bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical diagnosis of fat embolism syndrome with septic shock following polytrauma: a case report
Authors: Shahi Anil , Niraula Biraj , Santyan Bir B. , kafle Nischal , Gaud Shivendra K. , Gosain Dinesh , Gupta Manish , kharel Avash , khatri Mala
Published: May 2024

Introduction and importance:

Fat embolism syndrome (FES) arises from the systemic effects of fat emboli in microcirculation. While sepsis is characterized by pathological, physiological, and metabolic abnormalities caused by infection. Septic shock is identified by elevated blood lactate (>2 mmol/l) and the need for vasopressors to maintain a mean arterial pressure of 65 mmHg or higher in the absence of hypovolemia.

Case presentation:

This case report discusses the clinical course and treatment of a 50-year-old male involved in a road traffic accident resulting in polytrauma. The patient presented with multiple fractures, hemopneumothorax, lung contusions, and rib fractures. He was then stabilized following which fractures were reduced and managed operatively. Postoperatively, the patient developed FES with septic shock, manifested by altered consciousness, petechial rashes, and respiratory distress. He was managed with intubation, chest drainage, and a combination of antibiotics, anticoagulants, and vasoactive agents. A tracheostomy was performed due to respiratory insufficiency. Following 29 days in the SICU, the patient’s condition was stabilized and shifted to the general ward for further management. He was discharged after 48 days, with a complete recovery and a 2-week follow-up. This case report depicts the challenges in the management of FES with septic shock following polytrauma.

Conclusion:

This case report is a comprehensive overview of FES complicated with septic shock. It highlights the importance of supportive care as the primary treatment modality, incorporating various medical interventions. The successful outcome and complete recovery of the patient underline the significance of prolonged monitoring, wound care, and physiotherapy.
Do Rib-Based Anchors Impair Chest Wall Motion in Early Onset Scoliosis (EOS)?
Authors: Tong Yubing , Udupa Jayaram K. , McDonough Joseph M. , Xie Lipeng , Wu Caiyun , Akhtar Yusuf , Hosseini Mahdie , Alnoury Mostafa , Shaghaghi Shiva , Gogel Samantha , Biko David M. , Mayer Oscar H , Torigian Drew A. , Cahill Patrick J. , Anari Jason B.
Published: May 2024

Purpose

There is a concern in pediatric surgery practice that rib-based fixation may limit chest wall motion in early onset scoliosis (EOS). The purpose of this study is to address the above concern by assessing the contribution of chest wall excursion to respiration before and after surgery.

Methods

Quantitative dynamic magnetic resonance imaging (QdMRI) is performed on EOS patients (before and after surgery) and normal children in this retrospective study. QdMRI is purely an image-based approach and allows free breathing image acquisition. Tidal volume parameters for chest walls (CWtv) and hemi-diaphragms (Dtv) were analyzed on concave and convex sides of the spinal curve. EOS patients (1-14 years) and normal children (5-18 years) were enrolled, with an average interval of two years for dMRI acquisition before and after surgery.

Results

CWtv significantly increased after surgery in the global comparison including all EOS patients (p < 0.05). For main thoracic curve (MTC) EOS patients, CWtv significantly improved by 50.24% (concave side) and 35.17% (convex side) after age correction (p < 0.05) after surgery. The average ratio of Dtv to CWtv on the convex side in MTC EOS patients was not significantly different from that in normal children (p=0.78), although the concave side showed the difference to be significant.

Conclusion

Chest wall component tidal volumes in EOS patients measured via QdMRI did not decrease after rib-based surgery, suggesting that rib-based fixation does not impair chest wall motion in pediatric patients with EOS.
Temporal trends in online practices relating to autism and/or ADHD: a scoping review protocol
Authors: Leiser Ruth Finn , Flowers Paul , Miyake Esperanza
Published: May 2024

Background Increasing rates of neurodivergence diagnosis have received much attention in recent months. This is particularly true of autism and/or ADHD self-diagnoses precipitated by social media use. Mainstream media - at a minimum in English-speaking Western countries - has been quick to report on this, and it is clear that a social media-facilitated phenomenon is underway. To date, however, empirical evidence related to increased visibility of, and engagement with, autism and/or ADHD 'content' online over time is lacking. Objective To map temporal trends in online practices relating to neurodivergence - specifically confined here to autism and/or ADHD - within the published literature. Areas of interest include: how framing of the concept(s) change over time; the theories represented within research on this topic; whether the focal point of these online practices has changed over time. Inclusion criteria Published literature from any country and any time period after 1991, that relate to online activity involving what currently is often referred to as 'neurodivergence' - here specifically confined to autism and/or ADHD. 'Online practices' encompasses any aspect of online communication, information-seeking, support-seeking, awareness-raising, or associated practices that take place online - via search engines, chat rooms, forums, social media platforms. Studies looking at other conditions under the neurodivergence umbrella, and those pertaining to cyberbullying and internet addiction only will be excluded. Methods Following the Joanna Briggs Institute (JBI) methodology for scoping reviews, 4 databases (Web of Science, MEDLINE, CINAHL, and APA PsycInfo) will be searched. Inclusion criteria will be used to screen for, and select, appropriate studies. The JBI extraction tool will be adapted for this particular review, and the relevant data from included studies exported to this document. Both narrative accounts and figures of the data trends will be synthesised and presented. Keywords: Social media, neurodivergence, self-diagnosis, online community, health information-seeking
Patients Recovering from COVID-19 who Presented Anosmia During their Acute Episode have Behavioral, Functional, and Structural Brain Alterations
Authors: Kausel Leonie , Figueroa-Vargas Alejandra , Zamorano Francisco , Stecher Ximena , Aspé-Sánchez Mauricio , Carvajal-Paredes Patricio , Márquez-Rodríguez Victor , Martinez-Molina Maria Paz , Román Claudio , Soto-Fernández Patricio , Valdebenito-Oyarzo Gabriela , Manterola Carla , Uribe Reinaldo , Silva Claudio , Henríquez-Ch Rodrigo , Aboitiz Francisco , Polania Rafael , Guevara Pamela , Muñoz-Venturelli Paula , Soto-Icaza Patricia , Billeke Pablo
Published: May 2024

Patients recovering from COVID-19 commonly exhibit cognitive and brain alterations, yet the specific neuropathological mechanisms and risk factors that underlie these alterations remain elusive. Given the significant global incidence of COVID-19, identifying factors that can distinguish individuals at risk of developing medium or long-term brain alterations is crucial for prioritizing follow-up care. Here, we report findings from a sample of 100 patients who were affected by a respiratory infection during the COVID-19 pandemic. This sample comprised 73 adults with a mild to moderate SARS-CoV-2 infection (who did not require invasive ventilatory assistance) and 27 with infections attributed to other agents and no history of COVID-19. The participants underwent cognitive screening, a decision-making task to measure cognitive flexibility, and magnetic resonance imaging evaluations. We assessed two clinical factors during infection: the presence of anosmia and the requirement for hospitalization due to respiratory symptoms. Groups did not differ in age or cognitive performance, but clinical factors differentially affected task performance. Patients who presented anosmia during the acute episode exhibited more impulsive changes in alternatives after a shift in probabilities in the decision-making task, while patients who required hospitalization showed more perseverative choices. Interestingly, the presence of anosmia during SARS-CoV-2 infection correlated with several brain measures, including decreases in functional activity during the decision-making task, thinning of cortical thickness in parietal regions, and loss in white matter integrity in corticospinal tracts and parietal-thalamic fasciculi, among others. These results suggest that anosmia could be a risk factor for developing brain alterations after SARS-CoV-2 infection and may serve to identify at-risk populations for follow-up.
Prediction of antidepressant side effects in the Genetic Link to Anxiety and Depression Study
Authors: Li Danyang , Lin Yuhao , Davies Helena L. , Zvrskovec Johan Källberg , Wang Rujia , Armour Chérie , Jones Ian R. , McIntosh Andrew M. , Kingston Nathalie , Bradley John R. , Hübel Christopher , Kalsi Gursharan , Coleman Jonathan R. I. ,   the NIHR BioResource consortium, Hotopf Matthew , Eley Thalia C. , Vassos Evangelos , Iniesta Raquel , Breen Gerome
Published: May 2024

Antidepressants are the most common treatment for moderate or severe depression. Side effects are crucial indicators for antidepressants, but their occurrence varies widely among individuals. In this study, we leveraged genetic and medical data from self-reported questionnaires in the Genetic Links to Anxiety and Depression (GLAD) study to build prediction models of side effects and subsequent discontinuation across three antidepressant classes (SSRI, SNRI, tricyclic antidepressant (TCA)) at the first and the last (most recent) year of prescription. We included 259 predictors spanning genetic, clinical, illness, demographic, and antidepressant information. Six prediction models were trained, and their performance was compared. The final dataset comprised 4,354 individuals taking SSRI in the first prescription and 3,414 taking SSRI, SNRI or TCA in the last year of prescription. In the first year, the best area under the receiver operating characteristic curve (AUROC) for predicting SSRI discontinuation and side effects were 0.65 and 0.60. In the last year of SSRI prescription, the highest AUROC reached 0.73 for discontinuation and 0.87 for side effects. Models for predicting discontinuation and side effects of SNRI and TCA showed comparable performance. The history of side effects and discontinuation of antidepressant use were the most influential predictors of the outcomes in the last year of prescription. When examining 30 common antidepressant side effect symptoms, most of them were differentially prevalent between antidepressant classes. Our findings suggested the feasibility of predicting antidepressant side effects using a self-reported questionnaire, particularly for the last prescription. These results could contribute valuable insights for the development of clinical decisions aimed at optimising treatment selection with enhanced tolerability but require replication in medical record linkage or prospective data.
Exposure to per- and polyfluoroalkyl substances and age-related macular degeneration in U.S. middle-aged and older adults
Authors: Kang Habyeong , Park Sung Kyun , Kim Dong Hyun , Choi Yoon-Hyeong
Published: May 2024

Despite various health effects of per- and polyfluoroalkyl substances (PFAS) exposure, the association between PFAS exposure and age-related macular degeneration (AMD) has not been investigated. We aimed to assess associations of PFAS exposure with AMD, using data from 1,722 U.S. adults aged 40 years or more participating in the National Health and Nutrition Examination Survey 2005–2008 with complete data on PFAS measurement, AMD diagnosis, and covariates. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were measured. An overall PFAS burden score was calculated using item response theory scoring. Individual PFAS concentration and overall PFAS burden score were categorized into low (reference), medium, and high groups. Diagnosis of AMD was based on retinal image examination. Any AMD was defined as the presence of early or late AMD. Survey-weighted logistic regression adjusted for potential confounders was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for presence of AMD according to PFAS exposure. Overall, 132 (6.5%) individuals were diagnosed as any AMD, including 115 (5.7%) individuals with early AMD. A significant dose-response association was observed between serum PFOS concentration and any AMD (p-trend=0.03), with a significant OR of 1.99 (95% CI: 1.05, 3.79) for the high group compared to the reference. Overall PFAS burden showed a non-monotonic association with any AMD, with a significant OR of 2.18 (95% CI: 1.18, 4.04) for the medium. Inverted U-shaped associations were observed by restricted cubic spline analyses. Also, early AMD showed similar patterns in PFOS and overall PFAS burden and additionally an inverted U-shape association in PFNA. Our findings suggest that exposure to PFAS estimated by serum PFOS and PFNA as well as overall PFAS burden might be a risk factor for AMD in middle-aged and older population.
EXPLORING THE PHYSICAL WELL-BEING OF BREAST CANCER PATIENTS IN KUMASI METROPOLIS: A QUALITATIVE STUDY
Authors: Sefah Victoria , Budu Hayford Isaac , Tano Priscilla Felicia , Lawer Emmanuel Kofi , Tano Emile Kouakou
Published: May 2024

Background

Years back, cancer was thought to be a problem limited to the developed countries. Cancer is now a disease with lots of burden, leading cause of death and disability in developing countries. Physical health is very important for the overall well-being of breast cancer survivors, since it is the visible part of the dimensions of overall health and well-being. Prior studies have examined factors leading to late detection, financial burden and experiences of caregivers of breast cancer patients in Ghana, however, none of the studies have explored how breast cancer may specifically impact the physical well-being and the quality of life of these women. This study therefore seeks to explore how breast cancer impact the physical well-being and the quality of life of these women.

Methodology

The study site and setting was the Oncology directorate at Komfo Anokye Teaching Hospital where twelve respondents were recruited for the study. Breast care survivors were purposively sampled and interviewed (face-to-face) to explore how the BC has impacted on their physical wellbeing and their Quality of Life (QoL). Demographic data were obtained before the main interview. The interviews lasted between 30minutes to 45minutes. Data was analysed using thematic analysis of key information by using NVivo data management software.

Results

Participants described their physical wellbeing according to the way they encountered the disease from the onset through to the treatment administration. Five sub-themes emerged, namely: Fatigue/bodily weakness: impaired functional ability: pain; distorted sleep; and fertility.

Conclusion

Fatigue, impaired functional ability, pain, distorted sleep and fertility were consistent with constructs of the Quality of Life model. These physical symptoms negatively affected the total well-being of the BCSs.
Translation, adaptation, and measurement properties of the Muscle-Strengthening Exercise Questionnaire among university students in Indonesia
Authors: Ashari Reza Setyono , Sabirin Rahmaningsih Mara , Merlinda Stevani Tia Bella , Pratiwi Dilia Ananda , Tsania Melati Nilna , Wibowo Rakhmat Ari
Published: May 2024

Background

Despite the abundant evidence showing the benefits of muscle-strengthening exercise (MSE), no epidemiological tool is available for assessing MSE among Indonesian university students. This study aimed to adapt the Muscle-Strengthening Exercise Questionnaire (MSEQ) into the Indonesian context and test the validity and reliability of the MSEQ Indonesian version.

Methods

Translation and cultural adaptation, content validity studies, concurrent validity studies, and reliability studies were conducted with a total of 121 respondents. The concurrent validity study compared the results of measuring MSE frequency, intensity, duration, and volume with those of the 7-day diary and relative handgrip strength. For the reliability study, the respondents were asked to fill the MSEQ Indonesian version twice with a time interval of 7 days.

Results

Moderate-to-strong correlations were observed between the results for the weekly frequency, duration, intensity, and volume of MSE and those of the 7-day diary and hand grip strength. Test–retest reliabilities were good to excellent for machine weight, holistic, and overall MSE but poor for bodyweight MSE. In assessing the target muscle group, the MSEQ Indonesian version showed good test–retest reliability for machine-weight MSE but poor-to-very good test–retest reliability for bodyweight, free weight, and holistic MSE.

Conclusions

Our study showed acceptable validity and reliability of the MSEQ Indonesian version to be used for assessing MSE among university students in Indonesia. Further studies are warranted to ensure the generalizability of our findings among the adult population.
Performance of empirical and model-based classifiers for detecting sucrase-isomaltase inhibition using the13C-sucrose breath test
Authors: Van Wyk Hannah , Lee Gwenyth O. , Schillinger Robert J. , Edwards Christine A. , Morrison Douglas J. , Brouwer Andrew F.
Published: May 2024

Background

Environmental enteric dysfunction (EED) is a syndrome characterized by epithelial damage including blunting of the small intestinal villi and altered digestive and absorptive capacity which may negatively impact linear growth in children. The13C-sucrose breath test (13C-SBT) has been proposed to estimate sucrase-isomaltase (SIM) activity, which is thought to be reduced in EED. We previously showed how various summary measures of the13C-SBT breath curve reflect SIM inhibition. However, it is uncertain how the performance of these classifiers is affected by test duration.

Methods

We leveraged SBT data from a cross-over study in 16 adults who received 0, 100, and 750 mg of Reducose, a natural SIM inhibitor. We evaluated the performance of a pharmacokinetic-model-based classifier,ρ, and three empirical classifiers (cumulative percent dose recovered at 90 minutes (cPDR90), time to 50% dose recovered, and time to peak dose recovery rate), as a function of test duration using receiver operating characteristic curves. We also assessed the sensitivity, specificity, and accuracy of consensus classifiers.

Results

Test durations of less than 2 hours generally failed to accurately predict later breath curve dynamics. The cPDR90 classifier had the highest area-under-the-curve and, by design, was robust to shorter test durations. For detecting mild SIM inhibition,ρhad a higher sensitivity.

Conclusions

We recommend SBT tests run for at least a 2-hour duration. Although cPDR90 was the classifier with highest accuracy and robustness to test duration in this application, concerns remain about its sensitivity to misspecification of CO2production rate. More research is needed to assess these classifiers in target populations.
Apathy and Physical Activity: A Systematic Review and Meta-Analysis
Authors: Farajzadeh Ata , Hébert Alexe , Lahart Ian M. , Bilodeau Martin , Boisgontier Matthieu P.
Published: May 2024

Purpose

Patient motivation is essential for the success of their rehabilitation. Apathy, a state of primary motivational deficiency, may therefore hinder physiotherapists’ interventions, such as those aimed at increasing patients’ physical activity. This study aims to examine the relationship between apathy and physical activity and to identify the factors that influence this relationship.

Methods

Six databases were searched for articles including both a measure of apathy and physical activity. Two reviewers screened articles for inclusion, assessed risk of bias, and extracted data from each study. Pearson product-moment correlations were pooled from eligible studies using the generic inverse pooling and random effects method to examine the relationship between apathy and physical activity. Subgroup meta-analyses were conducted to examine the differences between studies that included participants with different health conditions and used different types of physical activity outcomes and apathy measures. Meta-regressions were conducted to examine the moderating effects of age and gender.

Results

Twenty-eight articles were included in the systematic review and 22 studies (n = 12,541 participants) in the main meta-analysis. Results showed a negative correlation between apathy and physical activity (r = -0.13; 95% CI: -0.18 to -0.09; p < 0.0001 based on Pearson’s r values; r = - 0.40; 95% CI: -0.68 to -0.02; p = 0.043 based on Spearman’s rho values). A subgroup meta-analysis revealed that the correlation was statistically significant in patients with Parkinson’s disease and in older adults who were healthy, depressed, fallers, or had mild cognitive impairment. A meta-regression showed an effect of age, with a stronger correlation between apathy and physical activity in older adults compared to younger adults (p = 0.003).

Conclusion

Our results suggest that higher levels of apathy are associated with lower levels of physical activity and that this negative association is stronger with age. Therefore, apathy may limit exercise therapy efficacy and carry prognostic implications for patients whose condition requires physical activity.
A polygenic predictor of baseline QTc is associated with sotalol-induced QT prolongation
Authors: Lancaster Megan C. , Davogustto Giovanni , Prifti Edi , Perret Claire , Funck-Brentano Christian , Roden Dan M. , Salem Joe-Elie
Published: May 2024

Background

Drug-induced QT interval prolongation raises the risk of fatal arrhythmia and is a central issue in safety pharmacology. Yet individual QT drug response is highly variable, and risk stratification remains a challenge. We hypothesized that genetic factors underlying the baseline QT influence this variation in QT drug response.

Methods

A cohort of 990 healthy subjects was prospectively challenged with a single 80 mg oral sotalol dose. Exclusion criteria included abnormal ECG, cardiac disease, and QT-prolonging drug use. ECGs were obtained at baseline and 3 hours post-dose. QT response was defined as absolute change in Fridericia heart-rate corrected QT (ΔQTc). Plasma sotalol was measured 3 hours post-dose. Subjects were genotyped on the MEGA array. Principal component analysis of genotypes was used to define genetic ancestry. A polygenic risk score (PRS) for the baseline QTc comprised of 465,399 common variants was calculated from assayed and imputed genotypes. The difference in PRS between subjects with high QT response (ΔQTc≥60 ms) and those with ΔQTc<60ms was assessed by Mann Whitney test. A multivariable regression model was used to assess the association between PRS and ΔQTc after covariate adjustment.Results:Of the 990 subjects, 978 (99%) passed genomic quality control and were included in analysis. 62% were female (n=607), with median age 23 (interquartile range (IQR) 21-33). The median ΔQTc 3 hours post-sotalol was 21 ms (IQR 12-30). Ten subjects (1%) had ΔQTc≥60 ms, and their PRS was significantly higher compared to those with ΔQTc<60 ms (P=0.0082). In the regression model, PRS was positively associated with ΔQTc (P=0.0002).

Conclusion

Common genetic variants associated with the baseline QT also capture part of the repolarization response to sotalol. This adds to the emerging concept that the genetic architecture of a trait can predict drug response.
Colistin resistance among the Gram-negative nosocomial pathogens in India: A systematic review and meta-analysis
Authors: Dwibedy Sambit K. , Padhy Indira , Panda Aditya K. , Mohapatra Saswat S.
Published: May 2024

Background

The rapid rise of nosocomial infections and the growing ineffectiveness of frontline antibiotics against Gram-negative bacteria (GNB) have put the healthcare sector under unprecedented stress. In this scenario, colistin, an antibiotic of the polymyxin class, has become the last resort treatment option. The unrestricted use of colistin in the preceding decades has led to the emergence of colistin-resistant (ColR) bacterial strains. Unfortunately, comprehensive data on the prevalence of ColRnosocomial pathogens in India are lacking. This study was conducted to address this information gap and to determine the prevalence of ColRamong the nosocomial GNB species in India.

Methods

A systematic review and meta-analysis were conducted to determine the prevalence of ColRamong the nosocomial GNB species in India and their geographical distribution. A systematic search of the online databases was performed and eligible studies meeting the inclusion criteria were used for qualitative synthesis. The combined event rate and 95% confidence interval were estimated using forest plot with a random-effect model. Cochrane Q statistics and I2statistics were used to detect possible heterogeneity.

Results

From a total of 1865 retrieved records from 4 databases, 36 studies were included in the study. Among the most common nosocomial pathogens, K. pneumoniaeshowed a rate of ColRat 17.4%, followed byP. aeruginosa(14.1%),E. coli(12.3%), andA. baumannii(12.2%). Interestingly, our analysis revealed thatE. cloacaehas the highest rate of ColRat 28.5%.

Conclusions

The level of resistance displayed byK. pneumoniae,P. aeruginosa, and to a lesser extent,E. coliandA. baumanniiin the Indian subcontinent poses a challenge for public health management. Though prevalence may differ among regions and over time, continued surveillance, and efforts to curb the spread of resistance are crucial to ensure the continued effectiveness of this critical antibiotic.
The interactive effect of intra-beat and inter-beat blood pressure variability on neurodegeneration in older adults
Authors: Lohman Trevor , Shenasa Fatemah , Sible Isabel , Kapoor Arunima , Engstrom Allison C , Dutt Shubir , Head Elizabeth , Sordo Lorena , M. Alitin John Paul , Gaubert Aimee , Nguyen Amy , Nation Daniel A
Published: May 2024

Blood pressure variability (BPV) and arterial stiffness are age-related hemodynamic risk factors for neurodegenerative disease, but it remains unclear whether they exert independent or interactive effects on brain health. When combined with high inter-beat BPV, increased intra-beat BPV indicative of arterial stiffness could convey greater pressure wave fluctuations deeper into the cerebrovasculature, exacerbating neurodegeneration. This interactive effect was studied in older adults using multiple markers of neurodegeneration, including medial temporal lobe (MTL) volume, plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Older adults (N=105) without major neurological or systemic disease were recruited and underwent brain MRI and continuous BP monitoring to quantify inter-beat BPV through systolic average real variability (ARV) and intra-beat variability through arterial stiffness index (ASI). Plasma NfL and GFAP were assessed. The interactive effect of ARV and ASI on MTL atrophy, plasma NfL, and GFAP was studied using hierarchical linear regression. Voxel-based morphometry (VBM) was used to confirm region-of-interest analysis findings. The interaction between higher ARV and higher ASI was significantly associated with left-sided MTL atrophy in both the region-of-interest and false discovery rate-corrected VBM analysis. The interactive effect was also significantly associated with increased plasma NfL, but not GFAP. The interaction between higher ARV and higher ASI is independently associated with increased neurodegenerative markers, including MTL atrophy and plasma NfL, in independently living older adults. Findings could suggest the increased risk for neurodegeneration associated with higher inter-beat BPV may be compounded by increased intra-beat variability due to arterial stiffness.
Alterations in aperiodic and periodic EEG activity in young children with Down syndrome
Authors: Geiger McKena , Hurewitz Sophie R. , Pawlowski Katherine , Baumer Nicole T. , Wilkinson Carol L.
Published: May 2024

Down syndrome is the most common cause of intellectual disability, yet little is known about the neurobiological pathways leading to cognitive impairments. Electroencephalographic (EEG) measures are commonly used to study neurodevelopmental disorders, but few studies have focused on young children with DS. Here we assess resting state EEG data collected from toddlers/preschoolers with DS (n=29, age 13-48 months old) and compare their aperiodic and periodic EEG features with both age-matched (n=29) and cognitive-matched (n=58) comparison groups. DS participants exhibited significantly reduced aperiodic slope, increased periodic theta power, and decreased alpha peak amplitude. A majority of DS participants displayed a prominent peak in the theta range, whereas a theta peak was not present in age-matched participants. Overall, similar findings were also observed when comparing DS and cognitive-matched groups, suggesting that EEG differences are not explained by delayed cognitive ability.
Uncovering COVID-19 Transmission Tree: Identifying Traced and Untraced Infections in an Infection Network
Authors: Lee Hyunwoo , Choi Hayoung , Lee Hyojung , Lee Sunmi , Kim Changhoon
Published: May 2024

We present a comprehensive analysis of COVID-19 transmission dynamics using an infection network derived from epidemiological data in South Korea, covering the period from January 3, 2020, to July 11, 2021. This network, illustrating infector-infectee relationships, provides invaluable insights for managing and mitigating the spread of the disease. However, significant missing data hinder the conventional analysis of such networks from epidemiological surveillance. To address this challenge, our research suggests a novel approach for categorizing individuals into four distinct groups, based on the classification of their infector or infectee status as either traced or untraced cases among all confirmed cases. Furthermore, the study analyzes the changes in the infection networks among untraced and traced cases across five distinct periods. The four types of cases emphasize the impact of various factors, such as the implementation of public health strategies and the emergence of novel COVID-19 variants, which contribute to the propagation of COVID-19 transmission. One of the key findings of this study is the identification of notable transmission patterns in specific age groups, particularly in those aged 20–29, 40–69, and 0–9, based on the four type classifications. Moreover, we develop a novel real-time indicator to assess the potential for infectious disease transmission more effectively. By analyzing the lengths of connected components, this indicator facilitates improved predictions and enables policymakers to proactively respond, thereby helping to mitigate the effects of the pandemic on global communities.
Moderating heritability with genomic data
Authors: Benstock Sarah E. , Prom-Wormley Elizabeth , Verhulst Brad
Published: May 2024

Environmental moderators may amplify or suppress the heritability (i.e., the proportion of genetic variation) of a phenotype. This genetic sensitivity to the environment is called gene-environment interaction (GxE). Existing GxE methods struggle to identify replicable interactions because they focus on the interaction coefficients. We propose a novel method for estimating GxE heritability using genetic marginal effects from GxE genome-wide analyses and LD Score Regression (LDSC). We demonstrate the effectiveness of our method for body mass index (BMI) treating biological sex (binary) and age (continuous) as moderators. We find robust, interpretable evidence for GxE that is not detected by existing methods.
Task-Relevant Stimulus Design Improves P300-Based Brain-Computer Interfaces
Authors: Kim Jongsu , Cho Yang Seok , Kim Sung-Phil
Published: May 2024

Objective

In the pursuit of refining P300-based brain-computer interfaces (BCIs), our research aims to propose a novel stimulus design focused on selective attention and task relevance to address the challenges of P300-based BCIs, including the necessity of repetitive stimulus presentations, accuracy improvement, user variability, and calibration demands.

Approach

In the oddball task for P300-based BCIs, we develop a stimulus design involving task-relevant dynamic stimuli implemented as finger-tapping to enhance the elicitation and consistency of event-related potentials (ERPs). We further improve the performance of P300-based BCIs by optimizing ERP feature extraction and classification in offline analyses.

Main Results

With the proposed stimulus design, online P300-based BCIs in 37 healthy participants achieves the accuracy of 91.2% and the information transfer rate (ITR) of 28.37 bits/min with two stimulus repetitions. With optimized computational modeling in BCIs, our offline analyses reveal the possibility of single-trial execution, showcasing the accuracy of 91.7% and the ITR of 59.92 bits/min. Furthermore, our exploration into the feasibility of across-subject zero-calibration BCIs through offline analyses, where a BCI built on a dataset of 36 participants is directly applied to a left-out participant with no calibration, yields the accuracy of 94.23% and the ITR of 31.56 bits/min with two stimulus repetitions and the accuracy of 87.75% and the ITR of 52.61 bits/min with single-trial execution. When using the finger-tapping stimulus, the variability in performance among participants is the lowest, and a greater increase in performance is observed especially for those showing lower performance using the conventional color-changing stimulus.

Signficance

Using a novel task-relevant dynamic stimulus design, this study achieves one of the highest levels of P300-based BCI performance to date. This underscores the importance of coupling stimulus paradigms with computational methods for improving P300-based BCIs.
Multiomics analysis of narcolepsy T cells: global hypomethylation linked to T cell proliferation
Authors: Shimada Mihoko , Honda Makoto , Honda Yoshiko , Kodama Tohru , Hitomi Yuki , Tokunaga Katsushi , Miyagawa Taku
Published: May 2024

Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a loss of orexin-producing cells in the brain and involves autoimmune mechanisms, including the presence of autoreactive T cells. We performed a genome-wide DNA methylation analysis using CD4+and CD8+T cells of NT1 patients. Analysis of differentially methylated regions as well as multiomics analysis with genomic and transcriptomic data obtained from the same samples indicated that cell chemotaxis pathways are implicated as a cause in the pathogenesis of NT1. Additionally, we found global hypomethylation in both the T cells of NT1 cases (CD4+:P= 1.69E-67; CD8+:P= 4.83E-12). These NT1-associated hypomethylated sites were significantly more abundant in solo-WCGW (sequences without neighboring CpGs, where W is an A or T base;P= 9.87E-194). Solo-WCGW tends to lose DNA methylation over the course of cell divisions, suggesting enhanced T cell proliferation in NT1.
Sliding Window INteraction Grammar (SWING): a generalized interaction language model for peptide and protein interactions
Authors: Omelchenko Alisa A. , Siwek Jane C. , Chhibbar Prabal , Arshad Sanya , Nazarali Iliyan , Nazarali Kiran , Rosengart AnnaElaine , Rahimikollu Javad , Tilstra Jeremy , Shlomchik Mark J. , Koes David R. , Joglekar Alok V. , Das Jishnu
Published: May 2024

The explosion of sequence data has allowed the rapid growth of protein language models (pLMs). pLMs have now been employed in many frameworks including variant-effect and peptide-specificity prediction. Traditionally, for protein-protein or peptide-protein interactions (PPIs), corresponding sequences are either co-embedded followed by post-hoc integration or the sequences are concatenated prior to embedding. Interestingly, no method utilizes a language representation of the interaction itself. We developed an interaction LM (iLM), which uses a novel language to represent interactions between protein/peptide sequences.SlidingWindowInteractionGrammar (SWING) leverages differences in amino acid properties to generate an interaction vocabulary. This vocabulary is the input into a LM followed by a supervised prediction step where the LM’s representations are used as features.

SWING was first applied to predicting peptide:MHC (pMHC) interactions. SWING was not only successful at generating Class I and Class II models that have comparable prediction to state-of-the-art approaches, but the unique Mixed Class model was also successful at jointly predicting both classes. Further, the SWING model trained only on Class I alleles was predictive for Class II, a complex prediction task not attempted by any existing approach. For de novo data, using only Class I or Class II data, SWING also accurately predicted Class II pMHC interactions in murine models of SLE (MRL/lpr model) and T1D (NOD model), that were validated experimentally.

To further evaluate SWING’s generalizability, we tested its ability to predict the disruption of specific protein-protein interactions by missense mutations. Although modern methods like AlphaMissense and ESM1b can predict interfaces and variant effects/pathogenicity per mutation, they are unable to predict interaction-specific disruptions. SWING was successful at accurately predicting the impact of both Mendelian mutations and population variants on PPIs. This is the first generalizable approach that can accurately predict interaction-specific disruptions by missense mutations with only sequence information. Overall, SWING is a first-in-class generalizable zero-shot iLM that learns the language of PPIs.
Mathematical model of intestinal lipolysis of a long-chain triglyceride
Authors: Rezhdo Oljora , West Richard , Kim Myriel , Ng Brandon , Saphier Sigal , Carrier Rebecca L.
Published: May 2024

Lipids are an important component of food and oral drug formulations. Upon release into gastrointestinal fluids, triglycerides, common components of foods and drug delivery systems, form emulsions and are digested into simpler amphiphilic lipids (e.g., fatty acids) that can associate with intestinal bile micelles and impact their drug solubilization capacity. Digestion of triglycerides is dynamic and dependent on lipid quantity and type, and quantities of other components in the intestinal environment (e.g., bile salts, lipases). The ability to predict lipid digestion kinetics in the intestine could enhance understanding of lipid impact on the fate of co-administered compounds (e.g., drugs, nutrients). In this study, we present a kinetic model that can predict the lipolysis of emulsions of triolein, a model long-chain triglyceride, as a function of triglyceride amount, droplet size, and quantity of pancreatic lipase in an intestinal environment containing bile micelles. The model is based on a Ping Pong Bi Bi mechanism coupled with quantitative analysis of partitioning of lipolysis products in colloids, including bile micelles, in solution. The agreement of lipolysis model predictions with experimental data suggests that the mechanism and proposed assumptions adequately represent triglyceride digestion in a simulated intestinal environment. In addition, we demonstrate the value of such a model over simpler, semi-mechanistic models reported in the literature. This lipolysis framework can serve as a basis for modeling digestion kinetics of different classes of triglycerides and other complex lipids as relevant in food and drug delivery systems.
PROPEL: a scalable model for postbaccalaureate training to promote diversity in the biomedical workforce
Authors: Allen Jessica , Abdiwahab Ekland , Morris Meghan D. , Le Saux Claude Jourdan , Betancur Paola , Ansel K. Mark , Hernandez Ryan D. , Nystul Todd G.
Published: May 2024

Promoting diversity in the scientific workforce is crucial for harnessing the potential of available talent and ensuring equitable access to Science, Technology, Engineering, Mathematics, and Medicine (STEM-M) careers. We have developed an innovative program called Post-baccalaureate Research Opportunity to Promote Equity in Learning (PROPEL) that provides scientific and career development training for postbaccalaureate scholars from historically excluded backgrounds in STEM-M fields with an interest in pursuing a PhD or MD/PhD degree. Our program is distinct from other postbaccalaureate programs in that scholars are hired by individual labs rather than funded centrally by the program. This funding mechanism removes the idea that central funding is necessary to encourage faculty to train diverse scholars and allows the program to scale dynamically according to the needs of the scientific community. The PROPEL program started in 2020 with six scholars and has since grown to an enrollment of over 100, making it the largest postbaccalaureate program for biomedical research in the country. Here, we describe the program structure and curriculum, our strategy for recruitment, the enrollment trends; the program demographics; metrics of scholar engagement; and outcomes for scholars who completed the program in 2023. Our experience demonstrates the strong demand from both scholars and faculty for programming of this type and describes the feasibility of implementation.
Detection of High-Frequency Oscillations from Intracranial EEG Data with Switching State Space Model
Authors: Gu Zeyu , Yang Shihao , Yu Zhongyuan , Liu Feng
Published: May 2024

High Frequency Oscillations (HFOs) is an important biomarker that can potentially pinpoint the epileptogenic zones (EZs). However, the duration of HFO is short with around 4 cycles, which might be hard to recognize when embedded within signals of lower frequency oscillatory background. In addition, annotating HFOs manually can be time-consuming given long-time recordings and up to hundreds of intracranial electrodes. We propose to leverage a Switching State Space Model (SSSM) to identify the HFOs events automatically and instantaneously without relying on extracting features from sliding windows. The effectiveness of the SSSM for HFOs detection is fully validated in the intracranial EEG recording from human subjects undergoing the presurgical evaluations and showed improved accuracy when capturing the HFOs occurrence and their duration.
Energetics of substrate transport in proton-dependent oligopeptide transporters
Authors: Selvam Balaji , Chiang Nicole , Shukla Diwakar
Published: May 2024

The PepTSotransporter mediates the transport of peptides across biological membranes. Despite advancements in structural biology, including cryogenic electron microscopy structures resolving PepTSoin different states, the molecular basis of peptide recognition and transport by PepTSois not fully elucidated. In this study, we employed molecular dynamics simulations, Markov State Models (MSMs), and Transition Path Theory (TPT) to investigate the transport mechanism of an alanine-alanine peptide (Ala-Ala) through the PepTSotransporter. Our simulations revealed conformational changes and key intermediate states involved in peptide translocation. We observed that the presence of the Ala-Ala peptide substrate lowers the free energy barriers associated with transition to the inward-facing state. Furthermore, we elucidated the proton transport model and analyzed the pharmacophore features of intermediate states, providing insights for rational drug design. These findings highlight the significance of substrate binding in modulating the conformational dynamics of PepTSoand identify critical residues that facilitate transport.
The correlation between lumbar and pelvic dysfunctions in non-post-surgical adult patients: a scoping review protocol
Authors: Manni Tiziana , Coaro Francesca , Nativo Monica , Stocco Marina
Published: May 2024

Objective

The objective of this scoping review is to understand the extent and type of evidence available on the correlation between pelvic and lumbar region dysfunction in adult non-surgical patients.

Introduction

It is well known that the pelvic and lumbar regions are connected, but the information about them is conflicting and often not useful for clinical practice. For this reason, we want to conduct a scoping review, to map all available evidence on the topic and provide clearer information for clinical work with on patients.

Inclusion criteria

This scoping review will consider adult patients with pelvic floor and and low back disfunction with related clinical conditions. The only limitation is post-surgical patients, who will be excluded from this review. This scoping review will consider any study design or type of publication.

Methods

An initial limited search of MEDLINE (PubMed) will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe these articles. This will lead to the development of a search strategy including identified keywords and index terms that fit each included database: CINAHL, Cochrane Library, PEDro, Scopus and grey literature. The research will be performed from inception to February 2024. No geographical, setting and language restrictions will be applied. Potentially relevant sources will be retrieved in full, and their citation details imported into Rayyan — a web and mobile app for systematic reviews. Additional records will be identified through searching in grey literature and the reference lists of all relevant studies. No study design, publication type, data and language restrictions will be applied. Two reviewers will independently screen all abstracts and full-text studies for inclusion. A data collection form will be used to extract the characteristics of the studies included. A tabular and accompanying narrative summary of the information will be provided. The results of the search and the study inclusion process will be presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR) flow diagram.
An Accelerated PETALUTE MRI Sequence forIn VivoQuantification of Sodium Content in Human Articular Cartilage at 3T
Authors: Villarreal Cameron X. , Shen Xin , Alhulail Ahmad A. , Buffo Nicholas M. , Zhou Xiaopeng , Pogue Evan , Özen Ali Caglar , Chiew Mark , Sawiak Stephen , Emir Uzay , Chan Deva D.
Published: May 2024

In this work, we demonstrate the sodium magnetic resonance imaging (MRI) capabilities of a three-dimensional (3D) dual-echo ultrashort echo time (UTE) sequence with a novel rosette petal trajectory (PETALUTE), in comparison to the 3D density-adapted (DA) radial spokes UTE sequence. We scanned five healthy subjects using a 3D dual-echo PETALUTE acquisition and two comparable implementations of 3D DA-radial spokes acquisitions, one matching the number of k-space projections (Radial – Matched Spokes) and the other matching the total number of samples (Radial – Matched Samples) acquired in k-space. The PETALUTE acquisition enabled equivalent sodium quantification in articular cartilage volumes of interest (168.8 ± 29.9 mM) to those derived from the 3D radial acquisitions (171.62 ± 28.7 mM and 149.8 ± 22.2 mM, respectively). We achieved a 41% shorter scan time of 2:06 for 3D PETALUTE, compared to 3:36 for 3D radial acquisitions. We also evaluated the feasibility of further acceleration of the PETALUTE sequence through retrospective compressed sensing with 2× and 4× acceleration of the first echo and showed structural similarity of 0.89 ± 0.03 and 0.87 ± 0.03 when compared to non-retrospectively accelerated reconstruction. Together, these results demonstrate improved scan time with equivalent performance of the PETALUTE sequence compared to the 3D DA-radial sequence for sodium MRI of articular cartilage.