bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable adrenomedullin analog mitigates placental ischemia-induced hypertension and fetal growth restriction in rats
Authors: Chang Chia Lin , Cai Zheqing , Hsu Sheau Yu Teddy 
Published: April 2023

Objective(s):
Preeclampsia is a heterogeneous hypertensive disorder of pregnancy. It affects multiorgans and may lead to fetal growth restriction, organ failure, seizure, and maternal death. Unfortunately, current treatments are ineffective at delaying the progression of preeclampsia even for a few days. Clinicians are often forced to deliver preterm fetus if severe preeclampsia occurred early during pregnancy, leading to premature birth-associated complications. Preeclampsia has been associated with defects at the maternal–fetal interface and maternal vascular dysfunction. Of interest, the adrenomedullin peptide and its cognate receptors, calcitonin receptor-like receptor (CLR)/ receptor activity-modifying protein (RAMP) receptor complexes, have been shown to be important regulators of cardiovascular adaptation and feto-placental development during pregnancy. Although the exact role of adrenomedullin-CLR/RAMP signaling in different feto-maternal compartments during pregnancy and how adrenomedullin expression affects preeclampsia development remains to be clarified, we hypothesized that the sustained activation of CLR/RAMP receptors could be a promising strategy to mitigate placental ischemia-associated vascular dysfunction and fetal growth restriction under preeclampsia-like conditions

Methods:
To explore this possibility, we have developed a stable adrenomedullin analog, ADE101, and investigated its effects on human lymphatic microvascular endothelial (HLME) cell proliferation, hemodynamics, and pregnancy outcomes in pregnant rats with reduced uteroplacental perfusion pressure (RUPP) induced by clipping of uterine arteries on gestation day 14

Results:
The ADE101 analog has a potent effect on CLR/RAMP2 receptor activation, and an enhanced stimulatory effect on HLME cell proliferation compared to wild-type peptides. ADE101 also exhibits a lasting effect on hemodynamics in normal and hypertensive rats. In addition, studies using the RUPP model showed that ADE101 significantly reduces placental ischemia-induced hypertension and fetal growth restriction in a dose-dependent manner. Infusion of ADE101 increased the weight of fetuses and placentas in RUPP animals to 252% and 202% of that of RUPP controls, respectively.

Conclusions:
These data suggested that long-acting adrenomedullin analog could be useful for quenching hypertension as well as the vascular ischemia-associated organ damages in preeclamptic patients.
InTraocular EMulsion of Silicone oil (ITEMS) grading system: an evidence-based expert-led consensus.
Authors: Romano Mario R , Ferrara Mariantonia , Coco-Martin Rosa M , Rickmann Annekatrin , Spitzer Martin S , Steel David HW , Pastor J Carlos 
Published: April 2023

Abstract

Purpose:
To propose the InTraocular EMulsion of Silicone oil (ITEMS) grading system for the assessment of silicone oil (SiO) emulsion, applicable in a routine clinical setting and validated through an expert-led consensus procedure.

Methods:
Seven experts on intraocular liquid tamponades, led by a facilitator, performed a literature review on the detection of SiO emulsion. Based on the proposed ideas, a questionnaire was developed and submitted to the experts on the methods to detect SiO emulsion and the items to grade. After two rounds of individual ranking using a nine-point scale and related discussion, the final grading system was developed including items that reached consensus (score ≥7 from ≥75% of members).

Results:
The agreed ITEMS grading system includes the identification of SiO microbubbles and large SiO bubbles through slit lamp biomicroscopy, gonioscopy, fundus examination under mydriasis or ultra-widefield fundus photography. Moreover, macular and disc OCT are used to detect SiO-associated hyperreflective dots.

Conclusion:
An evidence-based expert-led consensus was conducted to develop grading system of SiO emulsion, allowing, for the first time, homogenous collection of data on SiO emulsion. This has the potential to improve our understanding of the role and clinical relevance of SiO emulsion allowing comparisons between different studies.
The Chrysanthemum Phenotype of Idiopathic Multifocal Choroiditis
Authors: Ramtohul Prithvi , Cicinelli Maria Vittoria , Dolz-Marco Rosa , Gal-Or Orly , Mrejen Sarah , García-Martínez Jesús R , Goldberg Alla , Cunha de Souza Eduardo , Miserocchi Elisabetta , Cunningham Emmett T. , Yannuzzi Lawrence A. , Freund K. Bailey , Tsui Edmund 
Published: April 2023

Abstract

Purpose:
To describe the clinical characteristics and multimodal imaging (MMI) features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with grey-yellow chorioretinal lesions surrounded by smaller satellite dots, a presentation referred to as “chrysanthemum lesions”.

Methods:
Retrospective, observational, multi-center case series of eyes with active iMFC and chrysanthemum lesions. Multimodal imaging features were reviewed and presented.

Results:
Twenty-five eyes from 20 patients (12 women and 8 men), with a mean age of 35.8±17.0 years (range, 7 – 78 years) were included. Chrysanthemum lesions were equally located in the macula (48.0%) or the mid/far-periphery (52.0%). The number of lesions per eye varied from 1 (16.0%) to more than 20 (56.0%). On optical coherence tomography (OCT), chrysanthemum lesions showed typical features of iMFC, including subretinal hyperreflective material splitting the retinal pigment epithelium/Bruch’s membrane (RPE/BrM). Chrysanthemum lesions were hypoautofluorescent on fundus autofluorescence imaging, hyperfluorescent on fluorescein angiography, hypofluorescent on indocyanine green angiography, and associated with choriocapillaris flow signal deficit on OCT-angiography.

Conclusion:
Active iMFC may present with findings resembling chrysanthemum lesions. The distinctive lesion morphology on ophthalmoscopic examination, the high number of lesions, and the high prevalence of exclusive mid- and far-peripheral involvement may represent a distinctive phenotype of iMFC.
The evolution of refractive surgery training
Authors: Arboleda Nathan , Yi Joseph , Kang Joann J. 
Published: April 2023

Purpose of review
Although refractive surgery is one of the most commonly performed ophthalmic procedures, there is a relative paucity of literature on residency and fellowship refractive surgery education. The purpose of this article is to review the current state and recent updates to refractive surgery education and to evaluate the safety and visual outcomes of trainee performed refractive procedures.

Recent findings
Currently, there is no standard refractive surgery curriculum in the United States apart from required mandatory minimum refractive requirements for residents and fellows. Our survey of residency programs confirms that refractive training is extremely varied, ranging from a dedicated refractive rotation with direct surgical experience to only didactics or observation of procedures. There is a proposed standardized framework for refractive surgery training for the military, which may be a starting point in developing a more comprehensive refractive surgery curriculum in residency education. Multiple studies have reinforced the safety of resident and fellow performed refractive surgery.

Summary
Refractive surgery is an increasingly popular procedure and a more comprehensive refractive education is paramount. Future studies are needed to determine how best to provide the fundamental training and surgical experience for trainees in the fast-changing landscape of refractive surgery.
Research Progress of the Association of the Neutrophil Elastase with Sepsis-related Acute Lung Injury
Authors: Qiu Chuiyan , Zheng Xinglong , Qu Zhongkai , Zhang Luming , Hu Hai , Lu Xuehao , Yin Haiyan 
Published: April 2023

ABSTRACT
Sepsis is considered a life-threatening organ dysfunction resulting from a dysregulation of the body's response to the infection, a syndrome of physiological, pathological, and biochemical abnormalities caused by infection. The prevention and treatment of sepsis-related acute lung injury has become a hot spot in sepsis research in recent years. Neutrophil elastase (NE) is a multifunctional serine protease released by neutrophils cells, which can participate in the regulation of the inflammatory response in the body and directly affect the occurrence and development of inflammation. This article reviews the pathogenesis of sepsis-related lung injury and the mechanism of action, clinical application and prospect of neutrophil elastase inhibitor (NEI).
An interprofessional clinical experience to address social determinants of health
Authors: Hickey Mary T. , Stillo Marco , Marquez Crystal 
Published: April 2023

ABSTRACT
The importance of effective interprofessional communication and collaboration as a strategy to improve patient outcomes has been documented in the literature. Efforts to integrate interprofessional education have been difficult to actualize due to myriad factors in academic and clinical settings. The COVID public health emergency presented an unexpected opportunity to address the needs of an underserved community through an interprofessional clinical experience between medical and APRN students. A screening tool and resource-driven algorithm were developed and launched by students in the college of medicine, for the patients of a university hospital clinic. This initiative helped meet the needs of the community, with the value-added benefit of an interprofessional clinical experience. Using a train-the-trainer model, students were oriented to the project and an online platform for real-time collaboration. Results of this initiative were positive. Approximately 100 medical and APRN students participated and contacted 1,489 patients in the community. Medical and social needs were addressed for 681 patients, and urgent social needs were addressed for 30 people. Students gained valuable clinical experience and had opportunities to identify and address social determinants of health while collaborating with medical student counterparts.
Blood pressure surge with alarm is reduced after exercise and diet intervention in firefighters
Authors: Feairheller Deborah L , Smith Macie , Carty Megan , Reeve Emily H 
Published: April 2023

Background
Cardiac-related incidents are a public health concern for tactical occupations, and cardiovascular disease rates are higher in these populations compared with civilians. Research is needed to examine blood pressure (BP) responses in firefighters. The pager alert is one occupational hazard, and it is unknown if lifestyle change can reduce the systolic surge response.

Purpose
To measure BP surge with alarm in firefighters to determine whether the magnitude is lower after a 6-week tactical exercise and Mediterranean-diet intervention.

Methods
Systolic BP (SBP) and diastolic BP (DBP) surge levels, circulating markers, vascular health, and fitness were analyzed. BP surge with alarm was captured during a 12-hour workshift. Exercise and diet were self-reported. Diet was tracked with diet scores based on number of servings.

Results
A total of 25 firefighters (43.4 ± 13.9 years) participated. We found changes in the magnitude of BP surge with alarm (SBP surge from16.7 ± 12.9 to 10.5 ± 11.7 mmHg, P < 0.05; DBP surge from 8.2 ± 10.8 to 4.9 ± 5.6 mmHg, P > 0.05) after intervention. We confirm that clinical (127.6 ± 9.1 to 120 ± 8.2 mmHg) and central (122.7 ± 11.3 to 118.2 ± 10.7 mmHg) SBP levels improve with exercise and diet. We report for the first time in firefighters that oxidative stress markers superoxide dismutase (9.1 ± 1.5 to 11.2 ± 2.2 U/ml) and nitric oxide (40.4 ± 7 to 48.9 ± 16.9 μmol/l) levels improve with an exercise and diet intervention.

Conclusion
These findings have implications toward the benefit that short-term lifestyle changes make toward reducing the alarm stress response in first responders.
Renal effects of cullin 3 mutations causing familial hyperkalemic hypertension
Authors: Cornelius Ryan J. , Maeoka Yujiro , McCormick James A. 
Published: April 2023

Purpose of review
Mutations in the E3 ubiquitin ligase scaffold cullin 3 (CUL3) cause the disease familial hyperkalemic hypertension (FHHt) by hyperactivating the NaCl cotransporter (NCC). The effects of these mutations are complex and still being unraveled. This review discusses recent findings revealing the molecular mechanisms underlying the effects of CUL3 mutations in the kidney.

Recent findings
The naturally occurring mutations that cause deletion of exon 9 (CUL3-Δ9) from CUL3 generate an abnormal CUL3 protein. CUL3-Δ9 displays increased interaction with multiple ubiquitin ligase substrate adaptors. However, in-vivo data show that the major mechanism for disease pathogenesis is that CUL3-Δ9 promotes degradation of itself and KLHL3, the specific substrate adaptor for an NCC-activating kinase. CUL3-Δ9 displays dysregulation via impaired binding to the CSN and CAND1, which cause hyperneddylation and compromised adaptor exchange, respectively. A recently discovered CUL3 mutant (CUL3-Δ474–477) displays many similarities to CUL3-Δ9 mutations but some key differences that likely account for the milder FHHt phenotype it elicits. Furthermore, recent work suggests that CUL3 mutations could have unidentified complications in patients and/or a predisposition to renal injury.

Summary
This review summarizes recent studies highlighting advances in our understanding of the renal mechanisms by which CUL3 mutations modulate blood pressure in FHHt.
Clinical Outcomes of an Intensity Program for Children With Movement Challenges
Authors: Schreiber Joseph , Wenskovitch John , Belt Janice , O'Donnell Amy , Wolf Debra 
Published: April 2023

Purpose:
Physical therapists at an outpatient pediatric facility developed and implemented an Intensity Program for children with movement challenges. The program was initiated on the basis of best evidence, parent advocacy, and clinician expertise. The purpose of this investigation is to analyze outcome data gathered from the program since 2012 to determine the effect of the program along with any specific child characteristics that were more likely to lead to positive outcomes.

Methods:
A variety of outcome data were analyzed to compare preprogram performance with postprogram performance.

Results:
Program participants made statistically significant and clinically important improvement in most outcome measures. Parents were highly satisfied with the program, including 98% of respondents who indicated that they would like to repeat their participation in the program.

Conclusions:
The results of this investigation suggest that many children with movement challenges are likely to benefit from participation in an Intensity Program.
Intersectionality-informed analysis of durable viral suppression disparities in people with HIV
Authors: Rivera Adovich S. , Rusie Laura K. , Feinstein Matthew J. , Siddique Juned , Lloyd-Jones Donald M. , Beach Lauren B. 
Published: April 2023

Objective:
The aim of this study was to examine drivers of durable viral suppression (DVS) disparities among people with HIV (PWH) using quantitative intersectional approaches.

Design:
A retrospective cohort analysis from electronic health records informed by intersectionality to better capture the concept of interlocking and interacting systems of oppression.

Methods:
We analyzed data of PWH seen at a LGBTQ federally qualified health center in Chicago (2012–2019) with at least three viral loads. We identified PWH who achieved DVS using latent trajectory analysis and examined disparities using three intersectional approaches: Adding interactions, latent class analysis (LCA), and qualitative comparative analysis (QCA). Findings were compared with main effects only regression.

Results:
Among 5967 PWH, 90% showed viral trajectories consistent with DVS. Main effects regression showed that substance use [odds ratio (OR) 0.56, 0.46–0.68] and socioeconomic status like being unhoused (OR: 0.39, 0.29–0.53), but not sexual orientation or gender identity (SOGI) were associated with DVS. Adding interactions, we found that race and ethnicity modified the association between insurance and DVS (P for interaction <0.05). With LCA, we uncovered four social position categories influenced by SOGI with varying rates of DVS. For example, the transgender women-majority class had worse DVS rates versus the class of mostly nonpoor white cisgender gay men (82 vs. 95%). QCA showed that combinations, rather than single factors alone, were important for achieving DVS. Combinations vary with marginalized populations (e.g. black gay/lesbian transgender women) having distinct sufficient combinations compared with historically privileged groups (e.g. white cisgender gay men).

Conclusion:
Social factors likely interact to produce DVS disparities. Intersectionality-informed analysis uncover nuance that can inform solutions.
Mortality in hepatitis C virus-cured vs. hepatitis C virus-uninfected people with HIV
Authors: Requena Maria-Bernarda , Grabar Sophie , Lanoy Emilie , Pialoux Gilles , Billaud Eric , Duvivier Claudine , Merle Philippe , Piroth Lionel , Tattevin Pierre , Salmon Dominique , Weiss Laurence , Costagliola Dominique , Lacombe Karine 
Published: April 2023

Objective:
It is unknown whether hepatitis C virus (HCV)-cured people with HIV (PWH) without cirrhosis reached the same mortality risk as HCV-uninfected PWH. We aimed to compare mortality in PWH cured of HCV by direct-acting antivirals (DAAs) to mortality in individuals with HIV monoinfection.

Design:
Nationwide hospital cohort.

Methods:
HIV-controlled participants without cirrhosis and HCV-cured by DAAs started between September 2013 and September 2020, were matched on age (±5 years), sex, HIV transmission group, AIDS status, and body mass index (BMI) (±1 kg/m2) to up to 10 participants with a virally suppressed HIV monoinfection followed at the time of HCV cure ±6 months. Poisson regression models with robust variance estimates were used to compare mortality in both groups after adjusting for confounders.

Results:
The analysis included 3961 HCV-cured PWH (G1) and 33 872 HCV-uninfected PWH (G2). Median follow-up was 3.7 years in G1 [interquartile range (IQR): 2.0–4.6], and 3.3 years (IQR: 1.7–4.4) in G2. Median age was 52.0 years (IQR: 47.0–56.0), and 29 116 (77.0%) were men. There were 150 deaths in G1 [adjusted incidence rate (aIR): 12.2/1000 person-years] and 509 (aIR: 6.3/1000 person-years) in G2, with an incidence rate ratio (IRR): 1.9 [95% confidence interval (CI), 1.4–2.7]. The risk remained elevated 12 months post HCV cure (IRR: 2.4 [95% CI, 1.6–3.5]). Non-AIDS/non-liver-related malignancy was the most common cause of death in G1 (28 deaths).

Conclusions:
Despite HCV cure and HIV viral suppression, after controlling on factors related to mortality, DAA-cured PWH without cirrhosis remain at higher risk of all-cause mortality than people with HIV monoinfection. A better understanding of the determinants of mortality is needed in this population.
Altered methionine-sulfone levels are associated with impaired growth in HEU-children
Authors: Zhang Zhengzheng , Duri Kerina , Duisters Kevin L.W. , Schoeman Johannes C. , Chandiwana Panashe , Lindenburg Peter , Jaeger Julia , Ziegler Susanne , Altfeld Marcus , Kohler Isabelle , Harms Amy , Gumbo Felicity Z. , Hankemeier Thomas , Bunders Madeleine J. 
Published: April 2023

Objective:
To determine immune-metabolic dysregulation in children born to women living with HIV.

Methods:
Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women living with HIV (WLHIV) and 12 uninfected women and their children up to 1.5 years of age were performed.

Results:
Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signaling lipids) and 24 immune mediators (e.g. cytokines) were quantified. cART exposure was categorized as cART initiation preconception (long), cART initiation post-conception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HEU-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length.

Conclusion:
These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WLHIV is associated with restricted infant growth.
Pharmacokinetics and pharmacodynamics of adult dolutegravir tablets in treatment-experienced children with HIV weighing at least 20 kg
Authors: Martyn-Dickens Charles , Ojewale Oluwayemisi , Sly-Moore Eugenia , Dompreh Albert , Enimil Anthony , Amissah Aikins Kofi , Bosomtwe Dennis , Appiah Augustina Frimpong , Sarfo Ama D. , Opoku Theresah , Asiedu Priscilla , Dong Stephen K. , Kusi-Amponsah Isaac , Maranchick Nicole , Peloquin Charles A. , Antwi Sampson , Kwara Awewura 
Published: April 2023

Objective:
Limited pharmacokinetic/pharmacodynamic data are a barrier to the well tolerated scale-up of dolutegravir-based antiretroviral therapy (ART) in children. We examined the pharmacokinetic/pharmacodynamic of the adult film-coated dolutegravir 50 mg tablets in children with HIV infection weighing at least 20 kg.

Design:
A prospective, observational, pharmacokinetic, and safety study.

Methods:
Treatment-experienced children with HIV weighing at least 20 kg and evidence of viral load suppression on ART were enrolled and switched to dolutegravir-based therapy. After at least 4 weeks and 7 months on dolutegravir-based therapy, blood samples were collected at 0, 1, 4, 8, 12, and 24-h postdose. Dolutegravir concentrations were measured using validated LCMS/MS and pharmacokinetic parameters calculated by noncompartmental analysis. Descriptive statistics were used to summarize pharmacokinetic parameters and comparisons with published reference values.

Results:
Of 25 participants, 92% were on efavirenz-based ART and 60.0% were men. Dolutegravir mean exposure, peak and trough concentrations at both pharmacokinetic visits were higher than the mean reference values in adults and children weighing 20 kg to less than 40 kg treated with 50 mg once daily, but were closer to the mean values in adults given 50 mg twice a day. Children weighing 20 kg to less than 40 kg had even higher dolutegravir exposures. The regimens were well tolerated with good virologic efficacy through week 48.

Conclusion:
The higher dolutegravir exposure in our study population suggests that further studies and close monitoring should investigate the adverse effects of dolutegravir in more children and in the long term.