bluuebunny/crossref_metadata_2025 huggingface dataset:
Undenatured type II collagen mitigates inflammation and cartilage degeneration in healthy Labrador Retrievers during an exercise regimen
Authors: Varney J L , Fowler J W , Coon C N
Published: May 2021

The aim of this experiment was to evaluate the effect of undenatured type II collagen supplementation on inflammation and cartilage degeneration after exercise in healthy dogs. Forty healthy Labrador Retrievers (20 male/20 female; range 5-12 yr; average 8 yr) were sorted into two groups: undenatured type II collagen group receiving 40 mg UC-II (10 mg collagen type II/min. 3% undenatured type II collagen; Lonza Consumer Health, Inc.) and placebo group receiving 40 mg maltodextrin daily by capsule. After 2-wk loading, all dogs began an 11-wk endurance exercise regimen consisting of two weekly runs, starting at 5 km and increasing incrementally to 8 km, with one final 16 km run. Blood samples were collected at baseline, pre and post first 5 km run, and pre- and post-16 km run. Activity per kilometer was greater in male undenatured type II collagen vs. male placebo over all runs (P = 0.004), and average moving speed was greater in all undenatured type II collagen dogs compared with placebo over all runs (P < 0.001). Hematology analysis indicated that during the first insult, undenatured type II collagen dogs had a greater lymphocyte count (P < 0.001) and lymphocyte percentage (P = 0.001) vs. placebo dogs. Undenatured type II collagen dogs had a lesser neutrophil percentage (P = 0.042) and neutrophil to lymphocyte ratios (P = 0.001) compared to placebo dogs. For the final insult, undenatured type II collagen dogs had greater lymphocyte percentage (P = 0.013) and lesser mean corpuscular hemoglobin concentration (P = 0.043) compared with placebo dogs. Both groups had significant changes between timepoints for several hematological parameters. Biomarker IL-6 was lesser in undenatured type II collagen dogs compared with placebo at post 5 km (P = 0.037). Cartilage oligomeric matrix protein (COMP) was lesser in undenatured type II collagen dogs at post 16 km (P = 0.023), and only the placebo dogs had a significant increase in COMP from pre to post 16 km (P = 0.021). In summary, Labrador Retrievers supplemented with undenatured type II collagen had decreased inflammation and cartilage degeneration compared with nonsupplemented dogs during exercise.
The Tomato Brown Rugose Fruit Virus Movement Protein Overcomes Tm-22 Resistance in Tomato While Attenuating Viral Transport
Authors: Hak Hagit , Spiegelman Ziv
Published: May 2021

Tomato brown rugose fruit virus is a new virus species in the Tobamovirus genus, causing substantial damage to tomato crops. Reports of recent tomato brown rugose fruit virus (ToBRFV) outbreaks from around the world indicate an emerging global epidemic. ToBRFV overcomes all tobamovirus resistances in tomato, including the durable Tm-22 resistance gene, which had been effective against multiple tobamoviruses. Here, we show that the ToBRFV movement protein (MPToBRFV) enables the virus to evade Tm-22 resistance. Transient expression of MPToBRFV failed to activate the Tm-22 resistance response. Replacement of the original MP sequence of tomato mosaic virus (ToMV) with MPToBRFV enabled this recombinant virus to infect Tm-22-resistant plants. Using hybrid protein analysis, we show that the elements required to evade Tm-22 are located between MPToBRFV amino acids 1 and 216 and not the C terminus, as previously assumed. Analysis of ToBRFV systemic infection in tomato revealed that ToBRFV spreads more slowly compared with ToMV. Interestingly, replacement of tobacco mosaic virus (TMV) and ToMV MPs with MPToBRFV caused an attenuation of systemic infection of both viruses. Cell-to-cell movement analysis showed that MPToBRFV moves less effectively compared with the TMV MP (MPTMV). These findings suggest that overcoming Tm-22 is associated with attenuated MP function. This may explain the high durability of Tm-22 resistance, which had remained unbroken for over 60 years.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Natural Genetic Diversity in the Potato Resistance GeneRBConfers Suppression Avoidance fromPhytophthoraEffector IPI-O4
Authors: Karki Hari S. , Abdullah Sidrat , Chen Yu , Halterman Dennis A.
Published: May 2021

RB is a potato gene that provides resistance to a broad spectrum of genotypes of the late blight pathogen Phytophthora infestans. RB belongs to the CC-NB-LRR (coiled-coil, nucleotide-binding, leucine-rich repeat) class of resistance (R) genes, a major component of the plant immune system. The RB protein detects the presence of class I and II IPI-O effectors from P. infestans to initiate a hypersensitive resistance response, but this activity is suppressed in the presence of the Class III effector IPI-O4. Using natural genetic variation of RB within potato wild relatives, we identified two amino acids in the CC domain that alter interactions needed for suppression of resistance by IPI-O4. We have found that separate modification of these amino acids in RB can diminish or expand the resistance capability of this protein against P. infestans in both Nicotiana benthamiana and potato. Our results demonstrate that increased knowledge of the molecular mechanisms that determine resistance activation and R protein suppression by effectors can be utilized to tailor-engineer genes with the potential to provide increased durability.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Whole Genome Sequence of Fusarium redolens Strain YP04, a Pathogen that Causes Root Rot of American Ginseng
Authors: Fan Sanhong , Wang Qiang , Dai Jichen , Jiang Jinglong , Hu Xiaoping , Subbarao Krishna V.
Published: May 2021

Fusarium redolens was previously reported as a plant pathogen or an endophyte that is closely related to F. oxysporum, a notoriously significant soilborne phytopathogen. Subsequent studies demonstrated the unique nature of F. redolens, which was considered a distinct species that causes multiple symptoms on multiple hosts. It was recently identified as a pathogen that causes root rot of American ginseng. Currently, few high-quality F. redolens genome sequences exist in the public database. Here, we report the whole-genome sequence of F. redolens strain YP04, based on a hybrid assembly of long- and short-read sequencing with PacBio and Illumina platforms, respectively. The assembly consists of 40 configs with a total length of 52.8 Mb nuclear genomic DNA and 49.6 kb complete mitochondrial genomic DNA, and encodes a total of 18,985 genes, including 18,517 protein-coding genes and 469 RNA genes which were functionally annotated. In total, 4,606 proteins were identified in the pathogen–host interactions database, suggesting that they were likely involved in pathogenicity and host–pathogen interactions, while 41 secondary metabolite synthesis clusters were predicted and annotated. This is the first high-quality whole genome of F. redolens, providing an important community resource for genome evolution, host–pathogen interaction, and secondary metabolite biosynthesis studies.
FACE MASK CONTAMINATION DURING COVID-19 PANDEMIA. A STUDY ON PATIENTS RECEIVING INTRAVITREAL INJECTIONS
Authors: MARÍN-Nieto Juan , Reino-Perez Carmen , Santillana-Cernuda Genoveva , Díaz-Bernal José Manuel , Luque-Aranda Rafael , García-Basterra Ignacio
Published: May 2021

Purpose:

To investigate the bacterial growth in the surgical face masks used by patients who received intravitreal injections and study the effect of povidone–iodine on the periocular area (PA) of masks.

Methods:

Forty patients who attended for intravitreal injections were divided in those with less (<4 hours) and more (>4 hours) than 4 hours of mask use. Each group was divided depending on the application or not of povidone–iodine in the PA of the mask. Bacterial load was studied on PA and mouth area samples.

Results:

The bacterial load in the PA was higher in the >4 hours group compared with the <4 hours group (13.2 vs. 48.75 colony-forming units/μL; P = 0.03). The contamination in the PA significantly decreased after applying povidone–iodine in the >4 hours group (P = 0.01). The use or not of povidone–iodine was strongly correlated to a positive culture (OR = 9.0, P = 0.00. CI 1.63–49.44).

Conclusion:

Surgical face masks worn for more than 4 hours present higher contamination in the PA than those with less use. Bacterial load in the PA is reduced with povidone–iodine on masks used for more than 4 hours. This contamination should be considered in the asepsis protocol of intravitreal injections.
The management of neurotrophic keratitis
Authors: Jabbour Samir , Ashton Christopher , Balal Shafi , Kaye Abigail , Ahmad Sajjad
Published: May 2021

Purpose of review

The management of neurotrophic keratitis (NK) has evolved in the last decade. The present article reviews updated management guidelines of this entity, as well as future innovations in the field.

Recent findings

The advent of confocal microscopy has allowed for the first time to image corneal nerves. In addition, multiple novel topical treatments such as nerve growth factor have improved the prognosis of this disease, with many other in the pipeline. Finally, corneal nerve restoration is now possible with corneal neurotization procedures.

Many novel treatments based on agents that stimulate nerve regrowth are now available to treat NK. Improvement in neurotization procedures could also address advanced stages of this disease with surgery.
Validity Indices of the King-Devick Concussion Test in Hockey Players
Authors: Krause David A. , Hollman John H. , Breuer Logan T. , Stuart Michael J.
Published: May 2021

Objective:

To compare the validity indices of the King-Devick (KD) test in hockey players using any increase in test time over baseline to a 6-second increase as a positive concussion test. We hypothesized the KD test using the 6-second change would yield greater validity indices.

Design:

Prospective observational cohort study.

Setting:

Sports complex.

Participants:

Sixty-five male hockey players aged 13 to 20 years.

Independent Variable:

Concussion diagnosis.

Main Outcome Measures:

Time to complete the KD test. Sensitivity (SN), specificity (SP), and the positive likelihood ratios (LRs+) were calculated using 2 thresholds for a positive test: (1) any increase in time and (2) an increase of 6 seconds or greater.

Results:

Eighteen players (27.7%) were diagnosed with a concussion. Using any increase in time as a positive test yielded the following: SN 72.2%, SP 78.7%, LR+ 3.4, and LR− 0.4. Using the 6-second threshold yielded the following: SN 44.4%, SP 93.6%, LR+ 7.0, and LR− 0.6. A receiver operator curve analysis confirmed 6.40 seconds or greater maximized the LR+.

Conclusions:

A 6-second or greater increase in the KD test performance provides greater validity in diagnosing concussion as compared with any increase in performance time.
Sleep disruptions and bone health: what do we know so far?
Authors: Swanson Christine M.
Published: May 2021

Purpose of review

This review briefly summarizes the growing body of literature addressing the skeletal consequences of sleep and circadian disruption.

Recent findings

The most recent data in the field suggest that the diurnal variation in bone turnover markers are because of endogenous circadian rhythmicity linked to clock genes in all bone cells; in a small human intervention study, cumulative sleep restriction with concurrent circadian disruption negatively alter bone turnover markers in a way that could explain the lower BMD and increased fracture risk identified in some prior night shift work studies; abnormal sleep duration and obstructive sleep apnea are associated with low BMD and increased fracture risk in some but not all studies.

Normal physiology and some animal and human intervention studies suggest that sleep and circadian disruptions, such as night shift work, abnormal sleep durations and obstructive sleep apnea are detrimental to skeletal health. However, additional research in this area is needed to determine which sleep/circadian disturbances are most detrimental to skeletal health, the reversibility of such impairments, and underlying mechanisms.
Cellular components of the hematopoietic niche and their regulation of hematopoietic stem cell function
Authors: Ghosh Joydeep , Koussa Roy El , Mohamad Safa F. , Liu Jianyun , Kacena Melissa A. , Srour Edward F.
Published: May 2021

Purpose of review

Development and functions of hematopoietic stem cells (HSC) are regulated by multiple cellular components of the hematopoietic niche. Here we review the recent advances in studying the role of three such components -- osteoblasts, osteomacs, and megakaryocytes and how they interact with each other in the hematopoietic niche to regulate HSC.

Recent findings

Recent advances in transgenic mice models, scRNA-seq, transcriptome profile, proteomics, and live animal imaging have revealed the location of HSC within the bone and signaling molecules required for the maintenance of the niche. Interaction between megakaryocytes, osteoblasts and osteomacs enhances hematopoietic stem and progenitor cells (HSPC) function. Studies also revealed the niche as a dynamic entity that undergoes cellular and molecular changes in response to stress. Aging, which results in reduced HSC function, is associated with a decrease in endosteal niches and osteomacs as well as reduced HSC--megakaryocyte interactions.

Novel approaches to study the cellular components of the niche and their interactions to regulate HSC development and functions provided key insights about molecules involved in the maintenance of the hematopoietic system. Furthermore, these studies began to build a more comprehensive model of cellular interactions and dynamics in the hematopoietic niche.
Decreases in Reported Sexually Transmitted Infections During the Time of COVID-19 in King County, WA: Decreased Transmission or Screening?
Authors: Berzkalns Anna , Thibault Christina S. , Barbee Lindley A. , Golden Matthew R. , Khosropour Christine , Kerani Roxanne P.
Published: May 2021

Background

In response to the COVID-19 pandemic, Washington State's Stay Home, Stay Healthy (SHSH) order was implemented on March 24, 2020. We hypothesized that pandemic mitigation measures might reduce sexually transmitted infection (STI) screening and/or transmission.

Methods

We used King County, WA STI surveillance and sexual health clinic (SHC) data from January 1, 2019, to July 31, 2020. We calculated mean weekly case counts for gonorrhea, primary and secondary (P&S) syphilis, male urethral gonorrhea, and early latent (EL) syphilis for 3 periods in 2020: pre-SHSH (January 1–March 23), SHSH (March 24–June 5), and reopening (June 6–July 31). Primary and secondary syphilis and male urethral gonorrhea were used as proxies for sexual behavior, and EL syphilis was used as a proxy for STI screening. We compared SHC visits (2019 vs. 2020) and SHC gonorrhea treatment practices (across 2020 periods).

Results

Compared with January to July 2019, from January to July 2020, reported cases of gonorrhea, male urethral gonorrhea, P&S syphilis, and EL syphilis decreased by 9%, 5%, 16%, and 22%, respectively. Mean weekly case counts of gonorrhea, male urethral gonorrhea, and EL syphilis decreased pre-SHSH to SHSH, but all returned to pre-SHSH levels during reopening. Sexual health clinic visits during SHSH were 55% lower in 2020 than in 2019. In the SHC during SHSH, ceftriaxone treatment of gonorrhea decreased, whereas cefixime/cefpodoxime treatment and gonorrhea treatment with no testing increased.

Conclusions

Decreases in reported STIs concurrent with COVID-19 SHSH may reflect a true decline in STI transmission. However, the larger decreases in asymptomatic infections indicate that much of the observed decrease was likely due to decreased screening.
Continuous Renal-Replacement Therapy in Critically Ill Children: Practice Changes and Association With Outcome
Authors: Chen ZhiJiang , Wang HuiLi , Wu Zhu , Jin Ming , Chen YiTing , Li Jun , Wei QiuJu , Tao ShaoHua , Zeng Qiyi
Published: May 2021

OBJECTIVES:

This study was designed to evaluate practice changes and outcomes over a 10-year period in a large single-center PICU cohort that received continuous renal-replacement therapy.

DESIGN:

Retrospective study design.

SETTING:

A multidisciplinary tertiary PICU of a university-affiliated hospital in Guangzhou, China.

PATIENTS:

All critically ill children who were admitted to our PICU from January 2010 to December 2019 and received continuous renal-replacement therapy were included in this study.

MEASUREMENTS AND MAIN RESULTS:

A total of 289 patients were included in the study. Of the two study periods, 2010–2014 and 2015–2019, the proportion of continuous renal-replacement therapy initiation time greater than 24 hours was significantly reduced ([73/223] 32.73% vs. [40/66] 60.60%, p < 0.001), the percentage of fluid overload at continuous renal-replacement therapy initiation was lower (3.8% [1.6–7.2%] vs. 12.1% [6.6–23.3%], p < 0.001), the percentage of regional citrate anticoagulation protocol was increased ([223/223] 100% vs. [15/66] 22.7%, p < 0.001), and the ICU survival rate was significantly improved ([24/66] 36.4% vs. [131/223] 58.7%, p = 0.001) in the latter period compared with the former. In addition, subgroup analysis found that survival were higher in patients with continuous renal-replacement therapy initiation time less than 24 hours, regional citrate anticoagulation protocol, and fluid overload less than 10%.

CONCLUSIONS:

The survival rate of patients received continuous renal-replacement therapy treatment in our center has improved over past 10 years, and some changes have taken place during these periods. Among them, early initiation of continuous renal-replacement therapy, lower fluid overload, and regional citrate anticoagulation method seems to be related to the improvement of outcome. Ongoing evaluation of the practice changes and quality improvement of continuous renal-replacement therapy for critically ill pediatric patients still need attention.
Compliance With an Antibiotic Guideline for Suspected Ventilator-Associated Infection: The Ventilator-Associated INfection (VAIN2) Study*
Authors: Karsies Todd , Tarquinio Keiko , Shein Steven L. , Beardsley Andrew L , Prentice Elizabeth , Karam Oliver , Fontela Patricia , Moore-Clingenpeel Melissa , Willson Douglas F.
Published: May 2021

OBJECTIVES:

To evaluate a guideline for antibiotic decisions in children with suspected ventilator-associated infection.

DESIGN:

Prospective, observational cohort study conducted in 22 PICUs in the United States and Canada.

SETTING:

PICUs in 22 hospitals from April 2017 to January 2019.

SUBJECTS:

Children less than 3 years old on mechanical ventilation greater than 48 hours who had respiratory secretions cultured and antibiotics initiated for suspected ventilator-associated infection.

INTERVENTIONS:

After baseline data collection in children with suspected ventilator-associated infection (Phase 1), a consensus guideline was developed for advising antibiotic continuation or stopping at 48–72 hours (Phase 2) and implemented (Phase 3). Guideline-based antibiotic recommendations were provided to the treating clinicians once clinical and microbiologic data were available. Demographic and outcome data were collected, and guideline compliance and antibiotic utilization evaluated for Phase 1 and Phase 3.

MEASUREMENTS AND MAIN RESULTS:

Despite education and implementation efforts, guideline-concordant antibiotic management occurred in 158 of 227 (70%) Phase 3 subjects compared with 213 of 281 (76%) in Phase 1. Illness severity and positive respiratory cultures were the primary determinants of antibiotic continuation. For subjects with a positive respiratory culture but a score for which antibiotic discontinuation was recommended (score ≤ 2), only 27% of Phase 3 subjects had antibiotics discontinued. Antibiotic continuation was not associated with improved outcomes in these subjects and was associated with significantly longer duration of ventilation (median 5.5 d longer) and PICU stay (5 d longer) in the overall study population. Positive respiratory cultures were not associated with outcomes irrespective of antibiotic treatment.

CONCLUSIONS:

Antibiotic guideline efficacy and safety remain uncertain due to clinician failure to follow the guideline, instead primarily relying on respiratory culture results. Strategies to overcome clinician perceptions of respiratory cultures and other barriers will be vital for improving guideline adherence and antibiotic use in suspected ventilator-associated infection in future studies.
HPV vaccination to prevent recurrence of anal intraepithelial neoplasia in HIV+ MSM
Authors: Gosens Karien C.M. , van der Zee Ramon P. , van Heukelom Matthijs L. Siegenbeek , Jongen Vita W. , Cairo Irina , van Eeden Arne , van Noesel Carel J.M. , Quint Wim G.V. , Pasmans Hella , Dijkgraaf Marcel G.W. , de Vries Henry J.C. , Prins Jan M.
Published: May 2021

Objective:

Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ MSM. Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as posttreatment adjuvant in preventing HGAIN recurrence in HIV+ MSM.

Design:

Randomized, double-blind, placebo-controlled, multicentre trial.

Setting:

Three HIV outpatient clinics in Amsterdam, the Netherlands.

Subjects:

HIV+ MSM with CD4+ cell count more than 350 cells/μl, biopsy-proven intra-anal HGAIN successfully treated in the past year, and lesions still in remission at enrolment, as assessed by high-resolution anoscopy (HRA).

Intervention:

Participants were randomized to three doses of qHPV (Gardasil-4, MSD) or placebo with vaccinations at 0, 2, and 6 months. HRA was repeated at 6, 12, and 18 months.

Main outcome measure:

The primary outcome was cumulative, biopsy-proven HGAIN recurrence rate at 18 months, evaluated in an intention-to-treat (ITT) (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up).

Results:

We randomized 126 participants of which 64 (50.8%) received qHPV and 62 (49.2%) placebo. All participants received three vaccinations, and in both groups for two participants follow-up was incomplete. We found no difference (P = 0.38) in cumulative HGAIN recurrence rates between the qHPV (44/64, 68.8%) and placebo group (38/62, 61.3%) in the ITT analysis [absolute risk reduction −7.5 (95% confidence interval (CI) −24.1 to 9.2)]. This was similar in the per-protocol analysis.

Conclusion:

Despite adequate serological responses to qHPV vaccination, short-term recurrence of HGAIN was not prevented. These findings do not support qHPV vaccination as a treatment adjuvant to prevent HGAIN recurrence in HIV+ MSM.
Broadly neutralizing antibody-mediated protection of macaques against repeated intravenous exposures to simian-human immunodeficiency virus
Authors: Garber David A. , Guenthner Patricia , Mitchell James , Ellis Shanon , Gazumyan Anna , Nason Martha , Seaman Michael S. , McNicholl Janet M. , Nussenzweig Michel C. , Heneine Walid
Published: May 2021

Objective:

The opioid epidemic has increased parentally acquired HIV infection. To inform the development of a long-acting prevention strategy, we evaluated the protective efficacy of broadly neutralizing antibodies (bNAbs) against intravenous simian-human immunodeficiency virus (SHIV) infection in macaques.

Design:

Five cynomolgus macaques were injected once subcutaneously with 10-1074 and 3BNC117 (10 mg each kg−1) and were repeatedly challenged intravenously once weekly with SHIVAD8-EO (130 TCID50), until infection was confirmed via plasma viral load assay. Two control macaques, which received no antibody, were challenged identically.

Methods:

Plasma viremia was monitored via RT-qPCR assay. bNAb concentrations were determined longitudinally in plasma samples via TZM-bl neutralization assays using virions pseudotyped with 10-1074-sensitive (X2088_c9) or 3BNC117-sensitive (Q769.d22) HIV envelope proteins.

Results:

Passively immunized macaques were protected against a median of five weekly intravenous SHIV challenges, as compared to untreated controls, which were infected following a single challenge. Of the two bNAbs, 10-1074 exhibited relatively longer persistence in vivo. The median plasma level of 10-1074 at SHIV breakthrough was 1.1 μg ml−1 (range: 0.6–1.6 μg ml−1), whereas 3BNC117 was undetectable. Probit modeling estimated that 6.6 μg ml−1 of 10-1074 in plasma corresponded to a 99% reduction in per-challenge infection probability, as compared to controls.

Conclusions:

Significant protection against repeated intravenous SHIV challenges was observed following administration of 10-1074 and 3BNC117 and was due primarily to 10-1074. Our findings extend preclinical studies of bNAb-mediated protection against mucosal SHIV acquisition and support the possibility that intermittent subcutaneous injections of 10-1074 could serve as long-acting preexposure prophylaxis for persons who inject drugs.
The rise of illicit fentanyls, stimulants and the fourth wave of the opioid overdose crisis
Authors: Ciccarone Daniel
Published: May 2021

Purpose of review

This review provides an update on recently published literature on the rise of illicit fentanyls, risks for overdose, combinations with other substances, e.g. stimulants, consequences, and treatment.

Recent findings

Overdose due to illicit synthetic opioids (e.g. fentanyl and fentanyl analogs) continues to rise in the US both preceding and during the COVID-19 pandemic. Fentanyl-related overdose is rising in new geographic areas e.g. the western USA. Stimulant-related overdose is also increasing nationwide driven by methamphetamine and cocaine. Polysubstance use, e.g. the use of a stimulant along with an opioid is driving stimulant-related overdose. Other medical consequences of injection drug use are rising including HIV and hepatitis C infections. Medication approaches to treating opioid use disorder remain the standard of care and there are new promising pharmacological approaches to treating methamphetamine use disorder.

A ‘fourth wave’ of high mortality involving methamphetamine and cocaine use has been gathering force in the USA. Availability and use of illicit fentanyls are still the major drivers of overdose deaths and the current rise in stimulant-related deaths appears entwined with the ongoing opioid epidemic.
Synergistic tomographic image reconstruction: part 1
Authors: Tsoumpas Charalampos , Jørgensen Jakob Sauer , Kolbitsch Christoph , Thielemans Kris
Published: May 2021

This special issue focuses on synergistic tomographic image reconstruction in a range of contributions in multiple disciplines and various application areas. The topic of image reconstruction covers substantial inverse problems (Mathematics) which are tackled with various methods including statistical approaches (e.g. Bayesian methods, Monte Carlo) and computational approaches (e.g. machine learning, computational modelling, simulations). The issue is separated in two volumes. This volume focuses mainly on algorithms and methods. Some of the articles will demonstrate their utility on real-world challenges, either medical applications (e.g. cardiovascular diseases, proton therapy planning) or applications in material sciences (e.g. material decomposition and characterization). One of the desired outcomes of the special issue is to bring together different scientific communities which do not usually interact as they do not share the same platforms (such as journals and conferences).

This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 1’.
Fusing electrical and elasticity imaging
Authors: Hauptmann Andreas , Smyl Danny
Published: May 2021

Electrical and elasticity imaging are promising modalities for a suite of different applications, including medical tomography, non-destructive testing and structural health monitoring. These emerging modalities are capable of providing remote, non-invasive and low-cost opportunities. Unfortunately, both modalities are severely ill-posed nonlinear inverse problems, susceptive to noise and modelling errors. Nevertheless, the ability to incorporate complimentary datasets obtained simultaneously offers mutually beneficial information. By fusing electrical and elastic modalities as a joint problem, we are afforded the possibility to stabilize the inversion process via the utilization of auxiliary information from both modalities as well as joint structural operators. In this study, we will discuss a possible approach to combine electrical and elasticity imaging in a joint reconstruction problem giving rise to novel multi-modality applications for use in both medical and structural engineering.

This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 1’.
Physics-based reconstruction methods for magnetic resonance imaging
Authors: Wang Xiaoqing , Tan Zhengguo , Scholand Nick , Roeloffs Volkert , Uecker Martin
Published: May 2021

Conventional magnetic resonance imaging (MRI) is hampered by long scan times and only qualitative image contrasts that prohibit a direct comparison between different systems. To address these limitations, model-based reconstructions explicitly model the physical laws that govern the MRI signal generation. By formulating image reconstruction as an inverse problem, quantitative maps of the underlying physical parameters can then be extracted directly from efficiently acquired k-space signals without intermediate image reconstruction—addressing both shortcomings of conventional MRI at the same time. This review will discuss basic concepts of model-based reconstructions and report on our experience in developing several model-based methods over the last decade using selected examples that are provided complete with data and code.

This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 1’.
Evaluation of synergistic image registration for motion-corrected coronary NaF-PET-MR
Authors: Mayer Johannes , Jin Yining , Wurster Thomas-Heinrich , Makowski Marcus R. , Kolbitsch Christoph
Published: May 2021

Coronary artery disease (CAD) is caused by the formation of plaques in the coronary arteries and is one of the most common cardiovascular diseases. NaF-PET can be used to assess plaque composition, which could be important for therapy planning. One of the main challenges of NaF-PET is cardiac and respiratory motion which can strongly impair diagnostic accuracy. In this study, we investigated the use of a synergistic image registration approach which combined motion-resolved MR and PET data to estimate cardiac and respiratory motion. This motion estimation could then be used to improve the NaF-PET image quality. The approach was evaluated with numerical simulations andin vivoscans of patients suffering from CAD. In numerical simulations, it was shown, that combining MR and PET information can improve the accuracy of motion estimation by more than 15%. For thein vivoscans, the synergistic image registration led to an improvement in uptake visualization. This is the first study to assess the benefit of combining MR and NaF-PET for cardiac and respiratory motion estimation. Further patient evaluation is required to fully evaluate the potential of this approach.

This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 1’.
(An overview of) Synergistic reconstruction for multimodality/multichannel imaging methods
Authors: Arridge Simon R. , Ehrhardt Matthias J. , Thielemans Kris
Published: May 2021

Imaging is omnipresent in modern society with imaging devices based on a zoo of physical principles, probing a specimen across different wavelengths, energies and time. Recent years have seen a change in the imaging landscape with more and more imaging devices combining that which previously was used separately. Motivated by these hardware developments, an ever increasing set of mathematical ideas is appearing regarding how data from different imaging modalities or channels can be synergistically combined in the image reconstruction process, exploiting structural and/or functional correlations between the multiple images. Here we review these developments, give pointers to important challenges and provide an outlook as to how the field may develop in the forthcoming years.

This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 1’.
Clostridium difficile septic arthritis and periprosthetic joint infection in a patient with acute lymphoblastic leukaemia, T-/B-lymphocytopenia and hypogammaglobulinemia – a case report and review of the literature
Authors: Karczewski Daniel , Müllner Maximilian , Perka Carsten , Müller Michael
Published: May 2021

To the best of our knowledge, we report the first

Clostridium difficile

infection in a native hip joint with subsequent prosthetic joint infection in a patient at a state of hypogammaglobulinemia. The infection developed following chemotherapy for B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). After chemotherapy, hip arthroplasty was performed for destructive septic arthritis. However, infection in the hip persisted with several failing revisions for more than 3 years, until ultimately hypogammaglobulinemia and T-/B-lymphocytopenia were diagnosed, and supplementation with i.v. immunoglobulins was able to achieve infection control.
A Targeted Geospatial Approach to COVID-19 Vaccine Delivery: Findings from the Johns Hopkins Hospital Emergency Department
Authors: Solomon Sunil S , Hsieh Yu-Hsiang , Rothman Richard E , Laeyendecker Oliver , Mehta Shruti H , Anderson Mark , Cloherty Gavin , Quinn Thomas C
Published: May 2021

While COVID-19 vaccines have been shown to significantly decrease morbidity and mortality, there is still much debate about optimal strategies of vaccine rollout. We tested identity-unlinked stored remnant blood specimens of patients at least 18 years presenting to the Johns Hopkins Hospital emergency department (ED) between May to November 2020 for IgG to SARS-CoV-2. Data on SARS-CoV-2 RT PCR were available for patients who were tested due to suspected infection. SARS-CoV-2 infections was defined as either a positive IgG and/or RT-PCR. SARS-CoV-2 infection clustering by zipcode was analyzed by spatial analysis using the Bernoulli model (SaTScan software, Version 9.7). Median age of the 7,461 unique patients visiting the ED was 47 years and 50.8% were female; overall, 740 (9.9%) unique patients had evidence of SARS-CoV-2 infection. Prevalence of infection in ED patients by ZIP code ranged from 4.1% to 22.3%. The observed number of cases in ZIP code C was nearly double the expected (observed/expected ratio = 1.99; 95% CI: 1.62, 2.42). These data suggest a targeted geospatial approach to COVID vaccination should be considered to maximize vaccine rollout efficiency and include high-risk populations that may otherwise be subjected to delays, or missed.
A Direct Capture Method for Purification and Detection of Viral Nucleic Acid Enables Epidemiological Surveillance of SARS-CoV-2
Authors: Mondal Subhanjan , Feirer Nathan , Brockman Michael , Preston Melanie A. , Teter Sarah J. , Ma Dongping , Goueli Said A. , Moorji Sameer , Saul Brigitta , Cali James J.
Published: May 2021

Studies have demonstrated that SARS-CoV-2 RNA can be detected in the feces of infected individuals. This finding spurred investigation into using wastewater-based epidemiology (WBE) to monitor SARS-CoV-2 RNA and track the appearance and spread of COVID-19 in communities. SARS-CoV-2 is present at low levels in wastewater, making sample concentration a prerequisite for sensitive detection and utility in WBE. Whereas common methods for isolating viral genetic material are biased toward intact virus isolation, it is likely that a relatively low percentage of the total SARS-CoV-2 RNA genome in wastewater is contained within intact virions. Therefore, we hypothesized that a direct unbiased total nucleic acid extraction method could overcome the cumbersome protocols, variability and low recovery rates associated with the former methods. This led to development of a simple, rapid, and modular alternative to existing purification methods. In an initial concentration step, chaotropic agents are added to raw sewage allowing binding of nucleic acid from free nucleoprotein complexes, partially intact, and intact virions to a silica matrix. The eluted nucleic acid is then purified using manual or semi-automated methods. RT-qPCR enzyme mixes were formulated that demonstrate substantial inhibitor resistance. In addition, multiplexed probe-based RT-qPCR assays detecting the N1, N2 (nucleocapsid) and E (envelope) gene fragments of SARS-CoV-2 were developed. The RT-qPCR assays also contain primers and probes to detect Pepper Mild Mottle Virus (PMMoV), a fecal indicator RNA virus present in wastewater, and an exogenous control RNA to measure effects of RT-qPCR inhibitors. Using this workflow, we monitored wastewater samples from three wastewater treatment plants (WWTP) in Dane County, Wisconsin. We also successfully sequenced a subset of samples to ensure compatibility with a SARS-CoV-2 amplicon panel and demonstrated the potential for SARS-CoV-2 variant detection. Data obtained here underscore the potential for wastewater surveillance of SARS-CoV-2 and other infectious agents in communities.
Prodromal Progressive Supranuclear Palsy – insights from the UK Biobank
Authors: Street Duncan , Whiteside David , Rittman Timothy , Rowe James B
Published: May 2021

Background

Prodromal Parkinson’s Disease is well described but prodromal Progressive Supranuclear Palsy (PSP) is much less understood. The diagnosis of PSP is typically delayed by an average of three years after symptom onset. Understanding the changes that occur in the prodromal and pre-diagnostic period will aid earlier diagnosis, clarify the natural history, and aid the design of early disease-modifying therapy trials.

Objectives

To determine motor and cognitive markers of prodromal PSP, with Parkinson’s disease as a comparator condition, in a large prospective cohort.

Methods

Baseline UK Biobank data from 502,504 individuals were collected between 2006 and 2010. Subsequent PSP and Parkinson’s disease cases were identified from primary and secondary care electronic health records’ diagnostic coding data and death registry, with 5,404 matched controls.

Results

176 PSP cases (time to diagnosis 7.8±2.8 years) and 2,526 Parkinson’s disease cases (time to diagnosis 7.8±2.9 years) were identified. At baseline, those later diagnosed with PSP had slower reaction times, weaker hand grip, lower fluid intelligence, poorer prospective memory, worse self-rated health score and lower digit recall than controls. They had higher mortality than both Parkinson’s disease and control groups.

Conclusions

Motor slowing, cognitive dysfunction, and postural instability are clinical diagnostic features of PSP and are typically symptomatic three years before diagnosis. However, objective markers of these features are evident over seven years before diagnosis. This suggests a long prodromal course in PSP with subtle changes in motor and cognitive function.
FishPhyloMaker: An R package to generate phylogenies for ray-finned fishes
Authors: Nakamura Gabriel , Richter Aline , Soares Bruno E.
Published: May 2021

Phylogenies summarize evolutionary information that is essential in the investigation of ecological and evolutionary causes of diversity patterns. They allow investigating hypotheses from trait evolution to the relationship between evolutionary diversity and ecosystem functioning. However, obtaining a comprehensive phylogenetic hypothesis can be difficult for some groups, especially those with a high number of species, that is the case for fishes, particularly tropical ones. The lack of species in phylogenetic hypotheses, called Darwinian shortfalls, can hinder ecological and evolutionary studies involving this group. To tackle this problem, we developed FishPhyloMaker, an R package that facilitates the generation of phylogenetic trees through a reliable and reproducible procedure, even for a large number of species. The package adopts well-known rules of insertion based on cladistic hierarchy, allowing its use by specialists and non-specialists in fish systematics. We tested the reliability of our algorithm in maintaining important properties of phylogenetic distances running a sensitivity analysis. We also exemplified the use of the FishPhyloMaker package by constructing complete phylogenies for fishes inhabiting the four richest freshwater ecoregions of the world. Furthermore, we proposed a new method to calculate Darwinian shortfalls and mapped this information for the major freshwater drainages of the world. FishPhyloMaker will expand the range of evolutionary and ecological questions that can be addressed using ray-finned fishes as study models, mainly in the field of community phylogenetics, by providing an easy and reliable way to obtain comprehensive phylogenies. Further, FishPhyloMaker presents the potential to be extended to other taxonomic groups that suffer from the same difficulty in the obtention of comprehensive phylogenetic hypothesis.

Highlights

We provide the first automated procedure to check species names, construct phylogenetic trees and calculate Darwinian shortfalls for ray-finned fishes (Actinopterygii) by the R package FishPhyloMaker.

This package provides functions to assemble phylogenies through a fast, reliable, and reproducible method, allowing its use and replicability by specialists and non-specialists in fish systematics.

The package also provides an interactive procedure that gives more flexibility to the user when compared with other existing tools that construct phylogenetic trees for other highly speciose groups.

The package includes a new method to compute Darwinian shortfalls for ray-finned fishes, but the rationale of the provided algorithm can be extended in future studies to be used in other groups of organisms
ENIGMA HALFpipe: Interactive, reproducible, and efficient analysis for resting-state and task-based fMRI data
Authors: Waller Lea , Erk Susanne , Pozzi Elena , Toenders Yara J. , Haswell Courtney C. , Büttner Marc , Thompson Paul M. , Schmaal Lianne , Morey Rajendra A. , Walter Henrik , Veer Ilya M.
Published: May 2021

The reproducibility crisis in neuroimaging has led to an increased demand for standardized data processing workflows. Within the ENIGMA consortium, we developedHALFpipe(HarmonizedAnaLysis ofFunctional MRI pipeline), an open-source, containerized, user-friendly tool that facilitates reproducible analysis of task-based and resting-state fMRI data through uniform application of preprocessing, quality assessment, single-subject feature extraction, and group-level statistics. It provides state-of-the-art preprocessing usingfMRIPrepwithout the requirement for input data in Brain Imaging Data Structure (BIDS) format.HALFpipeextends the functionality offMRIPrepwith additional preprocessing steps, which include spatial smoothing, grand mean scaling, temporal filtering, and confound regression.HALFpipegenerates an interactive quality assessment (QA) webpage to assess the quality of key preprocessing outputs and raw data in general.HALFpipefeatures myriad post-processing functions at the individual subject level, including calculation of task-based activation, seed-based connectivity, network-template (or dual) regression, atlas-based functional connectivity matrices, regional homogeneity (ReHo), and fractional amplitude of low frequency fluctuations (fALFF), offering support to evaluate a combinatorial number of features or preprocessing settings in one run. Finally, flexible factorial models can be defined for mixed-effects regression analysis at the group level, including multiple comparison correction. Here, we introduce the theoretical framework in whichHALFpipewas developed, and present an overview of the main functions of the pipeline.HALFpipeoffers the scientific community a major advance toward addressing the reproducibility crisis in neuroimaging, providing a workflow that encompasses preprocessing, post-processing, and QA of fMRI data, while broadening core principles of data analysis for producing reproducible results. Instructions and code can be found athttps://github.com/HALFpipe/HALFpipe.
Expansion of tissue-resident CD8+ T cells and CD4+ Th17 cells in the nasal mucosa following mRNA COVID-19 vaccination
Authors: Ssemaganda Aloysious , Nguyen Huong Mai , Nuhu Faisal , Jahan Naima , Card Catherine M. , Kiazyk Sandra , Severini Giulia , Keynan Yoav , Su Ruey-Chyi , Ji Hezhao , Abrenica Bernard , McLaren Paul J. , Ball T. Blake , Bullard Jared , Van Caeseele Paul , Stein Derek , McKinnon Lyle R.
Published: May 2021

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the upper respiratory tract, remains lacking. We enumerated and phenotyped T cells in nasal mucosa and blood before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n =21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ expanded ∼12 days following the first and second doses, by 0.31 and 0.43 log10cells per swab respectively (p=0.058 and p=0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decreased post-vaccination. Similar increases in nasal CD8+CD69+CD103-T cells were observed, particularly following the second dose. CD4+ Th17 cells were also increased in abundance following both doses. Following stimulation with SARS-CoV-2 spike peptides, CD8+ T cells increased expression of CD107a and CD154. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.
Surface-based tracking for short association fibre tractography
Authors: Shastin Dmitri , Genc Sila , Parker Greg D. , Koller Kristin , Tax Chantal M.W. , Evans John , Hamandi Khalid , Gray William P. , Jones Derek K. , Chamberland Maxime
Published: May 2021

It is estimated that in the human brain, short association fibres (SAF) represent more than half of the total white matter volume and their involvement has been implicated in a range of neurological and psychiatric conditions. This population of fibres, however, remains relatively understudied in the neuroimaging literature. Some of the challenges pertinent to the mapping of SAF include their variable anatomical course and proximity to the cortical mantle, leading to partial volume effects and potentially affecting streamline trajectory estimation. This work considers the impact of seeding and filtering strategies and choice of scanner, acquisition, data resampling to propose a whole-brain, surface-based short (≤30-40 mm) SAF tractography approach. The framework is shown to produce longer streamlines with a predilection for connecting gyri as well as high cortical coverage. We further demonstrate that certain areas of subcortical white matter become disproportionally underrepresented in diffusion-weighted MRI data with lower angular and spatial resolution and weaker diffusion weighting; however, collecting data with stronger gradients than are usually available clinically has minimal impact, making our framework translatable to data collected on commonly available hardware. Finally, the tractograms are examined using voxel- and surfacebased measures of consistency, demonstrating moderate reliability, low repeatability and high between-subject variability, urging caution when streamline count-based analyses of SAF are performed.