bluuebunny/crossref_metadata_2025 huggingface dataset:
BioSimulators: a central registry of simulation engines and services for recommending specific tools
Authors: Shaikh Bilal , Smith Lucian P , Vasilescu Dan , Marupilla Gnaneswara , Wilson Michael , Agmon Eran , Agnew Henry , Andrews Steven S , Anwar Azraf , Beber Moritz E , Bergmann Frank T , Brooks David , Brusch Lutz , Calzone Laurence , Choi Kiri , Cooper Joshua , Detloff John , Drawert Brian , Dumontier Michel , Ermentrout G Bard , Faeder James R , Freiburger Andrew P , Fröhlich Fabian , Funahashi Akira , Garny Alan , Gennari John H , Gleeson Padraig , Goelzer Anne , Haiman Zachary , Hasenauer Jan , Hellerstein Joseph L , Hermjakob Henning , Hoops Stefan , Ison Jon C , Jahn Diego , Jakubowski Henry V , Jordan Ryann , Kalaš Matúš , König Matthias , Liebermeister Wolfram , Sheriff Rahuman S Malik , Mandal Synchon , McDougal Robert , Medley J Kyle , Mendes Pedro , Müller Robert , Myers Chris J , Naldi Aurelien , Nguyen Tung V N , Nickerson David P , Olivier Brett G , Patoliya Drashti , Paulevé Loïc , Petzold Linda R , Priya Ankita , Rampadarath Anand K , Rohwer Johann M , Saglam Ali S , Singh Dilawar , Sinha Ankur , Snoep Jacky , Sorby Hugh , Spangler Ryan , Starruß Jörn , Thomas Payton J , van Niekerk David , Weindl Daniel , Zhang Fengkai , Zhukova Anna , Goldberg Arthur P , Schaff James C , Blinov Michael L , Sauro Herbert M , Moraru Ion I , Karr Jonathan R
Published: April 2022

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations.
rRNA operon multiplicity as a bacterial genome stability insurance policy
Authors: Fleurier Sebastien , Dapa Tanja , Tenaillon Olivier , Condon Ciarán , Matic Ivan
Published: April 2022

Quick growth restart after upon encountering favourable environmental conditions is a major fitness contributor in natural environment. It is widely assumed that the time required to restart growth after nutritional upshift is determined by how long it takes for cells to synthesize enough ribosomes to produce the proteins required to reinitiate growth. Here we show that a reduction in the capacity to synthesize ribosomes by reducing number of ribosomal RNA (rRNA) operons (rrn) causes a longer transition from stationary phase to growth of Escherichia coli primarily due to high mortality rates. Cell death results from DNA replication blockage and massive DNA breakage at the sites of the remaining rrn operons that become overloaded with RNA polymerases (RNAPs). Mortality rates and growth restart duration can be reduced by preventing R-loop formation and improving DNA repair capacity. The same molecular mechanisms determine the duration of the recovery phase after ribosome-damaging stresses, such as antibiotics, exposure to bile salts or high temperature. Our study therefore suggests that a major function of rrn operon multiplicity is to ensure that individual rrn operons are not saturated by RNAPs, which can result in catastrophic chromosome replication failure and cell death during adaptation to environmental fluctuations.
A widespread family of WYL-domain transcriptional regulators co-localizes with diverse phage defence systems and islands
Authors: Picton David M , Harling-Lee Joshua D , Duffner Samuel J , Went Sam C , Morgan Richard D , Hinton Jay C D , Blower Tim R
Published: April 2022

Bacteria are under constant assault by bacteriophages and other mobile genetic elements. As a result, bacteria have evolved a multitude of systems that protect from attack. Genes encoding bacterial defence mechanisms can be clustered into ‘defence islands’, providing a potentially synergistic level of protection against a wider range of assailants. However, there is a comparative paucity of information on how expression of these defence systems is controlled. Here, we functionally characterize a transcriptional regulator, BrxR, encoded within a recently described phage defence island from a multidrug resistant plasmid of the emerging pathogen Escherichia fergusonii. Using a combination of reporters and electrophoretic mobility shift assays, we discovered that BrxR acts as a repressor. We present the structure of BrxR to 2.15 Å, the first structure of this family of transcription factors, and pinpoint a likely binding site for ligands within the WYL-domain. Bioinformatic analyses demonstrated that BrxR-family homologues are widespread amongst bacteria. About half (48%) of identified BrxR homologues were co-localized with a diverse array of known phage defence systems, either alone or clustered into defence islands. BrxR is a novel regulator that reveals a common mechanism for controlling the expression of the bacterial phage defence arsenal.
MtEFD and MtEFD2: Two transcription factors with distinct neofunctionalization in symbiotic nodule development
Authors: Jardinaud Marie-Françoise , Fromentin Justine , Auriac Marie-Christine , Moreau Sandra , Pecrix Yann , Taconnat Ludivine , Cottret Ludovic , Aubert Grégoire , Balzergue Sandrine , Burstin Judith , Carrere Sébastien , Gamas Pascal
Published: April 2022

Rhizobium–legume nitrogen-fixing symbiosis involves the formation of a specific organ, the root nodule, which provides bacteria with the proper cellular environment for atmospheric nitrogen fixation. Coordinated differentiation of plant and bacterial cells is an essential step of nodule development, for which few transcriptional regulators have been characterized. Medicago truncatula ETHYLENE RESPONSE FACTOR REQUIRED FOR NODULE DIFFERENTIATION (MtEFD) encodes an APETALA2/ETHYLENE RESPONSIVE FACTOR (ERF) transcription factor, the mutation of which leads to both hypernodulation and severe defects in nodule development. MtEFD positively controls a negative regulator of cytokinin signaling, the RESPONSE REGULATOR 4 (MtRR4) gene. Here we showed that that the Mtefd-1 mutation affects both plant and bacterial endoreduplication in nodules, as well as the expression of hundreds of genes in young and mature nodules, upstream of known regulators of symbiotic differentiation. MtRR4 expressed with the MtEFD promoter complemented Mtefd-1 hypernodulation but not the nodule differentiation phenotype. Unexpectedly, a nonlegume homolog of MtEFD, AtERF003 in Arabidopsis (Arabidopsis thaliana), could efficiently complement both phenotypes of Mtefd-1, in contrast to the MtEFD paralog MtEFD2 expressed in the root and nodule meristematic zone. A domain swap experiment showed that MtEFD2 differs from MtEFD by its C-terminal fraction outside the DNA binding domain. Furthermore, clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9 (CRISPR-Cas9) mutagenesis of MtEFD2 led to a reduction in the number of nodules formed in Mtefd-1, with downregulation of a set of genes, including notably NUCLEAR FACTOR-YA1 (MtNF-YA1) and MtNF-YB16, which are essential for nodule meristem establishment. We, therefore, conclude that nitrogen-fixing symbiosis recruited two proteins originally expressed in roots, MtEFD and MtEFD2, with distinct functions and neofunctionalization processes for each of them.
Developing and testing a case-management intervention to support the return to work of health care workers with common mental health disorders
Authors: Parsons V , Juszczyk D , Gilworth G , Ntani G , Henderson M , Smedley J , McCrone P , Hatch S L , Shannon R , Coggon D , Molokhia M , Griffiths A , Walker-Bone K , Madan I
Published: April 2022

Background

To assess the feasibility and acceptability of conducting a trial of the clinical effectiveness and cost-effectiveness of a new case-management intervention to facilitate the return to work of health care workers, on sick leave, having a common mental disorder (CMD).

Methods

A mixed methods feasibility study.

Results

Systematic review examined 40 articles and 2 guidelines. Forty-nine National Health Service Occupational Health (OH) providers completed a usual care survey. We trained six OH nurses as case managers and established six recruitment sites. Forty-two out of 1938 staff on sick leave with a CMD were screened for eligibility, and 24 participants were recruited. Out of them, 94% were female. Eleven participants received the intervention and 13 received usual care. Engagement with most intervention components was excellent. Return-to-work self-efficacy improved more in the intervention group than in the usual care group. Qualitative feedback showed the intervention was acceptable.

Conclusions

The intervention was acceptable, feasible and low cost to deliver, but it was not considered feasible to recommend a large-scale effectiveness trial unless an effective method could be devised to improve the early OH referral of staff sick with CMD. Alternatively, the intervention could be trialled as a new stand-alone OH intervention initiated at the time of usual OH referral.
Comparative Effectiveness of Antipsychotics in Preventing Readmission for First-Admission Schizophrenia Patients in National Cohorts From 2001 to 2017 in Taiwan
Authors: Lin Yi-Hsuan , Wu Chi-Shin , Liu Chen-Chung , Kuo Po-Hsiu , Chan Hung-Yu , Chen Wei J
Published: April 2022

Background and Hypothesis

Antipsychotics remain the main treatment for schizophrenia, but their effectiveness is challenging to compare. We aimed to assess the comparative real-world effectiveness of antipsychotics in preventing readmission among patients in Asia with early-stage schizophrenia to inform clinical decision making.

Study Design

We did a retrospective cohort study of first-admission schizophrenia patients (ICD-9-CM: 295; ICD-10-CM: F20 and F25) from January 1, 2001, to December 31, 2017. The cohort was identified from the National Health Insurance Research Database NHIRD for Psychiatric Inpatients. The exposure was any antipsychotics prescribed post-discharge. The primary outcome was the readmission risk due to psychotic disorders, which was measured by adjusted hazard ratios (aHRs). Within-individual extended Cox models were applied for analyses, where the periods of oral risperidone use served as his or her own control.

Study Results

We selected 75 986 patients (men, 53.4%; mean [SD] age, 37.6 [12.0] years; mean [SD] duration of follow-up, 8.9 [5.0]) who were first admitted to psychiatric wards with schizophrenia in Taiwan. Among them, 47 150 patients (62.05%) had at least one readmission within 4 years. Compared to the period under treatment with oral risperidone, that under monotherapy with long-acting injectable antipsychotics (LAIs) had the lowest risk for psychotic readmission, with a risk reduction of 15–20%. However, the prevalence of person-prescription prevalence of LAIs remained low (< 10%) during the follow-up period.

Conclusions

The use of LAIs after the first admission for schizophrenia has notable advantages in preventing readmission. Such formulations should be offered earlier in the course of illness.
Banging while Believing: The Intersection of Religiosity, Gang Membership, and Violence
Authors: Lauger Timothy R , Rivera Craig J
Published: April 2022

Religious groups and street gangs typically exhibit contrasting cultural systems that produce different behavioral consequences, especially relating to crime and violence. This study introduces and develops the isolated and integrated affiliation models to explain the potential intersection of gang membership and religious affiliation. The isolated affiliation model predicts that gang membership and personal religiosity are incompatible affiliations and will not overlap. The integrated affiliation model predicts that individuals can simultaneously embrace and negotiate gang and religious affiliations even when they seem opposed to each other. Using Add Health data, this study examines the intersection between religiosity, youth gang membership, and violence. Findings indicate that gang members do report being religious, although they are significantly less religious than non-gang peers on three of the four individual measures of religiosity, with a marginally significant difference on the overall religiosity scale. Among the full sample, religiosity is inversely associated with violence while gang membership is positively associated with violence. Among a gang-only subsample, personal religiosity is inversely related to the prevalence but not the extent of violence. These findings provide insight into potential role and identity conflicts experienced by religious youth gang members. Seemingly oppositional affiliations can overlap with religious life, influencing some forms of behavior.
Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Autistic-Like Behaviors of SHANK3 Mutant Beagle Dogs
Authors: Zhao Lu , Li Yuan , Kou Xiaoxing , Chen Benchi , Cao Jing , Li Jun , Zhang Jianqi , Wang Heng , Zhao Jianping , Shi Songtao
Published: April 2022

Mesenchymal stem cell-based therapy has emerged as a great potential approach to treat individuals with autism spectrum disorders (ASD), a group of developmental disabilities characterized by impairments in social interaction and communication. Stem cells from human exfoliated deciduous teeth (SHED), holding earlier developing characteristics, have immune-modulatory and anti-inflammatory properties. To investigate whether SHED transplantation can rescue autistic-like symptoms in SHANK3 mutant beagle dogs, 12 SHANK3 mutant beagle dogs were randomly assigned into 2 groups according to their behavior evaluated by social interaction tests. Six mutant dogs received 6 intravenous infusions of SHED and were followed up for 3 months by testing social interaction and inflammatory cytokine levels. We found that infusion of SHED significantly improved impaired social novel preference of SHANK3 mutant beagle dogs at 1- and 3-month follow-ups. Social intimacies (following, sniffing, and licking) between mutant beagle dogs and human experimenters were partly improved. Stressed tail posture, indicating social stress, was also significantly alleviated. In addition, we showed that the levels of serum interferon-γ and interleukin-10 were notably increased and decreased, respectively, in SHANK3 mutant beagle dogs. Infusion of SHED was able to rescue altered interferon-γ and interleukin-10 levels. We failed to observe any serious adverse events after infusion of SHED. In summary, SHED transplantation may be a safe and effective therapy for ASD. The correction in the levels of serum interferon-γ and interleukin-10 may serve as an index to predict autistic severity and therapeutic outcomes.
Practical and Comprehensive Diagnostic Guide for Black Rot of Brassicas
Authors: Dániel-Gómez Mario , Reeves Ella , Meadows Inga M.
Published: April 2022

Xanthomonas campestris pv. campestris (Pammel) Dowson is the bacterial pathogen responsible for black rot of brassicas that affects all cultivated brassicas worldwide. Black rot is considered the most devastating disease of brassica, affecting crops such as cabbage (Brassica oleracea var. capitata), broccoli (Brassica oleracea var. italica), and rapeseed (Brassica napus subsp. napus). Working with X. campestris pv. campestris can pose challenges due to the complex taxonomical race division and similarities to other species of Xanthomonas. As such, this diagnostic guide aims to provide information about the importance, taxonomy, geographic and host ranges, and best methods for pathogen isolation, identification, storage, and pathogenicity testing for the successful diagnosis of this pathogen.
Diagnostic Guide for Bacterial Spot of Tomato and Pepper
Authors: Larrahondo-Rodríguez Erika , Liao Ying-Yu , Huerta Alejandra I.
Published: April 2022

Bacterial spot of tomato and pepper, caused by four Xanthomonas species, X. euvesicatoria, X. vesicatoria, X. perforans, and X. gardneri (renamed X. hortorum pv. gardneri), is a disease that affects pepper and tomato production worldwide. Symptomatic plants often show dark brown or black lesions on all aboveground tissue including fruit, stems, and foliage. Defoliation, fruit spots, and fruit drop are the most important symptoms that contribute to yield loss. To manage the disease, a combination of cultural management tactics is recommended. Unfortunately, effective commercially available copper-based agrochemicals are limited due to the pathogen’s ability to develop tolerance in the field. Multiple breeding efforts have focused on generating genetically resistant cultivars; however, host resistance has been observed to be lost over time due to the pathogen’s adaptation to a deployed genotype and the evolution of new pathogenic races. Isolation of the pathogen from infected tissue can be performed by surface sterilization followed by tissue maceration and streaking the supernatant on nutrient agar or yeast–dextrose–calcium carbonate agar. Identification tools for these pathogens include semiselective media (i.e., Chang Kama Tween Medium and Tween agar), serological methods, biochemical tests, and molecular techniques. For the latter method, one can use species-specific primers to run conventional PCR, qPCR, and multiplex PCR. Lastly, differential genotypes can be used for identifying races.
Overcoming Mental Health Stigma
Authors: Fauteux Nicole
Published: April 2022

Signs of hope, but more action is needed.
New Drug for Atopic Dermatitis
Authors: Aschenbrenner Diane S.
Published: April 2022

Tralokinumab-ldrm (Adbry) is now approved for the treatment of moderate to severe atopic dermatitis in adults whose disease has not been controlled by topical therapies.

Nurses and NPs should teach patients how to administer the drug subcutaneously and that more than one injection is needed to fulfill the prescribed dose.
Tezspire Approved for Severe Asthma
Authors: Aschenbrenner Diane S.
Published: April 2022

Tezepelumab-ekko (Tezspire) has been approved by the Food and Drug Administration as an add-on maintenance therapy for people ages 12 years and older with severe asthma symptoms not controlled by current medication.

The drug must be given subcutaneously by a health care provider.
Age-Related Changes in Facial Soft Tissue of Han Chinese: A Computed Tomographic Study
Authors: Wang Dawei , Zhang Qi , Zeng Ning , Wu Yiping
Published: April 2022

BACKGROUND

Facial lifting and volume restoration are the major strategies of facial rejuvenation, but the aging of facial soft tissues has not been sufficiently explored.

OBJECTIVE

This study aimed to reveal the age-related changes in full facial soft tissue of Han Chinese by using computed tomography.

MATERIALS AND METHODS

The measurements were performed on head computed tomographic images of 200 Han Chinese subjects (100 men and 100 women). The thickness of facial soft tissue was measured at 20 anthropological landmarks of the skull.

RESULTS

The thickness at rhinion was increased, whereas the thickness at midphiltrum, supradentale, and infradentale was decreased, indicating the significant differences in both sexes. Besides, the thickness at glabella, nasion, supramentale, and menton was decreased significantly in women. The thickness at supraorbital and lateral orbit was increased with aging in either sex. The thickness at frontal eminence, infraorbital, supraglenoid, and gonion showed significant age-related increases in women, and the thickness at zygomatic arch, supra M2, and infra M2 was significantly decreased in men.

CONCLUSION

These results suggest that soft tissues in different areas of the face are selectively thickened or thinned with aging, thus providing a reference for rejuvenation procedures.
DEXAMETHASONE INTRAVITREAL IMPLANT COMPLICATIONS INCLUDING VITREOUS HEMORRHAGE AND HYPOTONY
Authors: Yu Jeffrey J. , Adrean Sean D.
Published: April 2022

Purpose:

To describe cases of visually significant vitreous hemorrhage (VH) following dexamethasone intravitreal implant in our practice and present two cases that required surgical intervention and a case of VH and hypotony following dexamethasone implant. An injection technique that may minimize the incidence of these complications is described and illustrated.

Methods:

Retrospective case series.

Results:

The overall incidence of VH was 1.7% (8 of 467 injections) and those that required surgical intervention was 0.4% (2/467) over a 10-year period, from June 2010 to June 2020 (Table 1). Overall, 75% (6 of 8) VH resolved spontaneously over time, without surgical intervention.

Conclusion:

Nonclearing VH and hypotony are rare but serious complications of dexamethasone implant.
NONARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY ASSOCIATED WITH IPSILATERAL HYPOPLASTIC INTERNAL CAROTID ARTERY
Authors: Abri Aghdam Kaveh , Aghajani Ali , Ghamari Kiandokht , Soltan Sanjari Mostafa
Published: April 2022

Background:

Vascular insufficiency of the optic nerve head is the cause of nonarteritic ischemic optic neuropathy (NAION). Carotid artery abnormalities are now considered as a predisposing factor for developing NAION. In this report, we present a case of NAION associated with ipsilateral internal carotid artery hypoplasia.

Methods:

A 69-year-old female with decreased vision in her right eye due to NAION was evaluated. the magnetic resonance imaging showed a considerably smaller left internal carotid artery than the right side. The magnetic resonance angiography confirmed the disparity and perfusion abnormalities of intracranial carotid arteries.

Results:

The diagnosis of left internal carotid artery hypoplasia was made and verified by depicting a left side small carotid canal on the computed tomography scan.

Conclusion:

This report suggests that internal carotid artery hypoplasia could be associated with NAION.
Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia
Authors: Lang Jason E. , Hornik Christoph P. , Elliott Carrie , Silverstein Adam , Hornik Chi , Al-Uzri Amira , Bosheva Miroslava , Bradley John S. , Borja-Tabora Charissa Fay Corazon , Di John David , Mendez Echevarria Ana , Ericson Jessica E. , Friedel David , Gonczi Ferenc , Isidro Marie Grace Dawn , James Laura P. , Kalocsai Krisztina , Koutroulis Ioannis , Laki Istvan , Ong-Lim Anna Lisa T. , Nad Marta , Simon Gabor , Syed Salma , Szabo Eva , Benjamin Daniel K. , Cohen-Wolkowiez Michael ,   on behalf of the SOLI-PEDS Program
Published: April 2022

Background:

Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP.

Methods:

This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (AEs) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy.

Results:

Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n = 73) or comparator (n = 24). There were 24 participants (34%, 95% CI, 23%–47%) with a treatment-emergent AE in the solithromycin group and 7 (29%, 95% CI, 13%–51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51%–76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58%–95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47%–72%) and 68% (95% CI, 43%–87%) for the solithromycin and comparator groups, respectively.

Conclusions:

Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.
Risk Factors for Carbapenem-resistant Pseudomonas aeruginosa Infection in Children
Authors: Li Lu , Huang Yanfeng , Tang Qiqin , Zheng Yuqiang
Published: April 2022

Background:

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is rapidly emerging as a life-threatening nosocomial infection. The study aimed to identify the risk factors for CRPA infection in children, especially antimicrobials use and invasive procedures.

Methods:

A retrospective study was conducted in the Children’s Hospital of Chongqing Medical University, which involved a cohort of patients with PA infection from January 2016 to December 2020. Patients were assigned to a carbapenem-susceptible PA group or to a CRPA group and matched using propensity-score matching. Univariate analysis and multivariate analysis were performed to estimate the risk factors of CRPA.

Results:

One-thousand twenty-five patients were included in the study but 172 children were analyzed. Several factors were associated with CRPA infection according to univariate analysis (P < 0.05), such as prior treatment with some antimicrobials and invasive procedures. However, only prior exposure to carbapenems (odds ratio [OR]: 0.102; confidence interval [CI]: 0.033–0.312; P < 0.001) and bronchoscopy (OR: 0.147; CI: 0.032–0.678; P = 0.014) during time at risk, previous invasive therapy in the last year (OR: 0.353; CI: 0.159–0.780; P = 0.013), and previous use of β-lactams/β-lactamase inhibitors within the last 90 days (OR: 0.327; CI: 0.121–0.884; P = 0.03) were considered independent risk factors by multivariate analysis.

Conclusions:

Those who had prior exposure to carbapenems and bronchoscopy were high-risk population to develop CRPA infection. The spread of CRPA could be influenced by invasive therapy, and we need pay attention to it. Moreover, we should take restrictions in the clinical use of carbapenems into account.
Effect of peer tutoring on social adjustment among English learners with hearing impairments in special primary schools
Authors: Ubah Josephine Chioma , Egbe Cajetan Ikechukwu , Ugwuanyi Leonard Tochukwu , Uzoamaka Akabogu Josephine , Dike Adannia Amalachukwu , Nnamani Ogechukwu , Chukwuma Ifeoma Salome , Otu Mkpoikanke Sunday , Adaka Terfa Ahon , Nnamani Amuche Patricia , Nwankwor Paulinus Paul , Ogele Ukpai Ibem , Okoyeukwu Ngozi Georgina , Ukoha Evelyn Oziri , Uloh-Bethels Annah Chinyeaka
Published: April 2022

Background/Objective:

Different studies have shown the prevalence of high level of social adjustment among English learners with hearing impairment. The objective of the present study was to investigate the effect of peer tutoring as a social adjustment intervention among English learners with hearing impairment in special primary schools in Enugu State, Nigeria.

Method:

The area of the study was Enugu State. The study adopted a pre-test–post-test quasi experimental research design. The population of the study comprised 30 pupils with language hearing impairment. There was no sampling because the population size was small and manageable. The instrument for data collection was a social adjustment scale with reliability coefficient of 0.88. After the experiment, the experimental group were taught using peer tutoring teaching strategy while the control group were taught with conventional teaching method. Analysis of covariance was used to test the formulated hypotheses at 0.05 level of significance.

Results:

Results showed that peer tutoring teaching strategy significantly increased social adjustment of pupils with language hearing impairment. Gender did not significantly influence social adjustment of pupils with language hearing impairment. The interaction effect of teaching strategies and gender on social adjustment of pupils with language hearing impairment was not significant.

Conclusion:

Peer tutoring can be used to alleviate social adjustment problem of pupils with language hearing impairment. The implications of the results for curriculum innovation were highlighted.
A Clinical and Physiological Prospective Observational Study on the Management of Pediatric Shock in the Post-Fluid Expansion as Supportive Therapy Trial Era*
Authors: Obonyo Nchafatso G. , Olupot-Olupot Peter , Mpoya Ayub , Nteziyaremye Julius , Chebet Martin , Uyoga Sophie , Muhindo Rita , Fanning Jonathon P. , Shiino Kenji , Chan Jonathan , Fraser John F. , Maitland Kathryn
Published: April 2022

OBJECTIVES:

Fluid bolus resuscitation in African children is harmful. Little research has evaluated physiologic effects of maintenance-only fluid strategy.

DESIGN:

We describe the efficacy of fluid-conservative resuscitation of septic shock using case-fatality, hemodynamic, and myocardial function endpoints.

SETTING:

Pediatric wards of Mbale Regional Referral Hospital, Uganda, and Kilifi County Hospital, Kenya, conducted between October 2013 and July 2015. Data were analysed from August 2016 to July 2019.

PATIENTS:

Children (≥ 60 d to ≤ 12 yr) with severe febrile illness and clinical signs of impaired perfusion.

INTERVENTIONS:

IV maintenance fluid (4 mL/kg/hr) unless children had World Health Organization (WHO) defined shock (≥ 3 signs) where they received two fluid boluses (20 mL/kg) and transfusion if shock persisted. Clinical, electrocardiographic, echocardiographic, and laboratory data were collected at presentation, during resuscitation and on day 28. Outcome measures were 48-hour mortality, normalization of hemodynamics, and cardiac biomarkers.

MEASUREMENT AND MAIN RESULTS:

Thirty children (70% males) were recruited, six had WHO shock, all of whom died (6/6) versus three of 24 deaths in the non-WHO shock. Median fluid volume received by survivors and nonsurvivors were similar (13 [interquartile range (IQR), 9–32] vs 30 mL/kg [28–61 mL/kg], z = 1.62, p = 0.23). By 24 hours, we observed increases in median (IQR) stroke volume index (39 mL/m2 [32–42 mL/m2] to 47 mL/m2 [41–49 mL/m2]) and a measure of systolic function: fractional shortening from 30 (27–33) to 34 (31–38) from baseline including children managed with no-bolus. Children with WHO shock had a higher mean level of cardiac troponin (t = 3.58; 95% CI, 1.24–1.43; p = 0.02) and alpha-atrial natriuretic peptide (t = 16.5; 95% CI, 2.80–67.5; p < 0.01) at admission compared with non-WHO shock. Elevated troponin (> 0.1 μg/mL) and hyperlactatemia (> 4 mmol/L) were putative makers predicting outcome.

CONCLUSIONS:

Maintenance-only fluid therapy normalized clinical and myocardial perturbations in shock without compromising cardiac or hemodynamic function whereas fluid-bolus management of WHO shock resulted in high fatality. Troponin and lactate biomarkers of cardiac dysfunction could be promising outcome predictors in pediatric septic shock in resource-limited settings.
Peripheral Vasoactive Administration in Critically Ill Children With Shock: A Single-Center Retrospective Cohort Study*
Authors: Levy Robert A. , Reiter Pamela D. , Spear Matthew , Santana Alison , Silveira Lori , Cox Shaina , Mourani Peter M. , Maddux Aline B.
Published: April 2022

OBJECTIVES:

Management of fluid refractory pediatric shock requires prompt administration of vasoactive agents. Although delivery of vasoactive therapy is generally provided via a central venous catheter, their placement can delay drug administration and is associated with complications. We characterize peripheral vasoactive administration in a cohort of critically ill children with shock, evaluate progression to central venous catheter placement, and describe complications associated with extravasation.

DESIGN:

Retrospective cohort study.

SETTING:

Single-center, quaternary PICU (January 2010 to December 2015).

PATIENTS:

Children (31 d to 18 yr) who received epinephrine, norepinephrine, or dopamine.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We compared patients based on the initial site of vasoactive infusion: peripheral venous access (PVA) or central venous access (CVA) and, within the PVA group, compared patients based on subsequent placement of a central catheter for vasoactive infusion. We also characterized peripheral extravasations. We evaluated 756 patients: 231 (30.6%) PVA and 525 (69.4%) CVA patients. PVA patients were older, had lower illness severity, and more frequently had vasoactive therapy initiated at night compared with CVA patients. In PVA patients, 124 (53.7%) had a central catheter placed after a median of 140 minutes (interquartile range, 65–247 min) of peripheral treatment. Patients who avoided central catheter placement had lower illness severity. Of the 93 patients with septic shock, 44 (47.3%) did not have a central catheter placed. Extravasations occurred in four of 231 (1.7% [95% CI, 0.03–3.4]) PVA patients, exclusively in the hand. Three patients received pharmacologic intervention, and none had long-term disabilities.

CONCLUSIONS:

In our experience, peripheral venous catheters can be used for vasoactive administration. In our series, the upper limit of the 95% CI for extravasation is approximately 1-in-30, meaning that this route may be an appropriate option while evaluating the need for central access, particularly in patients with low illness severity.
Lyophilized plasma resuscitation downregulates inflammatory gene expression in a mouse model of sepsis
Authors: Barry Mark , Wu Feng , Pati Shibani , Chipman Amanda , Geng Huimin , Kozar Rosemary
Published: April 2022

BACKGROUND

Plasma resuscitation may improve outcomes by targeting endotheliopathy induced by severe sepsis or septic shock. Given the logistical constraints of using fresh frozen plasma in military settings or areas with prolonged prehospital care, dried products such as lyophilized plasma (LP) have been developed. We hypothesized that resuscitation with LP would decrease lung injury, inflammation, and mortality in a mouse sepsis model.

METHODS

Adult male C57BL/6J mice received an intraperitoneal injection of cecal slurry. Twenty-two hours later, the mice were anesthetized, the femoral artery was cannulated, and the mice were randomized to receive resuscitation with LP (10 mL/kg) or lactated Ringer's (LR; 30 mL/kg) for 1 hour. At 48-hours post–cecal slurry injection, bronchoalveolar lavage fluid was collected, the lungs were harvested, and plasma was obtained. Mortality and bronchoalveolar lavage total protein concentration (as an indicator of permeability) were compared between groups. The lungs were analyzed for histopathology and inflammatory gene expression using NanoString, and the plasma was analyzed for biomarkers of inflammation and endothelial function.

RESULTS

There was no significant difference in short-term mortality between LR and LP mice, 38% versus 47%, respectively (p = 0.62). Bronchoalveolar lavage protein levels were similar among mice resuscitated with LR or LP, and there was a lack of significant histopathologic lung injury in all groups. However, LP resuscitation resulted in downregulation of pulmonary inflammatory genes, including signaling pathways such as Janus kinase-signal transducer and activator of transcription and nuclear factor κB, and a circulating inflammatory biomarker profile similar to sham animals.

CONCLUSION

Resuscitation with LP did not improve mortality or reduce permeability or injury in this model compared with LR. However, LP downregulated pulmonary inflammatory gene signaling and may also reduce circulating biomarkers of inflammation. Future studies should evaluate LP resuscitation in combination with antibiotics and other therapeutics to determine whether the anti-inflammatory effects of LP may improve outcomes in sepsis.
Failure to rescue in trauma: Early and late mortality in low- and high-performing trauma centers
Authors: Sangji Naveen F. , Gerhardinger Laura , Oliphant Bryant W. , Cain-Nielsen Anne H. , Scott John W. , Hemmila Mark R.
Published: April 2022

BACKGROUND

Failure to rescue (FTR) is defined as mortality following a complication. Failure to rescue has come under scrutiny as a quality metric to compare trauma centers. In contrast to elective surgery, trauma has an early period of high expected mortality because of injury sequelae rather than a complication. Here, we report FTR in early and late mortality using an externally validated trauma patient database, hypothesizing that centers with higher risk-adjusted mortality rates have higher risk-adjusted FTR rates.

METHODS

The study included 114,220 patients at 34 Levels I and II trauma centers in a statewide quality collaborative (2016–2020) with Injury Severity Score of ≥5. Emergency department deaths were excluded. Multivariate regression models were used to produce center-level adjusted rates for mortality and major complications. Centers were ranked on adjusted mortality rate and divided into quintiles. Early deaths (within 48 hours of presentation) and late deaths (after 48 hours) were analyzed.

RESULTS

Overall, 6.7% of patients had a major complication and 3.1% died. There was no difference in the mean risk-adjusted complication rate among the centers. Failure to rescue was significantly different across the quintiles (13.8% at the very low-mortality centers vs. 23.4% at the very-high-mortality centers, p < 0.001). For early deaths, there was no difference in FTR rates among the highest and lowest mortality quintiles. For late deaths, there was a twofold increase in the FTR rate between the lowest and highest mortality centers (9.7% vs. 19.3%, p < 0.001), despite no difference in the rates of major complications (5.9% vs. 6.0%, p = 0.42).

CONCLUSION

Low-performing trauma centers have higher mortality rates and lower rates of rescue following major complications. These differences are most evident in patients who survive the first 48 hours after injury. A better understanding of the complications and their role in mortality after 48 hours is an area of interest for quality improvement efforts.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level III.
Impact of OSA Treatment Success on Changes in Hypertension and Obesity: A Retrospective Cohort Study
Authors: Shanmugam Akash , Binney Zachary O. , Voyles Courtney B. , Bouldin Emerson , Raol Nikhila P.
Published: April 2022

Objective

Pediatric obstructive sleep apnea (OSA) has been shown to lead to the development of chronic cardiometabolic conditions, including obesity and cardiovascular disease. We sought to describe the impact of the success of continuous positive airway pressure (CPAP) and surgery, common treatment options for pediatric OSA, on cardiometabolic conditions.

Methods

A retrospective review of patients (≤18 years) diagnosed with OSA based on a polysomnogram at a tertiary care pediatric otolaryngology practice from 2015 to 2019 was conducted. Clinical data, including the systolic blood pressure (SBP) values, body mass index (BMI), overall apnea/hypopnea index (AHI) values, and CPAP compliance, were collected. Linear mixed-effects models were developed to observe the relationship between the clinical measurements of each comorbidity and OSA treatment modalities.

Results

507 patients were included. BMI and SBP measures were collected for 230 and 277 patients respectively. The difference-in-difference estimate for the SBP z-score percentile after successful treatment was -5.3 ± 2.0 percentile units per 100 days. The difference-in-difference estimate for SBP z-score percentile after successful CPAP treatment was -14.4 ± 4.9 percentile units per 100 days while the estimate after successful surgical treatment was -4.6 ± 2.3 percentile units per 100 days. No significant differences were found between clinical measures for obese patients in any treatment cohort.

Conclusions

The success of OSA management was shown to have a positive impact on SBP in hypertensive patients and no impact on BMI in obese patients. In hypertensive patients, CPAP success tripled improvements in SBP z-score percentile compared to surgical treatment success.
A resistance-gene-directed tolerance trait and selective inhibitors proffer HMG-CoA reductase as a new herbicide mode of action
Authors: Haywood Joel , Breese Karen J. , Zhang Jingjing , Waters Mark T. , Bond Charles S. , Stubbs Keith A. , Mylne Joshua S.
Published: April 2022

Decades of intense herbicide use has led to resistance in weeds. Without innovative weed management practices and new herbicidal modes of action, the unabated rise of herbicide resistance will undoubtedly place further stress upon food security. HMGR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) is the rate limiting enzyme of the eukaryotic mevalonate pathway successfully targeted by statins to treat hypercholesterolemia in humans. As HMGR inhibitors have been shown to be herbicidal, HMGR could represent a new mode of action target for the development of herbicides. Here we present the crystal structure of a HMGR from Arabidopsis thaliana (AtHMG1) which exhibits a wider active site than previously determined structures from different species. This plant conserved feature enabled the rational design of specific HMGR inhibitors, for which we engineered a tolerance trait through sequence analysis of fungal gene clusters. These results suggest HMGR to be a viable herbicide target modifiable to provide a tolerance trait.
Sperm-mediated regulation of region-specific responses in the oviduct during establishment of pregnancy in mice
Authors: Finnerty Ryan M. , Carulli Daniel J. , Winuthayanon Wipawee
Published: April 2022

The oviduct comprises 4 main regions: infundibulum (oocyte pick-up), ampulla (fertilization), isthmus (sperm capacitation and reservoir, preimplantation embryonic development), and uterotubal junction (UTJ; sperm and embryo transport). Mounting evidence in livestock and rodents suggest that gametes alter gene expression in secretory and ciliated epithelial cells of the oviduct. To elucidate whether adaptive interactions between the oviduct and gamete/embryo exist, we performed bulk RNA-sequencing on oviductal tissues collected from infundibulum+ampulla (IA) or isthmus+UTJ (IU) at various developmental stages (0.5, 1.5, 2.5-, and 3.5-days post coitus (dpc)) in mice. Samples were also collected during days 0.5, 1.5, 2.5, and 3.5 of pseudopregnancy (dpp). We found a strong region (IA vs. IU)-specific expression of large clusters of genes. The transition from 0.5 dpc to other pregnancy timepoints induces large sets of differentially expressed genes (DEGs) in pregnancy and pseudopregnancy in both IA and IU regions. Specifically, genes involved in pro-inflammatory responses were detected in both IU and IA regions. The presence of sperm at 0.5 dpc induces DEGs involved in pro-inflammatory responses in the IU region with an enrichment of biological processes for inflammatory cytokines, macrophage, and neutrophil recruitment. Additionally, DEGs are enriched in mitogen-activated protein kinase (MAPK) pathways along with genes in the Dusp family, Map3k8, Il1b, and Il1r2, among others. However, at 1.5 dpc we observed a strong shift to an anti-inflammatory condition in the IU region. These observations were absent in 0.5 and 1.5 dpp, suggesting that the DEGs observed for those inflammatory responses during pregnancy were likely induced by the presence of sperm. scRNA-seq analysis revealed that the inflammatory responsive genes were likely produced by secretory epithelial cells, compared to other cell types in the oviduct. In addition, multiple DEGs involved in pyruvate and glycolysis were enriched in the IU region, which could provide metabolic support for developing embryos. Lastly, we have also identified that there were cells that express immune markers in the oviduct, indicating that the oviduct is an immuno-dynamic tissue. In conclusion, our findings indicate that the oviduct is adaptive and responsive to the presence of sperm and embryos in a spatiotemporal manner. In this report, we intend to disseminate our findings on the transcriptional profiles during different stages of pregnancy. The complete study and validation at the protein level are currently underway and will be updated as soon as the data are available.
Route of oxytetracycline administration differentially impacts the growth and gut microbiome of pigs co-infected with Bordetella bronchiseptica and Pasteurella multocida
Authors: Mou Kathy T. , Trachsel Julian , Stephens Amali , Ricker Nicole , Brockmeier Susan L. , Allen Heather K. , Loving Crystal L.
Published: April 2022

Along with judicious antibiotic use, there is great interest in how the dose regimen of an antibiotic affects the animal gut microbiota. This study evaluated the impact of experimental respiratory infection alone or respiratory infection followed by oxytetracycline (oxytet) treatment on the animal’s health and its fecal microbiome. Piglets of approximately three weeks-of-age were separated into four groups (n=20 per group). One group remained non-infected and administered non-medicated feed and the other three groups were infected with Bordetella bronchiseptica (day 0) and Pasteurella multocida (day 4), with one group receiving non- medicated feed and the remaining two groups receiving oxytetr starting on day 7 by injection or in-feed (day 7-14). Infection with B. bronchiseptica and P. multocida negatively impacted piglet growth and induced mild pneumonia. Infection alone had minimal effect on the fecal microbiota community. When oxytet was administered either by injection or in-feed to treat the respiratory infections, both routes had minimal effect on clearing B. bronchiseptica and P. multocida in the animal. However, both routes appeared to limit lung lesion severity, and injected oxytet reduced the negative impact of infection on weight gain. Both routes had limited impact on the animal’s overall gut microbiome, including relative abundances of bacterial taxa and antibiotic resistance genes tet32, tetW, and aph2. Overall, oxytet administered by either route did not clear the respiratory infection, but oxytet administration minimized the negative health impacts of infection and had minor impact on the pig gut microbiome.

Importance

Efforts to address antibiotic resistance calls for improved antibiotic stewardship, including considering antibiotic administration route. While our previous study found in-feed oxytet had greater impact on the gut microbiome of healthy piglets than injected oxytet, it remained unknown if oxytet treatments would have the same impact on the microbiota of infected piglets. We evaluated the impact of respiratory infection alone or respiratory infection followed by oxytet treatment on the animals’ health and their gut microbiome profile. Respiratory infection negatively affected piglets’ health, but infection alone had minimal impact on the gut community. When oxytet was administered either in-feed or by injection to treat the respiratory infection, neither route of administration led to the clearance of the respiratory pathogens. However, oxytet minimized the negative health impacts of infection, and had minor impact on the pig gut microbiome. These findings are informative for disease management in food animals while integrating antibiotic stewardship practices.