bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population size rescaling significantly biases outcomes of forward-in-time population genetic simulations
Authors: Dabi Amjad , Schrider Daniel R 
Published: November 2024

Abstract
Simulations are an essential tool in all areas of population genetic research, used in tasks such as the validation of theoretical analysis and the study of complex evolutionary models. Forward-in-time simulations are especially flexible, allowing for various types of natural selection, complex genetic architectures, and non-Wright–Fisher dynamics. However, their intense computational requirements can be prohibitive to simulating large populations and genomes. A popular method to alleviate this burden is to scale down the population size by some scaling factor while scaling up the mutation rate, selection coefficients, and recombination rate by the same factor. However, this rescaling approach may in some cases bias simulation results. To investigate the manner and degree to which rescaling impacts simulation outcomes, we carried out simulations with different demographic histories and distributions of fitness effects using several values of the rescaling factor, Q, and compared the deviation of key outcomes (fixation times, allele frequencies, linkage disequilibrium, and the fraction of mutations that fix during the simulation) between the scaled and unscaled simulations. Our results indicate that scaling introduces substantial biases to each of these measured outcomes, even at small values of Q. Moreover, the nature of these effects depends on the evolutionary model and scaling factor being examined. While increasing the scaling factor tends to increase the observed biases, this relationship is not always straightforward; thus, it may be difficult to know the impact of scaling on simulation outcomes a priori. However, it appears that for most models, only a small number of replicates was needed to accurately quantify the bias produced by rescaling for a given Q. In summary, while rescaling forward-in-time simulations may be necessary in many cases, researchers should be aware of the rescaling procedure's impact on simulation outcomes and consider investigating its magnitude in smaller scale simulations of the desired model(s) before selecting an appropriate value of Q.
Nonparticipation in a Digital Health Intervention Study Among Older Adults: Uneven Involvement, Biased Outcomes, and the Effect of Weighting
Authors: Poli Arianna , Kåreholt Ingemar , Kelfve Susanne , Berg Katarina , Motel-Klingebiel Andreas 
Published: November 2024

Abstract

Background
The involvement of older adults in research on digital health is uneven with respect to, for example, age, gender, health status, and digital skills. However, little is known regarding the effect of the uneven involvement of older adults in digital health research on researched outcomes. This study helps to fill this knowledge gap, identifies the effects of uneven involvement of older adults in digital health research on researched outcomes, and also develops a correction for this.

Methods
Data are retrieved from a digital health intervention for postoperative monitoring of people who underwent day surgery in Sweden. Based on field information on the recruitment process and researched outcomes for the intervention, this study (i) tested intervention effects by using 2 standard unweighted procedures in a sample of 281 individuals aged 50 years or older, and then (ii) used the information on participants, nonparticipants, and their respective probabilities to be involved in the intervention study to perform a weighting of the intervention effects for each step of selection and for the study group membership.

Results
The intervention effects were found to be overestimated due to overrepresentation of groups that gained from receiving the intervention. No intervention effects were found after adjustment for participation bias.

Conclusions
Selective participation of older adults in digital health research biases research outcomes and can lead to overestimation of intervention effects. Weighting allows researchers to correct and describe the effect of selective participation on researched outcomes.
Metrics of Physiological Network Topology Are Novel Biomarkers to Capture Functional Disability and Health
Authors: Hao Meng , Zhang Hui , Jiang Shuai , Hu Zixin , Jiang Xiaoyan , Wu Jingyi , Li Yi , Jin Li , Wang Xiaofeng 
Published: November 2024

Abstract

Background
Physiological networks are highly complex, integrating connections among multiple organ systems and their dynamic changes underlying human aging. It is unknown whether individual-level network could serve as robust biomarkers for health and aging.

Methods
We used personalized network analysis to construct a single-sample network and examine the associations between network properties and functional disability in the Rugao Longevity and Aging Study (RuLAS), the China Health and Retirement Longitudinal Study (CHARLS), the Chinese Longitudinal Healthy Longevity Survey (CLHLS), and the National Health and Nutrition Examination Survey (NHANES).

Results
We observed impairments in interconnected physiological systems among long-lived adults in RuLAS. Single-sample network analysis was applied to reflect the co-occurrence of these multisystem impairments at the individual level. The activities of daily living (ADL)-disabled individuals’ networks exhibited notably increased connectivity among various biomarkers. Significant associations were found between network topology and functional disability across RuLAS, CHARLS, CLHLS, and NHANES. Additionally, network topology served as a novel biomarker to capture risks of incident ADL disability in CHARLS. Furthermore, these metrics of physiological network topology predicted mortality across 4 cohorts. Sensitivity analysis demonstrated that the prediction performance of network topology remained robust, regardless of the chosen biomarkers and parameters.

Conclusions
These findings showed that metrics of network topology were sensitive and robust biomarkers to capture risks of functional disability and mortality, highlighting the role of single-sample physiological networks as novel biomarkers for health and aging.
Supporting multidrug-resistant or rifampicin-resistant TB treatment adherence in people with harmful use of alcohol through person-centred care
Authors: Harrison Rebecca E , Shyleika Volha , Vishneuski Raman , Leonovich Olga , Vetushko Dmitri , Skrahina Alena , Mar Htay Thet , Garsevanidze Ekaterine , Falkenstein Christian , Sayakci Öznur , Martin Antonio Isidro Carrion , Tan Cecilio , Sitali Norman , Viney Kerri , Lonnroth Knut , Stringer Beverley , Ariti Cono , Sinha Animesh 
Published: November 2024

Abstract

Background
TB is concentrated in populations with complex health and social issues, including alcohol use disorders (AUD). We describe treatment adherence and outcomes in a person-centred, multidisciplinary, psychosocial support and harm reduction intervention for people with multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) with harmful alcohol use.

Methods
An observational cohort study, including multilevel mixed-effects logistic regression and survival analysis with people living in Minsk admitted with MDR/RR-TB and AUD during January 2019–November 2021 who received this person-centred, multidisciplinary, psychosocial support and harm reduction intervention, was conducted.

Results
There were 89 participants enrolled in the intervention, with a median follow-up of 12.2 (IQR: 8.1–20.5) mo. The majority (n=80; 89.9%) of participants had AUD, 11 (12.4%) also had a dependence on other substances, six (6.7%) a dependence on opioids and three (3.4%) a personality disorder. Fifty-eight had a history of past incarceration (65.2%), homelessness (n=9; 10.1%) or unemployment (n=55; 61.8%). Median adherence was 95.4% (IQR: 90.4–99.6%) and outpatient adherence was 91.2% (IQR: 65.1–97.0%). Lower adherence was associated with hepatitis C, alcohol plus other substance use and outpatient facility-based treatment, rather than video-observed treatment, home-based or inpatient treatment support.

Conclusions
This intervention led to good adherence to MDR/RR-TB treatment in people with harmful use of alcohol, a group usually at risk of poor outcomes. Poor outcomes were associated with hepatitis C, other substance misuse and outpatient facility-based treatment support.
Rapid viral suppression using integrase inhibitors during acute HIV-1 infection
Authors: McKellar Mehri S , Keys Jessica R , Filiatreau Lindsey M , McGee Kara S , Kuruc Joann D , Ferrari Guido , Margolis David M , Eron Joseph J , Hicks Charles B , Gay Cynthia L 
Published: November 2024

Abstract

Background
Antiretroviral therapy (ART) is recommended for all individuals with HIV infection, including those with acute HIV-1 infection (AHI). While recommendations are similar to those for chronic infection, efficacy data regarding treatment of acute HIV is limited.

Methods
This was a single arm, 96-week study of a once-daily integrase inhibitor (INSTI)-based regimen using elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) in AHI. Primary endpoint was proportion of participants with HIV-1 RNA &lt;200 copies/mL and &lt;50 copies/mL by treatment weeks 24 and 48, respectively. We also examined time to viral suppression and weight gain after treatment initiation. Outcomes and characteristics were compared with a historical AHI cohort using a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).

Results
Thirty-three participants with AHI were enrolled with 31 available for analyses. Most were African American (61%) and men who have sex with men (73%). Median age was 26 (IQR 22–42). Demographics were similar between the two AHI cohorts. By Week 24, 100% in the INSTI and 99% in the NNRTI cohort were &lt;200 copies/mL; by Week 48, 100% in both cohorts were &lt;50 copies/mL. Time to viral suppression was shorter in the INSTI cohort (median 54 versus 99 days). Mean weight change was similar with a 3.6 kg increase in the INSTI cohort and 2.4 kg in the NNRTI cohort at 96 weeks.

Conclusions
INSTI-based ART during AHI resulted in rapid and sustained viral suppression. Over 96 weeks, weight increased in the INSTI-based cohort but was similar to weight increase in a historical NNRTI-based AHI cohort.
Emergence of the mobile RND-type efflux pump gene cluster tmexCD1-toprJ1 in Klebsiella pneumoniae clinical isolates in Japan
Authors: Hirabayashi Aki , Yano Hirokazu , Yahara Koji , Aoki Sadao , Sugawara Yo , Kajihara Toshiki , Shibayama Naomi , Kayama Shizuo , Suzuki Masato , Sugai Motoyuki 
Published: November 2024

Abstract

Background
Tigecycline is an antimicrobial agent with a broad spectrum of activity against both Gram-positive and Gram-negative bacteria. However, mobile tigecycline resistance gene clusters, such as tnfxB-tmexCD-toprJ, have spread globally. The prevalence of tigecycline-resistant Enterobacterales in clinical settings in Japan is unknown.

Objectives
To investigate the tnfxB-tmexCD-toprJ gene cluster in the genome sequences of Enterobacterales clinical isolates in Japan.

Methods
We investigated the tnfxB-tmexCD-toprJ cluster from the genome sequences of 5143 Enterobacterales isolates collected from 175 hospitals around Japan between 2019 and 2020 as part of a national genomic surveillance program for antimicrobial-resistant bacteria.

Results
The tnfxB1-tmexCD1-toprJ1 cluster was detected in two Klebsiella pneumoniae isolates in 2019. One isolate possessed a 299.4 kb IncFIB(K) plasmid, pJBBGAAF19431, and the other possessed a 224.9 kb IncHI1B/IncFIB(K) hybrid plasmid, pJBEAACG19501, co-carrying multiple antimicrobial resistance genes, including extended-spectrum β-lactamase genes, blaOXA-1 and blaCTX-M-27, respectively, along with tnfxB1-tmexCD1-toprJ1. The genetic context of the tnfxB1-tmexCD1-toprJ1-surrounding structure on pJBBGAAF19431 was similar to that of a K. pneumoniae plasmid pHNAH8I-1 from a chicken in China in 2017, and the cluster was embedded in an apparently intact mobile DNA element: strand-biased circularizing integrative element. The tnfxB1-tmexCD1-toprJ1 on pJBEAACG19501 was embedded in a Tn3 family transposon related to TnAs1. The plasmid pJBEAACG19501 was highly similar to that of K. pneumoniae, isolated from humans in China in 2021.

Conclusions
tmexCD-toprJ was present in Japan as of 2019. Even in Japan, where the clinical use of tigecycline is significantly rare, tmexCD-toprJ-harbouring multidrug-resistant Enterobacterales is a public health threat and requires continuous monitoring.
Toward the bioleaching of bauxite residue by Gluconobacter oxydans
Authors: van Wyk Nathan , Fischer Dorte , Wilbers Derik , Harrison Susan T L , Kotsiopoulos Athanasios , Dopson Mark 
Published: November 2024

Abstract

Aim
This project evaluated a biologically mediated strategy to solubilize several rare earth elements and critical raw materials, including scandium, from bauxite residue. This work seeks to expand on previous research on contact leaching with bauxite.

Methods and results
In this study, Gluconobacter oxydans was shown to secrete mixed organic acids, including gluconic acid, which was superior to pure gluconic acid in the dissolution of bauxite residue, even at low molarities. In situ contact leaching with G. oxydans significantly promoted the dissolution yield (recovery of metal present in the ore) of yttrium, aluminum, calcium, and titanium (41.18%, 67.79%, 80.16%, and 59.41%, respectively) but allowed for only marginal dissolution yield of scandium, lanthanum, cerium, and neodymium (13.40%, 14.74%, 24.41%, and 10.67%, respectively) at relatively low pulp densities. In addition, the dissolution yields of rare earth elements were reduced further with time, presumably as the oxides of these elements fell out of solution.

Conclusion
This work builds on previous research that seeks to extract rare earth elements and critical raw materials from bauxite residue through contact leaching with organic acids. Some elements such as yttrium, aluminum, calcium, and titanium could be effectively solubilized; however some elements showed reduced solubility, possibly due to tight association with the iron phase of the residue. However, the relative ease and speed of leaching, and improved solubilization, suggest that this could be a viable method for securing critical raw material supplies.
Bcl2l12, a novel protein interacting with Arf6, triggers Schwann cell differentiation programme
Authors: Miyata Wakana , Sakaibara Naoko , Yoshinaga Kentaro , Honjo Asahi , Takahashi Mikito , Ooki Tatsuya , Yako Hideji , Sango Kazunori , Miyamoto Yuki , Yamauchi Junji 
Published: November 2024

Abstract
Schwann cells are glial cells in the peripheral nervous system (PNS); they wrap neuronal axons with their differentiated plasma membranes called myelin sheaths. Although the physiological functions, such as generating saltatory conduction, have been well studied in the PNS, the molecular mechanisms by which Schwann cells undergo their differentiation programme without apparent morphological changes before dynamic myelin sheath formation remain unclear. Here, for the first time, we report that Arf6, a small GTP/GDP-binding protein controlling morphological differentiation, and the guanine–nucleotide exchange factors cytohesin proteins are involved in the regulation of Schwann cell differentiation marker expression in primary Schwann cells. Specific inhibition of Arf6 and cytohesins by NAV-2729 and SecinH3, respectively, decreased expression of marker proteins 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) and glial fibrillary acidic protein (GFAP). Similar results using promoter assays were observed using the IMS32 Schwann cell line. Furthermore, using an affinity-precipitation technique, we identified Bcl2-like 12 (Bcl2l12) as a novel GTP-bound Arf6-interacting protein. Knockdown of Bcl2l12 using a specific artificial miRNA decreased expression of marker proteins. The knockdown also led to decreased filamentous actin extents. These results suggest that Arf6 and Bcl2l12 can trigger Schwann cell differentiation, providing evidence for a molecular relay that underlies how Schwann cells differentiate.
Consumers Prefer Products That Work Using Directionally Consistent Causal Chains
Authors: Bharti Soaham , Sussman Abigail B 
Published: November 2024

Abstract
Products often aim to help consumers achieve desired outcomes such as increasing energy levels or removing fabric stains. These products typically work via rich causal paths. The current research suggests that the structure of these paths influences consumer judgments of product efficacy. In particular, sequential steps in these paths can evoke distinct directionalities—either increasing or decreasing variables in each step along the way. For example, a face cream could be described as “increasing the turnover of skin cells to reduce wrinkles.” Under our framework, the action influencing skin cells would correspond to increasing directionality, while the action influencing wrinkles would correspond to decreasing directionality. Ten experiments provide evidence that consumers prefer products with directionally consistent causal chains (ie, all steps evoking the same directionality) over those with directionally inconsistent ones (ie, steps evoking contrasting directionalities). This occurs because consumers find directionally consistent causal chains easier to process which in turn leads them to infer higher efficacy from products working via such consistent chains. These findings advance our understanding of how consumers evaluate product descriptions and provide prescriptions for marketers tasked with composing product descriptions to convey efficacy.
Foraging behavior and work patterns of Bombus terrestris (Hymenoptera: Apidae) in response to tomato greenhouse microclimate
Authors: Wang Huan , Qu Yanyan , He Xujiang , Xu Xi-lian , Wang Rufang , Xue Meijing , Zeng Zhi-jiang 
Published: November 2024

Abstract
Bumblebees play a significant role as pollinators for many wild plants and cultivated crops, owing to their elongated proboscis, resilience to diverse weather conditions, robustly furred bodies, and their unique capacity for buzz-pollination. To better understand the effect of greenhouse microclimates on bumblebee foraging behavior and working modes, a long-term record of foraging activity for each Bombus terrestris L. (Hymenoptera: Apidae) forager was monitored by the Radio-frequency identification system. The pattern of task performance, including constant housing, foraging, and day-off rotation, was examined under the microclimate. In addition, the correlation between foraging activity of bumblebees and temperature, relative humidity, illumination in the greenhouse, and pollen viability of tomato plants was further analyzed. Our findings revealed that B. terrestris can respond to microclimatic factors and plant resources while also exhibiting a suitable working pattern within the colony. Day-off rotation was observed as a strategy employed by foragers to prolong their survival time. This division of labor and task rotation may serve as strategies for the survival and development of the colony. Our research may contribute to fully understanding how microclimate and plants influence pollinator behavior within greenhouses, thereby optimizing the pollination management of bumblebees on greenhouse crops.
Combining sterile insect releases with refuge areas to delay the evolution of resistance to Bt sugarcane: an agent-based modeling approach
Authors: Potgieter Linke , Human Dirk J , Downing Samantha 
Published: November 2024

Abstract
The strategic use of refuge areas is a well-known method for delaying the development of pest resistance to Bacillus thuringiensis (Bt) crop. A lesser-known method to control against resistance development is sterile insect releases. In this article, an agent-based simulation model is used to test the effectiveness of combining the use of Bt sugarcane, refuge areas, and sterile insect releases as an integrated strategy against Eldana saccharina Walker (Lepidoptera: Pyralidae) infestation and resistance development. Individual insects are modeled with their own genetic traits on a simulated sugarcane field that represents either Bt or refuge area. The model is applied to 2 hypothetical case studies. In the first experiment, resistance development and infestation dynamics in Bt sugarcane without refuge areas are considered using various sterile:wild sterile release ratios, and different release distributions. In the second experiment, the inclusion of a refuge area in Bt sugarcane is considered, using various sterile:wild releases ratios and different release distributions. A trade-off between sterile insect releases and the use of the refuge area was observed, and could, in some cases, work against each other.
Glutamine modulates neutrophil recruitment and effector functions during sterile inflammation
Authors: Hellenthal Katharina E M , Thomas Katharina , Ludwig Nadine , Cappenberg Anika , Schemmelmann Lena , Tekath Tobias , Margraf Andreas , Mersmann Sina , Henke Katharina , Rossaint Jan , Zarbock Alexander , Amini Wida 
Published: November 2024

Abstract
During sterile inflammation, tissue damage induces excessive activation and infiltration of neutrophils into tissues, where they critically contribute to organ dysfunction. Tight regulation of neutrophil migration and their effector functions is crucial to prevent overshooting immune responses. Neutrophils utilize more glutamine, the most abundant free α-amino acid in the human blood, than other leukocytes. However, under inflammatory conditions, the body's requirements exceed its ability to produce sufficient amounts of glutamine. This study investigates the impact of glutamine on neutrophil recruitment and their key effector functions. Glutamine treatment effectively reduced neutrophil activation by modulating β2-integrin activity and chemotaxis in vitro. In a murine in vivo model of sterile inflammation induced by renal ischemia-reperfusion injury, glutamine administration significantly attenuated neutrophil recruitment into injured kidneys. Transcriptomic analysis revealed, glutamine induces transcriptomic reprograming in murine neutrophils, thus improving mitochondrial functionality and glutathione metabolism. Further, glutamine influenced key neutrophil effector functions, leading to decreased production of reactive oxygen species and formation of neutrophil extracellular traps. Mechanistically, we used a transglutaminase 2 inhibitor to identify transglutaminase 2 as a downstream mediator of glutamine effects on neutrophils. In conclusion, our findings suggest that glutamine diminishes activation and recruitment of neutrophils and thus identify glutamine as a potent means to curb overshooting neutrophil responses during sterile inflammation.