bluuebunny/crossref_metadata_2025 huggingface dataset:
Applicability of the Modified Fels and Optimized Oxford Skeletal Maturity Estimation Systems to the Modern Pediatric Population
Authors: Furdock Ryan J. , Kuo Andy , Chen Kallie J. , Benedick Alexander J. , Liu Raymond W.
Published: December 2022

Background:

The recently developed modified Fels knee and optimized Oxford hip skeletal maturity systems (SMS) have demonstrated impressive performance compared with the Greulich and Pyle skeletal age atlas when applied to the same historical, mostly white, pediatric population. We sought to determine whether these 2 systems require modification before being used in modern children.

Methods:

We collected knee and hip radiographs between January 2015 and September 2020 from our electronic medical record from 4 groups of children: (1) white males, (2) black males, (3) white females, and (4) black females. Males between 9 and 17 years and females between 7 and 15 years were included. After reliability analyses, 5 nonpathologic radiographs for each age and joint were randomly selected from each group and evaluated with the appropriate SMS. The mean discrepancy between each group’s chronological age at the time of radiograph and estimated skeletal age was compared between our modern cohort and the historical Bolton-Brush children. After normality testing, paired t tests or Wilcoxon signed-rank tests were performed, as appropriate. A Bonferroni correction was applied to address multiple testing.

Results:

Three hundred sixty modern radiographs were evaluated (180 knees and 180 hips). All 7 modified Fels knee parameters and all 5 optimized Oxford hip parameters had inter and intrarater reliability coefficients ≥0.7, indicating good to very good reliability. For the modified Fels knee SMS, white males (Δ0.74 y, P<0.001), black males (Δ0.69 y, P<0.001), and black females (Δ0.4 y, P=0.04) had advanced skeletal age compared with their historical counterparts of the same sex. No differences were found between historical and modern patients for the optimized Oxford hip SMS. No differences were found for either SMS comparing modern patients along racial lines (P>0.05 for all).

Conclusions:

Discrepancies in skeletal age estimates made by the modified Fels knee SMS exist between modern pediatric white males, black males, and black females and their historic counterparts. No differences were found when using optimized Oxford hip SMS. Future studies should evaluate how these translate to clinical decision-making.

Level of Evidence:

Level III; retrospective chart review.
Outcomes of Secondary Intraocular Lens Implantation and Descemet Stripping Endothelial Keratoplasty—Comparing Staged Versus Combined Surgical Approach
Authors: Goodman Courtney F. , Mittal Rhiya , Awidi Abdelhalim , Vanner Elizabeth A. , Han Elaine , Daoud Yassine J. , Koo Ellen H.
Published: December 2022

Purpose:

The aim of this study was to compare the outcomes of staged versus combined surgical approach for secondary intraocular lens (IOL) implantation and Descemet stripping endothelial keratoplasty (DSEK).

Methods:

This is a retrospective review of 124 eyes from 124 patients who underwent either staged or combined secondary IOL implantation in addition to DSEK over a 5-year period at 2 academic tertiary referral centers, between January 1, 2014, and October 1, 2019. Corrected distance visual acuity (CDVA), presence of graft detachment, primary graft failure (PGF), and cystoid macular edema were documented and analyzed.

Results:

The CDVA for the 1- to 2- month follow-up period was significantly better in the staged group compared with the combined group (P = 0.011). By the postoperative 6- to 9-month follow-up period, there was no significant difference in the CDVA between the groups (P = 0.591). There was no significant difference in the incidence of PGF or graft detachment between the 2 groups (P > 0.05). In addition, there was no significant difference in the CDVA or rate of postoperative complications between the different methods of IOL fixation.

Conclusions:

The short-term visual outcomes were significantly better in eyes that underwent staged secondary IOL implantation and DSEK versus the combined surgical approach, although the difference was no longer present at 6 to 9 months. There was no difference in the rate of PGF or graft detachment between the 2 groups.
Congenital Cytomegalovirus Infection and Hearing Outcomes in Twins: A Systematic Review of Reported Cases
Authors: Cordray Holly , Liu-Lam Oliver , Tey Ching Siong , Alfonso Kristan
Published: December 2022

Objective

Congenital cytomegalovirus infection is the leading nonhereditary cause of pediatric sensorineural hearing loss. This systematic review evaluated infection concordance and comparative hearing abilities in twins/multiple births to model infection patterns.

Databases Reviewed

PubMed, Embase, Web of Science, and Google Scholar.

Methods

Studies that reported hearing outcomes of congenital cytomegalovirus infection in at least one multiple birth were eligible. Concordant infections (both twins) and discordant infections (single twin) were included. Multiple reviewers performed data extraction and quality assessment. Analyses involved relative risk of infection concordance by zygosity and chorionicity and odds of hearing loss by infection concordance. Hearing outcomes were compared between siblings.

Results

Of 247 studies screened, 31 were included (74.2% high quality). The review captured 40 eligible multiple births. Among infected patients, 42.9% (95% confidence interval, 31.2–55.2%) demonstrated hearing loss. All uninfected twins had normal hearing. Most infections were concordant, and infected patients experienced 4.11 (1.18–14.36) times greater odds of hearing loss if their twin was also infected (p = .02). Yet siblings’ hearing outcomes diverged in over 40% of concordant cases. If either twin is infected, infection risk in the second twin is 3.25 (1.83–5.79) times greater in monozygotic than dizygotic twins and 2.50 (1.61–3.88) times greater in monochorionic than dichorionic twins (both p < .001). We describe a case from our practice.

Conclusion

Congenital cytomegalovirus infection patterns and hearing outcomes can vary widely even within a shared fetal and postnatal environment. Suspected infection in a twin indicates that both should receive testing and continued monitoring for late-onset sequelae.
Evaluation of Disturbances in Hearing, Tinnitus, and Vestibular Symptoms as Signs of COVID-19 Infection
Authors: Africa Robert E. , Westenhaver Zack K. , Zimmerer René E. , McKinnon Brian J.
Published: December 2022

Background

There have been reports and studies indicating audiovestibular disturbances in COVID-19 patients with variations in the percentage of sensorineural hearing loss (SNHL). The purpose of this study is to compare the incidence of newly diagnosed SNHL, sudden idiopathic hearing loss (SIHL), tinnitus, and vestibular disturbances between infected and uninfected patients, as well as to identify population groups at risk.

Methods

This study used TriNetX to obtain statistics on COVID-19 (+) and COVID-19 (−) patients from 61 healthcare organizations. Propensity score with 1:1 matching was used to control confounding variables. This study evaluated the relative risk of developing audiovestibular disturbances up to 1 month after a COVID-19 test and further investigated the incidence in COVID-19 (+) subset groups.

Results

Between COVID-19 (+) and COVID-19 (−) patients who had an audiogram, there was no statistically significant difference in SNHL or SIHL (SNHL: relative risk [RR] = 0.69, 95% confidence interval [CI] = 0.46–1.04; SIHL: RR = 1.00, 95% CI = 0.42–2.40). Race/ethnicity or specified comorbidity did not affect the incidence of SNHL or SIHL. There was a statistically significant difference in tinnitus and vestibular disturbances between the COVID-19 (+) and the COVID-19 (−) groups (RR = 1.29, 95% CI = 1.01–1.66; RR = 2.33, 95% CI = 2.19–2.48).

Conclusion

New onset hearing loss is not more common in patients with a positive COVID-19 test than those with a negative COVID-19 test. Audiologic evaluation is needed to verify reported hearing disturbances. Although statistically significant in specific population groups, tinnitus and vestibular disturbances may not be clinically significant due to the low incidence.
Public Perception of Ménière’s Disease: A Social Media Analysis
Authors: Hamdi Osama A. , Bellinger Jeffrey R. , Wright Garrison P. , Churnin Ian T. , Strumpf Andrew M. , Casazza Geoffrey C. , Kesser Bradley W.
Published: December 2022

Objective

To analyze tweets associated with Ménière’s disease (MD), including type of users who engage, change in usage patterns, and temporal associations, and to compare the perceptions of the general public with healthcare providers.

Methods

An R-program code, academictwitterR API, was used to query Twitter. All tweets mentioning MD from 2007 to 2021 were retrieved and analyzed. Valence Aware Dictionary and Sentiment Reasoning was used as a model to assess sentiment of tweets. Two reviewers assessed 1,007 tweets for qualitative analysis, identifying the source and the topic of the tweet.

Results

A total of 37,402 tweets were analyzed. The number of tweets per user ranged from 1 to 563 (M = 33.7, SD = 91.1). Quantitative analysis showed no temporal or seasonal association; however, tweeting increased when celebrities were diagnosed with MD. Of the 1007 representative tweets analyzed, 60.6% of tweets came from the general public and were largely of negative sentiment focusing on quality of life and support, whereas healthcare providers accounted for 23% of all tweets and focused on treatment/prevention. Tweets by news sources accounted for the remaining 13% of all tweets and were primarily positive in sentiment and focused on awareness.

Conclusions

MD is commonly tweeted about by the general public, with limited input regarding the disease from healthcare providers. Healthcare providers must provide accurate information and awareness regarding MD, especially when awareness is highest, such as when celebrities are diagnosed.

Level of Evidence

Level IV.

Indicate IRB or IACUC

Not applicable.
COVID-19, HIV, and Syphilis Contact Tracing: What have we learned and where are we headed?
Authors: Sachdev Darpun , Chew Ng Rilene A. , Hernandez Katherine , Nguyen Trang Quyen , Cohen Stephanie E.
Published: December 2022

Contact tracing is a core public health intervention for a range of communicable diseases, in which the primary goal is to interrupt disease transmission and decrease morbidity. In this paper, we present lessons learned from COVID-19, HIV, and syphilis in San Francisco to illustrate factors that shape the effectiveness of contact tracing programs, and to highlight the value of investing in a robust disease intervention workforce with capacity to pivot rapidly in response to a range of emerging disease trends and outbreak response needs.
The Association Between Hospital High-volume Anesthesiology Care and Patient Outcomes for Complex Gastrointestinal Cancer Surgery
Authors: Hallet Julie , Jerath Angela , Perez d’Empaire Pablo , Eskander Antoine , Carrier François M. , McIsaac Daniel I. , Turgeon Alexis F. , Idestrup Chris , Flexman Alana M. , Lorello Gianni , Darling Gail , Kidane Biniam , Kaliwal Yosuf , Barabash Victoria , Coburn Natalie , Sutradhar Rinku
Published: December 2022

Objective:

To examine the association of between hospital rates of high-volume anesthesiology care and of postoperative major morbidity.

Background:

Individual anesthesiology volume has been associated with individual patient outcomes for complex gastrointestinal cancer surgery. However, whether hospital-level anesthesiology care, where changes can be made, influences the outcomes of patients cared at this hospital is unknown.

Methods:

We conducted a population-based retrospective cohort study of adults undergoing esophagectomy, pancreatectomy, or hepatectomy for cancer from 2007 to 2018. The exposure was hospital-level adjusted rate of high-volume anesthesiology care. The outcome was hospital-level adjusted rate of 90-day major morbidity (Clavien-Dindo grade 3–5). Scatterplots visualized the relationship between each hospital’s adjusted rates of high-volume anesthesiology and major morbidity. Analyses at the hospital-year level examined the association with multivariable Poisson regression.

Results:

For 7893 patients at 17 hospitals, the rates of high-volume anesthesiology varied from 0% to 87.6%, and of major morbidity from 38.2% to 45.4%. The scatter plot revealed a weak inverse relationship between hospital rates of high-volume anesthesiology and of major morbidity (Pearson: −0.23). The adjusted hospital rate of high-volume anesthesiology was independently associated with the adjusted hospital rate of major morbidity (rate ratio: 0.96; 95% CI, 0.95–0.98; P<0.001 for each 10% increase in the high-volume rate).

Conclusions:

Hospitals that provided high-volume anesthesiology care to a higher proportion of patients were associated with lower rates of 90-day major morbidity. For each additional 10% patients receiving care by a high-volume anesthesiologist at a given hospital, there was an associated reduction of 4% in that hospital’s rate of major morbidity.
Emergency Department Pediatric Readiness Among US Trauma Centers
Authors: Newgard Craig D. , Babcock Sean R. , Song Xubo , Remick Katherine E. , Gausche-Hill Marianne , Lin Amber , Malveau Susan , Mann N. Clay , Nathens Avery B. , Cook Jennifer N. B. , Jenkins Peter C. , Burd Randall S. , Hewes Hilary A. , Glass Nina E. , Jensen Aaron R. , Fallat Mary E. , Ames Stefanie G. , Salvi Apoorva , McConnell K. John , Ford Rachel , Auerbach Marc , Bailey Jessica , Riddick Tyne A. , Xin Haichang , Kuppermann Nathan ,   On behalf of the Pediatric Readiness Study Group
Published: December 2022

Objective:

We used machine learning to identify the highest impact components of emergency department (ED) pediatric readiness for predicting in-hospital survival among children cared for in US trauma centers.

Background:

ED pediatric readiness is associated with improved short-term and long-term survival among injured children and part of the national verification criteria for US trauma centers. However, the components of ED pediatric readiness most predictive of survival are unknown.

Methods:

This was a retrospective cohort study of injured children below 18 years treated in 458 trauma centers from January 1, 2012, through December 31, 2017, matched to the 2013 National ED Pediatric Readiness Assessment and the American Hospital Association survey. We used machine learning to analyze 265 potential predictors of survival, including 152 ED readiness variables, 29 patient variables, and 84 ED-level and hospital-level variables. The primary outcome was in-hospital survival.

Results:

There were 274,756 injured children, including 4585 (1.7%) who died. Nine ED pediatric readiness components were associated with the greatest increase in survival: policy for mental health care (+8.8% change in survival), policy for patient assessment (+7.5%), specific respiratory equipment (+7.2%), policy for reduced-dose radiation imaging (+7.0%), physician competency evaluations (+4.9%), recording weight in kilograms (+3.2%), life support courses for nursing (+1.0%–2.5%), and policy on pediatric triage (+2.5%). There was a 268% improvement in survival when the 5 highest impact components were present.

Conclusions:

ED pediatric readiness components related to specific policies, personnel, and equipment were the strongest predictors of pediatric survival and worked synergistically when combined.
Association of Health Professional Shortage Area Hospital Designation With Surgical Outcomes and Expenditures Among Medicare Beneficiaries
Authors: Mullens Cody L. , Lussiez Alisha , Scott John W. , Kunnath Nicholas , Dimick Justin B. , Ibrahim Andrew M.
Published: December 2022

Objective:

To compare surgical outcomes and expenditures at hospitals located in Health Professional Shortage Areas to nonshortage area designated hospitals among Medicare beneficiaries.

Background:

More than a quarter of Americans live in federally designated Health Professional Shortage Areas. Although there is growing concern that medical outcomes may be worse, far less is known about hospitals providing surgical care in these areas.

Methods:

Cross-sectional retrospective study from 2014 to 2018 of 842,787 Medicare beneficiary patient admissions to hospitals with and without Health Professional Shortage Area designations for common operations including appendectomy, cholecystectomy, colectomy, and hernia repair. We assessed risk-adjusted outcomes using multivariable logistic regression accounting for patient factors, admission type, and year were compared for each of the 4 operations. Hospital expenditures were price-standardized, risk-adjusted 30-day surgical episode payments. Primary outcome measures included 30-day mortality, hospital readmissions, and 30-day surgical episode payments.

Results:

Patients (mean age=75.6 years, males=44.4%) undergoing common surgical procedures in shortage area hospitals were less likely to be White (84.6% vs 88.4%, P<0.001) and less likely to have≥2 Elixhauser comorbidities (75.5% vs 78.2%, P<0.001). Patients undergoing surgery at Health Professional Shortage Area hospitals had lower risk-adjusted rates of 30-day mortality (6.05% vs 6.69%, odds ratio=0.90, CI, 0.90–0.91, P<0.001) and readmission (14.99% vs 15.74%, odds ratio=0.94, CI, 0.94–0.95, P<0.001). Medicare expenditures at Health Professional Shortage Area hospitals were also lower than nonshortage designated hospitals ($28,517 vs $29,685, difference= −$1168, P<0.001).

Conclusions:

Patients presenting to Health Professional Shortage Area hospitals obtain safe care for common surgical procedures without evidence of higher expenditures among Medicare beneficiaries. These findings should be taken into account as current legislative proposals to increase funding for care in these underserved communities are considered.
Asymptomatic Covid-19 Trauma Patients Have Worse Outcomes and Resource Utilization
Authors: Sozzi Marco , Lam Lydia , Nichols Chance , Demetriades Demetrios
Published: December 2022

Objective:

To evaluate the impact of COVID-19 positivity on outcomes and resource utilization in the trauma population.

Introduction:

COVID-19 infection worsens outcomes of trauma patients, but it is not known if asymptomatic COVID-19 trauma patients have different outcomes from COVID-19-negative patients.

Methods:

All trauma patients admitted to an urban level 1 trauma center between March 2020 and October 2021 were collected and reviewed for COVID-19 status. COVID-19-positive patients with symptoms or initial chest radiographs consistent with infections were excluded. Propensity score model 1:3 matched asymptomatic COVID-19-positive to COVID-19-negative trauma patients for their age, body mass index, MOA, injury severity score, SBP<90, GCS<9, and comorbidities. Outcomes included mortality, complications, and resource utilization.

Results:

A total of 185 asymptomatic COVID-19-positive patients were matched with 554 COVID-19-negative patients. Asymptomatic COVID-19 -positive patients had higher rates of myocardial infarction and cardiac arrest (3.2% vs. 0.9%, P=0.023), higher ventilator days (3.33 vs. 1.49 days, P<0.001), ICU-length of stay [LOS (4.92 vs. 3.41 d, P=0.034)], overall LOS (11.41 vs. 7.24 d, P<0.001), and hospital charges ($ 176.505.80 vs. 107.591.93, P=0.002).

Conclusion:

Asymptomatic COVID-19 trauma patients have significantly higher rates of cardiac events, longer LOS, and higher hospital charges when compared with similar trauma patients who are COVID-19-negative.
Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan
Authors: Valkovskaya Maria , Hassan Arsalan , Zartaloudi Eirini , Hussain Fahad , Umar Muhammad , Khizar Bakht , Khattak Inzemam , Gill Shamshad Ahmed , Khan Shams-Ud-Din Ahmad , Dogar Imtiaz Ahmad , Mustafa Ali Burhan , Ansari Moin Ahmed , Qalb I Hyder Syed , Ali Muhammad , Ilyas Nilofar , Channar Parveen , Mughal Nazish , Channa Sumera , Mufti Khalid , Mufti Ali Ahsan , Hussain Mian Iftikhar , Shafiq Sadia , Tariq Muhammad , Khan Muhammad Kamran , Chaudhry Shahzad Tahir , Choudhary Abdul Rashid , Ali Mian Nizam , Ali Gohar , Hussain Ashfaq , Rehman Muhammad , Ahmad Noman , Farooq Saeed , Naeem Farooq , Nasr Tanveer , Lewis Glyn , Knowles James A. , Ayub Muhammad , Kuchenbaecker Karoline
Published: December 2022

Introduction

Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan.

Methods

DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology.

Results and discussion

Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings.

Conclusion

DIVERGE is a carefully designed case–control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research.
A case series and literature review of infections due to Myroides spp. – Identification of contributing factors and emerging antibiotic susceptibility trends.
Authors: khan Uzair , Pandey Ellora , Gandham Nageswari , Das Nikunja , Mukhida Sahjid , Kannuri Sriram , Bhaumik Shalini , Mirza Shahzad
Published: December 2022

Introduction: Infections by Myroides spp. can lead to significant morbidity and mortality, particularly in immunocompromised patients with underlying co-morbidities. Recent reports have highlighted its intrinsic and acquired drug resistance, making it a particularly challenging infectious agent to combat.
Methods: Myroides spp. isolated and reported in clinically significant urine samples were considered for the study. Identification of the organism was done by VITEK 2C, BioMerieux. Antibiotic Susceptibility Testing was done using both manual and automated methods following Clinical and Laboratory Standards Institute (CLSI) guidelines. Existing literature was searched on MEDLINE using PubMed.
Results: We present a series of five catheter associated urinary tract infections (CAUTI) due to M. odoratimimus, with sensitivity to only minocycline. This is the first case from Western India, and the third case in existing literature that shows Myroides sensitivity only to minocycline.  Our literature review is the first to systemize possible contributory factors to infection, allowing us to devise a clinically relevant tool that delineates contributory factors and efficacious drugs in Myroidesspp. infection
Conclusion: Myroides spp. infections, earlier considered rare and opportunistic, need cognizance and diagnostic suspicion especially in certain associated conditions.
ICTV Virus Taxonomy Profile: Matonaviridae 2022
Authors: Mankertz Annette , Chen Min-Hsin , Goldberg Tony L. , Hübschen Judith M. , Pfaff Florian , Ulrich Rainer G. ,   ICTV Report Consortium
Published: December 2022

The family Matonaviridae comprises enveloped viruses with positive-sense RNA genomes of 9.6–10 kb. The genus Rubivirus includes rubella virus (species Rubivirus rubellae) infecting humans, ruhugu virus (species Rubivirus ruteetense) infecting bats and rustrela virus (species Rubivirus strelense) infecting rodents and zoo animals. Rubella virus is spread via droplets. Postnatal infection leads to benign disease with rash and fever. Infection of seronegative women with rubella virus during the first trimester of pregnancy will often result in severe foetal malformations, known as congenital rubella syndrome. Vaccines are globally available. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Matonaviridae, which is available at ictv.global/report/matonaviridae.
Massive sequencing of the V3–V4 hypervariable region of bronchoalveolar lavage from patients with COVID-19 and VAP reveals the collapse of the pulmonary microbiota
Authors: Durán-Manuel Emilio Mariano , Loyola-Cruz Miguel Ángel , Cruz-Cruz Clemente , Ibáñez-Cervantes Gabriela , Gaytán-Cervantes Javier , González-Torres Carolina , Quiroga-Vargas Edith , Calzada-Mendoza Claudia Camelia , Cureño-Díaz Monica Alethia , Fernández-Sánchez Verónica , Castro-Escarpulli Graciela , Bello-López Juan Manuel
Published: December 2022

Background. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a predisposing factor for the development of healthcare-associated infections, of which ventilator-associated pneumonia (VAP) is one.

Hypothesis. VAP is caused by ESKAPE bacteria and other pathogens not detected by microbiological culture.

Aim. To elucidate the bacterial pathogens of severe coronavirus disease 2019 (COVID-19) and VAP patients by massive sequencing and to predict their degree of relationship with the age and sex of the patients.

Methods. Analysis of ribosomal libraries of the V3–V4 hypervariable region obtained by Illumina sequencing of bronchoalveolar lavages from COVID-19 and VAP (first wave) patients from Hospital Juárez de México.

Results.

Acinetobacter

and

Pseudomonas

were the main bacterial genera in the bronchoalveolar lavages (BALs) analysed. Other members of the ESKAPE group, such as

Enterococcus

and

Klebsiella

, were also identified. Taxonomic composition per patient showed that non-ESKAPE genera were present with significant relative abundances, such as

Prevotella

, Stenotrophomas,

Enterococcus

,

Mycoplasma

,

Serratia

and

Corynebacterium

. Kruskal–Wallis analysis proved that VAP acquisition is an adverse event that is not influenced by the sex and age of COVID-19 patients.

Discussion. Metagenomic findings in COVID-19/VAP patients highlight the importance of implementing comprehensive microbiological diagnostics by including alternative tools for the detection of the causal agents of healthcare-associated infections (HAIs).

Conclusions. Timely identification of bacteria ‘not sought’ in diagnostic bacteriology laboratories will allow specific and targeted treatments. Implications for the restricted diagnosis of VAP causative agents in COVID-19 patients and the presence of pathogens not detected by classical microbiology are analysed and discussed.
A novel approach for combining the metagenome, metaresistome, metareplicome and causal inference to determine the microbes and their antibiotic resistance gene repertoire that contribute to dysbiosis
Authors: Stebliankin Vitalii , Sazal Musfiqur , Valdes Camilo , Mathee Kalai , Narasimhan Giri
Published: December 2022

The use of whole metagenomic data to infer the relative abundance of all its microbes is well established. The same data can be used to determine the replication rate of all eubacterial taxa with circular chromosomes. Despite their availability, the replication rate profiles (metareplicome) have not been fully exploited in microbiome analyses. Another relatively new approach is the application of causal inferencing to analyse microbiome data that goes beyond correlational studies. A novel scalable pipeline called MeRRCI (Metagenome, metaResistome, and metaReplicome for Causal Inferencing) was developed. MeRRCI combines efficient computation of the metagenome (bacterial relative abundance), metaresistome (antimicrobial gene abundance) and metareplicome (replication rates), and integrates environmental variables (metadata) for causality analysis using Bayesian networks. MeRRCI was applied to an infant gut microbiome data set to investigate the microbial community’s response to antibiotics. Our analysis suggests that the current treatment stratagem contributes to preterm infant gut dysbiosis, allowing a proliferation of pathobionts. The study highlights the specific antibacterial resistance genes that may contribute to exponential cell division in the presence of antibiotics for various pathogens, namely Klebsiella pneumoniae, Citrobacter freundii, Staphylococcus epidermidis, Veilonella parvula and

Clostridium perfringens

. These organisms often contribute to the harmful long-term sequelae seen in these young infants.
Flies adaptively control flight to compensate for added inertia
Authors: Salem Wael , Cellini Benjamin , Jaworski Eric , Mongeau Jean-Michel
Published: December 2022

Animal locomotion is highly adaptive, displaying a large degree of flexibility, yet how this flexibility arises from the integration of mechanics, sensing and neural control remains elusive. For instance, animals require flexible strategies to maintain performance as changes in mass or inertia impact stability. Compensatory strategies to mechanical loading are especially critical for animals that rely on flight for survival. To shed light on the capacity and flexibility of flight neuromechanics to mechanical loading, we pushed the performance of fruit flies (Drosophila) near its limit and implemented a control theoretic framework to quantify how flies compensated for added inertia. Flies with added inertia were placed inside a virtual reality arena which enabled free rotation about the vertical (yaw) axis. Adding inertia increased the fly’s response time yet had little influence on overall gaze performance. Flies maintained stability following the addition of inertia by adaptively modulating both visuomotor gain and damping. In contrast, mathematical modeling predicted a significant decrease in flight stability and performance. Adding inertia altered saccades, however flies compensated for the added inertia by increasing yaw torque production, indicating that flies sense that they are mechanically loaded. Taken together, in response to added inertia flies trade off reaction time to maintain flight performance through adaptive neural modulation. Our work highlights the flexibility and capacity of motor control in flight.
SIMplyBee: R package for simulating honeybee populations and breeding programs
Authors: Obšteter Jana , Strachan Laura K. , Bubnič Jernej , Prešern Janez , Gorjanc Gregor
Published: December 2022

Background

The Western honeybee is an economically important species globally, but has been experiencing colony losses that lead to economical damage and decreased genetic variability. This situation is spurring additional interest in honeybee breeding and conservation programs. Stochastic simulators are essential tools for rapid and low-cost testing of breeding programs and methods, yet no existing simulator allows for a detailed simulation of honeybee populations. Here we describe SIMplyBee, a holistic simulator of honeybee populations and breeding programs. SIMplyBee is an R package and hence freely available for installation from CRANhttp://cran.r-project.org/package=SIMplyBee.

Implementation

SIMplyBee builds upon the stochastic simulator AlphaSimR that simulates individuals with their corresponding genomes and quantitative genetic values. To enable a honeybee specific simulation, we extended AlphaSimR by developing classes for global simulation parameters,SimParamBee, for a honeybee colony,Colony, and multiple colonies,MultiColony. We also developed functions to address major specificities of the honeybees: honeybee genome, haplo-diploid inheritance, social organisation, complementary sex determination, polyandry, colony events, and quantitative genetics of honeybees.

Results

We describe and show implementation regarding simulating a honeybee genome, creating a honeybee colony and its members, haplodiploid inheritance and complementary sex determination, colony events, creating and managing multiple colonies at once, and obtaining genomic data and honeybee quantitative genetics. Further documentation athttp://SIMplyBee.infoprovides details on these operations and describes additional operations related to genomics, quantitative genetics, and other functionality.

Discussion

SIMplyBee is a holistic simulator of honeybee populations and breeding programs that simulates individual honeybees with their genomes, colonies with colony events, and individual- and colony-level quantitative values. SIMplyBee provides a research platform for testing breeding and conservation strategies and their effect on future genetic gain and variability. Future development of SIMplyBee will focus on improving the simulation of honeybee genomes, optimizing the performance of the simulator, and including spatial awareness to crossing functions and phenotype simulation. We welcome the honeybee genetics and breeding community to join us in the future development of SIMplyBee.
Ot2Rec: A Semi-Automatic, Extensible, Multi-Software Tomographic Reconstruction Workflow
Authors: Yee Neville B.-y. , Ho Elaine M. L. , Tun Win , Smith Jake L. R. , Dumoux Maud , Grange Michael , Darrow Michele C. , Basham Mark
Published: December 2022

Electron cryo-tomography (cryo-ET) is an imaging technique for probing 3D structures with at the nanometre scale. This technique has been used extensively in the biomedical field to study the complex structures of proteins and other macromolecules. With the advancement in technology, microscopes are currently capable of producing images amounting to terabytes of data per day, posing great challenges for scientists as the speed of processing of the images cannot keep up with the ever-higher throughput of the microscopes. Therefore, automation is an essential and natural pathway on which image processing – from individual micrographs to full tomograms – is developing. In this paper, we present Ot2Rec, an open-source pipelining tool which aims to enable scientists to build their own processing workflows in a flexible and automatic manner. The basic building blocks of Ot2Rec are plugins which follow a unified API structure, making it simple for scientists to contribute to Ot2Rec by adding features which are not already available. In this paper, we also present three case studies of image processing using Ot2Rec, through which we demonstrate the speedup of using a semi-automatic workflow over a manual one, the possibility of writing and using custom (prototype) plugins, and the flexibility of Ot2Rec which enables the mix-and-match of plugins. We also demonstrate, in the supplementary information, a built-in reporting feature in Ot2Rec which aggregates the metadata from all process being run, and output them in the Jupyter Notebook and/or HTML formats for quick review of image processing quality. Ot2Rec can be found athttps://github.com/rosalindfranklininstitute/ot2rec.

Impact Statement

The field of cryo electron tomography has grown substantially in recent years, bringing about new advances in hardware and software which enable visualisation of cell and tissue architecture and proteins found in their native context. These same advances have, in some ways, stratified the field into those with access and those without. On the software side, this has emphasised the need for open-source options that do not require high levels of computational literacy to access. Additionally, it has highlighted the need for ways to both mix-and-match software for easy prototyping and comparisons between parameters and methods. Ot2Rec addresses these needs through a simple, unified plugin structure allowing the addition of existing software or the development of new and does so in a way which democratises access.
Modeling a traffic light warning system for acute respiratory infections
Authors: Diaz-Infante Saul , Acuña-Zegarra M. Adrian , Velasco-Hernández Jorge X.
Published: December 2022

The high morbidity of acute respiratory infections constitutes a crucial global health burden. In particular, for SARS-CoV-2, non-pharmaceutical intervention geared to enforce social distancing policies, vaccination, and treatments will remain an essential part of public health policies to mitigate and control disease outbreaks. However, the implementation of mitigation measures directed to increase social distancing when the risk of contagion is a complex enterprise because of the impact of NPI on beliefs, political views, economic issues, and, in general, public perception. The way of implementing these mitigation policies studied in this work is the so-called traffic-light monitoring system that attempts to regulate the application of measures that include restrictions on mobility and the size of meetings, among other non-pharmaceutical strategies. Balanced enforcement and relaxation of measures guided through a traffic-light system that considers public risk perception and economic costs may improve the public health benefit of the policies while reducing their cost. We derive a model for the epidemiological traffic-light policies based on the best response for trigger measures driven by the risk perception of people, instant reproduction number, and the prevalence of a hypothetical acute respiratory infection. With numerical experiments, we evaluate and identify the role of appreciation from a hypothetical controller that could opt for protocols aligned with the cost due to the burden of the underlying disease and the economic cost of implementing measures. As the world faces new acute respiratory outbreaks, our results provide a methodology to evaluate and develop traffic light policies resulting from a delicate balance between health benefits and economic implications.
A patterned human heart tube organoid model generated by pluripotent stem cell self-assembly
Authors: Volmert Brett , Riggs Ashlin , Wang Fei , Juhong Aniwat , Kiselev Artem , Kostina Aleksandra , O’Hern Colin , Muniyandi Priyadharshni , Wasserman Aaron , Huang Amanda , Lewis-Israeli Yonatan , Park Sangbum , Qiu Zhen , Zhou Chao , Aguirre Aitor
Published: December 2022

Human pluripotent stem cells can recapitulate significant features of mammalian organ developmentin vitro, including key aspects of heart development. We hypothesized that the organoids thus created can be made substantially more relevant by mimicking aspects ofin uterogestation, leading to higher physiological and anatomical resemblance to theirin vivocounterparts. Here, we report steps towards generating developmentally inspired maturation methodologies to differentiate early human heart organoids into patterned heart-tube-like structures in a reproducible and high-throughput fashion by complete self-organization. The maturation strategy consists of the controlled and stepwise exposure to metabolic (glucose, fatty acids) and hormonal signals (T3, IGF-1) as present during early heart development. These conditions elicit important transcriptomic, cellular, morphological, metabolomic, and functional changes over a 10-day period consistent with continuously increasing heart complexity, maturation, and patterning. Our data reveals the emergence of atrial and ventricular cardiomyocyte populations, valvular cells, epicardial cells, proepicardial-derived cells, endothelial cells, stromal cells, conductance cells, and cardiac progenitors, all of them cell types present in the primitive heart tube. Anatomically, the organoids elongate and develop well-differentiated atrial and ventricular chambers with compacted myocardial muscle walls and a proepicardial organ. For the first time in a completely self-organizing heart organoid, we show anterior-posterior patterning due to an endogenous retinoic acid gradient originating at the atrial pole, where proepicardial and atrial populations reside, mimicking the developmental process present within the primitive heart tube. Collectively, these findings highlight the ability of self-organization and developmental maturation strategies to recapitulate human heart development. Our patterned human heart tube model constitutes a powerfulin vitrotool for dissecting the role of different cell types and genes in human heart development, as well as disease modeling congenital heart defects, and represents a step forward in creating fully synthetic human hearts.
Abundant deep ocean heterotrophic bacteria are culturable
Authors: Sanz-Sáez Isabel , Sánchez Pablo , Salazar Guillem , Sunagawa Shinichi , de Vargas Colomban , Bowler Chris , Sullivan Matthew B. , Wincker Patrick , Karsenti Eric , Pedrós-Alió Carlos , Agustí Susana , Gojobori Takashi , Duarte Carlos M. , Gasol Josep M. , Sánchez Olga , Acinas Silvia G.
Published: December 2022

Traditional culture techniques usually retrieve only a small fraction of the environmental marine microbial diversity, which mainly belong to the so-called rare biosphere. However, this paradigm has not been fully tested at a broad scale, especially in the deep ocean. Here, we examined the fraction of heterotrophic bacterial communities in photic and deep ocean layers that could be recovered by culture-dependent techniques at a large scale. We compared 16S rRNA gene sequences from a collection of 2003 cultured isolates of heterotrophic marine bacteria with global 16S rRNA metabarcoding datasets (16S TAGs) covering surface, mesopelagic and bathypelagic ocean samples that included 16 of the 22 samples used for isolation. These global datasets represent 60,322 unique 16S amplicon sequence variants (ASVs). Our results reveal a significantly higher proportion of isolates identical to ASVs in deeper ocean layers reaching up to a 28% of the 16S TAGs of the bathypelagic microbial communities, which included the isolation of 3 of the top 10 most abundant 16S ASVs in the global bathypelagic ocean, related to the generaSulfitobacter, Halomonas and Erythrobacter. These cultured isolates contributed differently to the prokaryotic communities across different plankton size fractions, recruiting between 38% in the free-living size fraction (0.2-0.8 μm) and up to 45% in the largest plankton size fraction (20-200 μm) in the bathypelagic ocean. Our findings support the hypothesis that sinking particles in the bathypelagic realm act as resource-rich habitats, suitable for the growth of heterotrophic bacteria with a copiotroph lifestyle that can be cultured, and that these cultivable bacteria can also thrive as free-living bacteria.
Zero-shot reconstruction of mutant spatial transcriptomes
Authors: Okochi Yasushi , Matsui Takaaki , Sakaguchi Shunta , Kondo Takefumi , Naoki Honda
Published: December 2022

Mutant analysis is the core of biological/pathological research, and measuring spatial gene expression can facilitate the understanding of the disorganised tissue phenotype1–5. The large numbers of mutants are worth investigating; however, the high cost and technically challenging nature of experiments to measure spatial transcriptomes may act as bottlenecks6. Spatial transcriptomes have been computationally predicted from single-cell RNA sequencing data based on teaching data of spatial gene expression of certain genes7; nonetheless, this process remains challenging because teaching data for most mutants are unavailable. In various machine-learning tasks, zero-shot learning offers the potential to tackle general prediction problems without using teaching data8. Here, we provide the first zero-shot framework for predicting mutant spatial transcriptomes from mutant single-cell RNA sequencing data without using teaching data, such as a mutant spatial reference atlas. We validated the zero-shot framework by accurately predicting the spatial transcriptomes of Alzheimer’s model mice3and mutant zebrafish embryos with lost Nodal signaling9. We propose a spatially informed screening approach based on zero-shot framework prediction that identified novel Nodal-downregulated genes in zebrafish. We expect that the zero-shot framework will provide novel phenotypic insights by leveraging the enormous mutant/disease single-cell RNA sequencing data collected.
Shark-dust: High-throughput DNA sequencing of processing residues unveils widespread trade in threatened sharks and rays
Authors: Prasetyo Andhika P. , Murray Joanna M. , Kurniawan Muh. Firdaus A. K. , Sales Naiara G. , McDevitt Allan D. , Mariani Stefano
Published: December 2022

Illegal fishing, unregulated bycatch, and market demand for certain products (e.g. fins) are largely responsible for the rapid global decline of shark and ray populations. Controlling trade of endangered species remains difficult due to product variety, taxonomic ambiguity and trade complexity. The genetic tools traditionally used to identify traded species typically target individual tissue samples, are time-consuming and/or species-specific. Here, we performed high-throughput sequencing of trace DNA fragments retrieved from dust and scraps left behind by trade activities. We metabarcoded ‘shark-dust’ samples from seven processing plants in the world’s biggest shark landing site (Java, Indonesia), and identified 54 shark and ray taxa (representing half of all chondrichthyan orders), half of which could not be recovered from tissue samples collected in parallel from the same sites. Importantly, over 80% of shark-dust sequences were found to belong to CITES-listed species. We argue that this approach is likely to become a powerful and cost-effective monitoring tool wherever wildlife is traded.

One-Sentence Summary

Shark-dust, the traces of biological material left behind from the processing of shark products, can now be DNA-sequenced in bulk to accurately reconstruct the biodiversity underlying trade.
Transformer-based tool recommendation system in Galaxy
Authors: Kumar Anup , Grüning Björn , Backofen Rolf
Published: December 2022

Galaxy is a web-based open-source platform for scientific analyses. Researchers use thousands of high-quality tools and workflows for their respective analyses. Tool recommender system predicts a collection of tools that can be used to extend an analysis. In this work, a tool recommender system is developed by training a Transformer-based neural network on workflows available on Galaxy Europe. Compared to the existing tool recommender system on Galaxy Europe that trains a recurrent neural network, the transformer-based neural network achieves two times faster convergence, has a four times lower model usage (model loading + prediction) time and shows a better generalisation that goes beyond training workflows. The scripts to create the recommendation model are available under MIT licence athttps://github.com/anuprulez/galaxy_tool_recommendation_transformers.