bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging strategies for antibody-mediated rejection
Authors: Malvezzi Paolo 
Published: August 2022

Purpose of the review
Antibody-mediated rejection (AMR) is the leading cause of kidney graft loss. Very few treatment options are available to the clinician to counter this disease process. In this review we describe the available therapeutics and the novel approaches that are being currently developed.

Recent findings
AMR treatment requires a multidrug approach. Imlifidase, a new immunoglobulin G cleaving agent, may prove to be the perfect replacement of apheresis. New complement blockers other than eculizumab are in development in order to block acute kidney damage in the delicate phase following antibody removal. Plasma cell depletion is being explored in chronic AMR: studies are in progress with daratumumab and felzartamab. Interleukin 6 inhibition is generating enthusiasm in the chronic setting with preliminary encouraging results.

Summary
In acute AMR, the clinicians will have to remove the antibodies, avoid rebound and block specific damage effectors. In chronic AMR they will need to reduce the inflammatory response induced by donor specific antibodies. New drugs are available and transplant physicians are starting to develop effective multidrug strategies to counter the complex disease mechanisms. Safety of these drugs needs to be further explored especially when used together with other potent immunosuppressive drugs.
Study Protocol
Authors: Klingman Karen J. , Skufca Joseph D. , Duncan Pamela W. , Wang Dongliang , Fulk George D. 
Published: August 2022

Background
A range of sleep disturbances and disorders are problematic in people after stroke; they interfere with recovery of function during poststroke rehabilitation. However, studies to date have focused primarily on the effects of one sleep disorder—obstructive sleep apnea (OSA)—on stroke recovery.

Objectives
The study protocol for the SLEep Effects on Poststroke Rehabilitation (SLEEPR) Study is presented with aims of characterizing proportion of non-OSA sleep disorders in the first 90 days after stroke, evaluating the effect of non-OSA sleep disorders on poststroke recovery, and exploring the complex relationships between stroke, sleep, and recovery in the community setting.

Methods
SLEEPR is a prospective cohort observational study across multiple study sites following individuals from inpatient rehabilitation through 90 days poststroke, with three measurement time points (inpatient rehabilitation; i.e., ~15 days poststroke, 60 days poststroke, and 90 days poststroke). Measures of sleep, function, activity, cognition, emotion, disability, and participation will be obtained for 200 people without OSA at the study’s start through self-report, capacity assessments, and performance measures. Key measures of sleep include wrist actigraphy, sleep diaries, overnight oximetry, and several sleep disorders screening questionnaires (Insomnia Severity Index, Cambridge-Hopkins Restless Legs Questionnaire, Epworth Sleepiness Scale, and Sleep Disorders Screening Checklist). Key measures of function and capacity include the 10-meter walk test, Stroke Impact Scale, Barthel index, and modified Rankin scale. Key performance measures include leg accelerometry (e.g., steps/day, sedentary time, upright time, and sit-to-stand transitions) and community trips via GPS data and activity logs.

Discussion
The results of this study will contribute to understanding the complex interplay between non-OSA sleep disorders and poststroke rehabilitation; they provide insight regarding barriers to participation in the community and return to normal activities after stroke. Such results could lead to strategies for developing new stroke recovery interventions.
Sociodemographic Factors Associated With Gonorrhea and Chlamydia Infection in Pregnancy
Authors: Gulersen Moti , Lenchner Erez , Eliner Yael , Grunebaum Amos , Chervenak Frank A. , Bornstein Eran 
Published: August 2022

Background
We explored the impact of maternal sociodemographic parameters on the prevalence of chlamydial and gonorrheal infection in pregnancy in a large United States population of live births.

Methods
Retrospective analysis of the Centers for Disease Control and Prevention Natality Live Birth database (2016–2019). We compared pregnancies complicated by maternal infection with either gonorrhea or chlamydia to those without gonorrheal or chlamydial infection, separately. Both analyses included assessment of multiple maternal sociodemographic factors, which were compared between the 2 groups. Multivariable logistic regression was performed to evaluate the association of these factors with gonorrheal or chlamydial infection in pregnancy.

Results
Of the 15,341,868 included live births, 45,639 (0.30%) were from patients who had gonorrheal infection, and 282,065 (1.84%) were from patients who had chlamydial infection during pregnancy. Concurrent infection with chlamydia and gonorrhea was associated with the highest risk of gonorrhea and chalmydia in pregnancy (adjusted odds ratio, 26.28; 95% confidence interval, 25.74–26.83, and adjusted odds ratio, 26.03; 95% confidence interval, 25.50–26.58, respectively). Young maternal age, low educational attainment, non-Hispanic Black race/ethnicity, concurrent infection with syphilis, and tobacco use were also associated with a substantial increase in the risk of gonorrheal and chlamydial infection in pregnancy.

Conclusions
Several sociodemographic factors including young maternal age, low educational attainment, Medicaid insurance, and non-Hispanic Black race/ethnicity, are associated with a marked increase in the risk for gonorrheal and chlamydial infection in current US pregnancies. These data may be used to better screen, educate, and treat pregnancies of vulnerable populations at risk for such infections.
Intravenous Smart Pumps at the Point of Care: A Descriptive, Observational Study
Authors: Giuliano Karen K. , Blake Jeannine W.C. , Bittner Nancy Phoenix , Gamez Vicki , Butterfield Robert 
Published: August 2022

Objective
This study was conducted to advance understanding of intravenous (IV) smart pump medication administration practices using the Baxter Spectrum IQ. The primary objective was to observe adherence with manufacturer required IV smart pump system setup at the point of care during actual clinical use.

Methods
The study was conducted in a 285-bed acute care community hospital near Boston, Massachusetts. The study design was observational and noninterventional, and all data were collected by a single observer. Observations included measurement and documentation of adherence with the Baxter Spectrum IQ system setup requirements.

Results
A total of 200 primary and secondary IV medication administration observations were included: 101 in critical care and 99 in medical-surgical. Overall adherence was found to be: 6.5% with IV smart pump position relative to the patient (aim 1); 6.5% with required position of the primary infusion bag (aim 2); and 69.5% adherence with required position of the secondary medication infusion bag (aim 3). Additional exploratory data were also collected.

Conclusions
These results add to the emerging body of knowledge, which support that adherence to required system setup for head-height dependent IV smart pumps is low and difficult to achieve during actual clinical use. Consideration of alternative human factors–designed technology to replace the current manual setup requirements is needed to improve the process of acute care IV medication administration in this very important area of patient safety.
Enhancing the use of pain assessment at emergency department: a best practice implementation project
Authors: Ubierna-Prieto Joana Aintzane , Ballesteros-Peña Sendoa , Casbas Mayte Moreno , Klugarová Jitka , Klugar Miloslav 
Published: August 2022

ABSTRACT

Objectives:
The main aim of the best practice implementation project was to enhance the use of pain assessment and the compliance with evidence-based criteria regarding pain assessment among incoming patients to emergency department.

Introduction:
Adequate approaches to pain assessment and documentation have been demonstrated beneficial for emergency department patients. Evidence-based recommendations establish a focus on education about the implications for evaluating and recording pain in order to improve outcome strategies and quality of care.

Methods:
The implementation project was undertaken in the emergency department following JBI Implementation framework in order to seek whether pain assessment was taken and registered as per protocols. Random selection for 100 anonymized emergency department admission episodes, which had to meet the specified inclusion criteria, was carried out.

Results:
The baseline audit showed low compliance in criterion 3 (C3) ‘Pain was documented in each assessment’ (6%), C4 ‘Pain was assessed after treatment’ (9%) and C5 ‘Pain was assessed prior to discharge’ (10%). In the follow-up audit, noticeable improvement was shown for four of the criteria; C3 (14%), C4 (22%) and for C5 (41%). C1 ‘Pain was assessed in a timely manner’ improved from 81% up to 95%. C2 ‘Use of a validated scoring tool’ had a compliance of 100% as the hospital's assessing system default has NRS-11 scale set up.

Conclusion:
We performed an audit of pain assessment documentation. Enhancing the use of pain assessment among emergency department nurses by means of specific training emphasizing the importance of documentation showed a positive impact on practice. Follow-up audit results justify the continuity of the implemented strategies.
Centuries of genome instability and evolution in soft-shell clam transmissible cancer
Authors: Hart Samuel F.M. , Yonemitsu Marisa A. , Giersch Rachael M. , Beal Brian F. , Arriagada Gloria , Davis Brian W. , Ostrander Elaine A. , Goff Stephen P. , Metzger Michael J. 
Published: August 2022

ABSTRACTTransmissible cancers are infectious parasitic clones of malignant cells that metastasize to new hosts, living past the death of the founder animal in which the cancer initiated. Several lineages of transmissible cancer have recently been identified in bivalves, including one that has spread through the soft-shell clam (Mya arenaria) population along the east coast of North America. To investigate the evolutionary history of this transmissible cancer lineage, we assembled a highly contiguous 1.2 Gb soft-shell clam reference genome and characterized somatic mutations from cancer sequences. We show that all cancer cases observed descend from a single founder and cluster into two geographically distinct sub-lineages. We discover a previously unreported clock-like mutational signature that predicts the cancer lineage to be 344 to 877 years old, indicating that it spread undetected long before it was first observed in the 1970s. We observe high mutation density, widespread copy number gain, structural rearrangement, loss of heterozygosity, variable telomere lengths, mitochondrial genome expansion, and transposable element activity, all indicative of an unstable cancer genome. Our study reveals the ability for an invertebrate cancer lineage to survive for centuries while its genome continues to structurally mutate, likely contributing to the ability of this lineage to adapt as a parasitic cancer.SUMMARYThe genome of a contagious cancer in clams reveals structural instability of multiple types throughout the ∼500 years since its origin.
State and trait dimensions of subjective memory concerns: Genetic influences across 30 years
Authors: Bell Tyler , Beck Asad , Gillespie Nathan , Reynolds Chandra , Williams McKenna E. , Gustavson Daniel E. , Lyons Michael J. , Neale Michael , Kremen William S. , Franz Carol E. 
Published: August 2022

AbstractINTRODUCTIONGenetic influences on the stability of subjective memory concerns (SMC) may confound its interpretation as a state-related risk indicator.METHODSWe estimated genetic influences on SMC and SMC change from average ages 38 to 67, genetic correlations of SMC with memory and depressive symptoms at average ages 56, 62, and 67, and correlations of SMC with polygenic scores for Alzheimer’s disease and neuroticism, APOE genotype, and parental history or dementia.RESULTSSMC was highly stable over this 30-year period. Heritability was .51. Phenotypically and genetically, SMC was more strongly related to depressive symptoms than to objective memory. It was also correlated with parental history of dementia and polygenic risk for neuroticism.DISCUSSIONSMC’s heritability and stability indicate a substantial trait-like component that is related more to depression and personality than objective memory. Improving it as an indicator of impending cognitive decline or dementia will require isolating its state-related component.
Fibrillarin-1 and Fibrillarin-2 are required for divergent cell lineage development in planarian homeostasis and regeneration
Authors: Chen Jiajia , Pan Xue , Xu Hao , Zhang Yuhong , Lei Kai 
Published: August 2022

AbstractRibosome heterogeneity has been revealed to exist in different cell types during development. However, the function and regulatory mechanisms of ribosome heterogeneity in missing tissue regeneration have yet to be reported. We used the planarian Schmidtea mediterranea with whole-body regenerative capability as a model and revealed the function of the rRNA modification protein fibrillarin in cell lineage development and tissue regeneration. We identified two fibrillarin homologs in planarian, Smed-fbl-1 (fbl-1) and Smed-fbl-2 (fbl-2), with distinct expression patterns. While fbl-2 regulates stem cell proliferation and multiple progenitor cell differentiation, fbl-1 participates in epidermal lineage late-stage specification and wound response. This study indicates that fibrillarin, a nucleolar protein, can respond to wounds and function in distinct cell types, suggesting the existence and critical roles of ribosome heterogeneity in stem cells and tissue regeneration.
A comparative analysis of the ontogeny of syngnathids (pipefishes & seahorses) reveals how heterochrony contributed to their diversification
Authors: Schneider Ralf Friedrich , Woltering Joost Marten , Adriaens Dominique , Roth Olivia 
Published: August 2022

AbstractBackgroundSyngnathids are a highly derived and diverse fish clade comprising the pipefishes, pipe-horses and seahorses. They are characterized by a plethora of iconic traits that increasingly capture the attention of biologists, including geneticists, ecologists and developmental biologists. The current understanding of the origins of their derived body plan is, however, hampered by incomplete and limited descriptions of the early syngnathid ontogeny.ResultsWe provide a comprehensive description of the development of Nerophis ophidion, Syngnathus typhle, Hippocampus erectus from early cleavage stages to release from the male brooding organ and beyond, including juvenile development. We comparatively describe skeletogenesis with a particular focus on dermal bony plates, the snout-like jaw morphology, and appendages.ConclusionsThis most comprehensive and detailed account of syngnathid development to date suggests that convergent phenotypes (e.g. reduction and loss of the caudal fins), likely arose by distinct ontogenetic means in pipefish and seahorses. Comparison of the ontogenetic trajectories of S. typhle and H. erectus provides indications that characteristic features of the seahorse body plan result from developmental truncation. Altogether this work provides a valuable resource and framework for future research to understand the evolution of the outlandish syngnathid morphology from a developmental perspective.Bullet pointsSyngnathids (pipefish, pipe-horses and seahorses) are a highly derived and diverse fish taxon and many of their most iconic traits – and these traits’ variation across species - develop during their early ontogeny.This study provides a detailed description and staging table of the entire pre-release development (and beyond) of three distinct syngnathids (two phylogenetically distinct pipefishes and a seahorse) with a focus on the skeletal elements forming the cranium, axial skeleton, appendages and the plate armor.The data provided in this study suggests that developmental heterochrony, i.e. alterations in the rate and timing of developmental processes between lineages, might be a central evolutionary process shaping the morphological diversity found in syngnathids today.
In vivo reduction of age-dependent neuromelanin accumulation mitigates features of Parkinson’s disease
Authors: Gonzalez-Sepulveda Marta , Compte Joan , Cuadros Thais , Nicolau Alba , Guillard-Sirieix Camille , Peñuelas Núria , Lorente-Picon Marina , Parent Annabelle , Romero-Giménez Jordi , Cladera-Sastre Joana M. , Laguna Ariadna , Vila Miquel 
Published: August 2022

AbstractHumans accumulate with age the dark-brown pigment neuromelanin inside specific neuronal groups. Neurons with the highest neuromelanin levels are particularly susceptible to degeneration in Parkinson’s disease, especially dopaminergic neurons of the substantia nigra (SN), the loss of which leads to characteristic motor Parkinson’s disease symptoms. In contrast to humans, neuromelanin does not appear spontaneously in most animals, including rodents, and Parkinson’s disease is an exclusively human condition. Using humanized neuromelanin-producing rodents, we recently found that neuromelanin can trigger Parkinson’s disease pathology when accumulated above a specific pathogenic threshold.Here, by taking advantage of this newly developed animal model, we assessed whether the intracellular buildup of neuromelanin that occurs with age can be slowed down in vivo to prevent or attenuate Parkinson’s disease. Because neuromelanin derives from the oxidation of free cytosolic dopamine, we enhanced dopamine vesicular encapsulation in the SN of neuromelanin-producing rats by viral vector-mediated overexpression of vesicular monoamine transporter 2 (VMAT2). This strategy reduced the formation of potentially toxic oxidized dopamine species that can convert into neuromelanin and maintained intracellular neuromelanin levels below their pathogenic threshold. Decreased neuromelanin production was associated with an attenuation of Lewy body-like inclusion formation and a long-term preservation of dopamine homeostasis, nigrostriatal neuronal integrity and motor function in these animals.Our results demonstrate the feasibility and therapeutic potential of modulating age-dependent intracellular neuromelanin production in vivo, thereby opening an unexplored path for the treatment of Parkinson’s disease and, in a broader sense, brain aging.
Pattern Of Some Inflammatory Mediators Among Adult Patients With Bronchial Asthma On Corticosteroids Attending Aminu Kano Teaching Hospital, Kano, Nigeria
Authors: Saidu H , Ismail M , Lawal U , Mannir H , Gwarzo MY , Rogo LD , Ibrahim A , Garba N , Danladi SB , Aliyu IA , Bala JA , Yahya IS 
Published: August 2022

AbstractBackgroundBronchial asthma in adults is typified by lingering allergic inflammation associated with elevation in the levels of certain acute phase reactants and indicators of mast cell activation. This study investigated the effect of corticosteroid treatment on the levels of C reactive protein (CRP), serum baseline tryptase (sBT), erythrocyte sedimentation rate (ESR) and granulocyte monocyte colony stimulating factor (GM-CSF) among asthmatics.MethodForty five adult patients with bronchial asthma on treatment with inhaled corticosteroids were enrolled. Forty five blood donors were used as control. Serum levels of CRP, sBT, ESR and GM-CSF were measured using sandwich ELISA.ResultThe GM-CSF, CRP, ESR and sBT were significantly elevated among asthmatics on treatment compared to normal healthy control. Significant difference in the level of GM-CSF, ESR and CRP was observed between asthmatics with mild and moderate disease severity.ConclusionTreatment with inhaled corticosteroids doesn’t restore the levels of GM-CSF, CRP, sBT and ESR to normalcy among asthmatics.
Developmental exposure to domoic acid targets reticulospinal neurons and leads to aberrant myelination in the spinal cord
Authors: Panlilio Jennifer M. , Hammar Katherine M. , Aluru Neelakanteswar , Hahn Mark E. 
Published: August 2022

ABSTRACTHarmful algal blooms (HABs) produce neurotoxins that affect human health. Developmental exposure of zebrafish embryos to the HAB toxin domoic acid (DomA) causes myelin defects, loss of reticulospinal neurons, and behavioral deficits. However, it is unclear whether DomA primarily targets myelin sheaths, leading to the loss of reticulospinal neurons, or reticulospinal neurons, causing myelin defects. Here, we show that while exposure to DomA at 2 dpf did not reduce the number of oligodendrocyte precursors prior to myelination, it led to fewer myelinating oligodendrocytes that produced shorter myelin sheaths and aberrantly wrapped neuron cell bodies. DomA-exposed larvae lacked Mauthner neurons prior to the onset of myelination, suggesting that axonal loss is not secondary to myelin defects. The loss of the axonal targets may have led oligodendrocytes to inappropriately myelinate neuronal cell bodies. Consistent with this, GANT61, which reduces oligodendrocyte number, caused a reduction in aberrantly myelinated neuron cell bodies in DomA-exposed fish. Together, these results suggest that DomA initially alters reticulospinal neurons and the loss of axons causes aberrant myelination of nearby cell bodies. The identification of initial targets and perturbed cellular processes provides a mechanistic understanding of how DomA alters neurodevelopment, leading to structural and behavioral phenotypes.
Steroidal glycoalkaloids contribute to anthracnose resistance in Solanum lycopersicum
Authors: Fabian Matthew L. , Zhang Chong , Sun Jianghao , Price Neil P. , Chen Pei , Clarke Christopher R. , Jones Richard W. , Stommel John R. 
Published: August 2022

AbstractAnthracnose is a widespread plant disease caused by various species of the fungal pathogen Colletotrichum. In solanaceous plants such as tomato (Solanum lycoperiscum), Colletotrichum infections exhibit a quiescent, asymptomatic state in developing fruit, followed by a transition to necrotrophic infections in ripe fruit. Through analysis of fruit tissue extracts of 95L368, a tomato breeding line that yields fruit with enhanced anthracnose resistance, we identified a role for steroidal glycoalkaloids (SGAs) in anthracnose resistance. The SGA α-tomatine and several of its derivatives accumulated at higher levels, in comparison to fruit of the susceptible tomato cultivar US28, 95L368 fruit extracts with fungistatic activity against Colletotrichum. Correspondingly, ripe and unripe 95L368 fruit displayed enhanced expression of glycoalkaloid metabolic enzyme (GAME) genes, which encode key enzymes in SGA biosynthesis. Metabolomics analysis incorporating recombinant inbred lines (RILs) generated from 95L368 and US28 yielded strong positive correlations between anthracnose resistance and accumulation of α-tomatine and several derivatives. Lastly, transient silencing of expression of the GAME genes GAME31 and GAME5 in anthracnose-susceptible tomato fruit yielded enhancements to anthracnose resistance. Together, our data support a role for SGAs in anthracnose defense in tomato, with a distinct SGA metabolomic profile conferring resistance to virulent Colletotrichum infections in ripe fruit.HighlightThis work describes an important role for steroidal glycoalkaloids (SGAs), abundant secondary metabolites in tomato fruit, in defense against anthracnose, a widespread fungal disease that impacts diverse crop species.