bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Behaviourally Informed Text Messages to Promote Retention in HIV Care: A Randomized Trial in Ekurhuleni District, South Africa
Authors: Govathson Caroline , Pascoe Sophie , Chetty-Makkan Candice , Schmucker Laura , Mistri Preethi , Thirumurthy Harsha , Mabuto Tonderai 
Published: October 2023

AbstractIntroductionSustained engagement in care among people living with HIV is vital for realising the individual and public health benefits of antiretroviral therapy (ART). We examined whether mobile phone-based text messages that leveraged behavioural science principles promoted timely clinic attendance among ART recipients.MethodsWe conducted a randomized controlled trial in three primary health clinics in Gauteng Province, South Africa between July 2021 and December 2021. ART recipients with an upcoming clinic appointment were randomised to standard of care appointment reminders or three enhanced reminders that leveraged behavioural science principles of loss aversion, social norms, and altruism. The primary outcome was a timely clinic visit, on or before the scheduled appointment day. Poisson regression with clinic fixed effects and controls for age, sex, and ART duration was used to examine the effect of the enhanced reminders on the primary outcome.ResultsAmong 1539 participants, 690 (44.8%) were male and median time on ART was 11 months (IQR, 3.7-51.9). The primary outcome of timely clinic visit was 50.3% in the standard of care arm, and similar in the loss aversion arm (53.5%; adjusted risk ratio, ARR 1.1; 95% CI: 0.9-1.2), social norms arm (48.0%; ARR 1.1; 95% CI: 0.8-1.1), and altruism arm (50.9% ARR 1.0; 95% CI: 0.9-1.5). In subgroup analyses, messages framed with loss aversion increased the timely clinic visits among participants with ART duration <90 days (ARR=1.37; 95% CI: 1.08-1.74).ConclusionsThe use of behavioural science principles to frame reminder messages did not increase timely clinic visits among HIV care recipients. Among those who recently initiated ART, however, loss aversion framing increased timely clinic visits. Future research should explore alternative behavioural science principles to revise health communication with HIV care recipients.Clinical Trials NumberNCT05010291
How feasible is it to mobilize $31 billion a year for pandemic preparedness and response? An economic growth modelling analysis
Authors: Shahid Minahil , Schäferhoff Marco , Brown Garrett , Yamey Gavin 
Published: October 2023

AbstractBackgroundCovid-19 has reinforced the strong health and economic case for investing in pandemic preparedness and response (PPR). The World Bank and World Health Organization (WHO) propose that low- and middle-income governments and donor countries should invest $31.1 billion each year for PPR. We analyse, based on the projected economic growth of countries between 2022 and 2027, how likely it is that low- and middle-income country governments and donors can mobilize the estimated funding.MethodsWe modelled trends in economic growth to project domestic health spending by low- and middle-income governments and official development assistance (ODA) by donors for years 2022 to 2027. We modelled two scenarios for countries and donors – a constant and an optimistic scenario. Under the constant scenario we assume that countries and donors continue to dedicate the same proportion of their health spending and ODA as a share of gross domestic product (GDP) and gross national income (GNI), respectively, as they did during baseline (the latest year for which data are available). In the optimistic scenario, we assume a yearly increase of 2.5% in health spending as a share of GDP for countries and ODA as a share of GNI for donors.FindingsOur analysis shows that low-income countries would need to invest on average 37%, lower-middle income countries 9%, and upper-middle income countries 1%, of their total health spending on PPR each year under the constant scenario to meet the World Bank WHO targets. Donors would need to allocate on average 8% of their total ODA across all sectors to PPR each year to meet their target.ConclusionsThe World Bank WHO targets for PPR will not be met unless low- and middle-income governments and donors spend a much higher share of their funding on PPR. Even under optimistic growth scenarios, low-income and lower-middle income countries will require increased support from global health donors. The donor target cannot be met using the yearly increase in ODA under any scenario. If the country and donor targets are not met, the highest-impact health security measures need to be prioritized for funding. Alternative sources of PPR financing could include global taxation (e.g., on financial transactions, carbon, or airline flights), cancelling debt, and addressing illicit financial flows. There is also a need for continued work on estimating current PPR costs and funding requirements in order to arrive at more enduring and reliable estimates.
Retinoic acid-dependent loss of synaptic output from bipolar cells impairs visual information processing in inherited retinal degeneration
Authors: Ganzen Logan , Yadav Shubhash Chandra , Wei Mingxiao , Ma Hong , Nawy Scott , Kramer Richard H 
Published: October 2023

AbstractIn retinitis pigmentosa (RP), rod and cone photoreceptors degenerate, depriving downstream neurons of light-sensitive input, leading to vision impairment or blindness. Although downstream neurons survive, some undergo morphological and physiological remodeling. Bipolar cells (BCs) link photoreceptors, which sense light, to retinal ganglion cells (RGCs), which send information to the brain. While photoreceptor loss disrupts input synapses to BCs, whether BC output synapses remodel has remained unknown. Here we report that synaptic output from BCs plummets in RP mouse models of both sexes owing to loss of voltage-gated Ca2+channels. Remodeling reduces the reliability of synaptic output to repeated optogenetic stimuli, causing RGC firing to fail at high stimulus frequencies. Fortunately, functional remodeling of BCs can be reversed by inhibiting the retinoic acid receptor (RAR). RAR inhibitors targeted to BCs present a new therapeutic opportunity for mitigating detrimental effects of remodeling on signals initiated either by surviving photoreceptors or by vision-restoring tools.Significance StatementPhotoreceptor degenerative disorders such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) lead to vision impairment or blindness. Vision mediated by surviving photoreceptors or artificial vision restoration technologies, rely on bipolar cells retaining normal function despite photoreceptor death. We find that in two animal models of RP, synaptic transmission from both rod and cone bipolar cells is severely impaired owing to diminished voltage-gated calcium current, preventing postsynaptic amacrine cells and retinal ganglion cells from properly receiving and encoding visual information. We find that an inhibitor of the retinoic acid receptor restores both the calcium current and synaptic release from bipolar cells. These discoveries about bipolar cells reveal a new functional deficit in blindness and a potential therapeutically important solution.
LysoTracker Deep Red exhibits photoconversion in multi-color structured illumination microscopy
Authors: Opstad Ida Sundvor , Larsen Kenneth Bowitz , Birgisdottir Åsa Birna , Agarwal Krishna 
Published: October 2023

AbstractIn new chemical environments or for untested combinations of illumination, unexpected changes to the fluorescent labels’ photophysical properties, such as photoconversion, can occur. This letter reports on photoblueing of a common cellular probe, LysoTracker Deep Red, in multi-color super-resolution structured illumination microscopy. The dye was found to exhibit a blue shift of its fluorescence spectrum as a step on the photobleaching pathway during such imaging. The observed photoblueing (emission spectrum shifted to lower wavelengths) of this probe is an important finding as many cellular assays rely on the spectral separation of this and such fluorescent cellular markers. No spectral shift of LysoTracker Deep Red was observed for longterm imaging using diffraction limited microscopy requiring significantly lower light dose. We expect that the knowledge of occurrence of photoconversion during super-resolved imaging using this popular dye will help researchers design better imaging experiments and avoid potentially erroneous interpretations in multi-color microscopy.
Telomere protein arrays stall DNA loop extrusion by condensin
Authors: Analikwu Brian T. , Deshayes Alice , van der Torre Jaco , Guérin Thomas , Katan Allard J. , Béneut Claire , Barth Roman , Phipps Jamie , Scolari Vittore , Veaute Xavier , Barrington Christopher , Busso Didier , Uhlmann Frank , Dubrana Karine , Mattarocci Stefano , Dekker Cees , Marcand Stéphane 
Published: October 2023

AbstractDNA loop extrusion by SMC proteins is a key process underlying chromosomal organization. It is unknown how loop extruders interact with telomeres where chromosome ends are covered with a dense array of tens of neighboring DNA-binding proteins. Using complementaryin vivoandin vitrosingle-molecule approaches, we study the interaction between loop-extruding condensin and arrays of Rap1, the double-stranded-DNA-binding telomeric protein ofSaccharomyces cerevisiae. We show that dense linear Rap1 arrays can completely halt DNA loop extrusion, where the blocking efficiency depends on the array length and the DNA gap size between neighboring proteins. In cells, Rap1 arrays in the chromosome are found to act as contact insulators and to accumulate condensin at their borders, with direct implications for the resolution of dicentric chromosomes produced by telomere fusions. Our findings show that linear arrays of DNA-bound proteins can efficiently halt DNA loop extrusion by SMC proteins, which may impact a wide range of cellular processes from telomere functions to transcription and DNA repair.
Activity-regulated micro-exon splicing programs underlie late-onset plasticity at the axon initial segment
Authors: Darwish Mohamed , Suzuki Satoko , Ogawa Yuki , Takase Akinori , Tanaka Masami , Iijima Yoko , Sato Yuji , Suzuki Mariko , Kanegae Yumi , Okada Chisa , Takana Masayuki , Okano Hirotaka-James , Kuba Hiroshi , Iijima Takatoshi 
Published: October 2023

AbstractThe axon initial segment (AIS) is a specialized neuronal compartment located at the proximal end of axons and initiates action potentials. AIS undergoes plastic changes with aging, disease, and activity levels; however, the molecular mechanisms underlying their plasticity remain unclear. We discovered that depolarization induces diffuse elongation of the AIS in cerebellar granule cells over the span of days via the Ca2+-dependent ERK/MAP kinase pathway. These structural changes were accompanied by a decrease in voltage-gated Na+channel density, resulting in a homeostatic attenuation in neuronal excitability. Notably, we found that the late-onset AIS plasticity is associated with depolarization-induced alternative splicing of smaller exons (<100 nt) of transcripts encoding AIS-enriched proteins. In addition, depolarization-induced the skipping of the 53-nt exon19 from the transcript of the splicing protein Rbfox1. CRISPR-mediated removal of exon 19 from Rbfox1 promoted its nuclear localization and sequentially induced a series of downstream micro-exon splicing changes in several AIS proteins, recapitulating cerebellar AIS plasticity. In a Rbfox1-independent mechanism, depolarization-induced insertion of the developmentally regulated micro-exon 34 into the key AIS scaffolding protein Ankyrin G (AnkG). The constitutive insertion of exon 34 into AnkG disrupted its interaction with the AIS cytoskeletal protein βIV spectrin and induced plastic changes in the AIS. Our findings provide fundamental mechanistic insights into the activity-mediated late-onset plasticity of AIS, highlighting the power of micro-scale splicing events in the homeostatic regulation of axonal remodeling.
Zinc finger domains bind low-complexity domain polymers
Authors: Iguchi Naohiko , Isozumi Noriyoshi , Hattori Yoshikazu , Imamura Tomohiro , So Masatomo , Nanaura Hitoki , Kiriyama Takao , Eura Nobuyuki , Yamaoka Minako , Nakanishi Mari , Mori Masashi , Ohki Shinya , Kumeta Hiroyuki , Koga Hironori , Watabe Mai , Mabuchi Takuya , Kanemura Shingo , Okumura Masaki , Yoshizawa Takuya , Ota Ichiro , Suzuki Naoki , Aoki Masashi , Yamashiro Yoshito , Saio Tomohide , Sugie Kazuma , Mori Eiichiro 
Published: October 2023

AbstractSelf-association of low-complexity protein sequences (LC domains) is important for polymer formation. Several molecular chaperones are involved in the regulation of LC domain polymer formation. However, the mechanisms underlying cell recognition of LC domain polymers remain unclear. Here we show that zinc finger domains (ZnFs) bind LC domains of RNA-binding proteins in a cross-β polymer-dependent manner. ZnFs bound to LC domain hydrogels and suppressed LC domain polymer formation. Moreover, ZnFs preferentially recognize LC domains in the polymeric state. These findings suggest that ZnFs act as physiological regulators of LC domain polymer formation.
Untangling the Role of Pathobionts from Bacteroides Species in Inflammatory Bowel Diseases
Authors: Shan Yue , Lake Joash , Cham Candace M. , Zhu Mingming , Kaur Deepinder , Ringus Daina , Fei Na , Weber Christopher R. , Spedale Melanie , Theriault Betty , Dalal Sushila , Rubin David T. , Fiebig Aretha , Crosson Sean , Lolans Karen , Comstock Laurie , Eren A. Murat , Basu Anindita , Pott Sebastian , Sogin Mitchell , Liu Cambrian , Chang Eugene B. 
Published: October 2023

AbstractInflammatory bowel diseases (IBD) arise from a convergence of underlying genetic susceptibility, environmental factors, and shifts in gut microbiota function and membership. Although the latter may trigger and contribute to IBD, there is little consensus on a specific causative pathogen. In this study, we demonstrate that commensalBacteroides fragilisstrains from ulcerative colitis (UC) patients before and during the development of ileal pouchitis engraft and promote colitis in specific pathogen free (SPF) IL-10 deficient (IL-10-/-) mice, but not in wild type SPF mice or when mono-associated in germ free mice. The colitis in IL-10-/-mice was also associated with significant alterations in commensal microbiota potentially important for maintaining intestinal and immune homeostasis. UC pouchitisB. fragilisalso engrafts in DSS-induced colitis in WT SPF mice, indicating a fitness advantage under conditions of mucosal inflammation over other commensals in the gut microbiota. These findings show that gut inflammation promotes the expansion and fitness of UC-derivedBacteroidesspecies that is associated with changes in the SPF gut microbiota and may be promote colitis in genetically susceptible hosts.ImportanceThis study supports the notion that human inflammatory bowel diseases arise from the emergence of indigenous pathobionts in genetically-prone subjects. Colitis-promoting pathobionts are well-suited to establish themselves in the host inflammatory environment and outcompete endogenous microbiota. Once engrafted, the pathobiont can further aggravate inflammation in a genetically-susceptible host. Such complex interplay among several factors creates a vicious pro-inflammatory cycle and promotes disease development. These findings are consistent with our previous clinical observation thatB. fragilis, an otherwise low-abundance commensal species, expands prior to the development of UC pouchitis. We believe these findings are relevant to the pathogenesis of UC pouchitis and possibly human inflammatory bowel diseases in general, underscoring the role of commensal to pathobiont transitions, rather than classical pathogens, in promoting and exacerbating the onset of human IBD.
Observations of Elemental Composition of Enceladus Consistent with Generalized Models of Theoretical Ecosystems
Authors: Muratore Daniel , Walker Sara I. , Graham Heather , House Christopher H. , Kempes Christopher P. 
Published: October 2023

AbstractRecent analysis of data from the Cassini Cosmic Dust Analyzer confirm geochemical modeling work that shows that the ocean of Enceladus contains considerable quantities of inorganic phosphorus as well as ammonium [55]. Technological advancement in flight instrumentation will continue to yield increasingly detailed data about the relative elemental and molecular composition of life detection candidates. Apart from speculating about threshold concentrations of bioactive compounds to support ecosystems, metabolic and ecological theory can provide a powerful interpretative lens to assess whether extraterrestrial environments are compatible with living ecosystems. Using multiple levels of ecological analysis, spanning from assuming strictly Earth-like organismal physiology to more agnostic understandings of putative biochemistries, we compare the proposed N:P stoichiometries of the Enceledus ocean to possible ecologies. We use chemostat models to predict potentially supportable biomass concentrations under different energy and matter flux regimes, macromolecular allometric theory to compare hypothetical biomass N:P ratios to possible environmental N:P supply ratios, and finally take a data-driven biogeochemical approach to predict possible biomass N:P ratios from the observed dissolved ratios. All three of our modeling approaches suggest marginal compatibility of an ecosystem with the ranges of dissolved N and P concentrations in the Enceledean ocean. Based on our analysis, we suggest two main priorities for further research into terrestrial analogs to improve our ability to interpret geochemical ratios as a life detection instrument.
TheDrosophilaCircadian Clock GeneCycleControls the Development of Clock Neurons
Authors: Biondi Grace , McCormick Gina , Fernandez Maria P. 
Published: October 2023

AbstractDaily behavioral and physiological rhythms are controlled by the brain’s circadian timekeeping system, a synchronized network of neurons that maintains endogenous molecular oscillations. These oscillations are based on transcriptional feedback loops of clock genes, which inDrosophilainclude the transcriptional activatorsClock (Clk)andcycle (cyc). While the mechanisms underlying this molecular clock are very well characterized, the roles that the core clock genes play in neuronal physiology and development are much less understood. TheDrosophilatimekeeping center is composed of ∼150 clock neurons, among which the four small ventral lateral neurons (sLNvs) are the most dominant pacemakers under constant conditions. Here, we show that downregulating the clock genecycspecifically in thePdf-expressing neurons prevents leads to decreased fasciculation both in larval and adult brains. This effect is due to a developmental role ofcyc, as both knocking downcycor expressing a dominant negative form ofcycexclusively during development lead to defasciculation phenotypes in adult clock neurons.Clkdownregulation also leads to developmental effects on sLNv morphology, althoughcycandClkmanipulations produce distinct phenotypes. Our results reveal a non-circadian role forcyc, shedding light on the additional functions of circadian clock genes in the development of the nervous system.
Serological markers and Post COVID-19 Condition (PCC) – A rapid review of the evidence
Authors: Collins Erin , Philippe Elizabeth , Gravel Chris , Hawken Steven , Langlois Marc-André , Little Julian 
Published: October 2023

AbstractBackgroundPost COVID-19 Condition (PCC) is highly heterogeneous, often debilitating, and may last for years after infection. The etiology of PCC remains uncertain. Examination of potential serological markers of PCC, accounting for clinical covariates, may yield emergent pathophysiological insights.MethodsIn adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting ≥12 weeks post-infection with those who did not. We examined relationships between serological markers and PCC status and investigated sources of inter-study variability, such as severity of acute illness, PCC symptoms assessed, and target antigen(s).ResultsOf 8,018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of PCC varied. In studies that reported anti-nucleocapsid (N) IgG (n=10 studies; n=989 participants in aggregate), full or partial anti-Spike IgG (i.e., the whole trimer, S1 or S2 subgroups, or receptor binding domain, n=19 studies; n=2606 participants), or neutralizing response (n=7 studies; n=1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders.ConclusionsPooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency, and comprehension of study findings.
Mendelian Randomization Study of Whole Blood Viscosity and Cardiovascular Diseases
Authors: Bhak Youngjune , Tenesa Albert 
Published: October 2023

AbstractAimsAssociation between whole blood viscosity (WBV) and an increased risk of cardiovascular disease (CVD) has been reported. However, the causal relationship between WBV and CVD remains not thoroughly investigated. The aim of this study was to investigate the causal relation between WBV and CVD.MethodsMendelian randomization was employed to investigate the casual relationship between WBV and CVD. Calculated WBV, derived polygenic risk score (PRS) for WBV, and medical records from 378,210 individuals participating in the UK biobank study were analyzed.ResultsThe means of calculated WBVs were 16.9 (standard deviation: 0.8) and 55.1 (standard deviation: 17.2) for high shear rate (HSR) and low shear rate (LSR), respectively. 37,859 (10.0%) major cardiovascular event (MACE) consisted of 23,894 (6.3%) cases of myocardial infarction (MI), 9,245 (2.4%) cases of ischemic stroke, 10,377 (2.7%) cases of revascularization, and 5,703 (1.5%) cases of Coronary heart disease-related death. WBVs of individuals with PRS above median were significantly higher than the group that were below median for both low shear rate (P<0.001) and high shear rate (P<0.001). The odd ratios (95% confidence intervals) for MACE in the higher WBV group were 1.22 (1.19 - 1.25) and 1.14 (1.12 - 1.16), for HSR and LSR, respectively. The higher PRS group was insignificant with all outcomes, for both HSR and LSR.ConclusionsThe Mendelian randomization analysis conducted in this study does not support a causal relationship between calculated WBV and CVD.