bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimorbidity networks associated with frailty among middle-aged and older people with HIV
Authors: Lorenz David R. , Mukerji Shibani S. , Misra Vikas , Uno Hajime , Gelman Benjamin B. , Moore David J. , Singer Elyse J. , Morgello Susan , Gabuzda Dana 
Published: July 2021

Objective:
People with HIV (PWH) have increased prevalence of multimorbidity and frailty at younger ages compared with the general population. This study investigated individual and combinatorial effects of neuropsychiatric and medical comorbidities as predictors of frailty in PWH.

Design:
Analysis of data from the National NeuroAIDS Tissue Consortium, a longitudinal observational cohort.

Methods:
Five hundred and twenty-four PWH over age 40 years were classified using Fried's Frailty criteria. Twelve comorbidities were documented from longitudinal data and associations between individual and co-occurring comorbidities with frailty were assessed using weighted network and logistic regression analyses.

Results:
At frailty assessment between 2015 and 2020, median age was 61 years, 76% were men, 94% were on antiretroviral therapy (ART), 73% had two or more comorbidities, 24% were frail, and 52% were prefrail. Among individual comorbidities, highest odds of frailty were in participants with depressive symptoms [adjusted odds ratio (aOR), 95% confidence interval (CI) 3.48 (2.22–5.46)], followed by bone disease and chronic obstructive pulmonary disease (COPD) [2.47 (1.28–4.72) and 2.13 (1.36–3.34), respectively]. Among co-occurring comorbidities, highest odds of frailty were in participants having depressive symptoms with diabetes, hypertension, or obesity [aORs (95% CIs) 5.29 (2.32–12.08), 5.21 (2.65–10.40), 4.85 (2.39–9.95), respectively], cognitive impairment with diabetes or renal disease [2.81 (1.38–5.68) and 2.53 (1.26–5.03), respectively], renal disease with cardiovascular disease [2.81 (1.32–6.01)], and diabetes with obesity [2.76 (1.39–5.45)].

Conclusion:
Co-occurrence of depressive symptoms, cognitive impairment, diabetes, or renal disease with other medical conditions substantially increases odds of frailty in older PWH. Identifying and treating these comorbidities may help to reduce functional decline with aging in PWH.
Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana
Authors: Moraka Natasha Onalenna , Garcia-Broncano Pilar , Hu Zixin , Ajibola Gbolahan , Bareng Ontlametse T. , Pretorius-Holme Molly , Maswabi Kenneth , Maphorisa Comfort , Mohammed Terence , Gaseitsiwe Simani , VanZyl Gert U. , Kuritzkes Daniel R. , Lichterfeld Mathias , Moyo Sikhulile , Shapiro Roger L. 
Published: July 2021

Objective:
To describe the occurrence of HIV drug resistance mutations (DRMs) in both intact and defective HIV-1 cell-associated DNA (HIV-1 CAD) among early-treated infants.

Design:
The Botswana EIT Study (ClinicalTrials.gov NCT02369406) initiated antiretroviral therapy (ART) in the first week of life and evaluated HIV-1 in plasma and peripheral blood mononuclear cells (PBMCs).

Methodology:
We analyzed 257 near-HIV-1 full-length sequences (nFLS) obtained by Illumina next-generation sequencing from infants near birth. Sanger sequencing of pol was performed for mothers at delivery and children with clinical failure through 96 weeks. DRMs were identified using the Stanford HIV Drug Resistance Database.

Results:
In 27 infants, median PBMC HIV-1 proviral load was 492 copies/ml [IQR: 78–1246 copies/ml] at a median of 2 days (range 1–32); 18 (66.7%) had no DRMs detected; six (22.2%) had DRMs detected in defective DNA only, and three (11.1%) had DRMs in both defective and intact DNA (P = 0.09). A total of 60 of 151 (37.7%) defective sequences had at least one DRM: 31.8% NNRTI, 15.2% NRTI, 5.3% protease inhibitor, and 15.5% INSTI-associated mutations. In intact sequences, 33 of 106 (31.1%) had at least 1 DRM: 29.2% NNRTI, 7.5% NRTI, 0.9% protease inhibitor, and no INSTI-associated mutations. For all three infants with intact sequence DRMs, corresponding DRMs occurred in maternal plasma at delivery. Archived DRMs were detectable at a later clinical rebound on only one occasion.

Conclusion:
Defective HIV-1 cell-associated DNA sequences may overestimate the prevalence of drug resistance among early-treated children. The impact of DRMs from intact proviruses on long-term treatment outcomes warrants further investigation.
Cross-frequency phase-amplitude coupling in repetitive movements in patients with Parkinson’s disease
Authors: Gong Ruxue , Mühlberg Christoph , Wegscheider Mirko , Fricke Christopher , Rumpf Jost-Julian , Knösche Thomas R. , Classen Joseph 
Published: July 2021

AbstractBradykinesia is a cardinal motor symptom in Parkinson’s disease whose pathophysiology is incompletely understood. When signals are recorded from the cortex or scalp at rest, affected patients display enhanced phase-amplitude coupling between β (13-30Hz) and broadband γ (50-150Hz) oscillatory activities. However, it remains unclear whether and how abnormal phase-amplitude coupling is involved in slowing Parkinsonian movements during their execution. To address these questions, we analyzed high-density EEG signals recorded simultaneously with various motor activities and at rest in 19 patients with Parkinson’s disease and 20 healthy controls. The motor tasks consisted of repetitive index finger pressing, and slow and fast tapping movements. Individual EEG source signals were computed for the premotor cortex, primary motor cortex, primary somatosensory cortex, and primary somatosensory complex. For the resting condition and the pressing task, phase-amplitude coupling averaged over the 4 motor regions and the entire movement period was larger in patients than in controls. In contrast, in all tapping tasks, state-related phase-amplitude coupling was similar between patients and controls. These findings were not aligned with motor performance and EMG data, which showed abnormalities in patients for tapping but not for pressing, suggesting that the strength of β-broadband γ phase-amplitude coupling during the movement period does not directly relate to Parkinsonian bradykinesia. Subsequently, we examined the dynamics of oscillatory EEG signals during motor transitions. When healthy controls performed the pressing task, dynamic phase-amplitude coupling increased shortly before pressing onset and decreased subsequently. A strikingly similar motif of coupling rise and decay was observed around the offset of pressing and around the onset of slow tapping, suggesting that such transient phase-amplitude coupling changes may be linked to transitions between different movement states – akin to preparatory states in dynamical systems theory of motor control. In patients, the modulation of phase-amplitude coupling was similar in (normally executed) pressing, but flattened in slow (abnormally executed) tapping compared to the controls. These deviations in phase-amplitude coupling around motor action transients may indicate dysfunctional evolution of neuronal population dynamics from the preparatory state to movement generation in Parkinson’s disease. These findings may indicate that cross-frequency coupling is involved in the pathophysiology of bradykinesia in Parkinson’s disease through its abnormal dynamic modulation.
Evaluation Of The Rims2 Locus As A Risk Locus For Parkinson’s Disease Dementia
Authors: Manuela MX Tan , Raquel Real , Michael A Lawton , Catherine Bresner , Kanavou Sofia , Foltynie Thomas , Nicholas W Wood , Mike A. Nalls , Nigel M Williams , Yoav Ben-Shlomo , Michele TM Hu , Donald G Grosset , John Hardy , Maryam Shoai , Huw R Morris 
Published: July 2021

AbstractIn their recent letter entitled “Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in parkinson’s disease”, Liu and colleagues report that in a genome-wide analysis of progression to dementia in parkinson’s disease (PD) the RIMS2 locus is a determinant of dementia in PD (1). In this study we have evaluated the nominated loci in a well-powered longitudinal clinical-genetic study of 2536 individuals in the tracking parkinson’s and oxford discovery cohorts. We have not identified any association between the RIMS2 locus or other loci from the discovery phase and the development of Parkinson’s dementia. further work is needed to understand the biological determinants of this important aspect of parkinson’s and to guide the search for new treatments.Brief paragraph/AbstractIn their recent letter entitled “Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson’s disease”, Liu and colleagues report that in a genome-wide analysis of progression to dementia in Parkinson’s disease (PD) the RIMS2 locus is a determinant of dementia in PD (1). In this study we have evaluated the nominated loci in a well-powered longitudinal clinical-genetic study of 2536 individuals in the Tracking Parkinson’s and Oxford Discovery cohorts. We have not identified any association between the RIMS2 locus or other loci from the discovery phase and the development of Parkinson’s dementia. Further work is needed to understand the biological determinants of this important aspect of Parkinson’s and to guide the search for new treatments.
Laboratory Study of Physical Barrier Efficiency for Worker Protection against SARS-CoV-2 while Standing or Sitting
Authors: Bartels Jacob , Estill Cheryl Fairfield , Chen I-Chen , Neu Dylan 
Published: July 2021

AbstractTransparent barriers were installed as a response to the SARS-COV-2 pandemic in many customer-facing industries. Transparent barriers are an engineering control that are utilized to intercept air traveling between customers to workers. Information on the effectiveness of these barriers against aerosols is limited. In this study, a cough simulator was used to represent a cough from a customer. Two optical particle counters were used (one on each side of the barrier, labeled reference and worker) to determine the number of particles that migrated around a transparent barrier. Nine barrier sizes and a no barrier configuration were tested with six replicates each. Tests of these 10 configurations were conducted for both sitting and standing scenarios to represent configurations common to nail salons and grocery stores, respectively. Barrier efficiency was calculated using a ratio of the particle count results (reference/worker). Barriers had better efficiency when they were 9 to 39 cm (3.5 to 15.5”) above cough height and at least 91 cm (36”) wide, 92% and 93% respectively. Barriers that were 91 cm (36”) above table height for both scenarios blocked 71% or more of the particles between 0.35–0.725 µm and 68% for particles between 1 to 3 µm. A barrier that blocked an initial cough was effective at reducing particle counts. While the width of barriers was not as significant as height in determining barrier efficiency it was important that a barrier be placed where interactions between customers and workers are most frequent.
Potential Health Benefits of Eliminating Traffic Emissions in Urban Areas
Authors: Heydari Shahram , Asgharian Masoud , Kelly Frank J , Goel Rahul 
Published: July 2021

AbstractTraffic is one of the major contributors to PM2.5 in cities worldwide. Quantifying the role of traffic is an important step towards understanding the impact of transport policies on the possibilities to achieve cleaner air and accompanying health benefits. We carried out a meta-analysis using the World Health Organisation (WHO) database of source apportionment studies of PM2.5 concentrations. Specifically, we used a Bayesian meta-regression approach, modelling both overall and traffic-related (tailpipe and non-tailpipe) concentrations simultaneously. We obtained the distributions of expected PM2.5 concentrations (posterior densities) of different types for 117 cities worldwide. For each city, we calculated the probabilities of exceeding the WHO-recommended concentration of PM2.5 if all of traffic emissions were removed. Using the non-linear Integrated Exposure Response (IER) function of PM2.5, we estimated percent reduction in different disease endpoints for a scenario with complete removal of traffic emissions. We found that this results in achieving the WHO-recommended concentration of PM2.5 only for a handful of cities that already have low concentrations of pollution. The percentage reduction in prevented mortality for cardiovascular and respiratory diseases increases up to a point (30-40 ug/m3), and above this concentration, it flattens off. For Diabetes-related mortality, the percentage reduction in mortality decreases with increasing concentrations—a trend that is opposite to other outcomes. For cities with high concentrations of pollution, the results highlight the need for multi-sectoral strategies to reduce pollution. The IER functions of PM2.5 result in diminishing returns of health benefits at high concentrations, and in case of Diabetes, there are even negative returns. The results show the significant effect of the shape of IER functions on health benefits. Overall, despite the diminishing results, a significant burden of deaths can be prevented by policies that aim to reduce traffic emissions even at high concentrations of pollution.
Brain connectivity-based prediction of real-life creativity is mediated by semantic memory structure
Authors: Ovando-Tellez Marcela , Kenett Yoed N. , Benedek Mathias , Bernard Matthieu , Belo Joan , Beranger Benoit , Bieth Theophile , Volle Emmanuelle 
Published: July 2021

AbstractCreative cognition relies on the ability to form remote associations between concepts, which allows to generate novel ideas or solve new problems. Such an ability is related to the organization of semantic memory; yet whether real-life creative behavior relies on semantic memory organization and its neural substrates remains unclear. Therefore, this study explored associations between brain functional connectivity patterns, network properties of individual semantic memory, and real-life creativity. We acquired multi-echo functional MRI data while participants underwent a semantic relatedness judgment task. These ratings were used to estimate their individual semantic memory networks, whose properties significantly predicted their real-life creativity. Using a connectome-based predictive modeling approach, we identified patterns of task-based functional connectivity that predicted creativity-related semantic memory network properties. Furthermore, these properties mediated the relationship between functional connectivity and real-life creativity. These results provide new insights into how brain connectivity supports the associative mechanisms of creativity.
Hormonal contraceptives alter amphetamine place preference and responsivity in the intact female rat
Authors: Hilz Emily N. , Olvera Marcelle , Jun Dohyun , Chadha Megha , Gillette Ross , Monfils Marie-H. , Gore Andrea C. , Lee Hongjoo J. 
Published: July 2021

AbstractHormonal contraceptives (HCs) are commonly used among reproductive aged women and alter the physiological state of the user by interfering with endogenous hormone concentrations and their actions on the reproductive tract. As hormones such as estradiol and progesterone modulate the incidence of substance abuse disorders in women, it is important to consider the influence HCs have on the female brain and behavior. This experiment explores how female sex steroid hormonal states associated with the rat estrous cycle, and modulating those states with HCs, influences measures of drug preference and responsivity. First, rats underwent food-light Pavlovian conditioning to measure conditioned orienting, a known predictor of amphetamine (AMP) place preference. Then, rats were conditioned and tested for AMP place preference with either an HC-implant or during estrous cycle stages associated with different ovarian hormone levels (i.e., proestrus (P) or metestrus/diestrus (M/D) while recording ultrasonic vocalizations (USVs) as an index of hedonic responsivity. Because of dopamine’s (DA) role in modulation of AMP actions, DA cell activity and availability were examined using tyrosine hydroxylase and FOS immunohistochemistry after final AMP challenge. Conditioned orienting did not differ between cycling and HC-implanted. P rats emitted more USVs during conditioning, showed higher AMP place preference throughout testing, and had higher DA cell activity in the substantia nigra compared to M/D and HC-implanted rats. Sex steroid hormone serum concentration and uterine horn thickness predicted some but not all of these measures. This experiment suggests ovarian hormones affect drug preference and responsivity, while providing novel insight into how hormone-altering contraceptives may reduce these measures.
Evaluating the Effect of Semantic Congruency and Valence on Multisensory Integration
Authors: Letts Elyse , Basharat Aysha , Barnett-Cowan Michael 
Published: July 2021

ABSTRACTPrevious studies demonstrate that semantics, the higher level meaning of multi-modal stimuli, can impact multisensory integration. Valence, an affective response to images, has not yet been tested in non-priming response time (RT) or temporal order judgement (TOJ) tasks. This study aims to investigate both semantic congruency and valence of non-speech audiovisual stimuli on multisensory integration via RT and TOJ tasks (assessing processing speed (RT), point of subjective simultaneity (PSS), and time-window when multisensory stimuli are likely to be perceived as simultaneous (Temporal Binding Window; TBW)). Forty participants (mean age: 26.25; females=17) were recruited from Prolific Academic resulting in 37 complete datasets. Both congruence and valence have a significant main effect on RT (congruent and high valence decrease RT) as well as an interaction effect (congruent/high valence condition being significantly faster than all others). For TOJ, images high in valence require visual stimuli to be presented significantly earlier than auditory stimuli in order for the audio and visual stimuli to be perceived as simultaneous. Further, a significant interaction effect of congruence and valence on the PSS revealed that the congruent/high valence condition was significantly earlier than all other conditions. A subsequent analysis shows there is a positive correlation between the TBW width (b-values) and RT (as the TBW widens, the RT increases) for the categories that differed most from 0 in their PSS (Congruent/High and Incongruent/Low). This study provides new evidence that supports previous research on semantic congruency and presents a novel incorporation of valence into behavioural responses.
Surface electric fields increase human osteoclast resorption through improved wettability on carbonate–incorporated apatite
Authors: Muguruza Leire Bergara , Mäkelä Keijo , Yrjälä Tommi , Salonen Jukka , Yamashita Kimihiro , Nakamura Miho 
Published: July 2021

AbstractOsteoclast-mediated bioresorption can be of an efficient means of incorporating the dissolution of biomaterials in the bone remodeling process. Because of compositionally and structurally close resemblance of biomaterials with the natural mineral phases of the bone matrix, synthetic carbonate-substituted hydroxyapatite (CA) is considered as an ideal clinical biomaterial. The present study therefore investigated the effects of electrical polarization on the surface characteristics and interactions with human osteoclasts of hydroxyapatite (HA) and CA. Electrical polarization was found to improve the surface wettability of these materials by increasing the surface free energy, and this effect was maintained for one month. Analyses of human osteoclast cultures established that CA subjected to a polarization treatment accelerated osteoclast resorption but did not affect the early differentiation phase or the adherent morphology of the osteoclasts as evaluated by staining. These data suggest that the surface characteristics of the CA promoted osteoclast resorption. The results of this work are expected to contribute to the design of cell-mediated biomaterials that can be resorbed by osteoclasts after fulfilling their primary function as a scaffold for bone regeneration.
Normalized coefficient of variation (nCV): a method to evaluate circadian clock robustness in population scale data
Authors: Wu Gang , Francey Lauren J. , Ruben Marc D. , Hogenesch John B. 
Published: July 2021

ABSTRACTRobust oscillation of clock genes is a core feature of the circadian system. Relative amplitude (rAMP) measures the robustness of clock gene oscillations, but only works for longitudinal samples. We lack a method for estimating robust oscillations from human samples without labeled time. We show that the normalized coefficient of variation (nCV) is linearly correlated with rAMP, independent of time labels. Using nCV, we found that clock gene oscillations are consistently dampened in tumors compared to non-tumors, suggesting a new therapeutic target in cancer treatment by enhancing clock robustness. nCV can provide a simple measure of the robustness of clock gene oscillations in any population-level dataset.Availability and implementationThe nCV web application is available on the GitHub repository (https://github.com/gangwug/nCV).
Inferring cell-cell interactions from pseudotime ordering of scRNA-Seq data
Authors: Li Dongshunyi , Velazquez Jeremy J. , Ding Jun , Hislop Joshua , Ebrahimkhani Mo R. , Bar-Joseph Ziv 
Published: July 2021

AbstractA major advantage of single cell RNA-Sequencing (scRNA-Seq) data is the ability to reconstruct continuous ordering and trajectories for cells. To date, such ordering was mainly used to group cells and to infer interactions within cells. Here we present TraSig, a computational method for improving the inference of cell-cell interactions in scRNA-Seq studies. Unlike prior methods that only focus on the average expression levels of genes in clusters or cell types, TraSig fully utilizes the dynamic information to identify significant ligand-receptor pairs with similar trajectories, which in turn are used to score interacting cell clusters. We applied TraSig to several scRNA-Seq datasets. As we show, using the ordering information allows TraSig to obtain unique predictions that improve upon those identified by prior methods. Functional experiments validate the ability of TraSig to identify novel signaling interactions that impact vascular development in liver organoid.