bluuebunny/crossref_metadata_2025 huggingface dataset:
Legacy of the British Mandate: Eliminating The Palestinian Right to Self‐Determination
Authors: Iriqat Dalal
Published: July 2024

In February 2024, Prime Minister Benjamin Netanyahu issued a plan for the “postwar” Gaza Strip that envisions Israel's military as unilaterally and indefinitely patrolling the enclave while an unnamed third party runs the local government. While even allies like the United States criticized this scheme, Palestine has never enjoyed autonomy as a state, and the institutions and practices of Israel's far‐right government—and even of the Palestinian elite—are rooted in the settler colonialism facilitated by the British mandate, 1922–1948. This period was the first and last time in modern history that Palestinian Arabs and Jews were administered as a single polity, albeit on radically unequal terms. This article examines how international law was used to suppress the Palestinians and privilege the creation of a Jewish state of Israel. The legacy of this regime can be seen in the present‐day thwarting of Palestinian self‐determination through Israel's use of the military for civil administration, digital surveillance, and the right‐wing agenda for annexation of the West Bank and perpetual war in Gaza.
Cassandra and A Room of One's Own: A common cry of frustration
Authors: Choperena Ana , Díaz‐Dorronsoro Inés
Published: July 2024

In this manuscript, we explore the connections between Florence Nightingale's Cassandra and Virginia Woolf's A Room of One's Own while taking the authors' personal and social contexts into account. We conduct a detailed textual analysis from a feminist perspective. Cassandra and A Room of One's Own exhibit singular textual commonalities, such as evidence of trauma, the integration of myth and fiction as literary devices aimed at facilitating the author's access to various social spheres, the use of interpellations to impact the audience, and an argument for education as a path by which privileged women can enter the public realm. Both authors' personal wounds and intellectual frustrations influenced their work, thus making their writing very powerful.
m6A demethylase OsALKBH5 is required for double‐strand break formation and repair by affecting mRNA stability in rice meiosis
Authors: Xue Feiyang , Zhang Jie , Wu Di , Sun Shiyu , Fu Ming , Wang Jie , Searle Iain , Gao Hongbo , Liang Wanqi
Published: July 2024

N6‐methyladenosine (m6A) RNA modification is the most prevalent messenger RNA (mRNA) modification in eukaryotes and plays critical roles in the regulation of gene expression. m6A is a reversible RNA modification that is deposited by methyltransferases (writers) and removed by demethylases (erasers). The function of m6A erasers in plants is highly diversified and their roles in cereal crops, especially in reproductive development essential for crop yield, are largely unknown.

Here, we demonstrate that rice OsALKBH5 acts as an m6A demethylase required for the normal progression of male meiosis.

OsALKBH5 is a nucleo‐cytoplasmic protein, highly enriched in rice anthers during meiosis, that associates with P‐bodies and exon junction complexes, suggesting that it is involved in regulating mRNA processing and abundance. Mutations of OsALKBH5 cause reduced double‐strand break (DSB) formation, severe defects in DSB repair, and delayed meiotic progression, leading to complete male sterility. Transcriptome analysis and m6A profiling indicate that OsALKBH5‐mediated m6A demethylation stabilizes the mRNA level of multiple meiotic genes directly or indirectly, including several genes that regulate DSB formation and repair.

Our study reveals the indispensable role of m6A metabolism in post‐transcriptional regulation of meiotic progression in rice.
How to do HRM with numbers? A performative lens on HR metrics, HR analytics and HR algorithms
Authors: Coron Clotilde , Scheibmayr Isabella , Lescoat Pierre
Published: July 2024

This study examines the performativity of using numbers in the context of human resource management (HRM). We use performativity as a theoretical lens to understand how such quantification affects individuals and work. We theorise three performative effects of quantification based on multiple case studies using internal documents and semi‐structured interviews. To do this we analysed six HRM quantification projects (including cases of algorithmic HRM) at a large French multinational corporation. Each use of quantification creates a specific form of performativity. Our work complements the sparse but growing literature on metrics, analytics and algorithms in Human Resources, focusing not on the kind of reality numbers represent but on how they impact different stakeholders.
A New Tissue Engineering Strategy to Promote Tendon–bone Healing: Regulation of Osteogenic and Chondrogenic Differentiation of Tendon‐derived Stem Cells
Authors: Shen Sinuo , Lin Yucheng , Sun Jiachen , Liu Yuanhao , Chen Yuzhi , Lu Jun
Published: July 2024

In the field of sports medicine, repair surgery for anterior cruciate ligament (ACL) and rotator cuff (RC) injuries are remarkably common. Despite the availability of relatively effective treatment modalities, outcomes often fall short of expectations. This comprehensive review aims to thoroughly examine current strategies employed to promote tendon‐bone healing and analyze pertinent preclinical and clinical research. Amidst ongoing investigations, tendon‐derived stem cells (TDSCs), which have comparatively limited prior exploration, have garnered increasing attention in the context of tendon‐bone healing, emerging as a promising cell type for regenerative therapies. This review article delves into the potential of combining TDSCs with tissue engineering methods, with ACL reconstruction as the main focus. It comprehensively reviews relevant research on ACL and RC healing to address the issues of graft healing and bone tunnel integration. To optimize tendon‐bone healing outcomes, our emphasis lies in not only reconstructing the original microstructure of the tendon‐bone interface but also achieving proper bone tunnel integration, encompassing both cartilage and bone formation. In this endeavor, we thoroughly analyze the transcriptional and molecular regulatory variables governing TDSCs differentiation, incorporating a retrospective analysis utilizing single‐cell sequencing, with the aim of unearthing relevant signaling pathways and processes. By presenting a novel strategy rooted in TDSCs‐driven osteogenic and chondrogenic differentiation for tendon‐bone healing, this study paves the way for potential future research avenues and promising therapeutic applications. It is anticipated that the findings herein will contribute to advancing the field of tendon‐bone healing and foster the exploration of TDSCs as a viable option for regenerative therapies in the future.
Ignited competition: Impact of bioactive extracellular compounds on organelle functions and photosynthetic systems in harmful algal blooms
Authors: Guo Huige , Wang Xiaochen , Li Changlin , Mohamed Hala F. , Li Dawei , Wang Lianghui , Chen Hongzhe , Lin Kunning , Huang Shuyuan , Pang Jinling , Zhang Yuanbiao , Krock Bernd , Luo Zhaohe
Published: July 2024

Prevalent interactions among marine phytoplankton triggered by long‐range climatic stressors are well‐known environmental disturbers of community structure. Dynamic response of phytoplankton physiology is likely to come from interspecies interactions rather than direct climatic effect on single species. However, studies on enigmatic interactions among interspecies, which are induced by bioactive extracellular compounds (BECs), especially between related harmful algae sharing similar shellfish toxins, are scarce. Here, we investigated how BECs provoke the interactions between two notorious algae, Alexandrium minutum and Gymnodinium catenatum, which have similar paralytic shellfish toxin (PST) profiles. Using techniques including electron microscopy and transcriptome analysis, marked disruptions in G. catenatum intracellular microenvironment were observed under BECs pressure, encompassing thylakoid membrane deformations, pyrenoid matrix shrinkage and starch sheaths disappearance. In addition, the upregulation of gene clusters responsible for photosystem‐I Lhca1/4 and Rubisco were determined, leading to weaken photon captures and CO2 assimilation. The redistribution of lipids and proteins occurred at the subcellular level based on in situ focal plane array FTIR imaging approved the damages. Our findings illuminated an intense but underestimated interspecies interaction triggered by BECs, which is responsible for dysregulating photosynthesis and organelle function in inferior algae and may potentially account for fitness alteration in phytoplankton community.
Coarse‐to‐fine adjustment for multi‐platform point cloud fusion
Authors: Zhao Xin , Li Jianping , Li Yuhao , Yang Bisheng , Sun Sihan , Lin Yongfeng , Dong Zhen
Published: July 2024

Leveraging multi‐platform laser scanning systems offers a complete solution for 3D modelling of large‐scale urban scenes. However, the spatial inconsistency of point clouds collected by heterogeneous platforms with different viewpoints presents challenges in achieving seamless fusion. To tackle this challenge, this paper proposes a coarse‐to‐fine adjustment for multi‐platform point cloud fusion. First, in the preprocessing stage, the bounding box of each point cloud block is employed to identify potential constraint association. Second, the proposed local optimisation facilitates preliminary pairwise alignment with these potential constraint relationships, and obtaining initial guess for a comprehensive global optimisation. At last, the proposed global optimisation incorporates all the local constraints for tightly coupled optimisation with raw point correspondences. We choose two study areas to conduct experiments. Study area 1 represents a fast road scene with a significant amount of vegetation, while study area 2 represents an urban scene with many buildings. Extensive experimental evaluations indicate the proposed method has increased the accuracy of study area 1 by 50.6% and the accuracy of study area 2 by 44.7%.
Optimisation of real‐scene 3D building models based on straight‐line constraints
Authors: Lv Kaiyun , Chen Longyu , He Haiqing , Zhou Fuyang , Yu Shixun
Published: July 2024

Due to the influence of repeated textures or edge perspective transformations on building facades, building modelling based on unmanned aerial vehicle (UAV) photogrammetry often suffers geometric deformation and distortion when using existing methods or commercial software. To address this issue, a real‐scene three‐dimensional (3D) building model optimisation method based on straight‐line constraints is proposed. First, point clouds generated by unmanned aerial vehicle (UAV) photogrammetry are down‐sampled based on local curvature characteristics, and structural point clouds located at the edges of buildings are extracted. Subsequently, an improved random sample consensus (RANSAC) algorithm, considering distance and angle constraints on lines, known as co‐constrained RANSAC, is applied to further extract point clouds with straight‐line features from the structural point clouds. Finally, point clouds with straight‐line features are optimised and updated using sampled points on the fitted straight lines. Experimental results demonstrate that the proposed method can effectively eliminate redundant 3D points or noise while retaining the fundamental structure of buildings. Compared to popular methods and commercial software, the proposed method significantly enhances the accuracy of building modelling. The average reduction in error is 59.2%, including the optimisation of deviations in the original model's contour projection.
What Is the Ideal Dimension of Law?
Authors: Kaehler Lorenz
Published: July 2024

Various authors have claimed that law has an ideal dimension owed to a claim to correctness. Against this thesis, this article argues that there are several ideal dimensions of law, namely, a moral, a legal, and an ontological one. All of them are independent of a claim to correctness. This claim can be understood in a strong and a weak way. Both versions are wanting because law claims neither that it is morally ideal nor that it is not grossly unjust. Consequently, the ideal dimension of law has to be found in features other than in a claim to correctness.
Damage evolution in layered rock masses of a mining floor under the influence of fluid–structure coupling
Authors: Liu Shiliang , Wang Ao , Li Weiguo , Zheng Yusheng , Wang Shanlin
Published: July 2024

Current research on rock damage in mining floors primarily focuses on the seepage‐stress coupling effect, overlooking the fact that rock masses in coal measure strata are predominantly layered. To address this gap, cyclic loading and unloading triaxial tests were conducted. Additionally, theoretical analysis, mathematical statistics, and other methods were used to investigate the damage evolution law of layered rock masses in coal measures. This investigation was carried out under the coupled effects of a specific stress path, characterized by ‘stress concentration‐stress unloading‐stress recovery’, and a high confined water seepage field. The results show that the compression modulus increases with the increase in confining pressure and osmotic pressure, but its increasing trend gradually slows down. Within a certain range, increasing the confining pressure and osmotic pressure helps to close rock fractures and increase stiffness.
COVID‐19 vaccine variety and dimensions of risks: What factors induced nations to introduce multiple vaccines?
Authors: Goel Rajeev K. , Jones James R. , Capasso Salvatore
Published: July 2024

Adding a new dimension to the body of research on COVID economics, this article considers the determinants of vaccine variety across nations. Driven by supply chain issues, development timelines, pricing, and vaccine nationalism, the number of available vaccines varies considerably across nations. Results show that greater pandemic severity and more populous nations had more vaccines, while nations with large land areas had fewer vaccines. Finally, while island nations were likely to have fewer vaccines, authoritarian regimes were mostly no different from other regimes. Greater COVID risks mostly lowered vaccine variety, as did supply chain issues and the prevalence of other infectious diseases. Finally, nations with worse institutional quality had more vaccines, ceteris paribus.
Assessing Illinois companion animal veterinarians' antimicrobial prescription practices and the factors that influence their decisions when treating bacterial infections in dogs and cats
Authors: Yudhanto Setyo , Reinhart Jennifer M. , de Souza Clarissa Pimentel , Gochenauer Alexandria , Sander William E. , Hung Chien‐Che , Maddox Carol W. , Varga Csaba
Published: July 2024

Aims

Judicious antimicrobial use in companion animal practice is critical for maintaining the effectiveness of antimicrobial agents against bacterial infections and reducing the selection of antimicrobial‐resistant bacteria. This study aimed to provide insights into companion animal veterinarians' antimicrobial treatment recommendations for common bacterial infections in dogs and cats and describe the factors influencing their prescription choices.

Methods and Results

An online survey using QualtricsXM® software was administered between September and November 2022 to companion animal veterinarians who were Illinois State Veterinary Medical Association members. Descriptive and text analyses were conducted to assess the participants' responses. A total of 78 surveys were included in the analysis. Skin infections were ranked as the most common bacterial infections for which veterinarians prescribed antimicrobial agents, followed by ear, urinary tract, respiratory, and enteric infections. The severity of clinical symptoms and the results of bacterial culture and susceptibility tests were the most influential factors for veterinarians when making antimicrobial prescription choices. Veterinarians were aware of the current antimicrobial prescription guideline recommendations when prescribing antimicrobials empirically to nine hypothetical scenarios of bacterial infections. According to the results of the text analysis that assessed veterinarians' responses to an open‐ended question, regarding their challenges when prescribing antimicrobial agents, the pairwise correlation of word frequencies within each response showed the highest correlations between the words ‘owner’ and ‘compliance’, ‘administration’ and ‘route’, ‘cost’ and ‘culture’, and ‘patients’ and ‘acceptance’.

Conclusions

The study results can support animal health stakeholders in the development of antimicrobial stewardship programmes to promote appropriate antimicrobial use and limit the emergence of antimicrobial resistance.
Amine plasma polymers deposited on porous hydroxyapatite artificial bone with bipolar pulsed discharges
Authors: Harumningtyas Anjar Anggraini , Ito Tomoko , Kita Hidekazu , Kodama Joe , Kaito Takashi , Hamaguchi Satoshi
Published: July 2024

A recent in vivo study [Kodama et al., Sci. Rep. 11, 1 (2021)] showed that porous artificial bones coated with amine-containing polymers deposited by plasma-enhanced chemical vapor deposition (PECVD) significantly enhanced bone regeneration. This article reports the chemical and physical properties of amine plasma polymers (PPs) formed under the same deposition conditions, including the film stability for up to two months, the effects of sterilization on the chemical compositions of the films, and the penetration of amine PPs into the inner surfaces of interconnected microscopic pores of the amine PP-coated porous artificial bone. It was found that, immediately after the plasma polymerization process, approximately 20% of nitrogen atoms on the surface of the deposited amine PP formed primary amines. However, the value decreased to approximately 5% over one month if the sample was exposed to ambient air. The relative concentration of primary amines also decreased to a similar value after the sample was sterilized by autoclaving or ethylene oxide gas. Molecular dynamics simulations were used to examine possible formation mechanisms of nitriles in deposit films under the PECVD conditions and found that ion impact can significantly reduce the nitrile content.
Influence of high-temperature thermal annealing on paramagnetic point defects in silicon-rich silicon nitride films formed in a single-wafer-type low-pressure chemical vapor deposition reactor
Authors: Kobayashi Kiyoteru , Miyauchi Ryo , Kimoto Kenshi
Published: July 2024

The influence of high-temperature thermal annealing on silicon dangling bonds called K centers in Si-rich silicon nitride films grown in a single-wafer-type low-pressure chemical vapor deposition reactor with the SiH2Cl2-NH3 system at 750 °C has been investigated by combining thermal desorption spectroscopy (TDS), Fourier transform infrared spectroscopy-attenuated total reflection, spectroscopic ellipsometry, and electron spin resonance. In the TDS analysis, H2 desorption from the nitride films was detected above about 600 °C. It is found that thermal annealing at 750 and 900 °C caused a slight decrease in the K center density and a change in the g value of K centers, which are considered to be caused by changes in the atomic structure of the nitride films. On the other hand, thermal annealing at 1050 °C resulted in a substantial decrease in the K center density and the generation of paramagnetic defects with unprecedented characteristics. The findings in this study are expected to provide important guidelines for the design of manufacturing processes of nonvolatile memories.
Speech intelligibility and talker identification with non-telephone frequencies
Authors: Wang Xianhui , Ge Jonathan , Meller Leo , Yang Ye , Zeng Fan-Gang
Published: July 2024

Although the telephone band (0.3–3 kHz) provides sufficient information for speech recognition, the contribution of the non-telephone band (<0.3 and >3 kHz) is unclear. To investigate its contribution, speech intelligibility and talker identification were evaluated using consonants, vowels, and sentences. The non-telephone band produced relatively good intelligibility for consonants (76.0%) and sentences (77.4%), but not vowels (11.5%). The non-telephone band supported good talker identification only with sentences (74.5%), but not vowels (45.8%) or consonants (10.8%). Furthermore, the non-telephone band cannot produce satisfactory speech intelligibility in noise at the sentence level, suggesting the importance of full-band access in realistic listening.
Sedentary Behavior and Cardiometabolic Markers in Adolescents: A 4-Year Longitudinal Study
Authors: Mendonça Gerfeson , Barbosa Arthur Oliveira , Moura Ially Rayssa Dias , Silva Juliana Maria da Penha Freire , Prazeres Filho Alcides , Silva Diego Júnio da , Toscano Chrystiane Vasconcelos Andrade , Farias Júnior José Cazuza de
Published: July 2024

Purpose: Analyzed the associations of sedentary behavior (SB) measured by questionnaire and accelerometer, with cardiometabolic markers in adolescents. Methods: Longitudinal study with 4 years of follow-up with adolescents from João Pessoa, Brazil. SB was measured using a questionnaire (305 adolescents: 54.5% females; age 11.7 [SD = 0.7]) and use of accelerometer (136 adolescents: 54.8% females; age 11.5 [SD = 0.7]). The cardiometabolic markers were body mass index, waist circumference, systolic and diastolic blood pressure, fasting glucose, total cholesterol, triglycerides, low-density lipoproteins and high-density lipoproteins (HDL-C), total cholesterol/HDL ratio, triglycerides/HDL ratio, and non-HDL-C. Generalized Estimating Equation analysis was used to for analyses. Results: The average time in SB by the accelerometer was greater (average 8.3 [SD = 1.5], 8.8 [SD = 1.6], and 8.4 [SD = 1.9] h/d/wk) than observed in the questionnaire (on average 6.0 [SD = 4.1], 7.2 [SD = 4.9], and 6.6 [SD = 5.4] h/d/wk), in all years of the study, but without a significant increasing trend (P > .05) over time for both measures. There was a significant and positive association between SB measured by the questionnaire and SBP (β = 0.148; 95% CI, 0.021–0.274). Conclusions: The SB generally does not seem to contribute to significant changes in cardiometabolic markers in adolescents, despite it being associated with increased systolic blood pressure levels.
Trait-mediated speciation and human-driven extinctions in proboscideans revealed by unsupervised Bayesian neural networks
Authors: Hauffe Torsten , Cantalapiedra Juan L. , Silvestro Daniele
Published: July 2024

Species life-history traits, paleoenvironment, and biotic interactions likely influence speciation and extinction rates, affecting species richness over time. Birth-death models inferring the impact of these factors typically assume monotonic relationships between single predictors and rates, limiting our ability to assess more complex effects and their relative importance and interaction. We introduce a Bayesian birth-death model using unsupervised neural networks to explore multifactorial and nonlinear effects on speciation and extinction rates using fossil data. It infers lineage- and time-specific rates and disentangles predictor effects and importance through explainable artificial intelligence techniques. Analysis of the proboscidean fossil record revealed speciation rates shaped by dietary flexibility and biogeographic events. The emergence of modern humans escalated extinction rates, causing recent diversity decline, while regional climate had a lesser impact. Our model paves the way for an improved understanding of the intricate dynamics shaping clade diversification.
Targeting ferritinophagy impairs quiescent cancer stem cells in acute myeloid leukemia in vitro and in vivo models
Authors: Larrue Clement , Mouche Sarah , Angelino Paolo , Sajot Maxime , Birsen Rudy , Kosmider Olivier , Mckee Thomas , Vergez François , Recher Christian , Mas Véronique Mansat-De , Gu Qiong , Xu Jun , Tsantoulis Petros , Sarry Jean-Emmanuel , Tamburini Jerome
Published: July 2024

Acute myeloid leukemia (AML) remains a challenging hematological malignancy with poor prognosis and limited treatment options. Leukemic stem cells (LSCs) contribute to therapeutic failure, relapse, and adverse outcome. This study investigates the role of quiescence and related molecular mechanisms in AML pathogenesis and LSC functions to identify potential therapeutic targets. Transcriptomic analysis revealed that the LSC-enriched quiescent cell population has a distinct gene signature with prognostic relevance in patients with AML. Mechanistically, quiescent blasts exhibit increased autophagic activity, which contributes to their sustained viability. Proteomic profiling uncovered differential requirements for iron metabolism between quiescent and cycling cells, revealing a unique dependence of quiescent cells on ferritinophagy, a selective form of autophagy mediated by nuclear receptor coactivator 4 (NCOA4), which regulates iron bioavailability. We evaluated the therapeutic potential of inhibiting NCOA4-mediated ferritinophagy using genetic knockdown and chemical inhibition approaches. In vitro assays showed that suppression of NCOA4 was toxic to leukemic blasts, particularly the CD34
+
CD38
−
LSC-enriched population, without affecting normal CD34
+
hematopoietic progenitors. In vivo studies using murine patient-derived xenograft (PDX) models of AML confirmed that NCOA4 inhibition reduced tumor burden and impaired LSC viability and self-renewal, indicating a specific vulnerability of these cells to ferritinophagy disruption. Our findings underscore the role of NCOA4-mediated ferritinophagy in maintaining LSC quiescence and function and suggest that targeting this pathway may be an effective therapeutic strategy for AML. This study highlights the potential of NCOA4 inhibition to improve AML outcomes and paves the way for future research and clinical development.
Elucidating the potential of isorhapontigenin in targeting the MgrA regulatory network: a paradigm shift for attenuating MRSA virulence
Authors: Liu Lihan , Wang Li , Liu Xiaolei , Wang Bingmei , Guo Xuerui , Wang Yueying , Xu Yueshan , Guan Jiyu , Zhao Yicheng
Published: July 2024

As methicillin-resistant
Staphylococcus aureus
(MRSA) exhibits formidable resistance to many drugs, the imperative for alternative therapeutic strategies becomes increasingly evident. At the heart of our study is the identification of a novel inhibitor through fluorescence anisotropy assays, specifically targeting the crucial multiple gene regulator A (MgrA) regulatory network in
S. aureus
. Isorhapontigenin (Iso), a natural compound, exhibits outstanding inhibitory efficacy, modulating bacterial virulence pathways without exerting direct bactericidal activity. This suggests a paradigm shift toward attenuating virulence instead of purely focusing on bacterial elimination. Through comprehensive
in vitro
and
in vivo
evaluations, we elucidated the complex interplay between Iso and MgrA, leading to reduced
S. aureus
adhesion, and overall virulence. At the cellular level, Iso offers significant protection to A549 cells infected with
S. aureus
, reducing cellular damage. Importantly, Iso augments the chemotaxis of neutrophils, curtailing the immune evasion capabilities of
S. aureus
. Furthermore,
in vivo
investigations highlight the notable effectiveness of Iso against MRSA-induced pneumonia and within the
Galleria mellonella
infection model, underscoring its pivotal role in the evolving realm of antibacterial drug discovery. Significantly, when Iso is used in combination with vancomycin, it outperforms its solo application, indicating a more pronounced therapeutic impact. This seminal research emphasizes Iso’s potential as a primary defense against the surge of multidrug-resistant pathogens, heralding new prospects in antimicrobial therapy.
Enhanced fatty acid biosynthesis by Sigma28 in stringent responses contributes to multidrug resistance and biofilm formation in
Helicobacter pylori
Authors: Xue Junyuan , Li Shutong , Wang Liyuan , Zhao Yican , Zhang Lu , Zheng Yantong , Zhang Wenxin , Chen Zhenghong , Jiang Ting , Sun Yundong
Published: July 2024

The metabolic state of bacteria significantly contributes to their resistance to antibiotics; however, the specific metabolic mechanisms conferring antimicrobial resistance in
Helicobacter pylori
remain largely understudied. Employing transcriptomic and non-targeted metabolomics, we characterized the metabolic reprogramming of
H. pylori
when challenged with antibiotic agents. We observed a notable increase in both genetic and key proteomic components involved in fatty acid biosynthesis. Inhibition of this pathway significantly enhanced the antibiotic susceptibility of the sensitive and multidrug-resistant
H. pylori
strains while also disrupting their biofilm-forming capacities. Further analysis revealed that antibiotic treatment induced a stringent response, triggering the expression of the
hp0560-hp0557
operon regulated by Sigma28 (σ
28
). This activation in turn stimulated the fatty acid biosynthetic pathway, thereby enhancing the antibiotic tolerance of
H. pylori
. Our findings reveal a novel adaptive strategy employed by
H. pylori
to withstand antibiotic stress.
Clofazimine inhibits innate immunity against
Mycobacterium tuberculosis
by NF-κB
Authors: Li Xinda , Luo Xiaoyi , Wang Bin , Fu Lei , Chen Xi , Lu Yu
Published: July 2024

Tuberculosis (TB) remains one of the infectious diseases with high incidence and high mortality. About a quarter of the population has been latently infected with
Mycobacterium tuberculosis
. At present, the available TB treatment strategies have the disadvantages of too long treatment duration and serious adverse reactions. The sustained inflammatory response leads to permanent tissue damage. Unfortunately, the current selection of treatment regimens does not consider the immunomodulatory effects of various drugs. In this study, we preliminarily evaluated the effects of commonly used anti-tuberculosis drugs on innate immunity at the cellular level. The results showed that clofazimine (CFZ) has a significant innate immunosuppressive effect. CFZ significantly inhibited cytokines and type I interferons (IFNα and IFNβ) expression under both lipopolysaccharide stimulation and CFZ-resistant strain infection. In further mechanistic studies, CFZ strongly inhibited the phosphorylation of nuclear factor kappa B (NF-κB) p65 and had no significant effect on the phosphorylation of p38. In conclusion, our study found that CFZ suppresses innate immunity against
Mycobacterium tuberculosis
by NF-κB, which should be considered in future regimen development.

IMPORTANCE

The complete elimination of
Mycobacterium tuberculosis
(Mtb), the etiologic agent of TB, from TB patients is a complicated process that takes a long time. The excessive immune inflammatory response of the host for a long time causes irreversible organic damage to the lungs and liver. Current antibiotic-based treatment options involve multiple complex drug combinations, often targeting different physiological processes of Mtb. Given the high incidence of post-tuberculosis lung disease, we should also consider the immunomodulatory properties of other drugs when selecting drug combinations.
A high-throughput, polymerase-targeted RT-PCR for broad detection of mammalian filoviruses
Authors: Cui Na , Perez Yael L. , Hume Adam J. , Nunley B. Ethan , Kong Kevin , Mills Margaret G. , Xie Hong , Greninger Alexander L.
Published: July 2024

Filoviruses are some of the most lethal viruses in the modern world, and increasing numbers of filovirus species and genera have been discovered in recent years. Despite the potential severity of filovirus outbreaks in the human population, comparably few sensitive pan-filovirus RT-PCR assays have been described that might facilitate early detection and prevention. Here, we present a new pan-filovirus RT-PCR assay targeting the L polymerase gene for detection of all known mammalian filoviruses. We demonstrate the detection of 10 synthetic filovirus RNA templates with analytical sensitivity ranging from 178 to 3,354 copies/mL, without cross-reactivity on 10 non-filoviral human viral species. We verified assay performance on 10 inactivated filovirus isolates, yielding initial sensitivities of 0.012–44.17 TCID
50
/mL. We coupled this broadly reactive RT-PCR with a deep sequencing workflow that is amenable to high-throughput pooling to maximize detection and discovery potential. In summary, this pan-filovirus RT-PCR assay targets the most conserved filovirus gene, offers the widest breadth of coverage to date, and may help in the detection and discovery of novel filoviruses.

IMPORTANCE

Filoviruses remain some of the most mysterious viruses known to the world, with extremely high lethality rates and significant pandemic potential. Yet comparably few filovirus species and genera have been discovered to date and questions surround the definitive host species for zoonotic infections. Here, we describe a novel broadly reactive RT-PCR assay targeting the conserved L polymerase gene for high-throughput screening for filoviruses in a variety of clinical and environmental specimens. We demonstrate the assay can detect all known mammalian filoviruses and determine the sensitivity and specificity of the assay on synthetic RNA sequences, inactivated filovirus isolates, and non-filoviral species.
Evaluation of chlorogenic acid and carnosol for anti-efflux pump and anti-biofilm activities against extensively drug-resistant strains of
Staphylococcus aureus
and
Pseudomonas aeruginosa
Authors: Sheikhy Mohaddeseh , Karbasizade Vajihe , Ghanadian Mustafa , Fazeli Hossein
Published: July 2024

Efflux pumps and biofilm play significant roles in bacterial antibiotic resistance. This study investigates the potential of chlorogenic acid (CGA) and carnosol (CL), as phenolic and diterpene compounds, respectively, for their inhibitory effects on efflux pumps. Among the 12 multidrug-resistant (MDR) strains of
Staphylococcus aureus
and
Pseudomonas aeruginosa
isolated from nosocomial skin infections, eight strains were identified as extensively drug resistant (XDR) using the disc diffusion method. The presence of efflux pumps in MDR strains of
S. aureus
and
P. aeruginosa
was screened using carbonyl cyanide-m-chlorophenylhydrazone. Between the 12 MDR strains of
S. aureus
and
P. aeruginosa
, 80% (4 out of 5) of the
S. aureus
strains and 85.7% (6 out of 7) of the
P. aeruginosa
strains exhibited active efflux pumps associated with gentamicin resistance. The checkerboard assay results, in combination with gentamicin, demonstrated that CGA exhibited a reduction in the minimum inhibitory concentration (MIC) for XDR
S. aureus
strain. Similarly, CL showed a synergistic effect and reduced the MIC for both XDR strains of
S. aureus
and
P. aeruginosa
. Flow cytometry was used to examine efflux pump activity at sub-MIC concentrations of 1/8, 1/4, and 1/2 MIC in comparison to the control. In XDR
S. aureus
, CGA demonstrated 39%, 70%, and 19% inhibition, while CL exhibited 74%, 73.5%, and 62% suppression. In XDR
P. aeruginosa
, CL exhibited inhibition rates of 25%, 10%, and 15%. The inhibition of biofilm formation was assessed using the microtiter plate method, resulting in successful inhibition of biofilm formation. Finally, the MTT assay was conducted, and it confirmed minimal cytotoxicity. Given the significant reduction in efflux pump activity and biofilm formation observed with CGA and CL in this study, these compounds can be considered as potential inhibitors of efflux pumps and biofilm formation, offering potential strategies to overcome antimicrobial resistance.

IMPORTANCE

In summary, CGA and CL demonstrated promising potentiating antimicrobial effects against XDR strains of
Staphylococcus aureus
and
Pseudomonas aeruginosa
, suggesting their probably potential as candidates for addressing nosocomial pathogens. They exhibited significant suppression of efflux pump activity, indicating a possible successful inhibition of this mechanism. Moreover, all substances effectively inhibited biofilm formation, while showing minimal cytotoxicity. However, further advancement to clinical trials is needed to evaluate the feasibility of utilizing CGA and CL for reversing bacterial XDR efflux and determining their efficacy against biofilms. These trials will provide valuable insights into the practical applications of these compounds in combating drug-resistant infections.
Eocene tearing and fragmentation of Indian lithosphere beneath the Woka rift, southern Tibet
Authors: Gong Lin , Wang Qiang , Kerr Andrew C. , Chen Huayong , Fan Jingjing , Wang Zilong , Xu Dongjing , Yang Qiji
Published: July 2024

When and how the syncontractional N-S–trending rifts formed in the Himalayan-Tibetan Plateau are crucial, yet unsolved issues that could help establish the interplay between geodynamic evolution and uplift of the plateau. Recent geophysical observations indicate that although Indian lithosphere tearing is the most likely trigger for rift formation, the timing of this tearing remains uncertain. To address this issue, we studied the Woka rift, which represents a typical N-S–trending rift in southern Tibet. Our results show that granitoids from the hanging wall and footwall of the Woka rift have significantly different magma crystallization temperatures (770–860 °C versus 650–750 °C) and crustal thickness (~40 km versus ~60 km) during the Eocene. These differences were most likely linked to tearing of the Indian lithosphere. The integration of crustal thickness trends and bedrock emplacement depth from the Eocene to the Oligocene suggest that the hanging wall exhumed at a faster rate than the footwall. From this information, it is clear that the Woka rift did not undergo E-W extension during this period. Integrating data from geophysics, thermochronology, mantle-derived, N-S–trending dikes, and adakitic rocks, we propose that Indian lithospheric tearing and fragmentation during the Eocene caused weakening of the Tibetan middle-lower crust rather than directly triggering surface extension of the Woka rift. This study has significant implications for the deep lithospheric processes and surface responses in the Himalayan-Tibetan Plateau.
Contourite-drift archive links Late Devonian bioevents with periodic anoxic shelf water cascading
Authors: Arwed Gibb M. , Hüneke Heiko , Jadhav Jayant , Gibb Laura M. , Mehlhorn Paul , Mayer Oliver , Sarah Aboussalam Z. , Thomas Becker R. , Hassani Ahmed El , Baidder Lahssen
Published: July 2024

Analysis of a Devonian contourite depositional system in the eastern Anti-Atlas of Morocco reveals the formation of widespread erosional hiatuses and organic-rich bioclastic contourites (ORCs) coinciding with the expansion of an anoxic water mass during Frasnian bioevents, ultimately culminating in the Kellwasser crisis (Frasnian–Famennian extinction event). The identified contourite terrace formed on the uppermost slope of the northern passive margin of Gondwana. Its inner part was bounded by an along-slope contourite channel and a small mounded drift at its downslope margin. Facies- and drift-scale contourite features evidence northwest-directed bottom currents driven by repeated overflows of dense, highly saline, anoxic water originating from the northern Gondwana Epicontinental Sea. These periodic overflows were channeled through the Ougarta trough, then deflected westward over the Tafilalt contourite terrace by the Coriolis force and cascaded downslope until reaching a density equilibrium level, probably forming an intermediate water mass. The cascading of dense, anoxic shelf water supports the photic-zone eutrophication (top-down) model proposed for the Kellwasser crisis and related Devonian anoxic events. We propose a direct link between the anoxic overflows and the Devonian evolutionary events.
Rupture segmentation on the East Anatolian fault (Turkey) controlled by along-strike variations in long-term slip rates in a structurally complex fault system
Authors: Wang Binhao , Barbot Sylvain
Published: July 2024

The East Anatolian fault in Turkey exhibits along-strike rupture segmentation, typically resulting in earthquakes with moment magnitude (Mw) up to 7.5 that are confined to individual segments. However, on 6 February 2023, a catastrophic Mw 7.8 earthquake struck near Kahramanmaraş (southeastern Turkey), defying previous expectations by rupturing multiple segments spanning over 300 km and overcoming multiple geometric complexities. We explore the mechanics of successive single- and multi-segment ruptures using numerical models of the seismic cycle calibrated to historical earthquake records and geodetic observations of the 2023 doublet. Our model successfully reproduces the observed historical rupture segmentation and the rare occurrence of multi-segment earthquakes. The segmentation pattern is influenced by variations in long-term slip rate along strike across the kinematically complex fault network between the Arabian and Anatolian plates. Our physics-based seismic cycle simulations shed light on the long-term variability of earthquake size that shapes seismic hazards.
Headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome with reversible cytotoxic lesion of the corpus callosum (CLOCC) on MRI of the brain
Authors: Nguyen Phuong Hien Duc , Kwon Gi Tae , Amin Mohammad Ruhul
Published: July 2024

Headache and neurological deficits with cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is a rare condition characterised by recurrent episodes of headache and transient neurological deficits. This case report presents a young patient initially diagnosed with hemiplegic migraine, having a normal brain CT, with focal cerebral perfusion mismatch not restricted to a single vascular territory on CT angiography. Brain MRI revealed a cytotoxic lesion of the splenium in the corpus callosum (CLOCC), a feature also reported in migraine. However, recurrent headaches with neurological deficits prompted further investigations with CSF analysis and brain MRI, confirming HaNDL and demonstrating reversibility of CLOCC. Recognising HaNDL as a differential diagnosis is essential in patients with recurrent headaches with focal neurological deficits, given the differences in therapeutic approach. The relationship between migraine and HaNDL is not fully understood, but they may share a pathophysiological link. Awareness of this is crucial for accurate diagnosis.
Falls and patterns of physical activity participation over 18 years in the Australian Longitudinal Study on Women’s Health
Authors: Kwok Wing S , Khalatbari-Soltani Saman , Dolja-Gore Xenia , Byles Julie , S Oliveira Juliana , Pinheiro Marina B , Tiedemann Anne , Sherrington Catherine
Published: July 2024

Objective

To explore the relationship between long-term physical activity (PA) participation and falls.

Methods

Participants in the Australian Longitudinal Study of Women’s Health born 1946–1951 self-reported amounts of PA every 3 years since 1998 (mean age: 54 years, n=11 796). Latent class analysis described profiles of self-reported PA participation over 18 years. Associations between patterns of PA participation and self-reported falls measured in 2019 were examined using multinomial logistic regression adjusted for directed-acyclic graph-informed potential confounders, with the highly active group as the reference category.

Results

Women were grouped into five PA participation profiles. Compared with consistently highly active patterns (maintaining ≥300 min/week, 22%), consistently lower levels of PA<100 min/week (18%), consistently some PA<150 min/week (18%) and decreasing PA but maintaining≥150 min/week (n=3540, 30%) had higher odds of non-injurious falls (odds Ratiolower level(OR): 1.59, 95% CI 1.29 to 1.97; ORsome PA: 1.27, 95% CI 1.04 to 1.55; ORdecreasing activity:1.29, 95% CI 1.02 to 1.63) and injurious falls (ORlow level: 1.32, 95% CI 1.06 to 1.64; ORsome PA: 1.27, 95% CI 1.04 to 1.54; ORdecreasing activity: 1.47, 95% CI 1.18 to 1.83). No association was found between increasing PA (≥150 min/week, 11%) for non-injurious (OR 1.07, 95% CI 0.89 to 1.29) and injurious falls (OR 1.07, 95% CI 0.90 to 1.29). After adjusting for potential confounders, consistently lower levels of PA remained associated with increased non-injurious falls odds (OR1998 survey: 1.40, 95% CI 1.11 to 1.77; OR2016 survey: 1.35, 95% CI 1.07 to 1.71).

Conclusion

The increased odds of falls among women with consistently lower levels of PA over 18 years supports ongoing participation of 150+ min/week of PA.
Towards inclusive biodesign and innovation: lowering barriers to entry in medical device development through large language model tools
Authors: Moon John T , Lima Nicholas J , Froula Eleanor , Li Hanzhou , Newsome Janice , Trivedi Hari , Bercu Zachary , Wawira Gichoya Judy
Published: July 2024

In the following narrative review, we discuss the potential role of large language models (LLMs) in medical device innovation, specifically examples using generative pretrained transformer-4. Throughout the biodesign process, LLMs can offer prompt-driven insights, aiding problem identification, knowledge assimilation and decision-making. Intellectual property analysis, regulatory assessment and market analysis emerge as key LLM applications. Through case examples, we underscore LLMs’ transformative ability to democratise information access and expertise, facilitating inclusive innovation in medical devices as well as its effectiveness with providing real-time, individualised feedback for innovators of all experience levels. By mitigating entry barriers, LLMs accelerate transformative advancements, fostering collaboration among established and emerging stakeholders.
Efficacy and safety of faricimab for neovascular age-related macular degeneration: a systematic review and network meta-analysis
Authors: Samacá-Samacá Daniel , Hernández-Castillo Claudia , Prieto-Pinto Laura , Rodríguez Francisco , Sardi Carolina , Ocampo Hugo , Kock Joshua , Hernández Fabián
Published: July 2024

Objective

To evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients.

Methods and analysis

A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for naïve population. Outcomes included changes in visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] letters), anatomical changes, frequency of injections and adverse events. The Cochrane Collaboration guidelines and the Confidence in Network Meta-Analysis framework were used for the SR and the certainty of evidence, respectively.

Results

From 4128 identified records through electronic databases and complementary searches, 63 randomised controlled trials (RCTs) met the eligibility criteria, with 42 included in the NMA. Faricimab showed a significant reduction in the number of annual injections compared with most fixed and flexible anti-VEGF treatment regimens, while showing no statistically significant differences in visual acuity through ETDRS letter gain, demonstrating a comparable efficacy. Retinal thickness results showed comparable efficacy to other anti-VEGF agents, and inferior only to brolucizumab. Results also showed that more patients treated with faricimab were free from post-treatment retinal fluid compared with aflibercept every 8 weeks, and both ranibizumab and bevacizumab, in the fixed and pro re nata (PRN) assessed schedules. Faricimab showed a comparable safety profile regarding the risk of ocular adverse events and serious ocular adverse events (SOAE), except for the comparison with brolucizumab quarterly, in which faricimab showed a significant reduction for SOAE risk.

Conclusion

Faricimab showed a comparable clinical benefit in efficacy and safety outcomes, with a reduction in annual injections compared with fixed and flexible anti-VEGF drug regimens, representing a valuable treatment option for nAMD patients.

PROSPERO registration number

CRD42023394226.