bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin 11 therapy causes acute left ventricular dysfunction
Authors: Sweeney Mark , O’Fee Katie , Villanueva-Hayes Chelsie , Rahman Ekhlas , Lee Michael , Tam Chung Nga , Pascual-Navarro Eneko , Maatz Henrike , Lindberg Eric L , Vanezis Konstantinos , Ramachandra Chrishan J , Andrew Ivan , Jennings Emma R , Lim Wei-Wen , Widjaja Anissa A , Carling David , Hausenloy Derek J , Hübner Norbert , Barton Paul J R , Cook Stuart A
Published: October 2024

Aims

Interleukin 11 (IL11) was initially thought important for platelet production, which led to recombinant IL11 being developed as a drug to treat thrombocytopenia. IL11 was later found to be redundant for haematopoiesis, and its use in patients is associated with unexplained and severe cardiac side effects. Here, we aim to identify, for the first time, direct cardiomyocyte toxicities associated with IL11, which was previously believed cardioprotective.

Methods and results

We injected recombinant mouse lL11 (rmIL11) into mice and studied its molecular effects in the heart using immunoblotting, qRT-PCR, bulk RNA-seq, single nuclei RNA-seq (snRNA-seq), and assay for transposase-accessible chromatin with sequencing (ATAC-seq). The physiological impact of IL11 was assessed by echocardiography in vivo and using cardiomyocyte contractility assays in vitro. To determine the activity of IL11 specifically in cardiomyocytes, we made two cardiomyocyte-specific Il11ra1 knockout (CMKO) mouse models using either AAV9-mediated and Tnnt2-restricted (vCMKO) or Myh6 (m6CMKO) Cre expression and an Il11ra1 floxed mouse strain. In pharmacologic studies, we studied the effects of JAK/STAT inhibition on rmIL11-induced cardiac toxicities. Injection of rmIL11 caused acute and dose-dependent impairment of left ventricular ejection fraction (saline: 62.4% ± 1.9; rmIL11: 32.6% ± 2.9, P < 0.001, n = 5). Following rmIL11 injection, myocardial STAT3 and JNK phosphorylation were increased and bulk RNA-seq revealed up-regulation of pro-inflammatory pathways (TNFα, NFκB, and JAK/STAT) and perturbed calcium handling. snRNA-seq showed rmIL11-induced expression of stress factors (Ankrd1, Ankrd23, Xirp2), activator protein-1 (AP-1) transcription factor genes, and Nppb in the cardiomyocyte compartment. Following rmIL11 injection, ATAC-seq identified the Ankrd1 and Nppb genes and loci enriched for stress-responsive, AP-1 transcription factor binding sites. Cardiomyocyte-specific effects were examined in vCMKO and m6CMKO mice, which were both protected from rmIL11-induced left ventricular impairment and molecular pathobiologies. In mechanistic studies, inhibition of JAK/STAT signalling with either ruxolitinib or tofacitinib prevented rmIL11-induced cardiac dysfunction.

Conclusions

Injection of IL11 directly activates IL11RA/JAK/STAT3 in cardiomyocytes to cause acute heart failure. Our data overturn the earlier assumption that IL11 is cardioprotective and explain the serious cardiac side effects associated with IL11 therapy.
Optimized biomedical entity relation extraction method with data augmentation and classification using GPT-4 and Gemini
Authors: Phan Cong-Phuoc , Phan Ben , Chiang Jung-Hsien
Published: October 2024

Despite numerous research efforts by teams participating in the BioCreative VIII Track 01 employing various techniques to achieve the high accuracy of biomedical relation tasks, the overall performance in this area still has substantial room for improvement. Large language models bring a new opportunity to improve the performance of existing techniques in natural language processing tasks. This paper presents our improved method for relation extraction, which involves integrating two renowned large language models: Gemini and GPT-4. Our new approach utilizes GPT-4 to generate augmented data for training, followed by an ensemble learning technique to combine the outputs of diverse models to create a more precise prediction. We then employ a method using Gemini responses as input to fine-tune the BioNLP–PubMed–Bert classification model, which leads to improved performance as measured by precision, recall, and F1 scores on the same test dataset used in the challenge evaluation.

Database URL: https://biocreative.bioinformatics.udel.edu/tasks/biocreative-viii/track-1/
Hypokalaemia in patients with type 2 diabetes and chronic kidney disease: the effect of finerenone—a FIDELITY analysis
Authors: Pitt Bertram , Agarwal Rajiv , Anker Stefan D , Rossing Peter , Ruilope Luis , Herzog Charles A , Greenberg Barry , Pecoits-Filho Roberto , Lambelet Marc , Lawatscheck Robert , Scalise Andrea , Filippatos Gerasimos
Published: October 2024

Aims

Hypokalaemia is associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). This exploratory FIDELITY analysis, a prespecified pooled patient-dataset from FIDELIO-DKD and FIGARO-DKD, investigated the incidence and effect of hypokalaemia in patients with CKD and type 2 diabetes (T2D) treated with finerenone vs. placebo.

Methods and results

Outcomes include the incidence of treatment-emergent hypokalaemia (serum potassium <4.0 or <3.5 mmol/L) and the effect of finerenone on cardiovascular composite outcome (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) and arrhythmia composite outcome (new diagnosis of atrial fibrillation/atrial flutter, hospitalization due to arrhythmia, or sudden cardiac death) by baseline serum potassium subgroups. In the FIDELITY population, treatment-emergent hypokalaemia with serum potassium <4.0 and <3.5 mmol/L occurred in 41.1% and 7.5%, respectively. Hazards of cardiovascular and arrhythmia composite outcomes were higher in patients with baseline serum potassium <4.0 vs. 4.0–4.5 mmol/L [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.02–1.32, P = 0.022 and HR 1.20; 95% CI 1.00–1.44, P = 0.055, respectively]. Finerenone reduced the incidence of hypokalaemia with serum potassium <4.0 mmol/L (HR 0.63; 95% CI 0.60–0.66) and <3.5 mmol/L (HR 0.46; 95% CI 0.40–0.53) vs. placebo. Finerenone lessened the hazard of cardiovascular and arrhythmia events vs. placebo, irrespective of baseline serum potassium.

Conclusion

A substantial proportion of patients with CKD and T2D experienced hypokalaemia, which was associated with an increased hazard of adverse cardiovascular outcomes. Finerenone reduced the incidence of hypokalaemia. Finerenone reduced the hazard of cardiovascular and arrhythmia outcomes irrespective of serum potassium subgroups.

Clinical trials registration: FIDELIO-DKD and FIGARO-DKD are registered with ClinicalTrials.gov, numbers NCT02540993 and NCT02545049, respectively (funded by Bayer AG).
Coevolution promotes the coexistence of Tasmanian devils and a fatal, transmissible cancer
Authors: Clement Dale T , Gallinson Dylan G , Hamede Rodrigo K , Jones Menna E , Margres Mark J , McCallum Hamish , Storfer Andrew
Published: October 2024

Emerging infectious diseases threaten natural populations, and data-driven modeling is critical for predicting population dynamics. Despite the importance of integrating ecology and evolution in models of host–pathogen dynamics, there are few wild populations for which long-term ecological datasets have been coupled with genome-scale data. Tasmanian devil (Sarcophilus harrisii) populations have declined range wide due to devil facial tumor disease (DFTD), a fatal transmissible cancer. Although early ecological models predicted imminent devil extinction, diseased devil populations persist at low densities, and recent ecological models predict long-term devil persistence. Substantial evidence supports the evolution of both devils and DFTD, suggesting coevolution may also influence continued devil persistence. Thus, we developed an individual-based, eco-evolutionary model of devil–DFTD coevolution parameterized with nearly 2 decades of devil demography, DFTD epidemiology, and genome-wide association studies. We characterized potential devil–DFTD coevolutionary outcomes and predicted the effects of coevolution on devil persistence and devil–DFTD coexistence. We found a high probability of devil persistence over 50 devil generations (100 years) and a higher likelihood of devil–DFTD coexistence, with greater devil recovery than predicted by previous ecological models. These novel results add to growing evidence for long-term devil persistence and highlight the importance of eco-evolutionary modeling for emerging infectious diseases.
Evolutionary Adaptation in Heterogeneous and Changing Environments
Authors: Chaturvedi Nandita , Chatterjee Purba
Published: October 2024

Organisms that are adapting to long-term environmental change almost always deal with multiple environments and trade-offs that affect their optimal phenotypic strategy. Here, we combine the idea of repeated variation or heterogeneity, like seasonal shifts, with long-term directional dynamics. Using the framework of fitness sets, we determine the dynamics of the optimal phenotype in two competing environments encountered with different frequencies, one of which changes with time. When such an optimal strategy is selected for in simulations of evolving populations, we observe rich behavior that is qualitatively different from and more complex than adaptation to long-term change in a single environment. The probability of survival and the critical rate of environmental change above which populations go extinct depend crucially on the relative frequency of the two environments and the strength and asymmetry of their selection pressures. We identify a critical frequency for the stationary environment, above which populations can escape the pressure to constantly evolve by adapting to the stationary optimum. In the neighborhood of this critical frequency, we also find the counter-intuitive possibility of a lower bound on the rate of environmental change, below which populations go extinct, and above which a process of evolutionary rescue is possible.
Antifungal activity of poly(lactic acid) nanofibers containing the essential oil from Corymbia citriodora Hook or the monoterpenes β-citronellol and citronellal against mycotoxigenic fungi
Authors: Caetano Alex Rodrigues Silva , Cardoso Maria das Graças , de Oliveira Juliano Elvis , Batista Luiz Roberto , Alves Eduardo , Natarelli Caio Vinicius Lima , Campolina Gabriela Aguiar , Ferreira Vanuzia Rodrigues Fernandes , Nelson David Lee
Published: October 2024

Food contamination by mycotoxigenic fungi is one of the principal factors that cause food loss and economic losses in the food industry. The objective of this work was to incorporate the essential oil from Corymbia citriodora Hook and its constituents citronellal and β-citronellol into poly(lactic acid) nanofibers; to characterize the nanofibers by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy and differential scanning calorimetry; to evaluate the antifungal activity by the fumigation method; to evaluate the antimycotoxigenic activity against Aspergillus carbonarius, Aspergillus ochraceus, Aspergillus westerdijkiae, Aspergillus flavus, and Aspergillus parasiticus; and to evaluate the morphology of these microorganisms. All the nanofibers had a regular, smooth, and continuous morphology. FTIR analyses confirmed that the active ingredients were incorporated into the polymer matrix. All samples exhibited antifungal and ochratoxigenic inhibitory activities of up to 100% and 99%, respectively, with the best results observed for (PLA + 30 wt% β-citronellol) nanofibers and (PLA + 30 wt% citronellal) nanofibers. However, 100% inhibition of the production of aflatoxin B1 and B2 was not observed. The images obtained by SEM indicated that the nanofibers caused damage to the hyphae, caused a decrease in the production of spores, and caused deformation, rupture, and non-formation of the conid head, might be an alternative for the control of mycotoxigenic fungi.
There are multiple clocks that time us: Cross-sectional and longitudinal associations among 14 alternative indicators of age and aging
Authors: Drewelies Johanna , Homann Jan , Vetter Valentin Max , Duezel Sandra , Kühn Simone , Deecke Laura , Steinhagen–Thiessen Elisabeth , Jawinski Philippe , Markett Sebastian , Lindenberger Ulman , Lill Christina M , Bertram Lars , Demuth Ilja , Gerstorf Denis
Published: October 2024

Aging is a complex process influenced by mechanisms operating at numerous levels of functioning. Multiple biomarkers of age have been identified, yet we know little about how the different alternative age indicators are intertwined. In the Berlin Aging Study II (nmin= 328; nmax= 1,517, women = 51%; 14.27 years of education), we examined how levels and seven-year changes in indicators derived from blood assays, MRI brain scans, other-ratings, and self-reports converge among older adults. We included eight epigenetic biomarkers (incl. five epigenetic “clocks”), a BioAge composite from clinical laboratory parameters, brain age, skin age, subjective age, subjective life expectancy, and future health horizon. We found moderate associations within aging domains, both cross-sectionally and longitudinally over seven years. However, associations across different domains were infrequent and modest. Notably, participants with older BioAge had correspondingly older epigenetic ages. Our results suggest that different aging clocks are only loosely interconnected and that more specific measures are needed to differentiate healthy from unhealthy aging.
Functional Impairments, Phenotypic Frailty, and Sector-Specific Incremental Healthcare Costs in Older Adults
Authors: Ensrud Kristine E , Schousboe John T , Kats Allyson M , Taylor Brent C , Duan-Porter Wei , Sheets Kerry M , Boyd Cynthia M , Cawthon Peggy M , Langsetmo Lisa
Published: October 2024

Background

This study quantifies incremental healthcare expenditures of functional impairments and phenotypic frailty in specific healthcare sectors.

Methods

Pooled 2023 analysis of 4 prospective cohort studies linked with Medicare claims including 4 318 women and 3 847 men attending an index examination (2002–2011). Annualized inpatient, skilled nursing facility (SNF), home healthcare (HHC), and outpatient costs (2023 dollars) ascertained for 36 months following index examination. Functional impairments (difficulty performing 4 activities of daily living) and frailty phenotype (operationalized using 5 components) derived from cohort data. Weighted multimorbidity index including demographics derived from claims.

Results

Mean age at index examination was 79.2 years. After accounting for multimorbidity and each other, average annualized incremental costs of 3–4 functional impairments versus no impairment in women (men) were $2 838 ($5 516) in inpatient, $1 572 ($1 446) in SNF, and $1 349 ($1 060) in HHC sectors; average incremental costs of phenotypic frailty versus robust in women (men) was $4 100 (not significant for men) in inpatient, $1 579 ($1 254) in SNF, and $645 ($526) in HHC sectors. Incremental inpatient costs were primarily due to a higher hospitalization risk, while incremental SNF and HHC costs were related to both increased risks of utilization and higher costs among individuals with utilization. Neither geriatric domain was associated with outpatient costs.

Conclusions

In this study of community-dwelling beneficiaries, functional impairments were independently associated with higher subsequent expenditures in inpatient, SNF, and HHC sectors among both sexes. Phenotypic frailty was independently associated with higher subsequent inpatient costs in women, and higher SNF and HHC costs in both sexes.
Cortical Surface Area Profile Mediates Effects of Childhood Disadvantage on Later-Life General Cognitive Ability
Authors: Tang Rongxiang , Elman Jeremy A , Reynolds Chandra A , Puckett Olivia K , Panizzon Matthew S , Lyons Michael J , Hagler Donald J , Fennema-Notestine Christine , Eyler Lisa T , Dorros Stephen M , Dale Anders M , Kremen William S , Franz Carol E
Published: October 2024

Objectives

Childhood disadvantage is associated with lower general cognitive ability (GCA) and brain structural differences in midlife and older adulthood. However, the neuroanatomical mechanisms underlying childhood disadvantage effects on later-life GCA remain poorly understood. Although total surface area (SA) has been linked to lifespan GCA differences, total SA does not capture the nonuniform nature of childhood disadvantage effects on neuroanatomy, which varies across unimodal and transmodal cortices. Here, we examined whether cortical SA profile—the extent to which the spatial patterning of SA deviates from the normative unimodal–transmodal cortical organization—is a mediator of childhood disadvantage effects on later-life GCA.

Methods

In 477 community-dwelling men aged 56–72 years old, childhood disadvantage index was derived from four indicators of disadvantages and GCA was assessed using a standardized test. Cortical SA was obtained from structural magnetic resonance imaging. For cortical SA profile, we calculated the spatial similarity between maps of individual cortical SA and MRI-derived principal gradient (i.e., unimodal–transmodal organization). Mediation analyses were conducted to examine the indirect effects of childhood disadvantage index through cortical SA profile on GCA.

Results

Around 1.31% of childhood disadvantage index effects on later-life GCA were mediated by cortical SA profile, whereas total SA did not. Higher childhood disadvantage index was associated with more deviation of the cortical SA spatial patterning from the principal gradient, which in turn related to lower later-life GCA.

Discussion

Childhood disadvantage may contribute to later-life GCA differences partly by influencing the spatial patterning of cortical SA in a way that deviates from the normative cortical organizational principle.
An abnormal increase in CD26(−)CD28(−) cytotoxic effector CD4 and CD8 T cell populations in patients with systemic lupus erythematosus
Authors: Hatano Ryo , Nakamura Hayato , Yamamoto Ayako , Otsuka Haruna , Itoh Takumi , Hosokawa Nao , Yu Jinghui , Ranjbar Sedigheh , Hasegawa Yuta , Sato Tsutomu , Dang Nam H , Ohnuma Kei , Morimoto Shinji , Sekigawa Iwao , Ishii Tomonori , Morimoto Chikao
Published: October 2024

CD26 is a human T cell costimulatory molecule as well as a T cell subset marker, and the increase of CD26+ T cells in inflamed tissues and peripheral blood has been reported in diverse autoimmune diseases. In contrast, our group has previously shown that levels of circulating CD26+ T cells are decreased in patients with systemic lupus erythematosus (SLE), although the role of reduced CD26 T cell surface expression in SLE pathology remains to be elucidated. In the present study, we conducted CD26-based T cell subset analyses utilizing peripheral blood mononuclear cells from 57 SLE patients and 31 healthy adult volunteers. We show that the increase in the CD26(−) T cell population reflects the abnormal expansion of CD26(−)CD28(−) cytotoxic subsets of both CD8 T cells and CD4 T cells in SLE patients. Single-cell RNA sequencing analysis of the CD26(−)CD28(−) CD4 and CD8 T cell populations reveals unique characteristics with similarities to natural killer T cells. In addition, the level of CD26(−)CD28(−) T cells is increased in some active-stage SLE patients with renal manifestation. Meanwhile, the effect of prednisolone treatment on these populations varies from patient to patient, with levels of these cytotoxic effector populations still being elevated in some inactive-stage SLE patients. Taken together, our data suggest that analysis of these populations in SLE may be a useful tool to classify this markedly heterogeneous condition.
Sulfur-oxidizing symbionts colonize the digestive tract of their lucinid hosts
Authors: Alcaraz Cristina M , Séneca Joana , Kunert Martin , Pree Christopher , Sudo Marta , Petersen Jillian M
Published: October 2024

Like many marine invertebrates, marine lucinid clams have an intimate relationship with beneficial sulfur-oxidizing bacteria located within specialized gill cells known as bacteriocytes. Most previous research has focused on the symbionts in the gills of these (and other) symbiotic bivalves, often assuming that the symbionts only persistently colonize the gills, at least in the adult stage. We used 16S rRNA gene sequencing and digital polymerase chain reaction with symbiont-specific primers targeting the soxB gene on the foot, mantle, visceral mass, and gills of the lucinid clam Loripes orbiculatus. We also used fluorescence in situ hybridization with symbiont-specific probes to examine symbiont distribution at the level of the whole holobiont. Despite 40 years of research on these symbioses, we detected previously unknown populations of symbiont cells in several organs, including the digestive tract. As in the well-studied gills, symbionts in the digestive tract may be housed within host cells. A 14-month starvation experiment without hydrogen sulfide to power symbiont metabolism caused a larger reduction in symbiont numbers in the gills compared to the visceral mass, raising the possibility that symbionts in the digestive tract are persistent and may have a distinct physiology and role in the symbiosis compared with the gill symbionts. Our results highlight the unexpectedly complex relationships between marine lucinid clams and their symbionts and challenge the view that chemosynthetic symbionts are restricted to the gills of these hosts.
Self-transcendence: Design Criticism in the 1928 Shanghai Exhibition of National Products
Authors: Ji Shaorong
Published: October 2024

After establishing the Shanghai port in 1843, Western machine-made products inundated the Chinese consumer market, disrupting the local Chinese economic system. To foster the advancement of national industries, the Nanking nationalist government held the Ministry of Industry, Commerce, and Labour’s Exhibition of National Products in 1928, providing a platform for public discourse on the design of national products. This article analyses the progression of three representative types of early design criticism that emerged from the Exhibition of National Products. These criticisms examined the design’s economic benefits, responsiveness to cultural needs, and influence on shaping social consensus. Their progressive development can be characterized as a form of self-transcendence, indicating a move by critics beyond past limited understandings of the value, sphere of influence, and design’s role in society. Their focus transitioned from the economic interests of minorities to the diverse needs of broader social groups. In the process of self-transcendence, these design criticisms expanded the horizons of designers’ work. They facilitated collaborations between design and various industries, including production, consumption, and education, influencing broader socioeconomic and ideological fronts.
The role of maize sap beetles (Coleoptera: Nitidulidae) and maize weevils (Coleoptera: Curculionidae) in the spread of Aspergillus flavus in pre-harvest maize in Kenya
Authors: Riungu Ginson , Muthomi James W , Buechs Wolfgang , Wagacha John M , Philip Esther Sheila , Meiners Torsten
Published: October 2024

The spread of toxigenic Aspergillus into maize by insects and the subsequent aflatoxin contamination poses a risk to humans and animals and has been investigated in North and South America. To evaluate this effect in an African context, Greenhouse studies were conducted in 2022 to determine the role of sap beetles, Carpophilus dimidiatus Fabricius, 1792 (Coleoptera: Nitidulidae) and maize weevils, Sitophilus zeamais Motschulsky, 1855 (Coleoptera: Curculionidae) on infection of maize kernels by Aspergillus flavus Link and the resultant aflatoxin accumulation. To test the beetles’ efficacy, treatments were applied on partially opened primary ears at 3 different stages of kernel development (BBCH 75, 83, and 87). The treatments were: (i) distilled water, (ii) water with A. flavus spores, (iii) maize grits, (iv) maize grits with A. flavus spores, (v) C. dimidiatus, (vi) C. dimidiatus with A. flavus spores, (vii) S. zeamais, and (viii) S. zeamais with A. flavus spores. Data on kernel infection, maize rotting, yield, and aflatoxin content in kernels were collected. The highest kernel spoilage and yield loss were recorded for the co-inoculation of S. zeamais and A. flavus spores, followed by S. zeamais without A. flavus spores, and then C. dimidiatus with the fungal spores. Inoculation of maize at the BBCH 83 growth stage resulted in the highest kernel damage and aflatoxin contamination. S. zeamais and, to a lesser extent, C. dimidiatus effectively spread the A. flavus inoculum into non-wounded ears, resulting in fungal and aflatoxin contamination. The yield loss from S. zeamais-Aspergillus co-inoculation occurred due to the grain rotting and actual feeding of the maize weevils. Thus, insect management is important in reducing pre-harvest contamination of maize with mycotoxigenic fungi and their resultant toxins.
Prevalence of cancer survivors diagnosed during adolescence and young adulthood in the United States
Authors: Page Lindsey L , Devasia Theresa P , Mariotto Angela , Gallicchio Lisa , Mollica Michelle A , Tonorezos Emily
Published: October 2024

Background

Adolescent and young adult (AYA) cancer incidence rates are rising, and survivors are at risk for numerous cancer- and treatment-related consequences. Despite growing attention to this population, prevalence estimates are lacking.

Objective

To estimate the number of individuals living in the United States with a history of cancer diagnosed during the AYA period.

Methods

Prevalence of cancer survivors diagnosed between the ages of 15 and 39 years was estimated using data from the Surveillance, Epidemiology, and End Results (SEER) program as of January 1, 2020. Limited duration prevalence data were also used to generate complete prevalence by sex, years since diagnosis (0-<1, 1-<5, 5-<10, 10-<15, 15-<20, 20+), and attained age (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70+) for the 15 most common AYA cancer sites.

Results

There were an estimated 2 111 838 survivors of AYA cancers in the United States as of January 1, 2020. More survivors were female (66%) and long-term (>5 years from diagnosis, 83%) or very long-term survivors (>10 years from diagnosis, 68.8%). A large percentage (44%) were more than 20 years from diagnosis. The most common cancer sites among female survivors were breast (24%) and thyroid cancers (23%) and, among male survivors, testicular cancer (31%). Across the population, the highest percentage of survivors of AYA cancers were 40 to 49 years of age (25.3%).

Conclusion

There are more than 2.1 million cancer survivors diagnosed in the AYA period who are living in the United States; most are more than 10 years from diagnosis.
Effectiveness of psychological interventions for compassion fatigue: a systematic review and meta-analysis
Authors: Lipsa Jose Mariya , Rajkumar Eslavath , Gopi Aswathy , Romate John
Published: October 2024

Objectives: Constant exposure to trauma and death adversely affects the physical, emotional, and mental stability of the helping professionals, leading to compassion fatigue (CF). Although research has explored the effect of various psychological interventions (PIs) on CF, no studies have quantitatively synthesized their effectiveness. Thus, the current systematic review and meta-analysis address this gap by examining the efficacy of PIs in reducing CF among helping professionals.

Methods: Databases such as Scopus, Web of Science, PubMed, JSTOR, ScienceDirect, and Google Scholar were searched to identify studies published between 2004 and 2023. Quantitative studies published in English that used any PI to reduce CF of helping professionals were selected for analysis. The risk of bias in studies was evaluated using Joanna Briggs Institute (JBI) checklists and the National Heart, Lung, and Blood Institute quality assessment tool.

Results: Of the 1995 records identified from databases, 82 intervention studies were included in the systematic review, and 11 randomized controlled trials were chosen for meta-analysis. Post-intervention means and SDs of the intervention group and the control group were used to run the meta-analysis. Random effects meta-analysis results revealed that PIs are highly effective in reducing CF (standardized mean difference (SMD) = −0.95; 95% CI, −1.63 to −0.27; P = .006).

Conclusion: Evidence suggests that PIs, especially online-delivered PIs, could reduce the CF of helping professionals. Health policymakers, concerned authorities, and intervention designers should focus on reducing the CF of helping professionals, as they need to work with vulnerable populations efficiently.
Puerarin improves Dioscorea bulbifera L.-induced liver injury by regulating drug transporters and the Nrf2/NF-κB/Bcl-2 signaling pathway
Authors: Wang Xin , Zhang Yuhan , Zhu Hongzhe , Shi Leilei , Shi Yong , Cao Shanshan , Liu Jiping , Xie Yundong
Published: October 2024

Purpose

Investigate the protective effect and mechanism of Puerarin (PU) against Dioscorea bulbifera L. (DB)-induced liver injury.

Materials and methods

The protective effect of PU against DB-induced liver injury was evaluated by the present animal experiment, which assessed the pathological changes in the liver of mice and detected Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (AKP), as well as inflammation and oxidative stress-related indexes. Finally, the transcription and expression of related proteins were detected using western blot and quantitative reverse transcription (PCR) techniques.

Results

PU significantly increased body weight, reduced liver index, and attenuated pathological changes in the liver compared to the DB group. It also decreased levels of AST, ALT, AKP, tumor necrosis factor-α, interleukin-1β, and malondialdehyde while increasing interleukin-10 levels and superoxide dismutase activity. Additionally, it upregulated inhibitor of NF-κB (IκB-α), B-cell lymphoma-2 (Bcl-2), Nuclear respiratory factor 2 (Nrf2), and Heme oxygenase 1 (HO-1) expression while down-regulating p-NF-κB p65 and bcl2-associated x (Bax) expression in the liver. Furthermore, PU upregulated protein and gene expression levels of Multidrug resistance-associated protein2, bile salt export pump, p-glycoprotein, and UDP-glucuronyltransferase 1A1 (UGT1A1) as well.

Conclusion

PU mitigates DB-induced liver injury by regulating the expression of drug transporters and modulating the Nrf2/NF-κB/Bcl-2 signaling pathway.
Prevalence of Mayaro infections in Amazonian peri-urban areas
Authors: Pimentel Edilene Pereira , Ribeiro Jessiane Rodrigues , Moreira Hillquias Monteiro , Teixeira Karolaine Santos , Roca Tárcio Peixoto , Passos-Silva Ana Maisa , da Silva Queiroz Jackson Alves , Villalobos-Salcedo Juan Miguel , Tada Mauro Shugiro , Fragoso Stenio Perdigão , Krieger Marco Aurelio , de Cássia Pontello Rampazzo Rita , Vieira Deusilene
Published: October 2024

A retrospective cohort with 967 acute febrile individuals negative for Dengue, Zika, Chikungunya and Malaria demonstrated two positive results by conventional polymerase chain reaction plus sequencing for Mayaro genotype D in a peri-urban region, indicating the need for changes in diagnosis protocols and active genomic surveillance in Brazil to prevent virus outbreaks.
Measuring the semantic headedness of English blends with token-based semantic vector space modeling: a corpus-based study
Authors: Meng Qingnan , Hilpert Martin
Published: October 2024

This article analyzes the semantic headedness of English blends with distributional semantics methods. The semantic head of a blend is the source word that transfers its semantic information to the blend as a whole. For example, a sitcom is a kind of comedy. But is FedEx a kind of express, and is wi-fi a kind of fidelity? We use corpus data and token-based semantic vector space modeling in order to address these questions. Specifically, we investigate whether Plag’s ternary division of endocentric, exocentric, and coordinative compounds based on semantic headedness can also be applied to English blends, and whether the general tendency of semantic right-headedness can be observed for all three subtypes. We analyze a dataset of fifty-five blends and their respective source words, using data from the Corpus of Contemporary American English and the English Web Corpus 2021. We measure the degree of semantic similarity between each blend and its two source words. The results show that for most endocentric blends, the hypothesis of semantic right-headedness holds true. At the same time, exocentric blends and coordinative blends are shown to behave differently. We conclude that Plag’s classification offers a useful point of departure for the semantic analysis of blends and that distributional semantics methods can provide new insights into their semantic behavior.
TRAPUM pulsar and transient search in the Sextans A and B galaxies and discovery of background FRB 20210924D
Authors: Carli E , Levin L , Stappers B W , Barr E D , Breton R P , Buchner S , Burgay M , Kramer M , Padmanabh P V , Possenti A , Venkatraman Krishnan V , Sridhar S S , Turner J D
Published: October 2024

The Small and Large Magellanic Clouds are the only galaxies outside our own in which radio pulsars have been discovered to date. The sensitivity of the MeerKAT radio interferometer offers an opportunity to search for a population of more distant extragalactic pulsars. The TRAPUM (TRansients And PUlsars with MeerKAT) collaboration has performed a radio-domain search for pulsars and transients in the dwarf star-forming galaxies Sextans A and B, situated at the edge of the Local Group 1.4 Mpc away. We conducted three 2-h multibeam observations at L band (856–1712 MHz) with the full array of MeerKAT. No pulsars were found down to a radio pseudo-luminosity upper limit of 7.9$\pm$0.4 Jy kpc$^{2}$ at 1400 MHz, which is 28 times more sensitive than the previous limit from the Murriyang telescope. This luminosity is 30 per cent greater than that of the brightest known radio pulsar and sets a cut-off on the luminosity distributions of the entire Sextans A and B galaxies for unobscured radio pulsars beamed in our direction. A fast radio burst was detected in one of the Sextans A observations at a dispersion measure (DM) of 737 pc cm$^{-3}$. We believe this is a background event not associated with the dwarf galaxy due to its large DM and its signal-to-noise ratio being strongest in the wide-field incoherent beam of MeerKAT.
Assessing the Role of Bacterial Innate and Adaptive Immunity as Barriers to Conjugative Plasmids
Authors: Siedentop Berit , Losa Mediavilla Carlota , Kouyos Roger D , Bonhoeffer Sebastian , Chabas Hélène
Published: October 2024

Plasmids are ubiquitous mobile genetic elements, that can be either costly or beneficial for their bacterial host. In response to constant viral threat, bacteria have evolved various immune systems, such as the prevalent restriction modification (innate immunity) and CRISPR-Cas systems (adaptive immunity). At the molecular level, both systems also target plasmids, but the consequences of these interactions for plasmid spread are unclear. Using a modeling approach, we show that restriction modification and CRISPR-Cas are effective as barriers against the spread of costly plasmids, but not against beneficial ones. Consequently, bacteria can profit from the selective advantages that beneficial plasmids confer even in the presence of bacterial immunity. While plasmids that are costly for bacteria may persist in the bacterial population for a certain period, restriction modification and CRISPR-Cas can eventually drive them to extinction. Finally, we demonstrate that the selection pressure imposed by bacterial immunity on costly plasmids can be circumvented through a diversity of escape mechanisms and highlight how plasmid carriage might be common despite bacterial immunity. In summary, the population-level outcome of interactions between plasmids and defense systems in a bacterial population is closely tied to plasmid cost: Beneficial plasmids can persist at high prevalence in bacterial populations despite defense systems, while costly plasmids may face extinction.
Development of an orthotopic medulloblastoma zebrafish model for rapid drug testing
Authors: van Bree Niek , Oppelt Ann-Sophie , Lindström Susanne , Zhou Leilei , Boutin Lola , Coyle Beth , Swartling Fredrik J , Johnsen John Inge , Bräutigam Lars , Wilhelm Margareta
Published: October 2024

Background

Medulloblastoma (MB) is one of the most common malignant brain tumors in children. Current preclinical in vivo model systems for MB have increased our understanding of molecular mechanisms regulating MB development. However, they may not be suitable for large-scale studies. The aim of this study was to investigate if a zebrafish-based xenograft model can recapitulate MB growth and enable rapid drug testing.

Methods

Nine different MB cell lines or patient-derived cells were transplanted into blastula-stage zebrafish embryos. Tumor development and migration were then monitored using live imaging. RNA sequencing was performed to investigate transcriptome changes after conditioning cells in a neural stem cell-like medium. Furthermore, drug treatments were tested in a 96-well format.

Results

We demonstrate here that transplantation of MB cells into the blastula stage of zebrafish embryos leads to orthotopic tumor growth that can be observed within 24 h after transplantation. Importantly, the homing of transplanted cells to the hindbrain region and the aggressiveness of tumor growth are enhanced by pre-culturing cells in a neural stem cell-like medium. The change in culture conditions rewires the transcriptome toward a more migratory and neuronal phenotype, including the expression of guidance molecules SEMA3A and EFNB1, both of which correlate with lower overall survival in MB patients. Furthermore, we highlight that the orthotopic zebrafish MB model has the potential to be used for rapid drug testing.

Conclusions

Blastula-stage zebrafish MB xenografts present an alternative to current MB mouse xenograft models, enabling quick evaluation of tumor cell growth, neurotropism, and drug efficacy.
Longitudinal multimodal profiling of IDH-wildtype glioblastoma reveals the molecular evolution and cellular phenotypes underlying prognostically different treatment responses
Authors: Lucas Calixto-Hope G , Al-Adli Nadeem N , Young Jacob S , Gupta Rohit , Morshed Ramin A , Wu Jasper , Ravindranathan Ajay , Shai Anny , Oberheim Bush Nancy Ann , Taylor Jennie W , de Groot John , Villanueva-Meyer Javier E , Pekmezci Melike , Perry Arie , Bollen Andrew W , Theodosopoulos Philip V , Aghi Manish K , Chang Edward F , Hervey-Jumper Shawn L , Raleigh David R , Molinaro Annette M , Costello Joseph F , Diaz Aaron A , Clarke Jennifer L , Butowski Nicholas A , Phillips Joanna J , Chang Susan M , Berger Mitchel S , Solomon David A
Published: October 2024

Background

Despite recent advances in the biology of IDH-wildtype glioblastoma, it remains a devastating disease with median survival of less than 2 years. However, the molecular underpinnings of the heterogeneous response to the current standard-of-care treatment regimen consisting of maximal safe resection, adjuvant radiation, and chemotherapy with temozolomide remain unknown.

Methods

Comprehensive histopathologic, genomic, and epigenomic evaluation of paired initial and recurrent glioblastoma specimens from 106 patients was performed to investigate the molecular evolution and cellular phenotypes underlying differential treatment responses.

Results

While TERT promoter mutation and CDKN2A homozygous deletion were early events during gliomagenesis shared by initial and recurrent tumors, most other recurrent genetic alterations (eg, EGFR, PTEN, and NF1) were commonly private to initial or recurrent tumors indicating acquisition later during clonal evolution. Furthermore, glioblastomas exhibited heterogeneous epigenomic evolution with subsets becoming more globally hypermethylated, hypomethylated, or remaining stable. Glioblastoma that underwent sarcomatous transformation had shorter interval to recurrence and were significantly enriched in NF1, TP53, and RB1 alterations and the mesenchymal epigenetic class. Patients who developed somatic hypermutation following temozolomide treatment had significantly longer interval to disease recurrence and prolonged overall survival, and increased methylation at 4 specific CpG sites in the promoter region of MGMT was significantly associated with this development of hypermutation. Finally, an epigenomic evolution signature incorporating change in DNA methylation levels across 347 critical CpG sites was developed that significantly correlated with clinical outcomes.

Conclusions

Glioblastoma undergoes heterogeneous genetic, epigenetic, and cellular evolution that underlies prognostically different treatment responses.
Genetic Signature of a Healthy Lifestyle: New Horizons for Preventing Noncommunicable Chronic Diseases by Modulating MicroRNA-155
Authors: Coutinho-Wolino Karen S , Brito Michele L , Trigueira Pricilla C , de Menezes Larissa O , do Nascimento Clara S , Stockler-Pinto Milena B
Published: October 2024

The development and progression of several noncommunicable diseases (NCDs) are associated with microRNA (miR) 155 (miR-155) activation, which promotes inflammation and oxidative stress. In particular, miR-155 regulates nuclear transcription factor–kappa B (NF-κB) by silencing gene expression of proteins involved in NF-κB suppression, such as suppressor of cytokine signaling 1 (SOCS1) and SH-2 containing inositol 5′ polyphosphate 1 (SHIP1), increases the production of reactive oxygen species, and suppresses gene expression of antioxidant enzymes through nuclear factor erythroid 2–related factor 2 (Nrf2) inhibition. In this context, a healthy lifestyle based on a diet rich in nutrients and bioactive compounds as well as regular physical activity may modulate the activity of several miRs. Following this concept, studies involving nutrients, bioactive compounds, and physical activity have been developed to modulate miR-155 activation. This narrative review aims to discuss how a healthy lifestyle based on a diet rich in nutrients, bioactive compounds, and physical activity may modulate the miR-155 pathway and consequently prevent the development and progression of NCDs. Nutrients and bioactive compounds from food may act by inhibiting pathways that promote miR-155 activation such as NF-κB and promote activation of pathways that are associated with the downregulation of miR-155, such as Nrf2, and SOCS1 pathways. Regular physical activity also seems to influence miR-155 levels through an improvement in the immune system during muscle recovery. There is relevant evidence that shows a positive effect of nutrients, bioactive compounds, and physical activity with the modulation of miR-155, which can potentially provide benefits in the clinical setting in cases of NCDs.
Rural children know cavity-nesting birds of the Atlantic Forest but may underappreciate their critical habitat
Authors: Bonaparte Eugenia Bianca , Ibarra José Tomás , Liefländer Anne K , Sosa Marcos Hugo , Cockle Kristina L
Published: October 2024

Cavity-nesting birds are a diverse and charismatic community, with a common need for tree cavities that make them vulnerable to land management by humans. However, little research has formally integrated human social aspects into management recommendations for the conservation of cavity-nesting birds. In agroecosystems, people’s management decisions modify and define the habitat availability for native cavity-nesting species. These behaviors during adulthood are related to people’s worldviews and are shaped, in part, by childhood experiences. Ongoing forest loss may reduce opportunities for children to interact with and learn from cavity-nesting birds and their habitats. We used a social–ecological framework to assess rural children’s knowledge and representations of native cavity-nesting birds and their habitats in agroecosystems of the threatened Atlantic Forest of Argentina. We employed “freelists” and “draw-and-explain” strategies with 235 children from 19 rural schools and then compared results with a 4-year dataset of trees (n = 328) and tree-cavity nests (n = 164) in the same study area. Children listed a high diversity (93 taxa) of native cavity-nesting birds, especially parrots (Psittacidae), toucans (Ramphastidae), and woodpeckers (Picidae), which they mostly recognized as cavity nesters. However, children drew agricultural landscapes with few of the habitat features that these birds require (e.g., tree cavities, native forest). Exotic trees were overrepresented in drawings (40% of mentions) compared to our field dataset of nests (10%) and trees on farms (15%). Although children mentioned and depicted a high diversity of native cavity-nesting birds, our results may reveal a problematic extinction of experience regarding how these birds interact with their habitat. To strengthen children’s contextualized knowledge and promote their long-term commitment to the conservation of cavity-nesting species, we recommend fostering meaningful experiences for children to interact with native cavity-nesting birds and recognize their habitat needs. A version of this article translated into Spanish is available in Supplementary Material 1.
OsKANADI1 and OsYABBY5 regulate rice plant height by targeting GIBERELLIN 2-OXIDASE6
Authors: He Qi , Wu Hao , Zeng Longjun , Yin Caiyun , Wang Li , Tan Yiqing , Lv Wanqing , Liao Zhiqiang , Zheng Xuelian , Zhang Shuting , Han Qinqin , Wang Danning , Zhang Yong , Xiong Guosheng , Wang Quan
Published: October 2024

Plant height is an important agronomic characteristic of rice (Oryza sativa L.). Map-based cloning analyses of a natural semi-dwarf rice mutant with inwardly curled leaves found in the field revealed that the defects were due to a mutation of a SHAQKYF-class MYB family transcription factor, OsKANADI1 (OsKAN1). OsKAN1 directly bound to the OsYABBY5 (OsYAB5) promoter to repress its expression and interacted with OsYAB5 to form a functional OsKAN1–OsYAB5 complex. GIBERELLIN 2-OXIDASE6 (OsGA2ox6), encoding an enzyme in the gibberellin (GA) catabolic pathway, was activated by OsYAB5. Furthermore, the OsKAN1–OsYAB5 complex suppressed the inhibitory effect of OsKAN1 toward OsYAB5 and inhibited OsYAB5-induced OsGA2ox6 expression. The proOsKAN1:OsYAB5 transgenic plants were taller than wild-type plants, whereas oskan1 proOsKAN1:OsYAB5 plants exhibited a severe dwarf phenotype due to the absence of the OsKAN1–OsYAB5 complex. The OsKAN1–OsYAB5 complex modulated OsGA2ox6 expression, thereby regulating the levels of bioactive gibberellins and, consequently, plant height. This study elucidated the mechanism underlying the effect of the OsKAN1-OsYAB5-OsGA2ox6 regulatory pathway on plant height at different positions in rice stems and provided insights on stem development and candidate genes for the aerial architecture improvement of crop plants.
Risk-Adjusted Returns of Private Equity Funds: A New Approach
Authors: Korteweg Arthur , Nagel Stefan
Published: October 2024

This paper introduces a new metric, α, to benchmark the performance of individual private equity funds. Our metric is substantially less sensitive to noise in fund cash flows compared to the popular public market equivalent (PME) and its generalization (GPME), while having the same aggregate pricing implications as GPME. For a large data set of fund cash flows, α estimates have much lower standard deviation across funds than does (G)PME. For buyout funds, PME and α are close, but deviate in certain subsamples. Using α increases power in regressions involving fund performance and improves performance predictability of future funds.