bluuebunny/crossref_metadata_2025 huggingface dataset:
Gimibacter soli gen. nov. sp. nov., isolated from mangrove soil and insight into its ecological distribution and metabolic potential
Authors: Liu Yang , Pei Tao , Duan Jiao , Du Juan , Zhu Honghui
Published: June 2023

A Gram-stain-negative, facultatively anaerobic, motile and rod-shaped bacterium, designated as 6D33T, was isolated from mangrove soil. Growth was found to occur at 15–32 °C (optimum, 28 °C), at pH 6–9 (optimum, pH 7) and in 0–3 % NaCl (optimum, 1 %, w/v). The results of 16S rRNA gene-based analysis showed that strain 6D33T belonged to the family

Temperatibacteraceae

, sharing 93.1–94.4 % identity with its close neighbours within the genus

Kordiimonas

. The phylogenomic results indicated that strain 6D33T formed an independent branch distinct from type strains of the genus

Kordiimonas

. The overall genome relatedness indices of digital DNA–DNA hybridization, average nucleotide identity and amino acid identity values showed that strain 6D33T represents a novel species of a novel genus. The results of chemotaxonomic characterization indicated that the major cellular fatty acids of strain 6D33T were summed feature 9 (C16 : 0 10-methyl and/or iso-C17 : 1
 ω9c), summed feature 3 (C16 : 1
 ω6c and/or C16 : 1
 ω7c) and iso-C15 : 0; the polar lipids comprised diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified aminolipid and three unidentified lipids; the only respiratory quinone was ubiquinone-10. The genomic size and DNA G+C contents were 3.59 Mbp and 60.84 mol%, respectively. The 16S rRNA gene sequence reads abundance profiles revealed that the rare taxon is prevalent in marine environments, especially in sediments. Genome-scale metabolic reconstruction of strain 6D33T revealed a heterotrophic lifestyle and many pathways responsible for the degradation of aromatic compounds, suggesting application potential in aromatic hydrocarbon removal. Based on its genotypic and phenotypic characteristics, strain 6D33T is concluded to represent a novel species of the novel genus in the family

Temperatibacteraceae

, for which the name Gimibacter soli gen. nov. sp. nov. is proposed. The type strain of the type species is 6D33T (=GDMCC 1.1959T=KCTC 82335T).
Machine learning in medicine using JavaScript: building web apps using TensorFlow.js for interpreting biomedical datasets
Authors: Pires Jorge Guerra
Published: June 2023

Contributions to medicine may come from different areas, and most of these areas are filled with researchers eager to contribute. In this paper, we aim to contribute through the intersection of machine learning and web development. We employed TensorFlow.js, a JavaScript-based library, to model biomedical datasets using neural networks obtained from Kaggle. The principal aim of this study is to present the capabilities of TensorFlow.js and promote its utility in the development of sophisticated machine learning models customized for web-based applications. We modeled three datasets: diabetes detection, surgery complications, and heart failure. While Python and R currently dominate, JavaScript and its derivatives are rapidly gaining ground, offering comparable performance and additional features associated with JavaScript. Kaggle, the public platform from which we downloaded our datasets, provides an extensive collection of biomedical datasets. Therefore, readers can easily test our discussed methods by using the provided codes with minor adjustments on any case of their interest. The results demonstrate an accuracy of 92% for diabetes detection, almost 100% for surgery complications, and 80% for heart failure. The possibilities are vast, and we believe that this is an excellent option for researchers focusing on web applications, particularly in the field of medicine.
Laser Coronary Atherectomy and polymeric coronary wires in uncrossable lesions – A word of caution
Authors: Marengo Giorgio , Cortés Carlos , Sánchez-Luna Juan Pablo , Gonzalez-Gutiérrez Jose Carlos , Herrero Javier Gómez , Sanz-Sanchez Jorge , Gutiérrez Hipólito , Serrador Ana , Campo Alberto , Blasco-Turrión Sara , Gasparini Gabriele , San Román J. Alberto , Amat-Santos Ignacio J.
Published: June 2023

Background

Excimer laser coronary atherectomy (ELCA) represents one of the last available options in case of balloon uncrossable lesions but no bench testing or clinical experience has been reported with polymeric wires. We aimed to assess whether ECLA use can disrupt or melt the cover and coating of coronary wires.

Methods

A total of 22 wires (10 polymer-jacketed and 12 hydrophilic non polymeric) were tested in an uncrossable lesion model. Two ELCA tests were performed over each wire at 8 and 4 cms from the tip with low and high settings, respectively. Microscopic analysis was performed at baseline images and after each test. Wire disruption was classified as Grade 1 (superficial scratches), Grade 2 (coil damage or solution of continuity of the polymeric cover) and Grade 3 (wire rupture/core disruption or de-coiling).

Results

After 44 ELCA simulations, wire disruption occurred in 16 cases (36.3%). Overall, events were more common for polymer-jacketed than for hydrophilic wires (12 vs 4, p=0.004). No grade 3 events occurred. Grade 2 events occurred in 9 cases (20.5%) and were more frequent with polymer- jacketed wires (8 vs 1, p=0.006). With low ELCA settings only polymer-jacketed wires suffered disruption (5 vs 0, p=0.009). With higher settings 11 events occurred (7 of Grade 2 and 4 of Grade 1) and incidence of grade 2 events was higher for polymer-jacketed wires (6 vs 1, p=0.02).

Conclusions

ELCA might be a safe option for coronary uncrossable lesions but its use with high settings over polymer-jacketed wires is discouraged.

CONDENSED ABSTRACT

We aimed to assess whether ECLA use can disrupt coronary wires in balloon/microcatheter uncrossable lesion model. Forty-four in-vitro experiments were performed over hydrophilic-coated and polymer-jacketed coronary wires with different ELCA settings. Wire disruption was classified as Grade 1 (scratches), Grade 2 (coil or polymeric cover damage) and Grade 3 (core disruption/de- coiling). Wire disruption occurred 36.3% of cases and was more common for polymer-jacketed wires than for hydrophilic-coated wires (p=0.004). With high ELCA settings the incidence of grade 2 events was higher for polymer-jacketed wires (p=0.02). This discourages the use of ELCA with high settings over polymer-jacketed wires.
Association of age-related spontaneous internal jugular vein reflux with cognitive impairment and incident dementia
Authors: Adachi Utako , Toi Sono , Hosoya Megumi , Hoshino Takao , Seki Misa , Yoshizawa Hiroshi , Tsutsumi Yukiko , Maruyama Kenji , Kitagawa Kazuo
Published: June 2023

Background and purpose

The vascular aspect of cognitive impairment focuses on cerebral small-vessel disease and arterial circulation. However, it remains unclear whether changes in the venous circulation contribute to cognitive decline. This study aimed to clarify whether the spontaneous jugular vein reflux (JVR) is associated with cognitive impairment and incident dementia.

Methods

The Tokyo Women’s Medical University Cerebrovascular Disease registry is a prospective observational registry in which patients with any evidence of cerebral vessel disease on magnetic resonance imaging (MRI) were consecutively enrolled between October 2015 to July 2019. We employed carotid duplex sonography to measure the internal jugular vein (IJV). The subjects were classified into two groups based on the degree of JVR on either side: none, mild (JVR(-) group) and moderate, severe (JVR (+) group) JVR. They underwent both the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment-Japanese (MoCA-J) global tests. Their cognitive status was prospectively assessed until March 2022.

Results

Among 906 patients with an MMSE score ≥ 24 enrolled in the registry, 302 underwent duplex sonography of the IJV. Among them, 91 had spontaneous JVR on either side. Both MMSE and MoCA-J were significantly lower in patients with JVR (+) group than in the JVR (-) group. After the adjustment for age, sex, years of education, risk factors, and MRI findings, including small-vessel disease and medial temporal atrophy, intergroup differences in MoCA-J remained significant. Among the cognitive subdomains, median executive function and memory scores were significantly lower in the JVR (+) group than in the JVR (-) group. During the median 5.2-year follow-up, 11 patients with incident dementia (Alzheimer disease: 10, vascular dementia: 1) were diagnosed. Patients with severe JVR were significantly more likely to be diagnosed with dementia (log-rank test, P= 0.031).

Conclusions

Spontaneous IJV reflux especially severe JVR, was associated with global cognitive function, and potentially with incident dementia.

Clinical Trial Registration:

URL:https://www.umin.ac.jp. Unique identifier: UMIN000026671.
Computational model of neuronal recruitment during ICMS for restoring somatosensation in the human somatosensory cortex
Authors: Kudela Pawel , Fifer Matthew S , Osborn Luke E , McMullen David P , Celnik Pablo A , Cantarero Gabriela L , Tenore Francesco V , Anderson William S
Published: June 2023

Objective

Intuitively providing touch feedback from artificial hands to users with sensory loss remains a challenge. Although localized fingertip sensations can be evoked via intracortical microstimulation (ICMS), feedback is generally optimized using psychometric tasks rather than mimicking the cortical response to touch.

Approach

We created an anatomically-informed and participant-specific model of the human somatosensory cortex (S1) region with an implanted microelectrode array (MEA). We performed simultaneous stimulation-and-recording from the study participant S1 region to characterize cortical responses elicited by single ICMS pulses. Pulses were delivered to a set of pre-selected electrodes mapped to tactile receptive fields. We next performed a 2D (i.e., in the plane of the MEA probe tips) current source density (CSD) analysis of recorded cortical responses to inform cortical network model parameters on how ICMS activates neurons and lateral synaptic connections in the area of the S1 sampled by MEA electrodes. Using information from planar CSD profiles obtained from ground truth data, we reconstructed lateral connections in the S1 model needed to produce the desired responses to single ICMS pulses. The effect of multiple ICMS was then simulated in the biologically realistic cortical model and the results were validated against ground truth cortical responses from the study participant.

Main results

A high-resolution cortical network model, calibrated to produce the known cortical responses to single ICMS pulses delivered to individual electrodes, predicted with a reasonable accuracy the cortical response to ICMS pulses delivered simultaneously to multiple electrodes.

Significance

These preliminary results suggest that high-resolution biologically realistic cortical network models can potentially be reliable predictors of cortical response to a given pattern of ICMS presentations and therefore useful in designing biomimetic stimulation patterns.
Prevalence of Post COVID-19 Condition among healthcare workers: self-reported online survey in four African countries
Authors: Elnadi Hager , Al-Mustapha Ahmad I. , Odetokun Ismail A. , Anjorin AbdulAzeez Adeyemi , Mosbah Rasha , Fasina Folorunso O. , Razouqi Youssef , Awiagah Kwame Sherrif , Nyandwi Jean Baptiste , Mhgoob Zuhal E. , Gachara George , Mohamud Mohamed Farah Yusuf , Damaris Bamu F. , Maisara Aala MohamedOsman , Radwan Mona
Published: June 2023

The impact of Post COVID-19 Condition is ongoing despite the WHO declaration that the pandemic has ended. In this study, we explore the prevalence of PCC among healthcare workers (HCWs) in four African Countries and its influence on their professional performance. This study was conducted as an online cross-sectional survey of healthcare workers from four African countries (Cameroon, Egypt, Nigeria, and Somalia) between the 20thof December 2021 to 12thof January 2022. We determined the prevalence of PCC based on the WHO case definition and assessed variables associated with a higher prevalence of PCC in these countries using univariable and multivariable logistic regression analyses. A total of 706 HCWs from four African countries were included in this survey. Most of the HCWs were aged between 18-34 years (75.8%, n=535). Our findings showed that 19.5% (n=138) of the HCWs had tested positive for SARS-CoV-2. However, 8.4% (n=59) were symptomatic for COVID-19 but tested negative or were never tested. Two-thirds of the HCWs (66.4%, n=469) have received a COVID-19 vaccine and 80.6% (n=378) of those vaccinated had been fully vaccinated. The self-reported awareness rate of PCC among the HCWs was 16.1% (n=114/706) whereas the awareness rate of PCC among COVID-19-positive HCWs was 55.3 % (n=109/197). The prevalence of PCC among HCWs was 58.8% (n=116). These changes include the self-reported symptoms of PCC which included headache (58.4%, n=115), fatigue (58.8%, n=116), and muscle pain (39.6%, n=78). Similarly, 30% (n=59) and 20.8% (n=41) of the HCWs reported the loss of smell and loss of taste long after their COVID-19 infection, respectively. Some HCWs (42%, n=83) believed that their work performance has been affected by their ongoing symptoms of PCC. There was no significant difference in the prevalence of PCC among the vaccinated and unvaccinated HCWs (p > 0.05). Of the socio-demographic variables, age (older HCWs between 45-54 years; OR:1.7; 95% CI: 1.06, 10.59; p = 0.001) and location (Egypt; OR:14.57; 95% CI: 2.62, 26.76; p = 0.001) were more likely to have experienced PCC than other age groups and countries respectively. The study revealed low prevalence of PCC among the surveyed HCC. In addition, it observed the need for adequate medical and psychological support to HCWs with PCC, improve their COVID-19 vaccination uptake, and conduct mass advocacy campaigns on PCC.

Graphical abstract

COVID-19 positivity rate (n =197), vaccination rate (n =706), PCC awareness rate (n = 114), and prevalence of PCC (n = 116) in HCWs across four African countries.
Serum High Sensitivity C-Reactive Protein Poorly Predicts Bone Mineral Density: A NHANES 2017-2020 Analysis
Authors: Little-Letsinger Sarah E.
Published: June 2023

Abstract

A reliable, widely available method to detect osteoporosis prior to fracture is needed. Serum levels of C-reactive protein may independently predict low bone mineral density (BMD) and high fracture risk. Existing empirical data focus on sexually and/or racially homogenous populations. This study tests the hypotheses that: C-reactive protein (1) negatively correlates with BMD and (2) fracture history, and (3) independently predicts BMD and fracture history in a diverse population. NHANES 2017-2020 pre-pandemic cycle data were analyzed in R studio. Strength and direction of relationships (-1 to +1) between variables were determined using Kendall’s rank correlation coefficient (τ). Linear models were optimized to predict femoral neck or lumbar spine BMD. C-reactive protein positively correlated with femoral (τ=0.09, p<0.0001) and spine BMD (τ=0.10, p<0.0001). Individuals identifying as female demonstrated more robust, but still weak, correlations between C-reactive protein and femoral neck (τ=0.15, p<0.0001; male, τ=0.06, p=0.051) and spine BMD (τ=0.16, p<0.0001; male, τ=0.06, p=0.04). C-reactive protein positively correlated with fracture history (τ=0.083, p=0.0009). C-reactive protein significantly predicted femoral neck (R2=0.022, p=0.0001) and spine BMD (R2=0.028, p<0.0001) and fracture history (R2=0.015, p<0.0001). Exploratory analyses identified weight was the single best predictor for femoral neck (R2=0.24, p<0.0001) and spine BMD (R2=0.21, p<0.0001). In sum, C-reactive protein statistically correlates with and predicts femoral neck and spine BMD, but the magnitude is too low to be biologically meaningful. While weight is a more robust predictor, individuals who are overweight or obese account for nearly half of all osteoporotic fractures, limiting the predictive power of this variable at identifying individuals at risk for osteoporosis. Identification of a robust predictor of fracture risk in a diverse population and across of range of body weights and compositions is needed.
Prospective screening for monkeypox infection among users of HIV pre-exposure prophylaxis (PrEP) in Denmark
Authors: Thomassen Sofie Ellen , Schreeb Sebastian von , Kirkby Nikolai Søren , Pinholt Mette , Lebech Anne-Mette , Kronborg Gitte , Engsig Frederik Neess
Published: June 2023

Introduction

During the 2022 outbreak of mpox (previously called monkeypox), which primarily affected men who have sex with men (MSM), testing was mainly limited to individuals with symptoms of infection. Although sporadic cases of mpox continue to be diagnosed in Denmark, the benefit of screening asymptomatic high-risk populations, such as those using HIV pre-exposure prophylaxis (PrEP), is still unknown.

Methods

During the autumn of 2022, a rectal swab test for mpox PCR was included in the routine sexually transmitted infections (STI) screening for PrEP users.

Results

The screening included 224 asymptomatic men with a median age of 36.5 years. One patient (0.4%) tested positive for mpox. Ten (4.5%) and nine (4.0%) had chlamydia and gonorrhea, respectively.

Discussion

We found one case of mpox, who developed symptoms three days after testing positive. This finding may reflect low to non-existing levels of asymptomatic infection among mpox patients. Based on the current study, screening for asymptomatic mpox infection among PrEP users does not seem warranted.
TM6SF2 Determines Both the Degree of Lipidation and the Number of VLDL Particles Secreted by the Liver
Authors: Reyes-Soffer Gissette , Liu Jing , Thomas Tiffany , Matveyenko Anastasiya , Seid Heather , Ramakrishnan Rajasekhar , Holleran Steve , Zaghloul Norann , Sztalryd-Woodle Carole , Pollin Toni , Ginsberg Henry N.
Published: June 2023

In 2014, exome-wide studies identified a glutamine176lysine (p.E167K) substitution in a protein of unknown function named transmembrane 6 superfamily member 2 (TM6SF2). The p.E167K variant was associated with increased hepatic fat content and reduced levels of plasma TG and LDL cholesterol. Over the next several years, additional studies defined the role of TM6SF2, which resides in the ER and the ER-Golgi interface, in the lipidation of nascent VLDL to generate mature, more TG-rich VLDL. Consistent results from cells and rodents indicated that the secretion of TG was reduced in the p.E167K variant or when hepatic TM6SF2 was deleted. However, data for secretion of APOB was inconsistent, either reduced or increased secretion was observed. A recent study of people homozygous for the variant demonstrated reduced in vivo secretion of large, TG-rich VLDL1 into plasma; both TG and APOB secretion were reduced. Here we present new results demonstrating increased secretion of VLDL APOB with no change in TG secretion in p.E167K homozygous individuals from the Lancaster Amish community compared to their wild-type siblings. Our in vivo kinetic tracer results are supported by in vitro experiments in HepG2 and McA cells with knock-down or Crispr-deletions of TM6SF2, respectively. We offer a model to potentially explain all of the prior data and our new results.
EMG-projected MEG High-Resolution Source Imaging of Human Motor Execution: Brain-Muscle Coupling above Movement Frequencies
Authors: Huang Ming-Xiong , Harrington Deborah L. , Angeles-Quinto Annemarie , Ji Zhengwei , Robb-Swan Ashley , Huang Charles W. , Shen Qian , Hansen Hayden , Baumgartner Jared , Hernandez-Lucas Jaqueline , Nichols Sharon , Jacobus Joanna , Song Tao , Lerman Imanuel , Bazhenov Maksim , Krishnan Giri P , Baker Dewleen G. , Rao Ramesh , Lee Roland R.
Published: June 2023

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trails needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing M1 during ∼l minute recordings of left and right self-paced finger movements (∼1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-90 Hz) bands in 13 healthy participants (26 datasets) and two presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) and gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In both presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement related brain-muscle coupling above the movement frequency and its harmonics.
Knowledge, attitude, and practice of geriatric trauma risk assessment: Instrument development and validation
Authors: Adeyemi Oluwaseun , Konda Sanjit , Grudzen Corita , DiMaggio Charles , Esper Garrett , Rogers Erin , Goldfeld Keith , Blecker Saul , Chodosh Joshua
Published: June 2023

Background

Emergency providers and nurses play pivotal roles in the initial triage and risk assessment of geriatric trauma patients. Their knowledge, attitudes, and practices of geriatric trauma risk assessment may significantly influence geriatric trauma outcomes. This study aims to develop scales that comprehensively assess emergency providers’ knowledge, attitudes, and practices of geriatric trauma triage and risk assessment.

Methods

We designed the knowledge (30 items), attitude (14 items), and practice (14 items) scale using the American College of Surgeons geriatric trauma management guidelines. Each of the surveys was designed using a five-point Likert scale. Content validation was performed by nine clinicians and instrument design experts. We computed Cohen’s Kappa, and item and scale content validity indices (CVIs).

Results

Of the 30 items in the knowledge scale, 27 were retained. The Cohen’s Kappa value ranged from 0.3 to 1.0 and the item and scale CVIs for the 27 items were each 0.90. Of the 14 items on the attitude scale, 13 were retained. The Cohen’s Kappa value ranged from 0.6 to 1.0 and the item and scale CVIs for the 13 items were each 0.94. All 14 items in the practice scale were retained. The Cohen’s Kappa value ranged from 0.6 to 1.0 and item and scale CVIs for the 14 items were each 0.86.

Conclusion

We present a content-validated survey instrument that can assess the knowledge, attitude, and practice of geriatric trauma risk assessment among emergency providers and nurses.
Revising and evaluating the Safe Recovery fall prevention education program with patients and staff in a hospital rehabilitation setting: A mixed methods study
Authors: Francis-Coad Jacqueline , Farlie Melanie K , Haines Terry , Weselman Tammy , Black Linda , Cummings Philippa , Hill Anne-Marie
Published: June 2023

Background

Providing patients with falls prevention education can improve their overall safety and reduce their risk of falling in hospital. Partnering with patients and staff in developing and evaluating such programs could better enable patient learning and translation of safety messages.

Aim

To create a revised version of the Safe Recovery falls prevention education program (SRP) in partnership with patients and hospital allied health staff, to improve patient engagement in undertaking strategies to reduce their risk of falling in hospital.

Methods

Two-phase sequential mixed methods participatory design. In phase 1 patient (n=10) and staff (n=10) consumer engagement surveys and discussions were undertaken to inform program revision. New resources (video and workbook) were co-produced and staff were trained to deliver the revised program to patients. In phase 2 patients (n=10) were surveyed pre and post revised program delivery and staff were surveyed regarding their reaction to the revised program. Deductive content analysis and Wilcoxon Signed Rank Tests were used respectively to analyse qualitative and quantitative findings.

Results

Patients and staff were very satisfied with the revised program, with patients demonstrating significant improvements in knowledge, awareness, motivation and intention to reduce their risk of falling. Staff perceived that the revised resources showed significant improvements in aesthetic appeal and ability to engage patients in learning.

Conclusion

Patients and staff contributed to successfully revising the Safe Recovery program with positive reactions to the co-produced resources. Participating in the revised program significantly improved patients’ knowledge and attitudes to reduce their risk of falling. Investigating the impact of the revised program on patients’ behaviour change and on reducing hospital falls is warranted.
Metabolome-wide Mendelian randomization characterizes heterogeneous and shared causal effects of metabolites on human health
Authors: Yin Xianyong , Li Jack , Bose Debraj , Okamoto Jeffrey , Kwon Annie , Jackson Anne U. , Silva Lilian Fernandes , Oravilahti Anniina , Stringham Heather M. , Ripatti Samuli , Daly Mark , Palotie Aarno , Scott Laura J. , Burant Charles F. , Fauman Eric B. , Wen Xiaoquan , Boehnke Michael , Laakso Markku , Morrison Jean
Published: June 2023

Metabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Nevertheless, their causal effects on human diseases have not been evaluated comprehensively. We performed two-sample Mendelian randomization to systematically infer the causal effects of 1,099 plasma metabolites measured in 6,136 Finnish men from the METSIM study on risk of 2,099 binary disease endpoints measured in 309,154 Finnish individuals from FinnGen. We identified evidence for 282 causal effects of 70 metabolites on 183 disease endpoints (FDR<1%). We found 25 metabolites with potential causal effects across multiple disease domains, including ascorbic acid 2-sulfate affecting 26 disease endpoints in 12 disease domains. Our study suggests that N-acetyl-2-aminooctanoate and glycocholenate sulfate affect risk of atrial fibrillation through two distinct metabolic pathways and that N-methylpipecolate may mediate the causal effect of N6, N6-dimethyllysine on anxious personality disorder. This study highlights the broad causal impact of plasma metabolites and widespread metabolic connections across diseases.
Racial/Ethnic Disparities Impact the Real-World Effectiveness of a Multicomponent Maternal Smoking Cessation Program: Findings from the CTTP Cohort
Authors: Wiles Stacey D. , Lee Jerry W. , Nelson Anna , Petersen Anne Berit , Singh Pramil N.
Published: June 2023

Introduction

Smoking during pregnancy adversely affects perinatal outcomes for both women and infants. We conducted a retrospective cohort study of the state-funded Comprehensive Tobacco Treatment Program (CTTP) – the largest maternal tobacco cessation program in San Bernardino County, California – to determine the real-world program effectiveness and to identify variables that can potentially improve effectiveness.

Methods

During 2012-2019, women who smoked during pregnancy were enrolled in CTTP’s multicomponent behavioral smoking cessation program that implemented components of known efficacy (i.e., incentives, biomarker testing, feedback, and motivational interviewing).

Results

We found that 40.1% achieved prolonged abstinence by achieving weekly, cotinine-verified, 7-day abstinence during 6 to 8 weeks of enrollment. Using intention-to-treat analyses, we computed that the self-reported point prevalence abstinence rate (PPA) at the six-month telephone follow-up was 36.7%. Cohort members achieving prolonged abstinence during the CTTP were five times more likely to achieve PPA six months after CTTP. Several non-Hispanic ethnicities (Black, Native American, White, or More than one ethnicity) in the cohort were two-fold less likely (relative to Hispanics) to achieve prolonged abstinence during CTTP or PPA at six months after CTTP. This disparity was further investigated in mediation analysis. Variables such as quitting during the first trimester and smoking fewer cigarettes at enrollment were also associated with achieving PPA at six months.

Discussion

Racial/ethnic health disparities that have long been linked to a higher rate of maternal smoking persist even when the pregnant smoker enrolls in a smoking cessation program.

Significance

What is already known on this subject?

Causal factors that enable pregnant smokers to achieve abstinence during and after enrollment in maternal smoking cessation programs are not well understood.

What does this study add?

We found that US (United States) racial/ethnic disparities that have long been linked to higher national rates of maternal smoking for several non-Hispanic ethnicities (Black, Native American/Alaskan, White) also persisted in the form of lower abstinence rates in non-Hispanic ethnicities (Black, Native American, White, More than one ethnicity) who enrolled in the maternal smoking cessation program we evaluated. This racial/ethnic disparity in maternal smoking cessation program outcomes is a new addition to the literature and needs further study to identify the underlying causal factors.
Artificial neural network predicts sex differences of patients with advanced Parkinson’s disease under Levodopa-Carbidopa Intestinal gel
Authors: Bougea Anastasia , Derikvand Tajedin , Efthymiopoulou Efthymia , Angelopoulou Efthalia
Published: June 2023

Objective

Although Levodopa-carbidopa intestinal gel (LCIG) treatment has shown to be efficacious in motor and some non-motor symptoms (NMS), not all the patients with advanced Parkinson’s disease (PD) are ideal candidates. To improve their selection analysis knowledge of prognostic factors is of great importance. We aimed to develop a novel machine learning model to predict the clinical outcomes of patients with advanced PD at 2 years under the LCIG therapy.

Methods

This was a longitudinal 24-month, observational study of 59 patients with advanced PD of a Greek multicenter registry under LCIG treatment from September 2019 to September 2021. Motor status was assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (off) and IV. NMS were assessed by the NMS Questionnaire (NMSQ) and the Geriatric Depression Scale (GDS), the quality of life by PDQ-39 and severity by Hoehn &Yahr (HY). Multivariate linear regression, ARIMA, SARIMA, and Long Short-Term Memory-recurrent neural network (LSTM-RNN) models were used.

Results

Dyskinesia duration and quality of life were significantly improved with LCIG (19% and 10% greater improvement for men than women, respectively). Multivariate linear regression models showed that UPDRS-III was decreased by 1.5 and 4.39 units per one unit of increase of the PDQ-39, UPDRS-IV indexes, respectively. Among all the time series models, the LSTM-RNN model predicts these clinical characteristics with highest accuracy (mean square error =0.0069)

Conclusions

Τhe LSTM-RNN model predicts with highest accuracy sex dependent clinical outcomes of patients with advanced PD after two years of LCIG therapy.
Identification of commensal gut microbiota signatures as predictors of clinical severity and disease progression in multiple sclerosis
Authors: Montgomery Theresa L , Wang Qin , Mirza Ali , Dwyer Deanna , Wu Qi , Dowling Catherine A , Martens Jacob WS , Yang Jennifer , Krementsov Dimitry N , Mao-Draayer Yang
Published: June 2023

Background

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and a leading cause of neurological disability in young adults. Clinical presentation and disease course are highly heterogeneous. Typically, disease progression occurs over time and is characterized by the gradual accumulation of disability. The risk of developing MS is driven by complex interactions between genetic and environmental factors, including the gut microbiome. How the commensal gut microbiota impacts disease severity and progression over time remains unknown.

Methods

In a longitudinal study, disability status and associated clinical features in 60 MS patients were tracked over 4.2 ± 0.97 years, and the baseline fecal gut microbiome was characterized via 16S amplicon sequencing. Progressor status, defined as patients with an increase in Expanded Disability Status Scale (EDSS), were correlated with features of the gut microbiome to determine candidate microbiota associated with risk of MS disease progression.

Results

We found no overt differences in microbial community diversity and overall structure between MS patients exhibiting disease progression and non-progressors. However, a total of 45 bacterial species were associated with worsening disease, including a marked depletion inAkkermansia,Lachnospiraceae,andOscillospiraceae, with an expansion ofAlloprevotella,Prevotella-9, andRhodospirillales. Analysis of the metabolic potential of the inferred metagenome from taxa associated with progression revealed a significant enrichment in oxidative stress-inducing aerobic respiration at the expense of microbial vitamin K2production (linked toAkkermansia), and a depletion in SCFA metabolism (linked toLachnospiraceaeandOscillospiraceae). Further, statistical modeling demonstrated that microbiota composition and clinical features were sufficient to robustly predict disease progression. Additionally, we found that constipation, a frequent gastrointestinal comorbidity among MS patients, exhibited a divergent microbial signature compared with progressor status.

Conclusions

These results demonstrate the utility of the gut microbiome for predicting disease progression in MS. Further, analysis of the inferred metagenome revealed that oxidative stress, vitamin K2and SCFAs are associated with progression.

Abstract Figure
pfb_fhir: A utility to extract clinical data systems into a portable format
Authors: Walsh Brian , Lee Jordan A. , Ellrott Kyle
Published: June 2023

Background

Fast Healthcare Interoperability Resources (FHIR) is a server specification and data model that allows for EHR systems to represent clinical metadata using a consistent API. There is a critical mass of EHR and clinical trial data stored in FHIR based systems. Research analysts can take advantage of existing FHIR tooling for de-identification, pseudonymization, and anonymization. More recently the BiodataCatalyst consortium has proposed the Portable Format for Bioinformatics (PFB) which is a carrier format for describing raw data and the data model in which it is structured, based on an efficient binary format (AVRO). PFB allows an entire cohort of metadata to be loaded into a research data system. Here, we describe an open source utility that will scan FHIR based systems and create PFB based archives.

Results

pfb_fhir scans data from FHIR based clinical data systems and converts the data into a self contained PFB file. This utility identifies types, customizations (extensions), and element connections. It then converts all of these components into a graph model compatible for storage in the PFB specification. The structure of the original FHIR system is faithfully reproduced using the PFB schema description system. All records from the system are downloaded, converted and stored as vertices in a graph described by the PFB file. This system has been tested against a number of different FHIR installations, including ones hosted by dbGAP, The Kids First Data Resource and AnVIL.

Conclusions

pfb_fhir helps to unlock the potential of EHR and clinical trial data. pfb_fhir allows researchers to easily scan and store FHIR resources and create self contained PFB archives, called FHIR in PFB. These archive files can easily be moved to new data systems, allowing the clinical data to be connected to more complex genomic analysis and data science platforms. The FHIR in PFB archives generated by pfb_fhir have been loaded into data platforms including the Broad’s Terra system, Gen3 based data system, custom graph query engines and Jupyter notebooks. This flexibility will enable genomics investigators to do more integrated genotype to phenotype association analysis using whichever tools suit their line of research.
Impact of Hypertension on Left Heart Remodelling: Echocardiography and Computed Tomography Study
Authors: Lange Aleksandra , Palka Viktoria , Bian Chris , Huntress Harry , Morgan Jill , Allwood Sean , Swann Rohan , Palka Przemysław
Published: June 2023

Background

Early recognition of left atrial (LA) and left ventricular (LV) remodelling may improve prognosis of patients with hypertension.

Methods

Left heart coupling indices were studied to investigate the adaptive effect of hypertension on cardiac remodelling. The ratio of LV to LA volumes was measured at selected phases of a cardiac cycle using computed tomography (CT) coronary angiography and transthoracic echocardiogram (TTE). A group of 180 patients was divided into Group 1 (no hypertension) and Group 2 (hypertension). Volume ratios were measured in diastasis by both CT and TTE: LVdiasand LAdias. Using TTE, volumes were measured at end-diastole (LVEDand LAmin)), and end-systole (LVESand LAmax). LA function and LV/LA ratios were analysed at: LVED/LAmax, LVdias/LAdias, LVED/LAmin, LVES/LAmin.

Results

There were no differences between the age groups, LVED, and LV mass index. Compared to Group 1, Group 2 had bigger mean LV wall thickness (0.90±0.16 cmvs0.83±0.14 cm; p=0.006), increased relative wall thickness ratio (0.39±0.09vs0.35±0.008, p=0.004), and more frequent concentric LV remodelling (31vs12, p=0.020). LA volumes were bigger in Group 2 for LAmax, LAdias, and LAmin. All LV/LA volume ratios were lower in Group 2 compared to Group 1 (LVED/LAmax1.55±0.56vs1.79±0.69, p=0.010; LVED/LAmin3.56±2.00vs4.59±2.56, p=0.003; LVES/LAmin1.36±0.77, p=0.005, LVdias/LAdias(TTE) 1.75±0.61vs2.24±1.24, p<0.001, LVdias/LAdias(CT) 1.49±0.23vs1.69±0.41, p<0.001). LA reservoir function and conduit function indexed by E/e’ ratio was lower in Group 2. Combined TTE parameters of relative wall thickness >40, LVdias/LAdias≤1.81, and indexed by E/e’ LA reservoir function ≤0.068 had the highest discriminate power to differential patients from Group 1 and Group 2 (area under the curve 0.737).

Conclusions

In hypertension, prior to the development of LV hypertrophy, adaptive remodelling is based on reduced LV/LA volume ratio, reduced indexed reservoir LA function, and increased relative LV wall thickness.
Combination of NY-ESO-1-TCR-T-cells coengineered to secrete SiRPα decoys with anti-tumor antibodies to augment macrophage phagocytosis
Authors: Stefanidis Evangelos , Semilietof Aikaterini , Pujol Julien , Seijo Bili , Scholten Kirsten , Zoete Vincent , Michielin Olivier , Sandaltzopoulos Raphael , Coukos George , Irving Melita
Published: June 2023

The adoptive transfer of T cell receptor (TCR)-engineered T cells (ACT) targeting the HLA-A2 restricted cancer-testis epitope NY-ESO-1157-165(A2/NY) has yielded favorable clinical responses against a variety of cancers. Two promising approaches to improve ACT efficacy are TCR affinity-optimization and combinatorial treatment strategies to reprogram the tumor microenvironment (TME). By computational design, we previously developed a panel of affinity-enhanced A2/NY-TCRs. Here, we have demonstrated improved tumor control and engraftment by T cells gene-modified to express one such TCR comprising a single amino acid replacement in CDR3β (A97L). To harness macrophages in the TME, we coengineered TCR-T cells to constitutively or inducibly secrete a high-affinity signal regulatory protein alpha (SiRPα) decoy (CV1) to block the CD47 ‘don’t eat me’ signal. We demonstrated better control of tumor outgrowth by CV1-Fc coengineered TCR-T cells but in subcutaneous xenograft tumor models we observed depletion of both CV1-Fc and CV1 coengineered T cells. Importantly, CV1 coengineered T cells were not depleted by human macrophages in vitro. Moreover, Avelumab and Cetuximab enhanced macrophage-mediated phagocytosis in vitro in the presence of CV1, and augmented tumor control upon ACT. Taken together, our study indicates important clinical promise for harnessing macrophages by combining CV1 coengineered TCR-T cells with tumor-targeting monoclonal antibodies.
Chirality-Enhanced Transport and Drug Delivery of Graphene Nanocarriers to Tumor-like Cellular Spheroid
Authors: Jeon Hyunsu , Zhu Runyao , Kim Gaeun , Wang Yichun
Published: June 2023

Chirality, defined as “a mirror image,” is a universal geometry of biological and nonbiological forms of matter. This geometry of molecules determines how they interact during their assembly and transport. With the development of nanotechnology, many nanoparticles with chiral geometry or chiroptical activity have emerged for biomedical research. The mechanisms by which chirality originates and the corresponding synthesis methods have been discussed and developed in the past decade. Inspired by the chiral selectivity in life, a comprehensive and in-depth study of interactions between chiral nanomaterials and biological systems has far-reaching significance in biomedicine. Here, we investigated the effect of the chirality of nanoscale drug carriers, graphene quantum dots (GQDs), on their transport in tumor-like cellular spheroids. Chirality of GQDs (L/D-GQDs) was achieved by the surface modification of GQDs withL/D-cysteines. As anin-vitrotissue model for drug testing, cellular spheroids were derived from a human hepatoma cell line (i.e., HepG2 cells) using the Hanging-drop method. Our results reveal that theL-GQDs had a 1.7-fold higher apparent diffusion coefficient than theD-GQDs, indicating that the left-handed chirality of GQDs can enhance their transport into tumor-like cellular spheroids. Moreover, when loaded with a common chemotherapy drug, Doxorubicin (DOX),viaπ-π stacking,L-GQDs are more effective as nanocarriers for drug delivery, resulting in 25% higher efficacy for cancerous cellular spheroids than free DOX. Overall, our studies indicated that the chirality of nanocarriers is essential for the design of drug delivery vehicles to enhance the transport of drugs in a cancerous tumor.
Clustering the Planet: An Exascale Approach to Determining Global Climatype Zones
Authors: Streich Jared , Furches Anna , Kainer David , Garcia Benjamin J. , Jones Piet , Romero Jonathon , Garvin Michael R. , Climer Sharlee , Thornton Peter E. , Joubert Wayne , Jacobson Daniel
Published: June 2023

We present an exascale approach for producing global scale, high resolution, longitudinally based geoclimate classifications. Using a GPU implementation of the DUO Similarity Metric on the Summit supercomputer, we calculated the pairwise environmental similarity of 156,384,190 vectors of 414,640 encoded elements derived from 71 environmental variables over a 50-year time span at 1km2resolution. GPU matrix-matrix (GEMM) kernels were optimized for the GPU architecture and their outputs were managed through aggressive concurrent MPI rank CPU communication, calculations, and transfers. Using vector transformation and highly optimized operations of generalized distributed dense linear algebra, calculation of all-vector-pairs similarity resulted in 5.07 × 1021element comparisons and reached a peak performance of 2.31 exaflops. We demonstrated this method using existing and synthesized climate layers to show how geography can be parsed using high-performance computing. Geoclimate zones are important tools for understanding how environmental variables impact natural systems, particularly for agriculture and conservation with relevance to climate change. Historically, classification systems have been low resolution, based on limited variables, or subjective. To identify climate classes, we clustered DUO outputs at varying stringency, producing 69, 133, 340, and 717 global geoclimate zones. Our approach produced global scale, high resolution, longitudinally informed climate classifications that can be used in precision agriculture, cultivar breeding efforts, and conservation programs.
Shifts in diversification influence rates of song evolution in honeyeaters
Authors: Hay Eleanor M. , Chown Steven L. , McGee Matthew D.
Published: June 2023

Birdsongs are acoustic signals that can play a role in sexual selection. Despite the established role of birdsong in selection and reproductive isolation at microevolutionary scales, the macroevolutionary relationships between song evolution and clade diversification remain largely unexplored. We test the hypothesis that shifts in diversification influence rates of song evolution in honeyeaters, a diverse clade of songbirds restricted to Australasia. Using a song dataset for 163 honeyeater species, we identify lineage-specific shifts in diversification, and test the influence of these shifts on song evolution with state-dependent, relaxed, multivariate Brownian motion models. We also explore the underlying patterns of song evolution and phylogenetic signal of song. Shifts to lower rates of diversification are associated with lower rates of song evolution. This suggests the two factors are correlated, but is contrary to expectations that elevated rates of diversification will be associated with elevated rates of song evolution. We also found that song follows a punctuated mode of evolution, implying that birdsong has an important role in speciation events, although this signal likely erodes over time and is subject to phylogenetic constraints.
A human primary airway microphysiological system infected with SARS-CoV-2 distinguishes the treatment efficacy between nirmatrelvir and repurposed compounds fluvoxamine and amodiaquine
Authors: Quezada Landys Lopez , Medie Felix Mba , Gabriel Elizabeth P. , Luu Rebeccah J. , Rubio Logan D. , Mulhern Thomas J. , Borenstein Jeffrey T. , Fisher Christine R. , Gard Ashley L.
Published: June 2023

The COVID-19 pandemic necessitated a rapid mobilization of resources toward the development of safe and efficacious vaccines and therapeutics. Finding effective treatments to stem the wave of infected individuals needing hospitalization and reduce the risk of adverse events was paramount. For scientists and healthcare professionals addressing this challenge, the need to rapidly identify medical countermeasures became urgent, and many compounds in clinical use for other indications were repurposed for COVID-19 clinical trials after preliminary preclinical data demonstrated antiviral activity against SARS-CoV-2. Two repurposed compounds, fluvoxamine and amodiaquine, showed efficacy in reducing SARS-CoV-2 viral loads in preclinical experiments, but ultimately failed in clinical trials, highlighting the need for improved predictive preclinical tools that can be rapidly deployed for events such as pandemic emerging infectious diseases. The PREDICT96-ALI platform is a high-throughput, high-fidelity microphysiological system (MPS) that recapitulates primary human tracheobronchial tissue and supports highly robust and reproducible viral titers of SARS-CoV-2 variants Delta and Omicron. When amodiaquine and fluvoxamine were tested in PREDICT96-ALI, neither compound demonstrated an antiviral response, consistent with clinical outcomes and in contrast with prior reports assessing the efficacy of these compounds in other human cell-basedin vitroplatforms. These results highlight the unique prognostic capability of the PREDICT96-ALI proximal airway MPS to assess the potential antiviral response of lead compounds.