bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moderators of Improvements in Fatigue Impact After a Self-management Intervention in Multiple Sclerosis
Authors: Knowles Lindsey M. , Hugos Cinda L. , Cameron Michelle H. , Haselkorn Jodie K. , Bourdette Dennis N. , Turner Aaron P. 
Published: August 2021

Abstract
Fatigue is one of the most common and disabling symptoms of multiple sclerosis. A recent randomized controlled trial comparing a fatigue self-management program and a general multiple sclerosis education program found that both programs improved fatigue in participants with multiple sclerosis. Participants were randomized to a self-management program (fatigue: take control, n = 109) or a multiple sclerosis education program (multiple sclerosis: take control, n = 109). This secondary analysis of that trial used multilevel moderation analysis to examine moderators of treatment-related effects on fatigue (Modified Fatigue Impact Scale) from baseline through the 6-mo follow-up. The following potential treatment moderators were examined: age, sex, cohabitation/marital status, and baseline levels of self-efficacy, depression symptoms, and sleep quality. Cohabitation status (living with or without a spouse/partner) interacted with intervention group and time to predict fatigue impact (P = 0.04). Fatigue: take control participants who lived with a spouse/partner showed a marginal effect in greater rate of improvement in fatigue compared with those who lived alone (P = 0.08). However, rates of improvement in fatigue in multiple sclerosis: take control participants were similar in those living with or without a spouse/partner. These findings suggest that living with a spouse or partner may facilitate benefit from self-management interventions for multiple sclerosis–related fatigue. Future research should investigate the contribution of supportive others in self-management of fatigue in multiple sclerosis.
Predictors of secondary HIV transmission risk in a cohort of adolescents living with HIV in South Africa
Authors: Toska Elona , Zhou Siyanai , Laurenzi Christina A. , Haghighat Roxanna , Saal Wylene , Gulaid Laurie , Cluver Lucie 
Published: August 2021

Objective:
Preventing secondary HIV transmission from adolescents and young people living with HIV (AYPLHIV) to their partners and children is critical to interrupting the HIV infection cycle in sub-Saharan Africa. We investigated predictors of secondary HIV transmission risk (past-year sexual risk combined with past-year viremia) among AYPLHIV in South Africa.

Design:
A prospective cohort of AYLPHIV in South Africa recruited n = 1046 participants in 2014–2015, 93.6% of whom were followed up in 2016–2017 (1.5% mortality). Questionnaires used validated scales where available and biomarkers were extracted from n = 67 health facilities.

Methods:
Multivariate logistic regressions tested baseline factors associated with secondary HIV transmission risk, controlling for covariates, with marginal effect modelling combinations.

Results:
About 14.2% of AYPLHIV reported high secondary HIV transmission risk. High-risk AYPLHIV were more likely to be sexually infected [adjusted odds ratio (aOR) 2.79, 95% confidence interval (95% CI) 1.66–4.68, P < 0.001], and report hunger (aOR 1.93, 95% CI 1.18–3.14, P = 0.008) and substance use (aOR 2.19, 95% CI 1.19–4.02, P = 0.012). They were more likely to be in power-inequitable relationships (aOR 1.77, 95% CI 1.08–2.92, P = 0.025) and be parents (aOR 4.30, 95% CI 2.16–8.57, P < 0.001). Adolescents reporting none of these factors had a 4% probability of secondary transmission risk, rising to 89% probability with all five identified factors. Older age and early sexual debut were also strongly associated with a higher risk of secondary HIV transmission.

Conclusion:
It is essential to identify and support AYPLHIV at a high risk of secondary transmission. Screening for factors such as mode of infection and parenthood during routine healthcare visits could help identify and provide resources to the most at-risk adolescents.
The Association Between Social and Spatial Closeness With PrEP Conversations Among Latino Men Who Have Sex With Men
Authors: Shrader Cho-Hee , Arroyo-Flores Juan , Stoler Justin , Skvoretz John , Carrico Adam , Doblecki-Lewis Susanne , Kanamori Mariano 
Published: August 2021

Background:
US Latino men who have sex with men (LMSM) are a group at highest risk for HIV. One driver of HIV among LMSM is inadequate access to pre-exposure prophylaxis (PrEP) information. The social network theory of homophily suggests that sharing similar sociodemographic factors could influence PrEP conversations within networks. This study aimed to determine how the effects of homophily across sociodemographic, immigration, cultural, and PrEP-related factors are associated with PrEP-related communication.

Setting:
This study was conducted in Miami-Dade County, FL.

Methods:
Data collected between August 2018 and October 2019 included 10 sociocentric friendship groups of 13 LMSM (N = 130). Participants were recruited using respondent-driven sampling by a community-based organization in Miami. We used the multiple regression quadratic assignment procedure to identify the effects of homophily and relationship characteristics on PrEP-related conversations using R software.

Results:
More frequent PrEP-related conversations were associated with dyadic friendships characterized by homophily on knowledge of PrEP effectiveness, heterophily on depressive symptom severity, home addresses proximity, friend closeness, and interaction frequency. Past PrEP-related conversation frequency also increased based on heterophily on the Latino cultural value of familism (ie, emotional support to family). Racial homophily, heterophily on severity of depressive symptoms, home addresses proximity, friendship closeness, and frequency of interactions increased likelihood to encourage a friend to use PrEP.

Discussion:
Social and spatial closeness and homophily play a role in PrEP-related conversations. Information from social networks contextualized in geographic settings can be elucidated to contribute toward the design of novel opportunities to end HIV.
Immunogenomic intertumor heterogeneity across primary and metastatic sites in a patient with lung adenocarcinoma
Authors: Chen Runzhe , Li Jun , Fujimoto Junya , Hu Xin , Quek Kelly , Tang Ming , Mitra Akash , Behrens Carmen , Chow Chi-Wan , Jiang Peixin , Little Latasha D. , Gumbs Curtis , Song Xingzhi , Zhang Jianhua , Tan Dongfeng , Heymach John V. , Wistuba Ignacio , Futreal P. Andrew , Gibbons Don L. , Byers Lauren A. , Zhang Jianjun , Reuben Alexandre 
Published: August 2021

AbstractBackgroundLung cancer is the leading cause of cancer death, partially owing to its extensive heterogeneity. The analysis of intertumor heterogeneity has been limited by an inability to concurrently obtain tissue from synchronous metastases unaltered by multiple prior lines of therapy.MethodsIn order to study the relationship between genomic, epigenomic and T cell repertoire heterogeneity in a rare autopsy case from a young female never-smoker with late-stage lung adenocarcinoma (LUAD), we did whole-exome sequencing (WES), DNA methylation and T-cell receptor (TCR) sequencing to characterize the immunogenomic landscape of one primary and 19 synchronous metastatic tumors.ResultsWe observed heterogeneous mutation, methylation, and T cell patterns across distinct metastases including a set of prevalent T cell clonotypes which were completely excluded from left-side thoracic tumors. Though a limited number of predicted neoantigens were shared, these were associated with homology of the T cell repertoire across metastases. Lastly, ratio of methylated neoantigen coding mutations was negatively associated with T-cell density, richness and clonality, suggesting neoantigen methylation may partially drive immunosuppression.ConclusionsOur study demonstrates heterogeneous genomic and T cell profiles across synchronous metastases and how restriction of unique T cell clonotypes within an individual may differentially shape the genomic and epigenomic landscapes of synchronous lung metastases.
The Effect of Blood Viscosity on Shear-Induced Hemolysis using a Magnetically Levitated Shearing Device
Authors: Krisher James A. , Malinauskas Richard A. , Day Steven W. 
Published: August 2021

AbstractIntroductionBlood contacting medical devices, including rotary blood pumps, can cause shear-induced blood damage that may lead to adverse effects in patients. Due in part to an inadequate understanding of how cell-scale fluid mechanics impact red blood cell membrane deformation and damage, there is currently not a uniformly accepted engineering model for predicting blood damage caused by complex flow fields within ventricular assist devices (VADs).MethodsWe empirically investigated hemolysis in an axial Couette flow device typical of a rotary VAD to expand our current understanding of shear-induced blood damage in two ways. First, we used a magnetically levitated device to accurately control the shear rate and exposure time experienced by blood and to minimize the effects of other uncharacterized stresses. Second, we explored the effects of both hematocrit and plasma viscosity on shear-induced hemolysis to characterize blood damage based on the viscosity-independent shear rate, rather than on shear stress.ResultsOver a shear rate range of 20,000-80,000 1/s, the Index of Hemolysis was found to be largely independent of hematocrit, bulk viscosity, or the suspension media viscosity.ConclusionIt is recommended that future investigations of shear-induced blood damage report findings with respect to the viscosity-neutral term of shear rate, in addition to the bulk whole blood viscosity measured at an appropriate shear rate relevant to the flow conditions of the device.
New insights into the earlier evolutionary history of epiphytic macrolichens
Authors: Yang Qiuxia , Wang Yanyan , Lücking Robert , Lumbsch H. Thorsten , Wang Xin , Du Zhenyong , Chen Yunkang , Bai Ming , Ren Dong , Wei Jiangchun , Li Hu , Wang Yongjie , Wei Xinli 
Published: August 2021

AbstractLichens are well known as pioneer organisms colonizing bare surfaces such as rocks and therefore have been hypothesized to play a role in the early formation of terrestrial ecosystems. Given the rarity of fossil evidence, our understanding of the evolutionary history of lichen-forming fungi is primarily based on molecular dating approaches. These studies suggest extant clades of macrolichens diversified after the K–Pg boundary. Here we corroborate the mid-Mesozoic fossil Daohugouthallus ciliiferus as an epiphytic macrolichen that predates the K-Pg boundary by 100 Mys. Based on new material and geometric morphometric analysis, we demonstrate that the Jurassic fossil is morphologically most similar to Parmeliaceae, but cannot be placed in Parmeliaceae or other similar family-level clades forming macrolichens as these evolved much later. Consequently, a new family, Daohugouthallaceae, is proposed here to accommodate this fossil, which reveals macrolichens may have been diverse long before the Cenozoic diversification of extant lineages.
Kinetic modelling of β-cell metabolism reveals control points in the insulin-regulating pyruvate cycling pathways
Authors: Rahul Rahul , Stinchcombe Adam R , Joseph Jamie , Ingalls Brian 
Published: August 2021

AbstractInsulin, a key hormone in the regulation of glucose homeostasis, is secreted by pancreatic β-cells in response to elevated glucose levels. Insulin is released in a biphasic manner in response to glucose metabolism in β-cells. The first phase of insulin secretion is triggered by an increase in the ATP:ADP ratio; the second phase occurs in response to both a rise in ATP:ADP as well as other key metabolic signals, including a rise in the NADPH:NADP+ratio. Experimental evidence indicates that pyruvate-cycling pathways play an important role in the elevation of the NADPH:NADP+ratio in response to glucose. In this work we developed a kinetic model for the tricarboxylic acid cycle and pyruvate cycling pathways. We successfully validated our model against recent experimental observations and performed local and global sensitivity analysis to identify key regulatory interactions in the system. The model predicts that the dicarboxylate carrier (DIC) and pyruvate transporter (PYC) are the most important regulators of pyruvate cycling and NADPH production. In contrast, our analysis showed that variation in the pyruvate carboxylase (PC) flux was compensated by a response in the activity of mitochondrial isocitrate dehydrogenase (ICDm) resulting in minimal effect on overall pyruvate cycling flux. The model predictions suggest starting points for further experimental investigation, as well as potential drug targets for treatment of type 2 diabetes.
Structural (dys)connectivity associates with cholinergic cell density of the nucleus basalis of Meynert in Alzheimer’s disease
Authors: Lin Chen-Pei , Frigerio Irene , Boon Baayla DC , Zhou Zihan , Rozemuller Annemieke JM , Bouwman Femke , Schoonheim Menno M , van de Berg Wilma DJ , Jonkman Laura 
Published: August 2021

AbstractCognitive deficits in Alzheimer’s disease, specifically amnestic (memory dominant) deficits, are associated with cholinergic degeneration in the basal forebrain. The cholinergic nucleus within the basal forebrain, the nucleus basalis of Meynert, exhibits local atrophy and reduced cortical tract integrity on MRI, and reveals amyloid-β and phosphorylated-tau pathology at autopsy. To better understand the pathophysiology of nucleus basalis of Meynert atrophy and its neocortical projections in Alzheimer’s disease, we utilized a combined post-mortem in-situ MRI and histopathology approach. A total of 19 Alzheimer’s disease (10 amnestic and 9 non-amnestic) and 9 non-neurological control donors underwent 3T T1-weighted MRI for anatomical delineation and volume assessment of the nucleus basalis of Meynert, and diffusion-weighted imaging for microstructural assessment of the nucleus and its projections. At subsequent brain autopsy, tissue dissection and immunohistochemistry were performed for amyloid-β, phosphorylated-tau and choline acetyltransferase. Compared to controls, we observed an MRI-derived volume reduction and altered microstructural integrity of the nucleus basalis of Meynert in Alzheimer’s disease donors. Furthermore, decreased cholinergic cell density was associated with reduced integrity of the nucleus and its tracts to the temporal lobe, specifically to the temporal pole of the superior temporal gyrus, and the parahippocampal gyrus. The association between cholinergic cell density and alteration to cortical tracts was specific for amnestic, compared to non-amnestic Alzheimer’s disease donors. Our study illustrates that the nucleus basalis of Meynert is severely affected in amnestic Alzheimer’s disease, both in terms of pathology within the nucleus, but also in terms of damage to its cortical projections, specifically to the temporal lobe, which may contribute to the observed cognitive deterioration.
Widely naturalized species are not more promiscuous in the use of different nitrogen forms, but benefit more from inorganic nitrogen
Authors: Zeng Jianjun , Liu Yanjie , van Kleunen Mark 
Published: August 2021

SummaryNitrogen (N) is an essential mineral nutrient necessary for plant growth and has been considered a crucial factor influencing invasion success. Former studies mainly focused on responses of alien plants to different levels of N availability. However, in natural soils, N comes in different forms. Few experimental studies have explored responses of naturalized alien species to different N forms, and whether such responses are related to their naturalization success globally.We selected 22 common herbaceous species native to Germany that have all become naturalized and thus been introduced elsewhere in the world. We grew these species under six different N conditions that differed in the amount or form of N, and assessed their growth performance in a greenhouse experiment.We found that plants produced more biomass when grown under high N levels than under low N levels, and when N was provided in inorganic form than when provided in organic form. Neither biomass production nor promiscuity to different N forms was related to naturalization success of the species. However, the biomass response to inorganic N, relative to organic N, was stronger for the widely naturalized species than for the less widely naturalized ones.Our study shows that although the widely naturalized alien species were not more promiscuous than the less widely naturalized species, they took more advantage of the inorganic-N forms. This indicates that naturalization success might be partly driven by a species’ ability to take advantage of increased inorganic N levels.
Auditory cortex activation is modulated nonlinearly by stimulation duration: A functional near-infrared spectroscopy (fNIRS) study
Authors: Zhang Yi Fan , Lasfargue Anne , Berry Isabelle 
Published: August 2021

AbstractFunctional near-infrared spectroscopy (NIRS) is an increasingly popular method in hearing research. However, few studies have considered efficient stimulation parameters for fNIRS auditory experimental design. The objectives of our study are (1) to characterize the auditory hemodynamic responses to trains of white noise with increasing stimulation durations (8s, 10s, 15s, 20s) in terms of amplitude and response linearity; (2) to identify the most-efficient stimulation duration using fNIRS; and (3) to generalize results to more ecological environmental stimuli. We found that cortical activity is augmented following the increments in stimulation durations and reaches a plateau after about 15s of stimulation. The linearity analysis showed that this augmentation due to stimulation duration is not linear in the auditory cortex, the non-linearity being more pronounced for longer durations (15s and 20s). The 15s block duration that we propose as optimal precludes signal saturation, is associated with a high response amplitude and a relatively short total experimental duration. Moreover, the 15s duration remains optimal independently of the nature of presented sounds. The sum of these findings suggests that 15s stimulation duration used in the appropriate experimental setup allows researchers to acquire optimal fNIRS signal quality.
Influence of anatomical features of different brain regions on the spatial localization of fiber photometry signals
Authors: Montinaro Cinzia , Pisanello Marco , Bianco Marco , Spagnolo Barbara , Pisano Filippo , Balena Antonio , De Nuccio Francesco , Lofrumento Dario Domenico , Verri Tiziano , De Vittorio Massimo , Pisanello Ferruccio 
Published: August 2021

ABSTRACTFiber photometry is widely used in neuroscience labs for in vivo detection of functional fluorescence from optical indicators of neuronal activity with a simple optical fiber. The fiber is commonly placed next to the region of interest to both excite and collect the fluorescence signal. However, the path of both excitation and fluorescence photons is altered by the uneven optical properties of the brain, due to local variation of the refractive index, different cellular types, densities and shapes. Nonetheless, the effect of the local anatomy on the actual shape and extent of the volume of tissue that interfaces with the fiber has received little attention so far. To fill this gap, we measured the size and shape of fiber photometry efficiency field in the primary motor and somatosensory cortex, in the hippocampus and in the striatum of the mouse brain, highlighting how their substructures determine the detected signal and the depth at which photons can be mined. Importantly, we show that the information on the spatial expression of the fluorescent probes alone is not sufficient to account for the contribution of local subregions to the overall collected signal, and it must be combined with the optical properties of the tissue adjacent to the fiber tip.
The sodium leak channel NALCN encodes the major background sodium ion conductance in mouse anterior pituitary cells
Authors: Belal Marziyeh , Mucha Mariusz , Monteil Arnaud , Winyard Paul G , Pawlak Robert , Walker Jamie J. , Tabak Joel , Belle Mino D C 
Published: August 2021

AbstractThe pituitary gland produces and secretes a variety of hormones that are essential to life, such as for the regulation of growth and development, metabolism, reproduction, and the stress response. This is achieved through an intricate signalling interplay between the brain and peripheral feedback signals that shapes pituitary cell excitability by regulating ion channel properties of these cells. In addition, endocrine anterior pituitary cells fire action potentials spontaneously to regulate intracellular calcium ([Ca2+]i) level, an essential signalling conduit for hormonal secretion. To this end, pituitary cells have to critically regulate their resting membrane potential (RMP) close to firing threshold, but the molecular identity of the ionic mechanisms involved remains largely unknown. Here, we revealed that the sodium leak channel NALCN, known to modulate neuronal excitability elsewhere in the brain, acts to regulate excitability in the mouse anterior endocrine pituitary cells. Using viral transduction combined with powerful electrophysiology methods and calcium imaging, we show that NALCN forms the major Na+ leak conductance in these cells, appropriately tuning cellular RMP for sustaining spontaneous firing activity. Genetic interruption of NALCN channel activity drastically hyperpolarised the cells, suppressing firing and ([Ca2+]i) oscillations. Remarkably, we uncover that NALCN conductance formed a very small fraction of the total cell conductance, but yet had a profound impact on pituitary cell excitability. Our results also provide a possible mechanism through which hypothalamic and hormone feedback signals can powerfully affect pituitary activity to influence hormonal function.
Bacteria.guru: comparative transcriptomics and co-expression database for bacterial pathogens
Authors: Lim Peng Ken , Davey Emilia E , Wee Sean , Seetoh Wei Song , Goh Jong Ching , Zheng Xinghai , Ann Phang Sean Kia , Kai Seah Eugene Sheng , Zhen Ng Janice Wan , Hui Wee Xavier Jia , Hui Quek Aloysius Jun , Lim Jordan JingHeng , Rodrigues Edbert Edric , Lee Heesoo , Lim Chin Yong , Tan Wei Zhi , Dan Yuet Ruh , Lee Bronson , Le Chee Samuel En , En Lim Zachary Ze , Guan Jia Sheng , Le Tan Ivan Jia , Arong Trinidad Jeremiah , Mutwil Marek 
Published: August 2021

AbstractSummaryThe bacterial kingdom comprises unicellular prokaryotes able to establish symbioses from mutualism to parasitism. To combat bacterial pathogenicity, we need an enhanced understanding of gene function and regulation, which will mediate the development of novel antimicrobials. Gene expression can predict gene function, but there lacks a database enabling expansive inter- and intraspecific exploration of gene expression profiles and co-expression networks for bacteria. To address this, we integrated the genomic and transcriptomic data of the 17 most notorious and studied bacterial pathogens, creating bacteria.guru, an interactive database that can identify, visualize, and compare gene expression profiles, co-expression networks, functionally enriched clusters, and gene families across species. Through illustrating antibiotic resistance mechanisms in P. aeruginosa, we demonstrate that bacteria.guru could potentially aid the discovery of multi-faceted antibiotic targets. Hence, we believe bacteria.guru will facilitate future bacterial research.AvailabilityThe database and co-expression networks are freely available from https://bacteria.guru/. The sample annotations are found in the supplemental data.