bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Right Ventricular Endocardial Fibroelastosis in Fetuses with Critical Pulmonary Stenosis and Pulmonary Atresia with Intact Ventricular Septum
Authors: Wang Yue , Luo Gang , Sun Yi , Chen Taotao , Pan Silin
Published: August 2023

Background

Systematic assessment of right ventricular (RV) endocardial fibroelastosis (EFE) in the fetus with critical pulmonary stenosis and pulmonary atresia with intact ventricular septum (CPS/PA-IVS) has not been reported. The implications of RV EFE for circulatory outcomes with or without fetal cardiac intervention (FCI) have also not been demonstrated.

Methods

The fetal echocardiographic data from July 2018 to January 2021 in a single-center institution were collected. Three reviewers independently graded EFE according to the presence and extent of endocardial echogenicity. The associations among EFE severity, anatomic variables, and postnatal outcomes were analyzed.

Results

81 cases with RV EFE were identified. By consensus, EFE severity was assessed as grade 1 (“mild”; n=66, 81.48%), grade 2 (“moderate”; n=11, 13.58%), and grade 3 (“severe”; n=4, 4.94%). RV sphericity values were greater in grade 2 and 3 EFE groups compared to the grade 1 EFE group, implying more severe noncompliance and worse diastolic function. 10/81(12.35%) fetuses underwent FCI. At the latest available follow-up, 59/81 (72.84%) patients had achieved biventricular circulation. Furthermore, 9/59 (15.25%)—four with grade 1 EFE, three with grade 2, and two with grade 3—had undergone FCI, whereas the other 50/59 (84.75%)—who all had grade 1 EFE—had not.

Conclusions

For the first time in CPS/PA-IVS, RV EFE was graded and the potential of FCI to improve the prognosis of non-mild RV EFE patients was revealed. Non-mild RV EFE was suggested to be a putative indicator of FCI.

Graphic Abstract
SARS-CoV-2 Pandemic Non-Pharmacologic Interventions Temporally Associated with Reduced Pediatric Infections Due toMycoplasma pneumoniaeand Co-Infecting Respiratory Viruses in Arkansas
Authors: Boyanton Bobby L. , Frenner Rachel A. , Ingold Ashton , Ambroggio Lilliam , Kennedy Joshua L.
Published: August 2023

Introduction

Non-pharmacologic interventions (NPIs), such as universal masking, implemented during the SARS-CoV-2 pandemic have reduced respiratory infections among children. This study focuses on evaluating the impact of NPIs onMycoplasma pneumoniaeinfections in children, analyzing data from two hospitals in Arkansas, and examining age-related differences and coinfections with other viruses.

Methods

The study was approved by the Institutional Review Board and included patients aged ≤18 years with upper respiratory tract symptoms. Data from the FilmArray® Respiratory Panel (FARP) were collected and divided into pre-NPI and NPI periods for analysis. Total test positivity rate and interval change in the positivity rate were evaluated. Statistical differences were determined by Chi-square (χ2-independence) analysis.

Results

A total of 68,949 tests were performed with a statistical increase in testing during the NPI period. The overall test positivity rate forM. pneumoniaedecreased by 74% (0.86% to 0.03%) during the NPI period, and the preschool age group had the highest number of positive tests in the pre- and NPI periods (Pre-NPI: n=40, NPI: n=12 positive tests, p=<0.001). The reduction inM. pneumoniaeinfections was consistent across age groups. Coinfections with other respiratory viruses, particularly human rhinovirus/enterovirus, were observed at much lower levels.

Conclusions

NPIs effectively reducedM. pneumoniaein pediatric patients in Arkansas, and coinfections with specific viruses still occurred, albeit at lower levels during the SARS-CoV-2 pandemic. As NPIs are relaxed and the pandemic ends, we expectM. pneumoniaeinfections to return to pre-pandemic levels within the next 1-2 years.
Genetic Elucidation of Ultrasonography Fetal Anomalies in Children with Autism Spectrum Disorder
Authors: Regev Ohad , Shil Apurba , Bronshtein Tal , Hadar Amnon , Meiri Gal , Zigdon Dikla , Michaelovski Analya , Dinstein Ilan , Hershkovitz Reli , Menashe Idan
Published: August 2023

Recent evidence suggests that certain fetal anomalies detected upon prenatal ultrasound screenings may be associated with autism spectrum disorder (ASD). In this cross-sectional study, we aimed to identify genetic variants associated with fetal ultrasound anomalies (UFAs) in children with ASD. The study included all children with ASD who are registered in the database of the Azrieli National Center of Autism and Neurodevelopment and for whom both prenatal ultrasound and whole exome sequencing (WES) data were available. We applied our in-house integrative bioinformatics pipeline,AutScore, to these WES data to prioritize gene-disrupting variants (GDVs) probably contributing to ASD susceptibily. Univariate statistics and multivariable regression were used to assess the associations between UFAs and GDVs identified in these children. The study sample comprised 126 children, of whom 43 (34.1%) had at least one UFA detected in the prenatal ultrasound scan. A total of 87 candidate ASD genetic variants were detected in 60 children, with 24 (40%) children carrying multiple variants. There was a weak, but significant, correlation between the number of mutations and the number of abnormalities detected in the same children (r = 0.21,P= 0.016). Children with UFAs were more likely to have loss-of-function (LoF) mutations (aOR=2.55, 95%CI: 1.13–5.80). This association was particularly noticeable when children with structural anomalies or children with UFAs in their head and brain scans were compared to children without UFAs (any mutation: aOR=8.28, 95%CI: 2.29–30.01; LoF: aOR=5.72, 95%CI: 2.08–15.71 and any mutation: aOR=6.39, 95%CI: 1.34–30.47; LoF: aOR=4.50, 95%CI: 1.32–15.35, respectively). GDVs associated with UFAs were enriched in genes highly expressed across all tissues (aOR=2.76, 95%CI: 1.14–6.68). The results provide valuable insights into the potential genetic basis of prenatal organogenesis abnormalities associated with ASD and shed light on the complex interplay between genetic factors and fetal development.
Age-related dysmodulation of systemic immune-inflammatory indices is associated with aggressive colorectal cancer in West Africa
Authors: Okoye Jude Ogechukwu , Chiemeka Michael Emeka , Menkiti Felix Emeka , Iheakwoaba Eric Chukwudi , Agbakoba Nneka
Published: August 2023

Introduction

Despite the high mortality rate among colorectal cancer (CRC) patients in Africa, patients still bear the huge cost-related burden of cancer management. To reduce this burden, there is a current search for affordable markers for disease assessment and treatment monitoring. Contributing to this effort, this study evaluated systemic immune-inflammatory indices (SIII) among CRC patients.

Methods

This study included 89 patients with CRC diagnosed from Jan. 2016 to Dec. 2022. The patients were sub-grouped based on age and chemotherapy response. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), 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.

Results

The median age of the patients was 58.0 years. Metastatic and stage III/IV CRCs were prevalent among patients older than 50 years compared with patients aged 50 years or less. Among patients aged > 50 years, the pre-treatment (pre-T) to post-treatment (post-T) total white blood cell count (TWBC), neutrophils, monocytes, and NLPR significantly increased whereas the post-T lymphocyte count and LMR significantly declined (p< 0.05). Post-T TWBC count and LMR of patients aged > 50 years were 1.5 times higher and 2.4 times lower, respectively compared with the post-T values of patients who were 50 years old or less (p< 0.05). The post-T PNLR/NLPR and LMR were 2.7/2.3 times higher and 4 times lower among chemotherapy-naïve patients compared with the post-T values of chemotherapy-experienced patients, respectively (p< 0.05). The post-T NLR, PLR, and PNLR among chemoresistance. patients were 2.4, 2.3, and 1.5 higher than the post-T values of chemosensitive patients at p= 0.027, 0.015, and 0.022, respectively.

Conclusion

This study revealed a higher frequency of CRC and mortality risk among patients older than 50 years. It suggests that SIII could be used as a prognostic tool for CRC.
Identification of new angio-architectural features of at-risk cranial dural arteriovenous fistulas using machine learning approaches
Authors: Frank Katharina , Shalchian-Tehran Paiman , Manu Mihai , Cinibulak Zafer , Poggenborg Jörg , Nakamura Makoto
Published: August 2023

Background

Cranial dural arteriovenous fistulas (dAVF’s) are rare complex vascular malformations that have a bleeding risk with potential lethal consequences. Despite this, the vascular architectural features associated with the rupture risk are not always clearly defined.

Methods

We retrospectively analyzed cranial arteriovenous fistulas in terms of their anatomical and angio-architectural features as evaluated on conventional subtraction angiography: Location of the fistula, fistula architecture, venous ectasia, reflux in cortical draining veins, presence of pial feeders, outflow stenosis, presence of a major sinus thrombosis, flow-associated arterial aneurysms as well as presenting symptoms. Patterns in the data were identified after multiple components analysis followed by automatic k-means clustering and their predictive power was confirmed using a neural network and a random forest classifier.

Results

New relevant features predictive of hemorrhage (venous outflow stenosis and fistula architecture) were identified using distinct but surprisingly converging modeling paradigms. Both the neural network and the random forest classifier achieved a relatively high performance metric, with area under the receiver operating characteristic curve (ROC AUC)) of 0.875 [95% CI, 0.75-1.0]. The relevance of these findings was verified by performing a multiple correspondence analysis followed by k-means clustering in the angiographic feature vector space. There was good agreement between the ground truth (hemorrhage) and the cluster labels (adjusted Rand score 0.273, purity index 0.82).

Conclusion

Machine learning approaches confirmed the importance of previously described features (reflux in a cortical vein and venous ectasia) but also uncovered novel relevant characters (outflow stenosis and fistula architecture) for the hemorrhage risk of dAVF’s.
WITHDRAWN: Period2-mediated downregulation of ERK/MAPK phosphorylation in nasopharyngeal carcinoma
Authors: Zhang Zhijuan , Ma Zheng , Kang Jing , Yang Jing , Xu Qianru , Niu Xinran , Luo Xiaoya , Wang Jingyuan , Li Hailiang , Hou Li
Published: August 2023

Withdrawal statement

The authors have withdrawn their manuscript owing to because authors want to do further study about period2-mediated downregulation of ERK/MAPK phosphorylation in nasopharyngeal carcinoma. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Trends and key disparities of obesity among US adolescents: the NHANES from 2007 to 2020
Authors: Deng Yangyang , Yli-Piipari Sami , El-Shahawy Omar , Tamura Kosuke
Published: August 2023

This study aimed to estimate the trends in the body mass index (BMI) and prevalence of obesity among United States (U.S.) adolescents (10-19 years), and to examine the associations between sociodemographic factors and both BMI and obesity prevalence. The 2007-2020 National Health and Nutrition Examination Survey (NHANES), a nationally representative repeated cross- sectional survey data (n = 9,826) were used. Outcomes included: 1) Mean BMI and 2) obesity (yes/no; defined as BMI ≥ 95% percentile). Sociodemographic variables included age, sex, race/ethnicity, and poverty income ratio (PIR; low-income <1.3, Middle-income ≥1.3 and <3.5, high-income ≥3.5). By accounting for the complex survey design, weighted generalized linear/Poisson models were used to conduct the analyses. Girls constituted 49 % of the sample. From 2007-2008 to 2017-2020, BMI and obesity prevalence increased across various subgroups, including Black and Hispanic adolescents, boys, and those from low- and middle-income families. Girls are a 12% lower likelihood of being obese than boys. Compared to White adolescents, Black and Hispanic adolescents had 22% and 19% greater risk of being obese. Compared to those from high-income families, adolescents from low- and middle-income families had 62% and 47% greater risk of being obese, respectively. The results indicated persistent disparities in obesity prevalence among different race/ethnic and sociodemographic groups. Future obesity intervention should address key disparities by targeting specific race/ethnic adolescents from low-income families and promoting health equality.
Risk Score Models for Unplanned Urinary Tract Infection Hospitalization
Authors: Alizadeh Nasrin , Vahdat Kimia , Shashaani Sara , Swann Julie L. , Ozaltin Osman
Published: August 2023

Annually, urinary tract infections (UTIs) affect over a hundred million people worldwide. Early detection of high-risk individuals can help prevent hospitalization for UTIs, which imposes significant economic and social burden on patients and caregivers. We present two methods to generate risk score models for unplanned UTI hospitalization. We utilize a sample of patients from the insurance claims data provided by the Centers for Medicare and Medicaid Services to develop and validate the proposed methods. Our dataset encompasses a wide range of features, such as demographics, medical history, and healthcare utilization of the patients along with provider quality metrics and community-based metrics. The proposed methods scale and round the coefficients of an underlying logistic regression model to create scoring tables. We present computational experiments to evaluate the prediction performance of both models. We also discuss different features of these models with respect to their impact on interpretability. Our findings emphasize the effectiveness of risk score models as practical tools for identifying high-risk patients and provide a quantitative assessment of the significance of various risk factors in unplanned UTI hospitalizations such as admission to ICU in the last 3 months, cognitive disorders and low inpatient, outpatient and carrier costs in the last 6 months.
Why some countries but not others? Urbanisation, GDP and endemic disease predict global SARS-CoV-2 excess mortality patterns
Authors: Fountain-Jones Nicholas M. , Charleston Michael , Flies Emily , Carver Scott , Yates Luke
Published: August 2023

The global impact of the SARS-CoV-2 pandemic has been uneven, with some regions experiencing significant excess mortality while others have been relatively unaffected. Yet factors which predict this variation remain enigmatic, particularly at large spatial scales. We used spatially explicit Bayesian models that integrate socio-demographic and endemic disease data at the country level to provide robust global estimates of excess SARS-CoV-2 mortality (P scores) for the years 2020 and 2021. We find that gross domestic product (GDP), spatial patterns and urbanization are strong predictors of excess mortality, with countries characterized by low GDP but high urbanization experiencing the highest levels of excess mortality. Intriguingly, we also observed that the prevalence of malaria and human immunodeficiency virus (HIV) are associated with country-level SARS-CoV-2 excess mortality in Africa and the Western Pacific, whereby countries with low HIV prevalence but high malaria prevalence tend to have lower levels of excess mortality. While these associations are correlative in nature at the macro-scale, they emphasize that patterns of endemic disease and socio-demographic factors are needed to understand the global dynamics of SARS-CoV-2.
The ABCD-GENE score influences vascular event rates in both users of clopidogrel and aspirin, as well as non-users of either drug in a population-based cohort study
Authors: Narasimhalu Kaavya , Mayerhofer Ernst , Parodi Livia , Georgakis Marios K , De Silva Deidre Anne , Rosand Jonathan , Anderson Christopher D
Published: August 2023

Background and Objectives

Clopidogrel is an antiplatelet used in both primary and secondary prevention of cardiovascular diseases. It is a prodrug, requiringCYP2C19for its metabolism to the active metabolite. The ABCD-GENE score, combining clinical attributes (age, body mass index, chronic kidney disease, diabetes mellitus), with genetic information (presence of 1 or 2 loss of function (LOF) alleles in theCYP2C19gene) has been shown to identify patients with higher risk of recurrent cardiovascular events in high-risk populations undergoing percutaneous coronary intervention. We aimed to determine if the ABCD-GENE score or LOF alleles were associated with an increased risk of vascular events among clopidogrel users in a general population.

Methods

We conducted a population based cohort study with UK Biobank’s primary care prescription records to identify clopidogrel users. ABCD-GENE scores were calculated with closest available data from the first date of clopidogrel prescription. The number of LOF alleles present, and the clinical component ABCD, were separate exposures. The outcome of interest was a composite endpoint of vascular events comprised of myocardial infarction, ischemic stroke, and death due to either of these. We performed Cox proportional hazards models with clopidogrel as a time varying exposure to predict hazards of these outcomes. In order to determine the drug specificity of these exposures, the analyses were repeated in aspirin users, and in non-users of either aspirin or clopidogrel.

Results

Among 11,248 clopidogrel users, 3,365 (30%) developed a vascular event over a mean follow-up of 5.95±3.94 years. ABCD-GENE score ≥10 was associated with an increased risk of vascular events (HR 1.13, 95% CI 1.03-1.23). In aspirin users, and in non-users of either aspirin or clopidogrel, the ABCD-GENE score was also associated with increased risk of vascular events. In clopidogrel users, aspirin users, and non-users of either drug, the ABCD score was associated with increased risk of vascular events. The presence of twoCYP2C19LOF alleles was associated with an increased risk of vascular events in aspirin and non-users but not in clopidogrel users.

Discussion

In this population-based cohort study, the ABCD-GENE score was associated with an increased risk of vascular events in clopidogrel users, aspirin users, and in non-users of either drug. The clinical component, ABCD was also associated with an increased risk of vascular events in all three groups. This suggests that the ABCD-GENE score is not specific to clopidogrel users in identifying persons at high risk of vascular events in a general sample with low baselineCYP2C19LOF allele frequency.
Impact of ventriculo-cisternal irrigation in preventing delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage
Authors: Umekawa Motoyuki , Yoshikawa Gakushi
Published: August 2023

Background

Delayed cerebral ischemia (DCI) due to vasospasm following subarachnoid hemorrhage (SAH) is considered a significant determinant of morbidity and mortality; however, no established method exists to prevent and treat vasospasm or DCI. This study aimed to evaluate the effectiveness of ventriculo-cisternal irrigation (VCI) in preventing vasospasms and DCI.

Methods

We retrospectively identified 340 SAH patients with ruptured intracranial aneurysms treated with postoperative VCI at our institution between December 2010 and January 2020. Ventricular/cisternal drainage (VD/CD) was inducted during aneurysm surgery, and lactated Ringer’s solution was used for irrigation until day 4 of SAH, followed by ICP control at 5–10 cmH2O until day 14. We collected data on total vasospasm, DCI, and modified Rankin Scale scores at discharge and analyzed the risk factors using logistic regression models.

Results

The median age was 65 years (interquartile range: 52–75), with 236 female patients (69%). The World Federation of Neurosurgical Societies grade distribution was as follows: Grade I or II, 175 cases (51%); Grade III or IV, 84 (25%); Grade V, 81 (24%). With VCI management in all cases, total vasospasm occurred in 162 patients (48%), but DCI incidence was low (23 patients [6.8%]). Major drainage-related complications were observed in five patients (1.5%). Early surgery, performed on SAH day 0 or 1, was identified as a preventivefactor against DCI occurrence (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.07–0.67;p= 0.008), while additional surgery (OR 4.76, 95% CI 1.62–13.98;p= 0.005) and dyslipidemia (OR 3.27, 95% CI 1.24–8.63;p= 0.017) were associated with DCI occurrence.

Conclusions

Managing vasospasms with VCI after SAH achieved a low incidence of 6.8% for DCI and is considered a safe and effective method. Early surgery after SAH occurrence was associated with a decreased risk of DCI with VCI therapy.
High-throughput detection of neutralizing antibodies to SARS-CoV-2 variants using flow cytometry
Authors: Zhang Xiaohan , Wang Yajie , Li Mansheng , Li Haolong , Zhang Xiaomei , Xu Xingming , Hu Di , Liang Te , Zhu Yunping , Li Yongzhe , Wang Bingwei , Yu Xiaobo
Published: August 2023

Detecting neutralizing antibodies (NAbs) to SARS-CoV-2 variants is crucial for controlling COVID-19 spread. We developed a high-throughput assay for the broad systematic examination of NAbs to eleven SARS-CoV-2 variants, which include D614G, Alpha, Beta, Gamma, Delta, Kappa, and Omicron sub-lineages BA.1-BA.5. The assay is cost-effective, reliable, 35-fold more sensitive than Luminex technology, and can include new variants during SARS-CoV-2 evolution. Importantly, our results highly correlated with a commercial IgG serological assay (R = 0.89), the FDA-approved cPass sVNT assay (R = 0.93), pseudivirus-based neutralizing assay (R = 0.96, R = 0.66, R = 0.65) and live virus based neutralization assay (R = 0.79, R = 0.64) . Using this platform, we constructed a comprehensive overview of the interactions between SARS-CoV-2 variants’ Spike trimer proteins and ACE2 receptors, and identified a polyclonal Ab with broad neutralizing activity. Furthermore, when compared to the D614G variant, we found that the serum NAbs elicited by the third dose vaccine demonstrated decreased inhibition to multiple SARS-CoV-2 variants, including Gamma (0.94×), Alpha (0.91×), Delta (0.91×), Beta (0.81×), Kappa (0.81×), BA.2 (0.44×), BA.1 (0.43×), BA.3 (0.41×), BA.5 (0.35×) and BA.4 (0.33×), in cohort of 56 vaccinated individuals. Altogether, our proteomics platform proves to be an effective tool to detect broad NAbs in the population and aid in the development of future COVID-19 vaccines and vaccination strategies.
Caffeinated or decaffeinated coffee consumption and risk of cancer incidence: meta-analyses of prospective cohort studies
Authors: Nguyen Thanh N. , Cherepakhin Olga S. , Eng Devin K. , Kawasumi Masaoki
Published: August 2023

Many epidemiological studies have investigated the association between coffee consumption and risks for various types of cancer, yet results are conflicting. To determine the impact of coffee consumption on cancer incidence, we systematically reviewed high-quality prospective cohort studies for 10 major cancer types and performed meta-analyses of 63 studies from different countries. For each cancer type, we calculated summary relative risks using the DerSimonian–Laird random-effects model and assessed dose-response relationships. Our meta-analyses found that caffeinated coffee consumption, but not decaffeinated coffee, prevented liver and skin cancers, highlighting the significant role of caffeine in cancer prevention. Furthermore, both caffeinated and decaffeinated coffee prevented endometrial cancer, indicating the role of other active compounds in coffee. Collectively, our meta-analyses revealed that coffee consumption, particularly caffeinated coffee, prevents the incidence of liver, endometrial, and skin cancers in a dose-dependent manner, suggesting that coffee consumption has a large impact on public health.
Maternal-fetal outcomes in patients with immune mediated inflammatory diseases, with consideration of comorbidities: a retrospective cohort study in a large U.S. healthcare system
Authors: Hwang Yeon Mi , Wei Qi , Piekos Samantha N. , Vemuri Bhargav , Molani Sevda , Mease Philip , Hood Leroy , Hadlock Jennifer J.
Published: August 2023

Background

Immune-mediated inflammatory diseases (IMIDs) are likely to complicate maternal health. However, literature data on patients with IMIDs undergoing pregnancy is scarce and often overlooks the impact of comorbidities.

Methods

We investigated 12 selected IMIDs: psoriasis, inflammatory bowel disease, rheumatoid arthritis, spondyloarthritis, multiple sclerosis, systemic lupus erythematosus, psoriatic arthritis, antiphospholipid syndrome, Sjögren’s syndrome, vasculitis, sarcoidosis, systemic sclerosis. We characterized patients with IMIDs prior to pregnancy (IMIDs group) based on pregnancy/maternal characteristics, comorbidities, and pre-pregnancy/prenatal immunomodulatory medications (IMMs) prescription patterns. We 1:1 propensity score matched the IMIDs cohort with people who had no IMID diagnoses prior to pregnancy (non-IMIDs cohort). Outcome measures were preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), and cesarean section.

Findings

The prevalence rate of pregnancy occurring with people with a previous IMID diagnosis has doubled in the past ten years. We identified 5,784 patients with IMIDs. 17% of the IMIDs group had at least one prenatal IMM prescription. Depending on the type of IMM, from 48% to 70% of the patients taking IMMs before pregnancy continued them throughout pregnancy. Patients with IMIDs had similar but slightly increased risks of PTB (Relative risk (RR)=1·1[1·0, 1·3]), LBW (RR=1·2 [1·0,1·4]), SGA (RR=1·1 [1·0,1·2]), and cesarean section (RR=1·1 [1·1,1·2]) compared to a matched cohort of people without IMIDs. Out of the 12 selected IMIDs, three for PTB, one for LBW, two for SGA, and six for cesarean section had results supporting increased risk.

Interpretation

The association between IMIDs and the increased risk of adverse pregnancy outcomes depend on both the nature of the IMID and the presence of comorbidities.

Funding

NIH
EEG to fMRI Synthesis for Medical Decision Support: A Case Study on Schizophrenia Diagnosis
Authors: Calhas David , Henriques Rui
Published: August 2023

Electroencephalography (EEG) measures the neuronal activity at the scalp, while functional magnetic resonance imaging (fMRI) provides a sub-cortical view of blood supply in the human brain. Although fMRI is known for providing rich spatial information, it is expensive and of restricted use. EEG to fMRI synthesis is a cross modal research area that bridges the gap between the two and has recently received attention. Although these studies promise lower healthcare costs and ambulatory assessments, their utility in diagnostic settings is still largely untapped. Using simultaneous EEG and fMRI recordings, this study combines a state-of-the-art synthesis model with a modified contrastive loss, and subsequent prediction layering, to unprecedentedly assess its predictive power in schizophrenia diagnosis. In addition, we perform an exhaustive search for the (synthesized) hemodynamic brain patterns able to discriminate schizophrenia. Schizophrenia diagnosis using synthesized hemodynamics yield an area under the ROC curve of 0.77, confirming the validity of the undertaken neuroimaging synthesis. Experiments further revealed schizophrenia-related patterns in frontal, left temporal and cerebellum regions of the brain. Altogether, our results suggest that a synthesized fMRI view is able to discriminate this pathology, and it contains discriminative patterns of brain activity in accordance with related work on schizophrenia.
Plasma CXCL8 and MCP-1 as biomarkers of latent tuberculosis infection
Authors: Selvavinayagam Sivaprakasam T , Aswathy Bijulal , Yong Yean K , Frederick Asha , Murali Lakshmi , Kalaivani Vasudevan , Jith Karishma S , Rajeshkumar Manivannan , Anusree Adukkadukkam , Kannan Meganathan , Gopalan Natarajan , Vignesh Ramachandran , Murugesan Amudhan , Tan Hong Yien , Zhang Ying , Chandramathi Samudi , Sivasankaran Munusamy Ponnan , Govindaraj Sakthivel , Byrareddy Siddappa N , Velu Vijayakumar , Larsson Marie , Shankar Esaki M , Raju Sivadoss
Published: August 2023

Background

Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision ofEnd Tuberculosis Strategy.

Methods

We investigated whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. We also measured the plasma cytokines using a commercialBio-Plex Pro Human Cytokine 17-plexassay.

Results

Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold.

Conclusions

We postulated that CXCL8 and MCP-1 could be the surrogate biomarkers of LTBI, especially in resource-limited settings.
Effect of sensor number and location on accelerometry-based vertical ground reaction force estimation during walking
Authors: Pimentel Ricky , Armitano-Lago Cortney , MacPherson Ryan , Sathyan Anoop , Twiddy Jack , Peterson Kaila , Daniele Michael , Kiefer Adam W. , Lobaton Edgar , Pietrosimone Brian , Franz Jason
Published: August 2023

Knee osteoarthritis is a major cause of global disability and is a major cost for the healthcare system. Lower extremity loading is a determinant of knee osteoarthritis onset and progression; however, technology that assists rehabilitative clinicians in optimizing key metrics of lower extremity loading is significantly limited. The peak vertical component of the ground reaction force (vGRF) in the first 50% of stance is highly associated with biological and patient-reported outcomes linked to knee osteoarthritis symptoms. Monitoring and maintaining typical vGRF profiles may support healthy gait biomechanics and joint tissue loading to prevent the onset and progression of knee osteoarthritis. Yet, the optimal number of sensors and sensor placements for predicting accurate vGRF from accelerometry remains unknown. Our goals were to: 1) determine how many sensors and what sensor locations yielded the most accurate vGRF loading peak estimates during walking; and 2) characterize how prescribing different loading conditions affected vGRF loading peak estimates.

We asked 20 young adult participants to wear 5 accelerometers on their waist, shanks, and feet and walk on a force-instrumented treadmill during control and targeted biofeedback conditions prompting 5% underloading and overloading vGRFs. We trained and tested machine learning models to estimate vGRF from the various sensor accelerometer inputs and identified which combinations were most accurate.

We found that a neural network using one accelerometer at the waist yielded the most accurate loading peak vGRF estimates during walking, with errors around 4.3% body weight. The waist-only configuration was able to distinguish between control and overloading conditions prescribed using biofeedback, matching measured vGRF outcomes. Including foot or shank acceleration signals in the model reduced accuracy, particularly for the overloading condition. Our results suggest that a system designed to monitor changes in walking vGRF or to deploy targeted biofeedback may only need a single accelerometer located at the waist.
Pediatric Device Clinical Trials Activity Compared to Drugs and Biologics Trials 1999-2022
Authors: Dienstman Joshua , Stachelek Stanley J. , Krieger Abba M. , Eskandanian Kolaleh , Espinoza Juan C. , Harrison Michael R. , Koh Chester J. , Peiris Vasum , Torjusen Erika , Levy Robert J.
Published: August 2023

Objective

This study assessed the state of PMD development by comparing PMD clinical trials to pediatric trials evaluating drugs and biologics, from 1999-2022. We hypothesized changes in numbers and types of PMD trials compared to drugs and biologics represent an indicator of PMD growth.

Study Design

www.clinicaltrials.govwas used to identify and quantify both PMD clinical trials and pediatric trials for drugs and biologics. Clinical specialty was also assessed. The institutions included were the seven children’s hospitals primarily affiliated with the FDA PDC grants program between 2018-2023.

Results

243 PMD clinical trials were identified based on the year of initiation. The average number of PMD trials initiated per year per institution was 1.5. PMD trials significantly increased (p=0.0083) from 2014 onward compared to pediatric clinical trials for drugs and biologics, which demonstrated no significant change in trial initiation activity. A more than five-fold increase in PMD trials was observed from 2014-2018 compared to previous time periods, and there were 48% more PMD trials from 2019-2022 compared to 2014-2018. PMD trials represented 5% of clinical trials at the institutions studied.

Conclusions

While clinical trial activity for drug and biologic development remained stable from 1999-2022, initiation of PMD trials significantly increased. The present results suggest that clinical trials growth reflects increased PMD development. Accommodation and promotion of PMD clinical trial activity, which is still relatively small, by relevant programs and policies at the institutional and government levels may foster the advancement of PMD to further address unmet needs.

Article Summary

This article is an analysis of device trials performed at seven children’s hospitals affiliated with the FDA Consortia grants program between 1999 and 2022.

What’s Known on This Subject

There have been no prior studies of device trial activity at a cohort of children’s hospitals at academic medical centers. Over the past decade, FDA programs have been initiated to assist stakeholders in advancing the development of pediatric medical devices.

What This Study Adds

Pediatric device trials account for only 5% of total trials at the institutions studied. Of note, only half of these PMD trials (2.4% of total clinical trials) were sponsored by industry and likely seeking pediatric labeling.
Impact of Advanced Therapy Centers on Characteristics and Outcomes of Heart Failure Admissions
Authors: Lu Daniel Y , Kanduri Jaya , Yeo Ilhwan , Goyal Parag , Krishnan Udhay , Horn Evelyn M , Karas Maria G , Sobol Irina , Majure David T , Naka Yoshifumi , Minutello Robert M , Cheung Jim W , Uriel Nir , Kim Luke K
Published: August 2023

Background

Although much attention has been paid to admission and transfer patterns for cardiogenic shock, contemporary data is lacking on decompensated heart failure (HF) admissions and transfers, and the impact of advanced therapy centers (ATCs) on outcomes.

Methods

HF hospitalizations were obtained from the Nationwide Readmissions Database 2016-2019. Centers performing at least one heart transplant or left ventricular assist device were classified as ATCs. Patient characteristics, outcomes, and procedural volume were compared among three cohorts: admissions to non-ATCs, admissions to ATCs, transfers to ATCs. A secondary analysis evaluated outcomes for severe HF hospitalizations (cardiogenic shock, cardiac arrest, mechanical ventilation).

Results

2,331,690 hospitalizations were admissions to non-ATCs (94.5% of centers), 525,037 were admissions to ATCs (5.5% of centers), and 15,541 were transfers to ATCs. Patients treated at ATCs (especially those transferred) had higher rates of HF decompensations, procedural frequency, lengths-of-stay, and costs. Unadjusted mortality was 2.6% at non-ATCs and was higher at ATCs, both for directly admitted (2.9%, p<0.01) and transferred (11.2%, p<0.01) patients. However, multivariable adjusted mortality was significantly lower at ATCs, both for directly admitted (OR 0.82, p<0.01) and transferred (OR 0.66, p<0.01) patients. For severe HF admissions, unadjusted mortality was 37.2% at non-ATCs and was lower at ATCs, both for directly admitted (25.3%, p<0.01) and transferred (25.2%, p<0.01) patients, with similarly lower multivariable adjusted mortality.

Conclusions

HF patients treated at ATCs were sicker but associated with higher procedural volume and lower adjusted mortality.

Clinical Perspective

Contemporary data is lacking on admissions and transfers for decompensated heart failure (HF) and the impact of advanced therapy centers (ATCs) on outcomes. Our findings show that decompensated HF patients treated at ATCs had higher rates of HF decompensations, procedural frequency, lengths-of-stay, and costs. While unadjusted mortality was higher at ATCs, multivariable adjusted mortality was significantly lower at ATCs, both for directly admitted and transferred patients. Our findings will hopefully prompt earlier recognition and referral of patients to ATCs, emphasize the need for increased numbers of ATCs, and spark further research into the decision-making process for referral to ATCs.
pADP-ribosylation Regulates the Cytoplasmic Localization, Cleavage and Pro-apoptotic Function of HuR
Authors: Ashour Kholoud , Hall Derek , Mubaid Souad , Busque Sandrine , Lian Xian Jin , Gagné Jean-Philippe , Khattak Shahryar , Marco Sergio Di , Poirier Guy G. , Gallouzi Imed-Eddine
Published: August 2023

HuR (ElavL1) is one of the main posttranscriptional regulators that determines cell fate. While the role of HuR in apoptosis is well-established, the posttranslational modifications that governs this function remain elusive. In this study we show that PARP1/2-mediated poly(ADP)-ribosylation (PARylation) is instrumental in the pro-apoptotic function of HuR. During apoptosis or in cells depleted of PARP1/2 enzymes, a substantial reduction in HuR PARylation is observed. This results in the cytoplasmic accumulation and the cleavage of HuR, both of which are essential events for apoptosis. These effects are mediated by a pADP-ribose (PAR) binding motif within the HuR-HNS region (HuR PAR Binding Site (HuR-PBS)). Under normal conditions, the association of HuR-PBS with PAR is responsible for the nuclear retention of HuR. Mutations within this motif prevents the binding of HuR to its import factor TRN2, leading to its cytoplasmic accumulation and cleavage. Collectively, our findings underscore the role of PARylation in controlling the proapoptotic function of HuR, offering insight into the mechanism by which PARP1/2 enzymes regulate cell fate and adaptation to various assaults.
Microglial cGAS deletion protects against amyloid-β induced Alzheimer’s disease pathogenesis
Authors: He Sijia , Li Xin , Mittra Namrata , Bhattacharjee Anindita , Wang Hu , Zhao Shangang , Liu Feng , Han Xianlin
Published: August 2023

Innate immune activation plays a vital role in the development of Alzheimer’s disease (AD) and related dementias (ADRD). Among which, the DNA sensing cyclic GMP-AMP synthase (cGAS)- STING pathway has been implicated in diverse aspects of AD progression.

In the current study, we showed that the cGAS-STING signaling was up-regulated in AD and this elevation was mainly contributed by the microglial population other than non-microglial cell types in the brain. By establishing an inducible, microglia-specific cGAS knockout mouse model in 5xFAD background, we found that deleting microglial cGAS at the onset of amyloid-β (Aβ) pathology significantly limited plaque formation, and protected mice from Aβ-induced cognitive impairment. Mechanistically, we found cGAS was necessary for plaque-associated microglial enrichment potentially driven by IRF8, and was indispensable for the development of disease-associated microglia (DAM) phenotype. Meanwhile, the loss of microglial cGAS reduced the levels of dystrophic neurites which led to preserved synaptic integrity and neuronal function. Our study provides new insights in understanding the effects of innate immune in AD via a cell-type specific manner, and lays the foundation for potential targeted intervention of the microglial cGAS-STING pathway toward the improvement of AD.
DeltaAI: Semi-Autonomous Tissue Grossing Measurements and Recommendations using Neural Radiance Fields for Rapid, Complete Intraoperative Histological Assessment of Tumor Margins
Authors: Suvarna Anish , Vempati Ram , Chacko Rachael , Srinivasan Gokul , Lu Yunrui , Hunt Brady , Torres Veronica , Samkoe Kimberly , Davis Matthew , Fu Lucy , Christensen Brock , Vaickus Louis , LeBoeuf Matthew , Levy Joshua
Published: August 2023

Mohs Micrographic Surgery (MMS) aims to excise cutaneous cancer with real-time margin analysis. However, manual tissue grossing and analysis can be inefficient, so we propose DeltaAI, a novel workflow that utilizes Neural Radiance Fields (NeRF) to enable rapid tissue grossing and generate a 3D model in an augmented reality (AR) environment. In our study, we captured 30-second videos of 17 MMS specimens using a photogrammetry turntable and cellphone camera. Preprocessing the tissues with segmentation models, we created a dataset of 923, 360-degree-view, images per video (17 videos). Using COLMAP, we estimated poses for sparse tissue reconstructions and trained the NeRF model for 3D volumetric tissue renderings. The results demonstrated that DeltaAI generated more accurate and complete 360-degree, 3D tissue renderings compared to previous models, while also achieving significantly faster runtimes. Our proposed semi-autonomous NeRF-based workflow has the potential to enhance the speed of MMS specimen processing, measurement, report generation, and margin assessment. It can inform real-time grossing decisions, automate the export of electronic health record data, and facilitate time-efficient and complete cancer excisions. Moreover, DeltaAI can contribute to the wider adoption of AI technology in clinical settings by improving tissue modeling for manual grossing.
Alteration of the chicken upper respiratory microbiota, following H9N2 avian influenza virus infection
Authors: Davis Tara , Bialy Dagmara , Leng Joy , Ragione Roberto La , Shelton Holly , Chrzastek Klaudia
Published: August 2023

Several studies have highlighted the importance of the gut microbiota in developing immunity against viral infections in chickens. We have previously shown that H9N2 avian influenza A virus (AIV) infection retards the diversity of the natural colon associated microbiota, which may further influence chicken health following recovery from infection. The effects of influenza infection on the upper respiratory tract (URT) microbiota are largely unknown. Here we showed that H9N2 AIV infection lowers alpha diversity indices in the acute phase of infection in URT, largely due to the family Lactobacillaceae being highly enriched during this time in the respiratory microbiota. Interestingly, microbiota diversity did not return to levels similar to control chickens in the recovery phase after viral shedding has ceased. Beta diversity followed similar trend following challenge.Lactobacillusassociate statistically with the disturbed microbiota of infected chickens at acute and recovery phase of infection. Additionally, we study age-related changes in the respiratory microbiota during maturation in chickens. From 7 to 28 days of age, species richness and evenness were observed to advance over time as the microbial composition evolved.

Maintaining microbiota homeostasis might be considered as a potential therapeutic target to prevent or aid recovery from H9N2 AIV infection.
The Hedgehog receptors PTCH1 and PTCH2 exist as active homomeric and heteromeric complexes
Authors: Timmis Alex J. , Cross Felix , Gkotsi Danai S. , Ollerton Hattie , Johnson Colin A. , Galdo Natalia A. Riobo-Del
Published: August 2023

With the importance of Hedgehog signalling in embryonic development, tissue homeostasis and disease, understanding the molecular mechanisms of signal transduction is paramount for the design of specific, effective therapeutics. The Hedgehog receptor PTCH1 and the less studied PTCH2 isoform are evolutionarily related to bacterial RND permeases and sterol sensing proteins, which mobilise hydrophobic compounds powered by a cation gradient. Here we demonstrate that, in the active state, PTCH1 and PTCH2 form homomeric and heteromeric complexes that are inhibited by binding of Sonic Hedgehog. We show that PTCH2, unlike PTCH1, appears to have minimal cholesterol transport activity, but that conserved residues involved in cation transport are essential for its function. Heteromeric PTCH1-PTCH2 complexes depend on PTCH1’s cholesterol transport capacity, but the cation transport can be provided in trans by PTCH2, suggesting that some deleterious mutations in either isoform can be silenced by formation of heteromers, enhancing the robustness of this signal transduction system. These findings provide the molecular basis for the intriguing behaviour of PTCH2 as semi-redundant and partially overlapping in function with PTCH1 and explain the dominant negative effect of mutations that disrupt the PTCH2 cation transport triad in rare cases of cancer.
The HuMet Repository: Watching human metabolism at work
Authors: Weinisch Patrick , Raffler Johannes , Römisch-Margl Werner , Arnold Matthias , Mohney Robert P. , Rist Manuela J. , Prehn Cornelia , Skurk Thomas , Hauner Hans , Daniel Hannelore , Suhre Karsten , Kastenmüller Gabi
Published: August 2023

The human metabolism constantly responds to stimuli such as food intake, fasting, exercise, and stress, triggering adaptive biochemical processes across multiple metabolic pathways. To understand the role of these processes and disruptions thereof in health and disease, detailed documentation of healthy metabolic responses is needed but still scarce on a time-resolved metabolome-wide level.

Here, we present the HuMet Repository, a web-based resource for exploring dynamic metabolic responses to six physiological challenges (exercise, 36 h fasting, oral glucose and lipid loads, mixed meal, cold stress) in healthy subjects. For building this resource, we integrated existing and newly derived metabolomics data measured in blood, urine, and breath samples of 15 young healthy men at up to 56 time points during the six highly standardized challenge tests conducted over four days. The data comprise 1.1 million data points acquired on multiple platforms with temporal profiles of 2,656 metabolites from a broad range of biochemical pathways. By embedding the dataset into an interactive web application, we enable users to easily access, search, filter, analyze, and visualize the time-resolved metabolomic readouts and derived results. Users can put metabolites into their larger context by identifying metabolites with similar trajectories or by visualizing metabolites within holistic metabolic networks to pinpoint pathways of interest. In three showcases, we outline the value of the repository for gaining biological insights and generating hypotheses by analyzing the wash-out of dietary markers, the complementarity of metabolomics platforms in dynamic versus cross-sectional data, and similarities and differences in systemic metabolic responses across challenges.

With its comprehensive collection of time-resolved metabolomics data, the HuMet Repository, freely accessible athttps://humet.org/, is a reference for normal, healthy responses to metabolic challenges in young males. It will enable researchers with and without computational expertise, to flexibly query the data for their own research into the dynamics of human metabolism.