bluuebunny/crossref_metadata_2025 huggingface dataset:
USING LARGE LANGUAGE MODELS FOR ARMCHAIR AUDITORS
Authors: O'Leary Jr Daniel E.
Published: July 2024

Armchair auditors are citizens who use open data to investigate and monitor government activities, typically using analytics and other approaches. Armchair auditors provide a valuable role in holding governments and organizations accountable. This paper investigates the potential use of large language models (LLM) to support armchair auditor analyzes of different governmental entities. Unfortunately, the literature, prior to the development of LLM suggested several challenges for armchair auditors. However, the analysis in this paper suggests that LLM can provide substantial data and analytic process support for armchair auditors mitigating issues such as, providing guidelines for analyses, guiding users to appropriate communities, suggesting potential data availability opportunities, doing analysis and other issues. As part of an approach to unifying armchair auditor searches, this paper also suggests a prompt library designed to support, standardize and promote best practice analyzes among armchair auditors. In addition to these issues, this paper also analyzes emerging ethical issues associated with armchair auditors and their use of open data and LLMs. Finally, this paper extends the activity theory model to account for LLMs.
Scalable Anonymous Authentication Scheme Based on Zero-Knowledge Set-Membership Proof
Authors: Wiraatmaja Christopher , Kasahara Shoji
Published: July 2024

In this article, we propose zero-knowledge named proof, a stateless replay attack prevention strategy that ensures the user’s anonymity against malicious administrators. We begin with adopting the zero-knowledge set-membership proof into an authentication setting in which users would delegate their requests to an agent that obstructs the user’s identity from the administrator. This anonymous agent carries the guarantee of authenticity, which the administrator through the set-membership proof can confirm. Next, we prevent replay attacks from other parties by binding the agent’s identity to the authentication proof verifiable by the administrators. By leveraging these properties, a scalable blockchain-based authentication scheme is then built. We quantitatively evaluate the security and measure the time and monetary cost of our scheme under both ideal and realistic environments. On top of it, we provide a third-party authorization scheme derived from our authentication framework to demonstrate its real-world applicability.
Ontogeny and Function of Plasmacytoid Dendritic Cells
Authors: Adams Nicholas M. , Das Annesa , Yun Tae Jin , Reizis Boris
Published: July 2024

Plasmacytoid dendritic cells (pDCs) represent a unique cell type within the innate immune system. Their defining property is the recognition of pathogen-derived nucleic acids through endosomal Toll-like receptors and the ensuing production of type I interferon and other soluble mediators, which orchestrate innate and adaptive responses. We review several aspects of pDC biology that have recently come to the fore. We discuss emerging questions regarding the lineage affiliation and origin of pDCs and argue that these cells constitute an integral part of the dendritic cell lineage. We emphasize the specific function of pDCs as innate sentinels of virus infection, particularly their recognition of and distinct response to virus-infected cells. This essential evolutionary role of pDCs has been particularly important for the control of coronaviruses, as demonstrated by the recent COVID-19 pandemic. Finally, we highlight the key contribution of pDCs to systemic lupus erythematosus, in which therapeutic targeting of pDCs is currently underway.
Poxvirus Immune Evasion
Authors: Hernaez Bruno , Alcamí Antonio
Published: July 2024

Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit signaling pathways within the infected cell. A unique feature of poxviruses is the production of secreted proteins that mimic cytokines and cytokine receptors, acting as decoy receptors to neutralize the activity of cytokines and chemokines. The capacity of these proteins to evade cellular immune responses by inhibiting cytokine activation is complemented by poxviruses’ strategies to block natural killer cells and cytotoxic T cells, often through interfering with antigen presentation pathways. Mechanisms that target complement activation are also encoded by poxviruses. Virus-encoded proteins that target immune molecules and pathways play a major role in immune modulation, and their contribution to viral pathogenesis, facilitating virus replication or preventing immunopathology, is discussed.
The Science, Engineering, and Validation of Marine Carbon Dioxide Removal and Storage
Authors: Doney Scott C. , Wolfe Wiley H. , McKee Darren C. , Fuhrman Jay G.
Published: July 2024

Scenarios to stabilize global climate and meet international climate agreements require rapid reductions in human carbon dioxide (CO2) emissions, often augmented by substantial carbon dioxide removal (CDR) from the atmosphere. While some ocean-based removal techniques show potential promise as part of a broader CDR and decarbonization portfolio, no marine approach is ready yet for deployment at scale because of gaps in both scientific and engineering knowledge. Marine CDR spans a wide range of biotic and abiotic methods, with both common and technique-specific limitations. Further targeted research is needed on CDR efficacy, permanence, and additionality as well as on robust validation methods—measurement, monitoring, reporting, and verification—that are essential to demonstrate the safe removal and long-term storage of CO2. Engineering studies are needed on constraints including scalability, costs, resource inputs, energy demands, and technical readiness. Research on possible co-benefits, ocean acidification effects, environmental and social impacts, and governance is also required.
Path Integral Simulations of Condensed-Phase Vibrational Spectroscopy
Authors: Althorpe Stuart C.
Published: July 2024

Recent theoretical and algorithmic developments have improved the accuracy with which path integral dynamics methods can include nuclear quantum effects in simulations of condensed-phase vibrational spectra. Such methods are now understood to be approximations to the delocalized classical Matsubara dynamics of smooth Feynman paths, which dominate the dynamics of systems such as liquid water at room temperature. Focusing mainly on simulations of liquid water and hexagonal ice, we explain how the recently developed quasicentroid molecular dynamics (QCMD), fast-QCMD, and temperature-elevated path integral coarse-graining simulations (Te PIGS) methods generate classical dynamics on potentials of mean force obtained by averaging over quantum thermal fluctuations. These new methods give very close agreement with one another, and the Te PIGS method has recently yielded excellent agreement with experimentally measured vibrational spectra for liquid water, ice, and the liquid-air interface. We also discuss the limitations of such methods.
A Hitchhiker's Guide Through the Cell: The World According to the Capsids of Alphaherpesviruses
Authors: Döhner Katinka , Serrero Manutea Christophe , Viejo-Borbolla Abel , Sodeik Beate
Published: July 2024

The nucleoplasm, the cytosol, the inside of virions, and again the cytosol comprise the world in which the capsids of alphaherpesviruses encounter viral and host proteins that support or limit them in performing their tasks. Here, we review the fascinating conundrum of how specific protein-protein interactions late in alphaherpesvirus infection orchestrate capsid nuclear assembly, nuclear egress, and cytoplasmic envelopment, but target incoming capsids to the nuclear pores in naive cells to inject the viral genomes into the nucleoplasm for viral transcription and replication. Multiple capsid interactions with viral and host proteins have been characterized using viral mutants and assays that reconstitute key stages of the infection cycle. Keratinocytes, fibroblasts, mucosal epithelial cells, neurons, and immune cells employ cell type–specific intrinsic and cytokine-induced resistance mechanisms to restrict several stages of the viral infection cycle. However, concomitantly, alphaherpesviruses have evolved countermeasures to ensure efficient capsid function during infection.
Enhancement of Charge-Discharge Properties and Temperature Stability of (Ba0.975Na0.05)Ti0.99Nb0.01O3 Ceramic by Doping High-Entropy Oxide
Authors: Bian Zheng-Xiang , Liu Qing-Qing , Li Zhi-Wei , Chen Zhi-Hui , Ren Yu-Rong
Published: July 2024

A bidirectional optimization strategy was adopted to fabricate (1-x)(Ba0.975Na0.05)Ti0.99Nb0.01O3)-xBi(Zn0.2Mg0.2Al0.2Sn0.2Zr0.2)O3(abbreviated as (1-x)BNNT-xBZMASZ, x = 0.02–0.10) ceramics, aimed to improve the energy storage performance. X-ray diffraction results revealed that Bi2+ cations entered the A site and the multiple cations occupied the B site of BNNT, thereby decreased the remnant polarization intensity and refined the hysteresis loop. Scanning electron microscopy images showed uniform morphologies with clear grain boundaries of the ceramics, and the average size decreased with x increasing. The substitution of multiple cations at the B-site induced the splitting of macroscopic ferroelectric domains into smaller polar nanodomains, leading to the formation of high-dynamic polar nanoregions and accelerating the transition from BNNT to relaxor ferroelectrics, thus improving relaxation properties of the material. The excellent energy storage density (Wrec ∼ 2.80 J cm−3) and efficiency (∼90.0%) can be obtained under 200 kV cm−1. Moreover, the discharge-charge testing revealed excellent current density (∼589.5 A cm−2), high power density (∼20.63 MW cm−2), and extremely short discharge time (t0.9 ∼ 50.4 ns), along with exceptional temperature stability and cycling stability under the equivalent electric field of 120 kV cm−1. The 0.92BNNT-0.08BZMASZ ceramic offers a new approach to the design and an improvement of pulsed dielectric capacitor materials.
Mechanical stress-induced connective tissue growth factor plays a critical role in intestinal fibrosis in Crohn’s-like colitis
Authors: Lin You-Min , Zhang Ke , Geesala Ramasatyaveni , Lipson Kenneth E. , Qiu Suimin , Powell Don W. , Cohn Steven , Shi Xuan-Zheng
Published: July 2024

We found that CTGF expression increased significantly not only in the inflammation site but in the distended segment proximal to inflammation in a rodent model of CD-like colitis. Release of mechanical distention prevented CTGF expression in CD rats, whereas direct stretch induced CTGF expression. Treatment with anti-CTGF antibody reduced fibrosis and collagen contents in CD rats. Thus, mechanical stress, via upregulating profibrotic mediators, i.e., CTGF, may play a critical role in fibrosis in CD.
Uterus Transplantation: the Translational Evolution of a Clinical Breakthrough
Authors: Brännström Mats , Adashi Eli Y. , Wu Joseph H. , Tsiartas Panagiotis , Racowsky Catherine
Published: July 2024

Women suffering from absolute uterine factor infertility (AUFI), due to either lack of a uterus or one unable to sustain neonatal viability, presented as one of the last frontiers in conquering infertility. Following systematic animal research for over a decade, uterus transplantation was tested as a treatment for AUFI in 2012, which culminated in the first human live birth in 2014. The development of uterus transplantation from mouse to human has followed both the Moore criteria for introduction of a surgical innovation and the IDEAL concept for evaluation of a novel major surgical procedure. In this article we review the important preclinical animal and human studies that paved the way for the successful introduction of human uterus transplantation a decade ago. We discuss this in the context of the Moore criteria and describe the different procedures of preparation, surgeries, postoperative monitoring, and use of assisted reproduction in human uterus transplantation. We review the worldwide activities and associated results in the context of the IDEAL concept for evaluation of surgical innovation and appraise the ethical considerations relevant to uterus transplantation. We conclude that rigorous application of the Moore criteria and strict alignment with the IDEAL concept have resulted in the establishment of uterus transplantation as a novel, safe, and effective infertility therapy that is now being used worldwide for the treatment of women suffering from AUFI.
PD‐L2 Expression in Breast Cancer Promotes Tumor Development and Progression
Authors: Sun Yuling , Yang Jie , Chen Yachun , Guo Yundi , Xiong Jian , Guo Xuqin , Zhang Yawen , Gu Li , Tong Min , Wang Weipeng , Sun Jing
Published: July 2024

Background. This work focused on investigating the role of programmed death ligand 2 (PD‐L2) in the progression of breast cancer by utilizing breast cancer specimens and cells. Materials and Methods. The serum levels of soluble PD‐L2 (sPD‐L2) in breast cancer patients and healthy individuals were analyzed by means of the enzyme‐linked immunosorbent assay, and the PD‐L2 levels within 416 resected breast cancer specimens were assessed through immunohistochemistry. Concurrently, in vitro cell experiments and in vivo animal experiments were carried out to analyze the relationship between PD‐L2 and the invasion and migration of breast cancer. Results. The concentration of sPD‐L2 in breast cancer patients significantly increased compared to that in the control groups. Additionally, breast cancer patients with high concentrations of sPD‐L2 had higher Ki67 values (≥30%) and tumor grades. PD‐L2 was expressed in 79.09% of the cancer samples, which exhibited a positive correlation with the progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2). Furthermore, we discovered that knockdown of PD‐L2 inhibited the migratory and invasive abilities of both MCF‐7 and MDA‐MB231 cells. Conclusion. Our findings demonstrated that knockdown of PD‐L2 suppressed tumor growth, providing novel insights into important biological functions.
Nonlinear Speed Control of Switched Reluctance Motor Drives Taking into Account Mutual Inductance
Authors: Alrifai M. , Zribi M. , Krishnan R. , Rayan M.
Published: July 2024

A speed control algorithm is proposed for variable speed switched reluctance motor (SRM) drives taking into account the effects of mutual inductances. The control scheme adopts two‐phase excitation; exciting two adjacent phases can overcome the problems associated with single‐phase excitation such as large torque ripple, increased acoustic noise, and rotor shaft fatigues. The effects of mutual coupling between two adjacent phases and their contribution to the generated electromagnetic torque are considered in the design of the proposed control scheme for the motor. The proposed controller guarantees the convergence of the currents and the rotor speed of the motor to their desired values. Simulation results are given to illustrate the developed theory; the simulation studies show that the proposed controller works well. Moreover, the simulation results indicate that the proposed controller is robust to changes in the parameters of the motor and to changes in the load torque.
Figure S2 from CD106 in Tumor-Specific Exhausted CD8+ T Cells Mediates Immunosuppression by Inhibiting TCR Signaling
Authors: Naoi Yuto , Morinaga Takao , Nagasaki Joji , Ariyasu Ryo , Ueda Youki , Yamashita Kazuo , Zhou Wenhao , Kawashima Shusuke , Kawase Katsushige , Honobe-Tabuchi Akiko , Ohnuma Takehiro , Kawamura Tatsuyoshi , Umeda Yoshiyasu , Kawahara Yu , Nakamura Yasuhiro , Kiniwa Yukiko , Yamasaki Osamu , Fukushima Satoshi , Kawazu Masahito , Suzuki Yutaka , Nishikawa Hiroyoshi , Hanazawa Toyoyuki , Ando Mizuo , Inozume Takashi , Togashi Yosuke
Published: July 2024

LAG3, HAVCR2, TIGIT, TNFRSF9, ENTPD1, and ITGAE expression using our scRNA-seq data and volcano plots (exhausted CD8+ T-cell vs. the others) using the publicly available datasets
Supplementary Fig S8 from A Tetravalent Bispecific Antibody Selectively Inhibits Diverse FGFR3 Oncogenic Variants
Authors: Yang Yan , Suhasini Avvaru N. , Jiang Zaoli , Liu Nina , Rosconi Michael , Zhang Bojie , Li Yinyin , Dudgeon Drew , Seong Changhyun , Kim Steven , Rafique Ashique , Huang Tammy , Bhosle Sangram , Krueger Pamela , Ullman Erica , Olson William , Lin John C. , Shen Yang , Daly Christopher
Published: July 2024

Supplementary Fig S8
Supplementary Figure 6 from Inhibition of MALT1 and BCL2 Induces Synergistic Antitumor Activity in Models of B-Cell Lymphoma
Authors: Plotnik Joshua P. , Richardson Adam E. , Yang Haopeng , Rojas Estela , Bontcheva Velitchka , Dowell Colleen , Parsons Sydney , Wilson Ashley , Ravanmehr Vida , Will Christine , Jung Paul , Zhu Haizhong , Partha Sarathy Karunan , Panchal Sanjay C. , Mali Raghuveer Singh , Kohlhapp Frederick J. , McClure Ryan A. , Ramathal Cyril Y. , George Mariam D. , Jhala Manisha , Elsen Nathaniel L. , Qiu Wei , Judge Russell A. , Pan Chin , Mastracchio Anthony , Henderson Jared , Meulbroek Jonathan A. , Green Michael R. , Pappano William N.
Published: July 2024

In vitro and in vivo combination of ABBV-MALT1 and venetoclax
Data from Assessment of Patient-Derived Xenograft Growth and Antitumor Activity: The NCI PDXNet Consensus Recommendations
Authors: Meric-Bernstam Funda , Lloyd Michael W. , Koc Soner , Evrard Yvonne A. , McShane Lisa M. , Lewis Michael T. , Evans Kurt W. , Li Dali , Rubinstein Lawrence , Welm Alana , Dean Dennis A. , Srivastava Anuj , Grover Jeffrey W. , Ha Min J. , Chen Huiqin , Huang Xuelin , Varadarajan Kaushik , Wang Jing , Roth Jack A. , Welm Bryan , Govinden Ramaswamy , Ding Li , Kaochar Salma , Mitsiades Nicholas , Carvajal-Carmona Luis , Herylyn Meenhard , Davies Michael A. , Shapiro Geoffrey I. , Fields Ryan , Trevino Jose G. , Harrell Joshua C. , Doroshow James H. , Chuang Jeffrey H. , Moscow Jeffrey A.
Published: July 2024

Abstract
Although patient-derived xenografts (PDX) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating the comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and assessing a suite of analytical tools will enhance information exchange and facilitate identification of promising novel therapies and biomarkers for guiding cancer therapy.
Supplementary Table 2 from Nfe2l2/NRF2 Deletion Attenuates Tumorigenesis and Increases Bacterial Diversity in a Mouse Model of Lynch Syndrome
Authors: Haller Felix , Jimenez Kristine , Baumgartner Maximilian , Lang Michaela , Klotz Anton , Jambrich Manuela , Busslinger Georg , Müllauer Leonhard , Khare Vineeta , Gasche Christoph
Published: July 2024

Supplementary Table 2: Antibodies with indicated dilutions.
Supplementary Figure S10 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Fig. S10. Competition/inhibition with soluble ligands/TAAs.
Supplementary Fig. S17 from Orchestrated Codelivery of Peptide Antigen and Adjuvant to Antigen-Presenting Cells by Using an Engineered Chimeric Peptide Enhances Antitumor T-Cell Immunity
Authors: Pan Haifeng , Yu Siyuan , Zhuang Haoyun , Yang Han , Jiang Jinlu , Yang Haihui , Ren Shuling , Luo Guoxing , Yu Xuan , Chen Shuping , Lin Yanhua , Sheng Roufang , Zhang Shiyin , Yuan Quan , Huang Chenghao , Zhang Tianying , Li Tingdong , Ge Shengxiang , Zhang Jun , Xia Ningshao
Published: July 2024

Supplementary Fig. S17. Analysis of antitumor effect of vaccination without specific antigens.
Do Not Forget the Granulocytic Compartment’s Role in T cell–Mediated Antitumor Immunity
Authors: Gaipl Udo S.
Published: July 2024

Antitumor immune responses are predominantly mediated by CD8+ cytotoxic T cells (CTLs). But immune-modulatory factors in the tumor microenvironment determine the effectiveness of these responses. In this issue, Wei and colleagues report a new role for CTL-derived IL3 in stimulating basophilic granulocytes to produce IL4, which, in turn, activates, reprograms, and stabilizes CTLs. These findings stress the importance of the crosstalk between the innate and adaptive immune systems to elicit efficient antitumor immunity.

See related article by Wei et al., p. 822 (3).
Movie 4 from Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei
Authors: Villagomez Fabian R. , Lang Julie , Rosario Fredrick J. , Nunez-Avellaneda Daniel , Webb Patricia , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: July 2024

Movie 4 - Merge
Figure 7 from Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei
Authors: Villagomez Fabian R. , Lang Julie , Rosario Fredrick J. , Nunez-Avellaneda Daniel , Webb Patricia , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: July 2024

Impact of claudin-4 in the expression of transporters of amino acids and the uptake of essential amino acids in HGSOC cells. The effect of claudin-4 manipulation (overexpression and downregulation) in the expression of SLC1A5 and LAT1 was measured via immunoblotting in HGSOC cells (OVCAR8, OVCA429, and OVCAR3). Direct amino acid uptake (essential amino acids, EAA; [3H]leucine) was analyzed in OVCAR3 cells (culture for 24 hours). A and B, Top, show representative immunoblots for SLC1A5 and LAT1 in HGSOC cells during claudin-4 disruption, respectively; (bottom), corresponding quantification (four independent experiments). C, Left, illustration highlighting a heterodimer formed by LAT and SLC3A2 which internalizes essential amino acids; right, uptake measurement of the essential amino acid leucine ([3H]leucine; three independent experiments; Two-tail t test). D, Model [adapted from reference: (54)] proposing an axis formed by claudin-4, SLC1A5, and LAT1 which could regulate autophagy in HGSOC cells. In this model, claudin-4 is contributing to determine the intracellular localization of theses transporters of amino acids, and possibly stabilizing their function in membranes. (significance, P < 0.05). Graphs show mean and SEM.
Figure 1 from Claudin-4 Modulates Autophagy via SLC1A5/LAT1 as a Mechanism to Regulate Micronuclei
Authors: Villagomez Fabian R. , Lang Julie , Rosario Fredrick J. , Nunez-Avellaneda Daniel , Webb Patricia , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: July 2024

Characterization of micronuclei during claudin-4 manipulation in HGSOC cells. HGSOC cells were treated with CMP (400 µmol/L; 48 hours). Then, cells were fixed and stained with DAPI to mark DNA and the components of the nuclear lamina, lamin B1 and lamin A/C. Subsequently, a morphometric characterization was performed through confocal microscopy. A, Illustration indicating the histological subtype of EOC cells used as in vitro system, as well as certain genetic alterations. B, (Left), frequency of micronuclei during claudin-4 overexpression; (right), confocal images (maximum projections) highlighting (dotted squares) micronuclei. Similar data is presented for claudin-4 downregulation in OVCA429 (C) and OVCAR3 cells (D). (n = 4,134 OVCAR8 cells; n = 3,315 OVCA429 cells; n = 4,653 OVCAR3 cells; Two-tailed Mann–Whitney test). E, Selected confocal images (OVCAR8 WT cells treated with the vehicle from (B) showing lamin B1 and lamin A/C. It is highlighted the lack of nuclear lamina in some micronuclei. Similar data is presented in (F and G) for OVCA429 and OVCAR3 cells, respectively. (three independent experiments; Kruskal–Wallis test with Dunn's multiple comparisons, P < 0.05). Graphs show mean and SEM, scale bar, 10 µm.
The dionysian Leibniz of Gilles Deleuze
Authors: Seabra Maria Luiza Lima
Published: July 2024

A interpretação deleuziana de Leibniz, mais conhecida pelo seu comentário a este em A Dobra (1995), tem suas principais premissas já delineadas em Diferença e Repetição (1968). Visando constituir uma filosofia da diferença, Deleuze questiona a fundamentação do Princípio de Razão Suficiente sobre o Princípio de Identidade. Isso leva a uma interpretação bastante heterodoxa de Leibniz que aparenta este a Nietzsche. Leibniz aparece como o pensador dionisíaco e obscuro de um racionalismo sui generis. Visamos explicar essa interpretação a partir da compreensão do projeto da filosofia da diferencia como a exigência de uma crítica radical do fundamento que conduz a um ao afundamento universal, à desrazão, ao sem-fundo. Neste quadro, torna-se necessário compreender a afinidade entre Leibniz e Nietzsche, sendo este aquele em que Deleuze encontra a “verdadeira razão suficiente”.
Alphaville: onde mora o processo criativo?
Authors: Rocha Ricardo Oliveira , Rubio Marcelo
Published: July 2024

The Nouvelle Vague is one of the most influential film movements of the 20th century. Moving away from surrealism, the films of the French Nouvelle Vague sought to embrace socially relevant themes. Jean-Luc Godard emerged as an important figure in this movement due to his experimental approach to filmmaking, evident in works such as À Bout de Souffle (1960) and Le Mépris (1963), which reached its apex with Alphaville (1965), his most famous work. This article investigates Godard's experimental and wandering creative process in the conception of Alphaville, exploring the poetic operation of Godardian creation and establishing a dialog between various sources of inspiration.
Narrative Conformation in Long Farewell
Authors: Kokin Iurii
Published: July 2024

The following article discusses the aesthetic configurations involved in the cinematic construction of The Long Farewell (1971), directed by Kira Muratova. The objective is to position the film within the concepts of modern cinema and auteur cinema. To complement this, the methodology incorporates film analysis and research on creative processes, allowing for the concretization and emphasis of thought elements from the material and practice of filmmaking. To achieve this, historical trends and components of mise-en-scène are analyzed, together with testimonies and interviews of those involved in the creative process, resulting in two parts: the first part dedicated to gathering data on historical events, and the second part aiming to analyze the stylistic principles in an attempt to understand them as the authentic imaginative thought of the filmmaker.
Skin thickness effects on failure mechanisms in foam infilled composite sandwich structures
Authors: Malekinejad Hossein , Farrokhabadi Amin , Rahimi Gholam Hossein , Carbas Ricardo , Marques Eduardo AS , da Silva Lucas
Published: July 2024

Sandwich structures are often prone to catastrophic failure due to premature separation between the core and skin layers. Geometric parameters, such as the thickness of the skin and core, along with the materials used in their manufacturing, directly influence the resistance to separation between the skin and core. This study explores how variations in skin thickness affect both failure modes and maximum load capacity in sandwich structures, utilizing both experimental testing and numerical simulations. Specimens were categorized as intact and pre-debonded samples. Each specimen featured four different skin thicknesses (3, 6, 8, and 10 layers of composite laminated skins, with corresponding thicknesses of 0.68, 1.33, 1.73, and 2.1 mm respectively). The specimens incorporated a foam-filled square corrugated core and underwent 3-point bending tests. Results revealed a significant shift in the failure mode: initially observed as upper skin fracture (V-shaped failure), it transitioned to separation between skins and cores with increased skin thickness, particularly in the presence of pre-debonding. Notably, the predominant failure mode did not involve separation between the skin and core in specimens without a pre-existing crack. Furthermore, numerical simulations effectively demonstrated the accurate capture of failure modes and loads using the Hashin and cohesive zone model (CZM).
Developing a lightweight corrugated sandwich panel based on tea oil camellia shell: correlation of experimental and numerical performance
Authors: Choupani Chaydarreh Kamran , Tan Jingyi , Zhou Yonghui , Li Yongtao , Hu Chuanshuang
Published: July 2024

This study presents an experimental and numerical comparison between the mechanical performance of a lightweight corrugated sandwich panel based on the tea oil camellia shell (TOCS). Hence, TOCS was mixed in two groups with Poplar particles and fibers. After that, in the experimental part, the conventional mechanical tests, including the 3-point bending test, flatwise compression, dowel bearing, and screw resistance, and in the numerical part, finite element analysis (FEA), including the normal, maximum principal, and equivalent (von Mises) stress by Ansys Mechanical software carried out. The specimens for experimental and numerical tests were prepared in transverse and longitudinal directions. Before that, the engineering data (shear modulus, Young's modulus, and Poisson's ratio) for improving the FEA simulation were obtained from TOCS-based flat panels fabricated with a mixture of Poplar particles and fibers. The results of FEA are used to compare the mechanical behavior and failure mechanism with the results of experimental tests. According to the mean values of bending stiffness and maximum bending moment, sandwich panels made with 100% particles demonstrated an advantage in both directions. Nevertheless, the compression strength and screw resistance showed the same trend, but the dowel bearing showed higher values for panels made with fibers. The observed results of equivalent (von Mises) stress indicated a coloration with the results of failure mechanisms.
Impairment of α-tubulin and F-actin interactions of GJB3 induces aneuploidy in urothelial cells and promotes bladder cancer cell invasion
Authors: Liu Junnan , Wang Xue , Jiang Wencheng , Azoitei Anca , Eiseler Tim , Eckstein Markus , Hartmann Arndt , Stilgenbauer Stephan , Elati Mohamed , Hohwieler Meike , Kleger Alexander , John Axel , Wezel Felix , Zengerling Friedemann , Bolenz Christian , Günes Cagatay
Published: July 2024

Background

We have previously identified an unsuspected role for GJB3 showing that the deficiency of this connexin protein induces aneuploidy in human and murine cells and accelerates cell transformation as well as tumor formation in xenograft models. The molecular mechanisms by which loss of GJB3 leads to aneuploidy and cancer initiation and progression remain unsolved.

Methods

GJB3 expression levels were determined by RT-qPCR and Western blot. The consequences of GJB3 knockdown on genome instability were assessed by metaphase chromosome counting, multinucleation of cells, by micronuclei formation and by the determination of spindle orientation. Interactions of GJB3 with α-tubulin and F-actin was analyzed by immunoprecipitation and immunocytochemistry. Consequences of GJB3 deficiency on microtubule and actin dynamics were measured by live cell imaging and fluorescence recovery after photobleaching experiments, respectively. Immunohistochemistry was used to determine GJB3 levels on human and murine bladder cancer tissue sections. Bladder cancer in mice was chemically induced by BBN-treatment.

Results

We find that GJB3 is highly expressed in the ureter and bladder epithelium, but it is downregulated in invasive bladder cancer cell lines and during tumor progression in both human and mouse bladder cancer. Downregulation of GJB3 expression leads to aneuploidy and genomic instability in karyotypically stable urothelial cells and experimental modulation of GJB3 levels alters the migration and invasive capacity of bladder cancer cell lines. Importantly, GJB3 interacts both with α-tubulin and F-actin. The impairment of these interactions alters the dynamics of these cytoskeletal components and leads to defective spindle orientation.

Conclusion

We conclude that deregulated microtubule and actin dynamics have an impact on proper chromosome separation and tumor cell invasion and migration. Consequently, these observations indicate a possible role for GJB3 in the onset and spreading of bladder cancer and demonstrate a molecular link between enhanced aneuploidy and invasive capacity cancer cells during tumor cell dissemination.

Graphical Abstract
RUNX1, FUS, and ELAVL1-induced circPTPN22 promote gastric cancer cell proliferation, migration, and invasion through miR-6788-5p/PAK1 axis-mediated autophagy
Authors: Ma Shuo , Xu Yanhua , Qin Xinyue , Tao Mei , Gu Xinliang , Shen Lei , Chen Yinhao , Zheng Ming , Qin Shiyi , Wu Guoqiu , Ju Shaoqing
Published: July 2024

Background

An increasing number of studies have demonstrated the association of circular RNAs (circRNAs) with the pathological processes of various diseases and their involvement in the onset and progression of multiple cancers. Nevertheless, the functional roles and underlying mechanisms of circRNAs in the autophagy regulation of gastric cancer (GC) have not been fully elucidated.

Methods

We used transmission electron microscopy and the mRFP-GFP-LC3 dual fluorescent autophagy indicator to investigate autophagy regulation. The cell counting kit-8 assay, colony formation assay, 5-ethynyl-2′-deoxyuridine incorporation assay, Transwell assay, and Western blot assay were conducted to confirm circPTPN22’s influence on GC progression. Dual luciferase reporter assays validated the binding between circPTPN22 and miR-6788-5p, as well as miR-6788-5p and p21-activated kinase-1 (PAK1). Functional rescue experiments assessed whether circPTPN22 modulates PAK1 expression by competitively binding miR-6788-5p, affecting autophagy and other biological processes in GC cells. We investigated the impact of circPTPN22 on in vivo GC tumors using a nude mouse xenograft model. Bioinformatics tools predicted upstream regulatory transcription factors and binding proteins of circPTPN22, while chromatin immunoprecipitation and ribonucleoprotein immunoprecipitation assays confirmed the binding status.

Results

Upregulation of circPTPN22 in GC has been shown to inhibit autophagy and promote cell proliferation, migration, and invasion. Mechanistically, circPTPN22 directly binds to miR-6788-5p, subsequently regulating the expression of PAK1, which activates protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) phosphorylation. This modulation ultimately affects autophagy levels in GC cells. Additionally, runt-related transcription factor 1 (RUNX1) negatively regulates circPTPN22 expression, while RNA-binding proteins such as FUS (fused in sarcoma) and ELAVL1 (recombinant ELAV-like protein 1) positively regulate its expression. Inhibition of the autophagy pathway can increase FUS expression, further upregulating circPTPN22 in GC cells, thereby exacerbating the progression of GC.

Conclusion

Under the regulation of the transcription factor RUNX1 and RNA-binding proteins FUS and ELAVL1, circPTPN22 activates the phosphorylation of Akt and Erk through the miR-6788-5p/PAK1 axis, thereby modulating autophagy in GC cells. Inhibition of autophagy increases FUS, which in turn upregulates circPTPN22, forming a positive feedback loop that ultimately accelerates the progression of GC.
Paracetamol overdose causing acute kidney injury without hepatotoxicity: a case report
Authors: Saad Micha , Flament Julien
Published: July 2024

Background

Paracetamol is a widely used analgesic and antipyretic. Paracetamol-induced hepatotoxicity is well known, but nephrotoxicity without hepatotoxicity is rarely seen.

Case presentation

We present a case of acute kidney injury without hepatotoxicity in paracetamol overdose. A 15-year-old girl was admitted 48 h after she had taken 10 g of paracetamol. She was complaining of abdominal pain and vomiting. Her blood level of creatinine was 1.20 mg/dL on admission, with a peak at 3.67 mg/dL 3 days later. The liver blood tests and blood paracetamol level were negative. She did not receive N-acetyl cysteine and was treated with intravenous fluid (crystalloid). The ultrasonography of the kidneys was normal. Her renal function returned almost to baseline 7 days after admission. It was concluded that the diagnosis was an acute kidney injury caused by acute tubular necrosis due to paracetamol overdose.

Conclusion

This case shows that nephrotoxicity can occur without hepatotoxicity in paracetamol overdose.
Hitac: a hierarchical taxonomic classifier for fungal ITS sequences compatible with QIIME2
Authors: Miranda Fábio M. , Azevedo Vasco C. , Ramos Rommel J. , Renard Bernhard Y. , Piro Vitor C.
Published: July 2024

Background

Fungi play a key role in several important ecological functions, ranging from organic matter decomposition to symbiotic associations with plants. Moreover, fungi naturally inhabit the human body and can be beneficial when administered as probiotics. In mycology, the internal transcribed spacer (ITS) region was adopted as the universal marker for classifying fungi. Hence, an accurate and robust method for ITS classification is not only desired for the purpose of better diversity estimation, but it can also help us gain a deeper insight into the dynamics of environmental communities and ultimately comprehend whether the abundance of certain species correlate with health and disease. Although many methods have been proposed for taxonomic classification, to the best of our knowledge, none of them fully explore the taxonomic tree hierarchy when building their models. This in turn, leads to lower generalization power and higher risk of committing classification errors.

Results

Here we introduce HiTaC, a robust hierarchical machine learning model for accurate ITS classification, which requires a small amount of data for training and can handle imbalanced datasets. HiTaC was thoroughly evaluated with the established TAXXI benchmark and could correctly classify fungal ITS sequences of varying lengths and a range of identity differences between the training and test data. HiTaC outperforms state-of-the-art methods when trained over noisy data, consistently achieving higher F1-score and sensitivity across different taxonomic ranks, improving sensitivity by 6.9 percentage points over top methods in the most noisy dataset available on TAXXI.

Conclusions

HiTaC is publicly available at the Python package index, BIOCONDA and Docker Hub. It is released under the new BSD license, allowing free use in academia and industry. Source code and documentation, which includes installation and usage instructions, are available at https://gitlab.com/dacs-hpi/hitac.
Common double-lumen tube selection methods overestimate adequate tube sizes in individual patients – a 3D reconstruction study
Authors: Mihatsch Lorenz L. , Weiland Sandra , Helmberger Thomas , Friederich Patrick
Published: July 2024

Background

Appropriate selection of double-lumen tube sizes for one-lung ventilation is crucial to prevent airway damage. Current selection methods rely on demographic factors or 2D radiography. Prediction of left bronchial diameter is indispensable for choosing the adequate tube size. This prospective observational study investigates if current selection methods sufficiently predict individuals’ left bronchial diameters for DLT selection compared to the 3D reconstruction.

Methods

100 patients necessitating thoracic surgery with one-lung ventilation and left-sided double-lumen tubes, ≥ 18 years of age, and a set of chest X-rays and 2D thorax CT scans for 3D reconstruction of the left main bronchus were included between 07/2021 and 06/2023. The cross-validated prediction error and the width of the 95%-prediction intervals of the 3D left main bronchial diameter utilizing linear prediction models were based on current selection methods.

Results

The mean bronchial diameter in 3D reconstruction was 13.6 ± 2.1 mm. The ranges of the 95%-prediction intervals for the bronchial diameter were 6.4 mm for demographic variables, 8.3 mm for the tracheal diameter from the X-ray, and 5.9 mm for bronchial diameter from the 2D-CT scans. Current methods violated the suggested ‘≥1 mm’ safety criterion in up to 7% (men) and 42% (women). Particularly, 2D radiography overestimated women’s left bronchial diameter. Current methods even allowed the selection of double-lumen tubes with bronchial tube sections greater than the bronchial diameter in women.

Conclusions

Neither demographic nor 2D-radiographic methods sufficiently account for the variability of the bronchial diameter. Wide 95%-prediction intervals for the bronchial diameter hamper accurate individual double-lumen tube selection. This increases women’s risk of bronchial damage, particularly if they have other predisposing factors. These patients may benefit from 3D reconstruction of the left main bronchus.

Trial registration

Not applicable.
Comparison of analgesic effectiveness between nefopam and propacetamol in living kidney donors following rectus sheath block after hand-assisted living donor nephrectomy: a prospective, randomized controlled trial
Authors: Hwang Won-Jung , Koo Jung Min , Yang A Rim , Park Yong Hyun , Chae Min Suk
Published: July 2024

Background

Nefopam and propacetamol are the most commonly used analgesics in postoperative multimodal analgesic regimens. Distinct mechanisms are involved in each drug’s anti-nociceptive effects. No studies have compared pain relief efficacy between the two drugs in patients undergoing transplantation surgery. Here, we investigated whether the administration of nefopam or propacetamol to healthy living kidney donors who underwent rectus sheath block (RSB) for parietal pain could reduce the subsequent opioid dose necessary to produce adequate analgesia.

Methods

This prospective, randomized controlled trial included 72 donors undergoing elective hand-assisted living donor nephrectomy into two groups: propacetamol (n = 36) and nefopam (n = 36). Intraoperative RSB was performed in all enrolled donors. The primary outcome was the total volume of intravenous opioid-based patient-controlled analgesia (PCA) used on postoperative day 1 (POD 1). Additionally, the Numeric Rating Scale scores for flank (visceral) and umbilicus (parietal) pain at rest and during coughing were compared, and the Korean adaptation of the Quality of Recovery-15 Questionnaire (QoR-15 K) was evaluated on POD 1.

Results

Both groups had similar preoperative and intraoperative characteristics. On POD 1, the total amount of PCA infusion was significantly lower in the nefopam group than in the propacetamol group (44.5 ± 19.3 mL vs. 70.2 ± 29.0 mL; p < 0.001). This group also reported lower pain scores at the flank and umbilical sites and required fewer rescue doses of fentanyl in the post-anesthesia care unit. However, pain scores and fentanyl consumption in the ward were comparable between groups. The QoR-15 K scores were similar between groups; there were substantial improvements in breathing, pain severity, and anxiety/depression levels in the nefopam group. The incidences of postoperative complications, including sweating and tachycardia, were similar between groups.

Conclusion

Compared with propacetamol, nefopam provides a greater analgesic effect for visceral pain and enhances the effects of blocks that reduce the opioid requirement in living kidney donors with parietal pain managed by RSB.

Trial registration

The trial was registered prior to patient enrollment in the clinical trial database using the Clinical Research Information Service (registration no. KCT0007351, Date of registration 03/06/2022).
Association between dietary patterns and the risk of all-cause mortality among old adults with obstructive sleep apnea
Authors: Zhao Wei , Gao Lu , Wu Zhiyuan , Qin Mingzhao
Published: July 2024

Background

Obstructive sleep apnea (OSA) was associated with the increased cardiovascular events and all-cause mortality. And anti-inflammatory dietary has potential to improve the prognosis of OSA. This study aimed to investigate the association of anti-inflammatory dietary patterns with all-cause mortality among individuals with OSA.

Methods

This retrospective cohort study involved 1522 older adults with OSA from 2005 to 2008 in the National Health and Nutrition Examinations Survey (NHANES). Mortality status was determined by routine follow-up through December 31, 2019, using the National Death Index. Anti-inflammatory dietary patterns included Alternate Mediterranean Diet Score (aMED), Healthy Eating Index-2015 (HEI-2015), and Alternate Healthy Eating Index-2010 (AHEI-2010). Weighted Cox proportional hazard regression models were performed to investigate the association between anti-inflammatory dietary pattern and all-cause mortality.

Results

After a median follow-up of 131 months, 604 participants were recorded all-cause mortality. The mean age of OSA patients was 68.99 years old, of whom 859 were male (52.34%). Higher adherence of aMED (HR = 0.61, 95%CI: 0.48 to 0.78) and HEI-2015 (HR = 0.75, 95%CI: 0.60 to 0.95) were associated with lower all-cause mortality risk in the elderly with OSA. Conversely, no association was found between AHEI-2010 dietary pattern and all-cause mortality in individuals with OSA. In the component analysis of aMED, it was found that a higher intake of vegetables and olive oil potentially contributes to the reduction all-cause mortality risk in the elderly with OSA (HR = 0.60, 95%CI: 0.48 to 0.76; HR = 0.67, 95%CI: 0.63 to 0.71).

Conclusion

Higher adherence to the aMED and the HEI-2015 was associated with a lower risk of all-cause mortality in OSA. Future interventions in the elderly with OSA should considering adopting anti-inflammatory dietary patterns.