bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated With Unfavorable Treatment Outcomes Among Persons With Pulmonary Tuberculosis: A Multicentric Prospective Cohort Study From India
Authors: Prakash Babu Senbagavalli , Ezhumalai Komala , Raghupathy Kalaivani , Karoly Meagan , Chinnakali Palanivel , Gupte Nikhil , Paradkar Mandar , Devarajan Arutselvi , Dhanasekaran Mythili , Thiruvengadam Kannan , Dauphinais Madolyn Rose , Gupte Akshay N , Shivakumar Shrivijay Balayogendra , Thangakunam Balamugesh , Christopher Devasahayam Jesudas , Viswanathan Vijay , Mave Vidya , Gaikwad Sanjay , Kinikar Aarti , Kornfeld Hardy , Horsburgh C Robert , Chandrasekaran Padmapriyadarsini , Hochberg Natasha S , Salgame Padmini , Gupta Amita , Roy Gautam , Ellner Jerrold , Sinha Pranay , Sarkar Sonali
Published: July 2024

In this prospective cohort of 2006 individuals with drug-susceptible tuberculosis in India, 18% had unfavorable treatment outcomes (4.7% treatment failure, 2.5% recurrent infection, 4.1% death, 6.8% loss to follow-up) over a median 12-month follow-up period. Age, male sex, low education, nutritional status, and alcohol use were predictors of unfavorable outcomes.
Amsterdam’s circular economy at a world-ecological crossroads: postcapitalist degrowth or the next regime of capital accumulation?
Authors: Thompson Matthew , Cator Charlotte , Beel David , Jones Ian Rees , Jones Martin , Morgan Kevin
Published: July 2024

This article conceptualises the circular economy as a space of immaterial, as well as material, metabolic flows mediated by capitalism and planetary urbanisation. World-ecology provides us with the critical lens to view the circular economy as part of an emergent regime of accumulation that may supersede neoliberalism. However, if each regime entails new frontier zones for appropriating cheap natures and dumping wastes, then the circular economy—as a strategy for revalorising waste—presents a possible structural limit to capitalism’s further expansion. Moreover, when combined with notions of degrowth and doughnut economics, the circular economy may provide an imaginary and set of prefigurative practices that point towards a postcapitalist economy. Through a case study of Amsterdam—a city aiming to be fully circular by 2050—we examine this contradictory crossroads, problematising the idea of circularity within capitalism and exploring the potential of postcapitalist alternatives within the circular economy.
Clinical impact of novel cardiovascular magnetic resonance technology on patients with congenital heart disease: a scientific statement of the Association for European Pediatric and Congenital Cardiology and the European Association of Cardiovascular Imaging of the European Society of Cardiology
Authors: Voges Inga , Raimondi Francesca , McMahon Colin J , Ait-Ali Lamia , Babu-Narayan Sonya V , Botnar René M , Burkhardt Barbara , Gabbert Dominik D , Grosse-Wortmann Lars , Hasan Hosan , Hansmann Georg , Helbing Willem A , Krupickova Sylvia , Latus Heiner , Martini Nicola , Martins Duarte , Muthurangu Vivek , Ojala Tiina , van Ooij Pim , Pushparajah Kuberan , Rodriguez-Palomares Jose , Sarikouch Samir , Grotenhuis Heynric B , Greil F Gerald , Bohbot Yohann , Cikes Maja , Dweck Marc , Donal Erwan , Grapsa Julia , Keenan Niall , Petrescu Aniela Monica , Szabo Liliana , Ricci Fabrizio , Uusitalo Valtteri
Published: July 2024

Cardiovascular magnetic resonance (CMR) imaging is recommended in patients with congenital heart disease (CHD) in clinical practice guidelines as the imaging standard for a large variety of diseases. As CMR is evolving, novel techniques are becoming available. Some of them are already used clinically, whereas others still need further evaluation. In this statement, the authors give an overview of relevant new CMR techniques for the assessment of CHD. Studies with reference values for these new techniques are listed in the Supplementary data online, supplement.
Full circumferential human tracheal replacement: a systematic review
Authors: Thierry Briac , Arakelian Lousineh , Denoyelle Françoise , Larghero Jérôme , Wurtz Alain
Published: July 2024

Full Circumferential Tracheal Replacement (FCTR) is a surgical challenge, indicated in rare cases of extensive tracheal resection, with no consensus on surgical technique or materials. A systematic review according to PRISMA guidelines was carried out from 2000 to 2022 to identify cases of FCTR, to compare surgical indications, the nature of the tracheal substitutes and their immunological characteristics, surgical replacement techniques and vascularization. Thirty-seven patients, including five children, underwent FCTR surgery using 4 different techniques: thyrotracheal complex allograft (n = 2), aorta (n = 12), autologous surgical reconstruction (n = 19), tissue-engineered decellularized trachea (n = 4). The mean follow-up was 4 years. Of the 15 deceased patients, 10 died of the progression of the initial pathology. For the majority of the teams, particular care was given to the vascularization of the substitute, in order to guarantee long-term biointegration. This included either direct vascularization via vascular anastomosis, or an indirect technique involving envelopment of the avascular substitute in a richly vascularized tissue. Stent placement was standard, except for autologous surgical reconstructions where tracheal caliber was stable. Internal stents were frequently complicated by granulation and stenosis. Although epithelial coverage is essential to limit endoluminal proliferation and act as a barrier, fully functional ciliated airway epithelium did not seem to be necessary. In order to facilitate future comparisons, a standardized clinical trial, respecting regulatory constraints, including routine follow-up with tracheal biomechanics assessment and scheduled biopsies could be proposed. It would help collecting information such as dynamics and mechanisms of tracheal bio-integration and regeneration.
Mck1-mediated proteolysis of CENP-A prevents mislocalization of CENP-A for chromosomal stability in Saccharomyces cerevisiae
Authors: Zhang Tianyi , Au Wei-Chun , Ohkuni Kentaro , Shrestha Roshan L , Kaiser Peter , Basrai Munira A
Published: July 2024

Centromeric localization of evolutionarily conserved CENP-A (Cse4 in Saccharomyces cerevisiae) is essential for chromosomal stability. Mislocalization of overexpressed CENP-A to noncentromeric regions contributes to chromosomal instability in yeasts, flies, and humans. Overexpression and mislocalization of CENP-A observed in many cancers are associated with poor prognosis. Previous studies have shown that F-box proteins, Cdc4 and Met30 of the Skp, Cullin, F-box ubiquitin ligase cooperatively regulate proteolysis of Cse4 to prevent Cse4 mislocalization and chromosomal instability under normal physiological conditions. Mck1-mediated phosphorylation of Skp, Cullin, F-box-Cdc4 substrates such as Cdc6 and Rcn1 enhances the interaction of the substrates with Cdc4. Here, we report that Mck1 interacts with Cse4, and Mck1-mediated proteolysis of Cse4 prevents Cse4 mislocalization for chromosomal stability. Our results showed that mck1Δ strain overexpressing CSE4 (GAL-CSE4) exhibits lethality, defects in ubiquitin-mediated proteolysis of Cse4, mislocalization of Cse4, and reduced Cse4–Cdc4 interaction. Strain expressing GAL-cse4-3A with mutations in three potential Mck1 phosphorylation consensus sites (S10, S16, and T166) also exhibits growth defects, increased stability with mislocalization of Cse4-3A, chromosomal instability, and reduced interaction with Cdc4. Constitutive expression of histone H3 (Δ16H3) suppresses the chromosomal instability phenotype of GAL-cse4-3A strain, suggesting that the chromosomal instability phenotype is linked to Cse4-3A mislocalization. We conclude that Mck1 and its three potential phosphorylation sites on Cse4 promote Cse4–Cdc4 interaction and this contributes to ubiquitin-mediated proteolysis of Cse4 preventing its mislocalization and chromosomal instability. These studies advance our understanding of pathways that regulate cellular levels of CENP-A to prevent mislocalization of CENP-A in human cancers.
On the nature of influence: identifying and characterizing superdiffusers in seven countries
Authors: Cruz Shannon M , Manata Brian , High Andrew C , Worley Timothy R
Published: July 2024

An important component of theoretical and applied work on social influence is identifying influential people. Boster et al.’s theoretical framework on superdiffusers provides one method of doing so, but important questions on the nature of influence remain. In particular, because existing studies have primarily sampled U.S. college students, it remains unclear whether (a) the framework adequately characterizes superdiffusers in different populations and (b) our current understanding of superdiffusers applies outside of the United States. To address these questions, we used an online survey to examine factorial validity, metric invariance, and correlates of superdiffuser characteristics in the United States, the United Kingdom, Singapore, South Africa, India, Pakistan, and Australia (total N = 3,476). Results suggest the superdiffuser framework can fruitfully be used to describe and identify influential individuals in diverse contexts. Influence also appears to be a relatively trait-like individual difference rather than a matter of unique fit to a particular country or culture.
Estimation of potential social support requirement for tuberculosis patients in India
Authors: Chatterjee Susmita , Stallworthy Guy , Das Palash , Vassall Anna
Published: July 2024

Providing social support to tuberculosis (TB) patients is a recommended strategy as households having TB patients find themselves in a spiral of poverty because of high cost, huge income loss and several other economic consequences associated with TB treatment. However, there are few examples of social support globally. The Indian government introduced the ‘Nikshay Poshan Yojana’ scheme in 2018 to provide nutritional support for all registered TB patients. A financial incentive of 500 Indian Rupee (6 United States Dollars) per month was proposed to be transferred directly to the registered beneficiaries’ validated bank accounts. We examined the reach, timing, amount of benefit receipt and the extent to which the benefit alleviated catastrophic costs (used as a proxy to measure the impact on permanent economic welfare as catastrophic cost is the level of cost that is likely to result in a permanent negative economic impact on households) by interviewing 1482 adult drug-susceptible TB patients from 16 districts of four states during 2019 to 2023, using the methods recommended by the World Health Organization for estimating household costs of TB nationally. We also estimated the potential amount of social support required to achieve a zero catastrophic cost target. At the end of treatment, 31–54% of study participants received the benefit. In all, 34–60% of TB patients experienced catastrophic costs using different estimation methods and the benefit helped 2% of study participants to remain below the catastrophic cost threshold. A uniform benefit amount of Indian Rupee 10 000 (127 United States Dollars) for 6 months of treatment could reduce the incidence of catastrophic costs by 43%. To improve the economic welfare of TB patients, levels of benefit need to be substantially increased, which will have considerable budgetary impact on the TB programme. Hence, a targeted rather than universal approach may be considered. To maximize impact, at least half of the revised amount should be given immediately after treatment registration.
Helmet wearing and related factors among electric personal mobility device users in Korea
Authors: Kim Eunbi , Kim Taehun , Park Sojeong , Park Sohyun , Park Juhwan , Lee Junhyeok , Lee Junhyung , Han Mi Ah
Published: July 2024

Using data from the 2022 Korea Community Health Survey (n = 13 320), this study investigated helmet use and related factors among Korean adults using personal mobility devices, without distinguishing between private and hired users. Among mobility device users, 32.1% responded that they always wore a helmet. The proportion of helmet use was 35.2% among men, 25.8% among women, 29.2% among those aged 19–44 years, 42.3% among those aged 45–64 years and 26.6% among those aged 65 years or older. Furthermore, those who drank less frequently and were physically active were more likely to wear helmets. Moreover, people who always wore a seat belt when driving a car or sitting in the rear seat and people who always wore a helmet when riding a motorcycle were more likely to wear a helmet while using electric personal mobility devices. Approximately one-third of users always wore a helmet. The helmet-wearing rate was related to general characteristics such as gender and education level, and to safety behaviors such as wearing a seat belt when driving a car, sitting in the rear seat of a car, or when riding a motorcycle. In addition to considering personal characteristics investigated in this study, the helmet-wearing rate should be improved through policies or systems at the national or regional levels.
Smartphones and video as security articulation infrastructures: evidencing Black Lives Matter
Authors: Andersen Rune Saugmann
Published: July 2024

Smartphone videos can co-constitute security reality. As smartphones spread in the 2010s, videos of deadly police violence against Black United States citizens became common, and over time these videos co-constituted anti-Black police violence as a security issue, which found its expression as Black Lives Matter (BLM). This article questions the role that smartphones and video play for BLM, and argues that security theory needs a better grasp of security articulation. Mapping the mediation of BLM's first decade, the article documents that smartphones are security articulation infrastructures as bystanders routinely rely on smartphone video to articulate security. The epistemic authority of video enables BLM videos to act as infrastructural gateways connecting established mass media to new vernacular media. Video mediation denies recognized figures of authority interpretive monopoly and enables non-elites to participate in constituting security reality, creating a room for non-elite Black Americans' articulation of insecurity. The article shows that still images and videos are different in this respect, and calls for security theory to take articulation formats and infrastructures seriously. When leaving ‘communication’ to other disciplines or enacting government responses as constitutive of (visual) security, scholarship risks overlooking the epistemic racism limiting security articulation in ‘old’ mass media, and risks making security theory complicit in epistemically silencing the voices of common, marginalized and racialized people.
Community pharmacists’ attitudes towards checking prescriptions: a cross-sectional survey
Authors: van Loon W Ellen , Lambert Maarten , Heringa Mette , Bouvy Marcel L , Taxis Katja
Published: July 2024

Background

The final prescription check is a mandatory but time-consuming process in Dutch community pharmacies. A safer dispensing process may have made the final prescription check obsolete.

Objective

To describe the final prescription check in Dutch community pharmacies and explore pharmacists’ attitudes towards changing this.

Methods

A cross-sectional survey among Dutch community pharmacists. The online questionnaire was based on literature and previous qualitative research, piloted in three pharmacies, and took 10 min to complete. Results were analysed descriptively.

Results

A total of 409 pharmacists participated. They saw the final prescription check as an important quality assurance of the dispensing process. Nevertheless, most pharmacists agreed that the final prescription check could be optimized as they thought that the time invested outweighed the benefits. Automation of the dispensing process, only checking selected high-risk prescriptions, and more in-process checks could reduce the need for an extensive final prescription check, rather than delegating the task to assistants. To implement changes, most pharmacists felt current dispensing guidelines needed to be adapted.

Conclusion

There was a widespread consensus that optimizing the final prescription check could enhance efficiency and allow more time for person-centred care. Most pharmacists expressed a preference for updated guidelines before implementing such changes.
Linking active rectal mucosa–attached microbiota to host immunity reveals its role in host–pathogenic STEC O157 interactions
Authors: Pan Zhe , Chen Yanhong , Zhou Mi , McAllister Tim A , Mcneilly Tom N , Guan Le Luo
Published: July 2024

The rectal–anal junction (RAJ) is the major colonization site of Shiga toxin–producing Escherichia coli (STEC) O157 in beef cattle, leading to transmission of this foodborne pathogen from farms to food chains. To date, there is limited understanding regarding whether the mucosa-attached microbiome has a profound impact on host–STEC interactions. In this study, the active RAJ mucosa–attached microbiota and its potential role in host immunity–STEC commensal interactions were investigated using RAJ mucosal biopsies collected from calves orally challenged with two STEC O157 strains with or without functional stx2a (stx2a+ or stx2a−). The results revealed that shifts of microbial diversity, topology, and assembly patterns were subjected to stx2a production post-challenge and Paeniclostridium and Gallibacterium were the keystone taxa for both microbial interactions and assembly. Additional mucosal transcriptome profiling showed stx2a−dependent host immune responses (i.e. B- and T-cell signaling and antigen processing and presentation) post-challenge. Further integrated analysis revealed that mucosa–attached beneficial microbes (i.e. Provotella, Faecalibacterium, and Dorea) interacted with host immune genes pre-challenge to maintain host homeostasis; however, opportunistic pathogenic microbes (i.e. Paeniclostridium) could interact with host immune genes after the STEC O157 colonization and interactions were stx2a−dependent. Furthermore, predicted bacterial functions involved in pathogen (O157 and Paeniclostridium) colonization and metabolism were related to host immunity. These findings suggest that during pathogen colonization, host–microbe interactions could shift from beneficial to opportunistic pathogenic bacteria driven and be dependent on the production of particular virulence factors, highlighting the potential regulatory role of mucosa–attached microbiota in affecting pathogen–commensal host interactions in calves with STEC O157 infection.
The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs
Authors: Wijk Marie , Gausi Kamunkhwala , Malatesta Samantha , Weber Sarah E , Court Richard , Myers Bronwyn , Carney Tara , Parry Charles D H , Horsburgh C Robert , White Laura F , Wiesner Lubbe , Warren Robin M , Uren Caitlin , McIlleron Helen , Kloprogge Frank , Denti Paolo , Jacobson Karen R
Published: July 2024

Background

In South Africa, an estimated 11% of the population have high alcohol use, a major risk factor for TB. Alcohol and other substance use are also associated with poor treatment response, with a potential mechanism being altered TB drug pharmacokinetics.

Objectives

To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB.

Methods

We prospectively enrolled participants ≥15 years old, without HIV, and initiating drug-susceptible TB treatment in Worcester, South Africa. Alcohol use was measured via self-report and blood biomarkers. Other illicit substances were captured through a urine drug test. Plasma samples were drawn 1 month into treatment pre-dose, and 1.5, 3, 5 and 8 h post-dose. Non-linear mixed-effects modelling was used to describe the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol. Alcohol and drug use were tested as covariates.

Results

The study included 104 participants, of whom 70% were male, with a median age of 37 years (IQR 27–48). Alcohol use was high, with 42% and 28% of participants having moderate and high alcohol use, respectively. Rifampicin and isoniazid had slightly lower pharmacokinetics compared with previous reports, whereas pyrazinamide and ethambutol were consistent. No significant alcohol use effect was detected, other than 13% higher ethambutol clearance in participants with high alcohol use. Methaqualone use reduced rifampicin bioavailability by 19%.

Conclusion

No clinically relevant effect of alcohol use was observed on the pharmacokinetics of first-line TB drugs, suggesting that poor treatment outcome is unlikely due to pharmacokinetic alterations. That methaqualone reduced rifampicin means dose adjustment may be beneficial.
Bone matrix properties in adults with osteogenesis imperfecta are not adversely affected by setrusumab—a sclerostin neutralizing antibody
Authors: Rummler Maximilian , Schemenz Victoria , McCluskey Samantha , Davydok Anton , Rauch Frank , Glorieux Francis H , Harrington Matthew J , Wagermaier Wolfgang , Willie Bettina M , Zimmermann Elizabeth A
Published: July 2024

Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by low bone mass and frequent fractures. Children with OI are commonly treated with bisphosphonates to reduce fracture rate, but treatment options for adults are limited. In the Phase 2b ASTEROID trial, setrusumab (a sclerostin neutralizing antibody, SclAb) improved bone density and strength in adults with type I, III, and IV OI. Here, we investigate bone matrix material properties in tetracycline-labeled trans iliac biopsies from 3 groups: (1) control: individuals with no metabolic bone disease, (2) OI: individuals with OI, (3) SclAb-OI: individuals with OI after 6 mo of setrusumab treatment (as part of the ASTEROID trial). In addition to bone histomorphometry, bone mineral and matrix properties were evaluated with nanoindentation, Raman spectroscopy, second harmonic generation imaging, quantitative backscatter electron imaging, and small-angle X-ray scattering. Spatial locations of fluorochrome labels were identified to differentiate inter-label bone of the same tissue age and intra-cortical bone. No difference in collagen orientation was found between the groups. The bone mineral density distribution and analysis of Raman spectra indicate that OI groups have greater mean mineralization, greater relative mineral content, and lower crystallinity than the control group, which was not altered by SclAb treatment. Finally, a lower modulus and hardness were measured in the inter-label bone of the OI-SclAb group compared to the OI group. Previous studies suggest that even though bone from OI has a higher mineral content, the extracellular matrix (ECM) has comparable mechanical properties. Therefore, fragility in OI may stem from contributions from other yet unexplored aspects of bone organization at higher length scales. We conclude that SclAb treatment leads to increased bone mass while not adversely affecting bone matrix properties in individuals with OI.
Temperature acclimation and response to acute thermal stress in the adults of the snow crab Chionoecetes opilio Fabricius, 1788 (Decapoda: Brachyura: Oregoniidae)
Authors: Thesslund Tina , Wittmann Astrid C , Timmerhaus Gerrit , Berg Ragnhild S , Hansen Marianne H S , Siikavuopio Sten , Evensen Tor H , Andersen Øivind
Published: July 2024

Ectothermic marine animals vary widely in their tolerance to temperature changes, and polar stenothermal species seem to have poor ability to compensate for a rise in water temperature. The sub-Arctic snow crab (Chionoecetes opilioFabricius, 1788) lives in the northwestern Atlantic Ocean and northern Pacific Ocean at temperatures ranging from about −1.5 °C to 4 °C. Since the metabolic costs overtake caloric intake above 7 °C, the snow crab appears to be energetically restricted to cold water. We investigated thermal stress responses in adult male crabs exposed to a sudden temperature increase to 9.5 °C for 24 hr after four weeks of acclimation at 2.5 °C or 5.5 °C. Heart-rate loggers implanted in a limited number of crabs showed 60% increase in cardiac activity during the thermal stress. Surplus oxygen supply in all crabs was inferred by the low hemolymph lactate and unchanged glucose levels, but only the crabs acclimated at 5.5 °C were still active at the elevated temperature. Low heat shock and oxidative stress responses were suggested by the missing upregulation of the genes encoding four heat shock proteins (Hsp70a, Hsc71, Hsp90a2, Hsp60) and the antioxidative enzymes superoxide dismutase and catalase. The trend towards inverse temperature-dependent on the expression of the hsp genes may be related to increased protein damage at low temperatures, or possible trade-offs between costs and benefits of producing heat shock proteins at elevated temperature. Although adult snow crabs seem to be able to cope with short-term heat stress, the tolerance to chronic elevated temperatures should be further examined using a larger number of individuals.
Effects of combining soil-applied insecticide and Bt corn for integrated pest management and resistance management of western corn rootworm (Coleoptera: Chrysomelidae)
Authors: McCulloch John B , Gassmann Aaron J
Published: July 2024

The western corn rootworm, (Diabrotica virgifera virgifera LeConte, Coleoptera: Chrysomelidae), is a serious pest of corn (Zea mays Linnaeus, Cyperales: Poaceae) in the midwestern United States. Management practices for corn rootworm larvae include crop rotation, transgenic corn producing insecticidal toxins from the bacterium Bacillus thuringiensis Berliner (Bacillales: Bacillaceae) (Bt), and soil-applied insecticides. The extent to which combining soil-applied insecticide with Bt corn would be beneficial from the perspective of insect resistance management (IRM) or integrated pest management (IPM) remains uncertain. We conducted a 3-yr field study to characterize the implications of combining a soil-applied insecticide and Bt corn for IRM and IPM of western corn rootworm. Experimental treatments were Bt corn, a soil-applied insecticide, the combination of these factors, and an experimental control in which both factors were absent. Data were collected on root injury to corn by rootworm, survival to adulthood, adult size, and emergence time for western corn rootworm. We found that mortality caused by the soil-applied insecticide was insufficient to delay resistance to Bt corn. While combining Bt corn and a soil-applied insecticide may provide a short-term economic benefit, additional research is needed to determine appropriate economic thresholds for combining these tactics. Additionally, combining a soil-applied insecticide and Bt corn would not be sustainable over multiple growing seasons because of its potential to rapidly select for Bt resistance. In general, a more sustainable IRM strategy for rootworm management would include using crop rotation and alternating between non-Bt corn with soil-applied insecticide and Bt corn without soil-applied insecticide.
Toxicity of cockroach gel baits to the oothecal parasitoid Aprostocetus hagenowii (Hymenoptera: Eulophidae) and implications for cockroach integrated pest management
Authors: Smith Chelsea M , Griffin Madeline P , Fadamiro Henry Y , Appel Arthur G
Published: July 2024

Aprostocetus hagenowii (Ratzeburg) is a parasitoid wasp that parasitizes the oothecae of peridomestic pest cockroaches. A. hagenowii has been used in integrated pest management (IPM) programs for cockroach control but little is known about how this parasitoid responds to the insecticides commonly used for cockroach management. Five insecticidal gel bait products containing indoxacarb, clothianidin, fipronil, dinotefuran, or abamectin B1 were tested for their toxicity towards A. hagenowii and the American cockroach, Periplaneta americana (L.; Blattodea: Blattidae), a host of A. hagenowii and a common pest. All baits were tested as fresh and 1-d aged deposits. Indoxacarb was the only active ingredient that did not cause significant (P < 0.05) A. hagenowii mortality compared to the control in both the fresh and aged gel experiments (Median survival time [MST]s: 168 h fresh, 72 h aged). Clothianidin caused the lowest A. hagenowii MSTs across experiments (24 h, fresh and aged). All baits caused significant P. americana mortality as fresh and 1-d aged deposits (P < 0.05). Indoxacarb appears most compatible with A. hagenowii in cockroach IPM.
In vivo and in silico elucidation of possible potential and mechanisms involved in the analgesic action of ethanolic extract of Lavandula Stoechas
Authors: Nazir Muhammad Muzammil , Inam Sana , Ijaz Muhammad Umar , Zafar Nimrah , Yeni Derya Karatas , Asad Farkhanda , Farzeen Iqra , Ashraf Asma
Published: July 2024

Objectives

Our research focused on plant’s ethanolic extract Lavandula stoechas flower part to investigate the potential analgesic effects and possible pathways involvements.

Methods

Four experimental tests were performed on Swiss albino mice with five animals in each group at different doses (50, 100, and 200mg/kg); formalin test, tail-flick test, acetic acid-induced writhing, and hot-plate test. The opioidergic, noradrenergic, cholinergic, and K channel blockers in the analgesic actions were also carried out for the potential route involvement.

Key finding

The percentage inhibition for abdominal writhing’s and formalin activity showed a dose-dependent manner for early and late phases reducing abdominal writhing’s and time period of licking, respectively. Tail immersion and hot-plate test demonstrated a substantial and dose-dependent increase in the latency time and time period of paw liking and jumping response respectively. GC–MS showed the abundantly present compounds were octadecatrienoic acid (34.35%), n-hexadecanoic acid (12.98%). In silico analyses have revealed three compounds that had good interactions with 6y3c receptor proteins, demonstrating strong binding affinities and satisfying docking parameters.

Conclusions

Overall, these studies showed that ethanolic extract of L. stoechas is an important medicinal plant, with both central and peripheral antinociceptive and analgesic activities supporting its traditional use for therapeutic purposes.
Anoectochilus roxburghii polysaccharide reduces D-GalN/LPS-induced acute liver injury by regulating the activation of multiple inflammasomes
Authors: Yan Yulu , Ye Xiqi , Huang Chunqing , Wu Junjun , Liu Yunbiao , Zheng Pingping , Shen Congqi , Bai Zhaofang , Tingming Shen
Published: July 2024

Background

Acute liver injury (ALI) is a serious syndrome with a high mortality rate due to viral infection, toxic exposure, and autoimmunity, and its severity can range from mildly elevated liver enzymes to severe liver failure. Activation of the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is closely associated with the development of ALI, and the search for an inhibitor targeting this pathway may be a novel therapeutic option. Anoectochilus roxburghii polysaccharide (ARP) is a biologically active ingredient extracted from Anoectochilus roxburghii with immunomodulatory, antioxidant, and anti-inflammatory bioactivities and pharmacological effects. In this study, we focused on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury by ARP through inhibition of NLRP3 inflammasome.

Methods

An inflammasome activation model was established in bone marrow-derived macrophages (BMDMs) to investigate the effects of ARP on caspase-1 cleavage, IL-1β secretion, and ASC oligomerization in inflammasomes under different agonists. We used the D-GalN/LPS-induced acute liver injury model in mice, intraperitoneally injected ARP or MCC950, and collected liver tissues, serum, and intraperitoneal lavage fluid for pathological and biochemical indexes.

Results

ARP effectively inhibited the activation of the NLRP3 inflammasome and had an inhibitory effect on non-classical NLRP3, AIM2, and NLRC4 inflammasomes. It also effectively inhibited the oligomerization of apoptosis-associated speck-like protein (ASC) from a variety of inflammatory vesicles. Meanwhile, ARP has good therapeutic effects on acute liver injury induced by D-GaIN/LPS.

Conclusion

The inhibitory effect of ARP on a wide range of inflammasomes, as well as its excellent protection against acute liver injury, suggests that ARP may be a candidate for acute liver injury.
The turnover of ABI5 by scaffold proteins to attenuate ABA signaling
Authors: Pollo-Rodríguez Fátima , Sánchez-Vicente Inmaculada , Lorenzo Oscar
Published: July 2024

This article comments on:

Li Z, Zhang D, Liang X, Liang J. 2024. Receptor for Activated C Kinase 1 counteracts ABSCISIC ACID INSENSITIVE5-mediated inhibition of seed germination and post-germinative growth in Arabidopsis. Journal of Experimental Botany 75, 3932–3945.
Heat stress in plants: sensing, signalling, and ferroptosis
Authors: Distéfano Ayelén Mariana , Bauer Victoria , Cascallares Milagros , López Gabriel Alejandro , Fiol Diego Fernando , Zabaleta Eduardo , Pagnussat Gabriela Carolina
Published: July 2024

In the current context of global warming, high temperature events are becoming more frequent and intense in many places around the world. In this context, understanding how plants sense and respond to heat is essential to develop new tools to prevent plant damage and address global food security, as high temperature events are threatening agricultural sustainability. This review summarizes and integrates our current understanding underlying the cellular, physiological, biochemical, and molecular regulatory pathways triggered in plants under moderately high and extremely high temperature conditions. Given that extremely high temperatures can also trigger ferroptosis, the study of this cell death mechanism constitutes a strategic approach to understand how plants might overcome otherwise lethal temperature events.
Bacterial networks and enzyme genes in bacterial floccules from hydrolysis and aeration reactors in a dairy wastewater treatment system
Authors: Song Zule , Hua Jia , Zhang Xiao , Li Kejun
Published: July 2024

The dairy industry generates substantial wastewater, which is commonly treated using integrated anaerobic hydrolysis and aerated biofilm reactors. However, the bacterial composition and functional differences within the generated floccules remain unclear. In this study, we employed 16S rRNA and metagenomic sequencing to compare bacterial communities and enzyme gene profiles between suspended floccules from the hydrolysis ponds and the aeration ponds. Results revealed that the bacterial phyla Firmicutes, Proteobacteria, and Bacteroidetes dominated the wastewater treatment system and the relative abundance of these bacterial phyla varied in each pond. Additionally, the aeration ponds exhibited higher bacterial operational taxonomic units and enzyme gene abundance. Network analysis demonstrated a more complex bacterial network structure in the hydrolysis ponds compared to the aeration ponds. Furthermore, enzyme gene abundance revealed higher metabolic enzyme genes in the hydrolysis ponds, while signal transduction enzyme genes were more abundant in the aeration ponds. Notably, the top 10 bacterial genera, primarily Hydromonas in the hydrolysis ponds and Ferruginibacter in the aeration ponds, exhibited distinct contributions to signal transduction enzyme genes. Hydromonas dominated the metabolic enzyme genes in both ponds. These findings provide crucial insights for optimizing dairy wastewater treatment technologies.
GalaxyFlow: upsampling hydrodynamical simulations for realistic mock stellar catalogues
Authors: Lim Sung Hak , Raman Kailash A , Buckley Matthew R , Shih David
Published: July 2024

Cosmological N-body simulations of galaxies operate at the level of ‘star particles’ with a mass resolution on the scale of thousands of solar masses. Turning these simulations into stellar mock catalogues requires ‘upsampling’ the star particles into individual stars following the same phase-space density. In this paper, we introduce two new upsampling methods. First, we describe GalaxyFlow, a sophisticated upsampling method that utilizes normalizing flows to both estimate the stellar phase-space density and sample from it. Secondly, we improve on existing upsamplers based on adaptive kernel density estimation (KDE), using maximum likelihood estimation to fine-tune the bandwidth for such algorithms in a way that improves both the density estimation accuracy and upsampling results. We demonstrate our upsampling techniques on a neighbourhood of the Solar location in two simulated galaxies: Auriga 6 and h277. Both yield smooth stellar distributions that closely resemble the stellar densities seen in the Gaia DR3 catalogue. Furthermore, we introduce a novel multimodel classifier test to compare the accuracy of different upsampling methods quantitatively. This test confirms that GalaxyFlow more accurately estimates the density of the underlying star particles than methods based on KDE, at the cost of being more computationally intensive.
Spectropolarimetric view of the gamma-ray emitting NLS1 1H0323 + 342
Authors: Jose Jincen , Rakshit Suvendu , Panda Swayamtrupta , Woo Jong-Hak , Stalin C S , Neha Sharma , Pandey Shivangi
Published: July 2024

The gamma-ray emitting narrow-line Seyfert 1 galaxies are a unique class of objects that launch powerful jets from relatively lower-mass black hole systems compared to the Blazars. However, the black hole masses estimated from the total flux spectrum suffer from the projection effect, making the mass measurement highly uncertain. The polarized spectrum provides a unique view of the central engine through scattered light. We performed spectropolarimetric observations of the gamma-ray emitting narrow-line Seyfert 1 galaxy 1H0323 + 342 using SPOL/MMT. The degree of polarization and polarization angle are 0.122 $\pm$ 0.040 per cent and 142 $\pm$ 9 degrees, while the H $\alpha$ line is polarized at 0.265 $\pm$ 0.280 per cent. We decomposed the total flux spectrum and estimated broad H $\alpha$ full width at half maximum of 1015 km s$^{-1}$. The polarized flux spectrum shows a broadening similar to the total flux spectrum, with a broadening ratio of 1.22. The Monte Carlo radiative transfer code ‘STOKES’ applied to the data provides the best fit for a small viewing angle of 9–24 deg and a small optical depth ratio between the polar and the equatorial scatters. A thick broad-line region with significant scale height can explain a similar broadening of the polarized spectrum compared to the total flux spectrum with a small viewing angle.
Following the Evolutionary Paths of Dscam1 Proteins toward Highly Specific Homophilic Interactions
Authors: Wiseglass Gil , Rubinstein Rotem
Published: July 2024

Many adhesion proteins, evolutionarily related through gene duplication, exhibit distinct and precise interaction preferences and affinities crucial for cell patterning. Yet, the evolutionary paths by which these proteins acquire new specificities and prevent cross-interactions within their family members remain unknown. To bridge this gap, this study focuses on Drosophila Down syndrome cell adhesion molecule-1 (Dscam1) proteins, which are cell adhesion proteins that have undergone extensive gene duplication. Dscam1 evolved under strong selective pressure to achieve strict homophilic recognition, essential for neuronal self-avoidance and patterning. Through a combination of phylogenetic analyses, ancestral sequence reconstruction, and cell aggregation assays, we studied the evolutionary trajectory of Dscam1 exon 4 across various insect lineages. We demonstrated that recent Dscam1 duplications in the mosquito lineage bind with strict homophilic specificities without any cross-interactions. We found that ancestral and intermediate Dscam1 isoforms maintained their homophilic binding capabilities, with some intermediate isoforms also engaging in promiscuous interactions with other paralogs. Our results highlight the robust selective pressure for homophilic specificity integral to the Dscam1 function within the process of neuronal self-avoidance. Importantly, our study suggests that the path to achieving such selective specificity does not introduce disruptive mutations that prevent self-binding but includes evolutionary intermediates that demonstrate promiscuous heterophilic interactions. Overall, these results offer insights into evolutionary strategies that underlie adhesion protein interaction specificities.
An Orphan Gene Enhances Male Reproductive Success in Plutella xylostella
Authors: Zhao Qian , Zheng Yahong , Li Yiying , Shi Lingping , Zhang Jing , Ma Dongna , You Minsheng
Published: July 2024

Plutella xylostella exhibits exceptional reproduction ability, yet the genetic basis underlying the high reproductive capacity remains unknown. Here, we demonstrate that an orphan gene, lushu, which encodes a sperm protein, plays a crucial role in male reproductive success. Lushu is located on the Z chromosome and is prevalent across different P. xylostella populations worldwide. We subsequently generated lushu mutants using transgenic CRISPR/Cas9 system. Knockout of Lushu results in reduced male mating efficiency and accelerated death in adult males. Furthermore, our findings highlight that the deficiency of lushu reduced the transfer of sperms from males to females, potentially resulting in hindered sperm competition. Additionally, the knockout of Lushu results in disrupted gene expression in energy-related pathways and elevated insulin levels in adult males. Our findings reveal that male reproductive performance has evolved through the birth of a newly evolved, lineage-specific gene with enormous potentiality in fecundity success. These insights hold valuable implications for identifying the target for genetic control, particularly in relation to species-specific traits that are pivotal in determining high levels of fecundity.
Model-informed drug development of envafolimab, a subcutaneously injectable PD-L1 antibody, in patients with advanced solid tumors
Authors: Cui Cheng , Wang Jing , Wang Chunyang , Xu Ting , Qin Lan , Xiao Shen , Gong John , Song Ling , Liu Dongyang
Published: July 2024

Background and Objectives

Envafolimab is the first and only globally approved subcutaneously injectable PD-L1 antibody for the treatment of instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors in adults, including those with advanced colorectal cancer that has progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. The aim of this investigation was to examine the pharmacokinetic and exposure-response (E-R) profile of envafolimab in patients with solid tumors to support the approval of fixed and alternative dose regimens.

Methods

In this study, a population pharmacokinetic (PopPK) modeling approach will be employed to quantitatively evaluate intrinsic and extrinsic covariates. Additionally, PopPK-estimated exposure parameters were used to evaluate E-R relationship for safety and efficacy to provide a theoretical basis for recommending optimal treatment regimens. Simulations were performed on the dosing regimens of body weight-based regimen of 2.50 mg/kg QW, fixed dose 150 mg QW, and 300 mg Q2W for the selection of alternative dosing regimens. Data from 4 clinical studies (NCT02827968, NCT03101488, NCT03248843, and NCT03667170) were utilized.

Results

The PopPK dataset comprised 182 patients with 1810 evaluable envafolimab concentration records. Finally, a one-compartment model incorporating first-order absorption, first-order linear elimination, and time-dependent elimination according to an Emax function was found to accurately describe the concentration-time data of envafolimab in patients with advanced solid tumors. Creatinine clearance and country were identified as statistically significant factors affecting clearance, but had limited clinical significance. A relative flat exposure-response relationship was observed between early measures of safety and efficacy to verify that no dose adjustment is required. Simulation results indicated that 2.50 mg/kg QW, 150 mg QW, and 300 mg Q2W regimen yield similar steady-state exposure.

Conclusions

No statistically significant difference was observed between weight-based and fixed dose regimens. Model-based simulation supports the adoption of a 150 mg weekly or 300 mg biweekly dosing regimen of envafolimab in the solid tumor population, as these schedules effectively balance survival benefits and safety risks.
How Far-Right Extremism Changed American Body Politic
Authors: Nacos Brigitte L , Bloch-Elkon Yaeli
Published: July 2024

Aggressive rhetoric was part and parcel of the rising Tea Party and the related anti-Obama conspiracy theories. The argument here is that Donald J. Trump, as the leading public promoter of Birther rumors, first-time presidential candidate, and U.S. president, played a starring role in bringing hate speech, violent threats, and political violence into the political mainstream. As a result, political violence increased significantly and several violent far-right extremist groups, domestic terrorist entities, were newly founded after Trump announced his presidential campaign in mid-2015. As ex-president and once again presidential candidate, Trump glorified the criminally convicted participants in the violent breach of the U.S. Capitol on 6 January 2021 and honored violent far-right fringe groups that were active in the late 20th century while threatening revenge against his political enemies. To assess, whether Trump, as 47th U.S. president, would be able to have his political foes investigated and jailed upon his return to the highest office, we looked for answers in the Heritage Foundation's “Project 2025,” the most detailed blueprint for the dismantling of the “deep state” and the best-laid plan for a takeover by Trump and vetted conservative “Make America Great Again” loyalists in January 2025.1 Although the sole focus here is on the rhetoric of far-right extremism and violence in the past 15 years, there were no similarly extreme far-left hate speech patterns and violent extremism related to the Democratic Party during the same time.
BMSCs promote alveolar epithelial cell autophagy to reduce pulmonary fibrosis by inhibiting core fucosylation modifications
Authors: Hu Jinying , Wang Nan , Jiang Yu , Li Yina , Qin Biaojie , Wang Zhongzhen , Gao Lili
Published: July 2024

Background

Idiopathic pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease characterized by alveolar epithelial cell (AEC) injury and fibroblast activation. Inadequate autophagy in AECs may result from the activation of several signaling pathways following AEC injury, with glycoproteins serving as key receptor proteins. The core fucosylation (CF) modification in glycoproteins is crucial. Mesenchymal stem cells derived from bone marrow (BMSCs) have the ability to regenerate damaged tissue and treat PF. This study aimed to elucidate the relationship and mechanism of interaction between BMSCs, CF modification, and autophagy in PF.

Methods

C57BL/6 male mice, AEC-specific FUT8 conditional knockout (CKO) mice, and MLE12 cells were administered bleomycin (BLM), FUT8 siRNA, and mouse BMSCs, respectively. Experimental techniques including tissue staining, Western blotting, immunofluorescence, autophagic flux detection, and flow cytometry were used in this study.

Results

First, we found that autophagy was inhibited while FUT8 expression was elevated in PF mice and BLM-induced AEC injury models. Subsequently, CKO mice and MLE12 cells transfected with FUT8 siRNA were used to demonstrate that inhibition of CF modification induces autophagy in AECs and mitigates PF. Finally, mouse BMSCs were used to demonstrate that they alleviate the detrimental autophagy of AECs by inhibiting CF modification and decreasing PF.

Conclusions

Suppression of CF modification enhanced the suppression of AEC autophagy and reduced PF in mice. Additionally, through the prevention of CF modification, BMSCs can assist AECs deficient in autophagy and partially alleviate PF.