bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

AbstractObjectivePediatric 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.MethodsA 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.Results507 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.ConclusionsThe 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

AbstractDecades 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

ABSTRACTThe 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.