bluuebunny/crossref_metadata_2025_split huggingface dataset:
(Z)-3-Hexenol integrates drought and cold stress signaling by activating abscisic acid glucosylation in tea plants
Authors: Jin Jieyang , Zhao Mingyue , Jing Tingting , Wang Jingming , Lu Mengqian , Pan Yuting , Du Wenkai , Zhao Chenjie , Bao Zhijie , Zhao Wei , Tang Xiaoyan , Schwab Wilfried , Song Chuankui 
Published: June 2023

Abstract
Cold and drought stresses severely limit crop production and can occur simultaneously. Although some transcription factors and hormones have been characterized in plants subjected each stress, the role of metabolites, especially volatiles, in response to cold and drought stress exposure is rarely studied due to lack of suitable models. Here, we established a model for studying the role of volatiles in tea (Camellia sinensis) plants experiencing cold and drought stresses simultaneously. Using this model, we showed that volatiles induced by cold stress promote drought tolerance in tea plants by mediating reactive oxygen species and stomatal conductance. Needle trap microextraction combined with GC-MS identified the volatiles involved in the crosstalk and showed that cold-induced (Z)-3-hexenol improved the drought tolerance of tea plants. In addition, silencing C. sinensis alcohol dehydrogenase 2 (CsADH2) led to reduced (Z)-3-hexenol production and significantly reduced drought tolerance in response to simultaneous cold and drought stress. Transcriptome and metabolite analyses, together with plant hormone comparison and abscisic acid (ABA) biosynthesis pathway inhibition experiments, further confirmed the roles of ABA in (Z)-3-hexenol–induced drought tolerance of tea plants. (Z)-3-Hexenol application and gene silencing results supported the hypothesis that (Z)-3-hexenol plays a role in the integration of cold and drought tolerance by stimulating the dual-function glucosyltransferase UGT85A53, thereby altering ABA homeostasis in tea plants. Overall, we present a model for studying the roles of metabolites in plants under multiple stresses and reveal the roles of volatiles in integrating cold and drought stresses in plants.
Genome- and transcriptome-wide off-target analyses of a high-efficiency adenine base editor in tomato
Authors: Sretenovic Simon , Green Yumi , Wu Yuechao , Cheng Yanhao , Zhang Tao , Van Eck Joyce , Qi Yiping 
Published: June 2023

Abstract
Adenine base editors (ABEs) are valuable, precise genome editing tools in plants. In recent years, the highly promising ADENINE BASE EDITOR8e (ABE8e) was reported for efficient A-to-G editing. However, compared to monocots, comprehensive off-target analyses for ABE8e are lacking in dicots. To determine the occurrence of off-target effects in tomato (Solanum lycopersicum), we assessed ABE8e and a high-fidelity version, ABE8e-HF, at 2 independent target sites in protoplasts, as well as stable T0 lines. Since ABE8e demonstrated higher on-target efficiency than ABE8e-HF in tomato protoplasts, we focused on ABE8e for off-target analyses in T0 lines. We conducted whole-genome sequencing (WGS) of wild-type (WT) tomato plants, green fluorescent protein (GFP)–expressing T0 lines, ABE8e-no-gRNA control T0 lines, and edited T0 lines. No guide RNA (gRNA)–dependent off-target edits were detected. Our data showed an average of approximately 1,200 to 1,500 single-nucleotide variations (SNVs) in either GFP control plants or base-edited plants. Also, no specific enrichment of A-to-G mutations were found in base-edited plants. We also conducted RNA sequencing (RNA-seq) of the same 6 base-edited and 3 GFP control T0 plants. On average, approximately 150 RNA–level SNVs were discovered per plant for either base-edited or GFP controls. Furthermore, we did not find enrichment of a TA motif on mutated adenine in the genomes and transcriptomes in base-edited tomato plants, as opposed to the recent discovery in rice (Oryza sativa). Hence, we could not find evidence for genome- and transcriptome-wide off-target effects by ABE8e in tomato.
S100A4-neutralizing monoclonal antibody 6B12 counteracts the established experimental skin fibrosis induced by bleomycin
Authors: Švec Xiao , Štorkánová Hana , Trinh-Minh Thuong , Tran Manh Cuong , Štorkánová Lenka , Hulejová Hana , Oreská Sabína , Heřmánková Barbora , Bečvář Radim , Pavelka Karel , Vencovský Jiří , Klingelhöfer Jörg , Hussain Rizwan I , Hallén Jonas , Šenolt Ladislav , Distler Jörg H W , Tomčík Michal 
Published: June 2023

Abstract

Objectives
Our previous studies have demonstrated that the Damage Associated Molecular Pattern (DAMP) protein, S100A4, is overexpressed in the involved skin and peripheral blood of patients with SSc. It is associated with skin and lung involvement, and disease activity. By contrast, lack of S100A4 prevented the development of experimental dermal fibrosis. Herein we aimed to evaluate the effect of murine anti-S100A4 mAb 6B12 in the treatment of preestablished experimental dermal fibrosis.

Methods
The effects of 6B12 were assessed at therapeutic dosages in a modified bleomycin-induced dermal fibrosis mouse model by evaluating fibrotic (dermal thickness, proliferation of myofibroblasts, hydroxyproline content, phosphorylated Smad3-positive cell count) and inflammatory (leukocytes infiltrating the lesional skin, systemic levels of selected cytokines and chemokines) outcomes, and transcriptional profiling (RNA sequencing).

Results
Treatment with 7.5 mg/kg 6B12 attenuated and might even reduce pre-existing dermal fibrosis induced by bleomycin as evidenced by reduction in dermal thickness, myofibroblast count and collagen content. These antifibrotic effects were mediated by the downregulation of TGF-β/Smad signalling and partially by reducing the number of leukocytes infiltrating the lesional skin and decrease in the systemic levels of IL-1α, eotaxin, CCL2 and CCL5. Moreover, transcriptional profiling demonstrated that 7.5 mg/kg 6B12 also modulated several profibrotic and proinflammatory processes relevant to the pathogenesis of SSc.

Conclusion
Targeting S100A4 by the 6B12 mAb demonstrated potent antifibrotic and anti-inflammatory effects on bleomycin-induced dermal fibrosis and provided further evidence for the vital role of S100A4 in the pathophysiology of SSc.
Responding to uncertainty in the COVID-19 pandemic: perspectives from Bavaria, Germany
Authors: Fiske Amelia , Lange Johannes , Buyx Alena , McLennan Stuart 
Published: June 2023

Abstract
The 2019 novel coronavirus (COVID-19) pandemic has created unprecedented challenges for policymakers and scientific experts charged with preventing the spread of the virus. In upending the usual mechanisms for political deliberation, the pandemic offers a window into the co-production of governmental policy decisions and scientific evidence. Taking the German state of Bavaria as a case study, this article draws on expert interviews with individuals directly involved in high-level pandemic decision-making to explore the changing relationships between policymakers and scientific experts. The challenges that emerged in the Bavarian context illustrate that while uncertainty has long been understood as constitutive of scientific knowledge, it became a stumbling block for policymakers due to newfound degrees of urgency and implications of decision-making in relation to the pandemic. In order to better address the emergent, evolving problems posed by public health crises, uncertainty must also be understood as formative in the work of policy.
New Technologies Provide Innovative Opportunities to Enhance Understanding of Major Virus Diseases Threatening Global Food Security
Authors: Kreuze Jan F. , Cuellar Wilmer J. , Kumar P. Lava , Boddupalli Prasanna , Omondi Aman B. 
Published: June 2023

Plant viruses pose a continuous and serious threat to crop production worldwide, and globalization and climate change are exacerbating the establishment and rapid spread of new viruses. Simultaneously, developments in genome sequencing technology, nucleic acid amplification methods, and epidemiological modeling are providing plant health specialists with unprecedented opportunities to confront these major threats to the food security and livelihoods of millions of resource-constrained smallholders. In this perspective, we have used recent examples of integrated application of these technologies to enhance understanding of the emergence of plant viral diseases of key food security crops in low- and middle-income countries. We highlight how international funding and collaboration have enabled high-throughput sequencing-based surveillance approaches, targeted field and lab-based diagnostic tools, and modeling approaches that can be effectively used to support surveillance and preparedness against existing and emerging plant viral threats. The importance of national and international collaboration and the future role of CGIAR in further supporting these efforts, including building capabilities to make optimal use of these technologies in low- and middle-income countries, are discussed.[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Long-term Radiographic and Clinical Outcomes After Selective Thoracic Fusion for Adolescent Idiopathic Scoliosis With Lenke 1C Curve
Authors: Park Se-Jun , Lee Chong-Suh , Park Jin-Sung , Ma Chang-Hyun , Shin Tae Soo , Jeon Chung-Youb 
Published: June 2023

Background:
Despite the promising results with selective thoracic fusion (STF) in patients with adolescent idiopathic scoliosis (AIS) of the Lenke 1C curve, postoperative coronal imbalance and progression of the unfused lumbar curve have been concerns in long-term follow-up. In this study, we aimed to investigate the radiographic and clinical outcomes after STF for AIS with Lenke 1C curve with long-term follow-up.

Methods:
A total of 30 patients with AIS with Lenke 1C curves who underwent STF between 2005 and 2017 were included. Minimum follow-up duration was 5 years. Time-dependent changes in radiographic parameters were investigated preoperatively, immediately postoperatively, and at the last follow-up. In addition, radiographic adverse events such as coronal decompensation (CD), lumbar decompensation (LD), distal adding-on (DA) phenomenon, and trunk shift were evaluated at the last follow-up. The Scoliosis Research Society-22 score was used for clinical outcome evaluation.

Results:
The mean age at the time of surgery was 13.8 years. The mean follow-up duration was 6.7 ± 0.8 years. The main thoracic curve significantly improved from 57 degrees to 23 degrees (60% correction), and the thoracolumbar/lumbar curve significantly improved from 47 degrees to 28 degrees (41% correction). Coronal balance was 15 mm after surgery but significantly improved to 10 mm at the last follow-up (P = 0.033). At the final follow-up, 11 patients (37%) sustained at least one of the radiographic adverse events: CD in 5 patients (17%), LD in 3 (10%), DA in 4 (13%), and trunk shift in 3 (10.%). However, there were no cases requiring revision surgery. In addition, there were no significant differences in any items or total Scoliosis Research Society-22 score between the patients with and without radiographic adverse events.

Conclusion:
STF in Lenke 1C curves showed an acceptable risk of adverse radiographic events such as CD, LD, DA, and trunk shift in long-term follow-up. We suggest that STF without fusion to the thoracolumbar/lumbar curve would be sufficient in treating AIS with Lenke 1C curve.

Level of Evidence:
Level III.
Modified Capsulorrhaphy Technique in Open Reduction of Developmental Dysplasia of the Hip
Authors: El-Sayed Mohamed M.H. , Hammad Mostafa E. , Khalifa Ahmed M. , Eltanahy Ahmed F. , Nada Abdullah A. 
Published: June 2023

Background:
Neglected patients with developmental dysplasia of the hip (DDH) are not uncommon. Various treatment modalities have been used. Capsulorrhaphy is one of the most critical steps during the process of open reduction of DDH. Inadequate capsulorrhaphy technique can increase the failure rate of open reduction procedures. This study presented the clinical and radiographic results of using a new capsulorrhaphy technique.

Methods:
Between November 2005 and March 2018, 540 DDH in 462 patients were retrospectively reviewed. The mean age at surgery was 31 months. All patients underwent a modified capsulorrhaphy technique developed by the main author (with or without additional pelvic or femoral procedures). Postoperative patient assessment during the follow-up period was performed both clinically and radiologically.

Results:
Follow-up period ranged between 36 months and 12 years. Based on the modified McKay score, good and excellent outcomes were obtained in 90.3%. Functional results were better in younger age (less than 39 mo). Both acetabular index and lateral center edge angle showed significant improvement at 3 years follow-ups. Proximal femoral growth disturbance (PFGD) was encountered in 92 hips. Classes 2 and 3 did not affect the functional results, whereas patients with PFGD classes 4 and 5 had fair to poor functional outcomes. There were 12 hips with redislocation. Revision was done using the same capsulorrhaphy technique.

Conclusion:
Using the index technique of capsulorrhaphy in DDH surgery is safe, reliable, and yields good functional and radiologic outcomes with a relatively low complication rate.

Level of Evidence:
Level IV—therapeutic retrospective case series.
Defining the Incidence of Residual Acetabular Dysplasia After Successful Reduction With a Harness
Authors: Paranjape Chinmay S. , Bomar James D. , Upasani Vidyadhar V. 
Published: June 2023

Background:
The purpose of this study was to evaluate the rate of residual acetabular dysplasia (RAD), defined as an acetabular index (AI) of >90th percentile of age and sex-matched controls, in a cohort of infants successfully treated with the Pavlik harness (PH).

Methods:
We retrospectively studied typically developing infants at a single center, with at least 1 dislocated hip, that was successfully treated with a PH and had a minimum of 48 months follow-up. Hip dislocation was defined as <30% femoral head coverage at rest on pretreatment ultrasound or IHDI grade 3 or 4 on the pretreatment radiograph.

Results:
Forty-six dislocated hips (41 infants) were studied (4 males and 37 females). Brace treatment was initiated at an average age of 1.8 months (range: 2 d to 9.3 mo) and was maintained for an average of 10.2 months (range: 2.3 to 24.9 mo). All hips achieved IHDI grade 1 reduction. Five of 46 hips (11%) had an AI >90th percentile at the conclusion of bracing. Average follow-up was 6.5 years (range: 4.0 to 15.2 y). We found a 30% incidence of RAD (14/46 hips) on final follow-up radiographs. Of these hips, 13/14 (93%) had AI <90th percentile at the end of brace treatment. Comparing children with and without RAD, there were no differences in age at the initial visit or brace initiation, total follow-up, femoral head coverage at the initial visit, alpha angle at the initial visit, or total time in the brace (P > 0.09).

Conclusion:
In a single-center cohort of infants with dislocated hips treated successfully with a PH, we observed a 30% incidence of RAD at a minimum 4.0-year follow-up. Normal acetabular morphology at the end of brace treatment did not result in normal acetabular morphology at the final follow-up in 13/41 hips (32%). We recommend that surgeons should pay close attention to the year-over-year change in both the AI and AI percentile.

Level of Evidence:
Level IV: case series.
Preferred Language Mediates Association Between Race, Ethnicity, and Delayed Presentation in Critically Ill Patients With COVID-19
Authors: Kelly Michael S. , Mohammed Adna , Okin Daniel , Alba George A. , Jesudasen Sirus J. , Flanagan Shelby , Dandawate Nupur A. , Gavralidis Alexander , Chang Leslie L. , Moin Emily E. , Witkin Alison S. , Hibbert Kathryn A. , Kadar Aran , Gordan Patrick L. , Bebell Lisa M. , Hauptman Marissa , Valeri Linda , Lai Peggy S. 
Published: June 2023

IMPORTANCE:
Which social factors explain racial and ethnic disparities in COVID-19 access to care and outcomes remain unclear.

OBJECTIVES:
We hypothesized that preferred language mediates the association between race, ethnicity and delays to care.

DESIGN, SETTING AND PARTICIPANTS:
Multicenter, retrospective cohort study of adults with COVID-19 consecutively admitted to the ICU in three Massachusetts hospitals in 2020.

MAIN OUTCOME AND MEASURES:
Causal mediation analysis was performed to evaluate potential mediators including preferred language, insurance status, and neighborhood characteristics.

RESULTS:
Non-Hispanic White (NHW) patients (157/442, 36%) were more likely to speak English as their preferred language (78% vs. 13%), were less likely to be un- or under-insured (1% vs. 28%), lived in neighborhoods with lower social vulnerability index (SVI) than patients from racial and ethnic minority groups (SVI percentile 59 [28] vs. 74 [21]) but had more comorbidities (Charlson comorbidity index 4.6 [2.5] vs. 3.0 [2.5]), and were older (70 [13.2] vs. 58 [15.1] years). From symptom onset, NHW patients were admitted 1.67 [0.71–2.63] days earlier than patients from racial and ethnic minority groups (p < 0.01). Non-English preferred language was associated with delay to admission of 1.29 [0.40–2.18] days (p < 0.01). Preferred language mediated 63% of the total effect (p = 0.02) between race, ethnicity and days from symptom onset to hospital admission. Insurance status, social vulnerability, and distance to the hospital were not on the causal pathway between race, ethnicity and delay to admission.

CONCLUSIONS AND RELEVANCE:
Preferred language mediates the association between race, ethnicity and delays to presentation for critically ill patients with COVID-19, although our results are limited by possible collider stratification bias. Effective COVID-19 treatments require early diagnosis, and delays are associated with increased mortality. Further research on the role preferred language plays in racial and ethnic disparities may identify effective solutions for equitable care.
Postoperative Day 1 Discharge in Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction
Authors: Tapp Marion W. , Duet Mary L. , Steele Thomas N. , Gallagher Robert J. , Kogan Samuel , Calder Bennett W. , Robinson J. Michael 
Published: June 2023

Background:
With high success rates of autologous breast reconstruction, the focus has shifted from flap survival to improved patient outcomes. Historically, a criticism of autologous breast reconstruction has been the length of hospital stay. Our institution has progressively shortened the length of stay after deep inferior epigastric artery perforator (DIEP) flap reconstruction and began discharging select patients on postoperative day 1 (POD1). The purpose of this study was to document our experience with POD1 discharges and to identify preoperative and intraoperative factors that may identify patients as candidates for earlier discharge.

Methods:
An institutional review board-approved, retrospective chart review of patients undergoing DIEP flap breast reconstruction from January 2019 to March 2022 at Atrium Health was completed, consisting of 510 patients and 846 DIEP flaps. Patient demographics, medical history, operative course, and postoperative complications were collected.

Results:
Twenty-three patients totaling 33 DIEP flaps were discharged on POD1. The POD1 group and the group of all other patients (POD2+) had no difference in age, ASA score, or comorbidities. BMI was significantly lower in the POD1 group (P = 0.039). Overall operative time was significantly lower in the POD1 group, and this remained true when differentiating into unilateral operations (P = 0.023) and bilateral operations (P = 0.01). No major complications occurred in those discharged on POD1.

Conclusions:
POD1 discharge after DIEP flap breast reconstruction is safe for select patients. Lower BMI and shorter operative times may be predictive in identifying patients as candidates for earlier discharge.
Single ethanol binge causes severe liver injury in mice fed Western diet
Authors: Yeh Yu-Te , Wu Xiangdong , Ma Yinyan , Ying Zhekang , He Ling , Xue Bingzhong , Shi Hang , Choi Youngshim , Yu Liqing 
Published: June 2023

Background and Aims:
Alcohol-associated liver disease (ALD) and NAFLD often coexist in Western societies that consume energy-rich and cholesterol-containing Western diets. Increased rates of ALD mortality in young people in these societies are likely attributable to binge drinking. It is largely unknown how alcohol binge causes liver damage in the setting of Western diets.

Approach and Results:
In this study, we showed that a single ethanol binge (5 g/kg body weight) induced severe liver injury as shown by marked increases in serum activities of the 2 aminotransferases AST and ALT in C57BL/6J mice that have been fed a Western diet for 3 weeks. The Western diet plus binge ethanol-fed mice also displayed severe lipid droplet deposition and high contents of triglycerides and cholesterol in the liver, which were associated with increased lipogenic and reduced fatty acid oxidative gene expression. These animals had the highest Cxcl1 mRNA expression and myeloperoxidase (MPO)-positive neutrophils in the liver. Their hepatic ROS and lipid peroxidation were the highest, but their hepatic levels of mitochondrial oxidative phosphorylation proteins remained largely unaltered. Hepatic levels of several ER stress markers, including mRNAs for CHOP, ERO1A, ERO1B, BIM, and BIP, as well as Xbp1 splicing and proteins for BIP/GRP78 and IRE-α were also the highest in these animals. Interestingly, Western diet feeding for 3 weeks or ethanol binge dramatically increased hepatic caspase 3 cleavage, and the combination of the 2 did not further increase it. Thus, we successfully established a murine model of acute liver injury by mimicking human diets and binge drinking.

Conclusions:
This simple Western diet plus single ethanol binge model recapitulates major hepatic phenotypes of ALD, including steatosis and steatohepatitis characterized by neutrophil infiltration, oxidative stress, and ER stress.
Preparing Clinicians for Roles in Academic Teaching: A Model for Clinical Associated Faculty Development
Authors: Bilyeu Catherine , Reilly Michelle , Niski Jessica 
Published: June 2023

Background and Purpose.
Clinical associated faculty (CAF) are typically expert clinicians but novice educators, lacking professional development opportunities targeted to their unique needs. This can result in unnecessary variability in content delivery and potentially negative student learning outcomes. The purpose of this article is to describe the development, implementation, and evaluation of a faculty development program designed specifically for CAF.

Method/Model Description and Evaluation.
Thirty-two CAF completed a longitudinal faculty development program designed by faculty at the University of Colorado Doctor of Physical Therapy Program (CU). Content was driven by faculty development literature, core concepts of CU's Doctor of Physical Therapy (DPT) program, and key constructs for excellence in DPT education. Changes in teaching confidence were examined with a modified version of the Nurse Educator Skill Acquisition Assessment (NESAA) in pre-test/post-test design. Creighton University DPT Program (Creighton) adapted the faculty development program for their own CAF and similarly assessed change in teaching skill in 21 CAF using the NESAA. Additional data were collected through session evaluations and review of student course evaluations for both programs.

Outcomes.
At CU and Creighton, 28 and 21 participants, respectively, completed the CAF development program and all desired outcome measures. Outcomes revealed a significant increase (P < .05) on NESAA scores. In addition, results demonstrated decreased negative student comments related to teaching inconsistencies on course evaluations and an overall positive perception of the program by participants.

Discussion and Conclusion.
A CAF longitudinal faculty development program was developed and successfully implemented at 2 universities. This model could be used as a template by other DPT programs to address the existing faculty development gap and support the distinctive needs of CAF.