bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Latent Class Analysis to Identify Subgroups of Post-Operative Older Adults
Authors: McLaughlin Kevin , Bettencourt Amie , Young Daniel , Hoyer Erik , Friedman Michael , Colantuoni Elizabeth , Goeddel Lee A. , Gozalo Pedro
Published: January 2025

Objective

Identify subgroups of postoperative older adults using electronic health record data.

Summary of Background Data

Postoperative older adults represent a vulnerable population who may benefit from tailored postoperative care pathways. Identifying clinical subgroups can inform the development of these pathways.

Methods

Retrospective cohort study of postoperative adults>65 years (N=2,036) from a single healthcare system. Latent class analysis was used to identify patient subgroups based on measures of frailty, mobility, activities of daily living, and general health status. Hospital outcomes were described among each subgroup, including extended lengths of stay (LOS) (>0.5 SD beyond mean LOS by surgical category), discharge disposition (i.e., home versus non-home discharge), and utilization (weekly visit frequency) of physical therapy (PT) and occupational therapy (OT).

Results

We identified 3 subgroups that we labeled Low Frailty-High Mobility (LF-HM), High Frailty-Low Mobility (HF-LM), and Low Frailty-Low Mobility (LF-LM), representing 15.3%, 27.6%, and 57.1% of the cohort, respectively. Discharge to home was highest among the LF-HM group (99%), followed by LF-LM (96%), and HF-LM (77%). Extended LOS was most common among the HF-LM group (27%), followed by LF-LM (18%), and LF-HM (6%). PT and OT visit frequencies were highest in the HF-LM group followed by the LF-LM and LF-HM groups.

Conclusions

This study identified 3 subgroups of postoperative older adults using routinely collected patient data. These groups may help to identify patients with increased odds of non-home discharge, extended LOS, and higher utilization of PT and OT and may inform the development of tailored postoperative care pathways for older adults.
Cohort-level analysis of humande novomutations points to drivers of clonal expansion in spermatogonia
Authors: Seplyarskiy Vladimir , Moldovan Mikhail A , Koch Evan , Kar Prathitha , Neville Matthew DC , Rahbari Raheleh , Sunyaev Shamil
Published: January 2025

In renewing tissues, mutations conferring selective advantage may result in clonal expansions1–3. In contrast to somatic tissues, mutations driving clonal expansions in spermatogonia (CES) are also transmitted to the next generation. This results in an effective increase ofde novomutation rate for CES drivers4–7. CES was originally discovered through extreme recurrence ofde novomutations causing Apert syndrome4. Here, we develop a systematic approach to discover CES drivers as hotspots of humande novomutation. Our analysis of 54,715 trios ascertained for rare conditions8–12, 6,065 control trios11,13–18, and population variation from 807,162 mostly healthy individuals19identifies genes manifesting rates ofde novomutations inconsistent with plausible models of disease ascertainment. We propose 15 genes hypermutable at loss-of-function (LoF) sites as candidate CES drivers. Additional 17 genes feature hypermutable missense mutations at individual positions, suggesting CES acting through gain-of-function (GoF). Among candidates are 5 of 13 known CES drivers6,7, 11 cancer drivers, and 16 members of major signaling pathways; notably, 12 genes show CES evidence in direct sperm sequencing20. CES increases the average mutation rate ∼16-fold for LoF genes in both control trios and sperm and ∼500-fold for pooled GoF sites in sperm. Positive selection in the male germline elevates the prevalence of genetic disorders and increases polymorphism levels, masking the effect of negative selection in human populations. Despite the excess of mutations in disease cohorts for 15 LoF CES driver candidates, only 5 show clear evidence of disease causality21, suggesting that CES may lead to false-positive disease associations.
Feasibility of real-time fMRI neurofeedback for rehabilitation of reading deficits in aphasia
Authors: Boukrina Olga , Yamin Abubakar , Yue Guang H , Kong Yekyung , Koush Yury
Published: January 2025

Background

Reading impairments, a common consequence of stroke-induced aphasia, significantly hinder life participation, affecting both functional and leisure activities. Traditional post-stroke rehabilitation strategies often show limited generalization beyond trained materials, underscoring the need for novel interventions targeting the underlying neural mechanisms.

Method

This study investigates the feasibility and potential effectiveness of real-time functional magnetic resonance imaging (fMRI) neurofeedback (NFB) intervention for reading deficits associated with stroke and aphasia. We enrolled left-hemisphere stroke survivors in the subacute recovery period and healthy controls in an fMRI NFB intervention study focusing on increasing activation within the left supramarginal gyrus (SMG), a critical region for reading supporting orthography-phonology conversion.

Results

Preliminary findings demonstrate that stroke participants showed significant improvements in reading comprehension and phonological awareness, as evidenced by marked gains on the Reading Comprehension Battery for Aphasia (RCBA) and a phonology two-alternative forced choice test. Functional MRI results indicated that stroke participants exhibited increased activation from day 1 to day 3 of NFB training within the left SMG and the broader left hemisphere reading network, particularly during challenging nonword reading tasks. Healthy controls also showed increased activation during NFB regulation and reading tasks, but these changes were outside the traditional reading network, involving regions associated with cognitive control, reward anticipation, and learning. In both stroke participants and healthy controls, we also found changes in dynamic functional connectivity of multiple resting state networks from before to after NFB training.

Conclusions

Although preliminary, this research contributes to the development of biologically informed interventions for reading deficits in aphasia, representing an early step towards improving post-stroke rehabilitation outcomes. Future randomized controlled trials are necessary to validate these findings by including a sham NFB control group within a larger participant sample.

Registration

The study was preregistered on ClinicalTrials.gov, NCT#NCT04875936
Pattern and association of immunoglobulin G antibodies to AMA1, GLURP, and MSP3 with protection from malaria in a cohort of Cameroonian children living in Mutengene: Anaemia a possible collateral damage?
Authors: Njua-Yafi Clarisse , Achidi Eric A. , Anchang-Kimbi Judith K. , Apinjoh Tobias O. , Mugri Regina N. , Chi Hanesh F. , Tata Rolland B. , Njumkeng Charles , Dodoo Daniel
Published: January 2025

Understanding the characteristics of naturally acquired immunity in different epidemiologic settings is essential for vaccine development and testing. The relationship between antibodies against four malaria vaccine candidate antigens and protection from malaria in a cohort of Cameroonian children was assessed. Immunoglobulin (Ig)G and IgG subclasses against recombinantPlasmodium falciparumapical membrane antigen 1 (AMA1), glutamate rich protein (GLURP) R0, GLURP R2 and merozoite surface protein 3 (MSP3) in the plasma of 357 Cameroonian children were measured by sandwich ELISA at three time points (baseline, 6 months and 12 months) during which time participants were monitored for malaria.Total IgG to all four antigens correlated positively with age (0.51≤ r ≤ 0.23, p < 0.001) at all three time points. Adjusting for age, total IgG, IgG1, IgG3, IgG2 (except for MSP3 IgG2) antibody levels to all four antigens were associated with protection against malaria parasitaemia at baseline. GLURP R0 IgG (F = 35.7, p < 0.001), GLURP R2 IgG (F = 16.5, p < 0.001), AMA1-3D7 IgG2 (F = 10.8, p < 0.001) and AMA1-3D7 IgG3 (F = 4.01, p = 0.019) decreased with a corresponding decrease in malaria cases (χ2= 10.4, p = 0.034) across the three time points, contrary to the increase observed in MSP3 IgG (F = 8.9, p < 0.001) and MSP3 IgG2 (F = 44.2, p < 0.001). Increased levels of AMA1-3D7 IgG [OR = 4.13, 95% CI (1.09 – 15.65), p = 0.037] and MSP3 IgG1 [OR = 8.16, 95% CI (1.06 – 62.64), p = 0.044] were associated with susceptibility to anaemia after controlling for age and parasitaemia.Total IgG, cytophilic subclasses and IgG2 to all the antigens (except MSP3 IgG2) were associated with malaria protection while MSP3 IgG seemed to persist longer. The relationship between malaria specific antibodies and anaemia warrants further studies.
Challenges and Facilitators for Physicians and Medical Schools to Promote Social Accountability in Rural Communities: A Scoping Review and Thematic Analysis
Authors: Wasim Aghna , Abud Ali , Wang Yihan , Tavakoli Ehsan , Moreno-Gris Athena , Joshi Samar , Wang Arthur , Neasadurai Angela , Shaw Nikki
Published: January 2025

Background

Social accountability aligns the health demands and priorities of the community and the commitment of medical schools. Existing literature has proposed contextually distinctive interventions encompassing geographical initiatives, acting networks or parties, and systematic categorizations for the implementation of social accountability in a rural setting. Research concerning social accountability implementation strategies has been insufficient. This study provides an overview of the existing literature surrounding the social accountability practice of physicians and medical schools, in rural settings, through evidence of the barriers and facilitators inherent to the rural communities.

Methods

This scoping review was conducted following the Arksey and O’Malley Framework. Web of Science, MEDLINE, EMBASE, SCOPUS, and CINAHL were searched for peer-reviewed studies published since 2000.

Results

A total of 2698 abstracts were identified, 180 full-text articles were reviewed, and 53 articles met the eligibility criteria across 15 different countries. Strategies used and problems inherent in promoting social accountability across physician practice and medical education are reported.

Conclusions

This scoping review synthesizes existing evidence on the barriers and facilitators of social accountability practices in rural settings globally. The identified literature captures recurring themes of medical infrastructure inadequacy, community immersion curriculum design, targeted admission, geographical isolation, and institutional or peer support.
Engineered Living Glues for Autonomous Detection and On-Demand Treatment of Inflammatory Bowel Disease
Authors: Ge Changhao , Jiang Shanshan , Dong Xiaomin , Jiang Xiaoyu , Zhi Weiliang , Xiang Yunqing , Yang Peilang , Zhang Qian , Chen Xin , Liu Yan , Huang Shuqiang , Liu Yifan , Lin Jing , An Bolin , Huang Peng , Zhong Chao
Published: January 2025

Smart biomaterials capable of autonomously sensing pathological conditions and executing targeted medical interventions offer therapeutic advantages over conventional passive biomaterials. However, their development remains a considerable challenge. Here, we introduce a therapeutic “living glue” for the automatic detection and on-demand treatment of inflammatory bowel disease (IBD). This living glue employs a genetically engineered, non-pathogenicEscherichia coliwith a highly sensitive blood-inducible gene circuit to monitor gastrointestinal bleeding, a key indicator of severe IBD. Upon detection, the bacteria respond by producing potent adhesive and therapeutic proteins around bleeding sites, enabling robust attachment to inflamed tissues and sustained treatment. In a dextran sulfate sodium (DSS)-induced mouse model, a single rectal administration of the living glue markedly improved weight recovery, reversed colonic shortening, and reduced intestinal bleeding. Additionally, the living glue decreased intestinal inflammation, promoted mucosal repair, and restored gut barrier integrity, demonstrating comprehensive therapeutic effects in alleviating IBD symptoms. This study highlights the potential of integrating programmable, living components into biomaterials for autonomous, targeted, and enhanced medical interventions.
High-efficiency Kemp eliminases by complete computational design
Authors: Listov Dina , Vos Eva , Hoffka Gyula , Hoch Shlomo Yakir , Berg Andrej , Hamer-Rogotner Shelly , Dym Orly , Kamerlin Shina Caroline Lynn , Fleishman Sarel J.
Published: January 2025

We present a fully computational workflow for de novo design of efficient enzymes using backbone fragments from natural proteins and without recourse to iterative experimental optimization. The best designed Kemp eliminase exhibits >140 mutations from any natural protein, high stability (>85 °C) and unprecedented catalytic efficiency (12,700 M-1s-1), surpassing previous computational designs by two orders of magnitude. We find that mutations both inside and outside the active site contribute synergistically to the high observed activity and stability. Mutation of an aromatic residue used in all prior Kemp eliminase designs increases efficiency to >10^5 M-1s-1. Our approach addresses critical limitations in design methodology, generating stable, high-efficiency, new-to-nature enzymes in complex folds and enables testing hypotheses on the fundamentals of biocatalysis through a limited experimental effort.
Pea-Saving Partners: Bacillus and Pseudomonas combat downy mildew in pea crops
Authors: Okechukwu Emeka Chibuzor , Jimenez-Quiros Catherine , Baysal Ömür , Kocamaz Süreyya , Arıkan Burhan , Webb Anne , Wood Thomas , Arora Sanu , Domoney Claire , Studholme David J. , Tör Mahmut
Published: January 2025

Downy mildew (DM) is a destructive disease that significantly reduces the yield and quality of important pulses (legumes) and horticultural crops, particularly during humid and cool seasons. This disease is caused by obligate and host-specific oomycete pathogens. Controlling the pathogen is challenging due to its long-term survival as spores and its rapid mutation. Use of chemical pesticides has been the most effective method to control DM pathogens, but their environmental hazards are a global concern. Current research is focused on exploring the potential of microbial biological control agents (MBCA), particularly rhizobacteria strains of the generaBacillusandPseudomonas, which have shown suppression of plant pathogens. However, to date, no MBCA has been reported to be effective against DM pathogens in pulses. We investigated the effectiveness ofBacillusandPseudomonasstrains as potential biopesticides against the pea downy mildew pathogenPeronospora viciaef. sp.pisi(Pvp). In our study,in vitrobioassays showed 100% inhibition ofPvpspore germination compared to the control.In plantaantagonism assays further demonstrated significant suppression (>80%) ofPvpsporulation in pea plants sprayed with strains ofBacillus velezensisorP. fluorescensor their filtrates. The drench application also showed significant effects where either aPseudomonasor cold-adaptedBacillusstrain was used. We observed a synergistic effect for the dual foliar application of the microbes compared to individual application (27.6 to 46.7% suppression). Furthermore, the results from the molecular biomass analysis were consistent with the results of the sporulation assays. This demonstrates the strong interactive and promotive benefits of usingBacillusandPseudomonasas biocontrol agents Based on these results, we conclude that these MBCAs could be effective in combattingPvpinfections in the field.
Ten species comprise half of the bacteriology literature, leaving most species unstudied
Authors: Jensen Paul A.
Published: January 2025

Microbiology research has historically focused on a few species of model organisms. Our bibliographic analysis finds extreme bias in the distribution of bacteriology research across species, with half of all papers referencing only ten species and 74% of all known species remaining unstudied. Microbiologists will need to broaden their perspective and embrace complexity to develop a complete understanding of the microbial world.
Single-cell multiomics data integration and generation with scPairing
Authors: Niu Jeffrey , Ding Jiarui
Published: January 2025

Single-cell multiomics technologies generate paired or multiple measurements of different cellular properties (modalities), such as gene expression and chromatin accessibility. However, multiomics technologies are more expensive than their unimodal counterparts, resulting in smaller and fewer available multiomics datasets. Here, we present scPairing, a variational autoencoder model inspired by Contrastive Language-Image Pre-Training, which embeds different modalities from the same single cells onto a common embedding space. We leverage the common embedding space to generate novel multiomics data following bridge integration, a method that uses an existing multiomics bridge to link unimodal data. Through extensive benchmarking, we show that scPairing constructs an embedding space that fully captures both coarse and fine biological structures. We then use scPairing to generate new multiomics data from retina and immune cells. Furthermore, we extend to co-embed three modalities and generate a new trimodal dataset of bone marrow immune cells. Researchers can use these generated multiomics datasets to discover new biological relationships across modalities or confirm existing hypotheses without the need for costly multiomics technologies.
Natural variation modifies centromere proximal meiotic crossover frequency and segregation distortion in Arabidopsis thaliana
Authors: Gorringe Nicola , Topp Stephanie , Burns Robin , Yamaguchi Sota , Rabanal Fernando A , Fernandes Joiselle B. , Weigel Detlef , Kakutani Tetsuji , Naish Matthew , Henderson Ian R
Published: January 2025

Background: Centromeres mediate chromosome segregation during cell division. In plants, centromeres are loaded with CENH3-variant nucleosomes, which direct kinetochore formation and spindle microtubule interaction. Plant centromeres are frequently composed of megabase-scale satellite repeat arrays, or retrotransposon nests. In monocentric genomes, such as Arabidopsis thaliana, extended regions of pericentromeric heterochromatin surround the CENH3-occupied satellite arrays. A zone of suppressed meiotic crossover recombination contains the centromere and extends into the pericentromeres. Here, we explore how Arabidopsis natural genetic variation influences centromere-proximal crossover frequency, and segregation distortion through meiosis, when homologous centromeres are structurally heterozygous. Results: We used fluorescent crossover reporters to survey the effect of natural variation on centromere-proximal recombination in twelve F1 hybrids, capturing Arabidopsis Eurasian and relict diversity. The majority of F1 hybrids showed either elevated or suppressed centromere-proximal crossovers (49 of 60), relative to inbreds. We relate hybrid crossover frequencies to patterns of centromeric structural variation, and in a subset of accessions, to epigenetic patterns of CENH3 loading and DNA methylation. The fluorescent reporters also allow segregation distortion through meiosis to be compared between inbred and hybrid strains. We observed a minority of hybrids (18 of 60) with distorted segregation through meiosis compared to inbreds, with and without simultaneous change to centromere-proximal crossover frequency. Conclusions: We reveal a complex relationship between centromere structural variation, epigenetic state, crossover recombination, and segregation distortion. We propose a model for how Arabidopsis centromere structural heterozygosity may cause segregation distortion during female meiosis.
Tripartite loops reverse antibiotic resistance
Authors: Chowdhury Farhan R. , Findlay Brandon L.
Published: January 2025

Antibiotic resistance threatens to undo many of the advancements of modern medicine. A slow antibiotic development pipeline makes it impossible to outpace bacterial evolution, making alternative strategies essential to combat resistance. In this study, we introduce cyclic antibiotic regimens composed of three drugs or “tripartite loops” to contain resistance within a closed drug cycle. We show that as bacteria sequentially evolve resistance to the drugs in a loop, they continually trade their past resistance for fitness gains, reverting back to sensitivity. Through fitness and genomic analyses, we find that tripartite loops guide bacterial strains towards evolutionary paths that mitigate fitness costs and reverse resistance to component drugs in the loops and drive levels of resensitization not achievable through previously suggested pairwise regimens. These findings open the door to sequential antibiotic regimens with high resensitization frequencies which will improve the longevity of existing antibiotics even in the face of antibiotic resistance.

TOC
Machine learning segmentation tool trained on synthetic data for tracking cytoskeleton polymerisation and depolymerisation
Authors: Elangovan Karan , Spelman Tamsin A. , Dupouy Gilles , Singh Gaurav , Chaboute Marie-Edith , Jonsson Henrik
Published: January 2025

The cytoskeleton is important in controlling the growth and morphology of plant cells, so tracking its morphological changes is essential. Here, we develop a new machine learning based segmentation tool for microtubules (MTs), which can distinguish between polymerised and depolymerised fibres. To circumvent the low abundance of data, we trained on synthetic images of microtubules from a computational micro-tubule model, pre-processed to reproduce microscope effects and partial depolymerisation. We used this tool to investigate how the MT network in anArabidopsis thalianaroot hair cell repolymerises after depolymerisation under Oryzalin (OZ) drug treatments. Specifically, we show the network initially repolymerises from the shank region. This work demonstrates the viability of using synthetic data to train machine learning systems handling cytoskeletal image data.
Mechanism-Based Inhibition of Histone Deacetylase 6 by a Selenocyanate is Subject to Redox Modulation
Authors: Stollmaier Juana Goulart , Czarnecki B. Abigail R. , Christianson David W.
Published: January 2025

Organoselenocyanates have attracted considerable attention in recent years due to their therapeutic potential and versatility in medicinal chemistry. Here, we report on the mechanism of inhibition by 5-phenylcarbamoylpentyl selenocyanide (SelSA-2), an analogue of the well-characterized histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA, a.k.a. Vorinostat). We show that histone deacetylases 6 and 10 can promote selenocyanate hydrolysis to generate a selenolate anion, and we explore the redox chemistry of selenium as it modulates inhibitory activity through reversible formation of the diselenide. The 2.15 Å-resolution crystal structure of histone deacetylase 6 cocrystallized with SelSA-2 conclusively demonstrates that it is not the selenocyanate, but instead the selenolate anion, that is the active pharmacophore responsible for enzyme inhibition.
Gamma-aminobutyric acid treatment reduces estradiol-stimulated breast cancer cell growth and estradiol-induced breast tumorigenesis
Authors: Nakamura Akihiro , Tanaka Sunao , Shimizu Haruna , Hokazono Hideki , Toi Masakazu , Itou Junji
Published: January 2025

Gamma-aminobutyric acid (GABA) is a non-protein amino acid and contained in various foods, such as fruits and vegetables. Although various health benefits of GABA have been reported, GABA seems to have unidentified functions. In this study, we first show increase in intracellular GABA level in GABA-treated breast cancer cell lines, MCF-7 and T-47D, in amino acid analyses and immunofluorescence. In our experimental condition, GABA treatment reduced estradiol-stimulated cell growth in these cell lines. In addition, we performed mouse early breast cancer induction model system to investigate GABA function in mammary dysplasia formation. In the results, GABA administration reduced dysplasia formation, suggesting that GABA prevents breast tumorigenesis. This study demonstrates a novel function of GABA to maintain normal breast tissues.
Oxygen Transport in Nanoporous SiN Membrane Compared to PDMS and Polypropylene for Microfluidic ECMO
Authors: Imtiaz Nayeem , Stoddard William A. , Day Steven W.
Published: January 2025

Extracorporeal Membrane Oxygenation (ECMO) serves as a crucial intervention for patients with severe pulmonary dysfunction by facilitating oxygenation and carbon dioxide removal. While traditional ECMO systems are effective, their large priming volumes and significant blood-contacting surface areas can lead to complications, particularly in neonates and pediatric patients. Microfluidic ECMO systems offer a promising alternative by miniaturizing the ECMO technology, reducing blood volume requirements, and minimizing device surface area to improve safety and efficiency. This study investigates the oxygen transport performance of three membrane types— polydimethylsiloxane (PDMS), polypropylene, and a novel nanoporous silicon nitride (SiN) membrane—in a microfluidic ECMO platform. While nanoporous membranes rely on pore-mediated diffusion and PDMS on polymer lattice diffusion, results show no significant differences in device oxygenation efficiency (p > 0.05). Blood-side factors, including the diffusion rate of oxygen through the red blood cell (RBC) membrane, RBC residence time, and hemoglobin binding kinetics, were identified as primary bottlenecks. Even computational models of a hypothetical infinitely permeable membrane corroborate the limited impact of membrane material. These findings suggest a shift in ECMO design priorities from membrane material to blood-side enhancements. This research provides a foundation for optimizing ECMO systems.
Olfactory Receptor Expression Profiles in Clear Cell Renal Cell Carcinoma Reveal Potential Diagnostic and Prognostic Markers
Authors: Hasegawa Kazuya , Yamaguchi Yuya
Published: January 2025

Background

Olfactory receptors (ORs) are G protein-coupled receptors that are aberrantly expressed in various cancers, including clear cell renal cell carcinoma (KIRC). However, the roles of ORs in KIRC are unknown. This study aimed to comprehensively analyze the expression profiles of OR genes in KIRC and evaluate their potential as diagnostic and prognostic biomarkers.

Methods

We analyzed RNA-seq data from The Cancer Genome Atlas KIRC dataset, which contains 72 normal and 530 tumor samples. We selected OR genes with median transcripts per million (TPM) values of 1 or higher in at least one group (normal or tumor). Differential expression analysis was performed using the Student’s t-test or Wilcoxon rank-sum test. The diagnostic potential of OR genes was evaluated using receiver operating characteristic (ROC) curve analysis. Kaplan-Meier analysis was employed to assess the association between OR gene expression and patient survival. Sex-based differences in OR gene expression were also examined.

Results

We identified 11 OR genes with significant changes in KIRC expression. Among them, OR2A4, OR51E1, and OR7E14P showed high diagnostic performance, with AUC values of 0.951, 0.924, and 0.910, respectively. Combining these three genes improved the AUC to 0.972. High OR2A20P expression was significantly associated with poorer prognosis, whereas high OR7E7P expression was associated with better prognosis. We also found sex-based differences in the expression of OR2A7, OR2I1P, and OR7E14P, with females exhibiting significantly higher expression.

Conclusions

Our findings suggest that ORs, especially OR2A4, OR51E1, and OR7E14P, could serve as potential diagnostic markers for KIRC. OR2A20P and OR7E7P may represent promising prognostic markers. The observed sex-based differences in OR gene expression highlight the need for personalized treatment of KIRC. Further studies are warranted to validate these findings and elucidate the functional roles of ORs in the pathogenesis of KIRC.
The Cost-effectiveness of a Continuous Glucose Monitoring Device for Adult Diabetes Patients in Ethiopia: A Semi-Markov Modelling Study
Authors: Mengesha Michael Endale
Published: January 2025

Background

Diabetes Mellitus is a chronic condition requiring regular blood glucose monitoring to prevent acute complications and long-term vascular damage. While standard glucometers are commonly used, continuous glucose monitoring (CGM) devices offer real-time insights into glucose fluctuations, improving glycemic control. However, cost-effectiveness data on CGM use in low-resource settings like Ethiopia remains limited.

Methods

A semi-Markov model was developed to evaluate the cost-effectiveness of CGM compared to standard self-monitoring of blood glucose in adult diabetes patients in Ethiopia. The analysis incorporated costs from a societal perspective and lifetime horizon, health utilities, and transition probabilities from local and global sources. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit (NMB) at a willingness-to-pay threshold of one times Ethiopia’s GDP per capita (ETB 165,000).

Results

CGM was associated with ICERs of ETB 155,625, ETB 135,353, and ETB 59,718 per QALY gained for males aged 20, 40, and 60 years, respectively. For females, the ICERs were higher at ETB 156,881, ETB 140,290, and ETB 69,791 per QALY for the same age groups, with cost-effectiveness improving with age. Net monetary benefit (NMB) results were positive for the average cohort starting age of 20, 40 and 60 in both male and female categories. One-way and probabilistic sensitivity analyses confirmed the robustness of these findings, with cost and health outcome discount rates identified as key drivers of parameter uncertainty.

Conclusion

CGM is a cost-effective intervention for diabetes management in Ethiopia, particularly in older adults. Its adoption could reduce complications and improve health outcomes, but affordability barriers for younger populations warrant further policy considerations.
Absolute Quantification of Aging-Associated Glycans in IgG for Biological Age Prediction: Insights from Glycomics and Transcriptomics
Authors: Zhao Huijuan , Fan Jiteng , Han Jing , Qin Wenjun , Sha Jichen , Zhang Weilong , Gu Yong , Ma Xiaonan , Gu Jianxin , Ren Shifang
Published: January 2025

Immunoglobulin G (IgG) N-glycans have been identified as associated with aging; however, previous studies predominantly quantified changes based on the relative percentages of each glycan within the total glycan pool, neglecting the absolute concentration changes of individual glycans. Additionally, relative quantification can limit practical applications, as these often require absolute concentration measurements for consistent and interpretable biomarker values. In this study, we introduce a novel strategy for discovering aging-associated IgG glycans and establishing a prediction model based on their absolute concentration alteration. We employed a glycome quantification technology to identify the alteration in IgG glycan amount in natural aging and anti-aging (caloric restriction) models, discovering aging-related glycans. The glycomics analysis revealed key features: downregulation of bisected glycan GP3 (F(6)A2B) and upregulation of digalactosylated glycan GP8 (F(6)A2G2). These glycan changes showed significant fold changes from an early stage. Using external standards of these two glycans, we subsequently measured the absolute concentrations of them, allowing us to establish a predictive model, abGlycoAge, for biological aging. The abGlycoAge index suggested a younger state under caloric restriction, with an average age reduction of 3.9-14 weeks. Additionally, we performed RNA sequencing on splenic B cells of mice, suggesting Derl3, Smarcb1, Ankrd55, Tbkbp1 and Slc38a10 could contribute to the alteration of GP3 and GP8 in aging. This analysis enhances our understanding of glycan alterations, accounts for individual variability, and aids in designing effective anti-aging strategies. These findings highlight the crucial roles of the GP3 and GP8 as potential biomarkers for aging and health.
NF-κB mediates transactivation of HNRNPD, resulting in PTEN destabilization and constitutive activation of the PI3K-AKT pathway in oral cancer cells
Authors: Kumar Vikas , Mittal Anjani , Kumar Anurag , Lone Moien Rasheed , Yadav Vandana , Verma Priya , Pradhan Dibyabhaba , Mishra Deepika , Thakar Alok , Chauhan Shyam Singh
Published: January 2025

Heterogeneous Ribonucleoprotein D (hnRNPD), an RNA binding protein transcriptionally upregulated by NF-κB transcription factor, is associated with poor outcome of Oral Squamous Cell Carcinoma (OSCC). However, the role of hnRNPD in OSCC remains elusive. This study reveals that hnRNPD positively affects the proliferation, migration, invasion, and survival of OSCC cells. Transcriptome profiling in hnRNPD knockout cells identified significant upregulation of PTEN and inhibition of the PI3K/AKT/mTOR axis. HnRNPD mediates the destabilization of PTEN mRNA by binding to the class II AU-Rich Element (ARE) in 3’UTR of PTEN. The expression of hnRNPD and PTEN are strongly negatively correlated in OSCC tissue specimens, further corroborating hnRNPD-mediated PTEN destabilization. The hnRNPD knockout inhibited autophagy, evident by an accumulation of autophagic vesicles and decreased autophagic flux. Mechanistically, the hnRNPD knockout reduced the expression of NF-κB, eventually downregulating its transcriptional target LC3b, a key mediator of autophagy. SA-β-Galactosidase staining in hnRNPD KO cells conclusively demonstrated the onset of cellular senescence. The present study demonstrates hnRNPD-driven positive modulation of autophagy via NF-κB, independent of the PI3K/AKT/mTOR axis, highlighting it as a novel therapeutic target for treating oral cancer.

Graphical Abstract

Highlights

HnRNPD mediates oral cancer cell proliferation, migration, invasion, and survival.

HnRNPD acts as a novel regulator of the PI3K/AKT/mTOR axis by destabilization of PTEN.

NF-κB/RelA downregulated on knockout of HNRNPD, inhibiting autophagy through downregulating its transcriptional target LCB-II.

HnRNPD mediates cellular senescence in oral cancer cells.
C. elegansinterprets dietary quality through context-dependent serotonergic modulation
Authors: Feng Likui , Marquina-Solis Javier , Yue Lishu , Harnagel Audrey , Greenfeld Yarden , Bargmann Cornelia I.
Published: January 2025

Animals sense their metabolic needs to guide foraging decisions using neuronal pathways that are only partly understood. Here, we systematically investigate how foraging in the nematodeCaenorhabditis elegansis influenced by its bacterial diet,E. coli. By screeningC. elegansbehavior on 3983E. coliknockout strains, we identified 22E. colimetabolic mutants that are aversive toC. elegansin a long-term foraging assay. These include the global metabolic regulator CRP and genes affecting cysteine synthesis, vitamin B6 synthesis, and iron uptake. Serotonin, a neurotransmitter associated with feeding in many animals, allowsC. elegansto distinguish wild-typeE. colifrom these “mediocre” diets through bidirectional signaling. Serotonin produced by the ADF serotonergic neurons supports attraction to wild-typeE. coliwith the serotonin receptor genesser-4andser-5, whereas serotonin produced by the NSM serotonergic neurons differentially drives aversion to two mediocre diets through four serotonin receptor genes,ser-1, ser-7, mod-1,andlgc-50.Serotonin receptors act in multiple target neurons, including octopamine-producing neurons that suppress aversion across all diets. In addition, dopamine promotes aversion, in part by inhibiting octopaminergic neurons. These results reveal interactions between neuromodulatory circuits in the context-dependent evaluation of dietary quality.
Caribbean octocoral communities: finding the forest for the trees?
Authors: Lasker Howard R , Bramanti Lorenzo , Edmunds Peter J. , Girard John F. , Pages Nolwenn , Tonra Kaitlyn , Wells Christopher D. , Guizien Katell
Published: January 2025

Octocorals have increased in abundance on many Caribbean coral reefs, and at some sites “octocoral forest” may be a better community descriptor than “coral reef.” Implicit to the concept of a forest is that structural elements, trees, colonies, etc., alter the environment in ways that affect the structural elements themselves and the organisms that inhabit the forest. At what density do the structural elements create the emergent properties of a “forest?” Communities traditionally characterized as hardgrounds and coral reefs around Puerto Rico and St John, US Virgin Islands, varied in density of octocoral colonies from a few to >100 colonies m-2in surveys conducted in 2021 and 2022. Canopy cover was correlated with the density of colonies. Among the quadrats with the highest octocoral density there was no significant correlation between numbers of colonies and canopy cover. Frontal area, a measure related to the community’s effect on water flow, as well as the volume occupied by colonies followed patterns similar to canopy cover. Vertical profiles of flow velocity were measured from the substratum to 3 m above the bottom on a reef on St John where octocoral population density ranged from 0 to 16 colonies m-2. Profiles of orbital velocity exhibited perturbations which were more pronounced in locations with > 12 colonies m-2. Using the effect on flow as a criterion, 4 of the 8 surveyed sites would function as forests. Understanding the density at which emergent properties appear is critical to understanding the bio-physical interactions affecting the community.
Reinvigorating the future of young women micro entrepreneurs in sub-Saharan Africa post COVID-19: a SEM reflective model approach with debt literacy as the mediator
Authors: Okello Candiya Bongomin George , Semukono Frederick , Yourougou Pierre , Balinda Rebecca
Published: January 2025

Purpose

The purpose of this study is to test for the mediating effect of debt literacy in the relationship between microcredit access and the survival of micro, small and medium enterprises (MSMEs) owned and operated by young women in rural sub-Saharan Africa post COVID-19.

Design/methodology/approach

This study uses a five-point Likert scale questionnaire to collect data from young women entrepreneurs with MSMEs located in rural northern Uganda. The Statistical Package for Social Sciences (SPSS) and SmartPLS with bootstrapping are used to test the magnitude and level of the mediation effect as recommended by Baron and Kenny (1986) and Hair et al. (2022).

Findings

The results reveal that debt literacy increases the impact of microcredit on the survival of young women entrepreneurs with MSMEs in rural sub-Saharan Africa post COVID-19 based on data collected from rural northern Uganda.

Research limitations/implications

A questionnaire was used to collect data for this study. Future studies could collect data using interviews and the experimental research design to evaluate the effect of debt literacy over time.

Practical implications

This study provides valuable insights on the importance of debt literacy in microcredit access and the survival of MSMEs. The results of this study can be used to inform policy and guide practitioners on how to integrate debt literacy into the national educational and literacy curriculum.

Originality/value

This study brings into the limelight the important role of debt literacy in helping young women microentrepreneurs learn to be more cautious when taking on future debts and helping them become more resilient in the post COVID-19 pandemic situation. This topic of debt literacy is limited in the microcredit literature and the theory of microfinance in rural Uganda post COVID-19.
Impact of inclusive marketing communication on brand love and brand attitude
Authors: Srivastava Juhi , Malik Nishtha , Sethi Deepa , Tripathi Shalini Nath
Published: January 2025

Purpose

There is an emerging paradigm with reference to marketing communication, i.e. inclusive marketing communication (IMC). This calls for brands to be sincere with their customers and give due recognition and representation to underrepresented groups, communities and individuals. In this constantly evolving and globalized world, consumers have become more sensitive towards authentic portrayals of inclusivity and diversity by brands while choosing one brand over another.

Design/methodology/approach

A mixed method approach was used whereas in the first study, a quantitative method was used. Standardized questionnaire was used for collecting data through a time-lagged method. While the second study adopted the qualitative method. Semi-structured interviews were performed which lasted for 30–45 min for most of the participants.

Findings

It was found that IMC has a positive and noticeable effect on brand attitude (BA) and brand love (BL) when mediated by social identity (SI). While stigmatization was found to positively and significantly moderate the relationship between IMC and SI. Moreover, it was also found from both the studies that if a brand fails to strengthen the SI of an individual it doesn’t affect the BA as well as BL of customers.

Originality/value

Very few studies have incorporated a quantitative method of study while studying IMC. Furthermore, a collective study on different aspects of inclusivity like ethnicity, sexual orientation, disability, physical attractiveness, etc., has not been explored yet. Scattered studies on aspects like skin tone, body size, religion, etc., have been explored individually in prior studies.
Gender-based pricing in Japan: changes in consumer perception and reputational risks
Authors: Kunitake Yuto
Published: January 2025

Purpose

The purpose of this study is to elucidate the risks and changes in consumer awareness associated with gender-based pricing, particularly women’s exclusive discounts, in Japan. By examining the case of Gyu-Kaku’s half-price campaign exclusively for women implemented in 2024, the study investigates the legal and reputational risks faced by companies and the rising awareness of consumer diversity and fairness.

Design/methodology/approach

A mixed research method combining qualitative and quantitative analysis was adopted. Social trends and expert opinions were grasped through news articles and professional insights, and users’ reactions on X (formerly Twitter) were statistically analyzed from the perspective of sentiment analysis.

Findings

It was suggested that gender-based pricing, while pursuing short-term profits, may significantly harm a company’s brand image and long-term profits by ignoring consumer diversity and fairness. In particular, the study indicates a possible link between increased criticism of women’s exclusive discounts and the rising dissatisfaction among young men, who perceive selective application of gender equality amidst a heightened awareness of equality. Additionally, there was a significant increase in negative posts about Gyu-Kaku on X, and even after the total number of mentions decreased, the proportion of negative posts remained high.

Originality/value

This study is an initial attempt to comparatively examine the extent to which gender-based pricing is accepted by consumers in Japan. In a field with few prior studies, it presents new perspectives and hypotheses, proposing directions for future discussions.
The dispositif is alive! Recovering social agents in Foucauldian analysis
Authors: Gøtzsche‐Astrup Johan , Villadsen Kaspar
Published: January 2025

Michel Foucault's concept of the dispositif is increasingly salient in sociological scholarship. We identify and criticise an ‘anonymous’ emphasis in this scholarship, which often presents the dispositif as an anonymous network that acts without human agents. To remedy this tendency we develop an agent‐inclusive version of the dispositif for sociological research. Turning to Foucault's work from the 1970s, we recover descriptions of how social groups act as instigators of dispositifs through their invention of tactics and techniques. We develop these into an agent‐inclusive version of dispositional analytics and suggest five steps to pursue in empirical analysis. We exemplify these steps through a historical case of protesting. Finally, we show how our revisionist version of the dispositif meets critiques of Foucault's agentless approach and discuss the implication for a further integration of sociological research with dispositional analytics.
Lagging behind by doing good: How volunteering prolongs unemployment
Authors: Holstein Elisabeth Lilleøre , Qvist Hans‐Peter Y.
Published: January 2025

This study contributes new insights into whether volunteering improves the employment prospects of jobless individuals by examining its relationship with the speed at which they secure new jobs— an outcome that has received limited attention in previous research. Our comprehensive data enables us to investigate this by constructing an event history dataset that merges information from the Danish Volunteer Survey with administrative register data. Our results show that when we adjust for variations in education and labor market experience, jobless individuals who volunteer remain unemployed approximately two weeks or 31 percent longer than those who do not. Although our results remain correlational, they challenge the wisdom of promoting volunteering as a reemployment strategy, which some governments in European countries already do while others consider doing so. We recommend that policymakers reconsider the promotion of volunteering as a reemployment tool and call for further research into the relationship between volunteering and unemployment duration, particularly in different national contexts.
Can norm‐based information campaigns reduce corruption?
Authors: Erlich Aaron , Gans‐Morse Jordan
Published: January 2025

Can norm‐based information campaigns reduce corruption? Such campaigns use messaging about how people typically behave (descriptive norms) or ought to behave (injunctive norms). Drawing on survey and lab experiments in Ukraine, we unpack and evaluate the distinct effects of these two types of social norms. Four findings emerge: First, injunctive‐norm messaging produces consistent but relatively small and temporary effects. These may serve as moderately effective, low‐cost anti‐corruption tools but are unlikely to inspire large‐scale norm transformations. Second, contrary to recent studies, we find no evidence that either type of norm‐based messaging “backfires” by inadvertently encouraging corruption. Third, descriptive‐norm messages emphasizing corruption's decline produce relatively large and long‐lasting effects—but only among subjects who find messages credible. Fourth, both types of norm‐based messaging have a substantially larger effect on younger citizens. These findings have broader implications for messaging campaigns, especially those targeting social problems that, like corruption, require mitigation of collective action dilemmas.