bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural antibiotics against antimicrobial resistance: sources and bioinspired delivery systems
Authors: Guedes Beatriz N. , Krambeck Karolline , Durazzo Alessandra , Lucarini Massimo , Santini Antonello , Oliveira M. Beatriz P. P. , Fathi Faezeh , Souto Eliana B. 
Published: June 2024

AbstractThe current burden associated to multidrug resistance, and the emerging superbugs, result in a decreased and even loss of antibiotic efficacy, which poses significant challenges in the treatment of infectious diseases. This situation has created a high demand for the discovery of novel antibiotics that are both effective and safe. However, while antibiotics play a crucial role in preventing and treating diseases, they are also associated with adverse effects. The emergence of multidrug-resistant and the extensive appearance of drug-resistant microorganisms, has become one of the major hurdles in healthcare. Addressing this problem will require the development of at least 20 new antibiotics by 2060. However, the process of designing new antibiotics is time-consuming. To overcome the spread of drug-resistant microbes and infections, constant evaluation of innovative methods and new molecules is essential. Research is actively exploring alternative strategies, such as combination therapies, new drug delivery systems, and the repurposing of existing drugs. In addition, advancements in genomic and proteomic technologies are aiding in the identification of potential new drug targets and the discovery of new antibiotic compounds. In this review, we explore new sources of natural antibiotics from plants, algae other sources, and propose innovative bioinspired delivery systems for their use as an approach to promoting responsible antibiotic use and mitigate the spread of drug-resistant microbes and infections.
Systematic micro-breaks affect concentration during cognitive comparison tasks: quantitative and qualitative measurements
Authors: Dianita Orchida , Kitayama Kakeru , Ueda Kimi , Ishii Hirotake , Shimoda Hiroshi , Obayashi Fumiaki 
Published: June 2024

AbstractAn approach to improve workers’ productivity performance without neglecting their well-being should be investigated. To elucidate the effects of systematic micro-break on intellectual concentration performance, a controlled laboratory experiment generated 31 participants’ data when each participant was performing cognitive comparison tasks. Systematic micro-break was given for 20 s after 7.5 min of cognitive work, for a total of 25 min of work tasks. Each participant performed the task under both conditions with and without micro-break intervention in a counterbalanced design. Two quantitative evaluations were made: the answering time and concentration time ratio. A subjective symptom questionnaire and the NASA task load index were applied for analytical consideration. The average answering time indicates that the performance under the influence of micro-break tends to be more stable over time and that it mitigates performance degradation compared to the performance in a condition without micro-break. For concentration time ratio scores, no significant difference was found between conditions with micro-break and without micro-break. However, a tendency was apparent by which the concentration time ratio score was higher in a condition with micro-break, which suggests higher cognitive performance. The subjective symptoms questionnaire indicated no significant difference between conditions with and without micro-break. Weighted NASA task load index questionnaire results indicated significant difference between both conditions with lower workload scores in conditions with micro-break. Results obtained from this study suggest that the implementation of systematic micro-break can support workers’ performance stability over time. Therefore, systematic micro-break can be promoted as a promising strategy for work recovery.
Review of non-conventional Hall effect thrusters
Authors: Chhavi Chhavi , Walker Mitchell L. R. 
Published: June 2024

AbstractElectric propulsion has become the favored approach for Low Earth Orbit (LEO) maneuvers, resulting in substantial expansion in its use in the satellite industry. The Hall effect thruster’s (HETs) high specific impulse and thrust-to-power ratio allow for a wide range of in-space propulsion applications, making it a viable alternative for various space missions. In the space sector, the mass production of HET is currently underway to fulfil the needs of the satellite industry for performing various maneuvers such as orbit boosting, station keeping, deorbitation, collision avoidance, and inter-orbital transfers. The increase in mass production has caused engineering challenges in manufacturing, necessitating an efficient batch production process to guarantee flight qualification within acceptable limits. Engineering production problems may cause manufacturing defects in HET components, leading to non-uniform magnetic field. The non- uniformities in the magnetic field can be observed azimuthally in the channel in various conditions resulting from electrical shorting and geometrical constraints. It is essential to comprehend the effect of such non-uniformities in the magnetic field on the performance of Hall-effect thrusters. An approach to understanding the potential effect of non-uniform magnetic field in HET is by analyzing the efficacy of non-conventional HETs possessing non-uniform magnetic fields. The article comprehensively reviews several non-conventional HETs with distinct channel cross-section geometries, such as linear, racetrack, and wall-less configurations. The paper presents a comparative analysis between non-conventional HETs and conventional HETs operating in low to mid-power configurations for performance evaluation. The review provides discussion of the effects of non-uniform magnetic field on the reduction of optimized HET operation by the presence of heightened erosion and reduction in stability. The review study highlights the importance of optimizing magnetic field topology for developing future thruster designs with enhanced performance and utilization.
The contradicting state of urban housing and neoliberal policy in India: a macro analysis
Authors: Biswas Arindam 
Published: June 2024

AbstractThe paper evaluates the adaptation of neoliberal policies in the Indian urban housing policy sector. While completing the objectives of this paper, the article also appraises the expression of neoliberalism as it unfolds in the literature. Neoliberalism is considered a loose set of philosophical, institutional, and political principles to safeguard individual and collective freedom like private property rights, goods and services exchange, movement of capital and labor, etc. Neoliberal policies promote open markets and trade to unbound creative potentials and entrepreneurial skills through efficient utilization of resources and upbringing of human well-being. In a neoliberal regime, cities compete to attract talented people, capital, and resources to achieve newer economic and social benchmarks. However, the constant pursuit of excessive achievements lets some negativities grow within. Large-scale inequality, deprivation, social unrest, and meager quality of life affect the sustainable and holistic development of seemingly most developed cities worldwide. Referring to literature from social sciences, urban planning, and development studies, this paper focuses on the consequences of neoliberalism and its impact on urban housing in India.
Peritoneal pseudomyxoma in a patient affected by appendicular mucocele: a case report
Authors: Anichini Matilde , Grazzini Giulia , Masserelli Antonella , Mattolini Lavinia , Miele Vittorio 
Published: June 2024

AbstractPseudomyxoma peritonei (PMP) is an uncommon clinical condition, characterized by mucinous ascites, generally associated with a rupture of an epithelial neoplasm of the appendix. Some authors also use the term PMP to indicate mucinous dissemination after rupture of mucin-producing tumors of other sites (i.e. colon, ovary). Clinical presentation is variable and depends on the progressive accumulation of mucinous ascites (obstructive symptoms); weight loss, elevated Ca 19.9 and Ca 125 levels can be present. Here, we report a case of a 58-year-old patient with a history of appendicular mucocele and HCV-related hepatopathy, who accessed to the emergency department of our institute for the onset of epigastric pain associated with food vomiting for 5 days. Blood tests demonstrated a mild leukocytosis, a mild anemia (Hb 12.8 g/dL), and increased transaminases and cholestasis indices. A contrast-enhanced CT (CECT) scan was performed: a peritoneal cavity filled with a neoformation with lobulated margins and over-water density leading to multiple incisions of the hepatic and splenic parenchyma was documented. Appendix had an increased caliber (4 cm) with coprolite near its origin. Hence, the suspicion of PMP was raised and later confirmed on surgical exploration.
Quantifying Seepage‐Face Evaporation and Its Effects on Groundwater Flow and Solute Transport in Small‐Slope Tidal Flat
Authors: Luo Manhua , Wang Tianwei , Geng Xiaolong , Yu Shengchao , Li Hailong 
Published: June 2024

AbstractLarge‐scale seepage faces occur on tidal flats with gentle slope, which are widely distributed worldwide. Evaporation on these seepage faces, leading to salt retention and accumulation, may significantly impact the density‐dependent groundwater flow beneath the tidal flats. However, due to nonlinear complexities of the groundwater flow and solute transport on seepage faces, explicit boundary conditions and numerical models to quantify these processes are lacking. In this study, we present both mathematical and numerical models to quantify these processes. Compared to the results of our previous study, this paper shows that seepage‐face evaporation can (a) significantly increase the groundwater salinity in the upper intertidal zone, and form multiple groundwater circulation cells in the intertidal zone, (b) cause the disappearance of multiple seepage‐faces and reduce the spatial extent of seepage faces notably, (c) and intensify the groundwater and salt exchange as well as the seawater‐groundwater circulation through the intertidal zone.
Role of Impact Angle on Equatorial Electrojet (EEJ) Response to Interplanetary (IP) Shocks
Authors: Nilam B. , Tulasi Ram S. , Oliveira Denny M. , Dimri A. P. 
Published: June 2024

AbstractInterplanetary (IP) shocks are one of the dominant solar wind structures that can significantly impact the Geospace when impinge on the Earth's magnetosphere. IP shocks severely distort the magnetosphere and induce dramatic changes in the magnetospheric currents, often leading to large disturbances in the geomagnetic field. Sudden enhancements in the solar wind dynamic pressure (PDyn) during IP shocks cause enhanced high‐latitude convection electric fields which penetrate promptly to equatorial latitudes. In response, the equatorial electrojet (EEJ) current exhibits sharp changes of magnitudes primarily controlled by the change in PDyn and the local time. In this paper, we further investigated the influence of shock impact angle on the EEJ response to a large number (306) of IP shocks that occurred during 2001–2021. The results consistently show that the EEJ exhibits a heightened response to the shocks that head‐on impact the magnetosphere (frontal shocks) than those with inclined impact (inclined shocks). The greater EEJ response during the frontal shocks could be due to a more intensified high‐latitude convection electric field resulting from the symmetric compression of the magnetosphere. Finally, an existing empirical relation involving PDyn and local time is improved by including the effects of impact angle, which can quantitatively better predict the EEJ response to IP shocks.
Tumor-resident microbiota contributes to colorectal cancer liver metastasis by lactylation and immune modulation
Authors: Gu Jian , Xu Xiaozhang , Li Xiangyu , Yue Lei , Zhu Xiaowen , Chen Qiuyang , Gao Ji , Takashi Maruyama , Zhao Wenhu , Zhao Bo , Zhang Yue , Lin Minjie , Zhou Jinren , Liang Yuan , Dai Shipeng , Pan Yufeng , Shao Qing , Li Yu , Wang Yiming , Xu Zibo , Qian Qufei , Huang Tianning , Qian Xiaofeng , Lu Ling 
Published: June 2024

AbstractThe role of tumor-resident microbiota in modulating tumor immunity remains unclear. Here, we discovered an abundance of intra-tumoral bacteria, such us E.coli, residing and resulting in Colorectal cancer liver metastasis (CRLM). E.coli enhanced lactate production, which mediated M2 macrophage polarization by suppressing nuclear factor-κB -gene binding (NF-κB) signaling through retinoic acid-inducible gene 1 (RIG-I) lactylation. Lactylation of RIG-I suppressed recruitment of NF-κB to the Nlrp3 promoter in macrophages, thereby reducing its transcription. This loss of Nlrp3 affected the immunosuppressive activities of regulatory T cells (Tregs) and the antitumor activities of and CD8+ T cells. Small-molecule compound screening identified a RIG-I lactylation inhibitor that suppressed M2 polarization and sensitized CRLM to 5-fluorouracil (5-FU). Our findings suggest that tumor-resident microbiota may be a potential target for preventing and treating CRLM.
Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets
Authors: Zhang Shaosen , Xiao Xinyi , Yi Yonglin , Wang Xinyu , Zhu Lingxuan , Shen Yanrong , Lin Dongxin , Wu Chen 
Published: June 2024

AbstractTumorigenesis is a multistep process, with oncogenic mutations in a normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic mutations and clonal expansion in normal tissues, their transformation into cancer remains a rare event, indicating the presence of additional driver events for progression to an irreversible, highly heterogeneous, and invasive lesion. Recently, researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution, independently of inducing mutations. Additionally, clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into tumors. However, the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully understood. In this review, we summarize the genetic, epigenetic, and external driver events, and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution. A deeper understanding of the earliest molecular events holds promise for translational applications, predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.
Irritability in young people with copy number variants associated with neurodevelopmental disorders (ND-CNVs)
Authors: Hall Jessica H. , Chawner Samuel J. R. A. ,   IMAGINE-ID consortium, Housby Harriet , Lee Irene , Skuse David , Wolstencroft Jeanne , Mandy William , Dexanas Spiros , Baker Kate , Raymond Lucy , van den Bree Marianne , Chawner Samuel , Hall Jeremy , Holmans Peter , Hope-Bell Josh , Le Roux Danielle , Morrin Sally , Owen Michael , Sivakumar Shreeya , Wolstencroft Jeanne , Skuse David , Hall Jeremy , Holmans Peter , Owen Michael J. , van den Bree Marianne B. M. 
Published: June 2024

AbstractA range of rare mutations involving micro-deletion or -duplication of genetic material (copy number variants (CNVs)) have been associated with high neurodevelopmental and psychiatric risk (ND-CNVs). Irritability is frequently observed in childhood neurodevelopmental conditions, yet its aetiology is largely unknown. Genetic variation may play a role, but there is a sparsity of studies investigating the presentation of irritability in young people with ND-CNVs. This study aimed to investigate whether there is a difference in irritability in young people with rare ND-CNVs compared to those without ND-CNVs, and to what extent irritability is associated with psychiatric diagnoses and cognitive ability (IQ). Irritability and broader psychopathology were assessed in 485 young people with ND-CNVs and 164 sibling controls, using the child and adolescent psychiatric assessment. Autism was assessed using the social communication questionnaire, and intelligence quotient (IQ) by the Wechsler abbreviated scale of intelligence. Fifty four percent of young people with ND-CNVs met the threshold for irritability; significantly more than controls (OR = 3.77, CI = 3.07–7.90, p = 5.31 × 10−11). When controlling for the presence of other psychiatric comorbidities, ND-CNV status was still associated with irritability. There was no evidence for a relationship between irritability and IQ. Irritability is an important aspect of the clinical picture in young people with ND-CNVs. This work shows that genetic variation is associated with irritability in young people with ND-CNVs, independent of psychiatric comorbidities or IQ impairment. Clinicians should be aware of this increased risk to inform management and interventions.
Real world predictors of response and 24-month survival in high-grade TP53-mutated myeloid neoplasms
Authors: Kaur Amandeep , Rojek Alexandra E. , Symes Emily , Nawas Mariam T. , Patel Anand A. , Patel Jay L. , Sojitra Payal , Aqil Barina , Sukhanova Madina , McNerney Megan E. , Wu Leo P. , Akmatbekov Aibek , Segal Jeremy , Tjota Melissa Y. , Gurbuxani Sandeep , Cheng Jason X. , Yeon Su-Yeon , Ravisankar Harini V. , Fitzpatrick Carrie , Lager Angela , Drazer Michael W. , Saygin Caner , Wanjari Pankhuri , Katsonis Panagiotis , Lichtarge Olivier , Churpek Jane E. , Ghosh Sharmila B. , Patel Ami B. , Menon Madhu P. , Arber Daniel A. , Wang Peng , Venkataraman Girish 
Published: June 2024

AbstractCurrent therapies for high-gradeTP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals withTP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 rate was 25.6% (50/195). We additionally identified several pre-therapy factors predictive of inferior CR1 including male gender (P = 0.026), ≥2 autosomal monosomies (P < 0.001), −17/17p (P = 0.011), multi-hitTP53allelic state (P < 0.001) andCUX1co-alterations (P = 0.010). In univariable analysis of the entire cohort, inferior OS24 was predicated by ≥2 monosomies (P = 0.004),TP53VAF > 25% (P = 0.002),TP53splice junction mutations (P = 0.007) and antecedent treated myeloid neoplasm (P = 0.001). In addition, mutations/deletions inCUX1,U2AF1,EZH2,TET2,CBL, orKRAS(‘EPI6’ signature) predicted inferior OS24 (HR = 2.0 [1.5–2.8];P < 0.0001). In a subgroup analysis of HMA +/-Ven treated individuals (N = 144),TP53VAF and monosomies did not impact OS24. A risk score for HMA +/-Ven treated individuals incorporating three pre-therapy predictors includingTP53splice junction mutations,EPI6and antecedent treated myeloid neoplasm stratified 3 prognostic distinct groups: intermediate, intermediate-poor, and poor with significantly different median (12.8, 6.0, 4.3 months) and 24-month (20.9%, 5.7%, 0.5%) survival (P < 0.0001). For the first time, in a seemingly monolithic high-risk cohort, our data identifies several baseline factors that predict response and 24-month survival.
AURKB/CDC37 complex promotes clear cell renal cell carcinoma progression via phosphorylating MYC and constituting an AURKB/E2F1-positive feedforward loop
Authors: Li Fang , Wang Xiaofei , Zhang Jinyuan , Jing Xintao , Zhou Jing , Jiang Qiuyu , Cao Li , Cai Shuang , Miao Jiyu , Tong Dongdong , Shyy John Y-J. , Huang Chen 
Published: June 2024

AbstractAs the second most common malignant tumor in the urinary system, renal cell carcinoma (RCC) is imperative to explore its early diagnostic markers and therapeutic targets. Numerous studies have shown that AURKB promotes tumor development by phosphorylating downstream substrates. However, the functional effects and regulatory mechanisms of AURKB on clear cell renal cell carcinoma (ccRCC) progression remain largely unknown. In the current study, we identified AURKB as a novel key gene in ccRCC progression based on bioinformatics analysis. Meanwhile, we observed that AURKB was highly expressed in ccRCC tissue and cell lines and knockdown AURKB in ccRCC cells inhibit cell proliferation and migration in vitro and in vivo. Identified CDC37 as a kinase molecular chaperone for AURKB, which phenocopy AURKB in ccRCC. AURKB/CDC37 complex mediate the stabilization of MYC protein by directly phosphorylating MYC at S67 and S373 to promote ccRCC development. At the same time, we demonstrated that the AURKB/CDC37 complex activates MYC to transcribe CCND1, enhances Rb phosphorylation, and promotes E2F1 release, which in turn activates AURKB transcription and forms a positive feedforward loop in ccRCC. Collectively, our study identified AURKB as a novel marker of ccRCC, revealed a new mechanism by which the AURKB/CDC37 complex promotes ccRCC by directly phosphorylating MYC to enhance its stability, and first proposed AURKB/E2F1-positive feedforward loop, highlighting AURKB may be a promising therapeutic target for ccRCC.
Synthesis and antibacterial action of 3’,6’-disubstituted spectinomycins
Authors: Dharuman Suresh , Phelps Gregory A. , Dunn Christine M. , Wilt Laura A. , Murphy Patricia A. , Lee Robin B. , Snoke Hannah E. , Selchow Petra , Haldimann Klara , Böttger Erik C. , Hobbie Sven N. , Sander Peter , Lee Richard E. 
Published: June 2024

AbstractSpectinomycin is an aminocyclitol antibiotic with a unique ribosomal binding site. Prior synthetic modifications of spectinomycin have enhanced potency and antibacterial spectrum through addition at the 6’-position to produce trospectomycin and to the 3’-position to produce spectinamides and aminomethyl spectinomycins. This study focused on the design, synthesis, and evaluation of three 3’,6’-disubstituted spectinomycin analogs: trospectinamide, N-benzyl linked aminomethyl, and N-ethylene linked aminomethyl trospectomycins. Computational experiments predicted that these disubstituted analogs would be capable of binding within the SPC ribosomal binding site. The new analogs were synthesized from trospectomycin, adapting the previously established routes for the spectinamide and aminomethyl spectinomycin series. In a cell-free translation assay, the disubstituted analogs showed ribosomal inhibition similar to spectinomycin or trospectomycin. These disubstituted analogs demonstrated inhibitory MIC activity against various bacterial species with the 3’-modification dictating spectrum of activity, leading to improved activity against mycobacterium species. Notably, N-ethylene linked aminomethyl trospectomycins exhibited increased potency against Mycobacterium abscessus and trospectinamide displayed robust activity against M. tuberculosis, aligning with the selective efficacy of spectinamides. The study also found that trospectomycin is susceptible to efflux in M. tuberculosis and M. abscessus. These findings contribute to the understanding of the structure-activity relationship of spectinomycin analogs and can guide the design and synthesis of more effective spectinomycin compounds.