bluuebunny/crossref_metadata_2025_split huggingface dataset:
The vacuolar H+/Ca transporter CAX1 participates in submergence and anoxia stress responses
Authors: Yang Jian , Mathew Iny Elizebeth , Rhein Hormat , Barker Richard , Guo Qi , Brunello Luca , Loreti Elena , Barkla Bronwyn J , Gilroy Simon , Perata Pierdomenico , Hirschi Kendal D 
Published: August 2022

Abstract
A plant’s oxygen supply can vary from normal (normoxia) to total depletion (anoxia). Tolerance to anoxia is relevant to wetland species, rice (Oryza sativa) cultivation, and submergence tolerance of crops. Decoding and transmitting calcium (Ca) signals may be an important component to anoxia tolerance; however, the contribution of intracellular Ca transporters to this process is poorly understood. Four functional cation/proton exchangers (CAX1–4) in Arabidopsis (Arabidopsis thaliana) help regulate Ca homeostasis around the vacuole. Our results demonstrate that cax1 mutants are more tolerant to both anoxic conditions and submergence. Using phenotypic measurements, RNA-sequencing, and proteomic approaches, we identified cax1-mediated anoxia changes that phenocopy changes present in anoxia-tolerant crops: altered metabolic processes, diminished reactive oxygen species production post anoxia, and altered hormone signaling. Comparing wild-type and cax1 expressing genetically encoded Ca indicators demonstrated altered cytosolic Ca signals in cax1 during reoxygenation. Anoxia-induced Ca signals around the plant vacuole are involved in the control of numerous signaling events related to adaptation to low oxygen stress. This work suggests that cax1 anoxia response pathway could be engineered to circumvent the adverse effects of flooding that impair production agriculture.
Exogenous GABA improves the resistance of apple seedlings to long-term drought stress by enhancing GABA shunt and secondary cell wall biosynthesis
Authors: Chen Xiao , Li Na , Liu Chenlu , Wang Hongtao , Li Yuxing , Xie Yuanmei , Ma Fengwang , Liang Jiakai , Li Cuiying 
Published: August 2022

Abstract
Drought stress is an important factor limiting apple production. γ-Aminobutyric acid (GABA) exists widely in plants and participates in the response to abiotic stress as a metabolite or signaling molecule. The role of exogenous GABA in apple plants, response to long-term drought stress remains unclear. Our study confirmed that exogenous GABA affects the drought resistance of apple plants under long-term drought stress. We found that 1 mM exogenous GABA improved the resistance of apple seedlings to long-term drought stress. The plants showed better growth, less reactive oxygen radical accumulation, less damage to cell membranes and greater active photosynthetic capacity. Under long-term drought stress, exogenous GABA facilitated GABA shunt, resulting in more accumulation of organic acids, namely citric acid, succinic acid and malic acid, in roots and stems of apple seedlings. In addition, exogenous GABA upregulated the expression of cellulose-related genes and lignin-related genes, and activated secondary cell wall-related transcription factors to synthesize more cellulose and lignin. A multiple factorial analysis confirmed that the GABA shunt and the biosynthesis of cellulose and lignin substantially contributed to the growth of apple seedlings with the application of exogenous GABA under long-term drought stress. Our results suggested that exogenous GABA improved the resistance of apple seedlings to long-term drought stress by enhancing GABA shunt and secondary cell wall biosynthesis.
Joint association between ambient air pollutant mixture and pediatric asthma exacerbations
Authors: Puvvula Jagadeesh , Poole Jill A. , Gonzalez Sandra , Rogan Eleanor G. , Gwon Yeongjin , Rorie Andrew C. , Ford Linda B. , Bell Jesse E. 
Published: August 2022

Background:
Exposure to air pollutants is known to exacerbate asthma, with prior studies focused on associations between single pollutant exposure and asthma exacerbations. As air pollutants often exist as a complex mixture, there is a gap in understanding the association between complex air pollutant mixtures and asthma exacerbations. We evaluated the association between the air pollutant mixture (52 pollutants) and pediatric asthma exacerbations.

Method:
This study focused on children (age ≤ 19 years) who lived in Douglas County, Nebraska, during 2016–2019. A seasonal-scale joint association between the outdoor air pollutant mixture adjusting for potential confounders (temperature, precipitation, wind speed, and wind direction) in relation to pediatric asthma exacerbation-related emergency department (ED) visits was evaluated using the generalized weighted quantile sum (qWQS) regression with repeated holdout validation.

Results:
We observed associations between air pollutant mixture and pediatric asthma exacerbations during spring (lagged by 5 days), summer (lag 0–5 days), and fall (lag 1–3 days) seasons. The estimate of the joint outdoor air pollutant mixture effect was higher during the summer season (adjusted-βWQS = 1.11, 95% confidence interval [CI]: 0.66, 1.55), followed by spring (adjusted-βWQS = 0.40, 95% CI: 0.16, 0.62) and fall (adjusted-βWQS = 0.20, 95% CI: 0.06, 0.33) seasons. Among the air pollutants, PM2.5, pollen, and mold contributed higher weight to the air pollutant mixture.

Conclusion:
There were associations between outdoor air pollutant mixture and pediatric asthma exacerbations during the spring, summer, and fall seasons. Among the 52 outdoor air pollutant metrics investigated, PM2.5, pollen (sycamore, grass, cedar), and mold (Helminthosporium, Peronospora, and Erysiphe) contributed the highest weight to the air pollutant mixture.
CHRONIC PEDIATRIC RETINAL DETACHMENT WITH MULTIPLE MACROCYSTS
Authors: Kasetty Venkatkrish M. , Regan Kaitlin R. , Aye Jennifer , Looysen Tyler , Patel Nish , Hamad Abdualrahman E. 
Published: August 2022

Purpose:
To describe a case of chronic pediatric retinal detachment with multiple macrocysts, its surgical management, and a review of the literature.

Methods:
Case report with fundus photography and optical coherence tomography.

Results:
We describe a case of an asymptomatic, 11-year-old boy with a chronic rhegmatogenous retinal detachment with multiple peripheral macrocysts. The patient had counting fingers visual acuity on presentation. The detachment was successfully surgically repaired with scleral buckling, subretinal fluid drainage, cryotherapy, and a SF6 tamponade. At the 12-month follow-up, the retina remained attached with improvement of visual acuity to 20/100 with resolution of the cysts. Optical coherence tomography revealed loss of macular ellipsoid zone. Genetic testing revealed a heterozygous dominant COL11A1 mutation.

Conclusion:
To the authors' knowledge, this is the first reported case of chronic retinal detachment presenting with multiple peripheral macrocysts in a pediatric patient with Stickler syndrome. More research is needed into the cause and significance of retinal macrocysts, particularly in the pediatric population.
Outcomes of Manual Small Incision Cataract Surgery in Hypermature Morgagnian cataract
Authors: Christy Josephine , Dhanaseelan Thamizhselvi , Vivekanandan Vellam Ramakrishnan , Venkatesh Rengaraj 
Published: August 2022

Purpose:
To evaluate the visual outcome and complication rate of Manual small incision cataract surgery (MSICS) in Hypermature Morgagnian Cataract (HMC)

Setting:
Aravind eye hospital, Puducherry, India

Design:
Retrospective, single center study

Methods:
Case records of patients diagnosed with hypermature morgagnian cataract and who underwent MSICS (manual small incision cataract surgery) from January to December 2019 were retrospectively collected. Data was analysed for demographic details, preoperative risk factors, intraoperative/postoperative complications and visual outcome at 1-month follow-up.

Results:
A total of 105 patients were included in the study. Preoperative risk factors like dense pseudoexfoliation were seen in 6 patients (5.7%), phacolytic glaucoma in 7 patients (6.7%), lens induced uveitis in 5 (4.7%), and phacodonesis in 30 patients (28.5%). Overall intraoperative complication rate was 14.3%, which included posterior capsular rent (n=4), zonular dialysis (n=7) and whole bag removal (n=4). Due to poor posterior capsular bag support, 7 patients (6.6%) did not receive IOL implantation in primary surgery. Both the intraoperative and postoperative complication rate were high in those with risk factors, and this difference was statistically significant (p<0.001 and 0.0005 respectively). On the first postoperative day, 70 patients (66.7%) had a BCVA better than 20/40, and at 1-month, 98 patients (93.3%) had a BCVA of 20/60 or better of which 89.5% had BCVA of ≥ 20/40.

Conclusion:
MSICS for hypermature cataract is relatively safe and yields adequate visual outcome. Preoperative risk factors, in addition to hypermaturity, increase the complication rate.
Symptom-associated alterations in functional connectivity in primary and secondary provoked vestibulodynia
Authors: Oughourlian Talia C. , Tun Guistinna , Antony Kevin M. , Gupta Arpana , Mays Vickie M. , Mayer Emeran A. , Rapkin Andrea J. , Labus Jennifer S. 
Published: August 2022

Abstract
Primary provoked vestibulodynia (PVD) is marked by the onset of symptoms at first provoking vulvar contact, whereas secondary PVD refers to symptom onset after some period of painless vulvar contact. Different pathophysiological processes are believed to be involved in the development and maintenance of primary PVD and secondary PVD. The primary aim of this study was to test the hypotheses that the resting state functional connectivity of the brain and brain stem regions differs between these subtypes. Deep clinical phenotyping and resting state brain imaging were obtained in a large sample of a women with primary PVD (n = 46), those with secondary PVD (n = 68), and healthy control women (n = 94). The general linear model was used to test for differences in region-to-region resting state functional connectivity and psychosocial and symptom assessments. Direct statistical comparisons by onset type indicated that women with secondary PVD have increased dorsal attention–somatomotor network connectivity, whereas women with primary PVD predominantly show increased intrinsic resting state connectivity within the brain stem and the default mode network. Furthermore, compared with women with primary PVD, those with secondary PVD reported greater incidence of early life sexual abuse, greater pain catastrophizing, greater 24-hour symptom unpleasantness, and less sexual satisfaction. The findings suggest that women with secondary PVD show greater evidence for central amplification of sensory signals, whereas women with primary PVD have alterations in brain stem circuitry responsible for the processing and modulation of ascending and descending peripheral signals.
Lucky Number Thirteen: Association Between Center-Specific Chest Wall Stabilization Volumes and Patient Outcomes
Authors: Tillman Anastasia C , Martin Thomas J. , Lueckel Stephanie N. , Kheirbek Tareq 
Published: August 2022

Abstract

Background
Chest wall stabilization (CWS) including improves outcomes for patients with chest wall injury (CWI). We hypothesized that patients treated at centers with higher annual CWS volumes experience superior outcomes.

Methods
Retrospective study of adults with acute CWI undergoing surgical stabilization of rib or sternal fractures within the 2019 Trauma Quality Improvement Program (TQIP) database, excluding those with 24-hour mortality or any Abbreviated Injury Scale (AIS) body region of six. Hospitals were grouped in quartiles by annual CWS volume. Our primary outcome was a composite of in-hospital mortality, ventilator-associated pneumonia (VAP), acute respiratory distress syndrome (ARDS), sepsis, and unplanned intubation or intensive care unit (ICU) readmission. Regression was controlled for age, sex, injury severity scale (ISS), flail chest, medical comorbidities, and AIS Chest. We performed cut point analysis and compared patient outcomes from high- and low-volume centers.

Results
We included 3,207 patients undergoing CWS at 430 hospitals with annual volumes ranging from 1 to 66. There were no differences between groups in age, sex, or ISS. Patients in the highest volume quartile (Q4) experienced significantly lower rates of the primary outcome (Q4: 14%; Q3: 18.4%; Q2: 17.4%; Q1: 22.1%) and significantly shorter hospital and ICU lengths of stay (LOS). Q4 vs Q1 had lower adjusted odds of the primary outcome (OR: 0.58, 95%CI: 0.43, 0.80). An optimal cut point of 12.5 procedures annually was used to define high- and low-volume centers. Patients treated at high-volume centers experienced significantly lower rates of the primary composite outcome, in-hospital mortality, and deep venous thrombosis with shorter LOS and higher rates of home discharge.

Conclusion
Center-specific CWS volume is associated with superior in-hospital patient outcomes. These findings support efforts to establish CWI centers of excellence. Further investigation should explore the impact of center-specific volume on patient-reported outcomes including pain and post-discharge quality of life.

LEVEL OF EVIDENCE
Level III Prognostic and Epidemiologic
Diagnosis and Management of Bile Leaks after Severe Liver Injury: A Trauma Association of Canada (TAC) Multicenter Study
Authors: Schellenberg Morgan , Ball Chad G. , Owattanapanich Natthida , Emigh Brent , Murphy Patrick B. , Moffat Bradley , Mador Brett , Beckett Andrew , Lee Jennie , Joos Emilie , Minor Samuel , Strickland Matt , Inaba Kenji ,   The TAC Bile Leaks Study Group
Published: August 2022

Abstract

Background
Optimal management of bile leaks (BL) after severe liver injury is unknown. Study objectives were to define current practices in diagnosis and management of BL to determine which patients may benefit from endoscopic retrograde cholangiopancreatography (ERCP).

Methods
AAST grade ≥ III liver injuries from 10 North American trauma centers were included in this retrospective study (02/2011-01/2021). Groups were defined as patients who developed BL vs. those who did not. Subgroup analysis of BL patients was performed by management strategy. Bivariate analysis compared demographics, clinical/injury data, and outcomes. ROC curves were performed to investigate the relationship between bilious drain output and ERCP.

Results
2,225 patients with severe liver injury met study criteria, with 108 (5%) BL. BL patients had higher AAST grade of liver injury (p < 0.001) and were more likely to have been managed operatively from the outset (69% vs. 25%, p < 0.001). BL was typically diagnosed on hospital day 6 [4-10] via surgical drain output (n = 37, 39%) and CT scan (n = 34, 36%). On the BL diagnosis day, drain output was 270 ml [125-555]. ERCP was the most frequent management strategy (n = 59, 55%), although 32 patients (30%) were managed with external drains alone. BL patients who underwent ERCP, surgery, or percutaneous transhepatic biliary drain (PTBD) had higher drain output than BL patients who were managed with external drains alone (320 [180-720] vs. 138 [85-330] ml, p = 0.010). ROC curve analysis of BL demonstrated moderate accuracy (AUROC 0.636) for ERCP at a cutoff point of 390 ml of bilious output on the day of diagnosis.

Conclusion
Patients with BL >300-400 ml were most likely to undergo ERCP, PTBD, or surgical management. Once external drainage of BL has been established, we recommend ERCP be reserved for patients with BL >300 ml of daily output. Prospective multicenter examination will be required to validate these retrospective data.

Level of Evidence
IV
Financial Vulnerability of American College of Surgeons-Verified Trauma Centers: A Statewide Analysis
Authors: Benham Derek A , Calvo Richard Y , Checchi Kyle , Carr Matthew J , Diaz Joseph , Krzyzaniak Andrea , Bansal Vishal , Martin Matthew J 
Published: August 2022

BACKGROUND:
Although trauma centers represent an integral part of healthcare in the US, characterization of their financial vulnerability has not been reported. We sought to characterize the financial health and vulnerability among California trauma centers and identify factors associated with high and low vulnerability.

STUDY DESIGN:
The RAND Hospital Data financial dataset was used to evaluate all American College of Surgeons (ACS)–verified trauma centers in California. Financial vulnerability of each center was calculated using 6 metrics to calculate a composite Financial Vulnerability Score (FVS). Tertiles of the FVS were generated to classify trauma centers as high, medium, or low financial vulnerability. Hospital characteristics were also analyzed and compared.

RESULTS:
Forty-seven ACS trauma centers were identified. Nine were Level I, 27 were Level II, and 8 were Level III. Level I centers encompassed the greatest proportion of the high FVS tier (44%), whereas Level II and III centers were the most likely to be in the middle and lower tiers, respectively (44%; 63%). Lower FVS centers had greater asset:liability ratios, operating margins, and days cash on hand compared with the 2 higher tiers, whereas high FVS centers showed a greater proportion of uncompensated care, outpatient share rates, outpatient surgeries, and longer days in net accounts. Lower FVS centers were more likely to be teaching hospitals and members of a larger corporate entity.

CONCLUSION:
Many ACS trauma centers are at moderate/high risk for financial vulnerability and disparate impacts of stressor events, and the FVS may represent a novel metric that could be used at the local or statewide level.
Impedance Planimetry (Endoflip) and Ideal Distensibility Ranges for Optimal Outcomes after Nissen and Toupet Fundoplication
Authors: Wu Hoover , Attaar Mikhail , Wong Harry J , Campbell Michelle , Kuchta Kristine , Denham Ervin Woodford , Linn John , Ujiki Michael B 
Published: August 2022

BACKGROUND:
Previous research has shown that impedance planimetry–based functional lumen imaging probe (FLIP) measurements are associated with patient-reported outcomes after laparoscopic antireflux surgery. We hypothesize that Nissen and Toupet fundoplications have different ideal FLIP profiles, such as distensibility.

STUDY DESIGN:
A retrospective review of a prospectively maintained quality database was performed. Patients who had FLIP measurements during fundoplications between 2013 and 2021 were included. Reflux Symptom Index, Gastroesophageal Reflux Disease-Health Related Quality of Life Questionnaire, and dysphagia score were collected for up to 2 years postoperatively. The Wilcoxon rank-sum test was used to compare FLIP measurements vs outcomes.

RESULTS:
Two hundred fifty patients (171 Toupet, 79 Nissen) were analyzed. Distensibility ranges were categorized as tight, ideal, or loose. The ideal distensibility index range of Toupet patients with the 30- and 40-mL balloon fills were 2.6 to 3.7 mm2/mmHg. This range was associated with less dysphagia at 1 year compared with the tight group (p = 0.02). For Nissen patients, the 30- and 40-mL ideal threshold was a distensibility index of ≥2.2 mm2/mmHg. Patients with distensibility exceeding this threshold had a better quality of life than the tight group, reporting better Gastroesophageal Reflux Disease-Health Related Quality of Life Questionnaire (p = 0.02) and lower dysphagia scores (p = 0.01) at 2 years.

CONCLUSIONS:
Impedance planimetry revealed different ideal distensibility ranges after Toupet and Nissen fundoplications that are associated with improved patient-reported outcomes, suggesting that intraoperative FLIP has the potential to tailor fundoplication.
ARAX: a graph-based modular reasoning tool for translational biomedicine
Authors: Glen Amy K. , Ma Chunyu , Mendoza Luis , Womack Finn , Wood E. C. , Sinha Meghamala , Acevedo Liliana , Kvarfordt Lindsey G. , Peene Ross C. , Liu Shaopeng , Hoffman Andrew S. , Roach Jared C. , Deutsch Eric W. , Ramsey Stephen A. , Koslicki David 
Published: August 2022

AbstractMotivationWith the rapidly growing volume of knowledge and data in biomedical databases, improved methods for knowledge-graph-based computational reasoning are needed in order to answer translational questions. Previous efforts to solve such challenging computational reasoning problems have contributed tools and approaches, but progress has been hindered by the lack of an expressive analysis workflow language for translational reasoning and by the lack of a reasoning engine—supporting that language—that federates semantically integrated knowledge-bases.ResultsWe introduce ARAX, a new reasoning system for translational biomedicine that provides a web browser user interface and an application programming interface. ARAX enables users to encode translational biomedical questions and to integrate knowledge across sources to answer the user’s query and facilitate exploration of results. For ARAX, we developed new approaches to query planning, knowledge-gathering, reasoning, and result ranking and dynamically integrate knowledge providers for answering biomedical questions. To illustrate ARAX’s application and utility in specific disease contexts, we present several use-case examples.Availability and ImplementationThe source code and technical documentation for building the ARAX server-side software and its built-in knowledge database are freely available online (https://github.com/RTXteam/RTX). We provide a hosted ARAX service with a web browser interface at arax.rtx.ai and a web application programming interface (API) endpoint at arax.rtx.ai/api/arax/v1.3/ui/.Contactdmk333@psu.edu
Development and validation of an end-to-end deep learning pipeline to measure pericardial effusion in echocardiography
Authors: Wu Cheng-Ching , Cheng Chi-Yung , Chen Huang-Chung , Hung Chun-Huei , Chen Tien-Yu , Lin Chun-Hung Richard , Chiu I-Min 
Published: August 2022

AbstractIntroductionCardiac tamponade, caused by pericardial effusion (PE), is a life-threatening condition that can be resolved by timely pericardiocentesis. Nevertheless, PE measurement remains operator-dependent and may be difficult in some circumstances. Our study aimed to develop a deep-learning pipeline that measures the amount of PE based on raw echocardiography clips.MethodsEchocardiographic examination data were collected from one medical center in southern Taiwan from 2010–2018. Four commonly used cardiac windows, including the parasternal long-axis, parasternal short-axis, apical four-chamber, and subcostal views from included ultrasound examinations, were used for analysis. We proposed a deep learning pipeline consisting of three steps: moving window view selection, automated segmentation, and width calculation from a segmented mask. The pipeline was then prospectively validated from 2019–2020 using a dataset from the same hospital, and externally validated using data from another medical center in Taiwan. Model performance was evaluated using mean absolute error, intraclass correlation coefficient (ICC), and R-squared value between the ground truth and predictions.ResultsIn this study, 995 echocardiographic examinations were included. Among these, 155 were used for internal validation and 258 were used for external validation. The proposed pipeline had a predictive performance of ICC=0.867 for internal validation and ICC=0.801 for external validation. It accurately detected PE with an area under the receiving operating characteristic curve (AUC) of 0.926 (0.902–0.951) for internal validation and 0.842 (0.794–0.889) for external validation. Regarding the recognition of moderate PE or worse, the AUC values improved to 0.941 (0.923–-0.960) and 0.907 (0.876–0.943) for internal and external validation, respectively. Of all the selected cardiac windows, our model had the best prediction in the parasternal long-axis and apical four-chamber views.ConclusionsThe machine-learning pipeline could automatically calculate the width of the PE from raw ultrasound clips. The novel concepts of moving window view selection for image quality control and computer vision techniques for maximal PE width calculation seem useful in the field of ultrasound.