bluuebunny/crossref_metadata_2025_split huggingface dataset:
Length of stay of hospitalized patients at tertiary psychiatry facilities in Uganda: the role of caregiver’s presence
Authors: Kaggwa Mark Mohan , Najjuka Maria Sarah , Kesande Claire , Nyemara Novatus , Kule Moses , Mamum Mohammed A. , Bongomin Felix , Ashaba Scholastic 
Published: July 2022

Abstract
Background
Whether the presence of caregivers during the hospital stay of patients with mental illness affects the length of hospital stay (LoS) remains inconclusive.

Aims
(1) To determine the average LoS and the associated factors, and (2) to determine the role of caregivers’ presences during inpatient stay on LoS.

Methods
We conducted a cross-sectional study in two hospitals in Uganda; one with caregivers and the other without caregivers between July to November 2020. Mann-Whitney U test was used to compare LoS in the two selected hospitals and linear regression was used to determine factors associated with LoS.

Results
A total of 222 participants were enrolled, the majority were males (62.4%). Mean age was 36.3 (standard deviation (SD) = 13.1) years. The average LoS was 18.3 (SD = 22.3) days, with patients in a hospital without caregivers having a longer median LoS (i.e., (30 (interquartile range (IQR) = 30) vs. 7 (7) days; χ2 = 68.95, p < 0.001). The factors significantly associated a longer LoS among our study participants included; being admitted in a hospital without caregivers (adjusted coefficient [aCoef]: 14.88, 95% CI 7.98–21.79, p < 0.001), a diagnosis of schizophrenia (aCoef: 10.68, 95 %CI 5.53–15.83, p < 0.001), being separated or divorced (aCoef: 7.68, 95% CI 1.09–14.27, p = 0.023), and increase in money spent during the admission (aCoef: 0.14, 95% CI 0.09–0.18, p < 0.001).

Conclusion
Patients with mental illness in southwestern Uganda have a short LoS (below 28 days), and the stay was much shorter for patients with fulltime caregivers. We recommend caregivers presence during patient’s hospital stay to reduce the LoS and minimize healthcare expenditure.
ANDRIA MOI ENNEPE: AN ALLUSION TO ODYSSEUS IN TERENCE, ANDRIA 560–2
Authors: Gellar-Goad T.H.M. 
Published: July 2022

AbstractThis note argues for a previously unnoticed allusion in Terence's Andria to Odysseus and the Sirens, in a wish expressed by the play's old man that his son will escape the alluring clutches of the sex-labourer next door.
PLINY, LETTERS 10.98. A METAPHOR FOR THE SOLUTION TO THE CHRISTIAN PROBLEM?
Authors: Beckmann Martin 
Published: July 2022

AbstractI argue that letter 98 of Book 10 of Pliny's Letters (= Epistulae) was deliberately moved from its original position in the sequence of letters in order to serve as a metaphor for the solution to the problem of Christians in Bithynia and Pontus. This solves a chronological problem in Pliny's Letters and is evidence of the hand of an active editor.
Rethinking the concept of God and the problem of evil from the perspective of African thought
Authors: Agada Ada 
Published: July 2022

AbstractIn this article, I show that: (1) There is a transcendence strain in African Traditional Religion (ATR) and traditional African thought that agrees perfectly with traditional monotheism and legitimizes the question of the relation of God with evil in the world. (2) There is incontrovertible evidence of the conception of God as a limited deity that subverts the categories of omnipotence and omniscience. (3) African philosophers of religion must show how a transcendent or, conversely, a limited God is related to the evil that exists in the world, since the overwhelming stance of ATR is that God is the creator of the world and wields effective power. I substitute the categories of omnipotence and omniscience with the novel categories of power and glory and argue that while a powerful and glorious God is not the author of evil and cannot eliminate evil in the world, such a God can be conceived as working to reduce the evil in the world through the instrumentality of human moral agency.
Learning conversational dependency: Children’s response using un in Japanese
Authors: TATSUMI Tomoko , SALA Giovanni 
Published: July 2022

AbstractThis study investigates how Japanese-speaking children learn interactional dependencies in conversations that determine the use of un, a token typically used as a positive response for yes-no questions, backchannel, and acknowledgement. We hypothesise that children learn to produce un appropriately by recognising different types of cues occurring in the immediately preceding turns. We built a set of generalised linear models on the longitudinal conversation data from seven children aged 1 to 5 years and their caregivers. Our models revealed that children not only increased their un production, but also learned to attend relevant cues in the preceding turns to understand when to respond by producing un. Children increasingly produced un when their interlocutors asked a yes-no question or signalled the continuation of their own speech. These results illustrate how children learn the probabilistic dependency between adjacent turns, and become able to participate in conversational interactions.
Changes in the Relative Importance of Biogenic Isoprene and Soil NOx Emissions on Ozone Concentrations in Nonattainment Areas of the United States
Authors: Geddes Jeffrey A. , Pusede Sally E. , Wong Anthony Y. H. 
Published: July 2022

AbstractReductions in anthropogenic emissions have drawn increasing attention to the role of the biosphere in O3 production chemistry in U.S. cities. We report the results of chemical transport model sensitivity simulations exploring the relative impacts of biogenic isoprene and soil nitrogen oxides (NOx) emissions on O3 and its temporal variability. We compare scenarios with high and low anthropogenic NOx emissions representing the reductions that have occurred in recent decades. As expected, summertime O3 concentrations become less sensitive to perturbations in biogenic isoprene emissions as anthropogenic NOx emissions decline. However, we demonstrate for the first time that across policy relevant O3 nonattainment areas of the United States, O3 becomes more sensitive to perturbations in soil NOx emissions than to identical perturbations in isoprene emissions. We show that interannual variability in soil NOx emissions may now have larger impacts on interannual O3 variability than isoprene emissions in many areas where the latter would have dominated in the recent past.
Shallow Water Records of the PETM: Novel Insights From NE India (Eastern Tethys)
Authors: Sarkar Suman , Cotton Laura J. , Valdes Paul J. , Schmidt Daniela N. 
Published: July 2022

AbstractThe Paleocene‐Eocene Thermal Maximum (PETM) is associated with major extinctions in the deep ocean, and significant paleogeographic and ecological changes in surface ocean and terrestrial environments. However, the impact of the associated environmental change on shelf biota is less well understood. Here, we present a new PETM record of a low paleolatitude shallow‐marine carbonate platform from Meghalaya, NE India (eastern Tethys). The biotic assemblage was distinctly different to other Tethyan PETM records dominated by larger benthic foraminifera and calcareous algae both in the Paleocene and Eocene. A change in taxa and forms indicating deeper waters with a concurrent decrease in abundance of shallow water algae suggests a sea‐level rise during the onset of the PETM. The record is lacking the ecological change from corals to larger foraminiferal assemblages and theLockhartiadominance, characteristic of several other sections in the Tethys. Comparison with a global circulation model (GCM) indicates high regional temperatures in the Thanetian which may have excluded corals from the region. Furthermore, the regional circulation pattern is isolating the site from the wider Paratethys. Our study highlights the need for a diverse global perspective on shallow‐marine response to the PETM and the strength of coupling data to global climate models for interpretation.
Sensitivity of Erosion‐Rate in Permafrost Landscapes to Changing Climatic and Environmental Conditions Based on Lake Sediments From Northwestern Alaska
Authors: Shelef Eitan , Griffore Melissa , Mark Sam , Coleman Tim , Wondolowski Nick , Lasher G. Everett , Abbott Mark 
Published: July 2022

AbstractErosion of landscapes underlaid by permafrost can transform sediment and nutrient fluxes, surface and subsurface hydrology, soil properties, and rates of permafrost thaw, thus changing ecosystems and carbon emissions in high latitude regions with potential implications for global climate. However, future rates of erosion and sediment transport are difficult to predict as they depend on complex interactions between climatic and environmental parameters such as temperature, precipitation, permafrost, vegetation, wildfires, and hydrology. Thus, despite the potential influence of erosion on the future of the Arctic and global systems, the relations between erosion‐rate and these parameters, as well as their relative importance, remain largely unquantified. Here we quantify these relations based on a sedimentary record from Burial Lake, Alaska, one of the richest datasets of Arctic lake deposits. We apply a set of bi‐ and multi‐variate techniques to explore the association between the flux of terrigenous sediments into the lake (a proxy for erosion‐rate) and a variety of biogeochemical sedimentary proxies for paleoclimatic and environmental conditions over the past 25 cal ka BP. Our results show that erosion‐rate is most strongly associated with temperature and vegetation proxies, and that erosion‐rate decreases with increased temperature, pollen‐counts, and abundance of pollen from shrubs and trees. Other proxies, such as those associated with fire frequency, aeolian dust supply, mass wasting and hydrologic conditions, play a secondary role. The marginal effects of the sedimentary‐proxies on erosion‐rate are often threshold dependent, highlighting the potential for strong non‐linear changes in erosion in response to future changes in Arctic conditions.
Variability in the Global Ocean Carbon Sink From 1959 to 2020 by Correcting Models With Observations
Authors: Bennington Val , Gloege Lucas , McKinley Galen A. 
Published: July 2022

AbstractThe ocean reduces human impact on the climate by absorbing and sequestering CO2. From 1950s to the 1980s, observations of pCO2 and related ocean carbon variables were sparse and uncertain. Thus, global ocean biogeochemical models (GOBMs) have been the basis for quantifying the ocean carbon sink. The LDEO‐Hybrid Physics Data product (LDEO‐HPD) interpolates sparse surface ocean pCO2 data to global coverage by using GOBMs as priors, and applying machine learning to estimate full‐coverage corrections. The largest component of the GOBM corrections are climatological. This is consistent with recent findings of large seasonal discrepancies in GOBMs, but contrasts the long‐held view that interannual variability is a major source of GOBM error. This supports extension of the LDEO‐HPD pCO2 product back to 1959, using a climatology of model‐observation misfits prior to 1982. Consistent with previous studies for 1980 onward, air‐sea CO2 fluxes for 1959–2020 demonstrate response to atmospheric pCO2 growth and volcanic eruptions.
Growth rate-dependent coordination of catabolism and anabolism in the archaeonMethanococcus maripaludisunder phosphate limitation
Authors: Gu Wenyu , Müller Albert L , Deutzmann Jörg S , Williamson James R , Spormann Alfred M 
Published: July 2022

AbstractCatabolic and anabolic processes are finely coordinated in microorganisms to provide optimized fitness under varying environmental conditions. Understanding this coordination and the resulting physiological traits reveals fundamental strategies of microbial acclimation. Here, we characterized the system-level physiology of Methanococcus maripaludis, a niche-specialized methanogenic archaeon, at different dilution rates ranging from 0.09 to 0.003 h−1 in chemostat experiments under phosphate (i.e., anabolic) limitation. Phosphate was supplied as the limiting nutrient, while formate was supplied in excess as the catabolic substrate and carbon source. We observed a decoupling of catabolism and anabolism resulting in lower biomass yield relative to catabolically limited cells at the same dilution rates. In addition, the mass abundance of several coarse-grained proteome sectors (i.e., combined abundance of proteins grouped based on their function) exhibited a linear relationship with growth rate, mostly ribosomes and their biogenesis. Accordingly, cellular RNA content also correlated with growth rate. Although the methanogenesis proteome sector was invariant, the metabolic capacity for methanogenesis, measured as methane production rates immediately after transfer to batch culture, correlated with growth rate suggesting translationally independent regulation that allows cells to only increase catabolic activity under growth-permissible conditions. These observations are in stark contrast to the physiology of M. maripaludis under formate (i.e., catabolic) limitation, where cells keep an invariant proteome including ribosomal content and a high methanogenesis capacity across a wide range of growth rates. Our findings reveal that M. maripaludis employs fundamentally different strategies to coordinate global physiology during anabolic phosphate and catabolic formate limitation.
Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?
Authors: Kou Meng , Huang Li , Yang Jinjuan , Chiang Zhixin , Chen Shaoxiang , Liu Jie , Guo Liyan , Zhang Xiaoxian , Zhou Xiaoya , Xu Xiang , Yan Xiaomei , Wang Yan , Zhang Jinqiu , Xu Aimin , Tse Hung-fat , Lian Qizhou 
Published: July 2022

AbstractMesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.
Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity
Authors: Ni Zhexin , Li Yangshuo , Song Di , Ding Jie , Mei Shanshan , Sun Shuai , Cheng Wen , Yu Jin , Zhou Ling , Kuang Yanping , Li Mingqing , Cai Zailong , Yu Chaoqin 
Published: July 2022

AbstractEndometriosis (EMs) occurs in approximately 50% of women with infertility. The main causes of EMs-related infertility are follicle dysplasia and reduced oocyte quality. Iron overload occurs in ovarian follicular fluid (FF) of patients with EMs, and this condition is associated with oocyte maturation disorder. However, the underlying molecular mechanism remains largely unknown. In the present study, we identified the mechanism underlying ferroptosis in ovarian granulosa cells and oocyte maturation failure in EMs based on a retrospective review of in vitro fertilization/intracytoplasmic sperm injection-frozen embryo transfer outcomes in infertile patients with EMs. Mouse granulosa cells were treated with EMs-related infertile patients' follicular fluid (EMFF) in vitro. Western blot analysis, quantitative polymerase chain reaction, fluorescence staining, and transmission electron microscopy were used to assess granulosa cells ferroptosis. The effects of exosomes were examined by nanoparticle tracking analysis, RNA-seq, and Western blot analysis. Finally, the therapeutic values of vitamin E and iron chelator (deferoxamine mesylate) in vivo were evaluated in an EMs-related infertility model. Patients with ovarian EMs experienced poorer oocyte fertility than patients with non-ovarian EMs. We observed that EMFF with iron overload-induced granulosa cell ferroptosis in vitro and in vivo. Mechanically, nuclear receptor coactivator four-dependent ferritinophagy was involved in this process. Notably, granulosa cells undergoing ferroptosis further suppressed oocyte maturation by releasing exosomes from granulosa cells. In therapeutic studies, vitamin E and iron chelators effectively alleviated EMs-related infertility models. Our study indicates a novel mechanism through which EMFF with iron overload induces ferroptosis of granulosa cells and oocyte dysmaturity in EMs-related infertility, providing a potential therapeutic strategy for EMs-related infertility.
The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors
Authors: Liu Lina , Vujovic Ana , Deshpande Nandan P. , Sathe Shashank , Anande Govardhan , Chen He Tian Tony , Xu Joshua , Minden Mark D. , Yeo Gene W. , Unnikrishnan Ashwin , Hope Kristin J. , Lu Yu 
Published: July 2022

AbstractChemo-resistance in acute myeloid leukemia (AML) patients is driven by leukemic stem cells (LSCs) resulting in high rates of relapse and low overall survival. Here, we demonstrate that upregulation of the splicing factor, RBM17 preferentially marks and sustains LSCs and directly correlates with shorten patient survival. RBM17 knockdown in primary AML cells leads to myeloid differentiation and impaired colony formation and in vivo engraftment. Integrative multi-omics analyses show that RBM17 repression leads to inclusion of poison exons and production of nonsense-mediated decay (NMD)-sensitive transcripts for pro-leukemic factors and the translation initiation factor, EIF4A2. We show that EIF4A2 is enriched in LSCs and its inhibition impairs primary AML progenitor activity. Proteomic analysis of EIF4A2-depleted AML cells shows recapitulation of the RBM17 knockdown biological effects, including pronounced suppression of proteins involved in ribosome biogenesis. Overall, these results provide a rationale to target RBM17 and/or its downstream NMD-sensitive splicing substrates for AML treatment.
Engineering probiotics to inhibit Clostridioides difficile infection by dynamic regulation of intestinal metabolism
Authors: Koh Elvin , Hwang In Young , Lee Hui Ling , De Sotto Ryan , Lee Jonathan Wei Jie , Lee Yung Seng , March John C. , Chang Matthew Wook 
Published: July 2022

AbstractClostridioides difficile infection (CDI) results in significant morbidity and mortality in hospitalised patients. The pathogenesis of CDI is intrinsically related to the ability of C. difficile to shuffle between active vegetative cells and dormant endospores through the processes of germination and sporulation. Here, we hypothesise that dysregulation of microbiome-mediated bile salt metabolism contributes to CDI and that its alleviation can limit the pathogenesis of CDI. We engineer a genetic circuit harbouring a genetically encoded sensor, amplifier and actuator in probiotics to restore intestinal bile salt metabolism in response to antibiotic-induced microbiome dysbiosis. We demonstrate that the engineered probiotics limited the germination of endospores and the growth of vegetative cells of C. difficile in vitro and further significantly reduced CDI in model mice, as evidenced by a 100% survival rate and improved clinical outcomes. Our work presents an antimicrobial strategy that harnesses the host-pathogen microenvironment as the intervention target to limit the pathogenesis of infection.
Structures and gating mechanisms of human bestrophin anion channels
Authors: Owji Aaron P. , Wang Jiali , Kittredge Alec , Clark Zada , Zhang Yu , Hendrickson Wayne A. , Yang Tingting 
Published: July 2022

AbstractBestrophin-1 (Best1) and bestrophin-2 (Best2) are two members of the bestrophin family of calcium (Ca2+)-activated chloride (Cl−) channels with critical involvement in ocular physiology and direct pathological relevance. Here, we report cryo-EM structures of wild-type human Best1 and Best2 in various states at up to 1.8 Å resolution. Ca2+-bound Best1 structures illustrate partially open conformations at the two Ca2+-dependent gates of the channels, in contrast to the fully open conformations observed in Ca2+-bound Best2, which is in accord with the significantly smaller currents conducted by Best1 in electrophysiological recordings. Comparison of the closed and open states reveals a C-terminal auto-inhibitory segment (AS), which constricts the channel concentrically by wrapping around the channel periphery in an inter-protomer manner and must be released to allow channel opening. Our results demonstrate that removing the AS from Best1 and Best2 results in truncation mutants with similar activities, while swapping the AS between Best1 and Best2 results in chimeric mutants with swapped activities, underlying a key role of the AS in determining paralog specificity among bestrophins.
Sex differences in heart mitochondria regulate diastolic dysfunction
Authors: Cao Yang , Vergnes Laurent , Wang Yu-Chen , Pan Calvin , Chella Krishnan Karthickeyan , Moore Timothy M. , Rosa-Garrido Manuel , Kimball Todd H. , Zhou Zhiqiang , Charugundla Sarada , Rau Christoph D. , Seldin Marcus M. , Wang Jessica , Wang Yibin , Vondriska Thomas M. , Reue Karen , Lusis Aldons J. 
Published: July 2022

AbstractHeart failure with preserved ejection fraction (HFpEF) exhibits a sex bias, being more common in women than men, and we hypothesize that mitochondrial sex differences might underlie this bias. As part of genetic studies of heart failure in mice, we observe that heart mitochondrial DNA levels and function tend to be reduced in females as compared to males. We also observe that expression of genes encoding mitochondrial proteins are higher in males than females in human cohorts. We test our hypothesis in a panel of genetically diverse inbred strains of mice, termed the Hybrid Mouse Diversity Panel (HMDP). Indeed, we find that mitochondrial gene expression is highly correlated with diastolic function, a key trait in HFpEF. Consistent with this, studies of a “two-hit” mouse model of HFpEF confirm that mitochondrial function differs between sexes and is strongly associated with a number of HFpEF traits. By integrating data from human heart failure and the mouse HMDP cohort, we identify the mitochondrial gene Acsl6 as a genetic determinant of diastolic function. We validate its role in HFpEF using adenoviral over-expression in the heart. We conclude that sex differences in mitochondrial function underlie, in part, the sex bias in diastolic function.