bluuebunny/crossref_metadata_2025 huggingface dataset:
Glutamate 1-semialdehyde aminotransferase is connected to GluTR by GluTR-binding protein and contributes to the rate-limiting step of 5-aminolevulinic acid synthesis
Authors: Sinha Neha , Eirich Jürgen , Finkemeier Iris , Grimm Bernhard
Published: August 2022

Tetrapyrroles play fundamental roles in crucial processes including photosynthesis, respiration, and catalysis. In plants, 5-aminolevulinic acid (ALA) is the common precursor of tetrapyrroles. ALA is synthesized from activated glutamate by the enzymes glutamyl-tRNA reductase (GluTR) and glutamate-1-semialdehyde aminotransferase (GSAAT). ALA synthesis is recognized as the rate-limiting step in this pathway. We aimed to explore the contribution of GSAAT to the control of ALA synthesis and the formation of a protein complex with GluTR. In Arabidopsis thaliana, two genes encode GSAAT isoforms: GSA1 and GSA2. A comparison of two GSA knockout mutants with the wild-type revealed the correlation of reduced GSAAT activity and ALA-synthesizing capacity in leaves with lower chlorophyll content. Growth and green pigmentation were more severely impaired in gsa2 than in gsa1, indicating the predominant role of GSAAT2 in ALA synthesis. Interestingly, GluTR accumulated to higher levels in gsa2 than in the wild-type and was mainly associated with the plastid membrane. We propose that the GSAAT content modulates the amount of soluble GluTR available for ALA synthesis. Several different biochemical approaches revealed the GSAAT–GluTR interaction through the assistance of GluTR-binding protein (GBP). A modeled structure of the tripartite protein complex indicated that GBP mediates the stable association of GluTR and GSAAT for adequate ALA synthesis.
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

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

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

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.
Health-related Internet Use by Caregivers of Children and Adolescents With Cancer
Authors: Harney Sarah , Chu Tzu-Chun , Trask Christine L. , Welch Jennifer J. G.
Published: August 2022

Caregivers of children with cancer have needs for information and social support related to their child’s diagnosis. The internet serves as a resource to help meet these needs. There is growing interest in health-related internet use (HRIU) by caregivers of pediatric patients as the internet rapidly evolves. This survey study describes patterns of internet use by caregivers of children with cancer and examines associations between socioeconomic status and internet use. 114 caregivers participated between 2014 and 2016. The majority (82%) reported frequent general internet use, but fewer (25-54%) reported frequent HRIU. Very few respondents (4%) reported difficulty accessing the internet; those reporting difficulty were more likely to report lower income, public/no insurance, and lower educational attainment. There were no consistent associations between socioeconomic status variables and frequency of HRIU. Less than half (43%) of caregivers reported that their internet use raised questions that they discussed or planned to discuss with the child’s nurse or doctor, and only 4% reported having changed medical decisions based on information found on the internet. We conclude that caregivers of children with cancer engage in HRIU, and this is an area for improvement in oncology anticipatory guidance and family-centered care.
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

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

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.
Detection of filovirus-reactive antibodies in Australian bat species
Authors: Barr Jennifer , Boyd Victoria , Todd Shawn , Smith Ina , Prada Diana , O'Dea Mark , Jackson Bethany , Pearce Lesley , Adams Timothy E. , Vanderduys Eric , Westcott David , McKeown Adam , Baker Michelle L. , Marsh Glenn A.
Published: August 2022

Bats have been implicated as the reservoir hosts of filoviruses in Africa, with serological evidence of filoviruses in various bat species identified in other countries. Here, serum samples from 190 bats, comprising 12 different species, collected in Australia were evaluated for filovirus antibodies. An in-house indirect microsphere assay to detect antibodies that cross-react with Ebola virus (Zaire ebolavirus; EBOV) nucleoprotein (NP) followed by an immunofluorescence assay (IFA) were used to confirm immunoreactivity to EBOV and Reston virus (Reston ebolavirus; RESTV). We found 27 of 102 Yinpterochiroptera and 19 of 88 Yangochiroptera samples were positive to EBOV NP in the microsphere assay. Further testing of these NP positive samples by IFA revealed nine bat sera that showed binding to ebolavirus-infected cells. This is the first report of filovirus-reactive antibodies detected in Australian bat species and suggests that novel filoviruses may be circulating in Australian bats.
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

Abstract

Motivation

With 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.

Results

We 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 Implementation

The 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/.

Contact

dmk333@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

Introduction

Cardiac 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.

Methods

Echocardiographic 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.

Results

In 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.

Conclusions

The 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.
Demographic and Viral-Genetic Analyses of COVID-19 Severity in Bahrain Identify Local Risk Factors and a Protective Effect of Polymerase Mutations
Authors: Koch Evan M. , Du Justin , Dressner Michelle , Alwasti Hashmeya Erahim , Al Taif Zahra , Shehab Fatima , Mohamed Afaf Merza , Ghanem Amjad , Alhajeri Amani , Alawadhi Amna , Almoamen Nabeel , Ashoor Khulood , Hasan Sara , Haghighi Alireza , Sunyaev Shamil , Farhat Maha
Published: August 2022

A multitude of demographic, health, and genetic factors are associated with the risk of developing severe COVID-19 following infection by the SARS-CoV-2. There is a need to perform studies across human societies and to investigate the full spectrum of genetic variation of the virus. Using data from 869 COVID-19 patients in Bahrain between March 2020 and March 2021, we analyzed paired viral sequencing and non-genetic host data to understand host and viral determinants of severe COVID-19. We estimated the effects of demographic variables specific to the Bahrain population and found that the impact of health factors are largely consistent with other populations. To extend beyond the common variants of concern in the Spike protein analyzed by previous studies, we used a viral burden approach and detected a protective effect of low-frequency missense viral mutations in the RNA-dependent RNA polymerase (Pol) gene on disease severity. Our results contribute to the survey of severe COVID-19 in diverse populations and highlight the benefits of studying rare viral mutations.
Fear of relapse and quality of life in multiple sclerosis: the mediating role of psychological resilience
Authors: Broche-Pérez Yunier , Jiménez-Morales Rodneys M. , Monasterio-Ramos Laura Ortiz , Vázquez-Gómez Lázaro A. , Bauer Johana , Fernández-Fleites Zoylen
Published: August 2022

The goal of this study was to examine the mediating role of psychological resilience in the relationship between fear of relapse and quality of life in a sample of patients with multiple sclerosis (PwMS). This cross-sectional study was developed online. A total of 240 PwMS were surveyed using the Multiple Sclerosis Quality of Life inventory, the Fear of Relapse Scale and the Connor-Davidson Resilience Scale. To perform the mediation analysis PROCESS macro was used. In our study, fear of relapse was a predictor of psychological resilience and quality of life, and psychological resilience was a predictor of quality of life. Finally, psychological resilience showed a mediating role in the relationship between fear of relapse and quality of life. Considering that resilience is a modifiable variable, the implementation of interventions aimed at enhancing resilience can have a favorable impact on the psychological well-being and quality of life of patients with multiple sclerosis.
Monkeypox virus shows potential to infect a diverse range of native animal species across Europe, indicating high risk of becoming endemic in the region
Authors: Blagrove Marcus SC , Pilgrim Jack , Kotsiri Aurelia , Hui Melody , Baylis Matthew , Wardeh Maya
Published: August 2022

Background

Monkeypox is a zoonotic virus which persists in animal reservoirs and periodically spills over into humans, causing outbreaks. During the current 2022 outbreak, monkeypox virus has persisted via human-human transmission, across all major continents and for longer than any previous record. This unprecedented spread creates the potential for the virus to ‘spillback’ into local susceptible animal populations. Persistent transmission amongst such animals raises the prospect of monkeypox virus becoming enzootic in new regions. However, the full and specific range of potential animal hosts and reservoirs of monkeypox remains unknown, especially in newly at-risk non-endemic areas.

Methods

Here, utilising ensembles of classifiers comprising different class balancing techniques and incorporating instance weights, we identify which animal species are potentially susceptible to monkeypox virus. Subsequently, we generate spatial distribution maps to highlight high-risk geographic areas at high resolution.

Findings

We show that the number of potentially susceptible species is currently underestimated by 2.4 to 4.3-fold, and that a high density of wild susceptible species are native to Europe. We provide lists of these species, and highlight high-risk hosts for spillback and potential long-term reservoirs, which may enable monkeypox virus to become endemic.

Interpretation

We highlight the European red fox and brown rat, as they have established interactions with potentially contaminated urban waste and sewage, which provides a mechanism for potential spillback. We anticipate that our results will enable targeted active surveillance of potential spillback event, to minimise risk of the virus becoming endemic in these regions. Our results also indicate the potential of domesticated cats and dogs (latter now confirmed) being susceptible to monkeypox virus, and hence support many health organisations’ advice for infected humans to avoid physical interaction with pets.
Sound localization acuity of the common marmoset (Callithrix jacchus)
Authors: Remington Evan D. , Chen Chenggang , Wang Xiaoqin
Published: August 2022

The common marmoset (Callithrix jacchus) is a small arboreal New World primate which has emerged as a promising model in auditory neuroscience. One potentially useful application of this model system is in the study of the neural mechanism underlying spatial hearing in primate species, as the marmoset’s visually occluded natural habitat in the forest would make sound localization an essential behavior for survival. However, interpretation of neurophysiological data on sound localization requires an understanding of perceptual abilities, and the sound localization behavior of marmosets has not been well studied. The present experiment measured sound localization acuity using an operant conditioning procedure in which marmosets were trained to discriminate changes in sound location in the horizontal (azimuth) or vertical (elevation) dimension. Our results showed that the minimum audible angle (MAA) for horizontal discrimination was on average 15° for band-passed Gaussian noise and 13° for Random Spectral Shape (RSS) stimuli, whereas the MAA for vertical locations was at 17° and 22° for band-passed Gaussian noises containing more and less high frequency energy, respectively.
Factors associated with low school readiness, a linked health and education data study in Wales, UK
Authors: Bandyopadhyay Amrita , Marchant Emily , Jones Hope , Parker Michael , Evans Julie , Brophy Sinead
Published: August 2022

Background

School readiness is a measure of a child’s cognitive, social, and emotional readiness to begin formal schooling. Children with low school readiness need additional support from schools for learning, developing required social and academic skills, and catching-up with their school-ready peers. This study aims to identify the modifiable risk factors associated with low school readiness using linked routine data for children in Wales.

Method

This was a longitudinal data linkage cohort study. The cohort comprises of children who completed the Foundation Phase assessment between 2012 and 2018. Individuals were identified by linking Welsh Demographic Service and Pre16 Education Attainment datasets. School readiness was assessed via the binary outcome of the Foundation Phase assessment (achieved/not achieved). This study used multivariable logistic regression model and decision tree to identify and weight the most important risk factors associated with low school readiness.

Results

In order of importance, logistic regression identified maternal learning difficulties (adjusted odds ratio 5.35(95% confidence interval 3.97-7.22)), childhood epilepsy (2.95(2.39-3.66)), very low birth weight (2.24(1.86-2.70), being a boy (2.11(2.04-2.19)), being on free school meals (1.85(1.78–1.93)), living in most deprived area (1.67(1.57–1.77)), maternal death (1.47(1.09-1.98)), and maternal diabetes (1.46(1.23 - 1.78)) as factors associated with low school readiness. Using a decision tree, eligibility for free school meals, being a boy, absence/low attendance at school, being a younger child (e.g., August born), being born low birth weight, and not being breastfed were factors found to be associated with low school readiness

Conclusion

This work suggests that public health interventions focusing on children who are: boys, living in deprived areas, have poor early years attendance, have parents with learning difficulties, have parents with an illness or have illnesses themselves, would make the most difference to school readiness in the population.
The COVID HOME study research protocol: Prospective cohort study of non-hospitalised COVID-19 patients
Authors: Tami A. , van der Gun B.T.F. , Wold K.I. , Vincenti-González M.F. , Veloo A.C.M. , Knoester M. , Harmsma V.P.R. , de Boer G.C. , Huckriede A.L.W. , Pantano D. , Gard L. , Rodenhuis-Zybert I. , Upasani V. , Smit J. , Dijkstra A. , de Haan J. , van Elst J. , van den Boogaard J. , O’ Boyle S. , Nacul L. , Niesters H.G.M. , Friedrich A.W.
Published: August 2022

Background

Guidelines on COVID-19 management are developed as we learn from this pandemic. However, most research has been done on hospitalised patients and the impact of the disease on non-hospitalised and their role in transmission are not yet well understood.

The COVID HOME study conducts research among COVID-19 patients and their family members who were not hospitalised during acute disease, to guide patient care and inform public health guidelines for infection prevention and control in the community and household.

Methods

An ongoing prospective longitudinal observational study of COVID-19 outpatients was established in March 2020 in the Netherlands. Laboratory confirmed SARS-CoV-2 infected individuals of all ages that did not merit hospitalisation, and their household (HH) members, were enrolled after written informed consent. Enrolled participants were visited at home within 48 hours after initial diagnosis, and then weekly on days 7, 14 and 21 to obtain clinical data, a blood sample for biochemical parameters/cytokines and serological determination; and a nasopharyngeal/throat swab plus urine, stool and sperm or vaginal secretion (if consenting) to test for SARS-CoV-2 by RT-PCR (viral shedding) and for viral culturing. Weekly nasopharyngeal/throat swabs and stool samples, plus a blood sample on days 0 and 21 were also taken from HH members to determine whether and when they became infected. All participants were invited to continue follow-up at 3-, 6-, 12- and 18-months post-infection to assess long-term sequelae and immunological status.

Preliminary Results

A total of 256 participants belonging to 103 HH were included of which, 190 (74.2%) were positive for SARS-CoV-2 infection. Most individuals (183/190, 96.3%) developed mild to moderate disease. At the time of writing, all participants had reached the 3 and 6 month time-points of the long-term follow-up, while approximately 78% reached 12 month and 23% the 18 month time-point. Preliminary analysis showed that 43% (52/121) positive individuals reported having complaints at 3 months post-infection, while 42.7% (61/143) had complaints at 6 months.
The Protein Common Assembly Database (ProtCAD) – A comprehensive structural resource of protein complexes
Authors: Xu Qifang , Dunbrack Roland L.
Published: August 2022

Proteins often act through oligomeric interactions with other proteins. X-ray crystallography and cryo-electron microscopy provide detailed information on the structures of biological assemblies, defined as the most likely biologically relevant structures derived from experimental data. In crystal structures, the most relevant assembly may be ambiguously determined, since multiple assemblies observed in the crystal lattice may be plausible. It is estimated that 10-15% of PDB entries may have incorrect or ambiguous assembly annotations. Accurate assemblies are required for understanding functional data and training of deep learning methods for predicting assembly structures. As with any other kind of biological data, replication via multiple independent experiments provides important validation for the determination of biological assembly structures. Here we present the Protein Common Assembly Database (ProtCAD), which presents clusters of protein assembly structures observed in independent structure determinations of homologous proteins in the Protein Data Bank (PDB). ProtCAD is searchable by PDB entry, UniProt identifiers, or Pfam domain designations and provides downloads of coordinate files, PyMol scripts, and publicly available assembly annotations for each cluster of assemblies. About 60% of PDB entries contain assemblies in clusters of at least 2 independent experiments. All clusters and coordinates are available on ProtCAD web site (http://dunbrack2.fccc.edu/protcad).
Disentangling the Neural Correlates of Agency, Ownership and Multisensory Processing
Authors: Harduf Amir , Shaked Ariel , Yaniv Adi Ulmer , Salomon Roy
Published: August 2022

The experience of the self as an embodied agent in the world is an essential aspect of human consciousness. This experience arises from the feeling of control over one’s bodily actions, termed the Sense of Agency (SoA), and the feeling that the body belongs to the self, Body Ownership (BO). Despite long-standing philosophical and scientific interest in the relationship between the body and brain, the neural systems involved in SoA and BO and especially their interactions, are not yet understood. In this preregistered study using the Moving Rubber Hand Illusion inside an MR-scanner, we aimed to uncover the relationship between BO & SoA in the human brain. Importantly, by using both visuomotor and visuotactile stimulations and measuring online trial-by-trial fluctuations in the illusion magnitude, we were able to disentangle brain systems related to objective sensory stimulation and subjective judgments of the bodily-self. Our results indicate that at both the behavioral and neural levels, BO and SoA are strongly interrelated. Multisensory regions in the occipital and fronto-parietal regions encoded convergence of sensory stimulation conditions. However, the subjective judgments of bodily-self were also related to BOLD fluctuations in regions not activated by the sensory conditions such as the insular cortex and precuneus. Our results highlight the convergence of multisensory processing in specific neural systems for both BO and SoA with partially dissociable regions for subjective judgments in regions of the default mode network.
Recombination between heterologous human acrocentric chromosomes
Authors: Guarracino Andrea , Buonaiuto Silvia , de Lima Leonardo Gomes , Potapova Tamara , Rhie Arang , Koren Sergey , Rubinstein Boris , Fischer Christian ,   Human Pangenome Reference Consortium, Gerton Jennifer L. , Phillippy Adam M. , Colonna Vincenza , Garrison Erik
Published: August 2022

The short arms of the human acrocentric chromosomes 13, 14, 15, 21, and 22 share large homologous regions, including the ribosomal DNA repeats and extended segmental duplications (Floutsakou et al. 2013; van Sluis et al. 2019). While the complete assembly of these regions in the Telomere-to-Telomere consortium’s CHM13 provided a model of their homology (Nurk et al. 2022), it remained unclear if these patterns were ancestral or maintained by ongoing recombination exchange. Here, we show that acrocentric chromosomes contain pseudo-homologous regions (PHRs) indicative of recombination between non-homologs. Considering an all-to-all comparison of the high-quality human pangenome from the Human Pangenome Reference Consortium (HPRC) (Liao et al. 2022), we find that contigs from all of the acrocentric short arms form a community similar to those formed by single chromosomes or the sex chromosome pair. A variation graph (Garrison et al. 2018) constructed from centromere-spanning acrocentric contigs indicates the presence of regions where most contigs appear nearly identical between heterologous CHM13 acrocentrics. Except on chromosome 15, we observe faster decay of linkage disequilibrium in the PHRs than in the corresponding short and long arms, indicating higher rates of recombination (N. Li and Stephens 2003; Huttley et al. 1999). The PHRs include sequences previously shown to lie at the breakpoint of Robertsonian translocations (Jarmuz-Szymczak et al. 2014), and we show that their arrangement is compatible with crossover in inverted duplications on chromosomes 13, 14, and 21. The ubiquity of signals of recombination between heterologous chromosomes seen in the HPRC draft pangenome’s acrocentric assemblies suggests that these shared sequences form the basis for recurrent Robertsonian translocations, providing sequence and population-based confirmation of hypotheses first developed cytogenetically fifty years ago (Hamerton et al. 1975).
The evolution of behavioral cues and signaling in displaced communication
Authors: Bernard Arthur , Wischmann Steffen , Floreano Dario , Keller Laurent
Published: August 2022

Displaced communication, whereby individuals communicate regarding a subject that is not immediately present (spatially or temporally), is one of the key innovations of human language. It also occurs in a few animal species, most notably the honeybee, where the waggle dance is used to communicate the location and quality of a patch of flowers. However, it is difficult to study how it emerged given the paucity of species displaying this capacity and the fact that it often occurs via complex multimodal signals. To address this issue, we developed a novel paradigm in which we conducted experimental evolution with foraging agents endowed with neural networks that regulate their movement and the production of signals. Displaced communication readily evolved but, surprisingly, agents did not use signal amplitude to convey information on food location. Instead, they used signal onset-delay and duration-based mode of communication, which depends on the motion of the agent within a communication area. When agents were experimentally prevented from using these modes of communication, they evolved to use signal amplitude instead. Interestingly, this mode of communication was more efficient and led to higher performance. Subsequent controlled experiments suggested that this more efficient mode of communication failed to evolve because it took more generations to emerge than communication grounded on the onset-delay and length of signaling. These results reveal that displaced communication is likely to initially evolve from non-communicative behavioral cues providing incidental information with evolution later leading to more efficient communication systems through a ritualization process.

Author Summary

The evolution of displaced communication, the process through which individuals share information about a remote object (in space or time), is a key innovation in language. By conducting experimental evolution we found that displaced communication is more likely to leverage and evolve from behavioural cues, such as the agent’s movement, rather than from dedicated communication modes, such as the amplitude of emitted signals. This phenomenon is shown to happen because communication via signal amplitude -although more efficient-is slower to evolve. The simple behaviors and neural networks of the agents studied here, also suggest that communication may evolve more frequently than expected via ritualization, a process whereby an action or behavior pattern in an animal loses its original function but is retained for its role in display or other social interactions.