infection in a recent outbreak of visceral leishmaniasis in South Omo Zone, Ethiopia
Authors: Belay Habtamu , Eyelachew Endawek , Abose Ebise , Aklilu Esayas , Gebrewold Gashaw , Tadesse Henok , Tadese Alemayehu , Belay Robel , Belachew Mahlet , van Henten Saskia , Bishaw Tesfahun , Manaye Nigus , Kebede Zeyede , Wossen Mesfin , Tadese Gemechu , Tasew Geremew , van Griensven Johan , Pareyn Myrthe , Erko Berhanu , Abera Adugna 
Published: October 2024

Abstract

Background
Ethiopia has a high burden of visceral leishmaniasis. Recently, there was a significant increase in cases in the South Omo Zone. This study aims to assess the prevalence of Leishmania donovani infection and its associated factors.

Methods
A household-based cross-sectional study was carried out in January 2023 in the South Omo Zone in Ethiopia. Dried blood spot samples were collected from 382 randomly selected study participants. Direct agglutination test (DAT) and kinetoplast DNA real-time PCR tests were performed to detect L. donovani infection. Participants’ sociodemographic, clinical and risk factors for L. donovani infection data were collected using questionnaires. Bivariate and multivariate logistic regressions were used to analyze the data. Febrile cases were checked for malaria with a multiplex PCR assay.

Results
Overall prevalence of L. donovani infection among the sampled population was 32.5% (n=124), of which 41.1% (n=51) was detected by PCR, 33.9% (n=42) by DAT and 25.0% (n=31) by both tests. The majority of the positives were from the Logira (28.2%; n=35) and Dilbayne (29.0%; n=36) villages. Participants residing in Logira (adjusted OR [AOR]: 5.80; 95% CI 1.85 to 18.15) and Dilbayne (AOR: 3.38; 95% CI 1.15 to 9.96) villages and owning cows (AOR: 2.31; 95% CI 1.03 to 5.15) showed an association with Leishmania infection. Plasmodium falciparum was detected in 3.4% (n=2) of 59 febrile participants.

Conclusions
The prevalence of L. donovani infection in the South Omo Zone is high. Further research on the role of cows in the transmission cycle is needed to design the best strategy to control Leishmania infection in the South Omo Zone. Such interventions should focus on the Logira and Dilbayne villages, where most of the infections were identified.
The benefits and limitations of establishing the PA profession globally
Authors: Turkewitz Arden R. , Sallen Jane P. , Smith Rachel M. , Pitchford Kandi , Lay Kimberly , Smalley Scott 
Published: October 2024

ABSTRACT

Objective:
Physician associates/assistants (PAs) and their equivalents offer a solution to the supply and demand crisis to alleviate global healthcare needs. This study investigated how PA and PA equivalents address global healthcare needs across different healthcare systems, revealing recommendations for their use. The study also sought to catalog the global healthcare needs that PAs and equivalents are successfully alleviating, the roles in which they function, and the barriers facing implementation.

Methods:
A systematic review was conducted from October 2021 to April 2022 and rerun in June 2023 following PRISMA 2020 guidelines; additionally, supporting interviews were conducted with PAs and global health experts. Primary outcomes were geographic region, economy, healthcare needs, and healthcare systems. Secondary outcomes were PA use, license recognition, and successes or barriers when implementing PAs.

Results:
The literature and interviews focused on the global use of PAs and PA equivalents in six geographic regions, 63 countries, and five US territories where PAs or PA equivalents are employed, have been employed, are volunteering, or are being considered to support global healthcare needs. Most countries have a developing economy and an out-of-pocket healthcare system. PAs and PA equivalents hold 35 different practice titles, and most work in primary care. PAs alleviate healthcare shortages and economic disparities, specifically related to inequitable healthcare access. Globally, the profession is limited by a lack of legislation, regulation, and support.

Conclusions:
PAs and PA equivalents worldwide belong to an adaptable profession that has well-documented success in alleviating the global healthcare shortage and addressing healthcare needs. Countries desiring PAs or PA equivalents should identify their specific needs, train their existing workforce, employ pilot programs, and focus on seeking early legislation and regulation. Broad support for existing PA and PA equivalent international organizations is recommended for global collaboration. This study serves as a guide for those advocating for the continued or future implementation of PAs and PA equivalents in their own country and provides a comprehensive resource to aid in the globalization of this profession. We offer recommendations to address the dire healthcare needs and workforce shortage faced across the globe.
Iron Chelators Augment Large Osteochondral Allograft Osseointegration in a Preclinical Canine Model
Authors: Cook James L. , Drager Justin , Bozynski Chantelle C. , Stoker Aaron M. , Kuroki Keiichi , Stannard James P. , Felice Hilary , Fahs Adam , Cook Cristi R. , Ramírez-GarcíaLuna José L. , Hadidi Lina , Merle Geraldine , Crist Brett D. 
Published: October 2024

OBJECTIVES:
Osteochondral allograft transplantation (OCAT) can be a successful joint restoration treatment option for large post-traumatic articular defects but is still associated with significant revision and failure rates. Despite recent advances that have improved OCAT success, insufficient osteochondral allograft (OCA) osseointegration remains a major cause of failure. Deferoxamine (DFO) is an effective angiogenic and osteo-anabolic iron chelator that consistently promotes bone neovascularization and regeneration. This study was designed to investigate local delivery of DFO for augmenting OCA osseointegration using a preclinical canine model for OCAT in the knee and hip as commonly affected joints.

METHODS:
On Institutional Animal Care and Use Committee (IACUC) approval, 12 purpose-bred dogs underwent OCAT of the femoral head or femoral condyles with DFO or DFO-free (controls) microspheres in recipient sites. OCA revascularization, cellular repopulation, and integration were evaluated based on functional, diagnostic imaging, microcomputed tomography, histology, and immunohistochemistry outcome measures.

RESULTS:
Local delivery of DFO into OCAT recipient sites was associated with maintained or improved joint function, superior radiographic appearance, significantly greater trabecular thickness, higher bone volume, and new bone ingrowth compared with DFO-free controls.

CONCLUSION:
OCA osseointegration is dependent on cellular repopulation and neovascularization, resulting in new bone ingrowth through creeping substitution, and insufficient osseointegration with resorption and subsidence of the OCA remains a major cause of failure after transplantation. The results of this study suggest that local delivery of DFO using a controlled microsphere release system may reduce resorption and improve revascularization and cellular repopulation to increase new bone ingrowth, potentially expediting OCA osseointegration after transplantation.
Biomechanical Analysis of a Modified Triangular Osteosynthesis Technique for Treatment of Spinopelvic Dissociation
Authors: Voort Wyatt Vander , O'Donnell Edmond , Haffner Max , Garcia-Nolan Tanya , Simister Samuel K. , Le Hai , Klineberg Eric , Eastman Jonathan G. , Saiz Augustine Mark 
Published: October 2024

OBJECTIVES:
The purpose of this study was to evaluate the biomechanical stability of a modified triangular osteosynthesis construct with S1 pedicle screws compared with other described lumbopelvic fixation constructs in a U-type sacral fracture model.

METHODS:
U-type sacral fractures were created in validated fourth-generation spinopelvic models. Four different constructs were cyclically loaded with displacement measured in all planes: (1) bilateral L5 pedicle screws with rods attached to iliac bolts, (2) bilateral L5 and S1 pedicle screws with rods attached to iliac bolts, (3) bilateral L5 pedicle screws with rods attached to iliac bolts with a transsacral–transiliac screw, and (4) bilateral L5 and S1 pedicle screws with rods attached to iliac bolts with a transsacral–transiliac screw.

RESULTS:
The bilateral L5 and S1 pedicle screws with rods attached to iliac bolts with a transsacral–transiliac screw construct had significantly decreased horizontal, vertical, and angular displacement compared with all other constructs.

CONCLUSIONS:
From a biomechanical perspective, a modified triangular osteosynthesis construct with S1 pedicle screws improves stability in fixation of U-type sacral fractures.
Ipsilateral Femoral Neck and Shaft Fractures: Complex Injuries With High Rates of Femoral Shaft Nonunion
Authors: Haase Douglas R. , Saiz Augustine M. , Eastman Jonathan G. , Achor Timothy S. , Choo Andrew M. , Munz John W. , Warner Stephen J. 
Published: October 2024

OBJECTIVE:
To investigate nonunion rates and risk factors in patients with ipsilateral femoral neck and shaft fractures.

METHODS:

Design:
Retrospective review.

Setting:
Two Level I trauma centers.

Patient Selection Criteria:
Two hundred seven patients treated for ipsilateral femoral neck (AO/OTA 31-B) and shaft (AO/OTA 32A-C) fractures from 2013 to 2022. Patients with less than 6 months of follow-up were excluded.

Outcome Measures and Comparisons:
The primary outcome of this study was femoral shaft nonunion. Risk factors for nonunion were evaluated, including smoking, open fracture, delay to full weight-bearing, blood transfusions, and AO/OTA classification.

RESULTS:
Two hundred twenty-seven patients were initially identified, but only 154 patients had sufficient follow-up and were included in final analysis. The mean age was 38.9 years (SD = 15.3), and injury severity score was 19.5 (9.7). One hundred ten patients (71%) were male and 69 (45%) required intensive care unit care. Thirty-eight patients (25%) experienced an open fracture, and 44 fractures (29%) were AO/OTA Type C. Thirty patients (20%) underwent initial external fixation, and 88 patients (57%) received a perioperative transfusion. Thirty-four patients (22%) developed a femoral shaft nonunion, and 5 (3%) experienced a surgical site infection. Nonunion was associated with perioperative blood transfusion, AO/OTA Type C fracture, postoperative non-weight-bearing, and delay to full weight-bearing ≥12 weeks. Multivariable regression identified perioperative blood transfusion ≥3 (risk ratio [RR] = 1.91; CI, 1.12–2.72; P = 0.02) and AO/OTA Type C fracture (RR = 2.45; CI, 1.50–3.34; P = 0.001) as independent risk factors.

CONCLUSIONS:
Ipsilateral femoral neck and shaft fractures remain difficult injuries to treat. Much attention is given to diagnosis and treatment of the femoral neck component. These results suggest that successful treatment of the femoral shaft component presents its own challenges with high nonunion rates.

LEVEL OF EVIDENCE:
Prognostic Level III.
Development of a Surgical Difficulty Score for Open Reduction Internal Fixation of Pilon Fractures
Authors: Burns David , Abbas Aazad , Dasari Suhas , Prabhakar Pooja , Hebert-Davies Jonah 
Published: October 2024

OBJECTIVES:
To identify characteristics that contribute to surgical complexity in pilon fractures and to develop a machine learning (ML) Pilon Surgical Difficulty Score (PSDS) based on these factors.

METHODS:

Design:
Retrospective cohort study.

Setting:
Academic Level I trauma center.

Patient Selection Criteria:
Pilon fractures (OTA/AO Type 43) in adult patients treated with open reduction internal fixation.

Outcomes Measures and Comparisons:
Various patient, injury, and radiological characteristics were assessed. Surgical difficulty was measured using 2 outcomes: (1) operative time and (2) perceived difficulty. Perceived difficulty was determined using the opinion of 16 fellowship-trained orthopaedic traumatologists on a 10-point scale. Significant predictors of difficulty were determined using univariate analyses. ML models were used to develop a PSDS for both operative time and surgical difficulty.

RESULTS:
One hundred operatively fixed pilon fractures were included. Predictors of operative time were age, OTA/AO classification, articular comminution, articular impaction, bone loss, delay to surgery, poor quality reduction, number of approaches, and number of articular fragments. Predictors of perceived difficulty included OTA/AO classification and delay to surgery. Operative time PSDS had a mean absolute error of 64 minutes and a 60-minute buffer accuracy of 59%. Perceived difficulty PSDS had a mean absolute error of 1.7 points and a 2-point buffer accuracy of 63%.

CONCLUSION:
ML was used to generate accurate PSDSs for operative time and difficulty for pilon fractures. Future work should aim to clinically validate these PSDSs, so they may improve patient outcomes.

LEVEL OF EVIDENCE:
Level III Diagnostic.
Social Disadvantage and Transportation Insecurity in Clubfoot Clinic
Authors: Bent Melissa A. , Jhun Michelle , Beltran Veronica , Fimbres Barbara , Wren Tishya A.L. 
Published: October 2024

Objectives:
This study aims to evaluate the association of missing clubfoot clinic visits with transportation barriers and measures of socioeconomic status including the child opportunity index (COI).

Methods:
An 11-question survey was administered to caregivers of patients with clubfoot seen at a single pediatric tertiary hospital between August 2020 and September 2023. A chart review was conducted to obtain zip codes used to determine COI 2.0 scores. The impact of race/ethnicity, income, persons per household, COI, and transportation methods on missing at least one clinic visit was analyzed using descriptive and nonparametric statistics.

Results:
The transportation survey was completed by a total of 99 caregivers. The median travel time to the clinic was 45 minutes (IQR: 33, range: 1 to 180). Most participants reported use of a personal car (108/128, 83%), and 72% took time off work to attend the appointment. Those with lower COI had longer travel time (P=0.02) and were less likely to use personal cars (P=0.05). Missed clubfoot clinic visits were more common for families reliant on transportation other than a personal vehicle (P=0.01) and those with annual income under $30,000 (P=0.02).

Conclusions:
Transportation insecurity was associated with greater social disadvantage as indicated by COI and more missed clinic visits.

Level of Evidence:
Level III.
Practice Patterns Vary Widely in the Care of Pediatric and Adolescent Pelvic and Acetabular Fractures: A CORTICES Survey
Authors: Roper Brennan , Purtell S. Rose , De Sayan , McLaughlin Dell , Truong Walter H. , Miller Mark L. , Swarup Ishaan , Ramalingam Wendy , Sanders Julia S. ,   Children’s Orthopaedic Trauma and Infection Consortium for Evidence-Based Studies (CORTICES)
Published: October 2024

Introduction:
Pediatric pelvic and acetabular fractures are rare but potentially devastating injuries and significant management variation exists across the United States. This study sought to elucidate treatment decision-making trends, involvement of adult trauma fellowship-trained surgeons in pediatric care, and pre- and postoperative transfer patterns.

Methods:
Pediatric orthopaedic surgeons who serve as trauma liaisons at 20 PTCs were surveyed regarding training, practice volume, and factors contributing to institutional management of pelvic and acetabular injuries. Five clinical scenarios of pelvic ring and acetabular fractures that varied by injury pattern, age, and sex were presented. Descriptive statistics were used to summarize the results.

Results:
Eighteen institutions responded to the survey (90% response rate, 16 Level, 1 PTC). All surgeons were pediatric fellowship-trained (77.7% in practice >5 y). The four most common factors affecting whether surgeons independently managed both pelvic ring and acetabular fractures were patient age, fracture characteristics, displacement and need for surgery. The majority reported managing <10 acetabular (72.2%) but >10 pelvic ring (77.8%) injuries per year. In the clinical scenarios, patients <10 were more likely to have treatment decisions made by a pediatric orthopaedic surgeon. Older patients were more likely to be transferred to another institution for surgery but were often transferred back to the PTC postoperatively. In all clinical scenarios other than posterior hip dislocation, a trauma fellowship-trained surgeon was more likely to be the operative surgeon, even when the patient was not transferred.

Conclusions:
There is substantial variation in the management of pediatric and adolescent pelvic and acetabular fractures. Even at tertiary care PTCs, volumes are low, and trauma fellowship-trained surgeons are often involved in decision-making and operative management. Age and injury pattern seem to play a large role in variation, and patient transfers between facilities are common.

Level of Evidence:
V
A survey of attitudes toward and experiences with traditional Chinese medicines among people in Taiwan
Authors: Chuang Cheng-Yu , Chung Hui-Yu , Chen Fu-Shih , Arai Ichiro 
Published: October 2024

Background:
Despite numerous surveys on traditional Chinese medicines (TCMs) and their impact on people in Taiwan, only a few directly assessed the perspectives of the users and their experiences with the practice. In this study, we aimed to explore the attitudes, experiences, and understanding of TCMs, and also to identify the TCMs that are commonly preferred among people in Taiwan.

Methods:
We conducted an online survey among people in Taiwan to reflect the viewpoints of the general public on TCMs in 2022. Individuals working in the medical field were excluded. Question topics included experience, impressions, access, and expectations.

Results:
According to the results of the questionnaire survey, of the 518 participants interviewed, more than 95% had used TCMs. "Work gently" was the most common positive impression, and "Take effect slowly" was the most common negative impression. Among the over-the-counter TCMs that were taken by the participants, "Si Wu Tang," which tends to be used for treating female diseases, was the most common. The main expectations for TCMs were to improve daily health and prevent diseases. Although the participants were well informed about TCMs, there was still room for improvement. For example, 30% of the participants still did not know that TCMs might have side effects.

Conclusion:
People in Taiwan who participated in the survey had a relatively positive impression of and experience with TCMs, but there were still some knowledge gaps that need to be filled with additional information. It is essential to strengthen the publicity and education about TCMs and improve the public's understanding and correct use of TCMs.