bluuebunny/crossref_metadata_2025 huggingface dataset:
Feeding a whole-cell inactivated Pichia guilliermondii yeast to gestating and lactating sows in a commercial production system
Authors: Thayer Morgan T , Garcia Ricardo M , Duttlinger Alan W , Mahoney Julie A , Schinckel Allan P , Asmus Matthew D , Jones Daniel B , Dunn Jim L , Richert Brian T
Published: December 2022

A total of 606 sows (PIC 1050) and their progeny (PIC 1050 × 280) were used to determine if feeding gestating and lactating sows a proprietary strain of Pichia guilliermondii as a whole-cell inactivated yeast product (WCY; CitriStim, ADM Animal Nutrition, Quincy, IL) improves sow and litter performance in a commercial production system. Once confirmed pregnant at d 35 post-breeding pregnancy check, sows were fed a basal gestation control (CON) diet (0.55% SID lysine) or the control diet fortified with 0.15% of the WCY replacing corn in the CON diet. Dietary treatments were also fed in lactation (1.05% SID lysine) once sows were moved into farrowing crates on approximately d 112 of gestation until weaning. Sows supplemented with WCY in gestation and lactation had increased total born piglets by 0.45 pigs (P < 0.04), piglets born alive (14.27 vs. 13.85; P < 0.04), and, therefore, heavier born alive litter weights (P < 0.001) compared to CON fed sows. A greater post cross-foster litter size (P < 0.001) meant that litter size at weaning was increased by 0.54 pigs when sows were fed WCY compared to CON (P < 0.001). However, litter weaning weights and 21-d adjusted litter weaning weights were similar (P > 0.158), although numerically greater, for WCY fed sows. Pigs from CON fed sows were 0.35 kg heavier at weaning compared to pigs from WCY fed sows (P < 0.001). This increase in weaning weight of pigs from CON fed sows is partially explained by their 0.93 d longer lactation (P < 0.001) and may also be due to the smaller litter size throughout lactation. The percent of litters treated for scours decreased from 38.3 to 14.2% when sows were fed WCY (P < 0.001). The distribution of birth and weaning weights was not impacted (P > 0.2461) by treatment. In conclusion, feeding gestating and lactating sows a proprietary strain of Pichia guilliermondii as a whole-cell inactivated yeast product increased the number of pigs born and weaned, and decreased the prevalence of scours during lactation.
Lipid dysregulation associated with progression of silica-induced pulmonary fibrosis
Authors: Ma Ruimin , Fan Yali , Huang Xiaoxi , Wang Jingwei , Li Shuang , Wang Yuanying , Ye Qiao
Published: December 2022

Silicosis is an irreversible, progressive, fibrotic lung disease caused by long-term exposure to dust-containing silica particles at the workplace. Despite the precautions enforced, the rising incidence of silicosis continues to occur globally, particularly in developing countries. A better understanding of the disease progression and potential metabolic reprogramming of silicosis is warranted. The low- or high-dose silica-induced pulmonary fibrosis in mice was constructed to mimic chronic or accelerated silicosis. Silica-induced mice lung fibrosis was analyzed by histology, lung function, and computed tomography scans. Non-targeted metabolomics of the lung tissues was conducted by ultra-high-performance liquid chromatography-mass spectrometry to show the temporal metabolic trajectory. The low-dose silica-induced silicosis characterized inflammation for up to 42 days, with the onset of cellular silicon nodules. Conversely, the high-dose silica-induced silicosis characterized inflammation for up to 14 days, after which the disease developed rapidly, with a large volume of collagen deposition, presenting progressive massive fibrosis. Both low- and high silica-induced fibrosis had aberrant lipid metabolism. Combined with the RNA-Seq data, this multiomics study demonstrated alterations in the enzymes involved in sphingolipid metabolism. Time-dependent metabolic reprogramming revealing abnormal glycerophospholipid metabolism was intimately associated with the process of inflammation, whereas sphingolipid metabolism was crucial during lung fibrosis. These findings suggest that lipid dysregulation, especially sphingolipid metabolism, was involved in the process of silicosis.
Trunk Injection of Oxytetracycline for Huanglongbing Management in Mature Grapefruit and Sweet Orange Trees
Authors: Archer Leigh , Kunwar Sanju , Alferez Fernando , Batuman Ozgur , Albrecht Ute
Published: December 2022

Huanglongbing (HLB) is a devastating bacterial disease associated with ‘ Candidatus Liberibacter asiaticus’. The location of the pathogen within the vasculature of the tree has left growers with limited options for the effective management of the disease. Trunk injection is a crop protection technique that applies therapeutics directly into the xylem of woody tree species and allows for their systemic uptake and transport, which may provide more effective management of vascular diseases such as HLB. In this study, mature ‘Valencia’ and ‘Hamlin’ sweet orange ( Citrus sinensis) and ‘Duncan’ grapefruit ( C. paradisi) trees were injected with oxytetracycline (OTC) in the spring and/or fall to evaluate the effects of injection timing and response to injection. In addition to seasonal evaluations of tree health and bacterial titer, preharvest fruit drop, yield, and fruit quality were measured at harvest to determine the effects of OTC injection. The benefits associated with injection included a reduction in fruit drop, an increase in fruit yield and fruit size, and improvements in juice quality. However, results varied due to the timing of injection and were not consistent across all three varieties. Residue analysis at different time points after injection suggests that trunk injection effectively delivers therapeutics to mature citrus trees. This study provides fundamental information on the short-term benefits associated with trunk injection of OTC for HLB management in citrus groves. The potential for use of trunk injection at the commercial scale and the possible risks are discussed.
Yard Age, Cultivar Susceptibility, and Spring Pruning Practices as Risk Factors for Overwintering of Podosphaera macularis on Hop
Authors: Laurie Robert W. , Richardson Briana J. , Ross Cameron J. , Gent David H.
Published: December 2022

Hop powdery mildew, caused by Podosphaera macularis, may be initiated by sexual or asexual spores of the pathogen, but only asexual reproduction has been reported in the Pacific Northwest United States. In this region, overwintering is via bud perennation, leading to "flag shoots" the following season. We expanded on previous research and analyzed 766 location-years of flag shoot data from Oregon hop yards collected from 2014 to 2020, examining potential risk factors of yard age, cultivar susceptibility to powdery mildew, pruning method (mechanical means or not), and pruning thoroughness. Bayesian logistic regression models were fitted to estimate the probability of flag shoot presence or absence. We found little evidence to support yard age as a significant risk factor for flag shoot presence, as the 95% credible interval for the parameter associated with yard age was consistently centered around 0 in each of our models. However, cultivar susceptibility to powdery mildew, spring pruning method, and spring pruning thoroughness were associated with increases in the probability of observing a flag shoot. Although yard age was not an important risk factor, there was an interrelationship between yard age, pruning method, and pruning thoroughness that suggests second-year yards may indirectly be at an elevated risk for flag shoot development because these yards are less often pruned using mechanical methods. Our research further identifies yards that are most at risk for overwintering of P. macularis and reinforces the importance of thorough pruning in yards with an elevated risk for possessing a flag shoot.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.
Patient Willingness to Dispose of Leftover Opioids After Surgery
Authors: Draper Phoebe , Bleicher Josh , Kobayashi Jaqueline K. , Stauder Elizabeth L. , Stoddard Gregory J. , Johnson Jordan E. , Cohan Jessica N. , Kaphingst Kimberly A. , Harris Alex H. S. , Huang Lyen C.
Published: December 2022

Objectives:

We examined how convenience and financial incentives influence patient willingness to dispose of leftover prescription opioids after surgery. We also identified additional barriers and facilitators to disposal.

Background:

In the United States, up to 70% of surgical patients are prescribed opioids and up to 92% will have leftover tablets. Most do not dispose of leftover opioids, increasing the risk for opioid-related harm. Current interventions promoting opioid disposal have shown mixed success.

Methods:

We conducted a mixed methods study using a standard gamble survey and semi-structured interviews. Participants estimated willingness to dispose in 16 scenarios with varying convenience (time requirements of <5, 15, 30, and 60 minutes) and financial incentives ($0, $5, $25, $50). We estimated the likelihood of disposal using a multivariable mixed effects modified Poisson regression model. Semi-structured interviews explored how convenience, financial incentives, and other barriers and facilitators influenced decisions to dispose.

Results:

Fifty-five participants were surveyed and 42 were interviewed. Most were willing to dispose when the time required was <15 minutes. Few were willing to dispose if the process required 60 minutes, although a $50 financial incentive increased rates from 9% to 36%. Anxiety about future pain, opioid scarcity, recreational use, family safety, moral beliefs, addiction, theft, and environmental harm also influenced decision-making.

Conclusions:

Interventions promoting opioid disposal should focus on convenience, but the selective use of financial incentives can be effective. Tailoring interventions to individual barriers and facilitators could also increase disposal rates.
Machine learning algorithm as a prognostic tool for Epstein-Barr virus reactivation after haploidentical hematopoietic stem cell transplantation
Authors: Fan Shuang , Hong Hao-Yang , Dong Xin-Yu , Xu Lan-Ping , Zhang Xiao-Hui , Wang Yu , Yan Chen-Hua , Chen Huan , Chen Yu-Hong , Han Wei , Wang Feng-Rong , Wang Jing-Zhi , Liu Kai-Yan , Shen Meng-Zhu , Huang Xiao-Jun , Hong Shen-Da , Mo Xiao-Dong
Published: December 2022

Epstein-Barr virus (EBV) reactivation is one of the most important infections after hematopoietic stem cell transplantation (HSCT) using haplo-identical related donors (HID). We aimed to establish a comprehensive model with machine learning, which could predict EBV reactivation after HID HSCT with anti-thymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis. We enrolled 470 consecutive acute leukemia patients, 60% of them (n = 282) randomly selected as a training cohort, the remaining 40% (n = 188) as a validation cohort. The equation was as follows: Probability (EBV reactivation) =

, where Y = 0.0250 × (age) – 0.3614 × (gender) + 0.0668 × (underlying disease) – 0.6297 × (disease status before HSCT) – 0.0726 × (disease risk index) – 0.0118 × (hematopoietic cell transplantation-specific comorbidity index [HCT-CI] score) + 1.2037 × (human leukocyte antigen disparity) + 0.5347 × (EBV serostatus) + 0.1605 × (conditioning regimen) – 0.2270 × (donor/recipient gender matched) + 0.2304 × (donor/recipient relation) – 0.0170 × (mononuclear cell counts in graft) + 0.0395 × (CD34+ cell count in graft) – 2.4510. The threshold of probability was 0.4623, which separated patients into low- and high-risk groups. The 1-year cumulative incidence of EBV reactivation in the low- and high-risk groups was 11.0% versus 24.5% (P < .001), 10.7% versus 19.3% (P = .046), and 11.4% versus 31.6% (P = .001), respectively, in total, training and validation cohorts. The model could also predict relapse and survival after HID HSCT. We established a comprehensive model that could predict EBV reactivation in HID HSCT recipients using ATG for GVHD prophylaxis.
Ultrasound-Guided Infraclavicular Axillary Vein Versus Internal Jugular Vein Cannulation in Critically Ill Mechanically Ventilated Patients: A Randomized Trial
Authors: Czarnik Tomasz , Czuczwar Miroslaw , Borys Michal , Chrzan Olimpia , Filipiak Kamil , Maj Magdalena , Marszalski Maciej , Miodonska Marta , Molsa Maciej , Pietka Marek , Piwoda Maciej , Piwowarczyk Pawel , Rogalska Zuzanna , Stachowicz Jakub , Gawda Ryszard
Published: December 2022

OBJECTIVES:

This clinical trial aimed to compare the ultrasound-guided in-plane infraclavicular cannulation of the axillary vein (AXV) and the ultrasound-guided out-of-plane cannulation of the internal jugular vein (IJV).

DESIGN:

A prospective, single-blinded, open label, parallel-group, randomized trial.

SETTING:

Two university-affiliated ICUs in Poland (Opole and Lublin).

PATIENTS:

Mechanically ventilated intensive care patients with clinical indications for central venous line placement.

INTERVENTIONS:

Patients were randomly assigned into two groups: the IJV group (n = 304) and AXV group (n = 306). The primary outcome was to compare the IJV group and AXV group through the venipuncture and catheterization success rates. Secondary outcomes were catheter tip malposition and early mechanical complication rates. All catheterizations were performed by advanced residents and consultants in anesthesiology and intensive care.

MEASUREMENTS AND MAIN RESULTS:

The IJV puncture rate was 100%, and the AXV was 99.7% (chi-square, p = 0.19). The catheterization success rate in the IJV group was 98.7% and 96.7% in the AXV group (chi-square, p = 0.11). The catheter tip malposition rate was 9.9% in the IJV group and 10.1% in the AXV group (chi-square, p = 0.67). The early mechanical complication rate in the IJV group was 3% (common carotid artery puncture—4 cases, perivascular hematoma—2 cases, vertebral artery puncture—1 case, pneumothorax—1 case) and 2.6% in the AXV group (axillary artery puncture—4 cases, perivascular hematoma—4 cases) (chi-square, p = 0.79).

CONCLUSIONS:

No difference was found between the real-time ultrasound-guided out-of-plane cannulation of the IJV and the infraclavicular real-time ultrasound-guided in-plane cannulation of the AXV. Both techniques are equally efficient and safe in mechanically ventilated critically ill patients.
Targeting cancer stem cell pathways for lung cancer therapy
Authors: Liu Mingxin , Wu Hong , Xu Chuan
Published: December 2022

Purpose of review

The unique properties of cancer stem cells (CSCs) make lung cancer untargetable for quite an extended period. The functional mechanism of this cell type has been illustrated step by step. However, the outcomes of lung cancer patients are still lower than expected clinically. The attempts made by scientists to make challenge history against stemness maintenance of lung cancer cells and their druggable targets are worth elucidating.

Recent findings

Many agents, including the Bispecific T-cell engager (BiTE) and AMG 119 targeting DLL3-positive cells, are a tremendous breakthrough in the preclinical and clinical treatment of SCLC. More studies focus on targeting CSCs to overcome TKI resistance in NSCLC. The combo targeting of CSC and the immune microenvironment can favor the treatment of lung cancer patients.

The current review elucidates the characteristics and related regulating pathways of lung CSCs from essential to preclinical research. We retrospectively introduce an update on the clinical development of therapeutics targeting CSC-associated developmental signaling pathways and discuss the opportunities to target CSC–immune interactions in lung cancer.
Hearing Outcome and Virologic Characteristics of Children With Congenital Cytomegalovirus Infection in Relation to Antiviral Therapy: A Retrospective Cohort Study
Authors: Venturini Elisabetta , Impagnatiello Luisa , Chiappini Elena , Galli Luisa
Published: December 2022

Background:

Congenital cytomegalovirus infection is one of the leading causes of nongenetic sensorineural hearing loss. The aim of our retrospective cohort study was to describe the changes in hearing in relation to antiviral therapy and the trend in viremia and viruria in children with congenital cytomegalovirus infection.

Methods:

In the present study, data were collected from infants treated with valganciclovir for 6 weeks or 6 months or untreated, seen between 2000 and 2021 at the Infectious Diseases Unit, Meyer Children’s University Hospital, Florence, Italy. Hearing deterioration was studied using Kaplan-Meier survival curves and risk factors for the outcome “deterioration” with Cox analysis.

Results:

Ninety-eight children were enrolled. Three children developed late hearing loss (2 children treated with valganciclovir for 6 weeks and 1 untreated). Kaplan-Meier survival curves of children treated for 6 weeks and 6 months overlapped until 36 months of life, after then 2 children of the 6-week group showed a worsening of hearing function (P = 0.609). Cox analysis did not show a significant impact of analyzed variables (group of therapy, viruria and viremia) on the outcome. The resolution of detectable viruria and viremia was significantly faster in the 6-month group (P = 0.011, <0.001, respectively).

Conclusions:

Our study is the first that reports audiological characteristics at follow-up after 24 months of life in treated and untreated children with congenital cytomegalovirus infection. In our population, 6 months therapy may prevent the development of late hearing loss, although the different regimens did not differ in influencing the progression of congenital deafness.
Asymptomatic Viral Presence in Early Life Precedes Recurrence of Respiratory Tract Infections
Authors: Zuurbier Roy P. , Bogaert Debby , de Steenhuijsen Piters Wouter A.A. , Arp Kayleigh , Chu Mei Ling J. N. , Sanders Elisabeth A. M. , van Houten Marlies A.
Published: December 2022

Background:

Respiratory tract infections (RTIs) in infants are often caused by viruses. Although respiratory syncytial virus (RSV), influenza virus and human metapneumovirus (hMPV) can be considered the most pathogenic viruses in children, rhinovirus (RV) is often found in asymptomatic infants as well. Little is known about the health consequences of viral presence, especially early in life. We aimed to examine the dynamics of (a)symptomatic viral presence and relate early viral detection to susceptibility to RTIs in infants.

Methods:

In a prospective birth cohort of 117 infants, we tested 1304 nasopharyngeal samples obtained from 11 consecutive regular sampling moments, and during acute RTIs across the first year of life for 17 respiratory viruses by quantitative PCR. Associations between viral presence, viral (sub)type, viral load, viral co-detection and symptoms were tested by generalized estimating equation (GEE) models.

Results:

RV was the most detected virus. RV was negatively associated [GEE: adjusted odds ratio (aOR) 0.41 (95% CI 0.18–0.92)], and hMPV, RSV, parainfluenza 2 and 4 and human coronavirus HKU1 were positively associated with an acute RTI. Asymptomatic RV in early life was, however, associated with increased susceptibility to and recurrence of RTIs later in the first year of life (Kaplan–Meier survival analysis: P = 0.022).

Conclusions:

Respiratory viruses, including the seasonal human coronaviruses, are often detected in infants, and are often asymptomatic. Early life RV presence is, though negatively associated with an acute RTI, associated with future susceptibility to and recurrence of RTIs. Further studies on potential ecologic or immunologic mechanisms are needed to understand these observations.
Chronic Active Epstein-Barr Virus Infection With Central Nervous System Involvement in Children: A Clinical Study of 22 Cases
Authors: Ou Wenxin , Zhao Yunze , Wei Ang , Ma Honghao , Zhang Liping , Lian Hongyun , Zhang Qing , Chen Sitong , Wang Dong , Li Zhigang , Wang Tianyou , Zhang Rui
Published: December 2022

Objective:

To analyze the clinical features, treatment, and prognosis of chronic active Epstein-Barr virus infection (CAEBV) with central nervous system (CNS) involvement in children.

Methods:

Patients with CAEBV admitted to Beijing Children’s Hospital, Capital Medical University, were enrolled in this study from January 2017 to December 2020. They were divided into a CNS group and a non-CNS group based on the presence of CNS involvement.

Results:

Twenty-two patients developed CNS disease, accounting for 23.9% (22/92) of CAEBV patients in the same period. Of these, only 2 of 22 patients presented initially with neurologic symptoms in the CNS group, and they all improved after treatment. Cerebrospinal fluid (CSF) examination demonstrated normal protein concentration and cell number in all patients with CNS involvement. Only 7 patients were positive for CSF EBV-DNA. Twenty-one patients had neuroimaging abnormalities, such as white matter signal abnormalities, encephalography or calcification. In the CNS group, 7 (31.8%) patients died, including 5 who died of active hemophagocytic lymphohistiocytosis, 1 died of unrelated causes, and 1 died of respiratory failure caused by pulmonary lymphoproliferative disease progression after transplantation. The 3-year overall survival was lower in the CNS group than in the non-CNS group (63.6% ± 11.9% versus 86.9% ± 4.1%, P = 0.027). Hemophagocytic lymphohistiocytosis (HLH) is an independent risk factor for CNS involvement in patients with CAEBV (OR = 2.946, 95% CI: 1.042–8.335, P = 0.042). Compared with the non-CNS group, blood EBV-DNA loads and CD4+/CD8+ ratio of T lymphocytes in the CNS group were higher (P < 0.001), while fibrinogen levels and natural killer (NK)-cell activity were lower (P = 0.047). Children with CAEBV were more likely to develop CNS diseases with low NK-cell activity (NK-cell activity < 14.00%, P = 0.023) or high alanine aminotransferase (ALT) levels (ALT levels > 40 U/L, P = 0.032).

Conclusion:

CAEBV with CNS involvement has nonspecific clinical manifestations, laboratory data, neuroimaging but has a worse prognosis. Blood fibrinogen levels and NK-cell activity in CAEBV children with CNS involvement are lower than in those without CNS involvement. In contrast, blood EBV-DNA loads and CD4+/CD8+ ratio of T lymphocytes are higher. Children with CAEBV who presented with HLH, NK-cell activity <14.00%, serum ALT >40 U/L and high-blood EBV-DNA loads are prone to develop CNS diseases.
Monoclonal Antibody and Antiviral Therapy for Mild-to-Moderate COVID-19 in Pediatric Patients
Authors: Vora Surabhi B. , Englund Janet A. , Trehan Indi , Waghmare Alpana , Kong Ada , Adler Amanda , Zerr Danielle M.
Published: December 2022

Multiple antiviral and monoclonal antibody therapies are now available for mild-moderate COVID-19 in high-risk patients ≥12 years of age. However, data for the use of these agents in children is limited. We reviewed 94 pediatric patients for whom early therapy was requested since the emergence of the Omicron variant and describe patient characteristics, treatment logistics and associated short-term events.
Infections in Pediatric Patients With Burn Injury: 6 Years of Experience
Authors: Karaaslan Ayşe , Çetin Ceren , Köle Mehmet Tolga , Dereli Murat , Demir Tekol Serap , Filinte Gaye , Akin Yasemin
Published: December 2022

Background:

This study aimed to determine the frequency of bloodstream and wound infections and their possible risk factors in hospitalized children with burn injury.

Methods:

We performed this retrospective descriptive study from 2015 to 2021. The study subjects consisted of all the pediatric patients hospitalized in the burn unit, from whom microorganisms were isolated either from blood or wound culture samples.

Results:

We detected a total of 142 microorganisms from 97 blood culture samples and 45 wound culture samples. Among the 115 patients, 44 (38.3%) were females and 71 (61.7%) were males, with a median age of 21 months (interquartile range: 14–39 months). Gram-positive bacteria were the most common causative agents of bloodstream infections in patients with burns (54.6%), followed by Gram-negative bacteria (32.9%) and fungi (12.3%). Gram-negative bacteria were the most common causative agent of wound infections (86.7%). Prolonged hospitalization positively correlated with the extent of the burn surface area (P: 0.031), degree of burn (P: 0.001), use of central venous catheter (P: 0.028), and intensive care unit stay (P: 0.044). Independent risk factors for Gram-negative bacteremia and Gram-negative wound infections were the extent of the burn surface area (P: 0.018), degree of burn (P: 0.024) and intensive care unit stay (P: 0.023). The independent risk factor for fungemia was prolonged hospitalization (P: 0.026).

Conclusions:

To reduce infections, minimizing invasive procedures using a multidisciplinary approach would be beneficial, especially in patients who have a large burn surface area and are expected to have a long hospital stay.
Serious Infusion Reactions in Two Adolescents Receiving Bebtelovimab
Authors: Peters Megan E. , Strayer Jill , Wald Ellen R.
Published: December 2022

There is scant literature available for pediatric prescribers regarding safety and efficacy of monoclonal antibody formulations against coronavirus disease 2019 (COVID-19). Here, we present 2 cases of serious infusion reactions in adolescent patients receiving the monoclonal antibody bebtelovimab and a succinct review of available antiviral medications for pediatric patients with mild or moderate COVID-19.
Bulging Anterior Fontanelle Caused by Severe Acute Respiratory Syndrome Coronavirus-2
Authors: Sethuraman Chidambaram , Holland Jonathon , Priego Gema , Khan Faizullah , Johnson Richard , Keane Morgan
Published: December 2022

Neurologic manifestations of the 2019 novel coronavirus disease in children are varied. We present the case of a 9-month-old child with bulging anterior fontanelle caused by severe acute respiratory syndrome coronavirus-2.
Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection in KwaZulu-Natal, South Africa
Authors: Chinniah Kogielambal , Bhimma Rajendra , Naidoo Kimesh Loganathan , Archary Moherndran , Jeena Prakash , Hoosen Ebrahim , Singh Shivani , Lawler Melissa , Naby Fathima , Masekela Refiloe
Published: December 2022

Background:

Multisystem inflammatory syndrome in children (MIS-C) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been infrequently described in Africa.

Objective:

To describe the clinical characteristics, outcomes and associations of severe disease in children hospitalized with MIS-C in KwaZulu-Natal.

Methods:

Retrospective multicenter study of children (0–13 years) who met the Centers for Disease Control and Prevention criteria for MIS-C. Children with shock were compared with children without shock to determine the characteristics of severe MIS-C.

Results:

Twenty-nine children with MIS-C were identified, the mean age was 55 (SD ±45) months, 25 (86%) were Black-African, and 8 (28%) had pre-existing comorbidities. The predominant presenting symptoms included fever 29 (100%), gastrointestinal symptoms 25 (83%), skin rash 19 (65%), and shock 17 (59%). Children with shock had significantly increased CRP (P = 0.01), ferritin (P < 0.001), troponin-T (P = 0.02), B-type natriuretic peptide (BNP) (P = 0.01), and lower platelets (P = 0.01). Acute kidney injury (P = 0.01), cardiac involvement (P = 0.02), and altered levels of consciousness (P = 0.03) were more common in children with shock. The median length of hospital stay was 11 (IQR 7–19) days, with a mortality of 20.6%. Children who did not survive had significantly higher ferritin levels 1593 (IQR 1069–1650) ng/mL versus 540 (IQR 181–1156) ng/mL; P = 0.03) and significantly more required mechanical ventilation (OR 18; confidence interval 1.7–191.5; P = 0.005).

Conclusions:

Hospitalized children with MIS-C in KwaZulu-Natal had more aggressive disease and higher mortality than children in better-resourced settings. Markedly elevated biomarkers and critical organ involvement were associated with severe disease. Risk factors for poor outcomes include higher ferritin levels and the need for mechanical ventilation.
The Safety and Efficacy of Dalbavancin and Active Comparator in Pediatric Patients With Acute Bacterial Skin and Skin Structure Infections
Authors: Giorgobiani Manana , Burroughs Margaret H. , Antadze Tinatin , Carrothers Timothy J. , Riccobene Todd A. , Patel Rinal , Lin Tao , Stefanova Penka
Published: December 2022

Background:

Acute bacterial skin and skin structure infections (ABSSSIs) are a significant source of morbidity in children. Dalbavancin, approved for the treatment of adults and children with ABSSSI, has a well-established safety profile in adults. We report safety and descriptive efficacy data for the treatment of ABSSSI in children.

Methods:

Children with ABSSSI (birth–<18 years old) or sepsis (<3 months old) known/suspected to be caused by susceptible Gram-positive organisms were enrolled in this phase 3, multicenter, open-label, comparator-controlled study (NCT02814916). Children ≥3 months old were randomized 3:3:1 to receive single-dose dalbavancin, 2-dose dalbavancin, or a comparator antibiotic in 4 age cohorts; those <3 months old received single-dose dalbavancin. Clinical response and microbiologic efficacy were evaluated 48–72 hours and 14, 28 and 54 days posttreatment. Bowel flora testing and audiology were collected in a subset of patients at baseline and day 28. Adverse events (AEs) were collected throughout the study.

Results:

Treatment-emergent AEs occurred in 7.2%, 9.0% and 3.3% of patients in dalbavancin single-dose, dalbavancin 2-dose and comparator arms, respectively. Three serious AEs occurred in the dalbavancin single-dose arm; no treatment-related AEs, serious AEs, or AEs leading to study discontinuation were reported. Favorable clinical response at 48–72 hours was documented in 97.4%, 98.6% and 89.7% of patients. Safety and efficacy were comparable across age cohorts. The microbiologic intent-to-treat population had comparable clinical response for all baseline pathogens, including methicillin-resistant Staphylococcus aureus.

Conclusion:

The safety profile of dalbavancin was consistent in children and adults with ABSSSI. No new safety signals were identified.
Addressing health equity through a telehealth maternal–newborn home visit for nurse practitioner students
Authors: Doucette Julianne A. , Rousseau Jennifer , Vondracek Hugh
Published: December 2022

This educational innovation describes the implementation and evaluation of a telehealth maternal–newborn home visit clinical experience for nurse practitioner students at an urban, private research university in the Midwest. The visits were conducted using the Family Connects evidence-based universal support program for families with newborns to evaluate each family's unique risks and to align their needs with available community resources. Students were prepared for the clinical experience through advanced practice didactic modules and simulation and then participated in the visits over a 2-week period. After the clinical opportunity, both students and community health nurse collaborators completed a survey about their experiences. The students reported feeling prepared to participate in the visits, that they were able to meet clinical objectives using telehealth, and learned about the community resources available for families with newborns. The nurses reported feeling prepared to collaborate with nurse practitioner students and that they benefitted from having a student participate in the visits. The experience prepared the students to meet the needs of a diverse patient population during the early postpartum/newborn period by providing newborn care advice, addressing access to health, assessing social determinants of health, and considering community resource referrals to reduce disparities and improve health equity. This article describes how a telehealth clinical experience addresses the American Association of Colleges of Nursing Essentials for advanced-level nursing students and provides recommendations for incorporating and evaluating telehealth clinical experiences in pediatric advanced practice education.
Patient Falls in Seclusion Rooms in Psychiatric Inpatient Care
Authors: Varpula Jaakko , Välimäki Maritta , Pulkkinen Johanna , Lantta Tella
Published: December 2022

Background:

Patient falls are a major adverse event in psychiatric inpatient care.

Purpose:

To model the risk for patient falls in seclusion rooms in psychiatric inpatient care.

Methods:

Sociotechnical probabilistic risk assessment (ST-PRA) was used to model the risk for falls. Data sources were the research team, literature review, and exploration groups of psychiatric nurses. Data were analyzed with fault tree analysis.

Results:

The risk for a patient fall in a seclusion room was 1.8%. Critical paths included diagnosis of a psychiatric disorder, the mechanism of falls, failure to assess and prevent falls, and psychological or physical reason. The most significant individual risk factor for falls was diagnosis of schizophrenia.

Conclusions:

Falls that occur in seclusion events are associated with physical and psychological risk factors. Therefore, risk assessment methods and fall prevention interventions considering patient behavioral disturbance and physiological risk factors in seclusion are warranted.
Nursing Home Patient Safety Culture Perceptions Among Licensed Practical Nurses
Authors: Weaver Susan H. , de Cordova Pamela B. , Ravichandran Arun , Cadmus Edna
Published: December 2022

Background:

Licensed practical nurses (LPNs) working in nursing homes are the primary licensed nurses providing care and ensuring patient safety in New Jersey. As such, it is important to understand LPNs' perception of patient safety culture (PSC) and job satisfaction, which may impact resident safety.

Purpose:

To describe the relationship between LPNs' perception of PSC in nursing homes and job satisfaction.

Methods:

A cross-sectional study design was used to survey LPNs in New Jersey.

Results:

LPNs working in nursing homes were less satisfied than LPNs working in other settings, and their perception of PSC was lower than that in 2019 national data report.

Conclusion:

LPNs in nursing homes indicated that PSC needs improvement. Now is an opportune time to implement initiatives to foster a culture of safety in nursing homes.
Carbonic Anhydrase IX (CAIX) Expressing Hypoxic Micro-environment Hampers CD8+ Immune Cell Infiltrate in Breast Carcinoma
Authors: Juhász Péter , Hasulyó Dóra , Bedekovics Judit , Beke Lívia , Kacsala Norbert , Török Miklós , Méhes Gábor
Published: December 2022

Background:

Hypoxia and necrosis are common features of invasive cancer. The dynamic upregulation of carbonic anhydrase IX (CAIX), triggered by hypoxia-inducible factor 1 (HIF-1) is 1 of the mechanisms supporting cellular adaptation to hypoxia in solid tumors, including breast carcinoma. CAIX activity results in extracellular acidosis and in a profound reorganization of the tumor micro-environment, influencing biological behavior and prognosis. The main focus of our study was to evaluate the mass and distribution of the immune infiltrate, more specifically of CD8+ effector T-cells, in relation with tumoral CAIX expression.

Materials and Methods:

Formalin-fixed and paraffin-embedded breast carcinoma sections were analyzed following double immunohistochemical staining for CAIX and CD8. Scanned digital slides were evaluated for both labelings, and CD8-related signal was determined within and outside CAIX-positive tumor areas using the HistoQuant (3DHistech) image analysis software. Statistical analysis was performed using GraphPad Prism software.

Results:

Of the 34 breast carcinomas, 18 tested partially positive for CAIX. The remaining 16 cases were used as the CAIX-negative control group. Necrotic foci were generally associated with CAIX overexpression, and tumors exhibiting signs of necrosis had a significantly higher rate of relative CAIX expression compared with samples without necrosis (11.47±5.505 vs. without necrosis 3.765±3.5 P-value=0.0216). On the other hand, no statistically significant difference was found when comparing relative CD8+ lymphocyte counts in cases with necrosis as opposed to those where necrosis was absent (134.7±55.7 vs. 97.70±57.25; P value=0.1579). No difference in gross CD8+ T-lymphocyte infiltrate could be measured between CAIX positive and negative samples (98.48±37.32 vs. 95.99±50 P value=0.5928). However, in CAIX-expressing tumors a statistical correlation between the CD8+ T-lymphocyte infiltrate and the extent of CAIX-positive areas was observed. Within the same tumor, CD8+ T-lymphocyte counts showed a significant difference betweeen CAIX+ and CAIX- areas (13.06±9.4 vs. 135.6±62.2 P value <0.0001).

Conclusion:

Our measurements demonstrate for the first time that tumor areas with CAIX expression potentially hamper CD8+ T-lymphocyte infiltration in breast carcinoma. The hypoxia-driven adaptive micro-environment likely interferes with the specific response to biological and immune therapies requiring intact effector T-cell response.
Real-time Lung Weight Measurement During Cellular Ex Vivo Lung Perfusion: An Early Predictor of Transplant Suitability
Authors: Kosaka Ryo , Sakota Daisuke , Sakanoue Ichiro , Niikawa Hiromichi , Ohuchi Katsuhiro , Arai Hirokuni , McCurry Kenneth R. , Okamoto Toshihiro
Published: December 2022

Background.

Increased extravascular lung water during ex vivo lung perfusion (EVLP) is associated with ischemia reperfusion injury and poor pulmonary function. A non-invasive technique for evaluating extravascular lung water during EVLP is desired to assess the transplant suitability of lungs. We investigated real-time lung weight measurements as a reliable method for assessing pulmonary functions in cellular EVLP using a porcine lung model.

Methods.

Fifteen pigs were randomly divided into 3 groups: control (no warm ischemia) or donation after circulatory death groups with 60 or 90 min of warm ischemia (n = 5, each). Real-time lung weight gain was measured by load cells positioned at the bottom of the organ chamber.

Results.

Real-time lung weight gain at 2 h was significantly correlated with lung weight gain as measured on a back table (R = 0.979, P < 0.01). Lung weight gain in non-suitable cases (n = 6) was significantly higher than in suitable cases (n = 9) at 40 min (51.6 ± 46.0 versus −8.8 ± 25.7 g; P < 0.01, cutoff = +12 g, area under the curve = 0.907). Lung weight gain at 40 min was significantly correlated with PaO2/FiO2, peak inspiratory pressure, shunt ratio, wet/dry ratio, and transplant suitability at 2 h (P < 0.05, each). In non-suitable cases, lung weight gain at 66% and 100% of cardiac output was significantly higher than at 33% (P < 0.05).

Conclusions.

Real-time lung weight measurement could potentially be an early predictor of pulmonary function in cellular EVLP.
Ultrastructural and kinetic evidence support that thick filaments slide through the Z-disc
Authors: Tomalka André , Heim Maximilian , Klotz Annika , Rode Christian , Siebert Tobias
Published: December 2022

How myofilaments operate at short mammalian skeletal muscle lengths is unknown. A common assumption is that thick (myosin-containing) filaments get compressed at the Z-disc. We provide ultrastructural evidence of sarcomeres contracting down to 0.44 µm—approximately a quarter of thick filament resting length—in long-lasting contractions while apparently keeping a regular, parallel thick filament arrangement. Sarcomeres produced force at such extremely short lengths. Furthermore, sarcomeres adopted a bimodal length distribution with both modes below lengths where sarcomeres are expected to generate force in classic force–length measurements. Mammalian fibres did not restore resting length but remained short after deactivation, as previously reported for amphibian fibres, and showed increased forces during passive re-elongation. These findings are incompatible with viscoelastic thick filament compression but agree with predictions of a model incorporating thick filament sliding through the Z-disc. This more coherent picture of mechanical mammalian skeletal fibre functioning opens new perspectives on muscle physiology.
Spatial scales of competition and a growth–motility trade-off interact to determine bacterial coexistence
Authors: Kuhn Thierry , Mamin Marine , Bindschedler Saskia , Bshary Redouan , Estoppey Aislinn , Gonzalez Diego , Palmieri Fabio , Junier Pilar , Richter Xiang-Yi Li
Published: December 2022

The coexistence of competing species is a long-lasting puzzle in evolutionary ecology research. Despite abundant experimental evidence showing that the opportunity for coexistence decreases as niche overlap increases between species, bacterial species and strains competing for the same resources are commonly found across diverse spatially heterogeneous habitats. We thus hypothesized that the spatial scale of competition may play a key role in determining bacterial coexistence, and interact with other mechanisms that promote coexistence, including a growth–motility trade-off. To test this hypothesis, we let twoPseudomonas putidastrains compete at local and regional scales by inoculating them either in a mixed droplet or in separate droplets in the same Petri dish, respectively. We also created conditions that allow the bacterial strains to disperse across abiotic or fungal hyphae networks. We found that competition at the local scale led to competitive exclusion while regional competition promoted coexistence. When competing in the presence of dispersal networks, the growth–motility trade-off promoted coexistence only when the strains were inoculated in separate droplets. Our results provide a mechanism by which existing laboratory data suggesting competitive exclusion at a local scale is reconciled with the widespread coexistence of competing bacterial strains in complex natural environments with dispersal.
A space of goals: the cognitive geometry of informationally bounded agents
Authors: Archer Karen , Catenacci Volpi Nicola , Bröker Franziska , Polani Daniel
Published: December 2022

Traditionally, Euclidean geometry is treated by scientists as
a priori
and objective. However, when we take the position of an agent, the problem of selecting a best route should also factor in the abilities of the agent, its embodiment and particularly its cognitive effort. In this paper, we consider geometry in terms of travel between states within a world by incorporating information processing costs with the appropriate spatial distances. This induces a geometry that increasingly differs from the original geometry of the given world as information costs become increasingly important. We visualize this
‘cognitive geometry’
by projecting it onto two- and three-dimensional spaces showing distinct distortions reflecting the emergence of epistemic and information-saving strategies as well as pivot states. The analogies between traditional cost-based geometries and those induced by additional informational costs invite a generalization of the notion of geodesics as cheapest routes towards the notion of
infodesics
. In this perspective, the concept of infodesics is inspired by the property of geodesics that, travelling from a given start location to a given goal location along a geodesic, not only the goal, but all points along the way are visited at optimal cost from the start.
Predator discrimination of prey promotes the predator-mediated coexistence of prey species
Authors: Iwashita Gen , Yamawo Akira , Kondoh Michio
Published: December 2022

The predator discrimination of prey can affect predation intensity and the prey density dependence of predators, which has the potential to alter the coexistence of prey species. We used a predator–prey population dynamics model accounting for the predator's adaptive diet choice and predator discrimination of prey to investigate how the latter influences prey coexistence. The model revealed that (i) prey species that are perceived as belonging to the same species by a predator are attacked in the same manner, and it is more difficult for them to coexist than those that are recognized as different prey species, and (ii) prey species that are not discriminated by a predator—and therefore cannot coexist—may coexist in the presence of an alternative predator that does discriminate between them. These results suggest that prey diversity, which favours the predator discrimination of prey, and the different capabilities of predators to identify prey species both enhance prey coexistence.
Investigation of the photoluminescent properties, scintillation behaviour and toxicological profile of various magnesium tungstate nanoscale motifs
Authors: Hurley Nathaniel , Srinivas Sailesh , Fang Justin , Sun Manli , Hong Simon , Chien Chia Te , Guo Alan , Khan Tamor A. , Li Mingxing , Cotlet Mircea , Moretti Federico , Bourret Edith , Radin Daniel , Tsirka Stella E. , Shelly Maya , Wong Stanislaus S.
Published: December 2022

We have synthesized several morphologies and crystal structures of MgWO
4
using a one-pot hydrothermal method, producing not only monoclinic stars and large nanoparticles but also triclinic wool balls and sub-10 nm nanoparticles. Herein we describe the importance of reaction parameters in demonstrating morphology control of as-prepared MgWO
4
. Moreover, we correlate structure and composition with the resulting photoluminescence and radioluminescence properties. Specifically, triclinic-phase samples yielded a photoluminescence emission of 421 nm, whereas monoclinic-phase materials gave rise to an emission maximum of 515 nm. The corresponding radioluminescence data were characterized by a broad emission peak, located at 500 nm for all samples. Annealing the wool balls and sub-10 nm particles to transform the crystal structure from a triclinic to a monoclinic phase yielded a radioluminescence (RL) emission signal that was two orders of magnitude greater than that of their unannealed counterparts. Finally, to confirm the practical utility of these materials for biomedical applications, a series of sub-10 nm particles, including as-prepared and annealed samples, were functionalized with biocompatible PEG molecules, and subsequently were found to be readily taken up by various cell lines as well as primary cultured hippocampal neurons with low levels of toxicity, thereby highlighting for the first time the potential of this particular class of metal oxides as viable and readily generated platforms for a range of biomedical applications.
Multistability, symmetry and geometric conservation in eightfold waterbomb origami
Authors: Grasinger Matthew , Gillman Andrew , Buskohl Philip R.
Published: December 2022

The nonlinearities inherent in the mechanics of origami make it a rich design space for multistable structures and mechanical metamaterials. Here, we investigate the multistability of a classic origami base: the symmetric eightfold waterbomb. We prove that the waterbomb is bistable for certain crease properties, and derive bounds on, and closed-form approximations of, its stable states. We introduce a simplified form of the waterbomb kinematics and present a design procedure for tuning the depth and the symmetry/asymmetry of its energy wells. By incorporating the concept of pretensioned torsional springs, we also demonstrate the existence of tristable cases for the waterbomb fold pattern. We then apply the analysis of a single waterbomb to study quasi-one-dimensional arrays of waterbombs, where we discover a conserved geometric-kinematic quantity in which the number of popped-up and popped-down vertices is determined uniquely through analysis of the origami structure’s boundaries. This culminates with a discussion of how the quasi-one-dimensional array may be designed to achieve stable states with various degeneracies, kinematics and gaps between energy levels. Collectively, this work presents an alternative approach for characterizing origami multistability properties and reveals an origami design motif that has potential applications in physically reconfigurable structures, mechanical energy absorption and metamaterials.