bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial resistance profiles of
Streptococcus suis
isolated from pigs, wild boars, and humans in France between 1994 and 2020
Authors: Dechêne-Tempier Manon , Jouy Eric , Bayon-Auboyer Marie-Hélène , Bougeard Stéphanie , Chauvin Claire , Libante Virginie , Payot Sophie , Marois-Créhan Corinne
Published: September 2023

Streptococcus suis,
an emerging zoonotic pathogen, causes invasive infections and substantial economic losses in the pig industry worldwide. Antimicrobial resistance against 22 antibiotics was studied for 200
S
.
suis
strains collected in different geographical regions of France. Most of the strains (86%) showed resistance to at least one antibiotic with a low rate of resistance to fluoroquinolones, penicillins, pleuromutilin, and diaminopyrimidine-sulfonamides, and a higher rate to macrolides-lincosamides and tetracycline. Multi-resistance patterns were observed in 138 strains; three of them being resistant to six antibiotic families. Statistical analyses highlighted a decrease in the resistance to trimethoprim-sulfamethoxazole, in our collection, between the two periods studied—before 2010 and after 2015—as well as an impact of the geographical origin with a higher rate of resistance to macrolides-lincosamides and penicillin in Brittany than in the other French regions. Furthermore, macrolides-lincosamides and tetracycline resistance patterns were more likely to be found in pig isolates than in human and wild boar isolates. A difference in resistance was also observed between serotypes. Most of the penicillin-resistant strains belong to serotypes 1, 5, 9, 11, 12, 15, 27, and 29. Finally, penicillin and pleuromutilin resistances were mostly found in “non-clinical” isolates. The empirical treatment of human and porcine infections due to
S. suis
in France can therefore still be carried out with beta-lactams. However, this study emphasizes the need to monitor antimicrobial resistance in this zoonotic pathogen.
Fungal organic acid uptake of mineral-derived K is dependent on distance from carbon hotspot
Authors: Bhattacharjee Arunima , Velickovic Dusan , Richardson Jocelyn A. , Couvillion Sneha P. , Vandergrift Gregory W. , Qafoku Odeta , Taylor Michael J. , Jansson Janet K. , Hofmockel Kirsten , Anderton Christopher R.
Published: September 2023

Fungal mineral weathering regulates the bioavailability of inorganic nutrients from mineral surfaces to organic matter and increase the bioavailable fraction of nutrients. Such weathering strategies are classified as biomechanical or biochemical. In the case of fungal uptake of mineral nutrients through biochemical weathering, it is widely hypothesized that uptake of inorganic nutrients occurs through organic acid chelation, but such processes have not been directly visualized. This is in part due to challenges in probing the complex and heterogeneous soil environment. Here, using an epoxy-based, mineral-doped soil micromodel platform, which emulates soil mineralogy and porosity, we visualize the molecular mechanisms of mineral weathering. Mass spectrometry imaging revealed differences in the distribution of fungal exudates, citric acid, and tartaric acid on the soil micromodels in presence of minerals. Citric acid was detected closer to the nutrient-rich inoculation point, whereas tartaric acid was highly abundant away from inoculation point. This suggested that the organic acid exuded by the fungi depended on the proximity from the carbon-rich organic substrate at the point of inoculation. Using a combination of X-ray fluorescence and X-ray near edge structure analysis, we identified citric acid- and tartaric acid-bound K within fungal hyphae networks grown in the presence of minerals. Combined, our results provide direct evidence that fungi uptake and transport mineral derived nutrient organic acid chelation. The results of this study provided unprecedented visualization of fungal uptake and transport of K
+
, while resolving the indirect weathering mechanism of fungal K uptake from mineral interfaces.

IMPORTANCE

Fungal species are foundational members of soil ecosystems with vital contributions that support interspecies resource translocation. The minute details of these biogeochemical processes are poorly investigated. Here, we addressed this knowledge gap by probing fungal growth in a novel mineral-doped soil micromodel platform using spatially-resolved imaging methodologies. We found that fungi uptake K from K-rich minerals using organic acids exuded in a distance-dependent manner from a carbon-rich hotspot. While identification of specific mechanisms within soil remains challenging, our findings demonstrate the significance of reduced complexity platforms such as the mineral-doped micromodel in probing biogeochemical processes. These findings provide visualization into hyphal uptake and transport of mineral-derived nutrients in a resource-limited environment.
Interferon inhibits the release of herpes simplex virus-1 from the axons of sensory neurons
Authors: Danastas Kevin , Guo Gerry , Merjane Jessica , Hong Nathan , Larsen Ava , Miranda-Saksena Monica , Cunningham Anthony L.
Published: September 2023

Herpes simplex virus-1 (HSV-1) has evolved mechanisms to evade the host immune system and limit the antiviral effects induced by interferon (IFN) produced by local epithelial and immune cells. In this study, we determined the effects of type I, II, and III IFNs on HSV-1 release from sensory axons. Using compartmentalized microfluidic devices separating axons from the neuronal cell bodies, we showed that treating axons with type I (IFNα and IFNβ), type II (IFNγ), and type III (IFNλ) IFNs inhibited the release of HSV-1 from axons, without altering the anterograde axonal transport of viral components. Furthermore, we showed that only type II IFN induced a cell-wide response following axonal treatment, with phosphorylated STAT1 and STAT3 present along axons and in the neuronal cell body, whereas type I and III IFNs only induced a local STAT1 and STAT3 response in axons. We also showed that HSV-1 infection alone, in the absence of exogenous IFN, activated STAT1 and STAT3 in both neuronal cell bodies and along axons. However, HSV-1 infection restricted the translocation of pSTAT1 and pSTAT3 to the nucleus even in the presence of IFNs, suggesting viral evasion mechanisms are involved in limiting the IFN response in the neuronal cell body. Overall, our study indicates a key and greater antiviral role of IFNs in inhibiting HSV-1 release from axon termini than in the ganglia during recurrent infections and identifies a novel intervention site, the neuro-epidermal junction, for the development of new immunotherapies.

IMPORTANCE

Herpes simplex virus-1 (HSV-1) is a human pathogen known to cause cold sores and genital herpes. HSV-1 establishes lifelong infections in our sensory neurons, with no cure or vaccine available. HSV-1 can reactivate sporadically and travel back along sensory nerves, where it can form lesions in the oral and genital mucosa, eye, and skin, or be shed asymptomatically. New treatment options are needed as resistance is emerging to current antiviral therapies. Here, we show that interferons (IFNs) are capable of blocking virus release from nerve endings, potentially stopping HSV-1 transmission into the skin. Furthermore, we show that IFNγ has the potential to have widespread antiviral effects in the neuron and may have additional effects on HSV-1 reactivation. Together, this study identifies new targets for the development of immunotherapies to stop the spread of HSV-1 from the nerves into the skin.
Complete genome sequences of agricultural azole-resistant
Penicillium rubens
encoding CYP51A and ERG11 paralogues
Authors: Gauthier Jeff , Mohammadi Sima , Huffman Jesse , Lawal Opeyemi U. , Kukavica-Ibrulj Irena , Potvin Marianne , Goodridge Lawrence , Levesque Roger C.
Published: September 2023

Azoles are major antifungals in agriculture and medicine. However, the surge of intrinsic azole resistance is critical for public health. Here, we present the complete long-read sequencing of three azole-resistant
Penicillium rubens
from food crops. The presence of CYP51A and ERG11 paralogues was confirmed, as in other azole-resistant
P. rubens
.
Assessment and verification of chemical inactivation of peste des petits ruminants virus by virus isolation following virus capture using Nanotrap magnetic virus particles
Authors: Das Amaresh , Ahmed Zaheer , Xu Lizhe , Jia Wei
Published: September 2023

This study reports development and optimization of a new method for the assessment and verification of the inactivation of peste des petits ruminants virus (PPRV) by chemical agents, including Triton X-100 and commercially available viral lysis buffers. Virus inactivation was confirmed by virus isolation (VI) on Vero cells following capture of the potential residual viruses from treated samples using Nanotrap magnetic virus particles (NMVPs). Since chemical agents are cytotoxic, treated PPRV samples could not be used directly for VI on Vero cell monolayers; instead, they were diluted in Eagle’s Minimum Essential Medium (EMEM) to neutralize cytotoxicity and then subjected to virus capture using NMVPs. The NMVPs and the captured viruses were then clarified on a magnetic stand, reconstituted in EMEM, and inoculated onto Vero cells that were examined for cytopathic effect (CPE). No CPE was observed on cells inoculated with treated viruses captured by NMVPs; but CPE was observed on cells inoculated with untreated viruses, including those captured by NMVPs. For further verification, the supernatants of the VI cultures (treated or untreated) were subjected to RNA extraction and PPRV-specific real-time RT-PCR (RT-qPCR). The cycle threshold values were undetectable for the supernatants of VI cultures inoculated with NMVPs reconstituted from treated PPRV but detectable for the supernatants of VI cultures inoculated with untreated PPRV or the NMVPs reconstituted from untreated PPRV, indicating complete inactivation of PPRV. This new method of verification of virus inactivation using NMVPs can be applied to other high impact viruses of agricultural or public health importance.

IMPORTANCE

Research including diagnosis on highly contagious viruses at the molecular level such as PCR and next-generation sequencing requires complete inactivation of the virus to ensure biosafety and biosecurity so that any accidental release of the virus does not compromise the safety of the susceptible population and the environment. In this work, peste des petits ruminants virus (PPRV) was inactivated with chemical agents, and the virus inactivation was confirmed by virus isolation (VI) using Vero cells. Since the chemical agents are cytotoxic, inactivated virus (PPRV) was diluted 1:100 to neutralize cytotoxicity, and the residual viruses (if any) were captured using Nanotrap magnetic virus particles (NMVPs). The NMVPs and the captured viruses were subjected to VI. No CPE was observed, indicating complete inactivation, and the results were further supported by real-time RT-PCR. This new protocol to verify virus inactivation can be applicable to other viruses.
Lipid metabolic reprogramming of hepatic CD4
+
T cells during SIV infection
Authors: Clain Julien A. , Boutrais Steven , Dewatines Juliette , Racine Gina , Rabezanahary Henintsoa , Droit Arnaud , Zghidi-Abouzid Ouafa , Estaquier Jérôme
Published: September 2023

While liver inflammation is associated with AIDS, little is known so far about hepatic CD4
+
T cells. By using the simian immunodeficiency virus (SIV)-infected rhesus macaque (RM) model, we aimed to characterize CD4
+
T cells. The phenotype of CD4
+
T cells was assessed by flow cytometry from uninfected (
n
= 3) and infected RMs, with either SIVmac251 (
n
= 6) or SHIVSF162p3 (
n
= 6). After cell sorting of hepatic CD4
+
T cells, viral DNA quantification and RNA sequencing were performed.Thus, we demonstrated that liver CD4
+
T cells strongly expressed the SIV coreceptor, CCR5. We showed that viremia was negatively correlated with the percentage of hepatic effector memory CD4
+
T cells. Consistent with viral sensing, inflammatory and interferon gene transcripts were increased. We also highlighted the presence of harmful CD4
+
T cells expressing
GZMA
and members of
TGFB
that could contribute to fuel inflammation and fibrosis. Whereas RNA sequencing demonstrated activated CD4
+
T cells displaying higher levels of mitoribosome and membrane lipid synthesis transcripts, few genes were related to glycolysis and oxidative phosphorylation, which are essential to sustain activated T cells. Furthermore, we observed lower levels of mitochondrial DNA and higher levels of genes associated with damaged organelles (reticulophagy and mitophagy). Altogether, our data revealed that activated hepatic CD4
+
T cells are reprogrammed to lipid metabolism. Thus, strategies aiming to reprogram T cell metabolism with effector function could be of interest for controlling viral infection and preventing liver disorders.

IMPORTANCE

Human immunodeficiency virus (HIV) infection may cause liver diseases, associated with inflammation and tissue injury, contributing to comorbidity in people living with HIV. Paradoxically, the contribution of hepatic CD4
+
T cells remains largely underestimated. Herein, we used the model of simian immunodeficiency virus (SIV)-infected rhesus macaques to access liver tissue. Our work demonstrates that hepatic CD4
+
T cells express CCR5, the main viral coreceptor, and are infected. Viral infection is associated with the presence of inflamed and activated hepatic CD4
+
T cells expressing cytotoxic molecules. Furthermore, hepatic CD4
+
T cells are reprogrammed toward lipid metabolism after SIV infection. Altogether, our findings shed new light on hepatic CD4
+
T cell profile that could contribute to liver injury following viral infection.
Impact of storage time in dried blood samples (DBS) and dried plasma samples (DPS) for point-of-care hepatitis C virus (HCV) RNA quantification and HCV core antigen detection
Authors: Troyano-Hernáez Paloma , Herrador Pedro , Gea Francisco , Romero-Hernández Beatriz , Reina Gabriel , Albillos Agustín , Galán Juan Carlos , Holguín África
Published: September 2023

The scale-up of hepatitis C virus (HCV) diagnosis and treatment requires affordable and simple tools to improve access to care, especially in low- and middle-income settings with limited infrastructure or high-risk populations. Dried blood and plasma samples (DBS and DPS) are useful alternative for hepatitis C detection in settings lacking adequate infrastructure. We evaluated the performance of DBS and DPS vs plasma in a point-of-care HCV RNA quantitative assay (Xpert HCV Viral Load-Cepheid), and compared HCV core antigen (HCVcAg) detection by the Architect HCV core antigen assay (Abbott) in DBS vs serum. The dried samples were stored at room temperature for different storage times to reproduce the time from sampling to testing in settings with centralized diagnosis or when testing mobile populations. HCV RNA quantification in DBS and DPS presented 100% sensitivity and specificity and a high correlation for up to 3 months of storage. HCV viremia showed a mean decrease of 0.5 log
10
IU/mL (DBS) and 0.3 log
10
IU/mL (DPS) for storage times up to 1 month. Architect HCVcAg detection presented high sensitivity/specificity (96%/100%) in DBS tested immediately after sampling, decreasing to 86% sensitivity after 7 days of storage. However, sensitivity increased when an optimized cut-off was applied for each storage time. We conclude that DBS and DPS are suitable samples for HCV RNA detection and quantification, being DPS more reliable for shorter storage times. DBS can be also used for HCVcAg qualitative detection and the sensitivity can be increased when adjusting the cut-off values.

IMPORTANCE

Hepatitis C infection remains a global burden despite the effectiveness of antivirals. In the WHO roadmap to accomplish HCV elimination by 2030, HCV diagnosis is one of the main targets. However, identifying patients in resource-limited settings and high-risk populations with limited access to healthcare remains a challenge and requires innovative approaches that allow decentralized testing. The significance of our research is in verifying the good performance of dried samples for HCV diagnosis using two different diagnostics assays and considering the effect of room temperature storage in this sample format. We confirmed dried samples are an interesting alternative for HCV screening and reflex testing in resource-limited settings or high-risk populations.
RecurrentBRCA2exon 3 deletion in Assyrian families
Authors: Hodan Rachel , Kingham Kerry , Kurian Allison W
Published: September 2023

We identified six patients from five families with a recurrent mutation: NM_000059.3 (BRCA2) exon 3 deletion. All families self-identified as Assyrian. Assyrians are an ethnoreligious population of ancient Mesopotamia, now mostly living in modern day Iraq, Syria, Turkey and Iran. They are historically a socially isolated population with intermarriage within their community, living as a religious and language minority in mostly Muslim countries. The probands of each family presented with a classicBRCA2-associated cancer including early-onset breast cancer, epithelial serous ovarian cancer, male breast cancer and/or high-grade prostate cancer, and family history that was also significant forBRCA2-associated cancer.BRCA2exon 3 deletion is classified as pathogenic and has been previously described in the literature, but it has not been described as a founder mutation in a particular population. We characterise this recurrentBRCA2pathogenic variant in five Assyrian families in a single centre cohort.
“And Then It Spreads”: contagion and disease as metaphors of sociomoral contamination in Charles Burns’ graphic novelBlack Hole
Authors: Nandi Arindam , Parui Avishek
Published: September 2023

This article attempts to demonstrate how Charles Burns’ graphic novelBlack Hole(1995) construes the prevalence of contagion and pathological transformation(s) as metaphors of social contamination operating within a biopolitics of segregation. Through a study of plague, infection and strange mutations in Burns’ novel, this article offers a critical evaluation of themonstrous bodyand investigates howBlack Holeportrays the social reception of a sexually contagious virus through conditions of sickness and exclusion, which become biopolitical in quality. It examines, through close reading, how Burns’ novel uses metaphors of contagion, abjection and desire, often fusing those in order to foreground the complex intercorporeal state of thesegregated subjectand in the process dramatises the urgent need to revaluate conventional strategies of isolation and otherisation through a reconsideration of the biopolitical notions around engagement, community and immunity.
Two large structure-forming sponges from opposite North American coasts: a taxonomic review of Arctic–Pacific Mycale (Mycale) loveni and the description of a new Arctic–Atlantic Mycale
Authors: Dinn Curtis , Ott Bruce , Bouchard Marmen Mariève , Steeves Royce , Côté Geneviève , Hayes Vonda , Nozères Claude , Everett Meredith V. , Powell Abigail , Chu Jackson W.F.
Published: September 2023

Mycale ( Mycale) loveni (Fristedt, 1887) is a very large structure-forming sponge that has previously been reported in the North Pacific, North Atlantic, and Arctic oceans. Through morphological and molecular examination, North Atlantic and Eastern Canadian Arctic specimens are now described as a new species, Mycale ( Mycale) lorea sp. nov. The two species have similar external morphology; however, the spicules that make up their skeletons differ in size and shape, and the species are also separated phylogenetically by multiple genetic markers.
Control optimization for parametric Hamiltonians by pulse reconstruction
Authors: Luchi Piero , Turro Francesco , Quaglioni Sofia , Wu Xian , Amitrano Valentina , Wendt Kyle , DuBois Jonathan L. , Pederiva Francesco
Published: September 2023

Optimal control techniques provide a means to tailor the control pulses required to generate customized quantum gates, which helps to improve the resilience of quantum simulations to gate errors and device noise. However, the significant amount of (classical) computation required to generate customized gates can quickly undermine the effectiveness of this approach, especially when pulse optimization needs to be iterated. We propose a method to reduce the computational time required to generate the control pulse for a Hamiltonian that is parametrically dependent on a time-varying quantity. We use simple interpolation schemes to accurately reconstruct the control pulses from a set of pulses obtained in advance for a discrete set of predetermined parameter values. We obtain a reconstruction with very high fidelity and a significant reduction in computational effort. We report the results of the application of the proposed method to device-level quantum simulations of the unitary (real) time evolution of two interacting neutrons based on superconducting qubits.
Landscape of High-Performance Python to Develop Data Science and Machine Learning Applications
Authors: Castro Oscar , Bruneau Pierrick , Sottet Jean-Sébastien , Torregrossa Dario
Published: September 2023

Python has become the prime language for application development in the data science and machine learning domains. However, data scientists are not necessarily experienced programmers. Although Python lets them quickly implement their algorithms, when moving at scale, computation efficiency becomes inevitable. Thus, harnessing high-performance devices such as multi-core processors and graphical processing units to their potential is generally not trivial. The present narrative survey can be thought of as a reference document for such practitioners to help them make their way in the wealth of tools and techniques available for the Python language. Our document revolves around user scenarios, which are meant to cover most situations they may face. We believe that this document may also be of practical use to tool developers, who may use our work to identify potential lacks in existing tools and help them motivate their contributions.
Cardiovascular responses to mild perinatal asphyxia in growth-restricted preterm lambs
Authors: Oyang Matthew , Piscopo Beth R. , Zahra Valerie , Malhotra Atul , Sutherland Amy E. , Sehgal Arvind , Hooper Stuart B. , Miller Suzanne L. , Polglase Graeme R. , Allison Beth J.
Published: September 2023

Preterm growth-restricted lambs maintain carotid blood flow for longer than control lambs during asphyxia and have a lower requirement for chest compressions than control lambs during resuscitation. Preterm growth-restricted, but not control, lambs displayed an overshoot in carotid blood flow following return of spontaneous circulation.
Phytochemical Characteristics and Anti‐Inflammatory, Immunoregulatory, and Antioxidant Effects of Portulaca oleracea L.: A Comprehensive Review
Authors: Ghorani Vahideh , Saadat Saeideh , Khazdair Mohammad Reza , Gholamnezhad Zahra , El-Seedi Hesham , Boskabady Mohammad Hossein
Published: September 2023

Portulaca oleracea L. (P. oleracea) or purslane is a plant from the Portulacaceae family, which is used as food and traditional medicine for various diseases. This review article provides comprehensive information on the antioxidant, immunomodulatory, and anti‐inflammatory properties of P. oleracea and its constituents. The literature survey of the different databases until the end of June 2023 was explored based on the keywords including the “P. oleracea, purslane, anti‐inflammatory, immunomodulatory, and antioxidant properties.” The plant contains flavonoids, alkaloids, terpenoids, fatty acids, vitamins, minerals, and some other compounds. The results indicated that P. oleracea and its constituents showed anti‐inflammatory and immunomodulatory properties through reduction of inflammatory mediators including interferon gama (IFN‐γ), interleukin (IL)‐10, IL‐4, tumor necrosis factor‐alpha (TNF‐α), and nitric oxide. Improvement in cytokines’ serum levels (IFN‐γ, IL‐10, and IL‐4) and increased IgG and IgM serum levels, as well as reduction of IgE, phospholipase A2, and total protein were demonstrated for P. oleracea. The plant and its constituents also improved oxidative stress by reduction of oxidant and increase of antioxidant markers. P. oleracea could be considered as an effective remedy for various inflammatory and immune diseases.
Towards Efficient Federated Learning Using Agile Aggregation in Internet of Vehicles
Authors: He Xin , Hu Xiaolin , Wang Guanghui , Yu Junyang , Zhao Zhanghong , Lu Xiaobin
Published: September 2023

Federated learning is an enabling technology for the services in Internet of vehicles because it can effectively alleviate privacy issues in data circulation and diversified intelligent applications. However, existing federated learning methods still confront the problem of low computational efficiency when applied to the scenario of high-dynamic vehicles. In order to address this problem, we present a multistep federated learning architecture including task release, vehicle model training, identity authentication, quality assessment, and weighted aggregation processes, where a novel agile aggregation model is established. Based on the agile aggregation model, an efficient federated learning (EFL) algorithm is proposed, which is specifically applied to the scenario of high-dynamic vehicles during the training model. We theoretically analyze its advantages over the existing traditional federated learning algorithms in terms of efficiency, training accuracy, and security. Simulations are conducted using the MNIST dataset to evaluate the performance of the proposed EFL algorithm. The results show that EFL improves the efficiency of the federated training process with effective accuracy and privacy preservation.
Characterization of Thermostable Cellulase from Bacillus licheniformis PANG L Isolated from the Himalayan Soil
Authors: Shyaula Manita , Regmi Sunil , Khadka Deegendra , Poudel Ram Chandra , Dhakal Agni , Koirala Devesh , Sijapati Jaishree , Singh Anjana , Maharjan Jyoti
Published: September 2023

This study aimed to isolate, purify, and characterize a potential thermophilic cellulase-producing bacterium from the Himalayan soil. Eleven thermophilic bacteria were isolated, and the strain PANG L was found to be the most potent cellulolytic producer. Morphological, physiological, biochemical, and molecular characterization identified PANG L as Bacillus licheniformis. This is the first study on the isolation of thermostable cellulase-producing Bacillus licheniformis from the Himalayan soil. This bacterium was processed for the production of cellulase enzyme. The optimum conditions for cellulase production were achieved at 45°C after 48 h of incubation at pH 6.5 in media-containing carboxymethyl cellulose (CMC) and yeast extract as carbon and nitrogen sources, respectively, in a thermo-shaker at 100 rpm. The enzyme was partially purified by 80% ammonium sulphate precipitation followed by dialysis, resulting in a 1.52-fold purification. The optimal activity of partially purified cellulase was observed at a temperature of 60°C and pH 5. The cellulase enzyme was stable within the pH ranges of 3–5 and retained 67% of activity even at 55°C. Cellulase activity was found to be enhanced in the presence of metal ions such as Cd2+, Pb2+, and Ba2+. The enzyme showed the highest activity when CMC was used as a substrate, followed by cellobiose. The Km and Vmax values of the enzyme were 1.8 mg/ml and 10.92 μg/ml/min, respectively. The cellulase enzyme obtained from Bacillus licheniformis PANG L had suitable catalytic properties for use in industrial applications.
Effect of Thermal Response and Vibration on the Multicracked Rotor Immersed in a Fluid Medium Using Finite Element Method
Authors: Yadao Adik , Majumder Himadri , Barik Debabrata , Dennison Milon Selvam
Published: September 2023

A rotor shaft under high rotating speeds and heavy loading may establish fatigue damage in terms of cracks due to the long duration of the operation. Analysis of the size and location of the crack in the rotor shaft becomes very difficult, especially while the rotor shaft revolves in a viscous fluid medium. This research is an attempt to measure the vibration signature of a multicracked cantilever rotor shaft with additional mass at the free end in a different fluid medium at a finite region. The dynamic response of a cracked cantilever rotor shaft, with additional mass at the free end, partly immersed in air and diverse viscous mediums are measured experimentally. The existence of open cracks in the rotor shaft in both transverse directions, along the crack and perpendicular to the crack, was considered. The experimental analysis is performed to examine the variation in vibration response with varying the size of the rotor shaft, crack depth, and fluid properties. The finite element analysis technique is employed by using ANSYS to authenticate the vibration response of the same multicracked cantilever rotor shaft in air and different viscous mediums.
A Flexible Multiband Dendritic Structure Fractal Antenna for 4G/5G/WLAN/Bluetooth Applications
Authors: Yu Zhen , Zhang Guodong , Ran Xiaoying , Niu Ruirong , Sun Runzhi , Lin Ziheng , Lu Zewei
Published: September 2023

In this study, a flexible multiband fractal antenna mimicking dendrite structure is proposed and designed by combining bionics and fractal theory. The dendritic structure of neurons is extracted and simplified into a simple and clear geometric structure. The initial antenna model is obtained by fractal operation on the geometric structure, and finally, four effective bands are obtained. The antenna is printed on a

50

∗

70

∗

0.1

 mm3 polyimide dielectric board and fed by a coplanar waveguide. This paper discusses the effect of the human body on the performance of the antenna and the robustness of the antenna in the bending regime. The gain, efficiency, and cross-polarization of the antenna were tested using a microwave anechoic chamber. The measured antenna covers 1.37 GHz-1.93 GHz (relative bandwidth 35%), 2.25 GHz-2.51 GHz (relative bandwidth 10.7%), 3.13 GHz-3.81 GHz (relative bandwidth 19.3%), and 4.46 GHz-5.5 GHz (relative bandwidth 21.1%) four operating frequency bands. The maximum gain is 6.05 dBi and the maximum efficiency is 91.05%. The antenna can be used for Bluetooth WLAN (Wireless Local Area Network), 4G (4th Generation Communication System), 5G (5th Generation Mobile Communication System), WiMAX (Worldwide Interoperability for Microwave Access), etc. The test results are in good agreement with the simulation results, which proves that the antenna can meet various wireless communication requirements.
Efficacy of Sofosbuvir/Daclatasvir in a Single Tablet for Treating Chronic Viral Hepatitis C
Authors: Debzi Nabil , Berkane Saadi , Manouni Chafika , Amani Nassima , Hemmam Sonia , Yousfi Mohamed , Taleb Ayoub , Guessab Nawal , Moulay Brahim Ahlem Sarah , Helal Sarah , Benbitour Ismahane , Noual Lynda , Kerbouche Rafik , Cheikh Ibtissem Ouled , Drir Othmane , Belimi Hibat Allah , Gourari Samir , Frigga Issam , Kassah-laouar Ahmed , Khaberi Mouna , Afredj Nawal
Published: September 2023

Background. Published data regarding the real-life application of the combination sofosbuvir/daclatasvir in Algeria are lacking. Therefore, we conducted an observational study to assess the efficacy and safety of this regimen in Algerian patients with chronic hepatitis C. Methods. We carried out a multicentric, observational, open-label study to assess the efficacy and safety of the generic fixed-dose combination (FDC) sofosbuvir/daclatasvir in patients with chronic hepatitis C. We included 100 patients with all genotypes for 12 or 24 weeks of treatment without ribavirin. The primary outcome was the proportion of patients with a sustained virologic response (SVR) 12 weeks after treatment cessation. The secondary outcome assessed the safety and occurrence of adverse events. This study is registered with ClinicalTrials.gov identifier: NCT05138523. Results. The full analysis set included 99 patients with a mean age of 51.4 ± 14.4 years and a sex ratio of M/F = 0.86. Our patients were infected with HCV genotype 1b (n = 47), 2 (n = 17), 1a (n = 3), 2a/2c (n = 2), 3 (n = 2), and 4 (n = 1). A total of 27 patients had missing genotype data. Most patients were naive noncirrhotic (n = 70) and took 12 weeks of treatment, 19 patients had cirrhosis, of which 68.42% (n = 13) were classified as Child–Pugh A, and 5 patients were treatment-experienced. Both cirrhotic and treatment-experienced patients took 24 weeks of treatment. Efficacy analysis was conducted on 95 patients, and the results showed that 91 patients achieved SVR12 with a response rate of 95.8% (95% CI: 92–100%). Six adverse events occurred and were minor and manageable. Conclusion. Our results demonstrate the efficacy and safety of sofosbuvir/daclatasvir in single tablets in treating Algerian HCV patients without ribavirin for 12 or 24 weeks. The promising results of this study warrant further trials to assess the efficacy and safety of this combination in treating special populations.
Supplemental Figures 1-4 from Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor through cMYC Repression and Recruitment of the DREAM Complex
Authors: Nyquist Michael D. , Coleman Ilsa M. , Lucas Jared M. , Li Dapei , Hanratty Brian , Meade Hannah , Mostaghel Elahe A. , Plymate Stephen R. , Corey Eva , Haffner Michael C. , Nelson Peter S.
Published: September 2023

Supplemental Figures 1-4
Table S4 from Breast Cancer Mutations HER2V777L and PIK3CAH1047R Activate the p21–CDK4/6–Cyclin D1 Axis to Drive Tumorigenesis and Drug Resistance
Authors: Cheng Xiaoqing , Sun Yirui , Highkin Maureen , Vemalapally Nagalaxmi , Jin Xiaohua , Zhou Brandon , Prior Julie L. , Tipton Ashley R. , Li Shunqiang , Iliuk Anton , Achilefu Samuel , Hagemann Ian S. , Edwards John R. , Bose Ron
Published: September 2023

Phosphopeptides in Volcano Plot
Supplementary Data from Nanoparticle-Based Combination Therapy Enhances Fulvestrant Efficacy and Overcomes Tumor Resistance in ER-Positive Breast Cancer
Authors: Li Bozhao , Qi Feilong , Zhu Fei , Lu Zefang , Wang Meiqi , Chu Tianjiao , Wu Suying , Wei Jingyan , Song Zhenchuan , Sukumar Saraswati , Zhang Cheng , Xu Jiangfei , Li Suping , Nie Guangjun
Published: September 2023

Supporting information for manuscript
Data from A non-conserved histidine residue on KRAS drives paralog selectivity of the KRASG12D inhibitor MRTX1133
Authors: Keats Miles , Han John J.W. , Lee Yeon-Hwa , Lee Chih-Shia , Luo Ji
Published: September 2023

Abstract
MRTX1133 is the first non-covalent inhibitor against the KRASG12D mutant that demonstrated specificity and potency in pre-clinical tumor models. Here, we used isogenic cell lines expressing a single Ras allele to evaluate the selectivity of this compound. In addition to KRASG12D, MRTX1133 showed significant activity against several other KRAS mutants as well as wildtype KRAS protein. In contrast, MRTX1133 exhibited no activity against both G12D and wildtype forms of HRAS and NRAS proteins. Functional analysis revealed that the selectivity of MRTX1133 towards KRAS is associated with its binding to H95 on KRAS, a residue that is not conserved in HRAS and NRAS. Reciprocal mutation of amino acid 95 among the three Ras paralogs resulted in reciprocal change in their sensitivity towards MRTX1133. Thus, H95 is an essential selectivity handle for MRTX1133 towards KRAS. Amino acid diversity at residue 95 could facilitate the discovery of pan‐KRAS inhibitors as well as HRAS and NRAS paralog‐selective inhibitors.
Data from Mesenchymal-like Tumor Cells and Myofibroblastic Cancer-Associated Fibroblasts Are Associated with Progression and Immunotherapy Response of Clear Cell Renal Cell Carcinoma
Authors: Davidson Guillaume , Helleux Alexandra , Vano Yann A. , Lindner Véronique , Fattori Antonin , Cerciat Marie , Elaidi Reza T. , Verkarre Virginie , Sun Cheng-Ming , Chevreau Christine , Bennamoun Mostefa , Lang Hervé , Tricard Thibault , Fridman Wolf H. , Sautes-Fridman Catherine , Su Xiaoping , Plassard Damien , Keime Celine , Thibault-Carpentier Christelle , Barthelemy Philippe , Oudard Stéphane M. , Davidson Irwin , Malouf Gabriel G.
Published: September 2023

Abstract
Immune checkpoint inhibitors (ICI) represent the cornerstone for the treatment of patients with metastatic clear cell renal cell carcinoma (ccRCC). Despite a favorable response for a subset of patients, others experience primary progressive disease, highlighting the need to precisely understand the plasticity of cancer cells and their cross-talk with the microenvironment to better predict therapeutic response and personalize treatment. Single-cell RNA sequencing of ccRCC at different disease stages and normal adjacent tissue (NAT) from patients identified 46 cell populations, including 5 tumor subpopulations, characterized by distinct transcriptional signatures representing an epithelial-to-mesenchymal transition gradient and a novel inflamed state. Deconvolution of the tumor and microenvironment signatures in public data sets and data from the BIONIKK clinical trial (NCT02960906) revealed a strong correlation between mesenchymal-like ccRCC cells and myofibroblastic cancer-associated fibroblasts (myCAF), which are both enriched in metastases and correlate with poor patient survival. Spatial transcriptomics and multiplex immune staining uncovered the spatial proximity of mesenchymal-like ccRCC cells and myCAFs at the tumor–NAT interface. Moreover, enrichment in myCAFs was associated with primary resistance to ICI therapy in the BIONIKK clinical trial. These data highlight the epithelial–mesenchymal plasticity of ccRCC cancer cells and their relationship with myCAFs, a critical component of the microenvironment associated with poor outcome and ICI resistance.
Significance:
Single-cell and spatial transcriptomics reveal the proximity of mesenchymal tumor cells to myofibroblastic cancer-associated fibroblasts and their association with disease outcome and immune checkpoint inhibitor response in clear cell renal cell carcinoma.
Data from Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study
Authors: Edwards Kathryn C. , Khan Asia , Sharma Eva , Wang Lanqing , Feng June , Blount Benjamin C. , Sosnoff Connie S. , Smith Danielle M. , Goniewicz Maciej L. , Pearson Jennifer , Villanti Andrea C. , Delnevo Cristine D. , Bover-Manderski Michelle T. , Hatsukami Dorothy K. , Niaura Raymond , Everard Colm , Kimmel Heather L. , Duffy Kara , Rostron Brian L. , Del Valle-Pinero Arseima Y. , van Bemmel Dana M. , Stanton Cassandra A. , Hyland Andrew
Published: September 2023

AbstractBackground:
Sex and racial/ethnic identity-specific cut-points for validating tobacco use using Wave 1 (W1) of the Population Assessment of Tobacco and Health (PATH) Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and total nicotine equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use.
Methods:
For exclusive and polytobacco cigarette use, weighted prevalence estimates based on W4 self-report alone and with exceeding the W1 cut-point were calculated to identify the percentage missed without biochemical verification. Sensitivity and specificity of W1 cut-points on W4 self-reported tobacco use status were examined. ROC curves were used to determine the optimal W4 cut-points to distinguish past 30-day users from non-users, and evaluate whether the cut-points significantly differed from W1.
Results:
Agreement between W4 self-reported use and exceeding the W1 cut-points was high overall and when stratified by demographic subgroups (0.7%–4.4% of use was missed if relying on self-report alone). The predictive validity of using the W1 cut-points to classify exclusive cigarette and polytobacco cigarette use at W4 was high (>90% sensitivity and specificity, except among polytobacco Hispanic smokers). Cut-points derived using W4 data did not significantly differ from the W1-derived cut-points [e.g., W1 exclusive = 40.5 ng/mL cotinine (95% confidence interval, CI: 26.1–62.8), W4 exclusive = 29.9 ng/mL cotinine (95% CI: 13.5–66.4)], among most demographic subgroups.
Conclusions:
The W1 cut-points remain valid for biochemical verification of self-reported tobacco use in W4.
Impact:
Findings from can be used in clinical and epidemiologic studies to reduce misclassification of cigarette smoking status.
Data from Predicted Proteome Association Studies of Breast, Prostate, Ovarian, and Endometrial Cancers Implicate Plasma Protein Regulation in Cancer Susceptibility
Authors: Gregga Isabelle , Pharoah Paul D. P. , Gayther Simon A. , Manichaikul Ani , Im Hae Kyung , Kar Siddhartha P. , Schildkraut Joellen M. , Wheeler Heather E.
Published: September 2023

AbstractBackground:
Predicting protein levels from genotypes for proteome-wide association studies (PWAS) may provide insight into the mechanisms underlying cancer susceptibility.
Methods:
We performed PWAS of breast, endometrial, ovarian, and prostate cancers and their subtypes in several large European-ancestry discovery consortia (effective sample size: 237,483 cases/317,006 controls) and tested the results for replication in an independent European-ancestry GWAS (31,969 cases/410,350 controls). We performed PWAS using the cancer GWAS summary statistics and two sets of plasma protein prediction models, followed by colocalization analysis.
Results:
Using Atherosclerosis Risk in Communities (ARIC) models, we identified 93 protein–cancer associations [false discovery rate (FDR) < 0.05]. We then performed a meta-analysis of the discovery and replication PWAS, resulting in 61 significant protein–cancer associations (FDR < 0.05). Ten of 15 protein–cancer pairs that could be tested using Trans-Omics for Precision Medicine (TOPMed) protein prediction models replicated with the same directions of effect in both cancer GWAS (P < 0.05). To further support our results, we applied Bayesian colocalization analysis and found colocalized SNPs for SERPINA3 protein levels and prostate cancer (posterior probability, PP = 0.65) and SNUPN protein levels and breast cancer (PP = 0.62).
Conclusions:
We used PWAS to identify potential biomarkers of hormone-related cancer risk. SNPs in SERPINA3 and SNUPN did not reach genome-wide significance for cancer in the original GWAS, highlighting the power of PWAS for novel locus discovery, with the added advantage of providing directions of protein effect.
Impact:
PWAS and colocalization are promising methods to identify potential molecular mechanisms underlying complex traits.
Supplementary Material and Methods S1 from A Bifunctional PARP-HDAC Inhibitor with Activity in Ewing Sarcoma
Authors: Ramos Louise , Truong Sarah , Zhai Beibei , Joshi Jay , Ghaidi Fariba , Lizardo Michael M. , Shyp Taras , Kung Sonia H.Y. , Rezakhanlou Alireza M. , Oo Htoo Zarni , Adomat Hans , Le Bihan Stephane , Collins Colin , Bacha Jeffrey , Brown Dennis , Langlands John , Shen Wang , Lallous Nada , Sorensen Poul H. , Daugaard Mads
Published: September 2023

Materials and methods for in vivo toxicity and cellular fluorescence assays
Supplementary Table S4 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: September 2023

Supplementary Table S4. Cluster marker genes of the Myeloid cell populations.
Supplementary Table S2 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: September 2023

Supplementary Table S2. Spatial TME1 (STME1) and TME2 (STME2) gene signatures.
Supplementary Figure S8 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: September 2023

Supplementary Figure S8. Additional MPNST analyses for CDK4/6-MEK inhibition plus anti-PD-L1 therapy study.
Supplementary Figure S3 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: September 2023

Supplementary Figure S3. Tumor growth kinetics of individual de novo MPNSTs during therapy
Supplementary Figure S2 from A Phase I/II Trial of HER2 Vaccine–Primed Autologous T-Cell Infusions in Patients with Treatment Refractory HER2–Overexpressing Breast Cancer
Authors: Disis Mary L. , Dang Yushe , Coveler Andrew L. , Childs Jennifer S. , Higgins Doreen M. , Liu Ying , Zhou Jing , Mackay Sean , Salazar Lupe G.
Published: September 2023

Overall survival in relation to clinical response in individual patient after T cell infusions.
Table S3 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

Pharmacokinetic properties of LY3214996 and abemaciclib
Figure S5 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

CSF1R Mouse IHC, CSF1R and STK10 Western Blot, CDK6 Human, phospho-Rb (S807/811) Human, and pRSK1 (S380) Human IHC
Figure S10 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

Western Blots