bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the relationship between sleep disturbances and white matter hyperintensities in older adults on the Alzheimer’s disease spectrum
Authors: Kamal Farooq , Morrison Cassandra , Dadar Mahsa 
Published: April 2023

AbstractBackgroundWhile studies report that sleep disturbance can have negative effects on brain vasculature, its impact on cerebrovascular disease such as white matter hyperintensities (WMHs) in beta-amyloid positive older adults remains unexplored.MethodsLinear regressions, mixed effects models, and mediation analysis examined the cross-sectional and longitudinal associations between sleep disturbance, cognition, and WMH burden, and cognition in normal controls (NCs), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) at baseline and longitudinally.ResultsPeople with AD reported more sleep disturbance than NC and MCI. AD with sleep disturbance had more WMHs than AD without sleep disturbances. Mediation analysis revealed an effect of regional WMH burden on the relationship between sleep disturbance and future cognition.ConclusionThese results suggest that WMH burden and sleep disturbance increases from aging to AD. Sleep disturbance decreases cognition through increases in WMH burden. Improved sleep could mitigate the impact of WMH accumulation and cognitive decline.
Low-versus conventional-dose trimethoprim-sulfamethoxazole for non-HIV PCP
Authors: Nagai Tatsuya , Matsui Hiroki , Fujioka Haruka , Homma Yuya , Otsuki Ayumu , Ito Hiroyuki , Ohmura Shinichiro , Miyamoto Toshiaki , Shichi Daisuke , Tomohisa Watari , Otsuka Yoshihito , Nakashima Kei 
Published: April 2023

AbstractTrimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment forPneumocystis jiroveciipneumonia (PCP); however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. We aimed to evaluate the efficacy and safety of low-dose TMP-SMX after adjusting for patient background characteristics.In this multicentre retrospective cohort study, we included patients diagnosed with non-human immunodeficiency virus (HIV) PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-(TMP equivalent <12.5 mg/kg) and conventional-dose groups (TMP equivalent 12.5–20 mg/kg/day). The primary endpoint was 30-day mortality, and the secondary endpoints were 180-day mortality, adverse events of grade 3 or greater per the Common Terminology Criteria for Adverse Events Version 5.0, and initial treatment completion rates. The background characteristics were adjusted using the overlap weighting method with propensity scores.Fifty-five patients in the low-dose and 81 in the conventional-dose groups were evaluated. There was no significant difference in 30-day mortality (7.6% vs. 14.9%,P= 0.215) or 180-day mortality (18.1% vs. 24.0%,P= 0.416) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (27.3% vs. 58.6%,P= 0.001). The initial treatment completion rates were 43.8% and 27.7% in the low-dose and conventional-dose groups, respectively.Low-dose TMP-SMX did not alter survival but reduced the incidence of adverse events in patients with non-HIV PCP, compared with conventional-dose TMP-SMX.
Acceptability of using mobile Health (mHealth) as an intervention tool for People with Drug Use Disorders in Tanga, Tanzania
Authors: Munishi Castory , Ndumwa Harrieth P , Massawe Josephine E , Njiro Belinda J , Ngowi Jackline , Suhartono Sanita , Busse Anja , Campello Giovanna , Garofalo Giovanna , Cipolla Pietro , Nyandindi Cassian , Ubuguyu Omary , Sunguya Bruno 
Published: April 2023

ABSTRACTBackgroundWith the increasing numbers of people with drug use disorders (PWDUD) in Tanzania as in other parts of the world the need for innovative interventions specifically tailored for this population has increased. Tanga, a coastal region on the Northeast of Tanzania has the second highest number of PWDUD in Tanzania. Evidence on the additional benefit in treatment and recovery process among PWDUD using digital health interventions is lacking. This study aimed to describe the acceptability of using a digital intervention to increase information access for PWDUD in Tanga region, Tanzania.MethodsA cross-sectional descriptive study using both quantitative and qualitative approaches was conducted in Tanga Municipality and Muheza District. The quantitative approach used face to face interviews with a pre-tested questionnaire with 465 participants, while the quantitative method was carried out through In-Depth Interviews with 12 participants by the saturation point. Analysis was done descriptively to generate frequencies, cross tabulations, and chi-square test used to examine associations between categorical variables. Thematic analysis using codes was used to analyze qualitative data.ResultsMajority of the PWDUD 67.6% do not own mobile phones. Out of the 156 participants with mobile phones, only 6.4% owned a smartphone. Most of the participants, 83.6%, reported to live with someone who owns a mobile phone. Importantly, a significant number of participants, 98.5% from both areas showed readiness to use mobile phones to access information about the harmful use of substance and substance use disorder treatment options. Participants described how mobile phones can be useful to them in accessing information related to treatment and access to treatment options. The reasons they gave for not owning mobile phones included the need of money to buy drugs and the lack of money to buy credit drives them to sell their phones. A digital app calledHuru appwas developed during study as part of an information sharing campaign on substance use.Conclusion and recommendationsThe findings of this study helped to inform the target audience for the developed Huru app that should not be only PWDUD but the community at large. Despite the participants having expressed high readiness to use mobile phones to access drug use disorder treatment information, only few of them were found to own mobile phones but reported to live with family members who own mobile phones. Thus, a mobile phone intervention should also target their family members who are key in supportive treatment.
Needlestick and Sharp Injuries Prevalence and Hepatitis B Vaccination Among Healthcare Workers: A cross sectional study in Six District Hospitals (Yaounde, Cameroon)
Authors: Lekeumo Cheuyem Fabrice Zobel , Lyonga Emilia Enjema , Kamga Hortense Gonsu , Mbopi – Keou François – Xavier , Takougang Innocent 
Published: April 2023

AbstractIntroductionAccidental exposure to blood and body fluids (AEB) in the workplace account for 40 % of contamination by hepatis B virus (HBV) and 2 – 3 % by HIV among healthcare workers (HCW). Developing countries are most affected. The present study sought to determine the prevalence of percutaneous injury and hepatitis B vaccination coverage among HCW.MethodsA cross-sectional study was carried out from January to April 2022 in six district hospitals in Yaounde using a self - administered questionnaire. Out of the 279 HCW who were solicited, 217 returned completed questionnaires.ResultsMore than half of HCW reported an AEB in the last 12 months (53,9 %). The prevalence of AEB varied among hospitals with the Nkolndongo DH reporting the highest prevalence (51.6 %). Healthcare workers were unvaccinated (53 %) or partially vaccinated against HBV (13,2 %); only one third were fully vaccinated (33,9 %). The lowest compliance with vaccination was observed among hygiene personnel (90 %). The high cost of the vaccine was the main reported reason for non - compliance (39 %).ConclusionThere is an urgent need to set up a monitoring system for the implementation of infection control and prevention in District Hospitals in Cameroon in order to raise awareness of AEB burden among healthcare workers and improve accessibility to HBV vaccine.
A Study of a Deterministic Model for Meningitis Epidemic
Authors: Yaga S. J , Saporu F .W. O 
Published: April 2023

ABSTRACTA compartmental deterministic model that allows (1) immunity from two stages of infection and carriage, and (2) disease induced death, is used in studying the dynamics of meningitis epidemic process in a closed population. It allows for difference in the transmission rate of infection to a susceptible by a carrier and an infective. It is generalized to allow a proportion (φ) of those susceptibles infected to progress directly to infectives in stage I. Both models are used in this study. The threshold conditions for the spread of carrier and infectives in stage I are derived for the two models. Sensitivity analysis is performed on the reproductive number derived from the next generation matrix. The case-carrier ratio profile for various parameters and threshold values are shown. So also are the graphs of the total number ever infected as influenced byϵandφ. The infection transmission rate (β), the odds in favor of a carrier, over an infective, in transmitting an infection to a susceptible (ϵ) and the carrier conversion rate (ϕ) to an infective in stage I, are identified as key parameters that should be subject of attention for any control intervention strategy. The case-carrier ratio profiles provide evidence of a critical case-carrier ratio attained before the number of reported cases grows to an epidemic level. They also provide visual evidence of epidemiological context, in this case, epidemic incidence (in later part of dry season) and endemic incidence (during rainy season). Results from total proportion ever infected suggest that the model, in whichφ= 0 obtained, can adequately represent, in essence, the generalized model for this study.
Humic substances mitigate adverse effects of elevated temperature with potentially critical repercussions for coral reef resilience
Authors: Stuij T.M. , Cleary D.F.R. , de Voogd N.J. , Rocha R.J.M. , Polonia A.R.M. , Silva D.A.M. , Frommlet J.C. , Louvado A. , Huang Y. M. , van der Windt N. , Gomes N.C.M. 
Published: April 2023

AbstractPrevious observational studies have suggested that terrestrially-derived compounds, most notably humic substances (HS) can protect coral reefs from thermal stress. No study hitherto has, however, tested this hypothesis. In the present study, we used a randomised-controlled microcosm setup to test to what extent HS are able to mitigate the adverse effects of elevated temperature and intense UVB radiation on coral photosynthetic activity, and environmental and host-associated bacterial ercommunities. Our results clearly demonstrate a significant protective effect of HS. Corals in HS-supplemented microcosms had significantly higher photosynthetic activities than those in microcosms subjected to elevated heat and intense UVB radiation. Our results, furthermore, showed that coral reef organisms in HS-supplemented microcosms contained unique bacterial communities enriched with known groups of potentially beneficial bacteria. Our findings have significant repercussions for reef resilience in the face of increasing climate-induced stressors and highlight the importance of restoring coastal forests and the land-sea interface in order to protect coral reefs.
Surface growth ofPseudomonas aeruginosareveals a regulatory effect of 3- oxo-C12-homoserine lactone in absence of its cognate receptor, LasR
Authors: de Oliveira Pereira Thays , Groleau Marie-Christine , Déziel Eric 
Published: April 2023

ABSTRACTSuccessful colonization of a multitude of ecological niches by the bacteriumPseudomonas aeruginosarelies on its ability to respond to concentrations of self-produced signal molecules. This intercellular communication system known as quorum sensing (QS) tightly regulates the expression of virulence determinants and a diversity of survival functions, including those required for social behaviours. In planktonic cultures ofP. aeruginosa, the transcriptional regulator LasR is generally considered on top of the QS circuitry hierarchy; its activation relies on binding to 3-oxo-C12-homoserine lactone (3-oxo-C12-HSL), a product of the LasI synthase. Transcription oflasIis activated by LasR, resulting in a positive feedback loop. Few studies have looked at the function of QS during surface growth even thoughP. aeruginosatypically lives in biofilm-like communities under natural conditions. Here, we show that surface-grownP. aeruginosareadily produces 3-oxo-C12-HSL in absence of LasR, and that this phenotype is frequent upon surface association in naturally occurring environmental and clinical LasR- defective isolates, suggesting a conserved alternative function for the signal. Indeed, even in the absence of the cognate regulator LasR, 3-oxo-C12-HSL upregulates the autologous expression of pyocyanin and of LasR-controlled virulence determinants in neighboring cells. This highlights a possible role for 3-oxo-C12-HSL in shaping community responses and provides a possible evolutive benefit for mixed populations to carry LasR-defective cells, a common feature of natural ofP. aeruginosa.IMPORTANCEThe bacteriumPseudomonas aeruginosacolonizes and thrives in many environments, in which it is typically found in surface-associated polymicrobial communities known as biofilms. Adaptation to this social behavior is aided by quorum sensing (QS), an intercellular communication system pivotal in the expression of social traits. Regardless of its importance in QS regulation, the loss of function of the master regulator LasR is now considered a conserved adaptation ofP. aeruginosa, irrespective of the origin of strains. By investigating the QS circuitry in surface-grown cells, we found accumulation of QS signal 3-oxo-C12-HSL in absence of its cognate receptor and activator, LasR. The current understanding of the QS circuit, mostly based on planktonic growing cells, is challenged by investigating the QS circuitry of surface-grown cells. This provides a new perspective on the beneficial aspects that underline the frequency of LasR-deficient isolates.
Learning induces unique transcriptional landscapes in the auditory cortex
Authors: Graham G. , Chimenti M.S. , Knudtson K.L. , Grenard D.N. , Co L. , Sumner M. , Tchou T. , Bieszczad K.M. 
Published: April 2023

AbstractLearning can induce neurophysiological plasticity in the auditory cortex at multiple timescales. Lasting changes to auditory cortical function that persist over days, weeks, or even a lifetime, require learning to inducede novogene expression. Indeed, transcription is the molecular determinant for long-term memories to form with a lasting impact on sound-related behavior. However, auditory cortical genes that support auditory learning, memory, and acquired sound-specific behavior are largely unknown. This report is the first to identify in young adult male rats (Sprague-Dawley) genome-wide changes in learning-induced gene expression within the auditory cortex that may underlie the formation of long-lasting discriminative memory for acoustic frequency cues. Auditory cortical samples were collected from animals in the initial learning phase of a two-tone discrimination sound-reward task known to induce sound-specific neurophysiological and behavioral effects (e.g., Shang et al., 2019). Bioinformatic analyses on gene enrichment profiles from bulk RNA sequencing identifiedcholinergic synapse (KEGG 04725), extra-cellular matrix receptor interaction (KEGG 04512), andneuroactive ligand-receptor interaction (KEGG 04080)as top biological pathways for auditory discrimination learning. The findings characterize key candidate effectors underlying changes in cortical function that support the initial formation of long-term discriminative auditory memory in the adult brain. The molecules and mechanisms identified are potential therapeutic targets to facilitate lasting changes to sound-specific auditory function in adulthood and prime for future gene-targeted investigations.
Reproducibility of biophysicalin siliconeuron states and spikes from event-based partial histories
Authors: Cudone Evan , Lower Amelia M. , McDougal Robert A 
Published: April 2023

AbstractBiophysically detailed simulations attempting to reproduce neuronal activity often rely on solving large systems of differential equations; in some models, these systems have tens of thousands of states per cell. Numerically solving these equations is computationally intensive and requires making assumptions about the initial cell states. Additional realism from incorporating more biological detail is achieved at the cost of increasingly more states, more computational resources, and more modeling assumptions. We show that for both point and morphologically-detailed cell models, the presence and timing of future action potentials is probabilistically well-characterized by the relative timings of a small number of recent synaptic events alone. Knowledge of initial conditions or full synaptic input history is not a requirement. While model time constants, etc. impact the specifics, we demonstrate that for both individual spikes and sustained cellular activity, the uncertainty in spike response decreases to the point of approximate determinism. Further, we show cellular model states are reconstructable from ongoing synaptic events, despite unknown initial conditions. We propose that a strictly event-based modeling framework is capable of representing the full complexity of cellular dynamics of the differential-equations models with significantly less per-cell state variables, thus offering a pathway toward utilizing modern data-driven modeling to scale up to larger network models while preserving individual cellular biophysics.
Cryo-EM structure of the folded-back state of human β-cardiac myosin*
Authors: Grinzato Alessandro , Auguin Daniel , Kikuti Carlos , Nandwani Neha , Moussaoui Dihia , Pathak Divya , Kandiah Eaazhisai , Ruppel Kathleen M. , Spudich James A. , Houdusse Anne , Robert-Paganin Julien 
Published: April 2023

SummaryDuring normal levels of exertion, many cardiac muscle myosin heads are sequestered in an off-state even during systolic contraction to save energy and for precise regulation. They can be converted to an on-state when exertion is increased. Hypercontractility caused by hypertrophic cardiomyopathy (HCM) myosin mutations is often the result of shifting the equilibrium toward more heads in the on-state. The off-state is equated with a folded-back structure known as the interacting head motif (IHM), which is a regulatory feature of all muscle myosins and class-2 non-muscle myosins. We report here the human β-cardiac myosin IHM structure to 3.6 Å resolution. The structure shows that the interfaces are hot spots of HCM mutations and reveals details of the significant interactions. Importantly, the structures of cardiac and smooth muscle myosin IHMs are dramatically different. This challenges the concept that the IHM structure is conserved in all muscle types and opens new perspectives in the understanding of muscle physiology. The cardiac IHM structure has been the missing puzzle piece to fully understand the development of inherited cardiomyopathies. This work will pave the way for the development of new molecules able to stabilize or destabilize the IHM in a personalized medicine approach.*This manuscript was submitted to Nature Communications in August 2022 and dealt efficiently by the editors. All reviewers received this version of the manuscript before 9208August 2022. They also received coordinates and maps of our high resolution structure on the 18208August 2022. Due to slowness of at least one reviewer, this contribution was delayed for acceptance by Nature Communications and we are now depositing in bioRxiv the originally submitted version written in July 2022 for everyone to see. Indeed, two bioRxiv contributions at lower resolution but adding similar concepts on thick filament regulation were deposited this week in bioRxiv, one of the contributions having had access to our coordinates.We hope that our data at high resolution will be helpful for all readers that appreciate that high resolution information is required to build accurate atomic models and discuss implications for sarcomere regulation and the effects of cardiomyopathy mutations on heart muscle function.
Neural representations of non-native speech reflect proficiency and interference from native language knowledge
Authors: Brodbeck Christian , Kandylaki Katerina Danae , Scharenborg Odette 
Published: April 2023

AbstractLearning to process speech in a foreign language involves learning new representations for mapping the auditory signal to linguistic structure. Behavioral experiments suggest that even listeners that are highly proficient in a non-native language experience interference from representations of their native language. However, much of the evidence for such interference comes from tasks that may inadvertently increase the salience of native language competitors. Here we tested for neural evidence of proficiency and native language interference in a naturalistic story listening task. We studied electroencephalography responses of native Dutch listeners to an English short story, spoken by a native speaker of either American English or Dutch. We modeled brain responses with multivariate temporal response functions, using acoustic and language models. We found evidence for activation of Dutch language statistics when listening to English, but only when it was spoken with a Dutch accent. This suggests that a naturalistic, monolingual setting decreases the interference from native language representations, whereas an accent in the listeners’ own native language may increase native language interference, by increasing the salience of the native language and activating native language phonetic and lexical representations. Brain responses suggest that words from the native language compete with the foreign language in a single word recognition system, rather than being activated in a parallel lexicon. We further found that secondary acoustic representations of speech (after 200 ms latency) decreased with increasing proficiency. This may reflect improved acoustic-phonetic models in more proficient listeners.