bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced endothelial caveolin-1 underlies deficits in brain insulin signalling in type 2 diabetes
Authors: Shetti Aashutosh U , Ramakrishnan Abhirami , Romanova Liudmila , Li Wenping , Vo Khanh , Volety Ipsita , Ratnayake Ishara , Stephen Terilyn , Minshall Richard D , Cologna Stephanie M , Lazarov Orly
Published: February 2023

Patients with type 2 diabetes exhibit severe impairments in insulin signalling in the brain and are five times more likely to develop Alzheimer’s disease. However, what leads to these impairments is not fully understood.

Here, we show reduced expression of endothelial cell caveolin-1 (Cav-1) in the db/db (Leprdb) mouse model of type 2 diabetes. This reduction correlated with alterations in insulin receptor expression and signalling in brain microvessels as well as brain parenchyma. These findings were recapitulated in the brains of endothelial cell-specific Cav-1 knock-out (Tie2Cre; Cav-1fl/fl) mice. Lack of Cav-1 in endothelial cells led to reduced response to insulin as well as reduced insulin uptake. Furthermore, we observed that Cav-1 was necessary for the stabilization of insulin receptors in lipid rafts. Interactome analysis revealed that insulin receptor interacts with Cav-1 and caveolae-associated proteins, insulin-degrading enzyme and the tight junction protein Zonula Occludence-1 in brain endothelial cells. Restoration of Cav-1 in Cav-1 knock-out brain endothelial cells rescued insulin receptor expression and localization.

Overall, these results suggest that Cav-1 regulates insulin signalling and uptake by brain endothelial cells by modulating IR-α and IR-β localization and function in lipid rafts. Furthermore, depletion of endothelial cell–specific Cav-1 and the resulting impairment in insulin transport leads to alteration in insulin signalling in the brain parenchyma of type 2 diabetics.
Tau–RNA complexes inhibit microtubule polymerization and drive disease-relevant conformation change
Authors: McMillan Pamela J , Benbow Sarah J , Uhrich Rikki , Saxton Aleen , Baum Misa , Strovas Timothy , Wheeler Jeanna M , Baker Jeremy , Liachko Nicole F , Keene C Dirk , Latimer Caitlin S , Kraemer Brian C
Published: February 2023

Alzheimer’s disease and related disorders feature neurofibrillary tangles and other neuropathological lesions composed of detergent-insoluble tau protein. In recent structural biology studies of tau proteinopathy, aggregated tau forms a distinct set of conformational variants specific to the different types of tauopathy disorders. However, the constituents driving the formation of distinct pathological tau conformations on pathway to tau-mediated neurodegeneration remain unknown. Previous work demonstrated RNA can serve as a driver of tau aggregation, and RNA associates with tau containing lesions, but tools for evaluating tau/RNA interactions remain limited. Here, we employed molecular interaction studies to measure the impact of tau/RNA binding on tau microtubule binding and aggregation. To investigate the importance of tau/RNA complexes (TRCs) in neurodegenerative disease, we raised a monoclonal antibody (TRC35) against aggregated tau/RNA complexes. We showed that native tau binds RNA with high affinity but low specificity, and tau binding to RNA competes with tau-mediated microtubule assembly functions. Tau/RNA interaction in vitro promotes the formation of higher molecular weight tau/RNA complexes, which represent an oligomeric tau species. Coexpression of tau and poly(A)45 RNA transgenes in Caenorhabditis elegans exacerbates tau-related phenotypes including neuronal dysfunction and pathological tau accumulation. TRC35 exhibits specificity for Alzheimer’s disease-derived detergent-insoluble tau relative to soluble recombinant tau. Immunostaining with TRC35 labels a wide variety of pathological tau lesions in animal models of tauopathy, which are reduced in mice lacking the RNA binding protein MSUT2. TRC-positive lesions are evident in many human tauopathies including Alzheimer’s disease, progressive supranuclear palsy, corticobasal degeneration and Pick’s disease. We also identified ocular pharyngeal muscular dystrophy as a novel tauopathy disorder, where loss of function in the poly(A) RNA binding protein (PABPN1) causes accumulation of pathological tau in tissue from post-mortem human brain. Tau/RNA binding drives tau conformational change and aggregation inhibiting tau-mediated microtubule assembly. Our findings implicate cellular tau/RNA interactions as modulators of both normal tau function and pathological tau toxicity in tauopathy disorders and suggest feasibility for novel therapeutic approaches targeting TRCs.
Clinical and MRI Evolution After Local Injection of Bone Marrow-Derived Mesenchymal Stem Cells in Perianal Fistulae in Crohn’s Disease: Results From a Prospective Monocentric Study
Authors: Reenaers Catherine , Gillard Romain P , Coimbra Carla , Gillard René M , Meunier Paul , Lechanteur Chantal , Baudoux Etienne , Boutaffala Layla , Beguin Yves , Louis Édouard
Published: February 2023

Background

Local injection of adipose tissue-derived mesenchymal stem cells [MSCs] is effective in fistulizing perianal Crohn’s disease [CD]. Less is known about bone marrow-derived MSCs and little is known about predictive factors of response and magnetic resonance imaging [MRI] evolution of the fistulae after MSC injection. Our aims were to evaluate the safety and clinical outcome of bone marrow-derived MSC injection for perianal fistulizing CD, to evaluate the MRI evolution of the fistulae and to identify factors associated with fistula closure.

Patients and methods

All CD patients with perianal fistula and appropriate drainage with a seton without abscess at MRI were eligible. Clinical examination, biomarkers and pelvic MRI were performed at weeks 0, 12 and 48. The clinical outcome was assessed by closure of the treated external openings at clinical examination and MRI exploration.

Results

Sixteen patients with a median age of 49 years and a median duration of perianal CD of 8 months were included. No unexpected safety event occurred. At weeks 12 and 48, 9/16 and 8/16 patients had complete fistula[e] closure, respectively, whereas 11/16 patients had at least partial closure. At MRI, the degree of fibrosis increased significantly after MSC injection. In total, 86% of patients with >80% of fibrosis of the fistula tract at week 48 had fistula closure. Fistula closure at week 12 was predictive of fistula closure at week 48. The MAGNIFI-CD did not change significantly over time.

Conclusion

Open-label injection of bone marrow-derived MSCs was safe and was effective in half of the patients in fistulizing perianal CD and induced significant MRI changes associated with favourable clinical outcome.
Which mouse multiparental population is right for your study? The Collaborative Cross inbred strains, their F1 hybrids, or the Diversity Outbred population
Authors: Keele Gregory R
Published: February 2023

Multiparental populations (MPPs) encompass greater genetic diversity than traditional experimental crosses of two inbred strains, enabling broader surveys of genetic variation underlying complex traits. Two such mouse MPPs are the Collaborative Cross (CC) inbred panel and the Diversity Outbred (DO) population, which are descended from the same eight inbred strains. Additionally, the F1 intercrosses of CC strains (CC-RIX) have been used and enable study designs with replicate outbred mice. Genetic analyses commonly used by researchers to investigate complex traits in these populations include characterizing how heritable a trait is, i.e. its heritability, and mapping its underlying genetic loci, i.e. its quantitative trait loci (QTLs). Here we evaluate the relative merits of these populations for these tasks through simulation, as well as provide recommendations for performing the quantitative genetic analyses. We find that sample populations that include replicate animals, as possible with the CC and CC-RIX, provide more efficient and precise estimates of heritability. We report QTL mapping power curves for the CC, CC-RIX, and DO across a range of QTL effect sizes and polygenic backgrounds for samples of 174 and 500 mice. The utility of replicate animals in the CC and CC-RIX for mapping QTLs rapidly decreased as traits became more polygenic. Only large sample populations of 500 DO mice were well-powered to detect smaller effect loci (7.5–10%) for highly complex traits (80% polygenic background). All results were generated with our R package musppr, which we developed to simulate data from these MPPs and evaluate genetic analyses from user-provided genotypes.
Right atrial myxoma after Amplatzer atrial septal defect closure device deployment
Authors: Li Pan , Song Laichun , Tao Liang , Chen Xufa
Published: February 2023

Right atrial (RA) myxoma is common; however, RA myxoma after the percutaneous atrial septal defect closure is very rare. To the best of our knowledge, this might be the first reported case of RA myxoma after Amplatzer closure of an atrial septal defect, leading to a pulmonary artery embolism. We removed all the RA mass, occluder and pulmonary embolus and reconstructed the atrial septum successfully. As a result of surgery, there were no other complications as following up.
Desiccant Dusts, With and Without Bioactive Botanicals, Lethal toRhipicephalus(Boophilus)microplusCanestrini (Ixodida: Ixodidae) in the Laboratory and on Cattle
Authors: Showler Allan T , Harlien Jessica L
Published: February 2023

The exotic southern cattle fever tick, Rhipicephalus (Boophilus) microplus (Canestrini) (Ixodida: Ixodidae), since its eradication from the United States in 1943, made a strong incursion into Texas, beginning 2016. The pest is arguably the most economically detrimental ectoparasite of cattle, Bos taurus L., worldwide. Current R. (B.) microplus control mostly relies on conventional synthetic acaricides to which the ixodid has been developing resistance. Our study demonstrates that commercially available desiccant dust products, with and without bioactive botanical additives, are strongly lethal, when applied dry, against larval R. (B.) microplus in the laboratory, and after being released on dust-treated cattle. Deadzone (renamed Celite 610, a diatomaceous earth product), Drione (silica gel + pyrethrins + piperonyl butoxide synergist), and EcoVia (silica gel + thyme oil), each prophylactically prevented larval R. (B.) microplus from attaching to and feeding on stanchioned calves. Desiccant dust-based products are less likely than conventional synthetic acaricides to decline in terms of efficacy as a result of ixodid resistance, and other desiccant dust advantages, including extended residual, flexibility in terms of application methods, environmental, animal, and human safety, and possible compatibility with organic, or ‘green’, production systems, are discussed. We anticipate that the desiccant dusts we evaluated, and others not included in this study (e.g., kaolin, perlite, and silica gel) will be effective when used with other control tactics in integrated pest management approaches for controlling R. (B.) microplus (and other ixodid species).
Upregulation of HBXIP contributed to the anti-DND by ginsenoside Rg1 after global cerebral ischemia-reperfusion
Authors: Zhang Zhi-Yong , Yuan Xia , He Hong-Yuan , He Wen-Bin , Zhang Zhao , Chu Shi-Feng
Published: February 2023

Objectives

Ginsenoside Rg1 (Rg1) has been well-documented to be effective against ischemic/reperfusion (I/R) injury. However, whether it has therapeutic effect on delayed neuronal death is still unclear. The aim of this study is to investigate the effect of Rg1 on delayed neuronal death and elucidate its underlying mechanism.

Methods

Delayed neuronal death model was prepared by global cerebral ischemia-reperfusion in rats, Rg1 was intravenously administered once a day. Nissl and Fluoro Jade B staining were carried out to evaluate the effect of Rg1 on delayed neuronal death. Western blot and qPCR were used to investigate the levels of HBXIP and Survivin. HBXIP/Survivin complex was observed by co-immunoprecipitation. AAV-CMV-shRNA (HBXIP) was used to observe the role of HBXIP on delayed neuronal death improved by Rg1.

Key findings

Rg1 attenuated delayed neuronal death at the dose of 20 mg/kg, which also improved the mRNA and protein levels of HBXIP, as well as Survivin. Moreover, administration of Rg1 promoted the formation of HBXIP/Survivin complex, which contributed to the reduction of caspases signaling pathway. Knockdown of HBXIP abolished the alleviation of DND and inhibition of caspase cascade induced by Rg1.

Conclusions

Rg1 alleviated delayed neuronal death by promoting anti-apoptosis effect by HBXIP/Survivin complex.
The ASAS-SN bright supernova catalogue – V. 2018–2020
Authors: Neumann K D , Holoien T W-S , Kochanek C S , Stanek K Z , Vallely P J , Shappee B J , Prieto J L , Pessi T , Jayasinghe T , Brimacombe J , Bersier D , Aydi E , Basinger C , Beacom J F , Bose S , Brown J S , Chen P , Clocchiatti A , Desai D D , Dong Subo , Falco E , Holmbo S , Morrell N , Shields J V , Sokolovsky K V , Strader J , Stritzinger M D , Swihart S , Thompson T A , Way Z , Aslan L , Bishop D W , Bock G , Bradshaw J , Cacella P , Castro-Morales N , Conseil E , Cornect R , Cruz I , Farfan R G , Fernandez J M , Gabuya A , Gonzalez-Carballo J-L , Kendurkar M R , Kiyota S , Koff R A , Krannich G , Marples P , Masi G , Monard L A G , Muñoz J A , Nicholls B , Post R S , Pujic Z , Stone G , Tomasella L , Trappett D L , Wiethoff W S
Published: February 2023

We catalogue the 443 bright supernovae (SNe) discovered by the All-Sky Automated Survey for Supernovae (ASAS-SN) in 2018−2020 along with the 519 SNe recovered by ASAS-SN and 516 additional mpeak ≤ 18 mag SNe missed by ASAS-SN. Our statistical analysis focuses primarily on the 984 SNe discovered or recovered in ASAS-SN g-band observations. The complete sample of 2427 ASAS-SN SNe includes earlier V-band samples and unrecovered SNe. For each SN, we identify the host galaxy, its UV to mid-IR photometry, and the SN’s offset from the centre of the host. Updated peak magnitudes, redshifts, spectral classifications, and host galaxy identifications supersede earlier results. With the increase of the limiting magnitude to g ≤ 18 mag, the ASAS-SN sample is nearly complete up to mpeak = 16.7 mag and is 90 per cent complete for mpeak ≤ 17.0 mag. This is an increase from the V-band sample, where it was roughly complete up to mpeak = 16.2 mag and 70 per cent complete for mpeak ≤ 17.0 mag.
Magnetic topologies of two weak-line T Tauri stars TAP 4 and TAP 40
Authors: Xiang Yue , Gu Shenghong , Donati J-F , Hussain G A J , Cameron A Collier , collaboration the MaT Y S S E
Published: February 2023

We present a Zeeman–Doppler imaging study of two weak-line T Tauri stars TAP 4 and TAP 40, based on the high-resolution spectropolarimetric observations with ESPaDOnS at the Canada–France–Hawaii Telescope in November 2013, in the framework of the Magnetic Topologies of Young Stars and Survival of close-in giant Exoplanets large programme. We apply two Zeeman–Doppler imaging codes to the Stokes I and V profiles to reconstruct their brightness and large-scale magnetic field images. The results given by the two imaging codes are in good agreement with each other. TAP 4 shows a large polar cool spot and several intermediate-latitude warm spots on its surface, whereas TAP 40 exhibits very weak variations in its Stokes I profiles, suggesting a mostly unspotted photosphere. We detect Zeeman signatures in the Stokes V profiles of both stars. The reconstructed magnetic maps reveal dominantly toroidal fields, which enclose about 60 per cent of the total magnetic energy for both TAP 4 and TAP 40. Both stars show prominent circular ring features of the azimuthal magnetic field. We derive a solar-like surface differential rotation on TAP 4 from the tomographic modelling. The brightness image of TAP 4 is used to predict the radial velocity (RV) jitters induced by its activity. After filtering out the activity jitter, the rms of its RVs is reduced from 1.7 to 0.2 km s−1, but we do not detect any periodic signals in the filtered RVs of TAP 4, implying that it is unlikely to host a close-in exoplanet more massive than ∼3.5MJup at 0.1 au.
Undisciplined
Authors: Lochhead Judith
Published: February 2023

My response to Stephen Lett initially takes a “glass half full” perspective on the current state of the Society for Music Theory, showing that in the early years of the Society there were substantive activities through what would become the Committee on the Status of Women (CSW) to diversify membership and work against biases. I provide a historical accounting of these activities from 1985 to 1995, documenting the many frictions within the operations of the Society. My response concludes with a “glass half empty” observation that more needs to be done and makes a radical suggestion for a Society for the Study of Music.
Roles and evolution of four LEAFY homologs in floral patterning and leaf development in woodland strawberry
Authors: Zhang Yunming , Kan Lijun , Hu Shaoqiang , Liu Zhongchi , Kang Chunying
Published: February 2023

The plant-specific transcription factor LEAFY (LFY), generally maintained as a single-copy gene in most angiosperm species, plays critical roles in flower development. The woodland strawberry (Fragaria vesca) possesses four LFY homologs in the genome; however, their respective functions and evolution remain unknown. Here, we identified and validated that mutations in one of the four LFY homologs, FveLFYa, cause homeotic conversion of floral organs and reiterative outgrowth of ectopic flowers. In contrast to FveLFYa, FveLFYb/c/d appear dispensable under normal growth conditions, as fvelfyc mutants are indistinguishable from wild type and FveLFYb and FveLFYd are barely expressed. Transgenic analysis and yeast one-hybrid assay showed that FveLFYa and FveLFYb, but not FveLFYc and FveLFYd, are functionally conserved with AtLFY in Arabidopsis (Arabidopsis thaliana). Unexpectedly, LFY-binding site prediction and yeast one-hybrid assay revealed that the transcriptional links between LFY and the APETALA1 (AP1) promoter/the large AGAMOUS (AG) intron are missing in F. vesca, which is due to the loss of LFY-binding sites. The data indicate that mutations in cis-regulatory elements could contribute to LFY evolution. Moreover, we showed that FveLFYa is involved in leaf development, as approximately 30% of mature leaves have smaller or fewer leaflets in fvelfya. Phylogenetic analysis indicated that LFY homologs in Fragaria species may arise from recent duplication events in their common ancestor and are undergoing convergent gene loss. Together, these results provide insight into the role of LFY in flower and leaf development in strawberry and have important implications for the evolution of LFY.
E3 ligase BRG3 persulfidation delays tomato ripening by reducing ubiquitination of the repressor WRKY71
Authors: Sun Chen , Yao Gai-fang , Li Li-xia , Li Ting-ting , Zhao Yu-qi , Hu Kang-di , Zhang Conghe , Zhang Hua
Published: February 2023

Hydrogen sulfide (H2S) is a gaseous signaling molecule reported to play multiple roles in fruit ripening. However, the molecular mechanisms underlying H2S-mediated delay in fruit ripening remain to be established. Here, the gene encoding a WRKY transcription factor, WRKY71, was identified as substantially upregulated in H2S-treated tomato (Solanum lycopersicum) via transcriptome profiling. The expression of WRKY71 was negatively associated with that of CYANOALANINE SYNTHASE1 (CAS1). Transient and stable genetic modification experiments disclosed that WRKY71 acts as a repressor of the tomato ripening process. CAS1 appears to play an opposite role, based on the finding that the ripening process was delayed in the cas1 mutant and accelerated in CAS1-OE tomatoes. Dual-luciferase reporter assay, yeast one-hybrid, electrophoretic mobility shift assay, and transient transformation experiments showed that WRKY71 bound to the CAS1 promoter and suppressed its activation. Moreover, the persulfidation of WRKY71 enhanced its binding ability to the CAS1 promoter. Data from luciferase complementation and Y2H assays confirmed that WRKY71 interacts with a BOI-related E3 ubiquitin-protein ligase 3 (BRG3) and is ubiquitinated in vitro. Further experiments showed that modification of BRG3 via persulfidation at Cys206 and Cys212 led to reduced ubiquitination activity. Our findings support a model whereby BRG3 undergoes persulfidation at Cys206 and Cys212, leading to reduced ubiquitination activity and decreased interactions with the WRKY71 transcript, with a subsequent increase in binding activity of the persulfidated WRKY71 to the CAS1 promoter, resulting in its transcriptional inhibition and thereby delayed ripening of tomatoes. Our collective findings provide insights into a mechanism of H2S-mediated regulation of tomato fruit ripening.
Crisscross multilayering of cell sheets
Authors: Sarkar Trinish , Yashunsky Victor , Brézin Louis , Blanch Mercader Carles , Aryaksama Thibault , Lacroix Mathilde , Risler Thomas , Joanny Jean-François , Silberzan Pascal
Published: February 2023

Hydrostatic skeletons such as the Hydra's consist of two stacked layers of muscle cells perpendicularly oriented. In vivo, these bilayers first assemble, and then the muscle fibers of both layers develop and organize with this crisscross orientation. In the present work, we identify an alternative mechanism of crisscross bilayering of myoblasts in vitro, which results from the prior local organization of these active cells in the initial monolayer. The myoblast sheet can be described as a contractile active nematic in which, as expected, most of the +1/2 topological defects associated with this nematic order self-propel. However, as a result of the production of extracellular matrix (ECM) by the cells, a subpopulation of these comet-like defects does not show any self-propulsion. Perpendicular bilayering occurs at these stationary defects. Cells located at the head of these defects converge toward their core where they accumulate until they start migrating on top of the tail of the first layer, while the tail cells migrate in the opposite direction under the head. Since the cells keep their initial orientations, the two stacked layers end up perpendicularly oriented. This concerted process leading to a crisscross bilayering is mediated by the secretion of ECM.
High performance w-stacking for imaging radio astronomy data: a parallel and accelerated solution
Authors: Gheller Claudio , Taffoni Giuliano , Goz David
Published: February 2023

Current and upcoming radio-interferometers are expected to produce volumes of data of increasing size that need to be processed in order to generate the corresponding sky brightness distributions through imaging. This represents an outstanding computational challenge, especially when large fields of view and/or high-resolution observations are processed. We have investigated the adoption of modern high performance computing systems specifically addressing the gridding, fast Fourier transform, and w-correction of imaging, combining parallel and accelerated solutions. We have demonstrated that the code we have developed can support data set and images of any size compatible with the available hardware, efficiently scaling up to thousands of cores or hundreds of graphic processing units, keeping the time to solution <1 h even when images of the size of the order of billions or tens of billions of pixels are generated. In addition, portability has been targeted as a primary objective, both in terms of usability on different computing platforms and in terms of performance. The presented results have been obtained on two different state-of-the-art high performance computing architectures.
Real-Time PCR Assays for Races of the Spinach Fusarium Wilt Pathogen, Fusarium oxysporum f. sp. spinaciae
Authors: Batson Alex M. , Woodhall James W. , du Toit Lindsey J.
Published: February 2023

Fusarium wilt of spinach, caused by Fusarium oxysporum f. sp. spinaciae, is a significant limitation for producers of vegetative spinach and spinach seed crops during warm temperatures and/or on acid soils. Identification of isolates of F. oxysporum f. sp. spinaciae, and distinction of isolates of the two known races, entails time-intensive pathogenicity tests. In this study, two real-time PCR assays were developed: one for a candidate effector gene common to both races of F. oxysporum f. sp. spinaciae, and another for a candidate effector gene unique to isolates of race 2. The assays were specific to isolates of F. oxysporum f. sp. spinaciae (n = 44) and isolates of race 2 (n = 23), respectively. Neither assay amplified DNA from 10 avirulent isolates of F. oxysporum associated with spinach, 57 isolates of other formae speciales and Fusarium spp., or 7 isolates of other spinach pathogens. When the assays were used to detect DNA extracted from spinach plants infected with an isolate of race 1, race 2, or a 1:1 mixture of both races, the amount of target DNA detected increased with increasing severity of wilt. Plants infected with one or both isolates could be distinguished based on the ratio in copy number for each target locus. The real-time PCR assays enable rapid diagnosis of Fusarium wilt of spinach and will facilitate research on the epidemiology and management of this disease, as well as surveys on the prevalence of this understudied pathogen in regions of spinach and/or spinach seed production.
First Report of Cucurbit Chlorotic Yellows Virus Affecting Squash and Pumpkin in Florida
Authors: Jailani A. Abdul Kader , Da Silva Susannah , Freeman Joshua H. , Dey Kishore , Velez-Climent Maria , McVay John , Bag Sudeep , Paret Mathews L.
Published: February 2023

A field survey was conducted in Florida during 2020-2021 in squash and pumpkin research fields to identify the viruses associated with leaf symptoms of yellowing, crumpling, and vein yellowing. The symptoms were similar to previously reported whitefly transmitted viruses such as cucurbit leaf crumple virus (CuLCrV), cucurbit yellow stunting disorder virus (CYSDV), and squash vein yellowing virus (SqVYV). Another potential virus of interest was the cucurbit chlorotic yellows virus (CCYV) that was recently reported on watermelon in Florida. Symptomatic leaves were tested by RT-PCR with coat protein (CP) gene-specific (GS) primers for CuLCrV, CYSDV, CCYV, and SqVYV with nuclear inclusion protein (NIa) GS primers. Amplifications for CuLCrV, CYSDV, and CCYV were detected in squash and pumpkin samples. The CCYV amplicons were further sequenced and compared with available CCYV sequences. The NCBI BLAST analysis revealed similarities of the RdRP (100%), HSP70h (99.75%), and CP (99.75%) to the Shanghai CCYV isolates (RNA KY400636 and RNA2 KY400633). To our knowledge, this is the first report of CCYV on squash and pumpkin in Florida.
A hybrid virtual nurse model
Authors: Russell Mary Beth
Published: February 2023

Impact on patient experience and quality of care
Interventions Addressing Cannabis Use During Pregnancy: A Systematic Review
Authors: Groff Destin , Bollampally Pooja , Buono Frank , Knehans Amy , Spotts Hannah , Bone Curtis
Published: February 2023

Objectives

The prevalence of cannabis use among pregnant women is increasing in the United States and places mothers and infants at risk of multiple adverse health outcomes. Given the uncertainty expressed by providers regarding how to approach cannabis use during pregnancy and the growing need for a systematic endeavor to curb use in this population, the aim of this study is to conduct a systematic review of interventions focused on reduction in cannabis use during pregnancy.

Methods

We conducted a systematic search of MEDLINE, PsycINFO, CINAHL, Web of Science, SCOPUS, and Cochrane Library to identify studies of interventions that target individuals that engaged in cannabis use during pregnancy. We included studies if they were randomized controlled trials, controlled studies, feasibility studies, pilot studies, as well as observational studies. The primary diagnostic outcome of interest is reduction in cannabis use.

Results

We identified 9 studies for inclusion with sample sizes ranging from 15 to 658 pregnant people. Interventions involved brief counseling, cognitive behavioral therapy (CBT), motivational interviewing (MI), motivational enhancement therapy + cognitive behavioral therapy (MET-CBT), computer-delivered psychotherapy, and psychoeducation. The interventions that were effective primarily used MI, CBT, and/or MET. There was just 1 study that implemented a home intervention and one that explored computer-based psychotherapy.

Conclusions

The studies uncovered through this systematic review suggest that interventions involving CBT and/or MI demonstrate promise for decreasing cannabis use during pregnancy. There is a tremendous need for high-quality studies focused on this population, and the potential for remote and computer-based interventions should be explored more fully.
Reconsidering Race Adjustment in Prenatal Alpha-Fetoprotein Screening
Authors: Burns Nicholas R. , Kolarova Teodora , Katz Ronit , Ma Kimberly , Delaney Shani
Published: February 2023

OBJECTIVE:

Black racial designation is the only race for which adjustment is recommended for maternal prenatal serum alpha-fetoprotein (AFP) screening. The objective of this study is to reevaluate the relationship between maternal race and maternal serum AFP values in prenatal analyte screening.

METHODS:

This was a single-center retrospective analysis of patients who underwent prenatal analyte screening between January 2007 and December 2020. Nomograms for raw maternal serum AFP values by gestational age were created and compared between patients identified as “Black” and “non-Black” on the laboratory requisition. Multivariable linear regression models were created to evaluate the relationship among gestational age, maternal weight, and maternal race on maternal serum AFP levels. The new models were compared with the laboratory-derived calculations, which used historically determined race adjustments.

RESULTS:

A total of 43,997 patients underwent analyte screening, and 27,710 patients had complete data for analysis. Of these, 6% were identified as Black. Black patients had laboratory blood draws at a mean gestational age of 123 days, compared with 120 days in non-Black patients (P<.001), and had higher maternal weight (mean 170 vs 161 lbs, P<.001). Nomograms for raw maternal serum AFP values did not differ between Black and non-Black patients (P=.065). When adjusted for gestational age and maternal weight, no difference in maternal serum AFP values was identified between Black and non-Black individuals (P=.81).

CONCLUSION:

No difference in maternal serum AFP values was identified between Black and non-Black pregnant individuals when adjusted by maternal weight and gestational age at blood draw. These findings suggest that routine race-based adjustment of maternal serum AFP screening should be discontinued.
Advances in Fetal Surgical Repair of Open Spina Bifida
Authors: Chmait Ramen H. , Monson Martha A. , Chon Andrew H.
Published: February 2023

Spina bifida remains a common congenital anomaly of the central nervous system despite national fortification of foods with folic acid, with a prevalence of 2–4 per 10,000 live births. Prenatal screening for the early detection of this condition provides patients with the opportunity to consider various management options during pregnancy. Prenatal repair of open spina bifida, traditionally performed by the open maternal–fetal surgical approach through hysterotomy, has been shown to improve outcomes for the child, including decreased need for cerebrospinal fluid diversion surgery and improved lower neuromotor function. However, the open maternal–fetal surgical approach is associated with relatively increased risk for the patient and the overall pregnancy, as well as future pregnancies. Recent advances in minimally invasive prenatal repair of open spina bifida through fetoscopy have shown similar benefits for the child but relatively improved outcomes for the pregnant patient and future childbearing.
Von Willebrand Disease, Hemophilia, and Other Inherited Bleeding Disorders in Pregnancy
Authors: Pacheco Luis D. , Saade George R. , James Andra H.
Published: February 2023

Inherited bleeding disorders, which comprise von Willebrand disease (VWD), hemophilia, other congenital clotting factor deficiencies, inherited platelet disorders, defects of fibrinolysis, and connective tissue disorders, have both maternal and fetal implications. Although mild platelet defects may actually be more prevalent, the most common diagnosed bleeding disorder among women is VWD. Other bleeding disorders, including hemophilia carriership, are much less common, but hemophilia carriers are unique in that they are at risk of giving birth to a severely affected male neonate. General guidance for maternal management of inherited bleeding disorders includes obtaining clotting factor levels in the third trimester, planning for delivery at a center with hemostasis expertise if factor levels do not meet the minimum threshold (eg, less than 0.50 international units/1 mL [50%] for von Willebrand factor, factor VIII, or factor IX), and using hemostatic agents such as factor concentrates, desmopressin, or tranexamic acid. General guidance for fetal management includes prepregnancy counseling, the option of preimplantation genetic testing for hemophilia, and consideration of delivery of potentially affected male neonates with hemophilia by cesarean delivery to reduce the risk of neonatal intracranial hemorrhage. In addition, delivery of possibly affected neonates should occur in a facility where there is newborn intensive care and pediatric hemostasis expertise. For patients with other inherited bleeding disorders, unless a severely affected neonate is anticipated, mode of delivery should be dictated by obstetric indications. Nonetheless, invasive procedures such as fetal scalp clip or operative vaginal delivery should be avoided, if possible, in any fetus potentially affected with a bleeding disorder.
Characteristics and Outcomes of Cancer Patients With Venous Thromboembolic Events After Treatment With Immune Checkpoint Inhibitors
Authors: Dutra Barbara , Garcia-Rodriguez Victor , Garcia Rogelio , Szafron David , Abraham Fiyinfoluwa , Khurana Shruti , Lockhart Jonathan , Amin Rajan , Wang Yinghong , Thomas Anusha
Published: February 2023

Objective:

This study aimed to describe the clinical characteristics and outcomes of patients with venous thromboembolism (VTE) after Immune checkpoint inhibitors (ICI), focusing on patients with gastrointestinal (GI) immune-related adverse events (irAE).

Methods:

In this retrospective, single-center study, we report the clinical outcomes of adult cancer patients who developed a VTE within 2 years of ICI initiation. Patients were excluded if alternate causes of VTE were present apart from malignancy and cancer therapy. The cohort was classified into those with GI-irAE, non-GI-irAE, and no irAE. A control group with ICI exposure without irAE and VTE was selected for comparative analysis.

Results:

Of all ICI-treated patients, 1891 (17.2%) were diagnosed with VTE. In all, 501 (4.6%) had no etiology for VTE aside from malignancy and cancer therapy. Of these, 137 patients were included and classified as: 44 GI-irAE, 42 non-GI-irAE, and 51 no irAE. Chemotherapy within 6 months of ICI therapy was associated with increased VTE risk. There was no difference in the clinical course between those exposed to chemotherapy versus ICI therapy alone, time from ICI initiation to VTE, and VTE type, recurrence, or related hospitalization. While there was no difference in VTE-related mortality, the GI-irAE group was associated with lower all-cause mortality and superior overall survival.

Conclusion:

Combined ICI and chemotherapy use increased VTE risk. There is a similar disease course of VTE after ICI exposure, regardless of other irAEs. Co-existing GI-irAE with VTE is associated with superior overall survival. Prospective studies are needed to evaluate the relationship between ICI therapy and VTE and irAE impact on VTE outcomes.
Opioid-related Mortality in United States Death Certificate Data: A Quantitative Bias Analysis With Expert Elicitation of Bias Parameters
Authors: Goldsmith Elizabeth S. , Krebs Erin E. , Ramirez Marizen R. , MacLehose Richard F.
Published: February 2023

Background:

Opioid-related mortality is an important public health problem in the United States. Incidence estimates rely on death certificate data generated by health care providers and medical examiners. Opioid overdoses may be underreported when other causes of death appear plausible. We applied physician-elicited death certificate bias parameters to quantitative bias analyses assessing potential age-related differential misclassification in US opioid-related mortality estimates.

Methods:

We obtained cause-of-death data (US, 2017) from the National Center for Health Statistics and calculated crude opioid-related outpatient death counts by age category (25–54, 55–64, 65+). We elicited beliefs from 10 primary care physicians on sensitivity of opioid-related death classification from death certificates. We summarized elicited sensitivity estimates, calculated plausible specificity values, and applied resulting parameters in a probabilistic bias analysis.

Results:

Physicians estimated wide sensitivity ranges for classification of opioid-related mortality by death certificates, with lower estimated sensitivities among older age groups. Probabilistic bias analyses adjusting for physician-estimated misclassification indicated 3.1 times more (95% uncertainty interval: 1.2–23.5) opioid-related deaths than the observed death count in the 65+ age group. All age groups had substantial increases in bias-adjusted death counts.

Conclusions:

We developed and implemented a feasible method of eliciting physician expert opinion on bias parameters for sensitivity of a medical record-based death indicator and applied findings in quantitative bias analyses adjusting for differential misclassification. Our findings are consistent with the hypothesis that opioid-related mortality rates may be substantially underestimated, particularly among older adults, due to misclassification in cause-of-death data from death certificates.
Glycolytic activity in human immune cells: inter-individual variation and functional implications during health and diabetes
Authors: Vrieling Frank , van Dierendonck Xanthe A. M. H. , Jaeger Martin , Janssen Anna W. M. , Hijmans Anneke , Netea Mihai G. , Tack Cees J. , Stienstra Rinke
Published: February 2023

An increase in glucose uptake driving aerobic glycolysis is a robust hallmark of immune cell activation. The glycolytic response supports functional alterations of the innate immune cells including the production and release of cytokines. Large inter-individual differences in the magnitude of this cytokine response are known to exist. In addition, the presence of disease is known to impact on immune cell function. Whether variation in metabolic responses of immune cells exist between individuals during health or disease is currently unknown. Here, we explore inter-individual differences in the glycolytic rate of immune cells using lactate production as readout upon activation using a variety of different stimuli. Glycolytic responses are subsequently associated to functional immune cell responses in healthy humans. In addition, we determined the glycolytic rate of immune cells and its association with immune function using patients diagnosed with diabetes mellitus. Based on the relative increase in lactate production after activation, distinct clusters of low, intermediate, and high responders could be identified, illustrating the existence of variation in glycolytic responses in healthy subjects. Interestingly, the production of cytokines mirrored these high-, intermediate-, and low-lactate patterns after pathogenic stimulation. In patients with diabetes mellitus, a reduced correlation was found between lactate and cytokine production, specifically for IL-6. Furthermore, based on the relative increase in lactate production, variability in the glycolytic response was reduced compared to healthy subjects. In conclusion, our results show a specific association between the glycolytic rate and function in human immune cells after stimulation with different pathogens. In addition to demonstrating the existence of glycolytic variability and specificity depending on the type of stimulus, the association between glycolysis and function in innate immune cells is altered during the presence of diabetes.
Giant Lacrimal Gland Cyst in a Pediatric Patient: Case Report and Review of the Literature
Authors: Luthra Shreya , Kim Esther , Homer Natalie A.
Published: February 2023

Lacrimal gland cysts are rare clinical entities in the pediatric population. Herein is described a 6-year-old male patient presenting with progressive left upper lid ptosis, found to have a large ipsilateral superotemporal orbital mass. Diagnosis of a giant lacrimal gland cyst was confirmed excisional biopsy. Despite the resolution of mechanical blepharoptosis, the patient maintained visual acuity limitation due to suspected deprivation amblyopia. The pathophysiology and clinical manifestations of lacrimal gland cysts in the pediatric population are reviewed to emphasize the importance of expedited identification and management in this patient cohort.
Validation of the IMPACT-III Questionnaire in French Children With Inflammatory Bowel Disease
Authors: Vanhelst Jérémy , Béghin Laurent , Drumez Elodie , Djeddi-Dine Djamal , Tuck Dominique , Coopman Stéphanie , Gottrand Frédéric , Ley Delphine
Published: February 2023

Objectives:

This study assessed the reliability and validity of the IMPACT-III questionnaire, a health-related quality of life (HRQoL) instrument, in French children with inflammatory bowel disease (IBD).

Methods:

Eighty-four children and adolescents (45 boys, aged 14.3 ± 2.7 years) were included in a validation study of the IMPACT-III questionnaire. Patients completed 2 questionnaires for measuring HRQoL: the IMPACT-III and the Pediatric Quality of Life Inventory 4.0 Generic Core Scale (PedsQL). Internal consistency was assessed using Cronbach α. Factor analysis was performed on data from the IMPACT-III to help construct domains. Concurrent validity was assessed by calculating Spearman correlation coefficients.

Results:

Cronbach α for the PedsQL total score was good (0.89). The most robust factor solution was a 3-domain structure: (a) Concerns, (b) Body Image and Physical Condition, and (c) Symptoms and Socializing. All domains had good reliability (0.674–0.863). Only 2 items had to be removed. Discriminant validity was demonstrated by significant differences (P < 0.001) in median IMPACT-III scores between inactive and active disease for the total score (83.3 vs 72.0), and for Concerns (P < 0.002) and Symptoms and Socializing (P < 0.001).

Conclusions:

These results suggest that IMPACT-III appears to be a useful instrument for measuring HRQoL in French children with IBD.
Psychosocial well-being and mental adjustment of patients with stage III melanoma in the re-entry phase: a scoping review
Authors: Visser Anna , Post Lenneke , Dekker Joost , Konings Inge R.
Published: February 2023

Background:

The number of patients with stage III melanoma is rising because of increasing incidence and improved survival thanks to newly available adjuvant treatments. Patients may face specific challenges in the re-entry phase, the first 18 months after treatment, because of a high risk of recurrence and the intensity and long-term side effects of adjuvant treatment. The aims of this scoping review included summarizing the current state of evidence concerning patient psychosocial well-being and mental adjustment to the re-entry phase, as well as identifying knowledge gaps.

Methods:

A systematic literature search was conducted in PubMed and CINAHL using the PRISMA-ScR checklist.

Results:

Two qualitative and seven quantitative studies were included. Some studies found no evidence of diminished social and emotional functioning compared with the general population, while others reported emotional distress and impairment in psychological health. Regarding existential health, frequently expressed concerns encompassed fear of recurrence, hopelessness, and uncertainty about the future. Patients typically used behavioral coping, cognitive coping, and meaning-making to manage challenges in the re-entry phase. Only one study considered the effects of adjuvant therapy use on the re-entry phase.

Conclusions:

Limited evidence is available on the psychosocial status of patients with stage III melanoma in the re-entry phase, a phase in which patients face existential concerns. It may be beneficial to provide patients with support regarding existential concerns and meaning-making, for example by developing a practical tool to help set meaningful goals for the re-entry phase. A better understanding of the psychosocial well-being of these patients, the impact of adjuvant therapy, and the relationship between emotional distress, existential concerns, and meaning-making will require further research.
Health-Related Quality of Life, Anxiety, and Self-Image in Young Patients With Crohn’s Disease and Ulcerative Colitis
Authors: Lund Ken , Knudsen Torben , Kjeldsen Jens , Nielsen Rasmus Gaardskær , Nørgård Bente Mertz
Published: February 2023

We examined health-related quality of life, anxiety, and self-image in patients aged 10–20 years with Crohn’s disease (CD) and ulcerative colitis (UC) in remission. These areas are key concerns in clinical care. We used the IMPACT-III for health-related quality of life and The Beck Youth Inventory-II for anxiety and self-image. Linear regression models were used to compare CD to UC. We included 67 patients, 44 (66%) with CD and 23 (34%) with UC. The mean score for IMPACT-III, anxiety, and self-image for CD versus UC was 78 (±SD: 13) versus 78 (±SD: 15), 44 (±SD: 9) versus 45 (±SD: 8), and 10 (±SD: 9) versus 9 (±SD: 6), respectively. We found no difference between CD and UC. Despite remission, we found an elevated score of anxiety and a low score of self-image. When evaluating mental health status, a varied approach may be beneficial for researchers.
HeartWatch: Implementing a Pediatric Heart Center Program to Prevent Cardiac Arrests Outside the ICU
Authors: Birely Alexandra , Avula Sravani , Butts Ryan J. , Wolovits Joshua S. , Lemler Matthew S. , Hoffman Olivia L.
Published: February 2023

Introduction:

Pediatric patients with cardiovascular disease are at increased risk of cardiopulmonary arrest. Despite utilization of Cardiac Pediatric Early Warning Scores to identify patients at risk of decompensation, our institution had a twofold increase in cardiac arrests (CAs) in the acute care cardiology unit (ACCU) over 2 years. Through a quality improvement initiative, we developed a watcher program, HeartWatch, to reduce the CA arrest rate in the ACCU by 50% over the first year of implementation.

Methods:

HeartWatch aims to identify patients not adequately captured by Cardiac Pediatric Early Warning Scores who are at high risk for sudden decompensation. Inclusion criteria were developed and evaluated during pilot and implemented phases (April 2020–April 2021) and then monitored in a sustained phase through June 2022. Our primary outcome was the reduction in the out-of-ICU CA rate.

Results:

During the 13 months, we enrolled 169 patients, and the CA rate decreased from 0.7 to 0.33 per 1,000 patient days, a 53% reduction. The CA rate further decreased to 0.28 events per 1,000 patient days, a 60% reduction, by June 2022. The most common indications for HeartWatch inclusion were high-risk single-ventricle patients (31%) and patients with diminished ventricular function (20%).

Conclusions:

Implementation of HeartWatch was associated with a meaningful reduction in CA in the ACCU. Creating shared mental models for high-risk patients is essential for patient safety. Future work will optimize local processes that focus on the sustainability of our gains. We will also evaluate opportunities to adapt and implement a similar framework in other institutions to assess reproducibility.