bluuebunny/crossref_metadata_2025 huggingface dataset:
There’s an App for That: Exploring the Market for Contraceptive Fertility Tracking Apps in the Philippines
Authors: Danna K , Harris DM , Rothschild CW , Brogaard B , LaCroix E , Paudel M
Published: August 2023

For generations, women have relied on fertility awareness methods (FAM) to plan and prevent pregnancy; for over a decade, many have been aided by digital tools to do so. New Contraceptive Fertility Tracking Apps (CFTAs)--that are backed by clinical efficacy trials to support their effectiveness as contraception--have the potential to enhance method choice and offer users a unique contraceptive option, but there is little evidence to inform the decisions around expanding access, particularly in low-and middle-income countries (LMICs). We conducted a mixed methods study with quantitative online surveys (n=1600) and qualitative components (n=36) to explore the potential appeal of and demand for a hypothetical CFTA in one such market, the Philippines. Interest in using a CFTA was high among our internet-engaged, urban study population, with 83.9% “definitely” or “probably” interested in using. Across demographic profiles, respondents perceived the appeal of the method as “natural” and “convenient.” A majority were willing to pay for the method, though notably at a price (5.20 USD) below that of currently available CFTAs. We explore various factors to be considered before bringing a method like this to new markets, including equity constraints and the prevalence of other period-tracking apps not intended as contraception.
Breast density prediction from low and standard dose mammograms using deep learning: effect of image resolution and model training approach on prediction quality
Authors: Squires Steven , Harkness Elaine , Mackenzie Alistair , Evans D. Gareth , Howell Sacha J , Astley Susan M
Published: August 2023

Purpose

To improve breast cancer risk prediction for young women, we have developed deep learning methods to estimate mammographic density from mammograms taken at approximately 1/10thof the usual dose. We investigate the quality and reliability of the density scores produced on low dose mammograms focussing on how image resolution and levels of training affect the low dose predictions.

Methods

Deep learning models are developed and tested, with two feature extraction methods and an end-to-end trained method, on five different resolutions of 15,290 standard dose and simulated low dose mammograms with known labels. The models are further tested on a dataset with 296 matching standard and real low dose images allowing performance on the low dose images to be ascertained.

Results

Prediction quality on standard and simulated low dose images compared to labels is similar for all equivalent model training and image resolution versions. Increasing resolution results in improved performance of both feature extraction methods for standard and simulated low dose images, while the trained models show high performance across the resolutions. For the trained models the Spearman rank correlation coefficient between predictions of standard and low dose images at low resolution is 0.951 (0.937 to 0.960) and at the highest resolution 0.956 (0.942 to 0.965). If pairs of model predictions are averaged, similarity increases.

Conclusions

Deep learning mammographic density predictions on low dose mammograms are highly correlated with standard dose equivalents for feature extraction and end-to-end approaches across multiple image resolutions. Deep learning models can reliably make high quality mammographic density predictions on low dose mammograms.
Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection
Authors: Hurst Jillian H. , Mohan Aditya A. , Dalapati Trisha , George Ian A. , Aquino Jhoanna N. , Lugo Debra J. , Pfeiffer Trevor S. , Rodriguez Javier , Rotta Alexandre T. , Turner Nicholas A. , Burke Thomas W. , McClain Micah T. , Henao Ricardo , DeMarco C. Todd , Louzao Raul , Denny Thomas N. , Walsh Kyle M. , Xu Zhaohui , Mejias Asuncion , Ramilo Octavio , Woods Christopher W. , Kelly Matthew S.
Published: August 2023

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age.

One Sentence Summary

Age is associated with distinct upper respiratory and peripheral blood transcriptional responses among children and adults with SARS-CoV-2 infection.
Oxidative Status of the Ultra-Processed Foods in the Western Diet
Authors: Maldonado-Pereira Lisaura , Barnaba Carlo , Medina-Meza Ilce Gabriela
Published: August 2023

Ultra-processed foods (UPFs) and their nutritional value have become a trending topic in the scientific community because of their increasing demand, and their potentially adverse effects on human health. Besides the poor nutritional value attributed to UPFs, countless studies have also reported the presence of different dietary oxidized substances in these meals. DOxS are associated with several chronic diseases such as cardiometabolic diseases (CMD), cancer, diabetes, Parkinson’s, and Alzheimer’s disease. In this study, a database of DOxS and other dietary metabolites detected in 63 UPFs meals part of the Western diet is reported. Significant differences were found in DOxS and phytosterol contents between ready-to-eat and fast food (FF). Putative biomarkers were suggested for RTE (brassicasterol) and FF (7α-OH and 7β-OH), as well as for all 6 different food categories: dairy (brassicasterol), eggs & derivatives (stigmasterol and β-sitosterol), meat & poultry (7α-OH), seafood, baby food (β-sitosterol), and others (campesterol). Ideally, the use of dietary biomarkers could potentially help in the future to identify in an early stage the presence of different chronic diseases, and even, prevent their development. Nevertheless, an exposure assessment is critical to understand the exposure level of DOxS and their relationship with different chronic diseases.
Clustering of shoulder movement patterns using K-means algorithm based on the shoulder range of motion
Authors: Kim Jun-hee
Published: August 2023

Context

Categorization in medicine is used to enhance understanding of a disease or syndrome and apply it to treatment and is based on human clinical experience or theory. Cluster analysis using the K-means algorithm is an unsupervised machine learning method that classifies clusters based on numerical data. The purpose of this study was to classify subjects into clusters using K-means algorithm based on shoulder range of motion (ROM) and identify the characteristics of the clusters.

Design

Cross-sectional study

Methods

551 data samples measured in the 5th Size Korea Anthropometric Survey (2003∼2004) were used. Clustering was performed using the K-means algorithm, and the appropriate number of clusters was determined using the elbow curve and silhouette score. The characteristics of the clusters were analyzed by comparing the average values of shoulder ROM in the clusters.

Results

The appropriate number of classifications of clusters according to the shoulder ROM was 8. Clusters 1 and 5 had the lowest flexion range, and clusters 7 and 8 had low internal rotation and shoulder horizontal adduction ranges. Clusters 2 and 6 exhibited the highest flexion and overall high flexibility. Clusters 3 and 4 showed moderate flexion ranges but low horizontal adduction ranges. Shoulder movement patterns were classified into a total of 8 clusters according to the shoulder ROM.

Conclusion

Based on this clustering system, it was possible to identify the pattern of shoulder movement in ordinary people, and it could be used as basic data to identify and treat diseases or syndromes according to the pattern.
Copy-number variants as modulators of common disease susceptibility
Authors: Auwerx Chiara , Jõeloo Maarja , Sadler Marie C. , Tesio Nicolò , Ojavee Sven , Clark Charlie J. , Mägi Reedik ,   Estonian Biobank Research Team, Reymond Alexandre , Kutalik Zoltán
Published: August 2023

Background

Copy-number variations (CNVs) have been associated with rare and debilitating genomic syndromes but their impact on health later in life in the general population remains poorly described.

Methods

Assessing four modes of CNV action, we performed genome-wide association scans (GWASs) between the copy-number of CNV-proxy probes and 60 curated ICD-10 based clinical diagnoses in 331,522 unrelated white UK Biobank participants with replication in the Estonian Biobank.

Results

We identified 73 signals involving 40 diseases, all of which indicating that CNVs increased disease risk and caused earlier onset. Even after correcting for these signals, a higher CNV burden increased risk for 18 disorders, mainly through the number of deleted genes, suggesting a polygenic CNV architecture. Number and identity of genes disturbed by CNVs affected their pathogenicity, with many associations being supported by colocalization with both common and rare single nucleotide variant association signals. Dissection of association signals provided insights into the epidemiology of known gene-disease pairs (e.g., deletions inBRCA1andLDLRincreased risk for ovarian cancer and ischemic heart disease, respectively), clarified dosage mechanisms of action (e.g., both increased and decreased dosage of 17q12 impacts renal health), and identified putative causal genes (e.g.,ABCC6for kidney stones). Characterization of the pleiotropic pathological consequences of recurrent CNVs at 15q13, 16p13.11, 16p12.2, and 22q11.2 in adulthood indicated variable expressivity of these regions and the involvement of multiple genes.

Conclusions

Our results shed light on the prominent role of CNVs in determining common disease susceptibility within the general population and provide actionable insights allowing to anticipate later-onset comorbidities in carriers of recurrent CNVs.
Normal values for mitral and tricuspid early inflow blood flow velocity variation using real time phase contrast cardiovascular magnetic resonance
Authors: Thalén Simon , Heiberg Einar , Sörensson Peder , Giese Daniel , Sigfridsson Andreas , Ugander Martin
Published: August 2023

Background

Diastolic ventricular interdependence influences the breathing-induced variation in early diastolic blood flow velocities across the mitral and tricuspid valve. The aim of this study was to develop a method to measure the respiratory variation in mitral and tricuspid early inflow velocities using semi-automatic analysis of real time phase contrast (RT-PC) cardiovascular magnetic resonance (CMR) images, and describe normal reference values.

Methods

Clinically referred patients (n=24, median [interquartile range] age 55 [46– 65] years, 48% female) with no pericardial effusion or pericardial thickening underwent through-plane RT-PC CMR imaging using a research sequence at 3T in a basal short-axis view over a 30 s acquisition during free breathing. One patient with constrictive pericarditis and one patient with a hemodynamically significant pericardial effusion were imaged to illustrate clinical feasibility. Image analysis was performed using an in-house developed plugin. A region of interest was prescribed over encompassing the mitral and tricuspid orifices, respectively. The highest (Vmax) and lowest (Vmin) early inflow velocities were then automatically recorded. Respiratory variation was defined as (Vmax-Vmin)/Vmax.

Results

The respiratory variation in mitral and tricuspid early inflow velocity in patients without constrictive pericarditis or pericardial effusion was (mean±SD) 22±7% (upper limit 35%) and 38±7% (upper limit 51%). The patient with constrictive pericarditis had a respiratory variation in mitral and tricuspid early inflow velocities of 60% and 44%, respectively. The patient with 35 mm pericardial effusion had a respiratory variation in mitral and tricuspid early inflow velocities of 62% and 64%, respectively.
Immuno-inflammatory-related vulnerabilities and high mortality risk among patients with aggressive early-onset epithelial ovarian cancers in West Africa: A retrospective study
Authors: Okoye Jude Ogechukwu , Ado-Okoye Tochukwu Juliet , Emeka Chiemeka Michael , Eleje George Uchenna , Uduchi Immaculata Ogochukwu , Okoye Uchechukwu Lilian
Published: August 2023

Introduction

This study evaluated systemic immune-inflammatory indices (SIII) among patients with epithelial ovarian cancer (EOC) to identify affordable markers for disease assessment and treatment monitoring. This study did not assess the rate of BRCA2 mutation and SIII in early-onset (≤ 50 years old) and late-onset (> 50 years old) EOC but also evaluated SIII in treatment outcomes.

Methods

This study included 100 patients diagnosed with EOC from Jan. 2016 to Dec. 2021. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelets-neutrophils-to-lymphocytes ratio (PNLR), and neutrophils-to-lymphocytes platelets ratio (NLPR) were assessed and analyzed accordingly. Significance was set at p< 0.05.

Result

The frequency of early menarche, serous adenocarcinoma, and late-stage disease was 3.3, 1.6, and 1.4 times higher among patients with early-onset EOC compared with their late-onset counterparts (p= 0.001, 0.025, and 0.397, respectively). The frequency of BRCA2 mutation, hypertension, and diabetes was 2.5, 2.5, and 5.7 times higher among the latter than among the former (p= 0.001, 0.006, and 0.064, respectively). The pre-/post-treatment NLR and PNLR were 2.2/2.4 and 1.7/2.3 times higher among patients who died in the hospital than patients who were stable on discharge, respectively (p< 0.05). Although the pre-chemotherapy PNLR was 2.1 times higher among patients with stages I/II EOC compared with patients with stages III/IV EOC (p= 0.031), there was a 2.5 times significant decline and 1.1 times insignificant decline in pre-to-post-chemotherapy PNLR among the former and latter (p= 0.003 and 0.433, respectively). The post-treatment PNLR, PLR, and TWBC of herbal medicine-experienced patients were 5.6, 1.6, and 1.5, higher than the post-treatment values of naïve counterparts, respectively (p< 0.05).

Conclusion

This study revealed a high frequency of late-onset EOC but poor chemotherapy response among patients with aggressive early-onset. It suggests that NLR, PNLR, and PLR could be used to monitor disease progression and treatment outcomes.
Critical Illness Risk and Long-Term Outcomes Following Intensive Care in Pediatric Hematopoietic Cell Transplant Recipients
Authors: Zinter Matt S. , Brazauskas Ruta , Strom Joelle , Chen Stella , Bo-Subait Stephanie , Sharma Akshay , Beitinjaneh Amer , Dimitrova Dimana , Guilcher Greg , Preussler Jaime , Myers Kasiani , Bhatt Neel S. , Ringden Olle , Hematti Peiman , Hayashi Robert J. , Patel Sagar , De Oliveira Satiro Nakamura , Rotz Seth , Badawy Sherif M. , Nishihori Taiga , Buchbinder David , Hamilton Betty , Savani Bipin , Schoemans Hélène , Sorror Mohamed , Winestone Lena , Duncan Christine , Phelan Rachel , Dvorak Christopher C.
Published: August 2023

Background

Allogeneic hematopoietic cell transplantation (HCT) can be complicated by the development of organ toxicity and infection necessitating intensive care. Risk factors for intensive care admission are unclear due to heterogeneity across centers, and long-term outcome data after intensive care are sparse due to a historical paucity of survivors.

Methods

The Center for International Blood and Marrow Transplant Research (CIBMTR) was queried to identify patients age ≤21 years who underwent a 1stallogeneic HCT between 2008-2014 in the United States or Canada. Records were cross-referenced with the Virtual Pediatric Systems pediatric ICU database to identify intensive care admissions. CIBMTR follow-up data were collected through the year 2020.

Results

We identified 6,995 pediatric HCT patients from 69 HCT centers, of whom 1,067 required post-HCT intensive care. The cumulative incidence of PICU admission was 8.3% at day +100, 12.8% at 1 year, and 15.3% at 5 years post HCT. PICU admission was linked to younger age, lower median zip code income, Black or multiracial background, pre-transplant organ toxicity, pre-transplant CMV seropositivity, use of umbilical cord blood and/or HLA-mismatched allografts, and the development of post-HCT graft-versus-host disease or malignancy relapse. Among PICU patients, survival to ICU discharge was 85.7% but more than half of ICU survivors were readmitted to a PICU during the study interval. Overall survival from the time of 1stPICU admission was 52.5% at 1 year and 42.6% at 5 years. Long-term post-ICU survival was worse among patients with malignant disease (particularly if relapsed), as well as those with poor pre-transplant organ function and alloreactivity risk-factors. In a landmark analysis of all 1-year HCT survivors, those who required intensive care in the first year had 10% lower survival at 5 years (77.1% vs. 87.0%, p<0.001) and developed new dialysis-dependent renal failure at a greater rate (p<0.001).

Conclusions

Intensive care management is common in pediatric HCT patients. Survival to ICU discharge is high, but ongoing complications necessitate recurrent ICU admission and lead to a poor 1-year outcome in many patients. Together, these data suggest an ongoing burden of toxicity in pediatric HCT patients that continues to limit long-term survival.
Estimation of Abortions in the Province of Buenos Aires, Argentina: a Bayesian Approach
Authors: Paz Andrea , Josid Sharon , Rodríguez María Carla , Lamela Giselle , Poullain Matías , Marín Lupe , Marsico Franco
Published: August 2023

Abortion is one of the reasons for hospital discharge among women of fertile age in Argentina. The criminalization of abortion prior to the enactment of the Voluntary Interruption of Pregnancy Act (IVE), coupled with fragmentation of the health system, has hindered the availability of reliable records to quantify induced abortions in the country. Given the lack of information reflecting the magnitude of these practices, it is necessary to perform an accurate estimation to characterize abortion access within the healthcare system. Using a Bayesian approach and abortion records in the province of Buenos Aires in 2021, the incidence of abortions per thousand women of fertile age was estimated. This study, based on a direct case count methodology, is the first of its kind in Argentina. The method used allows for the correction of bias caused by under-reporting of practices. An incidence of 29.92 (Credibility Interval, CI95: [29.38; 30.47]) abortions per thousand women of fertile age was obtained during 2021. The results are consistent with previous national research and agree with estimates made for the region. In conclusion, the estimates of abortion incidence highlight its frequency in the lives of people with gestational capacity, underlining the importance of fully guaranteeing the right to comprehensive sexual health through a wide network of abortion access.
Investigating the levels of polychlorinated biphenyls (PCBs) at three lactational stages: A comprehensive study in Ghana
Authors: Jonathan Justice Wiston Amstrong , Kabotso Daniel Elorm Kwame , Essumang David K. , Bentum John K. , Ofosu-Koranteng Francis , Mbroh Hintermann , Tampuori John
Published: August 2023

Introduction

The human breast secretes three types of milk during lactation – colostrum, transitional milk and mature milk However, like any other biofluid, human breast milk is not pristine

Objectives

The objectives of this study was to determine the levels of polychlorinated biphenyls congeners in colostrum, transitional milk and mature milk of mothers at the Ho Teaching Hospital to ascertain which portion contained the highest levels of PCPBs that could pose any significant health risks to neonates.

Methodology

A cross-sectional study design was employed to conduct the study at the Ho Teaching Hospital. Protocol for the study was reviewed and approved by the University of Health and Allied Sciences Research Ethics Committee (UHAS–REC). The study recruited forty-seven (47) mothers using purposive sampling. About 10.0 g of each aliquot of colostrum, transitional milk and mature milk were treated using a modified form of QuEChERS to extract PCBs and the resulting extract analyzed for fourteen (14) PCB congeners using GC–MS/MS.

Results

Fourteen (14) PCB congeners were examined in all the 141 breast samples, which represented three different types of human milk. All samples had levels that were below thresholds of detection. The lack of PCB residues in the examined samples may be viewed as positive news. It might suggest that the mothers were only minimally exposed to these industrial pollutants.

Conclusion

At any stage of lactation, no PCBs were found in the breast milk samples. As a result, there were no obvious health concerns for breastfed infants from the levels of PCBs found in the samples of breast milk that were examined. The result is good news for international efforts to eliminate PCBs in the environment and on people.
United States Air Force Academy Class of 1967 Survival
Authors: Wetzler Harry
Published: August 2023

Introduction

Air Force Academy cadets must meet medical standards to matriculate and be commissioned at graduation. However, during military service many graduates are exposed to significant occupational hazards. We examined the survival experience of the Air Force Academy class of 1967 (AFA67). Projections are provided for life expectancy and remaining quality adjusted life years, the number that will die in the next five years, and the number who will reach their 100thbirthday.

Methods

The dates of death as of September 1, 2022, were obtained from the Class of 1967 Memorial Ceremony booklet dated September 23, 2022. Birthdates were obtained for 94% of the known decedents. Simulated birthdates for the remainder were generated using a skew normal distribution. Likely death underreporting was accounted for. We used the National Health Interview Survey to derive US estimates to compare to AFA67. Parametric survival models using the Weibull distribution were used to calculate average survival time at age 78 (the median current age of AFA67), and standard life table techniques were used to estimate the number dying in the next five years and the number who will live to be centenarians.

Results

As of September 1, 2022, there were 130 known decedents, a 25.2% death incidence. After nearly fivefold excess mortality during the war in Southeast Asia, the class’s experience closely parallels that of contemporaneous college graduates. Adding 12 deaths to compensate for possible unreported deaths does not significantly alter the results. The point estimates for average life expectancy at 78, the number that will die in the next five years, and the number living to age 100 are 13.8 years, 74, and 76 respectively.

Conclusion

The AFA67 survival experience closely matches that of contemporaneous non-Hispanic white male college graduates in the US who were in excellent or very good health in their early twenties. There are numerous desirable opportunities to extend this research.
Bicuspid valve CT Registry of balloon expandable TAVR: BETTER TAVR Registry
Authors: Chavarria Jorge , Falcao Felipe , AlRaddadi Hatim , Aziz Amir , Dick Alexander , Chung Kevin , Sathananthan Janar , Meier David , Ali Noman , Velianou James , Natarajan Madhu , Jaffer Iqbal , Wood David , Fam Neil , Sheth Tej
Published: August 2023

Objectives

We evaluated determinants of stent geometry in bicuspid valves treated with balloon expandable TAVR.

Background

The anatomic substrate of bicuspid valves may lead to suboptimal TAVR stent expansion and geometry.

Methods

A multicentre observational registry of patients who underwent post TAVR CT to determine stent area (vs nominal valve area) and stent ellipticity (maximum diameter/minimum diameter). Predictors of relative stent expansion (minimum area/average of inflow + outflow area) and stent ellipticity were evaluated in a multivariable regression model including valve calcium volume, presence of raphe calcium, sinus diameters indexed for area derived annular diameter, and performance of pre-dilation and post-dilation.

Results

The registry enrolled 101 patients from 4 centres. Minimum stent area (vs nominal area) was 88.1% and maximum ellipticity was 1.10 with both observed near the midframe of the valve in all cases. Relative stent expansion ≥90% was observed in 64/101 patients. The only significant predictor of relative stent expansion ≥90% was performance of post-dilation (p<0.01). Relative stent expansion ≥90% was seen in 86% of patients with post dilation compared to 57% of without (p<0.001). The stent ellipticity ≥ 1.1 was observed in 47/101 patients. The significant predictors of stent ellipticity ≥1.1 was the presence of raphe calcification (p=0.02) and intercommisural diameter at 4 mm above the annular plane (p=0.004).

Conclusion

Relative stent expansion ≥90% was associated with the performance of post-dilation and stent ellipticity was associated with the presence of calcified raphe and sinus dimensions (Intercommisural diameter at 4 mm above the annular plane). Further studies to determine optimal deployment strategies in bicuspid valves are needed.

Abstract Figure

Graphical abstract

Predictors of stent expansion and ellipticity from a multicenter registry of patients with bicuspid anatomy undergoing TAVR with balloon expandable valves.
Sodium-glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome with Diabetes Mellitus
Authors: Kurozumi Atsumasa , Shishido Koki , Yamashita Takayoshi , Sato Daisuke , Uchida Syuhei , Koyama Eiji , Tamaki Yusuke , Hayashi Takahiro , Miyashita Hirokazu , Yokoyama Hiroaki , Ochiai Tomoki , Yamaguchi Masashi , Moriyama Noriaki , Tobita Kazuki , Matsumoto Takashi , Mizuno Shingo , Yamanaka Futoshi , Tanaka Yutaka , Murakami Masato , Takahashi Saeko , Saito Shigeru
Published: August 2023

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are widely used in cardiology and are effective in treating acute coronary syndrome (ACS). Their effects on unstable plaque in ACS patients remains unclear. This study aimed to examine the effectiveness of SGLT2i in coronary plaque phenotypes based on optical coherence tomography (OCT) images and the prognosis of ACS with type 2 diabetes mellitus (T2DM).

Methods

This retrospective study included 109 patients in the total cohort and 29 patients in the OCT cohort. Based on SGLT2i administration after ACS, the total cohort was categorized into non-SGLT2i (n = 69) and SGLT2i (n = 40) groups. The OCT cohort had 15 and 14 patients in non-SGLT2i and SGLT2i groups, respectively. OCT images of unstable plaque were analyzed in non-stented lesions during ACS catheterization and at 6-month follow-ups. The total cohort was assessed after 1 year for major adverse cardiovascular events (MACE), including all-cause mortality, revascularization, cerebrovascular disease, and heart failure hospitalization.

Results

SGLT2i improved unstable lesions with a significantly thicker fibrous cap (48 ± 15 μm vs. 26 ± 24 μm, p = 0.005), reduced lipid arc (-29 ± 12° vs. -18 ± 14°, p = 0.028), and higher % decrease in total lipid arc (-35 ± 13% vs. -19 ± 18%, p = 0.01) as well as a lower MACE incidence (Log rank p = 0.023, HR 4.72 [1.08, 20.63]) and revascularization rate (adjusted HR 6.77 [1.08, 42.52]) compared to the non-SGLT2i group.

Conclusions

SGLT2i stabilizes atherosclerosis and improves ACS prognosis in patients with T2DM.

Clinical Perspective

What is new?

We analyzed serial OCT images both baseline and follow-up in patients with ACS and T2DM undergoing PCI, and evaluated how effect SGLT2i had on unstable plaques.

ACS patients with SGLT2i administration showed coronary atherosclerotic lesions to be stabilized on follow-up.

What are the clinical implications?

SGLT2i can stabilize unstable plaques by controlling the inflammatory cascade on patients with T2DM.

SGLT2i administration will be one option to improve their prognosis in patients with ACS and T2DM undergoing PCI.
Computed tomography-derived normative values and z-scores of right ventricular outflow tract structures in the pediatric population
Authors: Soszyn Natalie , Schweigert Justin , Franco Salvador R. , Morgan Gareth J. , Mitchell Max , Zablah Jenny E.
Published: August 2023

Background

Recent advances in available percutaneous device technology require accurate measurements and quantification of relationships between right ventricular outflow tract (RVOT) structures in children with and without congenital heart disease to determine device suitability. To date, no population study has described normal reference ranges of these measurements by computed tomography (CT). We aimed to establish normative values for four CT-derived measurements between RVOT structures from a heterogeneous population without heart disease and develop z-scores useful for clinical practice.

Methods

Patients without heart disease who underwent cardiac CT between April 2014 and February 2021 at Children’s Hospital Colorado were included. Distance between the right ventricular (RV) apex to pulmonary valve (PV), PV to pulmonary trunk bifurcation, and bifurcation to the right and left pulmonary artery were measured. Previously validated models were used to normalize the measurements and calculate Z-scores. Each measurement was plotted against BSA and Z-scores distributions were used as reference lines.

Results

Three-hundred sixty-four healthy patients with a mean age of 8.8 years (range 1–21), 58% male, and BSA of 1 m2(range 0.4–2.1) were analyzed. The Haycock formula was used to present data as predicted values for a given BSA and within equations relating each measurement to BSA. Predicted values and Z-score boundaries for all measurements are presented.

Conclusion

We report CT-derived normative data for four measurements between RVOT structures from a heterogenous cohort of healthy children. Knowledge of this normative data will be useful in both determining device fit and customising future devices to accommodate the diverse pediatric size range.

Clinical Perspective

Recent advances in advanced percutaneous technology require accurate measurements and quantification of relationships between RVOT structures to determine patient selection and device suitability. The availability of a robust range of normal reference values can provide valuable information for current device selection and future development of customized devices for the RVOT tailored to accommodate the broad size, anatomic and physiologic heterogenicity seen in the pediatric population. We report CT-derived normative data for four measurements between cardio-pulmonary structures from a heterogenous cohort of healthy children and young adults. This data may be useful in planning surgical or catheter-guided interventions in the management of children with congenital heart disease.
Oxidative stress biomarkers in hypothyroid, non thyroid illness and euthyroid dogs
Authors: Mohanambal K , Satish Kumar K , Nagaraj P , Usha Rani M , Ravi Kumar Y
Published: August 2023

There are only a few numbers of published reports available on oxidative stress parameters in hypothyroidism and many of which are in the field of human medicine. Studies on hypothyroidism in dogs lack an assessment of oxidative stress and some are vague and inconclusive. So, the current study was formulated primarily to address variations in chief antioxidant parameters in dogs with hypothyroidism, non-thyroid illness and euthyroidism. Secondly, magnitude of oxidative stress was measured in hypothyroid dogs prior to and during the course of levothyroxine therapy, which were compared statistically. Evaluation of thyroid profile (TT4, fT4 and cTSH) was carried out prior to the assessment of oxidative stress biomarkers such as, serum malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and catalase. A total of 45 dogs were employed in the study, that includes 19 dogs with hypothyroidism, 11 dogs with non-thyroid illness and 15 dogs with euthyroidism. These dogs were brought either to the dermatological unit or the immunization unit. Dogs were divided into three groups: group 1 represented hypothyroidism (low fT4 or low TT4 and high cTSH); group 2 represented non-thyroid disease (low or normal TT4 and low cTSH i.e., inconclusive levels of thyroid hormones); and group 3 represented dogs with normal thyroid levels (euthyroid dogs). Descriptive statistics and normality plots were carried out using SPSS software version 21. Assuming that the variances were unequal, P values were calculated and compared by one-way ANOVA, post hoc multiple comparison analysis using the Games-Howell test. The mean thyroid hormone levels of hypothyroid dogs before (Day 0) and after (Day 60) treatment was significantly different (P<0.05). Hypothyroid dogs (group 1) displayed significantly lower mean fT4 levels (0.56±0.07) and higher mean cTSH levels (8.14±1.17) when compared to other groups. The mean values of serum biochemical parameters showed significant differences among groups (P<0.01). Various biomarkers showed a significant alteration viz., there was a significant reduction in catalase, SOD, GSH and increase in MDA in hypothyroid dogs when compared with euthyroid dogs. However, following therapy for 60 days, catalase, SOD and GSH levels elevated and MDA level reduced significantly and reached nearly to that of euthyroid dogs. Further, there was no significant difference between NTI and euthyroid dogs which demonstrated the antioxidant defence against oxidative stress in hypothyroid dogs. As an outcome, antioxidant measures and serum biochemical tests can be employed as a diagnostic tool to rule out oxidative stress in hypothyroid dogs.
KAT6Amutations in Arboleda-Tham syndrome drive epigenetic regulation of posteriorHOXCcluster
Authors: Singh Meghna , Spendlove Sarah , Wei Angela , Bondhus Leroy , Nava Aileen , N. de L. Vitorino Francisca , Amano Seth , Lee Jacob , Echeverria Gesenia , Gomez Dianne , Garcia Benjamin A. , Arboleda Valerie A.
Published: August 2023

Arboleda-Tham Syndrome (ARTHS) is a rare genetic disorder caused by heterozygous,de novotruncating mutations inLysine(K) acetyltransferase 6A(KAT6A). ARTHS is clinically heterogeneous and characterized by several common features including intellectual disability, developmental and speech delay, hypotonia and affects multiple organ systems.KAT6Ais highly expressed in early development and plays a key role in cell-type specific differentiation. KAT6A is the enzymatic core of a histone-acetylation protein complex, however the direct histone targets and gene regulatory effects remain unknown. In this study, we use ARTHS patient (n=8) and control (n=14) dermal fibroblasts and perform comprehensive profiling of the epigenome and transcriptome caused byKAT6Amutations. We identified differential chromatin accessibility within the promoter or gene body of 23%(14/60) of genes that were differentially expressed between ARTHS and controls. Within fibroblasts, we show a distinct set of genes from the posteriorHOXCgene cluster (HOXC10,HOXC11,HOXC-AS3, HOXC-AS2, HOTAIR) that are overexpressed in ARTHS and are transcription factors critical for early development body segment patterning. The genomic loci harboring HOXC genes are epigenetically regulated with increased chromatin accessibility, high levels of H3K23ac, and increased gene-body DNA methylation compared to controls, all of which are consistent with transcriptomic overexpression. Finally, we used unbiased proteomic mass spectrometry and identified two new histone post-translational modifications (PTMs) that are disrupted in ARTHS: H2A and H3K56 acetylation. Our multi-omics assays have identified novel histone and gene regulatory roles ofKAT6Ain a large group of ARTHS patients harboring diverse pathogenic mutations. This work provides insight into the role of KAT6A on the epigenomic regulation in somatic cell types.
EpiVar Browser: advanced exploration of epigenomics data under controlled access
Authors: Lougheed David R , Liu Hanshi , Aracena Katherine A , Grégoire Romain , Pacis Alain , Pastinen Tomi , Barreiro Luis B , Joly Yann , Bujold David , Bourque Guillaume
Published: August 2023

Motivation

Human epigenomic data has been generated by large consortia for thousands of cell types to be used as a reference map of normal and disease chromatin states. Since epigenetic data contains potentially identifiable information, similarly to genetic data, most raw files generated by these consortia are stored in controlled-access databases. It is important to protect identifiable information, but this should not hinder secure sharing of these valuable datasets.

Results

Guided by theFramework for responsible sharing of genomic and health-related datafrom the Global Alliance for Genomics and Health (GA4GH), we have developed a tool to facilitate the exploration of epigenomics datasets’ aggregate results, while filtering out identifiable information. Specifically, the EpiVar Browser allows a user to navigate an epigenetic dataset from a cohort of individuals and enables direct exploration of genotype-chromatin phenotype relationships. Because the information about individual genotypes is not accessible and aggregated in the output that is made available, no identifiable data is released, yet the interface allows for dynamic genotype - epigenome interrogation. This approach has the potential to accelerate analyses that would otherwise require a lengthy multi-step approval process and provides a generalisable strategy to facilitate responsible access to sensitive epigenomics data.

Availability and implementation

Online portal instance:https://computationalgenomics.ca/tools/epivar

Source code:https://github.com/c3g/epivar-browser
Evaluating the transmission risk of amyloid beta peptide via ingestion
Authors: Raine Joshua , Tolwinski Nicholas , Gruber Jan , Mathuru Ajay S.
Published: August 2023

Background

Recent reports suggest that amyloid beta (Aβ) peptides can exhibit prion-like pathogenic properties. Transmission of Aβ peptide and the development of associated pathologies after surgeries with contaminated instruments and intravenous or intracerebral inoculations have now been reported across fish, rodents, primates, and humans. This raises a worrying prospect of Aβ peptides also having other characteristics typical of prions, such as evasion of the digestive process. We asked if such transmission of Aβ aggregates via ingestion was possible.

Methods

We made use of a transgenicDrosophila melanogasterline expressing human Aβ peptide prone to aggregation. Fly larvae were fed to adult zebrafish under two feeding schemes. The first was a short-term, high-intensity scheme over 48 hours to determine transmission and retention in the gut. The second, long-term scheme specifically examined retention and accumulation in the brain. The gut and brain tissues were examined by histology, western blotting, and mass spectrometric analyses.

Results

None of the analyses could detect Aβ aggregates in the guts of zebrafish following ingestion, despite being easily detectable in the feed. Additionally, there was no detectable accumulation of Aβ in the brain tissue or development of associated pathologies after prolonged feeding.

Conclusions

While human Aβ aggregates do not appear to be readily transmissible by ingestion across species, two prospects remain open. First, this mode of transmission, if occurring, may stay below a detectable threshold and may take much longer to manifest. A second possibility is that the human Aβ peptide may not be able to trigger self-propagation or aggregation in other species. Either possibility requires further investigation, taking into account the possibility of such transmission from agricultural species used in the food industry.
A semi-automated method for quantifying optokinetic reflex tracking acuity
Authors: Kiraly James K. , Harris Scott C. , Al-Khindi Timour , Dunn Felice A. , Kolodkin Alex
Published: August 2023

The study of murine behavioral responses to visual stimuli is a key component of understanding mammalian visual circuitry. One notable response is the optokinetic reflex (OKR), a highly conserved innate behavior necessary for image stabilization on the retina. The OKR provides a robust readout of image tracking ability and has been extensively studied to understand the logic of visual system circuitry and function in mice from different genetic backgrounds. The OKR consists of two phases: a slow tracking phase as the eye follows a stimulus to the edge of the visual plane, and a compensatory fast phase saccade that maintains the image within the visual field. Assessment of the OKR has previously relied on counting individual compensatory eye saccades to estimate tracking speed. To obtain a more direct quantification of tracking ability, we have developed a novel, semi-automated analysis program that allows for rapid and reproducible quantification of unidirectional tracking gains, in addition to being adaptable to any video-oculography equipment. Our analysis program allows for the selection of slow tracking phases, modeling of the vertical and horizontal eye vectors, quantification of eye movement relative to the stimulus, and organization of resultant data into a usable spreadsheet for statistical and graphical comparisons. This quantitative and streamlined analysis pipeline provides a faster and more direct measurement of OKR responses, thereby facilitating further study of visual behavior responses.

We describe here a semi-automated quantitative analysis method that directly measures eye tracking resulting from murine visual system responses to two-dimensional image motion. A Python-based user interface and analysis algorithm allows for higher throughput and more quantitative measurements of eye tracking parameters than previous methods.
Differential functional reorganization of ventral and dorsal visual pathways following childhood hemispherectomy
Authors: Ayzenberg Vladislav , Granovetter Michael C. , Robert Sophia , Patterson Christina , Behrmann Marlene
Published: August 2023

Hemispherectomy is a surgical procedure in which an entire hemisphere of a patient’s brain is resected or functionally disconnected to manage seizures in individuals with drug-resistant epilepsy. Despite the extensive loss of input from both ventral and dorsal visual pathways of one hemisphere, pediatric patients who have undergone hemispherectomy show a remarkably high degree of perceptual function across many domains. In the current study, we sought to understand the extent to which functions of the ventral and dorsal visual pathways reorganize to the contralateral hemisphere following childhood hemispherectomy. To this end, we collected fMRI data from an equal number of left and right hemispherectomy patients who completed tasks that typically elicit lateralized responses from the ventral or the dorsal pathway, namely, word (left ventral), face (right ventral), tool (left dorsal), and global form (right dorsal) perception. Overall, there was greater evidence of functional reorganization in the ventral pathway than in the dorsal pathway. Importantly, because ventral and dorsal reorganization was tested in the very same patients, these results cannot be explained by idiosyncratic factors such as disease etiology, age at the time of surgery, or age at testing. These findings suggest that because the dorsal pathway may mature earlier, it may have a shorter developmental window of plasticity than the ventral pathway and, hence, be less malleable.
A special role for anterior cingulate cortex, but not orbitofrontal cortex or basolateral amygdala, in choices involving information
Authors: González Valeria V. , Ashikyan Sonya A. , Zhang Yifan , Rickard Anne , Yassine Ibrahim , Romero-Sosa Juan Luis , Blaisdell Aaron P. , Izquierdo Alicia
Published: August 2023

Subjects often are willing to pay a cost for information. In a procedure that promotes paradoxical choices, animals choose between a richer option followed by a cue that is rewarded 50% of the time (No-info)vsa leaner option followed by one of two cues that signal certain outcomes: one always rewarded (100%), and the other never rewarded, 0% (Info). Since decisions involve comparing the subjective value of options after integrating all their features, preference for information may rely on cortico-amygdalar circuitry. To test this, male and female rats were prepared with bilateral inhibitory DREADDs in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), basolateral amygdala (BLA), or null virus (control). We inhibited these regions after stable preference was acquired. We found that inhibition of ACC destabilized choice preference in female rats without affecting latency to choose or response rate to cues. A logistic regression fit revealed that the previous choice strongly predicted preference in control animals, but not in female rats following ACC inhibition. The results reveal a causal, sex-dependent role for ACC in decisions involving information.