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The decision of the Union Internationale de Pentathlon Moderne to replace horse riding with Obstacle after the 2024 Olympic Games challenges training, testing, and recovery management in Modern Pentathlon. This commentary discusses physiological, technical, and tactical effects of rule changes in the 5 disciplines with a specific focus on the new discipline Obstacle. Modern Pentathlon requires athletes to develop specific endurance capacities relying on both the aerobic and anaerobic systems while simultaneously increasing lower- and upper-body strength capabilities. In addition, movements must be repeatedly executed in an explosive and precise manner. Running and swimming must be fast but economical. Swapping from horse riding to Obstacle will prioritize the explosive strength of the upper extremities and core while keeping high levels of endurance and precision in swimming, fencing, and shooting. Moreover, condensing the Modern Pentathlon competition to a 90-minute television-friendly format enables more competitions in the future. Athletes and coaches will thus also need to develop and maintain effective individual peri-exercise routines (before, during, and after the competition) to successfully meet the resulting tactical and physical challenges of the new format. This commentary aims to stimulate the discussion on the effect of the Union Internationale de Pentathlon Moderne's decisions to replace riding with the new Obstacle discipline and implement a more television-friendly format with a focus on physiological, technical, and tactical aspects. [ABSTRACT FROM AUTHOR]

Race has been a market force in society for centuries. Still, the question of what constitutes focused and sustainable consumer research engagement with race remains opaque. We propose a guide for scholars and scholarship that extends the current canon of race in consumer research toward understanding race, racism, and related racial dynamics as foundational to global markets and central to consumer research efforts. We discuss the nature, relevance, and meaning of race for consumer research and offer a thematic framework that critically categorizes and synthesizes extant consumer research on race along the following dimensions: (1) racial structuring of consumption and consumer markets, (2) consumer navigation of racialized markets, and (3) consumer resistance and advocacy movements. We build on our discussion to guide future research that foregrounds racial dynamics in consumer research and offers impactful theoretical and practical contributions. [ABSTRACT FROM AUTHOR]

This study examines the phenotypic differences between wild-derived F2 Central Valley mosquitoes and the insecticide-susceptible Rockefeller (Rock) lab strain of Ae. aegypti. Given the rarity of wild pyrethroid-susceptible populations, the focus of this work is to develop an understanding of the resistance physiology in this invasive mosquito population and explore the potential of metabolites as diagnostic biomarkers for metabolic resistance. This study utilizes metabolomic, gene expression, and lifespan data for a comparison between strains. The findings indicate that wild-derived mosquitoes with greater metabolic resistance have a lifespan sensitivity to restricted larval nutrition. In terms of metabolism and gene expression, Central Valley mosquitoes show increased activity in oxidoreductase, glutathione metabolism, and the pentose phosphate pathway. Conversely, Rock mosquitoes display signs of metabolic inefficiency and mitochondrial dysregulation, likely tolerated due to the consistency and nutritional abundance of a controlled lab environment. The study also examines Ae. aegypti P450 and GSTE profiles in relation to other insecticide-resistant groups. While metabolomic data can differentiate our study groups, the challenges in biomarker development arise from few detected markers meeting high fold change thresholds.

This thesis explores resistance work in Nazi-occupied France and Vichy France during World War II. The research uses paramilitary acts of resistance as a foil to political resistance, intelligence gathering and evasive resistance, and the home front as a site of resistance to spotlight women’s contributions to the French resistance. By exploring several types of resistance work and women’s participation (or lack thereof) in various resistance organizations, this thesis seeks to not only establish the extent of women’s participation in the French resistance but also explore their challenge to the established gender roles within the resistance. This thesis explores the extent of women’s resistance activities across World War II France through internal organizations, such as the French Communist Party and the French Resistance, and external organizations like the Bureau Central de Renseignements et d’Action (BCRA), British Special Operatives Executive’s F (French) Section (SOE), the British Secret Intelligence Service, and the American Office of Strategic Services (OSS). In the context of these organizations’ activities, this thesis analyzes the gendering of resistance while considering the presence of women in various resistance organizations and their resistance activities to contextualize scope and scale of women’s contributions to resistance work in occupied and Vichy France.

Purpose: To screen for the cisplatin resistance-related prognostic signature in oral squamous cell carcinoma (OSCC) and assess its correlation with the immune microenvironment. Materials and Methods: The gene expression data associated with OSCC and cisplatin-resistance were downloaded from TCGA and GEO databases. Cisplatin-resistant genes were selected through taking the intersection of differentially expressed genes (DEGs) between tumor and control groups as well as between cisplatin-resistant samples and parental samples. Then, prognosis-related cisplatin-resistant genes were further selected by univariate Cox regression and LASSO regression analyses to construct a survival prognosis model. A GSEA (gene set enrichment analysis) between two risk groups was conducted with the MSigDB v7.1 database. Finally, the immune landscape of the sample was studied using CIBERSORT. The IC50 values of 57 drugs were predicted using pRRophetic 0.5. Results: A total 230 candidate genes were obtained. Then 7 drug-resistant genes were selected for prognostic risk-score (RS) signature construction using LASSO regression analysis, including STC2, TBC1D2, ADM, NDRG1, OLR1, PDGFA and ANO1. RS was an independent prognostic factor. Additionally, a nomogram model was established to predict the 1-, 2-, and 3-year survival rates of samples. The GSEA identified several differential pathways between two risk groups, such as EMT, hypoxia, and oxidative phosphorylation. Fifteen immune cells were statistically significantly different in infiltration level between the two groups, such as macrophages M2, and resting NK cells. A total of 57 drugs had statistically significantly different IC50 values between two risk groups. Conclusion: These model genes and immune cells may play a role in predicting the prognosis and chemoresistance in OSCC. [ABSTRACT FROM AUTHOR]

Brain metastatic breast cancer is particularly lethal largely due to therapeutic resistance. Almost half of the patients with metastatic HER2-positive breast cancer develop brain metastases, representing a major clinical challenge. We previously described that cancer-associated fibroblasts are an important source of resistance in primary tumors. Here, we report that breast cancer brain metastasis stromal cell interactions in 3D cocultures induce therapeutic resistance to HER2-targeting agents, particularly to the small molecule inhibitor of HER2/EGFR neratinib. We investigated the underlying mechanisms using a synthetic Notch reporter system enabling the sorting of cancer cells that directly interact with stromal cells. We identified mucins and bulky glycoprotein synthesis as top-up-regulated genes and pathways by comparing the gene expression and chromatin profiles of stroma-contact and no-contact cancer cells before and after neratinib treatment. Glycoprotein gene signatures were also enriched in human brain metastases compared to primary tumors. We confirmed increased glycocalyx surrounding cocultures by immunofluorescence and showed that mucinase treatment increased sensitivity to neratinib by enabling a more efficient inhibition of EGFR/HER2 signaling in cancer cells. Overexpression of truncated MUC1 lacking the intracellular domain as a model of increased glycocalyx-induced resistance to neratinib both in cell culture and in experimental brain metastases in immunodeficient mice. Our results highlight the importance of glycoproteins as a resistance mechanism to HER2-targeting therapies in breast cancer brain metastases.

BACKGROUND: This study explores the impacts of attacks perpetrated in the context of armed conflict, to female health workers in three Colombian territories. METHODS: We conducted a document review of the reports and databases of the Colombian Truth Commission, 17 in-depth semi-structured interviews with experts on the national and regional armed conflict and the medical mission, and 26 female health workers who were victims of attacks. RESULTS: Experts and female health workers reported attacks to health activities, facilities, equipment, and personnel, including attacks to traditional doctors belonging to indigenous communities. The most frequent attacks were threats and retention of health personnel; theft of supplies and medicines; damage and use of infrastructure and means of transport for purposes other than health care; and hinderance of health service provision. The attacks occurred in a framework of structural violence that intersects with poverty, racism, and gender bias. The impacts of these attacks include gender-based violence, significant disruption of the lives of health workers, and physical, emotional, psychological, social, and economic effects on the victims and their families. The government response to protect victims and populations has been absent or insufficient. CONCLUSIONS: Attacks to health care were reported in all the studied territories obstructing adequate health care. Impacts of these attacks affect negatively the professional and personal life of the workers and are aggravated by structural violence and absent or little institutional response.

IntroductionThis study determined the safety and recommended phase 2 dose (RP2D) of the multikinase inhibitor cabozantinib in combination with trifluridine/tipiracil (FTD/TPI) in refractory metastatic colorectal carcinoma (mCRC).Patients and methodsSingle institution investigator-initiated phase 1 study using 3+3 design. Eligible mCRC patients had received prior standard regimens. Cabozantinib was given orally (p.o.) at 20 mg (dose level [DL] 0) or 40 mg (DL 1) daily on days 1-28, and FTD/TPI p.o. at 35 mg/m2 on days 1-5 and 8-12 every 28 days. Prophylactic growth-factor support was allowed.ResultsFifteen patients were enrolled. Median age 56 years (31-80), male (12/15), ECOG 0/1 = 9/6. Three patients were treated at DL 0 and another nine were treated at DL 1, none exhibiting a DLT. Most common any grade (G) treatment related adverse events (TRAE) were diarrhea (50%), nausea (42%), neutropenia (42%), fatigue (33%), and rash (25%). G3-4 TRAE were neutropenia (25%) and thrombocytopenia, hypokalemia, and weight loss (each 8%). No serious TRAE or G5 were reported. The RP2D was determined to be DL 1. Median PFS was 3.8 months (95% CI 1.9-6.8) and disease control rate was 86.7%.ConclusionThe combination of cabozantinib and FTD/TPI is feasible and tolerable at standard doses with the use of growth factors and showed encouraging clinical activity in refractory mCRC.ClinicaltrialsGOV: NCT04868773.

While more research is emerging about the development of masculinity during adolescence, not much is known about how masculine-type behaviors develop over time in middle to late adolescence within the context of friendships and peer experiences. This study examined trajectories of masculine-typed behavior from ages 14 to 17. Multilevel modeling was used to account for cross-time and within-time variability in masculine-typed behavior and examined the role of positive and negative peer experiences in predicting this variability. This was done in a sample of 334 U.S. adolescents (51% boys; 50% White, 19% Black, 15% Latina/o/e). At the between-person level, boys and girls decreased in masculine-typed behavior over time. At the within-person level, negative peer experiences predicted fluctuations toward greater masculine-typed behavior, whereas friend support predicted fluctuations toward less masculine-typed behavior. Adolescence is a key period for navigating masculinity norms, and peer experiences are a key context for the development of masculine-typed behavior.

Invasive candidiasis (IC) is an increasingly prevalent, costly, and potentially fatal infection brought on by the opportunistic yeast, Candida. Previously, IC has predominantly been caused by C. albicans which is often drug susceptible. There has been a global trend towards decreasing rates of infection secondary to C. albicans and a rise in non-albicans species with a corresponding increase in drug resistance creating treatment challenges. With advances in management of malignancies, there has also been an increase in the population at risk from IC along with a corresponding increase in incidence of breakthrough IC infections. Additionally, the emergence of C. auris creates many challenges in management and prevention due to drug resistance and the organisms ability to transmit rapidly in the healthcare setting. While the development of novel antifungals is encouraging for future management, understanding the changing epidemiology of IC is a vital step in future management and prevention.

[This corrects the article DOI: 10.3389/fimmu.2023.1332057.].

Although there is now a substantial body of literature exploring the effects of language diversity in international management contexts, little attention has been paid to the ethical dimensions of language diversity at work. This conceptual paper draws on the concept of epistemic injustice in order to explore how language, and in particular corporate language policies, may act as a source of epistemic injustice within the workplace. It demonstrates how language competence affects credibility judgements about a speaker, and also considers how corporate language policies can create situations of hermeneutic injustice, in which marginalised groups are denied the vocabularies to understand their own experiences. Finally, ways in which such epistemic harms can be reduced are discussed, and the possibilities for management education to create epistemically responsible managers are highlighted. [ABSTRACT FROM AUTHOR]

Polypropylene materials have attracted much attention due to their wide using temperature zones and are nonpoisonous. However, the poor electrical and thermal properties limit their application. In this work, the Cu nanowires with the single phase structure and uniform microstructure were successfully synthesized by tuning the reaction time. Then, the Cu nanowires were in the polypropylene matrix to optimize the electrical transport properties and thermal transport properties. The results show that the resistance of Cu nanowire-composited samples decreases by orders of magnitude, the resistance for the PP+0.5wt% Cu nanowires sample is 2.5 × 1010Ω, which is two orders of magnitude lower than that of the pristine sample due to the addition carrier transport path. Besides, the thermal diffusion coefficient of the Cu nanowire-composited sample increases to 0.194mm2s−1, which is 12.7% higher than that of the pristine sample. The improvement in electrical transport properties and thermal transport properties for polypropylene materials can be applied in the field of package materials, which can reduce energy consumption and the occurrence of safety accidents in the production process. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectivesMethodsResultsConclusionBacteroides fragilis group species are the most frequently encountered bacteria involved in anaerobic bacteraemia and associated with high mortality rates. In 2012, we performed the first national study of antimicrobial susceptibility in the B. fragilis group from blood cultures in Denmark.The purpose of the present study was to compare the antimicrobial susceptibility rates of piperacillin-tazobactam, meropenem, clindamycin and metronidazole in the B. fragilis group from blood cultures in Denmark in 2022 with susceptibility rates from 2012. In addition, we wanted to investigate whether changes to susceptibility was related to the overall use of the specified antimicrobial agents from 2012 to 2022.Antimicrobial susceptibility testing was performed in accordance with EUCAST guidelines using the agar dilution method and the disc diffusion method.The study showed a seemingly considerable increase in resistance in the B. fragilis group (n = 234) to piperacillin-tazobactam from a reported 8.5% in 2012 to 42.7% in 2022. Resistance towards meropenem also increased from a reported 3.4% to 10.7%. Most of the increase in resistance for piperacillin-tazobactam and meropenem is caused by a recent EUCAST breakpoint change. Metronidazole still has the lowest resistance rate for the B. fragilis group (one isolate, 0.4%) in this study. The sales of piperacillin-tazobactam in the same period revealed a corresponding increase (+130%), whereas meropenem sales were stable.The results underscore the need for timely routine antimicrobial susceptibility testing of B. fragilis group species and questions piperacillin-tazobactam monotherapy as empiric treatment for septic patients with a suspected abdominal source. [ABSTRACT FROM AUTHOR]

Immunotherapy is a novel treatment approach for malignant tumors, which has opened a new journey of anti-tumor therapy. Although some patients will show a positive response to immunotherapy, unfortunately, most patients and cancer types do not achieve an ideal response to immunotherapy. Therefore, it is urgent to search for the pathogenesis of sensitized immunotherapy. This review indicates that Fusobacterium nucleatum, Coprobacillus cateniformis, Akkermansia muciniphila, Bifidobacterium, among others, as well as intestinal microbial metabolites are closely associated with resistance to anti-tumor immunotherapy. While natural products of pectin, inulin, jujube, anthocyanins, ginseng polysaccharides, diosgenin, camu-camu, and Inonotus hispidus (Bull).Fr. P. Karst, Icariside I, Safflower yellow, Ganoderma lucidum, and Ginsenoside Rk3, and other Chinese native medicinal compound prescriptions to boost their efficacy of anti-tumor immunotherapy through the regulation of microbiota and microbiota metabolites. However, current research mainly focuses on intestinal, liver, and lung cancer. In the future, natural products could be a viable option for treating malignant tumors, such as pancreatic, esophageal, and gastric malignancies, via sensitizing immunotherapy. Besides, the application characteristics of different types, sources and efficacy of natural products in different immune resistance scenarios also need to be further clarified through the development of future immunotherapy-related studies. [ABSTRACT FROM AUTHOR]

Given the increasing concern about antimicrobial resistance among the microorganisms that cause infections in our society, there is an urgent need for new drug discovery. Currently, this process involves testing many low-quality compounds, resulting from the in vivo testing, on mammal models, which not only wastes time, resources, and money, but also raises ethical questions. In this review, we have discussed the potential of D. melanogaster as an intermediary experimental model in this drug discovery timeline. We have tackled the topic from a methodological perspective, providing recommendations regarding the range of drug concentrations to test based on the mechanism of action of each compound; how to treat D. melanogaster , how to monitor that treatment, and what parameters we should consider when designing a drug screening protocol to maximize the study's benefits. We also discuss the necessary improvements needed to establish the D. melanogaster model of infection as a standard technique in the drug screening process. Overall, D. melanogaster has been demonstrated to be a manageable model for studying broad-spectrum infection treatment. It allows us to obtain valuable information in a cost-effective manner, which can improve the drug screening process and provide insights into our current major concern. This approach is also in line with the 3R policy in biomedical research, in particular on the replacement and reduce the use of vertebrates in preclinical development. [ABSTRACT FROM AUTHOR]

Since the discovery of antibiotics, they have served as a potent weapon against bacterial infections; however, natural evolution has allowed bacteria to adapt and develop coping mechanisms, ultimately leading to the concerning escalation of multidrug resistance. Bacterial persisters are a subpopulation that can survive briefly under high concentrations of antibiotic treatment and resume growth after lethal stress. Importantly, bacterial persisters are thought to be a significant cause of ineffective antibiotic therapy and recurrent infections in clinical practice and are thought to contribute to the development of antibiotic resistance. Therefore, it is essential to elucidate the molecular mechanisms of persister formation and to develop precise medical strategies to combat persistent infections. However, there are many difficulties in studying persisters due to their small proportion in the microbiota and their non-heritable nature. In this review, we discuss the similarities and differences of antibiotic resistance, tolerance, persistence, and viable but non-culturable cells, summarize the molecular mechanisms that affect the formation of persisters, and outline the emerging technologies in the study of persisters. [ABSTRACT FROM AUTHOR]

Background: Sooty mold (SM), caused by Cladosporium species, is a pervasive threat to tea plant health, affecting both canopy structure and crop yield. Despite its significance, understanding the complex interplay between defense genes and metabolites in tea plants across various SM-infected canopy layers remains limited. Our study employed hyperspectral imaging, transcriptomic profiling, and metabolomic analysis to decipher the intricate mechanisms underlying the tea plant's response to SM infection. Results: Our hyperspectral imaging identified three critical wavelengths (552, 673, and 800 nm) inflection points associated with varying degrees of SM infection. This non-invasive method allows for the precise assessment of disease progression. Concurrently, transcriptome analysis revealed a wealth of differentially expressed genes (DEGs) enriched in metabolic pathways, secondary metabolite biosynthesis, and plant-pathogen interactions. Cluster analysis highlighted an intensified immune response in A2 and A3 samples. A comprehensive metabolomic profile identified 733 co-changed metabolites in SM-infected leaves, with alcohols, lipids (free fatty acids), hydrocarbons, and amino acids significantly accumulating in A1, while flavonoids were predominantly upregulated in A2 and A3. Weighted Gene Co-Expression Network Analysis (WGCNA) uncovered five hub genes (Dormancy-associated protein, Serine/threonine-protein phosphatase, ABC transporter, and some uncharacterized proteins) and two hub metabolites (D-Mannitol and 17-Hydroxylinolenic Acid) that exhibit significant relationships with DEGs and metabolites. Further co-expression analysis indicated that tea plants mainly employed genes and metabolites related to the biosynthesis of secondary metabolites, plant hormone signal transduction, and plant-pathogen interaction to combat SM. Conclusion: This study establishes a foundation for understanding the immune mechanisms of tea plants across different canopy layers in response to SM infection. It not only sheds light on the complex defense strategies employed by tea plants but also identifies candidate genes and metabolites crucial for enhancing tea plant breeding and resistance to SM. [ABSTRACT FROM AUTHOR]

Background: Visceral leishmaniasis (VL) is a zoonotic disease caused by Leishmania infantum and transmitted by the sand fly Lutzomyia longipalpis. Dogs are the major domestic reservoir of L. infantum. To prevent the spread of the disease, dog collars impregnated with 4% deltamethrin have been effectively used in VL endemic areas. However, this approach may contribute to the emergence of insecticide resistance in sand flies. Therefore, it is important to characterize the susceptibility of different populations of Lu. longipalpis to deltamethrin in areas where insecticide-impregnated dog collars are used. Methods: Six field sand fly populations from Brazil were exposed to deltamethrin in CDC bottle bioassays at the diagnostic doses (DD) of 21.9 μg/bottle and 30 μg/bottle. For the dose–response (DR) experiments, doses of 1, 3, 5, 7, 9 and 11 μg/bottle of deltamethrin were used to impregnate bottles; control group bottles were impregnated with acetone only. Each bottle contained an average of 20 sand flies, both male and female, and they were exposed to either deltamethrin or acetone for 60 min. Results: Based on the DD of 21.9 μg/bottle, three populations were susceptible to deltamethrin. In contrast, two populations collected from the states of Ceará and Minas Gerais exhibited mortality rates of 94.9% and 95.7%, indicating possible resistance, and one population from the state of Ceará showed resistance, with a mortality rate of 87.1%. At the DD of 30 μg/bottle, two populations from the states of Ceará and Piauí showed possible resistance, while the other four populations were susceptible. The resistance ratio (RR50) ranged from 2.27 to 0.54, and RR95 ranged from 4.18 to 0.33, indicating a low resistance intensity. Conclusions: This study established a DD for Lu. longipalpis using the CDC bottle bioassay. We found that Lu. longipalpis populations in three Brazilian states where insecticide-impregnated dog collars were used for VL control were susceptible to deltamethrin. However, one population in Ceará State was classified as resistant to deltamethrin. These results contribute to the current knowledge on sand fly resistance and surveillance, and highlight the need for a better understanding of the resistance mechanisms of Lu. longipalpis in areas where insecticide-impregnated dog collars have been widely used. [ABSTRACT FROM AUTHOR]

While ceftriaxone remains the first-line treatment for gonorrhea, the US Centers for Disease Control and Prevention recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021 and 2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176), and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was highest among women (16.4%, 10/61), followed by men who have sex with women (6.4%, 7/109) and men who have sex with men (5.8%, 57/982). The prevalence of cefixime-resistant N gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; thus, cefixime treatment would have limited benefits in Australia. [ABSTRACT FROM AUTHOR]

Hormone receptor-positive breast cancer may recur or metastasize years or decades after its diagnosis. Furthermore, hormone receptor expression may persist in relapsed or metastatic cancer cells. Endocrine therapy is one of the most efficacious treatments for hormone receptor-positive breast cancers. Nevertheless, a considerable proportion of patients develop resistance to endocrine therapy. Previous studies have identified numerous mechanisms underlying drug resistance, such as epigenetic abnormalities in the estrogen receptor (ER) genome, activation of ER-independent ligands, and alterations in signaling pathways including PI3K/AKT/mTOR, Notch, NF-κB, FGFR, and IRE1-XBP1. This article reviews the mechanisms of endocrine resistance in hormone receptor-positive advanced breast cancer, drawing from previous studies, and discusses the latest research advancements and prospects. [ABSTRACT FROM AUTHOR]

Species persist through resistance and recovery traits induced by natural stressors. Whether human activities exacerbate or moderate the effects of natural stressors is an open question. Because eelgrass (Zostera marina) creates coastal habitat, its response to natural stressors and human activities is of particular management importance. In this study, traits of intertidal eelgrass were examined across cumulative stressors of emersion and oyster culture, including two culture types: oysters grown directly on sediment (ground culture) or supported by gear above the sediment (off-bottom culture). Summer eelgrass was larger above- and below-ground and branched less than in spring, while density and cover were similar seasonally but declined at higher elevation and in ground culture. Eelgrass traits were divided into those related to resistance (larger above-ground size and below-ground storage) and recovery (increased flowering, branching, and rhizome extension). Resistance traits responded additively to intertidal elevation and oyster culture, with above- and below-ground size reduced in all conditions except that rhizome mass was maintained in ground culture. Smaller above-ground size may confer resistance to emersion stress, as a departure from expectations for other stressors. For resilience traits, flowering increased and internode length declined at higher elevation, whereas these traits did not change in ground culture, and off-bottom culture was associated with shorter internodes (additive cumulative stressor) and tended to moderate the enhanced flowering at higher elevations (non-additive, P=0.058). Transitory disturbance in ground culture may reduce eelgrass density with few effects on resilience, whereas off-bottom culture involves longer-term gear placement and trait responses by eelgrass. [ABSTRACT FROM AUTHOR]

Heat stress has become one of the abiotic stresses that pose an increasing threat to maize production due to global warming. The Hsp20 gene family confers tolerance to various abiotic stresses in plants. However, very few Hsp20s have been identified in relation to maize thermotolerance. In this study, we conducted a comprehensive study of Hsp20s involved in thermotolerance in maize. A total of 33 maize Hsp20 genes (ZmHsp20s) were identified through scanning for a conserved α-crystalline domain (ACD), and they were categorized into 14 subfamilies based on phylogenetic analysis. These genes are distributed across all maize chromosomes and nine of them are in regions previously identified as heat-tolerance quantitative trait loci (hrQTL). These hrQTL-associated ZmHsp20s show variation in tissue-specific expression profiles under normal conditions, and seven of them possess 1–5 heat stress elements in their promoters. The integration of RNA-seq data with real-time RT-PCR analysis indicated that ZmHsp23.4, ZmHsp22.8B and ZmHsp18 were dramatically induced under heat stress. Additionally, these genes exhibited co-expression patterns with key ZmHsfs, which are crucial in the heat tolerance pathway. When a null mutant carrying a frame-shifted ZmHsp18 gene was subjected to heat stress, its survival rate decreased significantly, indicating a critical role of ZmHsp18 in maize thermotolerance. Our study lays the groundwork for further research into the roles of ZmHsp20s in enhancing maize's thermotolerance. [ABSTRACT FROM AUTHOR]

Acquired or de novo resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) is a major challenge to ovarian cancer treatment. Therefore, strategies to overcome PARPi resistance are critical to improve prognosis. The purpose of this study is to evaluate whether inhibition of ADAM17 sensitizes ovarian cancer to treatment with olaparib, a PARPi, thereby bypassing resistance mechanisms and improving treatment response. Thus, we analyzed the effect of olaparib in combination with the ADAM17 inhibitor GW280264X in ovarian cancer using a 2D monolayer and a 3D spheroid model followed by a multicontent readout (viability, caspase activation and cytotoxicity). To emphasize the translational aspect of our work, we performed corresponding experiments on primary cells derived from ovarian cancer patients initially screened for their mutation status of the breast cancer gene (BRCA 1/2). In 2D, we observed a significant reduction in cell viability and a subsequent increase in apoptosis of the combined treatment (olaparib + GW280264X) compared with olaparib mono-treatment. The combined treatment allows a substantial dose reduction of olaparib rendering a strong synergistic effect. Using a 3D spheroid model from primary cells, we confirmed the 2D monoculture results and demonstrated not only increased caspase activity under the combined treatment but also a substantial gain in cytotoxicity compared to the mono-treatment. Our study proposes ADAM17 inhibition sensitizing ovarian cancer to olaparib treatment and improving treatment response. [ABSTRACT FROM AUTHOR]

Research in recent decades shows that private military and security contractors have reshaped the tenor and reach of US military power abroad while also accelerating the militarization of domestic policing. Previous work on militarized policing has primarily centered on urban environments. This article examines Blackwater North, a facility in a rural Illinois community, which provided privatized, militarized police training from 2007 through 2010. Drawing from newspaper accounts, government records, and ethnographic fieldwork conducted in the community after the facility's closure, I analyze residents’ recollections of the local support of and opposition to Blackwater North. I argue that local supporters promoted a culture of perpetual preparedness that positioned militarized policing as a rational form of harm reduction, as well as one that could yield economic benefits to struggling host communities. I also examine the opposition and analyze the insider/outsider divides that emerged within the debate surrounding Blackwater North. At stake for both supporters and opponents were differing cultural conceptions of what increases, and what erodes, security. This case study focuses on rural spaces’ role in the landscape of militarized policing and illuminates the cultural processes by which privatized military power and militarized policing become accepted and resisted at the community level. [ABSTRACT FROM AUTHOR]

Introduction: The epidemic spread of the harmful bacterium Xylella fastidiosa causing the "olive quick decline syndrome", decimating olive trees in southern Italy, in the region of Apulia, prompted investigations to search for olive genotypes harbouring traits of resistance. Methods: A prospecting survey was carried out to identify, in the heavily infected area of Apulia, olive genotypes bearing resistance. Given the limited genetic diversity in the commercial olive groves with few cultivars widely cultivated, surveys targeted predominantly spontaneous olive genotypes in natural and uncultivated areas. Trees, selected for the absence of symptoms, were subjected to diagnostic tests and parentage analysis to disclose their genetic background. Transcriptomic analyses were also employed to decipher the molecular pathways in resistant genotypes. Artificial inoculations were carried out to confirm the resistant phenotypes of four open-pollinated seedlings of the cultivar Leccino. Results: Among the 171 olive collected genotypes, 139 had unique simple sequence repeat (SSR) profiles, with the cultivars Leccino, Cellina di Nardò, and Ogliarola salentina being the most frequent candidate parents. Among the Leccino progeny (n. 61), 67% showed a highly resistant (HR), resistant (R), or tolerant (T) phenotype to infection by X. fastidiosa. The occurrence of such phenotypes among those deriving from Cellina di Nardò and Ogliarola salentina was 32% and 49%, respectively. Analyses of the transcriptomic profiles of three Leccino-bearing genotypes, naturally infected and not showing symptoms, unravelled that a total of 17,227, 13,031, and 4,513 genes were found altered in the expression, including genes involved in photosynthesis, cell wall, or primary and secondary metabolism. Discussion: Indeed, transcriptomic analyses showed that one of these genotypes (S105) was more resilient to changes induced by the natural bacterial infection than the remaining two (S215 and S234). This study consolidates the evidence on the presence and heritage of resistance traits associated with the cv. Leccino. Moreover, valuable insights were gathered when analysing their transcriptomic profiles, i.e., genes involved in mechanisms of response to the bacterium, which can be used in functional genetic approaches to introduce resistance in susceptible cultivars and initiate strategies in olive-breeding programs through marker-assisted selection. [ABSTRACT FROM AUTHOR]

Excellent germplasm resources are the foundation for cultivating high-quality, disease-resistant, and stress-tolerant varieties. In this study, simple sequence repeat (SSR) markers were used to identify 138 potato accessions collected from worldwide, and genetic cluster analysis was used to characterize the genetic diversity of the tested germplasm resources. The Potato virus Y (PVY) resistance of these potato accessions was identified by artificial friction inoculation combined with molecular marker detection, and potato accessions with different PVY resistance were screened based on disease index and incidence rate. Using SSR markers, 138 potato accessions were identified, and the results showed that the genetic distances between the tested potato germplasm resources ranged from 0.025 to 0.660, and the genetic similarity coefficients ranged from 0.489 to 0.975. The 138 accessions could be clustered into five subgroups using Unweighted Pair-Group Method with Arithmetic Mean (UPGMA). Among them, Z173, Biyin No. 4, Suyin No. 2, XN995, XN987, Biyin No 22, Bibiao104, Sarpo mira, XN996, XN979, Desiree, RUNSHI, Actrice, Jia 1219, Heyin No 12, and Moyin No.1 have relatively distant genetic relationship with another 122 accessions. Based on the disease index, the following different accessions were screened: five highly resistant, 11 resistant, 45 moderately resistant, 35 susceptible, and 42 highly susceptible. Fourteen resource materials with good resistance (disease index ≤ 33.74%, and a grading of high resistance (HR) or medium resistance (MR); incidence rate ≤ 67.58%) were identified. By combining genetic cluster analysis and PVY resistance identification, six accessions showed PVY resistance and had distant genetic relationships with other accessions selected which provided important materials for disease resistance breeding and quality improvement of potato. In this study, the genetic diversity and PVY resistance of global potato germplasm resources was explored, and potato germplasm materials with important utilization value were screened. The results obtained in this study could provide important references for the research and utilization of global potato germplasm resources. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a group of both acute and chronic parasitic trematode infections of the genus Schistosoma. Research into schistosomiasis has been minimal, leading to its classification as a neglected tropical disease, yet more than 140 million people are infected with schistosomes globally. There are no treatments available for early-stage infections, schistosomal dermatitis, or Katayama syndrome, other than symptomatic control with steroids and antihistamines, as the maturing organisms seem to be mostly resistant to typical antiparasitics. However, praziquantel (PZQ) has been the drug of choice for schistosomiasis for decades in the latter stages of the disease. Though it is effective against all three clinically relevant species, heavy reliance on PZQ has led to concerns of schistosome resistance, especially in areas that have implemented this drug in mass drug administration (MDA) programs. This article summarizes the available literature concerning the available evidence for and against a warranted concern for PZQ resistance, genomic studies in schistosomes, proposed mechanisms of resistance, and future research in alternative methods of schistosomiasis treatment. [ABSTRACT FROM AUTHOR]

Disinfectants are essential for biosecurity, preventing the persistence and spread of zoonotic pathogens on farms and subsequent human infections. In this study, transcriptomics and genomics were utilised to assess the effect of disinfectant exposure on pathogenic Escherichia coli. The exposure of E. coli O157:H7 to sub-optimal concentrations of commonly used farm disinfectants elicited changes in both the transcriptome and genome. The transcriptomics identified upregulation of >300 genes and downregulation of >100 genes with functions, which included stress response, metabolism, transcription, transportation, membrane-associated and virulence genes. The phage shock protein (psp) operon was highly upregulated in response to a quaternary ammonium compound (QAC)-containing disinfectant, which has not previously been associated with a response to chemical stress. Disinfectant-adapted isolates generated by exposure to sub-lethal disinfectants levels demonstrated resistance to several common antibiotics and decreased sensitivity to biocides. Whole genome sequencing of the mutant strains indicated that they had acquired mutations in the genes associated with the upregulation of the multiple antibiotic resistance (MAR) efflux system (lon protease and marR) and topoisomerase genes (gyrA and gyrB). The disinfectant-adapted isolates also exhibited increased expression of transcription, respiration and several pH stress response genes localised in the "acid fitness island." This study demonstrated that sub-optimal disinfectant concentrations allow E. coli O157:H7 to adapt and survive disinfection and develop antibiotic resistance. These changes could have implications for disease treatment and elimination on farms. Although E. coli O157:H7 and farm disinfectants were the focus of this study, we believe these findings are also applicable to other settings, including hospitals. [ABSTRACT FROM AUTHOR]

Background: The heterogeneous and complex genetic landscape of NSCLC impacts the clinical outcomes of patients who will eventually develop resistance to osimertinib. Liquid biopsy (LB) analysis as a minimally invasive approach is a key step to efficiently identify resistance mechanisms and adjust to proper subsequent treatments. Materials and methods: In the present study, we combined plasma-cfDNA and CTC analysis from 30 NSCLC patients in samples collected before treatment and at the progression of disease (PD). We detected molecular alterations at the DNA mutation (EGFR, PIK3CA, KRAS G12C, BRAF V600E), DNA methylation (RASSF1A, BRMS1, FOXA1, SLFN1, SHISA3, RARβ,, WIF-1, RASSF10 and APC), gene expression (CK-19, CK-18, CK-8, AXL, TWIST-1, PD-L1, PIM-1, Vimentin, ALDH-1 , and B2M) and chromosomal level (HER2 and MET amplification) as possible resistance mechanisms and druggable targets. We also studied the expression of PD-L1 in single CTCs using immunofluorescence. Results: In some cases, T790M resistance EGFR mutation was detected at baseline in CTCs but not in the corresponding plasma cfDNA. PIK3CA mutations were detected only in plasma-cfDNA but not in corresponding CTCs. KRAS G12C and BRAF V600E mutations were not detected in the samples analyzed. MET amplification was detected in the CTCs of two patients before treatment whereas HER2 amplification was detected in the CTCs of three patients at baseline and in one patient at PD. DNA methylation analysis revealed low concordance between CTCs and cfDNA, indicating the complementary information obtained through parallel LB analysis. Results from gene expression analysis indicated high rates of vimentin-positive CTCs detected at all time points during osimertinib. Moreover, there was an increased number of NSCLC patients at PD harboring CTCs positive in PD-L1. AXL and PIM-1 expression detected in CTCs during treatment suggesting new possible therapeutic strategies. Discussion: Our results reveal that comprehensive liquid biopsy analysis can efficiently represent the heterogeneous molecular landscape and provide prominent information on subsequent treatments for NSCLC patients at PD since druggable molecular alterations were detected in CTCs. [ABSTRACT FROM AUTHOR]

Genomic instability is a core characteristic of cancer, often stemming from defects in DNA damage response (DDR) or increased replication stress. DDR defects can lead to significant genetic alterations, including changes in gene copy numbers, gene rearrangements, and mutations, which accumulate over time and drive the clonal evolution of cancer cells. However, these vulnerabilities also present opportunities for targeted therapies that exploit DDR deficiencies, potentially improving treatment efficacy and patient outcomes. The development of PARP inhibitors like Olaparib has significantly improved the treatment of cancers with DDR defects (e.g., BRCA1 or BRCA2 mutations) based on synthetic lethality. This achievement has spurred further research into identifying additional therapeutic targets within the DDR pathway. Recent progress includes the development of inhibitors targeting other key DDR components such as DNA-PK, ATM, ATR, Chk1, Chk2, and Wee1 kinases. Current research is focused on optimizing these therapies by developing predictive biomarkers for treatment response, analyzing mechanisms of resistance (both intrinsic and acquired), and exploring the potential for combining DDR-targeted therapies with chemotherapy, radiotherapy, and immunotherapy. This article provides an overview of the latest advancements in targeted anti-tumor therapies based on DDR and their implications for future cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Freeze-thaw is a common stress at high altitudes in northern China. There is a risk of cadmium (Cd) contamination in the region. γ-aminobutyric acid (GABA) is a natural product that regulates plant growth. Rye (Secale cereale) was used as research material to investigate the physiological effects of exogenous GABA on rye seedlings under the single and combined stresses of freeze-thaw and cadmium. The results showed that the combined stress severely inhibited shoot length, root length, fresh weight, and dry weight, increased malondialdehyde and hydrogen peroxide contents, and significantly decreased superoxide dismutase (SOD) activity. Foliar application of 5 mM GABA alleviated the negative effects of stress on seedling growth, increased soluble protein content, and reduced malondialdehyde and hydrogen peroxide contents. Exogenous GABA application also enhanced the activities of SOD and peroxidase (POD). Additionally, the presence of exogenous GABA activated the GABA metabolic process and encouraged the accumulation of phytochelatins, glutathione, and non-protein thiol. These results indicate that exogenous GABA can effectively improve the resistance of rye seedlings to freeze-thaw and Cd by regulating the antioxidant enzyme system and enhancing its own detoxification mechanism, and they provide a basis for future applications of exogenous GABA, which is beneficial for ecological protection. In high-altitude or cold regions of northern China, plants may simultaneously face two environmental stresses: (1) heavy metal cadmium; and (2) freeze-thaw. The study showed that γ-aminobutyric acid (GABA) significantly improved the growth of rye (Secale cereale) seedlings under these stresses, enhancing their resistance. This finding provides an innovative bioregulation strategy for plant response to environmental stressors, highlighting the potential application value of GABA as a natural plant growth regulator. [ABSTRACT FROM AUTHOR]

One of the most chemically adaptable elements is boron which is found in the periodic table between two groups, i.e., metals and nonmetals and may create more than 16 polymorphs that are bulk and made of connected boron polyhedra. Given that boron and carbon are comparable elements, it has been questioned whether two-dimensional (2D) boron could serve as a conceptual starting point for the construction of other boron nanostructures. Using boron as fundamental building blocks, boron nanosheets were synthesized known as borophenes. Borophene is found to be a crystalline form of atomic monolayer boron which was theoretically first predicted in mid-1990s and experimentally synthesized very recently in 2015. In this work, we studied both armchair and zigzag formation of borophene and presented a comparative analysis of their minimum sub-band energy, effective mean free path E n , number of conduction channels N ch , scattering resistance per unit length. The N ch for armchair BNR is 3,2,1 for 22 nm, 13 nm, 7 nm, respectively, which is comparatively more than zigzag BNR. We later proposed Top-Contact BNR (TC-BNR) and Side-Contact BNR (SC-BNR). Our analysis shows that SC-BNR offers 9 6 % less resistance compared to TC-BNR and it is of the order of SC-GNR. Further, if we compare with copper interconnects, BNR is better in terms of performance and copper can be replaced with BNR due to high bulk mean free paths 300 nm and 400 nm compared to copper's 40 nm. Boron, a metalloid, displays remarkable adaptability, giving rise to over sixteen polymorphs, including borophenes—2D boron nano sheets synthesized in 2015. Armchair borophenes demonstrate greater conduction channels (Nch) compared to zigzag counterparts, with Side- Contact BNR (SC-BNR) boasting 96% less resistance than Top-Contact BNR (TC-BNR). These properties position boron nanostructures as competitive alternatives to copper interconnects, offering significantly longer mean free paths (300nm–400nm for BNR versus 40nm for copper). Borophene, akin to graphene in its honeycomb structure, boasts greater strength and flexibility, alongside a slightly reduced mean free path and fourfold higher fermi velocity. Its resistance is comparable to graphene, yet it offers advantages over copper, including excellent superconductivity with results on par with graphene. [ABSTRACT FROM AUTHOR]

Background: One of the biggest threats to global health is the prevalence of antimicrobial resistance (AMR) in respiratory tract infections, which results in significant morbidity and mortality worldwide. This study aimed to decrease the prevalence of bacterial resistance in those suffering from pleuropulmonary infections. Methods: This Retrospective cross sectional study was conducted at the Chest Department and Chest ICU at Zagazig University Hospital on 120 patients with pleuropulmonary infections. During this study, Patients with pleuropulmonary infections were considered for analysis and identification of the clinical isolates. Results: The most common organisms isolated were gram-ve in 110 cases (79.7%), distributed as k. pneumoniae 58 (42.0%), E.coli 21 (15.2%), P.aeruginosa 20 (14.4%), acinetobacter baumannii 11 (7.9), while gram +ve organisms were isolated in 28 cases (20.2%), distributed as Staph Arouse 12 (8.6%) Coagulase -VE Staph 11 (7.9%), and Staph haemolyticus 5 (3.6%). K.Pneumonia, E. coli and P.aeruginosa were predominantly isolated from sputum 42.9%, 15.2%, 15.2% respectively, K.Pneumonia, Staph Aureus, P.aeruginosa, Acinetobacter baumannii and Staph haemolyticus were predominantly isolated from infected Pleural fluid with 36.0%, 20, 12.0%, 12.0%, respectively. Conclusions: the most common organisms that isolated from our cases were k. pneumoniae, E.coli and P.aeruginosa, Acinetobacter baumannii as a gram -ve were Susceptible for Carpenems, Colisten while resistance for Pipracillin, Ciprofloxacin, Levofloxacin and Ceftazidime, Cefipime. On the other hand, the gram + ve isolates were Coagulase negative staph, Staph.aureus and Staph haemolyticus found susceptible for Gentamycin, Vancomycin, Linezolid, while resistance for Flouroqoinolones and, Erthromycine. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) presents a significant challenge in oncology due to its aggressive nature and limited targeted therapeutic options. This study explores the potential of autocrine motility factor (AMF) and an AMF-derived peptide as novel treatments for TNBC. AMF, primarily secreted by neoplastic cells, plays a crucial role in cancer cell motility, metastasis, and proliferation. The research demonstrates that AMF and its derived peptide inhibit TNBC cell proliferation by modulating cellular migration, redox homeostasis, apoptotic pathways, and drug efflux mechanisms. Dose-dependent antiproliferative effects were observed across three TNBC cell lines, with higher concentrations impairing cellular migration. Mechanistic studies revealed decreased glucose-6-phosphate dehydrogenase expression and elevated reactive oxygen species production, suggesting redox imbalance as a primary mediator of apoptosis. Combination studies with conventional therapeutics showed near-complete eradication of resistant TNBC cells. The observed reduction in p53 levels and increased intranuclear doxorubicin accumulation highlight the AMF/AMF peptide's potential as multidrug resistance modulators. This study underscores the promise of using AMF/AMF peptide as a novel therapeutic approach for TNBC, addressing current treatment limitations and warranting further investigation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide and is responsible for numerous deaths. 5-fluorouracil (5-FU) is an effective chemotherapy drug commonly used in the treatment of CRC, either as monotherapy or in combination with other drugs. However, half of CRC cases are resistant to 5-FU-based therapies. To contribute to the understanding of the mechanisms underlying CRC resistance or recurrence after 5-FU-based therapies, we performed a comprehensive study integrating in silico, in vitro, and in vivo approaches. We identified differentially expressed genes and enrichment of pathways associated with recurrence after 5-FU-based therapies. Using these bioinformatics data as a starting point, we selected a group of drugs that restored 5-FU sensitivity to 5-FU resistant cells. Interestingly, treatment with the novel Rac1 inhibitor, 1A-116, reversed morphological changes associated with 5-FU resistance.. Moreover, our in vivo studies have shown that 1A-116 affected tumor growth and the development of metastasis. All our data allowed us to postulate that targeting Rac1 represents a promising avenue for the development of new treatments for patients with CRC resistant to 5-FU-based therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: The standard therapy for advanced lung cancer is immunotherapy with or without chemotherapy. In this review, we summarize clinical trials that have been completed or are ongoing that concern the treatment of advanced lung cancer which has been treated previously with standard immunotherapies and has become resistant to these. Many different therapies such as vaccines, immune checkpoint therapies, and cellular therapies are currently in development, but the majority are still in early-phase trials. Immunotherapy with PD-1/PD-L1 inhibitors is the standard method of care for the treatment of newly diagnosed advanced or metastatic NSCLC, with or without chemotherapy. Many tumors, however, develop resistance to these immunotherapy agents. There is a need to develop more effective therapies for patients with metastatic NSCLC in the second-line setting and beyond. In this review, we present an overview of novel immunotherapies being investigated regarding the treatment of these patients. We summarize completed, as well as ongoing, trials investigating these therapies as monotherapy or in combination with PD-1/PD-L1 inhibitors. These include immune co-stimulatory antibodies, T-cell agonists, oncolytic viruses, vaccines, TIL therapies, and CAR-T therapies. [ABSTRACT FROM AUTHOR]

Introduction: Identifying accurate biomarkers for predicting response to chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) is a critical challenge. The protein SIRT1, recognized for its implications in longevity, has been associated with tumor promotion in ESCC. However, data regarding its correlation with CRT sensitivity remain unreported. Therefore, in this study, we aimed to investigate the relationship between SIRT1 expression and CRT sensitivity and concurrently assess the effect of SIRT1 knockdown on CRT sensitivity in ESCC. Methods: This study included 73 patients who underwent radical esophagectomy after CRT. SIRT1 expression in pre-treatment endoscopic biopsies was assessed through immunostaining, followed by a comparative analysis of CRT effects on surgical specimens. Small interfering RNA was used to attenuate SIRT1 expression in TE5 and TE10 cells, which were then subjected to cisplatin treatment at varying doses and concentrations and irradiation with X-rays, respectively. Results: High SIRT1 tissue expression was significantly associated with CRT resistance. Multivariate analysis identified high SIRT1 expression as an independent biomarker for poor CRT response. In TE-5 and TE-10 cells, SIRT1 knockdown significantly decreased cell viability and increased sensitivity to cisplatin and radiation treatment compared to that of the negative control. Conclusion: Our study results demonstrate the potential of SIRT1 as a predictive biomarker for CRT response in ESCC, highlighting the heightened sensitivity to CRT upon the transcriptional inactivation of SIRT1. Targeting SIRT1 emerges as a promising strategy for enhancing the efficacy of CRT for ESCC. [ABSTRACT FROM AUTHOR]

Drought is an increasing risk to the biodiversity within rivers—ecosystems which are already impacted by human activities. However, the long‐term spatially replicated studies needed to generate understanding of how anthropogenic stressors alter ecological responses to drought are lacking.We studied aquatic invertebrate communities in 2500 samples collected from 179 sites on rivers emerging from England's chalk aquifer over three decades. We tested two sets of alternative hypotheses describing responses to and recovery from drought in interaction with human impacts affecting water quality, fine sediment, water temperature, channel morphology, flow and temporal change in land use. We summarized communities using taxa richness, an index indicating tolerance of anthropogenic degradation (average score per taxon, ASPT) and deviation from the average composition.Responses to drought were altered by interactions with human impacts. Poor water quality exacerbated drought‐driven reductions in taxa richness. Drought‐driven deviations from the average community composition were reduced and enhanced at sites impacted by flow augmentation (e.g. effluent releases) and flow reduction (e.g. abstraction), respectively.Human impacts altered post‐drought recovery. Increases in richness were lower at sites impacted by water abstraction and higher at sites with augmented flows, in particular as recovery trajectories extended beyond 3 years. ASPT recovered faster at sites that gained woodland compared to urban land, due to their greater recovery potential, that is, their lower drought‐driven minimum values and higher post‐drought maximum values.Synthesis and applications. We show that communities in river ecosystems exposed to human impacts—in particular poor water quality, altered flow volumes and land use change—are particularly vulnerable to drought. These results provide evidence that management actions taken to enhance water quality, regulate abstraction and restore riparian land use could promote ecological resilience to drought in groundwater‐dominated rivers such as globally rare chalk streams and other rivers of the Anthropocene, as they adapt to a future characterized by increasing climatic extremity. [ABSTRACT FROM AUTHOR]

Patients with chronic myeloid leukemia (CML) who have failed conventional tyrosine kinase inhibitors (cTKIs) and asciminib constitute a complex group of patients with few therapeutic options. A retrospective descriptive multicenter observational study was carried out including patients with CML who had presented a therapeutic failure to ≥ 2 cTKIs and asciminib, and had received or were not candidates to ponatinib. Of the 19 patients enrolled, 8 patients failed asciminib due to intolerance and 11 due to resistance. The most common strategy for intolerant patients was to initiate a previously administered cTKI (6/8) with dose adjustments or symptomatic management of adverse events (AEs). Of the patients who failed due to resistance, only patients who underwent progenitor transplantation achieved profound long-term responses. A frequent strategy was to use ponatinib (4/11) in patients previously considered non-candidates, with poor responses in patients in whom dose reductions were used, and severe AEs in patients at standard doses. In the remaining patients, cTKIs and other agents (interferon, hydroxyurea, citarabine, busulfan) were used with poor responses. Patients who progressed to advanced stages had a dismal prognosis. With a median follow-up of 11.2 months, overall survival of the global cohort was 73%; 100% for intolerant patients, 71% for resistant patients and 25% for those who discontinue asciminib in accelerated/blastic phase. [ABSTRACT FROM AUTHOR]

Heat extremes are becoming more frequent and severe owing to contemporary climate change, and the observed ecological impacts from past extremes are expected to be exceeded by current and future heat extremes. Although the vulnerabilities of species to heat extremes are increasingly being investigated, the resulting dynamics of populations and communities, including various response stages during and after heat extremes, are rarely considered. Several biological mechanisms can buffer ecological responses at different response stages (exposure, resistance, recovery), but also induce debts that become apparent at later stages. These debts amplify and extend ecological responses over longer periods, especially with sequential climatic (or other disturbance) events. Integrating mechanisms across response stages, with their associated ecological debts, is key to identifying settings where large heat-induced ecological impacts are most likely. Heat extremes have become the new norm in the Anthropocene. Their potential to trigger major ecological responses is widely acknowledged, but their unprecedented severity hinders our ability to predict the magnitude of such responses, both during and after extreme heat events. To address this challenge we propose a conceptual framework inspired by the core concepts of ecological stability and thermal biology to depict how responses of populations and communities accumulate at three response stages (exposure, resistance, and recovery). Biological mechanisms mitigating responses at a given stage incur associated costs that only become apparent at other response stages; these are known as 'ecological debts'. We outline several scenarios for how ecological responses associate with debts to better understand biodiversity changes caused by heat extremes. [ABSTRACT FROM AUTHOR]

I present a research study aimed at understanding the discourses and practices regarding police violence that human rights defenders in Chile have. Using an ethnographic methodology (2020-2022), I worked with defenders from a state institution, a civil organization that supports victims, and another civil organization that monitors protests. I conducted 16 interviews, document reviews, and daily activities observations. The integrated ethnographic analysis aimed to understand how discourses and practices maintain and promote certain social relations. This research allowed me to identify practices directed toward the State, society, and the organizations themselves. The meanings of these resistance practices come together in three interrelated areas that characterize this institutional violence: invisibilization, naturalization and impunity. I conclude that filing complaints and educating to promote cultural changes create paths to face the causes of police abuses associated with the productive role of the police in a racialized and class-based order. [ABSTRACT FROM AUTHOR]

SUMMARY: Wheat (Triticum aestivum L.) is a globally staple crop vulnerable to various fungal diseases, significantly impacting its yield. Plant cell surface receptors play a crucial role in recognizing pathogen‐associated molecular patterns (PAMPs) and activating PAMP‐triggered immunity, boosting resistance against a wide range of plant diseases. Although the role of plant chitin receptor CERK1 in immune recognition and defense has been established in Arabidopsis and rice, its function and potential agricultural applications in enhancing resistance to crop diseases remain largely unexplored. Here, we identify and characterize TaCERK1 in Triticeae crop wheat, uncovering its involvement in chitin recognition, immune regulation, and resistance to fungal diseases. By a comparative analysis of CERK1 homologs in Arabidopsis and monocot crops, we demonstrate that AtCERK1 in Arabidopsis elicits the most robust immune response. Moreover, we show that overexpressing TaCERK1 and AtCERK1 in wheat confers resistance to multiple fungal diseases, including Fusarium head blight, stripe rust, and powdery mildew. Notably, transgenic wheat lines with moderately expressed AtCERK1 display superior disease resistance and heightened immune responses without adversely affecting growth and yield, compared to TaCERK1 overexpression transgenics. Our findings highlight the significance of plant chitin receptors across diverse plant species and suggest potential strategies for bolstering crop resistance against broad‐spectrum diseases in agricultural production through the utilization of plant immune receptors. Significance Statement: CERK1 acts as a chitin immune receptor for plant defense and survival, but its role and applied potential in Triticeae crops remain unknown. We identify TaCERK1 in wheat, revealing distinct characteristics of CERK1 homologs in chitin recognition and immune activation between cereals and the dicot Arabidopsis. Notably, overexpressing CERK1s from both cereal and Arabidopsis in wheat confers broad‐spectrum resistance to fungal diseases. Our findings highlight the potential of plant immune receptors in controlling crop diseases. [ABSTRACT FROM AUTHOR]