bluuebunny/crossref_metadata_2025 huggingface dataset:
Birth weight and subclinical cardiovascular and renal damage in a population-based study (the STANISLAS cohort study)
Authors: Lopez-Sublet Marilucy , Merkling Thomas , Girerd Nicolas , Xhaard Constance , Flahault Adrien , Bozec Erwan , Leroy Celine , Fujikawa Tomona , Vaag Allan Arthur , Mebazaa Alexandre , Kistorp Caroline Michaela , Heude Barbara , Boivin Jean Marc , Zannad Faiez , Wagner Sandra , Rossignol Patrick
Published: April 2023

Objective:

Although preterm-born and low-birth-weight individuals have an increased risk of cardiovascular diseases in adulthood, little is known regarding early cardiovascular and renal damage (CVRD) or hypertension in adulthood. Our study investigated the association of birth weight with early CVRD markers as well as the heritability of birth weight in an initially healthy family-based cohort.

Methods:

This study was based on 1028 individuals from the familial longitudinal STANISLAS cohort (399 parents/629 children) initiated in 1993–1995, with a fourth examination conducted in 2011–2016. Analyses performed at the fourth visit included pulse-wave velocity, central pressure, ambulatory blood pressure, hypertension status, diastolic dysfunction/distensibility, left ventricular mass indexed (LVMI), carotid intima–media thickness and kidney damage. The family structure of the cohort allowed birth weight heritability estimation.

Results:

Mean (±SD) birth weight was 3.3 ± 0.6 kg. Heritability was moderate (42–44%). At the fourth visit, individuals were 37 years old (32.0–57.0), 56% were women and 13% had antihypertensive treatment. Birth weight was strongly and negatively associated with hypertension [odds ratio (OR) 95% confidence interval (CI) 0.61 (0.45–0.84)]. A nonlinear association was found with LVMI, participants with a birth weight greater than 3 kg having a higher LVMI. A positive association (β 95% CI 5.09 (1.8–8.38)] was also observed between birth weight and distensibility for adults with normal BMI. No associations were found with other CVRD.

Conclusion:

In this middle-aged population, birth weight was strongly and negatively associated with hypertension, and positively associated with distensibility in adults with normal BMI and with LVMI for higher birth weights. No associations were found with other CVRD markers.
The association between arterial compliance, as assessed by PTC1 and PTC2 from radial artery waveforms, and age, sex, and race/ethnicity
Authors: Brumback Lyndia C. , Andrews Leah I.B. , Jacobs David R. , Duprez Daniel A. , Thepaksorn Elizabeth Hom , Kaufman Joel D. , Denenberg Julie O. , Allison Matthew A.
Published: April 2023

Background:

There is limited literature on differences in arterial compliance, as assessed from arterial pressure waveforms, with age, sex, and race/ethnicity. PTC1 and PTC2 are indices of arterial compliance, which are derived from a Windkessel model of the waveform, relatively easy to obtain, and associated with cardiovascular disease.

Method:

PTC1 and PTC2 were computed from radial artery waveforms from participants of the Multi-Ethnic Study of Atherosclerosis at baseline and again 10 years later. We evaluated the association of PTC1, PTC2, and 10-year change in PTC1 and PTC2 with age, sex, and race/ethnicity.

Results:

Among 6245 participants in 2000–2002 (mean ± SD of age was 62 ± 10 years; 52% female; 38% White, 12% Chinese, 27% Black, and 23% Hispanic/Latino), means ± SDs for PTC1 and PTC2 were 394 ± 334 and 94 ± 46 ms. After adjustment for cardiovascular disease risk factors, mean PTC2 was 1.1 ms (95% confidence interval: 1.0, 1.2) lower (arterial stiffness was greater) per year older age, was 22 ms (19, 24) lower for females, and varied by race/ethnicity (P < 0.001; e.g., 5 ms lower for Blacks compared with Whites), although the differences were smaller at older ages (P < 0.001 for age-sex, P < 0.001 for age-race/ethnicity interactions). Among 3701 participants with repeat measurements in 2010–2012, arteries had stiffened (mean ± SD 10-year decrease in PTC2: 13 ± 46 ms) consistent with cross-sectional age-trend and tended to stiffen less for females and Blacks consistent with cross-sectional age-interactions.

Conclusion:

Differences in arterial compliance by age, sex, and race/ethnicity lend support to identify and act on societal factors that may drive health disparities.
Amlodipine limits microglia activation and cognitive dysfunction in aged hypertensive mice
Authors: Kerkhofs Danielle , Helgers Robin , Hermes Denise , Steinbusch Hellen P.J. , Van Essen Helma , Leenders Peter , Prickaerts Jos , Staals Julie , Biessen Erik A. , Van Oostenbrugge Robert J. , Foulquier Sébastien
Published: April 2023

Background:

SBP and blood pressure variability are independent risk factors for cerebral small vessel disease, a leading cause for stroke and dementia. Calcium-channel blockers are known to reduce blood pressure variability and may thus offer benefit against dementia. Beyond this effect, the impact of calcium-channel blockers on hypertension-induced neuroinflammation, and especially, microglial phenotype remains unknown. We aimed to study the ability of amlopidine to alleviate microglia inflammation, and slow down cognitive dysfunction in aged hypertensive mice.

Methods:

Hypertensive BPH/2J and normotensive BPN/3J mice were studied until 12 months of age. Hypertensive mice were untreated or received amlodipine (10 mg/kg per day). Blood pressure parameters were measured by telemetry and tail cuff plethysmography. Mice underwent repeated series of cognitive tasks. Brain immunohistochemistry was performed to study blood–brain barrier dysfunction and microglial pro-inflammatory phenotype (CD68+Iba1+ cells; morphological analysis).

Results:

Amlodipine normalized SBP over the entire life span and decreased blood pressure variability. BPH/2J mice exhibited impaired short-term memory that was prevented by amlodipine at 12 months (discrimination index 0.41 ± 0.25 in amlodipine-treated vs. 0.14 ± 0.15 in untreated BPH/2J mice, P = 0.02). Amlopidine treatment of BPH/2J did not prevent blood–brain barrier leakage, a measure of cerebral small vessel disease, but limited its size. Microglia's inflammatory phenotype in BPH/2J, characterized by an increased number of Iba1+CD68+ cells, increased soma size and shortened processes, was partly reduced by amlodipine.

Conclusion:

Amlodipine attenuated the short-term memory impairment in aged hypertensive mice. Beyond its blood pressure lowering capacity, amlodipine may be cerebroprotective by modulating neuroinflammation.
The United States Navy and Employees with Cancer: The Time for Change Is Now
Authors: Sowers Daniel , Caffrey Emily , Harris Jason , Specht Aaron , Hamrick Barbara , Frandsen Jared , Dant Tyler
Published: April 2023

The US Navy, including the US Marine Corps and Naval Nuclear Propulsion Program (NNPP), has a robust radiological protection and monitoring program meeting (and typically exceeding, in the name of conservatism) federal law requirements. The program covers the variety of ways in which the Navy produces and uses ionizing radiation and radioactive sources: in medicine, nuclear ship propulsion and repair, industrial and aircraft radiography, and myriad other unique uses in carrying out its vital mission. In executing these programs, thousands of people across the world are employed as active-duty Sailors and Marines, government civilians, and government contractors. These workers include physicians, reactor operators, radiation safety officers, and nuclear repair workers, to name but a few. The health protection standards for these workers are promulgated in the publicly available Navy Medicine P-5055 Radiation Health Protection Manual (NAVMED P-5055), published February 2011 with Change 2 published December 2022, and are applicable to Navy and Marine Corps and NNPP radiation protection programs. The NAVMED P-5055 outlines the individual medical requirements for those qualified and able to receive exposure to ionizing radiation as part of their duties and requires that “Radiation workers receive focused medical examinations to establish whether or not cancer is present which would medically disqualify a person from receiving occupational radiation exposure.” Additionally, without scientific or medical basis, the NAVMED P-5055 requires disqualifying those employees who have a history of cancer, cancer therapy, radiation therapy including radiopharmaceuticals received for therapeutic purposes, or bone marrow suppression from drawing dosimetry, entering radiation areas, or handling radioactive material. This policy, which exists regardless of lifetime occupational radiation dose or projected future radiation dose, applies to all cancers except adequately treated basal cell carcinoma. The policy is not supported by relevant scientific and medical literature; does not align with reasonable professional ethical standards; does not conform to US Navy radiological training, which stipulates the assumed increased risk of developing cancer from Navy and Marine Corps and NNPP occupational radiation exposure is small; and removes critical leadership and mentoring capability from the workforce unnecessarily. This article discusses in detail (1) this policy and its ramifications to the Navy and Marine Corps and NNPP workforce and (2) recommendations, benefits, and impacts for the Navy and Marine Corps and NNPP to remove this policy and still maintain a robust radiation protection program.
Evaluation of sagittal root position and labial alveolar bone concavity in the maxillary anterior tooth area for immediate implant placement
Authors: Ikbal Muhammad , Shen Yen-Wen , Ruslin Muhammad , Fuh Lih-Jyh , Hsu Jui-Ting
Published: April 2023

Background:

The anatomical characteristics of the maxillary labial alveolar bone play a crucial role in the treatment planning of immediate implant placement. The sagittal root position (SRP) and alveolar bone concavity are closely related to anatomical characteristics in determining the ideal implant position. This study evaluated the SRP and labial alveolar bone concavity in the maxillary anterior teeth area.

Methods:

Cone-beam computed tomography images of 120 samples involving 720 teeth were uploaded to the medical imaging software. The SRP was classified as Class I, II, III, or IV, and the concavity of labial alveolar bone was measured. A T test was performed to compare measurements between the central and lateral incisors, between the central incisors and canines, and between the lateral incisors and canine.

Results:

The majority of the SRPs of the maxillary anterior teeth were class I (engaging the labial cortical plate) with frequencies of 98.3%, 85.8%, and 81.7% for the canines, lateral incisors, and central incisors, respectively. In terms of concavity of labial alveolar bone in maxillary tooth area, canines also had the largest mean value (139.5°), followed by lateral incisors, whereas central incisors has the smallest mean value (131.7°). The results of the T test revealed a significant difference (p < 0.001) in labial alveolar bone concavity between central and lateral incisors, between central incisors and canines, and between lateral incisors and canines.

Conclusion:

Most maxillary anterior teeth were classified as Class I SRP, Class III SRP was the least prevalent, and the concavity of the labial alveolar bone significantly differed between the central and lateral incisors, between the central incisors and canines, and between the lateral incisors and canines. In addition, the canines had the highest mean alveolar bone concavity angle, indicating that less concavity in the canines area.
Probiotics and Antibiotic-Associated Diarrhea in Pediatric Complicated Appendicitis
Authors: Garcia Mayra G. , Dutton Hayden , Cochrum Bailey , Chen Peng
Published: April 2023

Introduction

An appendectomy is the most common urgent surgical intra-abdominal procedure performed on children. Approximately one third of the population ends up having complicated appendicitis requiring the use of intravenous antibiotics and a prolonged hospital stay. Antibiotic-associated diarrhea (AAD) is a common obstacle seen in both outpatient and inpatient settings. Use of probiotics in a pediatric population exposed to antibiotics and gastrointestinal surgery such as an appendectomy may provide a protective effect and prevent AAD.

Methods

This study was a prospective randomized controlled trial conducted at a large freestanding pediatric hospital. Patients in the treatment group received a standard dose of Lactobacillus rhamnosus GG capsule twice a day until discharge, and those in the control group received a placebo twice a day until discharge. In this study, we hypothesize that patients given probiotics will decrease the overall length of stay (LOS) by 25% versus the LOS in those patients who do not receive probiotics.

Results

Ninety-eight patients were randomized, with 93 included in the data analysis, into the probiotic group ( n = 57) and the placebo group ( n = 41). The LOS for the probiotic group ( n = 53; M = 121.55, SD = 59.51) was lower than that for the placebo group ( n = 40; M = 131.69, SD = 74.27) but was not found to be statistically different ( t(91) = 0.731, p = .467). The average total number of diarrhea counts was higher in the probiotic group ( M = 13, SD = 16) than in the placebo group ( M = 10, SD = 11) but was not found to be statistically different ( t(91) = −1.017, p = .312).

Discussion

Use of probiotics to reduce AAD has been found to be effective in other patient populations. Because of the small sample size, we were unable to determine if the use of L. rhamnosus in patients with complicated appendicitis was effective in reducing the LOS or average diarrhea counts.
Case Report: Corneal Inlay Removal after Myofibroblast Detection under in Vivo Confocal Microscopy
Authors: Yoshitomi Suzu , Chikama Taiichiro , Kiuchi Yoshiaki
Published: April 2023

SIGNIFICANCE

Corneal inlays, one of the treatment options for presbyopia, are effective and safe, and various such devices have been developed. However, there have been cases of inlay removal due to complications or patient dissatisfaction.

PURPOSE

The purpose of this study was to report a case of inlay removal due to corneal opacity after inlay implantation and the results of 5 years of follow-up.

CASE REPORT

A 63-year-old man was referred to our hospital with visual disturbance and double vision in his left eye. Two years before presentation at our hospital, he had undergone bilateral laser in situ keratomileusis with corneal inlay implantation in the left eye at another clinic. Slit-lamp examinations showed paracentral corneal opacity. The patient was treated with tranilast eye drops for 18 months, with no progression of symptoms. However, 6 months after stopping the eye drop treatment, the opacity recurred, and vision acuity decreased, along with the formation of myofibroblasts around the inlay, as revealed by in vivo confocal microscopy. Consequently, the inlay was removed at the previous clinic. During the subsequent 5-year follow-up period, ophthalmic examination revealed reduced corneal opacity, although visual acuity did not change; moreover, no myofibroblast was found.

CONCLUSIONS

Corneal inlays can sometimes cause complications. In this case, the patient experienced corneal fibrosis and associated vision loss. In vivo confocal microscopy detected myofibroblasts that cause corneal stromal fibrosis; thus, the removal was decided to avoid fibrosis progression.
Examining the Comprehensiveness of Amended Flavored Tobacco Product Sales Restrictions
Authors: Donovan Emily M. , Azadi Mona , Akbar Maham , Schillo Barbara A.
Published: April 2023

Context:

Flavored tobacco products contribute significantly to youth tobacco initiation and tobacco use disparities. In the last decade, 362 jurisdictions have enacted policies restricting the sale of flavored tobacco products; however, many policies are not fully comprehensive due to menthol and adult-only retailer exemptions. Although several of these restrictions have been amended since their original passage, to date, little is known about how amendments have affected policy comprehensiveness.

Objective:

To describe how amendments to flavored tobacco product sales restrictions affect policy comprehensiveness.

Design:

We identified flavored tobacco product sales restrictions that had been amended at least once using an internal database of US state and local flavored tobacco product sales restrictions. To characterize policy comprehensiveness, we applied a 6-level flavored tobacco policy classification scheme—level 6 being most comprehensive—to amended restrictions. We conducted a descriptive analysis of each initial policy and its most recent amendment to identify changes in retailer, product, and flavor inclusions, as well as overall comprehensiveness.

Main Outcome Measure(s):

Comprehensiveness of amended flavored tobacco product sales restrictions.

Results:

As of March 31, 2022, no states and 50 localities had amended their flavored tobacco product sales restriction. Amendments largely increased policy comprehensiveness; most laws prior to amendment were categorized as level 1 (n = 28, 56.0%), while after amendment, the plurality were categorized as level 6 (n = 25, 50.0%). Most commonly, amendments removed menthol exemptions (n ≥ 30, 60.0%) and adult-only retailer exemptions (n = 12, 24.0%).

Conclusions:

Several local flavored tobacco product sales restrictions have been amended. Nearly all amendments increased policy comprehensiveness, primarily by removing exemptions for menthol products and exemptions for adult-only retailers. While policy advocates remain focused on passing comprehensive policies at initial passage, amendments have served as a tool to strengthen existing sales restrictions. This study along with ongoing flavored tobacco product sales restriction surveillance can inform policy advocacy and evaluation efforts.
“Systematic review of nonsyndromic craniosynostosis: genomic alterations and impacted signaling pathways.”
Authors: Albaugh Shaley L. , Diaz Ashley , Wang Esther , Shen Timothy C. , Williams Lydia , He Tong-Chuan , Reid Russell R.
Published: April 2023

Background:

Genetic research in nonsyndromic craniosynostosis remains limited compared to syndromic craniosynostosis. This systematic review aimed to comprehensively summarize the genetic literature of nonsyndromic craniosynostosis and highlight key signaling pathways.

Methods:

The authors performed a systematic literature search of PubMed, Ovid, and Google Scholar databases from inception until December 2021 using search terms related to nonsyndromic craniosynostosis and genetics. Two reviewers screened titles and abstract for relevance, and three reviewers independently extracted study characteristics and genetic data. Gene networks were constructed using STRING11 analysis.

Results:

Thirty-three articles published between 2001 and 2020 met inclusion criteria. Studies were further classified into candidate gene screening and variant identification studies (16), genetic expression studies (13) and common and rare variant association studies (4). Most studies were good quality. Using our curated list of one-hundred and sixteen genes extracted from the studies, 2 main networks were constructed.

Conclusions:

This systematic review concerns the genetics of nonsyndromic craniosynostosis, with network construction revealing TGF-β/BMP, Wnt, and NF-kB/RANKL as important signaling pathways. Future studies should focus on rare rather than common variants to examine the missing heritability in this defect and going forward, adopt a standard definition.
Performance of a modified fracture risk assessment tool for fragility fracture prediction among older veterans living with HIV
Authors: Womack Julie A. , Murphy Terrence E. , Leo-Summers Linda , Kidwai-Khan Farah , Skanderson Melissa , Gill Thomas M. , Gulanski Barbara , Rodriguez-Barradas Maria C. , Tien Phyllis C. , Yin Michael T. , Hsieh Evelyn
Published: April 2023

Objective:

Fragility fractures (fractures) are a critical outcome for persons aging with HIV (PAH). Research suggests that the fracture risk assessment tool (FRAX) only modestly estimates fracture risk among PAH. We provide an updated evaluation of how well a ‘modified FRAX’ identifies PAH at risk for fractures in a contemporary HIV cohort.

Design:

Cohort study.

Methods:

We used data from the Veterans Aging Cohort Study to evaluate veterans living with HIV, aged 50+ years, for the occurrence of fractures from 1 January 2010 through 31 December 2019. Data from 2009 were used to evaluate the eight FRAX predictors available to us: age, sex, BMI, history of previous fracture, glucocorticoid use, rheumatoid arthritis, alcohol use, and smoking status. These predictor values were then used to estimate participant risk for each of two types of fractures (major osteoporotic and hip) over the subsequent 10 years in strata defined by race/ethnicity using multivariable logistic regression.

Results:

Discrimination for major osteoporotic fracture was modest [Blacks: area under the curve (AUC) 0.62; 95% confidence interval (CI) 0.62, 0.63; Whites: AUC 0.61; 95% CI 0.60, 0.61; Hispanic: AUC 0.63; 95% CI 0.62, 0.65]. For hip fractures, discrimination was modest to good (Blacks: AUC 0.70; 95% CI 0.69, 0.71; Whites: AUC 0.68; 95% CI 0.67, 0.69]. Calibration was good in all models across all racial/ethnic groups.

Conclusion:

Our ‘modified FRAX’ exhibited modest discrimination for predicting major osteoporotic fracture and slightly better discrimination for hip fracture. Future studies should explore whether augmentation of this subset of FRAX predictors results in enhanced prediction of fractures among PAH.
Experiencing homelessness and progression through the HIV cascade of care among people who use drugs
Authors: Reddon Hudson , Fairbairn Nadia , Grant Cameron , Milloy M-J
Published: April 2023

Objective:

To investigate the longitudinal association between periods of homelessness and progression through the HIV cascade of care among people who use drugs (PWUD) with universal access to no-cost HIV treatment and care.

Design:

Prospective cohort study.

Methods:

Data were analysed from the ACCESS study, including systematic HIV clinical monitoring and a confidential linkage to comprehensive antiretroviral therapy (ART) dispensation records. We used cumulative link mixed-effects models to estimate the longitudinal relationship between periods of homelessness and progression though the HIV cascade of care.

Results:

Between 2005 and 2019, 947 people living with HIV were enrolled in the ACCESS study and 304 (32.1%) reported being homeless at baseline. Homelessness was negatively associated with overall progression through the HIV cascade of care [adjusted partial proportional odds ratio (APPO) = 0.56, 95% confidence interval (CI): 0.49–0.63]. Homelessness was significantly associated with lower odds of progressing to each subsequent stage of the HIV care cascade, with the exception of initial linkage to care.

Conclusions:

Homelessness was associated with a 44% decrease in the odds of overall progression through the HIV cascade of care, and a 41–54% decrease in the odds of receiving ART, being adherent to ART and achieving viral load suppression. These findings support calls for the integration of services to address intersecting challenges of HIV, substance use and homelessness among marginalized populations such as PWUD.
Pilot imaging of the colony stimulating factor 1 receptor in the brains of virally-suppressed individuals with HIV
Authors: Rubin Leah H. , Du Yong , Sweeney Shannon Eileen , O’Toole Riley , Harrington Courtney K. , Jenkins Katelyn , Lesniak Wojciech G. , Veenhuis Rebecca T. , Dastgheyb Raha , Severson Joan , Fan Hong , Holt Daniel P. , Hall Andrew W. , Dannals Robert F. , Horti Andrew G. , Pomper Martin G. , Coughlin Jennifer M.
Published: April 2023

Objective:

Neuroimmune activation is a putative driver of cognitive impairment in people with HIV (PWH), even in the age of modern antiretroviral therapy. Nevertheless, imaging of the microglial marker, the 18 kDa translocator protein (TSPO), with positron emission tomography (PET) in treated PWH has yielded inconclusive findings. One potential reason for the varied TSPO results is a lack of cell-type specificity of the TSPO target.

Design:

[11C]CPPC, 5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl) furan-2-carboxaminde, is a radiotracer for use with PET to image the colony stimulating factor 1 receptor (CSF1R). The CSF1R is expressed on microglia and central nervous system macrophages, with little expression on other cell types. We used [11C]CPPC PET in virally-suppressed- (VS)-PWH and HIV-uninfected individuals to estimate the effect sizes of higher CSF1R in the brains of VS-PWH.

Methods:

Sixteen VS-PWH and 15 HIV-uninfected individuals completed [11C]CPPC PET. [11C]CPPC binding (VT) in nine regions was estimated using a one-tissue compartmental model with a metabolite-corrected arterial input function, and compared between groups.

Results:

Regional [11C]CPPC VT did not significantly differ between groups after age- and sex- adjustment [unstandardized beta coefficient (B) = 1.84, standard error (SE) = 1.18, P = 0.13]. The effect size was moderate [Cohen's d = 0.56, 95% confidence interval (CI) −0.16, 1.28), with strongest trend of higher VT in VS-PWH in striatum and parietal cortex (each P = 0.04; Cohen's d = 0.71 and 0.72, respectively).

Conclusions:

A group difference in [11C]CPPC VT was not observed between VS-PWH and HIV-uninfected individuals in this pilot, although the observed effect sizes suggest the study was underpowered to detect regional group differences in binding.
Stunted Growth Is Associated With Dyslipidemia in Young Adults With Perinatal HIV Infection
Authors: Lesiapeto Maemo , Shults Justine , Mmunyane Mogakolodi , Matshaba Mogomotsi , Lowenthal Elizabeth D.
Published: April 2023

Background:

HIV increases the risk of atherosclerosis and cardiovascular diseases (CVD). This risk maybe even higher in adult survivors of perinatal HIV infection because of prolonged exposure to HIV and its treatments. Nutritional deprivation in early life may further increase CVD risk.

Setting:

Botswana-Baylor Children's Clinical Centre of Excellence, Gaborone.

Methods:

This study examined dyslipidemia in 18- to 24-year olds with perinatally-acquired HIV with and without linear growth retardation (“stunting”). Anthropometry and lipid profiles were measured following a minimum 8-hour fast. Stunting was defined by a height-for-age z-score of <2 SDs below the mean. Dyslipidemia was defined by non–high-density lipoprotein cholesterol (HDL-C) of ≥130 mg/dL, low-density lipoprotein cholesterol (LDL-C) of ≥100 mg/dL, or HDL of <40 mg/dL for male subjects and <50 mg/dL for female subjects. We used logistic regression to determine whether dyslipidemia was associated with stunting while adjusting for demographic and HIV treatment variables.

Results:

Of 107 young adults (46 males; 61 females) enrolled, 36 (33.6%) were stunted. Prevalence of dyslipidemia was 11.2%, 24.3%, and 65.4% for high non-HDL-C, high LDL-C, and low HDL-C, respectively. In univariable analysis, being stunted was associated with elevated LDL-C (odds ratio [OR], 2.52; 95% confidence interval [CI] =1.02 to 6.25) but not with elevated non-HDL-C (OR = 2.17; 95% CI: = 0.65 to 7.28) or with low HDL-C (OR = 0.75; 95% CI: = 0.33 to 1.73). The association between stunting and elevated LDL-C (OR = 4.40; 95% CI: = 1.49 to 12.98) remained significant after controlling for measured confounders.

Conclusion:

Dyslipidemia was common among perinatally HIV-infected youth and those with evidence of early nutritional deprivation who were more likely to have elevated LDL-C.
ALTERED LEVELS OF H3K9AC, H3K4ME3, AND H3K27ME3 IN PROMOTERS OF DIFFERENTIALLY EXPRESSED GENES RELATED TO INNATE IMMUNE RESPONSE IN SEPTIC PATIENTS WITH DIFFERENT CLINICAL OUTCOMES
Authors: Falcão-Holanda Renata Brito , Leite Giuseppe Gianini Figueirêdo , Brunialti Milena Karina Colo , Jasiulionis Miriam Galvonas , Salomão Reinaldo
Published: April 2023

Sepsis is one of the leading causes of morbidity and mortality worldwide. Monocytes seem to undergo functional reprogramming during sepsis, resulting in dysregulated host immune response. To clarify this dysregulation mechanism, we investigated three histone modifications found in promoters of genes involved in innate immune response, and associated these findings with gene transcription in septic patients. These results were compared with public transcriptome data of the target genes and epigenetic enzymes that modulate the histone modifications. We used peripheral blood mononuclear cell from surviving and nonsurviving septic patients, and healthy volunteers to evaluate the expression of genes involved in innate immune response and the enrichment of H3K9ac, H3K4me3, and H3K27me3 in their promoters, by RT-qPCR and ChIP, respectively. Finally, we used transcriptome data sets to validate our findings. We found alterations in the chromatin enrichment of different genes, with an increase in H3K9ac in the anti-inflammatory cytokine IL-10 and the antimicrobial gene FPR1, as well as an increase in H3K27me3 in the IL-10 and HLA-DR promoter in nonsurvivors septic patients when compared with survivors. These alterations were partially associated with the gene expression profile. In addition, we found moderate to strong correlation between gene transcription and the enzymes that modulate these histone modifications in the transcriptome data sets. Our study, one of the pioneering by evaluating septic patients’ samples, suggests that epigenetic enzymes modulate the prevalent histone marks in promoters of genes involved in the immune-inflammatory response, altering the transcription of these specific genes during sepsis. Furthermore, nonsurviving sepsis patients have a more pronounced epigenetic dysregulation compared with survivors, suggesting a more dysfunctional response.
Decision-making About Premortem Interventions for Donation: Navigating Legal and Ethical Complexities
Authors: Then Shih-Ning , Martin Dominique E. , McGee Andrew , Gardiner Dale , El Moslemani Nadia
Published: April 2023

Premortem interventions (PMIs) for organ donation play a vital role in preserving opportunities for deceased donation or increasing the chances of successful transplantation of donor organs. Although ethical considerations relating to use of particular PMIs have been well explored, the ethical and legal aspects of decision-making about the use of PMIs have received comparatively little attention. In many countries, there is significant uncertainty regarding whether PMIs are lawful or, if they are, who can authorize them. Furthermore, emphasis on consideration of therapeutic goals in substitute decision-making frameworks may discourage consideration of donation goals. In this article, we examine the fundamental questions of who should have the authority to make decisions about the use of PMIs on behalf of a potential donor and how such decisions should be made. We draw on international examples of legal reform that have sought to clarify the legal position in relation to administering PMIs and identify potential elements of an effective regulatory model for PMIs. In doing so, we argue that reforms are needed in many countries to provide legal certainty for clinicians who are responsible for supporting decision-making about PMIs and to ensure that the goals and preferences of potential donors are accorded due consideration in the decision-making process.
Two artificial tears outbreak-associated cases of XDRPseudomonas aeruginosadetected through whole genome sequencing-based surveillance
Authors: Sundermann Alexander J. , Srinivasa Vatsala Rangachar , Mills Emma G. , Griffith Marissa P. , Waggle Kady D. , Ayres Ashley M. , Pless Lora , Snyder Graham M. , Harrison Lee H. , Van Tyne Daria
Published: April 2023

We describe two cases of XDRPseudomonas aeruginosainfection caused by a strain of public health concern recently associated with a nationwide outbreak of contaminated artificial tears. Both cases were detected through database review of genomes in the Enhanced Detection System for Hospital-Associated Transmission (EDS-HAT), a routine genome sequencing-based surveillance program. We generated a high-quality reference genome for the outbreak strain from one of the case isolates from our center and examined the mobile elements encodingblaVIM-80andblaGES-9carbapenemases. We then used publicly availableP. aeruginosagenomes to explore the genetic relatedness and antimicrobial resistance genes of the outbreak strain.
Exploring non-linear associations of maternal pre-pregnant body mass index with risk of stillbirth, infant and neonatal mortality in over 21 million US births
Authors: Thornton Hannah V , Cornish Rosie P , Lawlor Deborah A
Published: April 2023

Background

Higher maternal pre-pregnancy body mass index (BMI) has been associated with higher risk of stillbirth, infant and neonatal mortality. Few studies have explored associations of underweight, with those that have varying in their conclusions. Our aim was to examine the risk of stillbirth, infant and neonatal mortality across the pre-pregnancy BMI distribution and establish a likely healthy BMI range.

Methods

We used publicly available birth, infant death and fetal death datasets from the US National Center for Health Statistics National Vital Statistics System, 2014–2020. Fractional polynomial multivariable logistic regression was used to examine the nature of associations between maternal pre-pregnant BMI and stillbirth (birth with no signs of life at ≥24 weeks), infant mortality (death of a live born baby aged <365 days) and neonatal mortality (death of a live born baby aged <28 days).

Findings

There were 56,376/21,437,556 (0.26%) stillbirths, 108,413/24,742,273 (0.44%) infant deaths and 66,801/24,742,273 (0.27%) neonatal deaths among complete cases. Mean BMI was 27.0 kg/m2. We found non-linear associations between pre-pregnant BMI and all three outcomes - risk was elevated at both low and high BMIs although, for stillbirth, the increased risk at low BMI was less marked than for infant and neonatal mortality. The lowest risk was at a BMI of 21 kg/m2for infant and neonatal mortality and, for stillbirth, at 18 kg/m2.

Interpretation

Public health messaging for preconception and postnatal care should focus on healthy weight to maximise maternal and child health, and not focus solely on maternal overweight or obesity.
Nowcasting and Forecasting the 2022 U.S. Mpox Outbreak: Support for Public Health Decision Making and Lessons Learned
Authors: Charniga Kelly , Madewell Zachary J. , Masters Nina B. , Asher Jason , Nakazawa Yoshinori , Spicknall Ian H.
Published: April 2023

In June of 2022, the U.S. Centers for Disease Control and Prevention (CDC) Mpox Response wanted timely answers to important epidemiological questions which can now be answered more effectively through infectious disease modeling. Infectious disease models have shown to be valuable tool for decision making during outbreaks; however, model complexity often makes communicating the results and limitations of models to decision makers difficult. We performed nowcasting and forecasting for the 2022 mpox outbreak in the United States using the R package EpiNow2. We generated nowcasts/forecasts at the national level, by Census region, and for jurisdictions reporting the greatest number of mpox cases. Modeling results were shared for situational awareness within the CDC Mpox Response and publicly on the CDC website. We retrospectively evaluated forecast predictions at four key phases during the outbreak using three metrics, the weighted interval score, mean absolute error, and prediction interval coverage. We compared the performance of EpiNow2 with a naïve Bayesian generalized linear model (GLM). The EpiNow2 model had less probabilistic error than the GLM during every outbreak phase except for the early phase. We share our experiences with an existing tool for nowcasting/forecasting and highlight areas of improvement for the development of future tools. We also reflect on lessons learned regarding data quality issues and adapting modeling results for different audiences.
Interference between Venus-A Valve and Anterior Mitral Valve Leaflets after Transcatheter Aortic Valve Replacement: Insight from FEops HEARTguide simulation
Authors: Wang Yong , Liu Ting , Zeng Ying , Debusschere Nic , Rocatello Giorgia , Cheng Sihang , Li Ping , Qian Dehui , Yu Shiyong , Jin Jun
Published: April 2023

Background

Scarce data exist regarding the occurrence of mitral valve interference after transcatheter aortic valve replacement (TAVR) with Venus-A valve implantation. Several case reports have noted that the anterior mitral leaflet (AML) is mechanically affected by the prosthesis frame, particularly when implanted in a low position. This study aimed to investigate the potential factors influencing the clinical outcomes of AML interference after Venus-A valve implantation.

Methods

We retrospectively included 20 severe aortic valve stenosis patients who had undergone TAVR and had been implanted with the Venus-A valve at our hospital between October 2020 and June 2021. Pre- and post-procedural CT scans were used for the FEops HEARTguide simulation. Anatomically influencing factors were measured using the 3mensio software and derived from the FEops HEARTguide. The prosthesis-AML interference (PAI) was defined when it met both of two criteria:1) significant interference and limited AML movement shown by transthoracic or transoesophageal echocardiography, and 2) more than half cell intersection between the simulated Venus-A valve and the reconstructed AML revealed by the FEops HEARTguide. Anatomical factors and clinical outcomes were compared between the PAI and non-PAI groups.

Results

Nine PAI patients and 11 non-PAI cases were identified. PAI was associated with shorter mitral-aortic annulus distance (2.7±1.7 mm vs 5.0±2.2 mm,P= 0.019), larger prosthesis valve size (P= 0.013), deeper implantation (12.2±3.3 mm vs 6.2±2.9 mm at non-coronary cusp side,P< 0.001) and less calcification of non-coronary cusp (median calcification score, 52.2 mm3vs 156.0 mm3,P= 0.046). Regarding the clinical impact, PAI was associated with a higher rate of moderate or severe perivalvular leakage before discharge than those associated with the absence of PAI, with no difference in haemodynamic parameters and incidence of adverse events at the 30-day and 12-month follow-ups between the groups.

Conclusions

Interference between the Venus-A prosthesis valve and AML after TAVR was associated with a shorter mitral-aortic annulus distance, larger prosthesis usage, greater implantation depth, and less calcification of the non-coronary cusp. However, further studies are required to explore its long-term clinical impact.
Aspergillus SUMOylation mutants have normal dynein function but exhibit chromatin bridges
Authors: Zhang Jun , Qiu Rongde , Bieger Baronger D. , Oakley C. Elizabeth , Oakley Berl R. , Egan Martin J. , Xiang Xin
Published: April 2023

Abstract

Functions of protein SUMOylation remain incompletely understood in different cell types. The budding yeast SUMOylation machinery interacts with LIS1, a protein critical for dynein activation, but dynein-pathway components were not identified as SUMO-targets in the filamentous fungusAspergillus nidulans. ViaA. nidulansforward genetics, here we identifiedubaBQ247*, a loss-of-function mutation in a SUMO-activation enzyme UbaB. Colonies of theubaBQ247*, ΔubaBand ΔsumOmutants looked similar and less healthy than the wild-type colony. In these mutants, about 10% of nuclei are connected by abnormal chromatin bridges, indicating the importance of SUMOylation in the completion of chromosome segregation. Nuclei connected by chromatin bridges are mostly in interphase, suggesting that these bridges do not prevent cell-cycle progression. UbaB-GFP localizes to interphase nuclei just like the previously studied SumO-GFP, but the nuclear signals disappear during mitosis when the nuclear pores are partially open, and the signals reappear after mitosis. The nuclear localization is consistent with many SUMO-targets being nuclear proteins, for example, topoisomerase II whose SUMOylation defect gives rise to chromatin bridges in mammalian cells. Unlike in mammalian cells, however, loss of SUMOylation inA. nidulansdoes not apparently affect the metaphase-to-anaphase transition, further highlighting differences in the requirements of SUMOylation in different cell types. Finally, loss of UbaB or SumO does not affect dynein-and LIS1-mediated early-endosome transport, indicating that SUMOylation is unnecessary for dynein or LIS1 function inA. nidulans.
An explainable graph neural framework to identify cancer-associated intratumoral microbial communities
Authors: Liu Zhaoqian , Sun Yuhan , Ma Anjun , Wang Xiaoying , Xu Dong , Spakowics Daniel , Ma Qin , Liu Bingqiang
Published: April 2023

Microbes are extensively present among various cancer tissues and play a vital role in cancer prevention and treatment responses. However, the underlying relationships between intratumoral microbes and tumors are still not well understood. Here, we developed a MIcrobial Cancer-association Analysis using a Heterogeneous graph transformer (MICAH) to identify intratumoral cancer-associated microbial communities. MICAH integrates metabolic and phylogenetic relationships among microbes into a heterogeneous graph representation. It uses a graph attention transformer to holistically capture the relationships between intratumoral microbes and cancer tissues, which improves the explainability of the association between identified microbial communities and cancer. We applied MICAH to intratumoral microbiome data across five cancer types and demonstrated its good generalizability and reproducibility. We believe this graph neural network framework can provide novel insights into cancer pathogenesis associated with the intratumoral microbiome.
Gender differences in the distribution of children’s physical activity: evidence from nine countries
Authors: Kretschmer Luke , Salali Gul Deniz , Andersen Lars Bo , Hallal Pedro C , Northstone Kate , Sardinha Luís B. , Dyble Mark , Bann David ,   International Children’s Accelerometry Database (ICAD) Collaborators
Published: April 2023

Background

Physical activity in childhood is thought to influences health and development. Previous studies have found that boys are typically more active than girls, yet the focus has largely been on differences in average levels or proportions above a threshold rather than the full distribution of activity across all intensities. We thus examined differences in the distribution of physical activity between girls and boys in a multi-national sample of children.

Methods

We used the harmonised International Children Accelerometery Database (ICAD), including waist-worn accelerometery data from 15,461 individuals (Boys: 48.3%) from 9 countries. Employing Generalised Additive Models of Location, Shape, and Scale (GAMLSS) we investigated gender differences in the distribution of individuals, including comparisons of variability (SD) and average physical activity levels (mean and median) and skewness. We conducted this analysis for each activity intensity (Sedentary, Light, and Moderate-to-Vigorous (MVPA)) and a summary measure (counts per minute (CPM)).

Results

Sizable gender differences in the distribution of activity were found for moderate to vigorous activity and counts per minute, with boys having higher average levels (38% higher mean volumes of MVPA, 20% higher CPM), yet substantially more between-person variability (30% higher standard deviation (SD) for MVPA, 17% higher SD for CPM); boys’ distributions were less positively skewed than girls. Conversely, there was little to no difference between girls and boys in the distribution of sedentary or light-intensity activity.

Conclusions

Inequality in activity between girls and boys was driven by MVPA. The higher mean volumes of MVPA in boys occurred alongside greater variability. This suggests a need to consider the underlying distribution of activity in future research; for example, interventions which target gender inequality in MVPA may inadvertently lead to increased inequality within girls.
Disrupted-in-schizophrenia 1 (DISC1) protein aggregates in cerebrospinal fluid are elevated in first-episode psychosis patients
Authors: Pils Marlene , Rutsch Julia , Eren Feride , Engberg Göran , Piehl Fredrik , Cervenka Simon , Sellgren Carl , Troßbach Svenja , Willbold Dieter , Erhardt Sophie , Bannach Oliver , Korth Carsten
Published: April 2023

The Disrupted-in-schizophrenia 1 (DISC1) protein is a key regulator at the intersection of signaling pathways relevant for adaptive behavior. It is prone to posttranslational changes such as misassembly and aggregation but the significance of such transformations for human mental illness has remained unclear.

Here we demonstrate that DISC1 protein aggregates are increased in CSF samples of patients with first episode psychosis (n=50) compared to healthy controls (n=47), as measured by the highly sensitive surface-based fluorescence intensity distribution analysis technology that enables single aggregate detection. The concentration was in the low femtomolar range. No correlations were found to symptom levels, but the difference was particularly significant in the subset of patients receiving the diagnoses “schizophrenia, unspecified” (DSM IV 295.9) or schizoaffective disorder (DSM IV 295.70) at 18-month follow-up.

The occurrence of protein aggregatesin vivoin patients with psychotic disorders has not been previously reported. It underscores the significance of posttranslational modifications of proteins both as pathogenetic mechanisms and as potential diagnostic markers in these disorders.
Sentence superiority in the reading brain
Authors: Dufau Stéphane , Yeaton Jeremy , Badier Jean-Michel , Chen Sophie , Holcomb Phillip J. , Grainger Jonathan
Published: April 2023

When a sequence of written words is briefly presented and participants are asked to identify just one word at a post-cued location, then word identification accuracy is higher when the word is presented in a grammatically correct sequence compared with an ungrammatical sequence. This sentence superiority effect has been reported in several behavioral studies and two EEG investigations. Taken together, the results of these studies support the hypothesis that the sentence superiority effect is primarily driven by rapid access to a sentence-level representation via partial word identification processes that operate in parallel over several words. Here we used MEG to examine the neural structures involved in this early stage of written sentence processing, and to further specify the timing of the different processes involved. Source activities over time showed grammatical vs. ungrammatical differences first in the left inferior frontal gyrus (IFG: 325-400 ms), then the left anterior temporal lobe (ATL: 475-525 ms), and finally in both left IFG and left posterior superior temporal gyrus (pSTG: 550-600 ms). We interpret the early IFG activity as reflecting the rapid bottom-up activation of sentence-level representations, including syntax, enabled by partly parallel word processing. Subsequent activity in ATL and pSTG is thought to reflect the constraints imposed by such sentence-level representations on on-going word-based semantic activation (ATL), and the subsequent development of a more detailed sentence-level representation (pSTG). These results provide further support for a cascaded interactive-activation account of sentence reading.