bluuebunny/crossref_metadata_2025 huggingface dataset:
Facile preparation of SeCF3-substituted alkenes from alkenyl iodides and selenium powder
Authors: Matsui Haruka , Kojima Yuki , Hirano Koji
Published: April 2024

A synthetic method of SeCF3-substituted alkenes by a copper-mediated trifluoromethylselenolation of alkenyl iodides has been developed. In the presence of CuI and bpy, AgSeCF3 generated in-situ from Ag salt, TMSCF3, and commercially available Se powder, can be successfully coupled with alkenyl iodides to produce the trifluoromethylselenoalkenes with high chemoselectivity. The reaction shows a broad substrate scope including alkenyl iodides derived from biologically active molecules. Moreover, the feasibility of its scale-up synthesis has been demonstrated, thereby underscoring the practicality of the protocol.
Who gets the goods? Disentangling the effects of parliamentary representation and collective action on social spending
Authors: Calnitsky David , Wind Ella
Published: April 2024

A century of activist and academic analysis of the welfare state can be sorted into insider and outsider theories of social change. One perspective argues that working-class and poor people can achieve income redistribution through insider strategies, primarily through the legislative efforts of left-wing political parties. A competing perspective argues that political parties themselves have no inner motor and merely channel the outside pressure from disruptive collective action. This article makes a substantive and methodological contribution to the debate over the generosity of the welfare state. We analyse the extent to which collective action confounds, moderates, or operates independently of left-wing parliamentary power to explain the history of social spending in 22 countries. Our results support a strong version of the insider intuition that the parliamentary road is crucial to winning gains for poor and working people. It does so without channelling the power of mass mobilization: accounting for various forms of collective action does not reduce the impact of left parliamentary representation on public social expenditures. Nonetheless, we do find that strikes, in particular, have independent effects on social spending. These results together provide some support for what can be called a Marxist–social democratic alliance. We also find evidence for the outsider view that protests and riots matter when combined; these mobilizations, like strikes, operate independently of the role of left-wing parliamentary power.
Arctic cyanobacterial mat community diversity decreases with latitude across the Canadian Arctic
Authors: Hooper Patrick M , Bass David , Feil Edward J , Vincent Warwick F , Lovejoy Connie , Owen Christopher J , Tsola Stephania L , Jungblut Anne D
Published: April 2024

Cyanobacterial mats are commonly reported as hotspots of microbial diversity across polar environments. These thick, multilayered microbial communities provide a refuge from extreme environmental conditions, with many species able to grow and coexist despite the low allochthonous nutrient inputs. The visibly dominant phototrophic biomass is dependent on internal nutrient recycling by heterotrophic organisms within the mats; however, the specific contribution of heterotrophic protists remains little explored. In this study, mat community diversity was examined along a latitudinal gradient (55–83°N), spanning subarctic taiga, tundra, polar desert, and the High Arctic ice shelves. The prokaryotic and eukaryotic communities were targeted, respectively, by V4 16S ribosomal RNA (rRNA) and V9 18S rRNA gene amplicon high-throughput sequencing. Prokaryotic and eukaryotic richness decreased, in tandem with decreasing temperatures and shorter seasons of light availability, from the subarctic to the High Arctic. Taxonomy-based annotation of the protist community revealed diverse phototrophic, mixotrophic, and heterotrophic genera in all mat communities, with fewer parasitic taxa in High Arctic communities. Co-occurrence network analysis identified greater heterogeneity in eukaryotic than prokaryotic community structure among cyanobacterial mats across the Canadian Arctic. Our findings highlight the sensitivity of microbial eukaryotes to environmental gradients across northern high latitudes.
Trends in Number and Appropriateness of Prescription Medication Utilization Among Community-Dwelling Older Adults in the United States: 2011–2020
Authors: Pan Shaoxi , Li Shanshan , Jiang Shaoxiang , Shin Jung-Im , Liu Gordon G , Wu Hongyan , Lyu Beini
Published: April 2024

Background

Contemporary data on the quantity and quality of medication use among older adults are lacking. This study examined recent trends in the number and appropriateness of prescription medication use among older adults in the United States.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and March 2020 were used, and 6 336 adult participants aged 65 and older were included. We examined the number of prescription medication, prevalence of polypharmacy (≥5 prescription drugs), use of potentially inappropriate medication (PIM), and use of recommended medications (angiotensin-converting enzyme inhibitor [ACEI]/angiotensin receptor blockers [ARBs] plus beta-blockers among patients with heart failure and ACEI/ARBs among patients with albuminuria).

Results

There has been a slight increase in the prevalence of polypharmacy (39.3% in 2011–2012 to 43.8% in 2017–2020, p for trend = .32). Antihypertensive, antihyperlipidemic, antidiabetic medications, and antidepressants are the most commonly used medications. There was no substantial change in the use of PIM (17.0% to 14.7%). Less than 50% of older adults with heart failure received ACEI/ARBs plus beta-blockers (44.3% in 2017–2020) and approximately 50% of patients with albuminuria received ACEI/ARBs (54.0% in 2017–2020), with no improvement over the study period. Polypharmacy, older age, female, and lower socioeconomic status were generally associated with greater use of PIM but lower use of recommended medications.

Conclusions

The medication burden remained high among older adults in the United States and the appropriate utilization of medications did not improve in the recent decade. Our results underscore the need for greater attentions and interventions to the quality of medication use among older adults.
Impact of the inaccessible genome on genotype imputation and genome-wide association studies
Authors: König Eva , Mitchell Jonathan Stewart , Filosi Michele , Fuchsberger Christian
Published: April 2024

Genotype imputation is widely used in genome-wide association studies (GWAS). However, both the genotyping chips and imputation reference panels are dependent on next-generation sequencing (NGS). Due to the nature of NGS, some regions of the genome are inaccessible to sequencing. To date, there has been no complete evaluation of these regions and their impact on the identification of associations in GWAS remains unclear. In this study, we systematically assess the extent to which variants in inaccessible regions are underrepresented on genotyping chips and imputation reference panels, in GWAS results and in variant databases. We also determine the proportion of genes located in inaccessible regions and compare the results across variant masks defined by the 1000 Genomes Project and the TOPMed program. Overall, fewer variants were observed in inaccessible regions in all categories analyzed. Depending on the mask used and normalized for region size, only 4%–17% of the genotyped variants are located in inaccessible regions and 52 to 581 genes were almost completely inaccessible. From the Cooperative Health Research in South Tyrol (CHRIS) study, we present a case study of an association located in an inaccessible region that is driven by genotyped variants and cannot be reproduced by imputation in GRCh37. We conclude that genotyping, NGS, genotype imputation and downstream analyses such as GWAS and fine mapping are systematically biased in inaccessible regions, due to missed variants and spurious associations. To help researchers assess gene and variant accessibility, we provide an online application (https://gab.gm.eurac.edu).
For-profit or for-CSR: decisions of power batteries recovery in the supply chain
Authors: Xing Ruxiao , Zhuang Mengmeng , Li Bo
Published: April 2024

Accepted by: M. Zied Babai

The importance of recovering retired batteries from new energy vehicles (NEVs) has garnered widespread attention in both scholarly literature and practical applications. This paper discusses the decisions of battery recovery in a supply chain consisting of a supplier and a manufacturer. Utilizing the Stackelberg game, we construct relevant models and compare the equilibrium solutions in two decision-making modes, for-profit and for-CSR (corporate social responsibility). We shows that the firms’ pursuit of CSR contributes to increasing collection prices. However, if environmental damage is severe, the firms’ pursuit of CSR leads to high retail prices, which is detrimental to the sale of NEVs. Furthermore, although not all members’ collection amounts increase when considering CSR, the overall collection effect will be better. Meanwhile, we find that both the supplier and the manufacturer have incentives to practice CSR because their pursuit of CSR leads to high profits. Finally, this paper has verified all the above conclusions using theoretical data.
Antibody Titers and the Risk of Infection During the SARS-CoV-2 Omicron Phase in Bizen City, Japan
Authors: Kadowaki Tomoka , Sasaki Ayako , Matsumoto Naomi , Mitsuhashi Toshiharu , Hagiya Hideharu , Takao Soshi , Yorifuji Takashi
Published: April 2024

Background

Understanding the association between the immune response and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has implications for forthcoming prevention strategies. We evaluated the association between antibody titers and the risk of infection for the general population during the Omicron-dominant phase.

Methods

This was a prospective cohort study of residents or people affiliated with institutions in Bizen City, which included 1899 participants. We measured the titers of antibodies against SARS-CoV-2 repeatedly every 2 months from June 2022 to March 2023. Infection status was obtained from self-reported questionnaires and the official registry. We estimated risk ratios (RRs) for infection within 2 months of the date of each antibody measurement with 95% confidence intervals (CIs) based on antibody titer categories and spline functions.

Results

Compared with the <2500 arbitrary unit (AU)/mL category, the 2500–5000, 5000–10 000, and ≥10 000 AU/mL categories had adjusted RRs of 0.81 (95% CI, .61–1.08), 0.51 (95% CI, .36–.72), and 0.41 (95% CI, .31–.54), respectively. The spline function showed a nonlinear relationship between antibody titer and risk.

Conclusions

Higher antibody titers were associated with a lower risk. We demonstrate the usefulness of measuring an antibody titers to determine the appropriate timing for future prevention strategies.
Foreign Military Training and Socialization: An Examination of Human Capital and Norm Transmission Between Allies
Authors: Fábián Sándor , Boutton Andrew
Published: April 2024

Abstracts

Foreign military personnel routinely participate in educational and cultural programs administered by the U.S. military. In addition to bolstering the capacity of the recipient military, one of the primary goals of these programs is to professionalize the military of the recipient state. It is hoped not only that the soldiers will internalize norms of human rights and democracy themselves but also that they will become influential members of the military in the future. Existing cross-national research, along with selective anecdotes of U.S.-trained soldiers leading coups and rebellions, suggests that military aid may be ineffective. To date, however, a nuanced understanding of the more granular effects of military aid on the recipient country has been hindered by a lack of data and a focus on the macro-level. We address this lacuna by examining norm transmission among a sample of the Hungarian officer corps. We show that while soldiers who graduated from IMET programs display more favorability toward human rights and democracy, they do not believe the military should remain insulated from policymaking. We believe this is a valuable step toward a deeper understanding of how U.S. military aid shapes recipient militaries and, more broadly, how norms are transmitted between allies.
Fear or Anger? Leaders’ Childhood War Trauma and Interstate Conflict Initiation
Authors: Kim James D
Published: April 2024

How does a leader’s childhood exposure to war influence their propensity to initiate conflicts? While much research explains leaders’ national security policies using their combat and rebel experiences, few scholars have examined the effects of childhood wartime violence. I develop and test two competing arguments about the effects of childhood war trauma on future conflict behavior. One argument expects that leaders exposed to war at a young age will be less likely to initiate conflict because they fear its consequences. An alternative perspective expects that these leaders are more likely to initiate conflict out of anger and a desire for revenge. I test my hypotheses using an original dataset and a research design that reduces inference barriers. Leveraging variations in the level of violence experienced during wartime, I only compare leaders who were exposed to foreign military invasions as children. I find that those who experienced severe war trauma, such as family deaths, injuries, or displacement, are less likely to initiate interstate conflicts than those who did not experience such traumatic events. These effects are substantial, particularly when political constraints are weak. My results suggest that childhood war trauma has a long-term impact on leaders’ conservatism about using force.
Bioactive metabolites of Asparagopsis stabilized in canola oil completely suppress methane emissions in beef cattle fed a feedlot diet
Authors: Cowley Frances C , Kinley Robert D , Mackenzie Sigrid L , Fortes Marina R S , Palmieri Chiara , Simanungkalit Gamaliel , Almeida Amelia K , Roque Breanna M
Published: April 2024

Asparagopsis taxiformis (Asparagopsis) has been shown to be highly efficacious at inhibiting the production of methane (CH4) in ruminants. To date, Asparagopsis has been primarily produced as a dietary supplement by freeze-drying to retain the volatile bioactive compound bromoform (CHBr3) in the product. Steeping of Asparagopsis bioactive compounds into a vegetable oil carrier (Asp-Oil) is an alternative method of stabilizing Asparagopsis as a ruminant feed additive. A dose–response experimental design used 3 Asp-Oil-canola oil blends, low, medium, and high Asp-Oil which provided 17, 34, and 51 mg Asparagopsis derived CHBr3/kg dry matter intake (DMI), respectively (in addition to a zero CHBr3 canola oil control), in a tempered-barley based feedlot finisher diet, fed for 59 d to 20 Angus heifers (five replicates per treatment). On four occasions, live weight was measured and CH4 emissions were quantified in respiration chambers, and blood, rumen fluid, and fecal samples were collected. At the end of the experiment, all animals were slaughtered, with carcasses graded, and samples of meat and edible offal collected for testing of consumer sensory qualities and residues of CHBr3, bromide, and iodide. All Asp-Oil treatments reduced CH4 yield (g CH4/kg DMI, P = 0.008) from control levels, with the low, medium, and high Asp-Oil achieving 64%, 98%, and 99% reduction, respectively. Dissolved hydrogen increased linearly with increasing Asp-Oil inclusion, by more than 17-fold in the high Asp-Oil group (P = 0.017). There was no effect of Asp-Oil treatment on rumen temperature, pH, reduction potential, volatile fatty acid and ammonia production, rumen pathology, and histopathology (P > 0.10). There were no differences in animal production and carcass parameters (P > 0.10). There was no detectable CHBr3 in feces or any carcass samples (P > 0.10), and iodide and bromide residues in kidneys were at levels unlikely to lead to consumers exceeding recommended maximum intakes. Overall, Asp-Oil was found to be safe for animals and consumers of meat, and effective at reducing CH4 emissions and yield by up to 99% within the range of inclusion levels tested.
Calcineurin-NFAT signaling controls neutrophils’ ability of chemoattraction upon fungal infection
Authors: Vymazal Ondrej , Papatheodorou Ioanna , Andrejčinová Ivana , Bosáková Veronika , Vascelli Gianluca , Bendíčková Kamila , Zelante Teresa , Hortová-Kohoutková Marcela , Frič Jan
Published: April 2024

Calcineurin–nuclear factor of activated T cells (CN-NFAT) inhibitors are widely clinically used drugs for immunosuppression, but besides their required T cell response inhibition, they also undesirably affect innate immune cells. Disruption of innate immune cell function can explain the observed susceptibility of CN-NFAT inhibitor–treated patients to opportunistic fungal infections. Neutrophils play an essential role in innate immunity as a defense against pathogens; however, the effect of CN-NFAT inhibitors on neutrophil function was poorly described. Thus, we tested the response of human neutrophils to opportunistic fungal pathogens, namely Candida albicans and Aspergillus fumigatus, in the presence of CN-NFAT inhibitors. Here, we report that the NFAT pathway members were expressed in neutrophils and mediated part of the neutrophil response to pathogens. Upon pathogen exposure, neutrophils underwent profound transcriptomic changes with subsequent production of effector molecules. Importantly, genes and proteins involved in the regulation of the immune response and chemotaxis, including the chemokines CCL2, CCL3, and CCL4 were significantly upregulated. The presence of CN-NFAT inhibitors attenuated the expression of these chemokines and impaired the ability of neutrophils to chemoattract other immune cells. Our results amend knowledge about the impact of CN-NFAT inhibition in human neutrophils.
Effects of stubble height on stump sprouting and nutrient accumulation and allocation of Hippophae rhamnoides ssp. sinensis
Authors: Liu Shenghong , Li Zhongmu , Nie Kaihong , Lu Sai , Yao Zengyu , Li Genqian
Published: April 2024

As a main method of forest regeneration, stump sprouting plays a crucial role in forest community succession and vegetation restoration. We aimed to investigate the response of stump sprouting capacity to stubble height, unveil its nutrient-accumulation and allocation strategies and determine the appropriate stubble height most favorable for stump sprouting of Hippophae rhamnoides ssp. sinensis. Fifteen-year plants with signs of premature aging were coppiced at 0, 10 and 20 cm from the ground level. With the increase in stubble height, the number of stump sprouts increased linearly, and the survival rate decreased linearly. The height, diameter and cluster width of stump sprouts first increased, reached the highest level at a stubble height of 10 cm and then decreased. The contents and reserves of N, P, K, Ca and Mg showed a similar trend as the growth, positively correlating with each other. Compared with the control (no coppicing), the coppicing increased the nutrient element allocation of leaves, vertical roots and horizontal roots. Magnesium plays an important role in stump sprouting. The findings suggest that coppicing changed the accumulation ability and allocation pattern of nutrient elements, and further affected the sprouting ability of stumps. The best stubble height for stump sprouting and nutrient accumulation potential was 11.0–14.0 cm estimated by the regression.
SifiNet: a robust and accurate method to identify feature gene sets and annotate cells
Authors: Gao Qi , Ji Zhicheng , Wang Liuyang , Owzar Kouros , Li Qi-Jing , Chan Cliburn , Xie Jichun
Published: April 2024

SifiNet is a robust and accurate computational pipeline for identifying distinct gene sets, extracting and annotating cellular subpopulations, and elucidating intrinsic relationships among these subpopulations. Uniquely, SifiNet bypasses the cell clustering stage, commonly integrated into other cellular annotation pipelines, thereby circumventing potential inaccuracies in clustering that may compromise subsequent analyses. Consequently, SifiNet has demonstrated superior performance in multiple experimental datasets compared with other state-of-the-art methods. SifiNet can analyze both single-cell RNA and ATAC sequencing data, thereby rendering comprehensive multi-omic cellular profiles. It is conveniently available as an open-source R package.
Decreased glucagon in diabetic peripheral neuropathy patients with long duration type 2 diabetes
Authors: Shen Ziyang , Chen Mengxing , Li Qian , Ma Jianhua
Published: April 2024

Objective

The aim of this study was to investigate the association of fasting C-peptide and glucagon with diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2DM).

Methods

A comprehensive evaluation was conducted on 797 patients with T2DM to assess the various risk factors affecting DPN. The subjects were categorized into short duration and long duration group according to the duration of diabetes with a threshold of 10 years. Logistic regression analysis was employed to examine the association between DPN and islet function, as well as other parameters. Receiver operating characteristic curve analysis was performed to evaluate the predictive capability of glucagon.

Results

The fasting C-peptide levels were significantly lower in the DPN patients with short duration of diabetes, but lost significance in the long duration group. Conversely, a decreased level of glucagon was only observed in DPN patients with long duration of diabetes. For the group with long duration of diabetes, glucagon was the sole risk factor associated with DPN. The receiver operating characteristic curve analysis revealed that glucagon in the long duration group exhibited a moderate area under the curve of 0.706.

Conclusions

The serum glucagon levels in T2DM patients with DPN exhibited bidirectional changes based on the duration of diabetes. Decreased glucagon was associated with DPN in T2DM patients with long duration of diabetes.
A Theory of Socially Responsible Investment
Authors: Oehmke Martin , Opp Marcus M
Published: April 2024

We characterize the conditions under which a socially responsible (SR) fund induces firms to reduce externalities, even when profit-seeking capital is in perfectly elastic supply. Such impact requires that the SR fund’s mandate permits the fund to trade off financial performance against reductions in social costs—relative to the counterfactual in which the fund does not invest in a given firm. Based on such an impact mandate, we derive the social profitability index, an investment criterion that characterizes the optimal ranking of impact investments when SR capital is scarce. If firms face binding financial constraints, the optimal way to achieve impact is by enabling a scale increase for clean production. In this case, SR and profit-seeking capital are complementary: Surplus is higher when both investor types are present.
Association of Lamotrigine Plasma Concentrations With Efficacy and Toxicity in Patients With Epilepsy: A Retrospective Study
Authors: Lee Ze-Ning , van Nuland Merel , Bognàr Tim , Leijten Frans S. S. , van der Elst Kim C. M.
Published: April 2024

Background:

There is limited evidence to support the currently suggested lamotrigine (LTG) therapeutic reference range of 2.5–15 mg/L for the treatment of seizures. The objective of this study was to evaluate the association of LTG plasma concentrations with the efficacy and toxicity of the treatment in patients with epilepsy.

Methods:

Patients whose LTG plasma concentration was measured between January 2013 and February 2022 were included. Efficacy was defined as seizure freedom for at least 6 months around the time of measured LTG concentration. Toxicity was defined as any LTG-related adverse drug effect documented in each patient's health record or when the reason for measuring the LTG concentration was toxicity. In addition, the dose–concentration relationship of LTG was assessed.

Results:

In total, 549 concentrations from 259 patients with epilepsy were included. The most common reasons for therapeutic drug monitoring were suspected inefficacy (39%) and pregnancy (21%). The LTG plasma concentration was not associated with efficacy (adjusted odds ratio = 0.94; 95% confidence interval, 0.85–1.04). The LTG plasma concentration was positively associated with the incidence of toxicity after adjusting for age, sex, and number of antiepileptic drugs (odds ratio = 1.11; 95% confidence interval, 1.04–1.19). The daily dose had a significant linear correlation with the LTG plasma concentration (P < 0.001).

Conclusions:

The LTG plasma concentration was associated with toxicity, whereas no association with efficacy was found. A reference range of 2.5–10 mg/L may be considered to decrease the risk of toxicity while maintaining similar efficacy. Therapeutic drug monitoring may be useful when LTG-related toxicity is suspected and in cases of pharmacokinetic changes (eg, pregnancy and concomitant use of interacting drugs) that can influence the LTG plasma concentration.
The “Ukiyo” of Moxibustion Reflected in the Ukiyo-e
Authors: JIANG Shan
Published: April 2024

Ukiyo-e (浮世絵) was a genre of popular art during the Edo and Meiji periods in Japan. Moxibustion, which was originally introduced from China, was also in its heyday and became one of the popular topics for ukiyo-e artists at that time. Using the images as historical evidence perspective, this article focuses on the moxibustion used in daily life in Japan depicted in the ukiyo-e arts. With the perspective of acu-moxa therapy, one may identify some specific issues in the acupoint selection, leading to the discovery of special application of moxibustion used by the group of yūjo (遊女) at that time. The article concludes by exploring gender issues in ukiyo-e arts and the implications of punishment attached to moxibustion treatment.
Determinants of Nurse Managers' Transformational Leadership
Authors: Labrague Leodoro J.
Published: April 2024

OBJECTIVE

The aim of this study was to examine the relationship between various factors and self-perceived transformational leadership among a sample of Filipino nurse managers (NMs).

BACKGROUND

Transformational leadership plays a crucial role in promoting positive outcomes in healthcare settings, particularly for NMs. Understanding the factors that influence NMs' self-perceived transformational leadership is essential for improving leadership practices and enhancing organizational effectiveness.

METHODS

A cross-sectional research design was used to collect data from 260 NMs using standardized measures.

RESULTS

Employment status, the number of units managed, the type of hospital employment, psychological distress, and job satisfaction were factors that significantly influenced their leadership perceptions.

CONCLUSION

By addressing the identified factors, nursing organizations can create an environment that promotes effective leadership practices, ultimately enhancing patient outcomes, staff satisfaction, and overall organizational performance.
Trends of Antimicrobial Susceptibility of Neisseria gonorrhoeae Isolates Between 2012 and 2023: Results From an Open Italian Cohort
Authors: Lucente Maria Francesca , Raccagni Angelo Roberto , Galli Laura , Lolatto Riccardo , Ranzenigo Martina , Ripa Marco , Ponta Giacomo , Monardo Roberta , Gona Floriana , Clementi Nicola , Burioni Roberto , Carletti Silvia , Castagna Antonella , Nozza Silvia
Published: April 2024

Background

Neisseria gonorrhoeae (Ng) is a public health priority because of the rapid evolution of antimicrobial resistance, the emergence of antibiotic resistance, and the absence of a vaccine against Ng. The aim of this study was to investigate trends in the minimum inhibitory concentration and resistance (R) or reduced susceptibility (DS) of Ng cases to ceftriaxone (CRO), azithromycin (AZM), tetracycline (TET), benzylpenicillin (PenG), and ciprofloxacin (CIP) during a 10-year period.

Methods

We conducted a retrospective analysis on an open cohort of Ng cases diagnosed on rectal, urethral, and pharyngeal samples at San Raffaele Scientific Institute, between September 2012 and February 2023. Minimum inhibitory concentrations of antibiotics were determined by gradient-test strips. Bivariate linear regression models were applied on logarithmic minimum inhibitory concentrations values; Cochran-Armitage test was used to determine a linear trend in the proportions of resistant strains.

Results

A total of 436 Ng isolates from 352 individuals were analyzed. Minimum inhibitory concentrations of CRO and PenG reduced over time (P < 0.001, P = 0.030), AZM increased (P = 0.001), and CIP and TET did not change (P = 0.473, P = 0.272). The percentages of resistant strains were as follows: PenG, 89.9%; TET, 90.8%; CIP, 48.2%; AZM, and 4.4%. CRO-DS strains were 8.7%, and only 1 case of CRO-R was identified. The proportion of resistant strains increased over time for AZM (P = 0.007), TET (P = 0.001), and CIP (P < 0.001), whereas it decreased for PenG (P < 0.001) and CRO-DS/R strains (P < 0.001).

Conclusions

Ng strains showed high susceptibility to CRO, although we identified cases of DS/R and observed high levels of susceptibility to AZM. Overall, the recommended primary regimen for Ng treatment was confirmed to be effective.
Valuing nature: the case of tropical forests and Costa Rica
Authors: Umaña Quesada Alvaro
Published: April 2024

The paper focuses on the failure to account for the value of standing tropical forests, and of ecosystem services in general, in economic decision-making. This blindness to the values of nature has led to overexploitation, degradation and destruction of tropical forests, which, in turn, has also significantly contributed to greenhouse gas emissions. Forest conservation and restoration has a critical role to play in the fight against climate change and brings a vast array of additional benefits, from security in water, energy, food, health and livelihoods to maintaining biodiversity itself as a core component of our living planet. As first Minister of Environment and Energy under President Oscar Arias (1986–1990), I brought these views into societal decision-making in Costa Rica and here I briefly describe how.

This article is part of the theme issue ‘Bringing nature into decision-making’.
Early versus Later Anticoagulation in Post-Stroke patients with Atrial Fibrillation: A systematic review and Meta-analysis
Authors: Zavaleta-Corvera Carlos , Vasquez-Paredes Gino , Sarmiento-Falen Joaquín , Riveros-Hernandez Olmedo , Caballero-Alvarado José
Published: April 2024

Background

Atrial fibrillation (AF) is the most common cardiac arrhythmia and significantly increases the risk of ischemic stroke, one of its most serious complications. The intricate relationship between AF and stroke necessitates careful consideration in the timing of anticoagulant therapy initiation to prevent stroke recurrence, hemorrhagic transformation, and other complications.

Aim

This study aims to evaluate the efficacy and safety of early versus late initiation of anticoagulant treatment in patients with AF after an ischemic stroke, addressing the critical gap in optimal timing to balance the risk of recurrent stroke against bleeding risks.

Methods

A systematic review and meta-analysis was conducted following the PRISMA-2020 guidelines, with searches performed across multiple databases including PubMed, Scopus, Web of Science, EMBASE, and Cochrane. Randomized controlled trials comparing early versus later initiation of anticoagulation in AF patients post-stroke were included. Data synthesis was performed using a random-effects model, considering recurrent ischemic stroke, symptomatic intracerebral hemorrhage, and mortality as primary outcomes.

Results

From 1444 identified records, three studies and 2989 patients were included, comprising a diverse population in terms of geography and demographics. Meta-analysis revealed that early anticoagulation initiation might be associated with a reduced risk of recurrent ischemic stroke (RR 0.72, 95% CI [0.51-1.00])(p=0.05), although statistical significance was borderline. No significant differences were found in symptomatic intracerebral hemorrhage or mortality rates between early and late initiation. Early intervention was, however, associated with a reduction in other adverse outcomes (RR 0.72, 95% CI [0.54-0.96])(p=0.03).

Conclusions

Early initiation of anticoagulation therapy in AF patients post-ischemic stroke may offer a protective effect against recurrent ischemic events with no significant increase in bleeding or mortality risks. This suggests that early anticoagulation can be safely considered, particularly in light of reducing other adverse outcomes.
Seeing halos: Spatial and consumer-resource constraints to landscape of fear patterns
Authors: Ong Theresa W. , McManus Lisa C. , Vasconcelos Vítor V. , Yang Luojun , Su Chenyang
Published: April 2024

Coral halos are algae-free space surrounding coral patches linked to the landscape of fear hypothesis, where risk-averse herbivores avoid grazing too far from coral shelter. Halo patterns thus provide insight into the state of overfished predator populations on reefs. However, halos are absent in some protected reefs and their sizes are uncorrelated with predator abundance. Here, we show that these observations are consistent with the landscape of fear hypothesis. When coral are dispersed, herbivores have more even shelter from predators across the seascape, allowing herbivores to overgraze and halos to oscillate. When coral are clustered, shelter is limited and halos can stabilize, but reducing herbivore limitation drives critical transitions to cycles that are difficult to recover from. Discordance between theory and observations may, therefore, arise from differences in underlying coral spatial distributions, with broad implications for how the landscape of fear influences pattern formation and ecological resilience in patchy ecosystems.
Unveiling the influence of tumor and immune signatures on immune checkpoint therapy in advanced lung cancer
Authors: Kim Nayoung , Park Sehhoon , Jo Areum , Eum Hye Hyeon , Kim Hong Kwan , Lee Kyungjong , Cho Jong Ho , Ku Bo Mi , Jung Hyun Ae , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Lee Jung-Il , Choi Jung Won , Jeong Dasom , Na Minsu , Kang Huiram , Kim Jeong Yeon , Choi Jung Kyoon , Lee Hae-Ock , Ahn Myung-Ju
Published: April 2024

This study investigates the variability among patients with non-small cell lung cancer (NSCLC) in their responses to immune checkpoint inhibitors (ICI). Recognizing that patients with advanced-stage NSCLC rarely qualify for surgical interventions, it becomes crucial to identify biomarkers that influence responses to ICI therapy. We conducted an analysis of single-cell transcriptomes from 33 lung cancer biopsy samples, with a particular focus on 14 core samples taken before the initiation of palliative ICI treatment. Our objective was to link tumor and immune cell profiles with patient responses to ICI. We discovered that ICI non-responders exhibited a higher presence of CD4+ regulatory T cells, resident memory T cells, and TH17 cells. This contrasts with the diverse activated CD8+ T cells found in responders. Furthermore, tumor cells in non-responders frequently showed heightened transcriptional activity in the NF-kB and STAT3 pathways, suggesting a potential inherent resistance to ICI therapy. Through the integration of immune cell profiles and tumor molecular signatures, we achieved an discriminative power (AUC) exceeding 95% in identifying patient responses to ICI treatment. These results underscore the crucial importance of the interplay between tumor and immune microenvironment, including within metastatic sites, in affecting the effectiveness of ICIs in NSCLC.
Transgenerational epigenetic inheritance increases trait variation but is not adaptive
Authors: Shahmohamadloo René S. , Fryxell John M. , Rudman Seth M.
Published: April 2024

Understanding processes that can produce adaptive phenotypic shifts in response to rapid environmental change is critical to reducing biodiversity loss. The ubiquity of environmentally induced epigenetic marks has led to speculation that epigenetic inheritance could potentially enhance population persistence in response to environmental change. Yet, the magnitude and fitness consequences of epigenetic marks carried beyond maternal inheritance are largely unknown. Here, we tested how transgenerational epigenetic inheritance (TEI) shapes the phenotypic response ofDaphniaclones to the environmental stressorMicrocystis. We split individuals from each of eight genotypes into exposure and control treatments (F0 generation) and tracked the fitness of their descendants to the F3 generation. We found transgenerational epigenetic exposure toMicrocystisled to reduced rates of survival and individual growth and no consistent effect on offspring production. Increase in trait variance in the F3 relative to F0 generations suggests potential for heritable bet hedging driven by TEI, which could impact population dynamics. Our findings are counter to the working hypothesis that TEI is a generally adaptive mechanism likely to prevent extinction for populations inhabiting rapidly changing environments.

One sentence summary

Transgenerational epigenetic inheritance inDaphniaexposed toMicrocystisrevealed negative fitness effects on survival and growth rates, challenging hypotheses of a general selective advantage.
The response to single-gene duplication implicates translation as a key vulnerability in aneuploid yeast
Authors: Dutcher H. Auguste , Hose James , Howe Hollis , Rojas Julie , Gasch Audrey P.
Published: April 2024

Aneuploidy produces myriad consequences in health and disease, yet models of the deleterious effects of chromosome amplification are still widely debated. To distinguish the molecular determinants of aneuploidy stress, we measured the effects of duplicating individual genes in cells with varying chromosome duplications, in wild-type cells and cells sensitized to aneuploidy by deletion of RNA-binding protein Ssd1. We identified gene duplications that are nearly neutral in wild-type euploid cells but significantly deleterious in euploids lackingSSD1orSSD1+aneuploid cells with different chromosome duplications. Several of the most deleterious genes are linked to translation; in contrast, duplication of other translational regulators, including eI5Fa Hyp2, benefitssd1Δaneuploids over controls. Using modeling of aneuploid growth defects, we propose that the deleterious effects of aneuploidy emerge from an interaction between the cumulative burden of many amplified genes on a chromosome and a subset of duplicated genes that become toxic in that context. Our results suggest that the mechanism behind their toxicity is linked to a key vulnerability in translation in aneuploid cells. These findings provide a perspective on the dual impact of individual genes and overall genomic burden, offering new avenues for understanding aneuploidy and its cellular consequences.
Horizontally transferred glycoside hydrolase 26 may aid hemipteran insects in plant tissue digestion
Authors: Walt Hunter K. , Ahn Seung-Joon , Hoffmann Federico
Published: April 2024

Glycoside hydrolases are enzymes that break down complex carbohydrates into simple sugars by catalyzing the hydrolysis of glycosidic bonds. There have been multiple instances of adaptive horizontal gene transfer of genes belonging to various glycoside hydrolase families from microbes to insects, as glycoside hydrolases can metabolize constituents of the carbohydrate-rich plant cell wall. In this study, we characterize the horizontal transfer of a gene from the glycoside hydrolase family 26 (GH26) from bacteria to insects of the order Hemiptera. Our phylogenies trace the horizontal gene transfer to the common ancestor of the superfamilies Pentatomoidea and Lygaeoidea, which include stink bugs and seed bugs. After horizontal transfer, the gene was assimilated into the insect genome as indicated by the gain of an intron, and a eukaryotic signal peptide. Subsequently, the gene has undergone independent losses and expansions in copy number in multiple lineages, suggesting an adaptive role of GH26s in some insects. Finally, we measured tissue-level gene expression of multiple stink bugs and the large milkweed bug using publicly available RNA-seq datasets. We found that the GH26 genes are highly expressed in tissues associated with plant digestion, especially in the principal salivary glands of the stink bugs. Our results are consistent with the hypothesis that this horizontally transferred GH26 was co-opted by the insect to aid in plant tissue digestion and that this HGT event was likely adaptive.
Gra-CRC-miRTar: The pre-trained nucleotide-to-graph neural networks to identify potential miRNA targets in colorectal cancer
Authors: Yin Rui , Zhao Hongru , Li Lu , Yang Qiang , Zeng Min , Yang Carl , Bian Jiang , Xie Mingyi
Published: April 2024

Colorectal cancer (CRC) is the third most diagnosed cancer and the second deadliest cancer worldwide representing a major public health problem. In recent years, increasing evidence has shown that microRNA (miRNA) can control the expression of targeted human messenger RNA (mRNA) by reducing their abundance or translation, acting as oncogenes or tumor suppressors in various cancers, including CRC. Due to the significant up-regulation of oncogenic miRNAs in CRC, elucidating the underlying mechanism and identifying dysregulated miRNA targets may provide a basis for improving current therapeutic interventions. In this paper, we proposed Gra-CRC-miRTar, a pre-trained nucleotide-to-graph neural network framework, for identifying potential miRNA targets in CRC. Different from previous studies, we constructed two pre-trained models to encode RNA sequences and transformed them into de Bruijn graphs. We employed different graph neural networks to learn the latent representations. The embeddings generated from de Bruijn graphs were then fed into a Multilayer Perceptron (MLP) to perform the prediction tasks. Our extensive experiments show that Gra-CRC-miRTar achieves better performance than other deep learning algorithms and existing predictors. In addition, our analyses also successfully revealed 172 out of 201 functional interactions through experimentally validated miRNA-mRNA pairs in CRC. Collectively, our effort provides an accurate and efficient framework to identify potential miRNA targets in CRC, which can also be used to reveal miRNA target interactions in other malignancies, facilitating the development of novel therapeutics.
Chromatin-focused genetic and chemical screens identify BRPF1 as a targetable vulnerability in Taxol-resistant triple-negative breast cancer
Authors: Yedier-Bayram Ozlem , Cingöz Ahmet , Yilmaz Ebru , Aksu Ali Cenk , Esin Beril , Pınarbaşı-Değirmenci Nareg , Cavga Ayse Derya , Dedeoğlu Beyza , Cevatemre Buse , Syed Hamzah , Philpott Martin , Cribbs Adam P. , Oppermann Udo , Lack Nathan A. , Acilan Ceyda , Onder Tamer T. , Bagci-Onder Tugba
Published: April 2024

Triple-negative breast cancer (TNBC) stands out as a particularly aggressive and frequently recurring form of breast cancer. Due to the absence of hormone receptors, the available treatment avenues are constrained, making chemotherapy the primary approach. Unfortunately, the development of resistance to chemotherapy poses a significant challenge, further restricting the already limited therapeutic alternatives for recurrent cases. Understanding the molecular basis of chemotherapy resistance in TNBC is pivotal for improving treatment outcomes. Here, we generated two different Taxol-resistant TNBC cell lines with a dose-escalation method to mimic chemotherapy resistancein vitro. These cells exhibited hallmark features of resistance, including reduced cell growth, altered morphology, and evasion of apoptosis. Transcriptome analysis uncovered elevatedABCB1expression and multidrug-resistant phenotype in the resistant cells. To comprehensively investigate the key epigenetic regulators of Taxol resistance, we conducted chromatin-focused genetic and chemical screens and pinpointed Bromodomain and PHD Finger Containing 1 (BRPF1) as a novel regulator of Taxol resistance in TNBC cells. Knockout of BRPF1, the reader protein in the MOZ/MORF histone acetyl-transferase complex, but not the other complex members, sensitized resistant cells to Taxol. Additionally, BRPF1 inhibitors, PFI-4 and OF-1, in combination with Taxol significantly reduced cell viability. Transcriptome analysis upon BRPF1 loss or inhibition revealed a negative impact on ribosome biogenesis-related gene sets, resulting in a global decrease in protein translation in Taxol-resistant cells. Our ChIP-qPCR analysis demonstrated that active BRPF1 directly interacts with theABCB1promoter, enhancing its expression towards inducing a multidrug-resistant phenotype. Conversely, knockout or inhibition of BRPF1 leads to decreased ABCB1 expression. This dual mechanism critically sensitizes Taxol-resistant TNBC cells to chemotherapy. Our findings uncover a comprehensive molecular framework, highlighting the pivotal role of epigenetic reader protein BRPF1 in Taxol resistance and providing potential avenues for therapeutic intervention in TNBC.
FOXA1 is required for ErbB2 expression and luminal differentiation in HER2-positive breast cancer
Authors: Jeong Jaekwang , Lee Jongwon , Lim Jaechul , Shin Jaehun , Yoo Kwangmin , Kim Jonghun , Tanaka Yoshiaki , Tae Hyun Seop , Kim Lark Kyun , Park In-Hyun , Wysolmerski John , Choi Jungmin
Published: April 2024

Abstract

Forkhead box protein A1 (FOXA1), a pioneering transcriptional factor known for its critical roles in prostate and ERα−positive breast cancer, is also expressed in human epidermal growth factor receptor-2 (HER2/ErbB2)-positive breast cancers. However, its role in HER2-pos tumors is less well understood. Here we investigate the function of FOXA1 in HER2/ErbB2- positive breast cancers. The loss of FOXA1 was associated with a marked decrease in the viability of HER2-positive and HER2 amplified cell lines, suggesting a pivotal involvement of FOXA1 in these breast cancers. Employing patient-derived single-cell RNA sequencing and spatial transcriptomics, we demonstrate thatFOXA1is co-expressed withErbB2in HER2- positive breast cancers. Suppression of FOXA1 expression led to the reduction of HER2 expression and signaling. Chromatin Immunoprecipitation Sequencing (ChIP-seq) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) identified FOXA1 binding motifs in theErbB2promoter and regulatory element regions, which controlledErbB2 geneexpression. Notably, FOXA1 knockdown was observed to enhance Epithelial-Mesenchymal Transition (EMT) signaling and impede luminal tumor differentiation. Furthermore, we find that FOXA1 and TRPS1 combine to regulate TEAD/YAP-TAZ activity. Taken together, these findings highlight the essential role of FOXA1 in maintaining HER2 expression and a luminal cell phenotype in HER2-positive breast cancers.