bluuebunny/crossref_metadata_2025 huggingface dataset:
Frog call transmission in forestry monocultures: Are there drawbacks?
Authors: Escalona Moisés , Castroviejo‐Fisher Santiago , Simões Pedro Ivo
Published: August 2023

Anuran males emit advertisement calls for the purpose of attracting females and repelling conspecific males. Call transmission is influenced by the acoustics of the propagation environment, including vegetation. Thus, forestry monocultures of non‐native trees represent artificial environments that could modify call transmission. These monocultures have substituted large areas of Atlantic Forest in southern Brazil, representing a conservation challenge. Considering this context, we hypothesized that anurans have calls that are less attenuated in their native environment than in forest plantations. To test it, we performed sound transmission experiments using calls of three anuran species native to southern Brazil: Boana bischoffi, B. leptolineata, and Hylodes meridionalis. We compared sound attenuation between the native forest and forestry monocultures (Eucalyptus sp. and Pinus sp. forests), and included distance from the sound source, air temperature, humidity, and vegetation density as cofactors in linear mixed models. Our results show that the advertisement calls of the two tree frogs (Boana) attenuate less in tree plantations than in native forests, while the third species shows either no differences or less attenuation in native forests. Our results can be understood according to differences in natural history and microhabitat use among the studied species. The two tree frog species vocalize perched from vegetation so their calls become better transmitted in forestry monocultures, which have fewer trees than the native forest. On the other hand, H. meridionalis calls from rocks on streams and the propagation is finely tuned to this peculiar microhabitat. We discuss the conservation implications of our findings for anurans and for the Atlantic Forest. Abstract in Portuguese and Spanish are available with online material.
Editorial: Primum non nocere – are adverse events accurately reported in studies on psychological interventions for children?
Authors: Purgato Marianna , Cortese Samuele
Published: August 2023

Adverse Events (AEs) are defined as any unfavorable and unintended sign or symptom, that may occur during or after receipt of any intervention. The principle of non‐maleficence requires careful consideration to ensure that existing or new psychological interventions are not harmful before they can be considered beneficial. In this context, the safety of psychological interventions, including the possible occurrence of AEs, is increasingly important for patients, families, and clinicians. The evaluation of AEs is crucial to obtain a complete understanding of the risk/benefit balance of psychological interventions. There is a need for researchers and clinicians to assess and report AEs comprehensively and in a coordinated manner. It is necessary to have more accurate data on the recording of AEs in protocols to enhance transparency and consistency, as well as to improve practice. Finally, and to facilitate this process, there is a need for standards for data collection.
Generative Adversarial Shaders for Real‐Time Realism Enhancement
Authors: Salmi A. , Cséfalvay Sz. , Imber J.
Published: August 2023

Application of realism enhancement methods, particularly in real‐time and resource‐constrained settings, has been frustrated by the expense of existing methods. These achieve high quality results only at the cost of long runtimes and high bandwidth, memory, and power requirements. We present an efficient alternative: a high‐performance, generative shader‐based approach that adapts machine learning techniques to real‐time applications, even in resource‐constrained settings such as embedded and mobile GPUs. The proposed learnable shader pipeline comprises differentiable functions that can be trained in an end‐to‐end manner using an adversarial objective, allowing for faithful reproduction of the appearance of a target image set without manual tuning. The shader pipeline is optimized for highly efficient execution on the target device, providing temporally stable, faster‐than‐real time results with quality competitive with many neural network‐based methods.
Expression and prognostic value of Cripto‐1 in early non‐small cell lung cancer
Authors: Zhong Jian , Li Li , Zhang Qian , Zou Jue , Liu Wei , Xu Chun Hua
Published: August 2023

Objective

We aim to explore the expression of Cripto‐1 (CR‐1) protein in patients with early stage non‐small cell lung cancer (NSCLC).

Methods

We investigated CR‐1 expression status in specimens obtained from 240 patients with resected NSCLC and 30 cases of para‐carcinous normal lung tissues.

Results

Compared with normal lung tissue, the positive expression of CR‐1 protein in NSCLC was significantly increased (p < 0.005). Cox multivariate regression analysis showed that the expression of CR‐1 protein was an independent prognostic factor for early stage NSCLC (p = 0.002).

Conclusion

Detecting CR‐1 protein can predict the prognosis and recurrence in patients with NSCLC.
Intracranial squamous papillary lesion
Authors: Vidal‐Robau Nuria , Reyes Luis Alberto , Enseñat Nora Joaquim , Capurro Ferrer Sebastian , Perez Muñoz Francisco Manuel , Ribalta Teresa , Aldecoa Iban
Published: August 2023

Intracranial lesions with squamous differentiation raise a diagnostic challenge, which can include benign or malignant, primary and metastatic lesions. Here is the case of a 49‐year‐old woman, in which intraoperative cytology helped the differential and final diagnosis.
Ultrasound‐guided hepatic portal vein injection is not a reproducible technique for delivery of cell therapies to the liver in mice
Authors: Walker Sophie L. , Noble June , Thomson Adrian , Moran Carmel M. , Mellis David , Lee I‐Ning , White Lisa J. , Forbes Shareen
Published: August 2023

Aims

Our aim was to determine if ultrasound‐guided HPV injection in mice would provide reproducible and reliable results, as is currently obtained via open laparotomy techniques, and offer a surgical refinement to emulate islet transplantation in humans.

Methods

Fluorescent‐polymer microparticles (20 μm) were injected (27G‐needle) into the HPV via open laparotomy (n = 4) or under ultrasound‐guidance (n = 4) using an MX550D‐transducer with a Vevo3100‐scanner (FUJIFILM VisualSonics, Inc.). Mice were culled 24‐h post injection; organs were frozen, step sectioned (10 μm‐slices) and 10 sections/mouse (50 μm‐spacing) were quantified for microparticles in the liver and other organs by fluorescent microscopy.

Results

Murine HPV injection, via open laparotomy‐route, resulted in widespread distribution of microparticles in the liver, lungs and spleen; ultrasound‐guided injection resulted in reduced microparticle delivery (p < 0.0001) and microparticle clustering in distinct areas of the liver at the site of needle penetration, with very few/no microparticles being seen in lung and spleen tissues, hypothesised to be due to flow into the body cavity: liver median (interquartile range) 4.15 (0.00–4.15) versus 0.00 (0.00–0.00) particle‐count mm−2, respectively.

Conclusions

Ultrasound‐guided injection results in microparticle clustering in the liver, with an overall reduction in microparticle number when compared to open laparotomy HPV injection, and high variability in microparticle‐counts detected between mice. Ultrasound‐guided injection is not currently a technique that can replace open laparotomy HPV of islet transplantation in mice.
The influence of flow on movement of a headwater specialist in an intermittent urban headwater stream
Authors: Curtis Katherine , Sanders Adam , Urbanic Megan , Israel Gabriyelle , McCombs Connoe , Pastura Logan , Matter Stephen F. , Booth Michael T.
Published: August 2023

Fish movement in freshwater streams is often tied to patterns of flow, especially when the stream is intermittent, flashy, or some combination thereof. Relationships between flow and fish movement are exacerbated in small urban streams in impervious surface‐dominated watersheds that lead to extreme flow conditions. Here we examined the response of Creek Chub (Semotilus atromaculatus), a common pioneer fish species in eastern North America, to flow events of various sizes in a small intermittent urban headwater stream. Our primary goals were to determine (1) the level of Creek Chub movement occurring in an intermittent headwater stream, (2) the influence of flow on movement direction and magnitude, (3) the degree of variation in individual movement behaviour, and (4) mortality rates in the system. The study used PIT tagging and telemetry surveys to monitor Creek Chub movement over a six‐month period. We found that individual Creek Chub in our study system were generally mobile (71%), but usually moved short distances only; however, a few individuals moved much farther, with a maximum single movement of 521 m. Moderate or major flow events increased the probability and magnitude of Creek Chub movement, but there was no detectable asymmetry towards upstream or downstream directionality. Movement was variable among individual fish and fish were able to respond to large and small flow events to move among habitats. Finally, we observed relatively high, but episodic, mortality in our study site, potentially related to pollution events. Evidence of elevated mortality points to the potential importance of movement in highly disturbed streams, as it may enable recolonization after local extirpation.
The spatial distribution of insect communities of a mountaintop forest archipelago is not correlated with landscape structure: A multitaxa approach
Authors: Camarota Flávio , Dáttilo Wesley , da Silva Pedro Giovâni , de Castro Flávio Siqueira , do Vale Beirão Marina , Perillo Lucas Neves , Corro Erick , Fernandes Geraldo Wilson , de Siqueira Neves Frederico
Published: August 2023

Understanding community assembly in habitat patches requires an integrative approach, considering the potential role of local and regional factors and organisms' dispersal abilities among patches. For this, assessing the degree of species overlap between patches (nestedness) can be particularly informative, especially regarding different taxa and distinct patch properties.

We assessed the potential role of landscape‐patch structure in shaping the nestedness patterns of five taxonomic groups with distinct dispersal abilities (ants, bees, dung beetles, fruit‐feeding butterflies and aculeate wasps).

We collected insects from 11 forest patches in the Espinhaço mountain range in southeast Brazil. We assessed the potential contribution of three forest island attributes (size, distance and shape) to the nestedness of insect communities and then tested if metacommunities were significantly nested with respect to habitat (forest islands). Finally, we evaluated how species of each taxonomic group contribute to metacommunity nestedness.

While there was a substantial variation in the contribution to the nested pattern within each taxon, all taxa studied exhibited a significantly nested pattern of species distribution. The landscape‐patch structure and the vagility of the different taxa did not influence the contribution of sites to the metacommunity nested pattern.

Our integrative approach provides critical data on the role of different factors in shaping species distribution in natural patches. Species with different dispersal abilities and patches with distinct landscape properties contributed similarly to nestedness, indicating the potential role of the vegetation matrix permeability in shaping the distribution of organisms in the studied forest archipelago.
Upadacitinib treatment withdrawal and retreatment in patients with moderate‐to‐severe atopic dermatitis: Results from a phase 2b, randomized, controlled trial
Authors: Guttman‐Yassky Emma , Silverberg Jonathan I. , Thaçi Diamant , Papp Kim A. , Ständer Sonja , Beck Lisa A. , Kim Brian S. , Hu Xiaofei , Liu Jianzhong , Calimlim Brian M. , Vigna Namita , Crowley Jameson T. , Teixeira Henrique D. , Thyssen Jacob P.
Published: August 2023

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic eczematous lesions. The effect of treatment withdrawal after response to upadacitinib oral treatment is not fully characterized.

Objectives

Assess the effect of upadacitinib withdrawal on skin clearance and itch improvement in adult patients with moderate‐to‐severe AD and evaluate the kinetics of recovery on rescue treatment.

Methods

Data from a phase 2b randomized, placebo‐controlled trial (NCT02925117) of upadacitinib in patients with moderate‐to‐severe AD were analysed. Patients were randomized 1:1:1:1 to receive upadacitinib 7.5 mg, 15 mg, 30 mg or placebo, and then at Week 16, patients were re‐randomized 1:1 to receive the same dose of upadacitinib (upadacitinib 30 mg for patients initialized to placebo) or placebo. From Week 20, those who experienced loss of response defined as Eczema Area and Severity Index <50% improvement from baseline (EASI 50) received rescue treatment with upadacitinib 30 mg.

Results

Patients who withdrew from upadacitinib experienced a rapid loss of skin clearance response, while those who switched from placebo to upadacitinib gained response. Loss of skin clearance response occurred within 4 weeks and worsening of itch occurred within 5 days. In patients who originally received placebo or a lower dose of upadacitinib leading to a loss of EASI response, rescue treatment with upadacitinib 30 mg resulted in rapid recovery or improvement of both skin and itch responses; most patients who were re‐randomized to placebo achieved EASI 75 and IGA 0/1 by 8 weeks of rescue treatment. No new safety risks were observed.

Conclusions

Continuous treatment with upadacitinib is suggested to maintain skin clearance and antipruritic effects.
Predictive factors of atopic‐like dermatitis induced by IL‐17A inhibitors in patients with psoriasis: A 2‐year follow‐up study
Authors: Tang Xin , Li Qian , Zhou Ying , Zheng Xuyu , Zhou Cui , Hu Yulian , Wang Ping , Chen Aijun , Huang Kun
Published: August 2023

Background

Atopic‐like dermatitis (ALD) is a common side effect of interleukin‐17A (IL‐17A) inhibitors.

Objective

To determine the prevalence, risk factors, outcomes and treatment of ALD in a cohort of psoriasis patients treated with IL‐17A inhibitors.

Methods

This retrospective study included 226 psoriasis patients treated with an IL‐17A inhibitor in our dermatology department between July 2020 and July 2022. The patients were reviewed over 2 years. A logistic regression model in rare events data (relogit) was used to predict the risk factors for ALD.

Results

Of the 226 patients, 14 had ALD. Data including age, body mass index, IL‐17A inhibitor use, personal and family history of atopic disease, pet ownership history, and immunoglobulin E (IgE) levels were analysed using the relogit regression model. It indicated a personal history of atopic disease (odd ratio [OR] 27.830, 95% confidence interval [CI] 3.801–203.770; p = 0.001) and elevated IgE levels (OR 5.867, 95% CI 1.131–30.434; p = 0.035) as independent predictors of incident ALD. In one patient, anti‐IL‐17A therapy was discontinued, and treatment was switched to tofacitinib. Thirteen patients who continued with IL‐17A inhibitor were treated with topical therapy and/or antihistamines, and their ALD was partially or completely resolved.

Conclusion

In this study, the incidence rate of ALD was 6.19%. Elevated IgE levels and a personal history of atopic disease were found to be the risk factors for ALD. Our study findings suggest that treatment should be provided based on the severity of psoriasis and incident ALD. Prior to treatment, psoriasis patients who have the risk factors for ALD should be informed of the possible development of ALD, and alternative psoriatic therapeutic options should be considered if severe ALD develops.
Impact of balance on the energetic cost of walking and gait speed
Authors: Brown Colleen , Simonsick Eleanor , Schrack Jennifer , Ferrucci Luigi
Published: August 2023

Background

Examine the relationship between balance test performance and the energetic cost of walking (ECW) and gait speed.

Methods

Cross‐sectional and longitudinal analyses of data from the Baltimore Longitudinal Study of Aging. Men (48%) and women aged 60–96 years enrolled in the BLSA between 2007 and 2020 (n = 1132). Balance was assessed using narrow walk (NW) and progressive standing balance tests (SB). ECW measured during 2.5‐min usual paced walk while participants wore a portable indirect calorimeter. Gait speed assessed over 6‐m. Each test parameterized using validated methods. Statistical analysis to compare balance measures to ECW, and gait speed used generalized logistic regression models and adjustments for age, sex, race, height, weight, and comorbidities.

Results

Cross‐sectionally, mean ECW was higher and gait speed slower in persons who failed the NW than those who passed (0.189 vs. 0.164 mL/kg/m, p < 0.0001 and 0.96 vs. 1.15 m/s, p < 0.0001, respectively). Mean ECW was increasingly higher and gait speed slower over three progressively challenging SB tests (0.207 vs. 0.171 vs. 0.164 mL/kg/m, p < 0.0001 and 0.95 vs. 1.05 vs. 1.15 m/s, p < 0.0001). Over an average 2.4 years, those who declined in SB and NW had a higher ECW and slower gait speed than persons who maintained performance (SB: 0.18 vs. 0.160 mL/kg/m, p = 0.0003, and 1.00 vs. 1.13 m/s, p = <0.001; NW: 0.175 vs. 0.160 mL/kg/m, p = 0.002, and 1.04 vs. 1.14 m/s, p = 0.001). Persons who improved had lower ECW and faster gait speed than those who failed at both visits (SB: 0.169 vs. 0.240 mL/kg/m, p = 0.0002, and 0.99 vs. 0.94 m/s, p = 0.67, NW: 0.163 vs. 0.195 mL/kg/m, p = 0.0005, and 1.10 vs. 0.92 m/s, p < 0.001).

Conclusion

Instability contributes to higher ECW and slower gait speed which suggests that rehabilitation efforts to improve balance may help maintain function further into older adulthood and delay mobility limitation.
Complementary and alternative treatments for insomnia disorder: a systematic umbrella review
Authors: Ell Johanna , Schmid Sarah R. , Benz Fee , Spille Lukas
Published: August 2023

Insomnia is a common disorder and cognitive behavioural therapy for insomnia (CBT‐I) is recommended as first‐line treatment. However, CBT‐I is not widely distributed and infrequently available while medication is not indicated for long‐term use. To close this evident gap in supply, alternative treatments could be utilised. High‐quality research on this topic is scarce, and there is currently no comprehensive publication on the effectiveness of alternative treatments. To address this pressing question, we systematically summarised the existing research on alternative treatments for insomnia. A comprehensive search of systematic reviews and (network) meta‐analyses of randomised controlled trials investigating the efficacy of alternative treatments compared to waiting‐list control or placebo in adults with insomnia disorder with or without comorbidities was conducted in PubMed, MEDLINE, PsycInfo, and PsycArticles on December 6, 2022, yielding 391 records. Finally, 15 eligible studies were included. Evidence on acupuncture, exogenous melatonin, mind–body interventions and exercise, repetitive transcranial magnetic stimulation (rTMS), valerian, and light exposure was found. Acupuncture, rTMS and mind–body exercises significantly improved sleep quality and insomnia severity but effects on objectively assessed outcomes were inconclusive. Melatonin led to a reduction in both self‐reported and objectively assessed sleep onset latency. Light exposure and valerian did not significantly improve sleep outcomes. Overall, the quality of studies was rated as low. Results indicate that alternative treatments are effective mostly on subjective outcomes. However, evidence on the efficacy of some intervention types is sparse and there is a need for high‐quality original studies. Future research could investigate whether combining different alternative treatment aspects with CBT‐I improves individual treatment.
Trigger warnings as tools for learning—theorising an evolving cultural concept
Authors: Nolan Helen Anne , Roberts Lesley
Published: August 2023

Background

While definitions of trigger warnings vary, it is generally accepted that they caution about potential reactions arising from exposure to distressing material. Controversy surrounds use of warnings in education, with concerns noted regarding impacts on academic freedom, “coddling”, thereby undermining resilience, reinforcement of traumatised identity and enablement of avoidance. Proponents of warnings position them as accommodations for those affected by trauma, enhancing inclusion, and suggest warnings empower choice and enable informed engagement in learning. A recent meta‐analysis of warnings' efficacy demonstrated no effect on affective responses or comprehension. Findings regarding avoidance suggested warnings mayincreaseengagement with material. Synthesis of heterogeneous results relating to context of warning application necessitates cautious interpretation of findings. Furthermore, controlled experimental designs do not reflect complex ecologies of social learning environments.

Methods

Evidence relating to warnings in healthcare professions education remains limited. We undertake a narrative review and synthesis of evidence regarding the role and functions of trigger warnings from a range of disciplines, to inform healthcare education practice. We apply this evidence in considering how warnings may act within a range of theoretical frameworks for healthcare professionals educations including andragogy, self‐directed learning and, ultimately, transformative learning. Tensions between exposure to emotionally stimulating learning episodes and the necessity of emotion for learning while simultaneously attending to learners' needs and fulfilling educators' responsibilities are explored. We probe gaps and contentions in existing theoretical frameworks for learning, and consider implications of recognised limitations with reference to warnings. We summarise by proposing a conceptual model for the role of warnings that considers wider salient factors for fostering effective learning.

Discussion and conclusions

Difficulties associated with deriving contextually‐relevant evidence and conclusions relating to warnings as an evolving cultural concept are highlighted. We propose warnings as tools to enable critical reflection and emotional literacy, to curate effective learning environments and support humanistic healthcare professional identity formation, within wider trauma‐informed pedagogies and educator practice.
Transfusion management in thalassemia
Authors: Boudreaux Jeanne
Published: August 2023

This review describes the current challenges and recommendations in the transfusion management of thalassemia patients. In addition, it reviews the components of blood safety and blood product modification in special populations. Adverse transfusion reactions are described as are some of the newer technologies being utilized to reduce potential transfusion‐associated pathogens. Lastly, research in blood storage and in manufactured blood is briefly described.
On Wittgenstein's remarks about the standard metre
Authors: Büttner Kai Michael
Published: August 2023

In a notorious passage from his Philosophical Investigations, Wittgenstein writes that one can state of the standard metre neither that it is one metre long, nor that it is not one metre long. While many commentators have rejected this claim, it has been commonly assumed that Wittgenstein himself endorsed it. In a recently published article, Thomas Müller not only provides a novel argument against Wittgenstein's claim about the standard metre but also claims that Wittgenstein did not actually endorse that claim. In this paper, I argue that Müller's exegetical thesis is false and that his novel argument against Wittgenstein's claim about the standard metre is unsound.
Novel method for laparoscopic rectus sheath tunneling with Lin's tube in peritoneal dialysis catheter implantation
Authors: Chang Yuntzu , Chang Wei‐Jung , Cheng‐Yen Huang , Chiu Ping‐Fang , Lin Kuo‐Hua
Published: August 2023

Laparoscopic implantation of a catheter through rectus sheath tunnel minimizes the risks of catheter failure and reduces some complications like catheter migration, hernias, and leaks. We described a novel method for laparoscopic catheter rectus sheath tunneling using an aspiration tube and a silk tie (Lin's tube). This material is easily available and yields a small fascial defect with an equivalent cannula size to minimize tissue disruption. The technique is feasible, reproducible and it may reduce the risks of postoperative leakage and hemorrhage.
The novel HLA‐DQA1*03:01:12 allele identified using next‐generation sequencing in a Melanesian individual
Authors: Raz Maxime , Demortier Justine , Frassati Coralie , Picard Christophe , Pedini Pascal
Published: August 2023

HLA‐DQA1*03:01:12 differs from HLA‐DQA1*03:01:01:01 by one nucleotide substitution in codon 21 in exon 2.
Characterization of the novel HLA‐B*35:546 allele by next‐generation sequencing
Authors: Dong Lina , Pi Wenwen , Chen Nanying , Zhang Wei , Zhu Faming
Published: August 2023

HLA‐B*35:546 differs from HLA‐B*35:03:01:01 by a single nucleotide substitution at position 397 C > T.
Comparative constraint‐based modelling of fruit development across species highlights nitrogen metabolism in the growth‐defence trade‐off
Authors: Colombié Sophie , Prigent Sylvain , Cassan Cédric , Hilbert‐Masson Ghislaine , Renaud Christel , Dell'Aversana Emilia , Carillo Petronia , Moing Annick , Beaumont Chloé , Beauvoit Bertrand , McCubbin Tim , Nielsen Lars Keld , Gibon Yves
Published: August 2023

Although primary metabolism is well conserved across species, it is useful to explore the specificity of its network to assess the extent to which some pathways may contribute to particular outcomes. Constraint‐based metabolic modelling is an established framework for predicting metabolic fluxes and phenotypes and helps to explore how the plant metabolic network delivers specific outcomes from temporal series. After describing the main physiological traits during fruit development, we confirmed the correlations between fruit relative growth rate (RGR), protein content and time to maturity. Then a constraint‐based method is applied to a panel of eight fruit species with a knowledge‐based metabolic model of heterotrophic cells describing a generic metabolic network of primary metabolism. The metabolic fluxes are estimated by constraining the model using a large set of metabolites and compounds quantified throughout fruit development. Multivariate analyses showed a clear common pattern of flux distribution during fruit development with differences between fast‐ and slow‐growing fruits. Only the latter fruits mobilise the tricarboxylic acid cycle in addition to glycolysis, leading to a higher rate of respiration. More surprisingly, to balance nitrogen, the model suggests, on the one hand, nitrogen uptake by nitrate reductase to support a high RGR at early stages of cucumber and, on the other hand, the accumulation of alkaloids during ripening of pepper and eggplant. Finally, building virtual fruits by combining 12 biomass compounds shows that the growth‐defence trade‐off is supported mainly by cell wall synthesis for fast‐growing fruits and by total polyphenols accumulation for slow‐growing fruits.
Plant-derived extracts P2Et and Anamu-SC affect NO and ROS levels in leukemic cells
Authors: Juan José Arévalo-Ferrin  , Jimmy Alejandro García-Ortiz  , Cindy Mayerli Arévalo-Olaya  , Sandra Milena Quijano-Gómez  , Susana Fiorentino-Gómez  , Rodríguez Pardo Viviana Marcela
Published: August 2023

Leukemic cells often show high nitric oxide (NO) and reactive oxygen species (ROS) levels. These can lead to resistance to apoptosis and therapy and increased proliferation. Plant-derived extracts decrease chemoresistance in cancer cells. In this study, we evaluated the effects of the plant-derived extracts P2Et (Caesalpinia spinosa) and Anamu-SC (Petiveria alliacea) and their combination with chemotherapeutic agents on NO and ROS levels in leukemic cell lines K562 and Reh. NO and ROS were determined using the DAF-FM DA and H2DCFDA probes. The mean fluorescence intensity for each variable was measured by flow cytometry. The extracts showed an antioxidant effect on both cell lines leading to a significant decrease in ROS levels without decreasing cell viability. Anamu-SC also increased NO levels in K562 cells when combined with idarubicin. Both extracts reduced the number of leukemic cells after 12 hours of treatment. Further studies are necessary to evaluate their effect on primary human leukemia cells. These findings suggest the potential of P2Et and Anamu-SC as adjuncts in leukemia treatment.
NPRC deletion attenuates cardiac fibrosis in diabetic mice by activating PKA/PKG and inhibiting TGF-β1/Smad pathways
Authors: Meng Linlin , Lu Yue , Wang Xinlu , Cheng Cheng , Xue Fei , Xie Lin , Zhang Yaoyuan , Sui Wenhai , Zhang Meng , Zhang Yun , Zhang Cheng
Published: August 2023

Cardiac fibrosis plays a key role in the progression of diabetic cardiomyopathy (DCM). Previous studies demonstrated the cardioprotective effects of natriuretic peptides. However, the effects of natriuretic peptide receptor C (NPRC) on cardiac fibrosis in DCM remains unknown. Here, we observed that myocardial NPRC expression was increased in mice and patients with DCM. NPRC
−/−
diabetic mice showed alleviated cardiac fibrosis, as well as improved cardiac function and remodeling. NPRC knockdown in both cardiac fibroblasts and cardiomyocytes decreased collagen synthesis and proliferation of cardiac fibroblasts. RNA sequencing identified that NPRC deletion up-regulated the expression of TGF-β–induced factor homeobox 1 (TGIF1), which inhibited the phosphorylation of Smad2/3. Furthermore, TGIF1 up-regulation was mediated by the activation of cAMP/PKA and cGMP/PKG signaling induced by NPRC deletion. These findings suggest that NPRC deletion attenuated cardiac fibrosis and improved cardiac remodeling and function in diabetic mice, providing a promising approach to the treatment of diabetic cardiac fibrosis.
Inducible nonhuman primate models of retinal degeneration for testing end-stage therapies
Authors: Ail Divya , Nava Diane , Hwang In Pyo , Brazhnikova Elena , Nouvel-Jaillard Céline , Dentel Alexandre , Joffrois Corentin , Rousseau Lionel , Dégardin Julie , Bertin Stephane , Sahel José-Alain , Goureau Olivier , Picaud Serge , Dalkara Deniz
Published: August 2023

The anatomical differences between the retinas of humans and most animal models pose a challenge for testing novel therapies. Nonhuman primate (NHP) retina is anatomically closest to the human retina. However, there is a lack of relevant NHP models of retinal degeneration (RD) suitable for preclinical studies. To address this unmet need, we generated three distinct inducible cynomolgus macaque models of RD. We developed two genetically targeted strategies using optogenetics and CRISPR-Cas9 to ablate rods and mimic rod-cone dystrophy. In addition, we created an acute model by physical separation of the photoreceptors and retinal pigment epithelium using a polymer patch. Among the three models, the CRISPR-Cas9–based approach was the most advantageous model in view of recapitulating disease-specific features and its ease of implementation. The acute model, however, resulted in the fastest degeneration, making it the most relevant model for testing end-stage vision restoration therapies such as stem cell transplantation.
SUMO-activated target traps (SATTs) enable the identification of a comprehensive E3-specific SUMO proteome
Authors: Salas-Lloret Daniel , Jansen Nicolette S. , Nagamalleswari Easa , van der Meulen Coen , Gracheva Ekaterina , de Ru Arnoud H. , Otte H. Anne Marie , van Veelen Peter A. , Pichler Andrea , Goedhart Joachim , Vertegaal Alfred C.O. , González-Prieto Román
Published: August 2023

Ubiquitin and ubiquitin-like conjugation cascades consist of dedicated E1, E2, and E3 enzymes with E3s providing substrate specificity. Mass spectrometry–based approaches have enabled the identification of more than 6500 SUMO2/3 target proteins. The limited number of SUMO E3s provides the unique opportunity to systematically study E3 substrate wiring. We developed SUMO-activated target traps (SATTs) and systematically identified substrates for eight different SUMO E3s, PIAS1, PIAS2, PIAS3, PIAS4, NSMCE2, ZNF451, LAZSUL (ZNF451-3), and ZMIZ2. SATTs enabled us to identify 427 SUMO1 and 961 SUMO2/3 targets in an E3-specific manner. We found pronounced E3 substrate preference. Quantitative proteomics enabled us to measure substrate specificity of E3s, quantified using the SATT index. Furthermore, we developed the Polar SATTs web-based tool to browse the dataset in an interactive manner. Overall, we uncover E3-to-target wiring of 1388 SUMO substrates, highlighting unique and overlapping sets of substrates for eight different SUMO E3 ligases.
Hysteresis of the El Niño–Southern Oscillation to CO
2
forcing
Authors: Liu Chao , An Soon-Il , Jin Fei-Fei , Shin Jongsoo , Kug Jong-Seong , Zhang Wenjun , Stuecker Malte F. , Yuan Xinyi , Xue Aoyun , Geng Xin , Kim Soong-Ki
Published: August 2023

El Niño–Southern Oscillation (ENSO) is the strongest interannual climate variability with far-reaching socioeconomic consequences. Many studies have investigated ENSO-projected changes under future greenhouse warming, but its responses to plausible mitigation behaviors remain unknown. We show that ENSO sea surface temperature (SST) variability and associated global teleconnection patterns exhibit strong hysteretic responses to carbon dioxide (CO
2
) reduction based on the 28-member ensemble simulations of the CESM1.2 model under an idealized CO
2
ramp-up and ramp-down scenario.

There is a substantial increase in the ensemble-averaged eastern Pacific SST anomaly variance during the ramp-down period compared to the ramp-up period. Such ENSO hysteresis is mainly attributed to the hysteretic response of the tropical Pacific Intertropical Convergence Zone meridional position to CO
2
removal and is further supported by several selected single-member Coupled Model Intercomparison Project Phase 6 (CMIP6) model simulations. The presence of ENSO hysteresis leads to its amplified and prolonged impact in a warming climate, depending on the details of future mitigation pathways.
Investigation of hydrated channels and proton pathways in a high-resolution cryo-EM structure of mammalian complex I
Authors: Grba Daniel N. , Chung Injae , Bridges Hannah R. , Agip Ahmed-Noor A. , Hirst Judy
Published: August 2023

Respiratory complex I, a key enzyme in mammalian metabolism, captures the energy released by reduction of ubiquinone by NADH to drive protons across the inner mitochondrial membrane, generating the proton-motive force for ATP synthesis. Despite remarkable advances in structural knowledge of this complicated membrane-bound enzyme, its mechanism of catalysis remains controversial. In particular, how ubiquinone reduction is coupled to proton pumping and the pathways and mechanisms of proton translocation are contested. We present a 2.4-Å resolution cryo-EM structure of complex I from mouse heart mitochondria in the closed, active (ready-to-go) resting state, with 2945 water molecules modeled. By analyzing the networks of charged and polar residues and water molecules present, we evaluate candidate pathways for proton transfer through the enzyme, for the chemical protons for ubiquinone reduction, and for the protons transported across the membrane. Last, we compare our data to the predictions of extant mechanistic models, and identify key questions to answer in future work to test them.
Autonomous hydrogel locomotion regulated by light and electric fields
Authors: Yang Yang , Li Chuang , Palmer Liam C. , Stupp Samuel I.
Published: August 2023

Autonomous robotic functions in materials beyond simple stimulus-response actuation require the development of functional soft matter that can complete well-organized tasks without step-by-step control. We report the design of photo- and electroactivated hydrogels that can capture and deliver cargo, avoid obstacles, and return without external, stepwise control. By incorporating two spiropyran monomers with different chemical substituents in the hydrogel, we created chemically random networks that enabled photoregulated charge reversal and autonomous behaviors under a constant electric field. In addition, using perturbations in the electric field induced by a dielectric inhomogeneity, the hydrogel could be attracted to high dielectric constant materials and autonomously bypasses the low dielectric constant materials under the guidance of the electric field vector. The photo- and electroactive hydrogels investigated here can autonomously perform tasks using constant external stimuli, an encouraging observation for the potential development of molecularly designed intelligent robotic materials.
Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo
Authors: Geretz Aviva , Ehrenberg Philip K. , Clifford Robert J. , Laliberté Alexandre , Prelli Bozzo Caterina , Eiser Daina , Kundu Gautam , Yum Lauren K. , Apps Richard , Creegan Matthew , Gunady Mohamed , Shangguan Shida , Sanders-Buell Eric , Sacdalan Carlo , Phanuphak Nittaya , Tovanabutra Sodsai , Russell Ronnie M. , Bibollet-Ruche Frederic , Robb Merlin L. , Michael Nelson L. , Ake Julie A. , Vasan Sandhya , Hsu Denise C. , Hahn Beatrice H. , Kirchhoff Frank , Thomas Rasmi
Published: August 2023

Host restriction factors play key roles in innate antiviral defense, but it remains poorly understood which of them restricts HIV-1 in vivo. Here, we used single-cell transcriptomic analysis to identify host factors associated with HIV-1 control during acute infection by correlating host gene expression with viral RNA abundance within individual cells. Wide sequencing of cells from one participant with the highest plasma viral load revealed that intracellular viral RNA transcription correlates inversely with expression of the gene
PTMA
, which encodes prothymosin α. This association was genome-wide significant (
P
adjusted
< 0.05) and was validated in 28 additional participants from Thailand and the Americas with HIV-1 CRF01_AE and subtype B infections, respectively. Overexpression of prothymosin α in vitro confirmed that this cellular factor inhibits HIV-1 transcription and infectious virus production. Our results identify prothymosin α as a host factor that restricts HIV-1 infection in vivo, which has implications for viral transmission and cure strategies.
Powering up antifungal treatment: using small molecules to unlock the potential of existing therapies
Authors: Shapiro Rebecca S. , Gerstein Aleeza C.
Published: August 2023

Fungal pathogens are increasingly appreciated as a significant infectious disease challenge. Compared to bacteria, fungal cells are more closely related to human cells, and few classes of antifungal drugs are available. Combination therapy offers a potential solution to reduce the likelihood of resistance acquisition and extend the lifespan of existing antifungals. There has been recent interest in combining first-line drugs with small-molecule adjuvants. In a recent article, Alabi et al. identified 1,4-benzodiazepines as promising molecules to enhance azole activity in pathogenic
Candida
spp. (P. E. Alabi, C. Gautier, T. P. Murphy, X. Gu, M. Lepas, V. Aimanianda, J. K. Sello, I. V. Ene, 2023, mBio
https://doi.org/10.1128/mbio.00479-23
). These molecules have no antifungal activity on their own but exhibited significant potentiation of fluconazole in azole-susceptible and -resistant isolates. Additionally, the 1,4-benzodiazepines increased the fungicidal activity of azoles that are typically fungistatic to
Candida
spp., inhibited filamentation (a virulence-associated trait), and accordingly increased host survival in
Galleria mellonella
. This research thus provides another encouraging step on the critical pathway toward reducing mortality due to antimicrobial resistance.
Health conditions among retired elite rugby players: a scoping review
Authors: Le Roux Johan , Anema Flo , Janse van Rensburg Dina Christa , Kerkhoffs Gino , Gouttebarge Vincent
Published: August 2023

The aim of this scoping review was to present an overview of the existing epidemiological evidence in retired male and female elite rugby players regarding the prevalence rates of musculoskeletal, cardiovascular, neurocognitive, psychological and gynaecological health conditions. A systematic search was carried out across MEDLINE (via PubMed), SPORTDiscus (via EBSCOhost), PsycINFO (via EBSCOhost) and EMBASE for musculoskeletal (eg, osteoarthritis), cardiovascular (eg, hypertension), neurocognitive (eg, dementia) and psychological health (eg, disordered eating, alcohol misuse) conditions in retired elite male and female rugby players and gynaecological health conditions (menorrhagia) in retired female rugby players. Primary research studies describing the prevalence rates of health conditions in retired elite male and female rugby players written in English, Dutch or French and with full text available online were included. Five hundred and seventy-three citations were originally identified and 16 studies were ultimately included in our review. No studies on health conditions in retired elite female rugby players were found. Four individual studies showed there was a significant higher prevalence rate of osteoarthritis in retired elite male rugby players compared with control groups. Various neurocognitive health conditions were investigated and showed, among others, a prevalence rate of 57% for mild cognitive disorder. The prevalence of self-reported depression and hazardous alcohol use in retired elite male rugby players was significantly higher than in control groups matched for age and education. Our review found relatively high prevalence rates of musculoskeletal health conditions such as osteoarthritis and psychological health conditions such as depression and hazardous alcohol use in retired elite male rugby players. More research needs to be conducted to understand better the health conditions of retired elite rugby players, especially among retired elite female players.
VEXAS syndrome: a diagnostic puzzle
Authors: Ruffer Nikolas , Krusche Martin
Published: August 2023

The VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an adult-onset systemic autoinflammatory condition that is caused by an acquired deficiency of the UBA1 gene in hematopoietic progenitor cells. The clinical spectrum of the VEXAS syndrome currently comprises a broad range of phenotypes such as vasculitis, relapsing polychondritis and Sweet’s syndrome. In the past, VEXAS patients have left clinicians puzzled and the true nature of this disease has not been captured until late 2020. This viewpoint describes the relevant clinical features of the VEXAS syndrome and reviews different approaches to establish the diagnosis. Finally, future directions within the field of systemic inflammatory diseases caused by somatic mutations are being discussed.
Effects of Rosa roxburghii Tratt on Ulcerative Colitis: An Integrated Analysis of Network Pharmacology and Experimental Validation
Authors: Kang Yu-Hong , Zhou Ting , Wu Shou-Xun , Li Xing-Jie , Huang Xiao-Yi , Xia Rui , Ling Yi-Han , Zhou He-Ting , Zhang Shu-Wen , Yin Wen-Ya
Published: August 2023

Rosa roxburghii Tratt is a traditional Chinese plant that has been used to treat different inflammatory diseases. The purpose of this study was to investigate the mechanism of action of Rosa roxburghii Tratt extract (RRTE) against ulcerative colitis (UC) using network pharmacology and experimental validation. HPLC-Q/Orbitrap MS was used to rapidly identify the substances contained in RRTE after extracting the active components from the fruit. Then, network pharmacology combined with molecular docking was used to explore the critical target and potential mechanism of RRTE against UC using the active ingredients in RRTE as the research object. Data are presented in a visual manner. Finally, the pharmacological effects of RRTE in alleviating UC were further verified using a DSS-induced UC model of NCM460. The results showed that 25 components in RRTE were identified. A total of 250 targets of the active components and 5376 targets associated with UC were collected. Furthermore, a systematic analysis of the Protein–Protein Interaction (PPI) networks suggests that epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and serine/threonine kinase 1 (AKT1) are critical targets for RRTE in the treatment of UC. A comprehensive regulatory network analysis showed that RRTE alleviated UC through the EGFR-mediated PI3K/Akt pathway, and molecular docking showed that active components could strongly bind to EGFR, PIK3R1, and AKT1. In addition, RRTE alleviated dextran sulfate sodium salt (DSS)-induced cell injury and significantly decreased the protein expression levels of EGFR, PIK3R1, and p-AKT in NCM460 cells in vitro. Furthermore, RRTE significantly regulated the expression of the apoptosis-related proteins Apoptotic protease-activating factor 1 (Apaf1), cleaved caspase-3, B-cell lymphoma-2 (Bcl2), and Bcl2 associated X protein (Bax). In conclusion, the components of RRTE are complex, and RRTE can relieve UC through the EGFR-mediated PI3K/Akt pathway.
The impact of leverage on investment and firm value during the COVID-19: Evidence from Chinese listed firms
Authors: Xue Shuyu , Luo Zijing , Liu Yuchen
Published: August 2023

This study examines the relations between leverage and investment and the relations between leverage and firm value during the COVID-19 period using data from Chinese listed companies. We find that the COVID-19 pandemic has strengthened the inhibition of leverage on corporate investment and firm value, while alleviated the constraint of leverage on corporate cash holdings. Furthermore, the pandemic-induced negative relationships are stronger for non-SOEs, firms holding less cash, multinational firms and firms in severe epidemic areas. Overall, our results are consistent with the risk-aversion theory. Higher economic uncertainty increases the firms’ risk aversion and eventually strengthens the negative relations between leverage and investment.
HKG: A Novel Approach for Low Resource Indic Languages to Automatic Knowledge Graph Construction
Authors: Vats Preeti , Sharma Nonita , Sharma Deepak Kumar
Published: August 2023

Knowledge graph (KG), a visual representation of text data as a semantic network, holds enormous promise for the development of more intelligent robots. It leads to significant potential solutions for many tasks like question answering, recommendation, and information retrieval. However, this area is confined to using English text only. Since low-resource languages are now being used in the world of AI, it is necessary to develop a semantic network for them as well. In this research work, the authors provide state-of-the-art techniques for automatic knowledge graph construction for the Hindi language, which is still unexplored in ontology. Constructing a knowledge graph faces several hurdles and obstacles in the linguistic domain, primarily when it deals with the Hindi language. With an emphasis on the Indian perspective, this research intends to introduce a novel approach ‘HKG’ for knowledge graph construction framework for Hindi. It also implements the LSTM model to evaluate the accuracy of newly constructed knowledge graphs and compute different evaluation metrics such as accuracy and F1-score. This knowledge graph evaluates the accuracy of 87.50 using Doc2Vec word embedding with a train-test split of 7:3.