bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonminimum Phase Zeros of Multi-Degrees-of-Freedom Damped Flexible Systems
Authors: Rath Siddharth , Radgolchin Moeen , Maheshwari Arunav , Awtar Shorya 
Published: January 2025

Abstract
This article investigates the nonminimum phase (NMP) zeros in the transfer function, between actuated load input and measured displacement output, of a multi-degrees-of-freedom (DoF) flexible system in the presence of proportional viscous damping. NMP zeros have a negative impact on the dynamics and control of flexible systems and therefore are generally undesirable. Viscous damping is one potential means to guarantee that no NMP zeros exist in the system. However, the impact of viscous damping on NMP zeros of multi-DoF flexible systems is not adequately studied or understood in the literature. To address this gap, a change of variable method is used to first establish a simple mathematical relationship between the zeros of a multi-DoF undamped flexible system and its proportionally damped counterpart. The “proportional” viscous damping model is used due to its practical amenability, conceptual simplicity, and ease of application. This mathematical relationship (between zeros of an undamped system and its damped counterpart) is used to derive the necessary and sufficient condition for the absence of NMP zeros in proportionally damped flexible systems. A graphical analysis of this necessary and sufficient condition is provided, which leads to the formulation of simple proportional damping strategies. A case study of a 4DoF flexible system is presented to demonstrate how a proportional viscous damping strategy can be used to simultaneously guarantee the absence of NMP zeros in multiple single-input single-output (SISO) transfer functions of a multi-DoF flexible system.
Sensing of SARS-CoV-2-infected cells by plasmacytoid dendritic cells is modulated via an interplay between CD54/ICAM-1 and CD11a/LFA-1 α
L
integrin
Authors: Cai ChenRongRong , Pham Tram N. Q. , Adam Damien , Brochiero Emmanuelle , Cohen Éric A. 
Published: January 2025

ABSTRACT

SARS-CoV-2 infection induces interferon (IFN) response by plasmacytoid dendritic cells (pDCs), but the underlying mechanisms are poorly defined. Here, we show that the bulk of the IFN-I release comes from pDC sensing of infected cells and not cell-free virions. Physical contact (or conjugates) between pDCs and infected cells is mediated through CD54-CD11a engagement, and such conjugate formation is required for efficient IFN-I production. Interestingly, CD11a is inducible on infected epithelial cells when they are co-cultured with PBMCs, thus allowing for potentially bidirectional cross-talks between CD54 and CD11a, which further amplify the sensing. SARS-CoV-2 variants of concern (VOCs) are sensed less efficiently than the Wuhan ancestral strain (LSPQ1), but the mechanisms driving the defect are different among the VOCs. CD11a induction on infected cells is correlated with their ability to form cell conjugates with pDCs. Impaired sensing of the Alpha variant is linked to reduced CD11a induction on infected cells and to fewer conjugates formed with pDCs. Collectively, our findings provide new insights into how SARS-CoV-2-infected cells are sensed by pDCs and reveal that this process is targeted by some VOCs to limit IFN-I production.

IMPORTANCE
Type I interferons (IFN-I) represent an important component of the host’s innate defense against initial SARS-CoV-2 infections. Plasmacytoid dendritic cells (pDCs) produce large quantities of IFN-I upon recognition of viral particles or infected cells. This study shows that pDCs sense infected cells more efficiently than viral particles, leading to a higher production of IFN-I. Physical contact between a pDC and an infected cell is critical to this process; the interaction is mediated via CD11a and ICAM-1 complex and potentially is bidirectional. SARS-CoV-2 variants of concern (VOCs) have evolved to limit the IFN response through different mechanisms. For the Alpha variant, reduced level of CD11a on infected cells is linked to less contact with pDCs and decreased IFN-I release. Overall, our study characterizes some of the early steps involved in pDC-mediated response against SARS-CoV-2 infection and shows that these processes are targeted by VOCs to likely limit IFN-I response and enhance viral spread.
Genome sequence data of
Bacillus spizizenii
GM2: a lipopeptide producer
Authors: Lutfullina Guzel , Pudova Daria , Lutfullin Marat , Nikolaeva Anastasia , Abubakirova Adela , Akosah Yaw , Shagimardanova Elena , Sharipova Margarita , Mardanova Ayslu 
Published: January 2025

ABSTRACT

We present the findings from the genome-sequencing project of
Bacillus spizizenii
GM2, sourced from rhizospheric soil and renowned for its lipopeptide production. The genome spans 4,216,713 base pairs with an average G + C content of 43,6%.
Complete genome sequence of the first
Capnocytophaga canimorus
strain isolated from a red fox (
Vulpes vulpes
) in Germany
Authors: Kuhnert Peter , Brodard Isabelle , Jores Joerg 
Published: January 2025

ABSTRACT

The zoonotic pathogen
Capnocytophaga canimorsus
is part of the oral microbiome of dogs and cats. We report the genome sequence of strain KM3195_24, isolated from a red fox. It has a circular genome of 2,718,701 bp with a G + C content of 36%, 2,419 CDS, 3 rRNA operons, and 45 tRNAs.
Group a
Streptococcus
remains viable inside fibrin clots and gains access to human plasminogen for subsequent fibrinolysis and dissemination
Authors: Vu Henry M. , Moran Thomas E. , Liang Zhong , Bao Yun-Juan , Carles Paulina G. , Keane Jessica C. , Cerney Madelyn G. , Dahnke Caitlyn N. , Flores-Mireles Ana L. , Ploplis Victoria A. , Castellino Francis J. , Lee Shaun W. 
Published: January 2025

ABSTRACT

Group A
Streptococcus
(GAS) is a major human pathogen that causes several invasive diseases including necrotizing fasciitis. The host coagulation cascade initiates fibrin clots to sequester bacteria to prevent dissemination into deeper tissues. GAS, especially skin-tropic bacterial strains, utilize specific virulence factors, plasminogen binding M-protein (PAM) and streptokinase (SK), to manipulate hemostasis and activate plasminogen to cause fibrinolysis and fibrin clot escape. A major unresolved question regards the temporal dynamics of how GAS enmeshed in a fibrin clot can access plasminogen for clot dissolution and eventual dissemination. Here, we reveal through live imaging studies that GAS trapped inside a fibrin clot can remain viable in a latent state, until access to plasminogen activates fibrinolysis and dissemination. RNA-sequencing (RNA-seq) analysis shows marked changes in the wild-type (WT)-GAS transcriptome from the time bacteria were enmeshed inside the clot (4 h) to when dissemination was initiated (8 h). To gain a more fully realized model of how GAS trapped in fibrin clots can disseminate in the blood system, we utilized a novel 3D endothelial microfluidic device to demonstrate that GAS is fully capable of fibrinolysis in an endothelial environment, revealing a major underappreciated route by which GAS may cause more invasive outcomes. Our findings reveal for the first time that GAS can engage a latent, growth-suspended phase whereby physical structures such as fibrin clots that immobilize an invading pathogen allow bacteria to remain viable until sufficient access to plasminogen allows it to initiate fibrinolysis and escape into surrounding blood system and tissues.

IMPORTANCE
Group A Streptococcus (GAS) is a human-specific bacterial pathogen that causes infections ranging in severity from mild to severe infections that can often be fatal. To protect the host, the innate immune system creates fibrin clots to trap bacteria and prevent deeper spread. GAS produces several factors that can initiate the dissolution of these fibrin clots to spread to deeper tissues, but we lack specific understanding of the timing of these events. Our studies demonstrate for the first time that GAS can delay their escape from fibrin clots to gain access to deeper tissues during infection, suggesting a key strategy that GAS utilize to cause more invasive disease.
Wannabe Bounded Treewidth Graphs Admit a Polynomial Kernel for Directed Feedback Vertex Set
Authors: Lokshtanov Daniel , Ramanujan Maadapuzhi-Sridharan , Saurabh Saket , Sharma Roohani , Zehavi Meirav 
Published: January 2025

In the
Directed Feedback Vertex Set (DFVS)
problem, given a digraph
D
and a positive integer
k
, the goal is to check if there exists a set of at most
k
vertices whose deletion from
D
results in a directed acyclic graph. The existence of a polynomial kernel for
DFVS
, parameterized by the solution size
k
, is a central open problem in kernelization. In this article, we give a polynomial kernel for
DFVS
parameterized by
k
plus
the size of a treewidth-η modulator (of the underlying undirected graph), where η is any fixed positive integer. Since the status of the existence of a polynomial kernel for
DFVS
(parameterized by the solution size) has been open for a very long time now, and it is known to not admit a polynomial kernel when the parameter is the size of a treewidth-2 modulator, solution size plus the size of the treewidth-η modulator makes for an interesting choice of parameter to study. In fact, the polynomial kernelization complexity of
DFVS
parameterized by the size of the undirected feedback vertex set (treewidth-1 modulator) in the underlying undirected graph has already been studied in literature. Our choice of parameter strictly encompasses previous positive kernelization results on
DFVS
. Our result is based on a novel application of the tool of
important separators
embedded in state-of-the-art machinery such as protrusion decompositions.
Imperatorin’s Effect on Myocardial Infarction Based on Network Pharmacology and Molecular Docking
Authors: Zhang Ruizhe , Wang Peng , Jin Yao , Xie Qingya , Xiao Pingxi 
Published: January 2025

Purpose: Myocardial infarction (MI), a severe cardiovascular disease, is the result of insufficient blood supply to the myocardium. Despite the improvements of conventional therapies, new approaches are needed to improve the outcome post‐MI. Imperatorin is a natural compound with multiple pharmacological properties and potential cardioprotective effects. Therefore, this work investigated imperatorin’s therapeutic effects and its mechanism of action in an MI mouse model.Methods: Network pharmacology, molecular docking, and experimental validation were performed for exploring the pharmacokinetic properties, therapeutic effects, and molecular targets of imperatorin in MI. Permanent ligation of the left anterior descending artery was performed in male C57BL/6 mice to induce MI before treatment with imperatorin once per day for 1 week. Echocardiography, heart histology, RNA sequencing, and quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR) as well as western blotting were carried out for evaluating cardiac function and structure, as well as gene and protein expression.Results: Imperatorin significantly improved cardiac function, preserved cardiac structure, attenuated cardiac remodeling and fibrosis, and reduced cardiomyocyte apoptosis in MI mice. Eight differentially expressed genes overlapping with key target genes were found, two upregulated and six downregulated. A key target in signaling pathways associated with imperatorin effect in MI was angiotensin‐converting enzyme (ACE). Imperatorin inhibited ACE–angiotensin II (Ang II)–angiotensin II Type 1 receptor (AT1R) axis in MI mice.Conclusion: Imperatorin attenuated MI by inhibiting the ACE–Ang II–AT1R axis. Thus, imperatorin might be considered a potential therapeutic agent to cure MI.
Therapeutic Efficacy of Reward Circuit‐Targeted Transcranial Magnetic Stimulation (TMS) on Suicidal Ideation in Depressed Patients: A Sham‐Controlled Trial of Two TMS Protocols
Authors: Huang Xinyu , Xi Chunhua , Fang Ya , Ye Rong , Wang Xin , Zhang Shu , Cui Yuqiu , Guo Yang , Zhang Jingyi , Ji Gong-Jun , Zhu Chunyan , Luo Yuejia , Chen Xiaofen , Wang Kai , Tian Yanghua , Yu Fengqiong 
Published: January 2025

Background: Suicide is one of the leading causes of premature death, and dysfunctional reward processing may serve as a potential mechanism. However, effective treatment targeting reward circuits is rarely reported.Objective: The present study investigated the therapeutic efficacy of two individualized protocols, repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), targeting the left dorsolateral prefrontal cortex (lDLPFC)–nucleus accumbens (NAcc) circuit on suicidal ideation among patients with major depressive disorder (MDD).Methods: Here, 40 healthy controls (HCs) and 70 MDD patients (MDDs) were recruited for this double‐blinded, sham‐controlled clinical trial. The reward learning process during the Iowa gambling task (IGT) was initially measured at the baseline. Further, 62 MDDs were assigned to receive 15 daily sessions of individualized rTMS (n = 25), iTBS (n = 15), or sham treatment (n = 22) to the site of strongest lDLPFC–NAcc connectivity.Results: We found MDDs demonstrated abnormalities in both IGT performance and reward‐associated event‐related potential (ERP) components compared to HCs. MDDs in the rTMS and iTBS groups showed significant improvements in suicidal ideation and anhedonia symptoms compared to the sham group. The rTMS group also exhibited a more negative‐going N170 and feedback‐related negativity (FRN) after treatment, and the increase in N170 absolute amplitude posttreatment showed a trend of correlation with improved Temporal Experience Pleasure Scales (TEPSs) and TEPS‐anticipatory (TEPS‐ant) scores.Conclusion: The current study indicates that reward circuit‐based rTMS and iTBS showed comparable antisuicidal effects in depressive patients, suggesting that the lDLPFC–NAcc pathway may serve as a potential treatment target.Trial Registration: ClinicalTrials.gov identifier: NCT03991572
Investigating the Multidomain Impact of Palliative Care on End‐of‐Life Patients: A Comprehensive Evaluation
Authors: Abu Hasheesh Mohammad O. 
Published: January 2025

Background: Palliative care is recognized for its holistic approach in improving the quality of life for patients and their families, focusing on pain relief, symptom management, and addressing emotional, social, and spiritual needs. However, the field is evolving due to increasing demand for these specialized services, emphasizing the need for the ongoing research into palliative care practices.Research Purpose: Is to investigate the multidomain impact of palliative care on end‐of‐life patients and evaluate their effectiveness on these domains.Method: A quantitative descriptive design was adopted for conducting the current study. Approval obtained from a designated hospital in Amman, Jordan, and official permission to carry out the study. The study’s participants consisted primarily of physicians and nurses who were involved in providing care to terminally ill patients. The research tool employed in this study is a standardized palliative care assessment that was used in Australia, with modifications based on the literature review. The validity and reliability of the adapted tool have been ensured through rigorous testing procedures.Results: Findings indicated that the implementation of standardized practical palliative care exhibited an average level across all domains, specifically, the spiritual domain received the highest mean score (1.80), while the structural domain had the lowest (1.69). There were significant differences in palliative care provision across specialized work sites, with radiotherapy and blood disease sites scoring higher (M = 2.04 and M = 1.87, respectively). Educational levels significantly influenced care perceptions, favoring BSc holders. Age did not significantly affect palliative care provision, probably because of standardized care protocols and sample size. In addition, nurses rated palliative care higher than physicians, likely due to their more direct patient involvement.Conclusion: In light of the results, it is evident that there is a pressing need to consistently evaluate the healthcare services offered to meet the needs of the increasing population of terminally ill patients.
Conquering Overtreatment of DCIS: Lessons from PRECISION
Authors: Bhattacharjee Proteeti , Lips Esther H. , Sawyer Elinor J. , Hwang E. Shelley , Thompson Alastair M. , Wesseling Jelle ,   the Cancer Grand Challenges PRECISION Consortium, Behbod Fariba , Bhattacharjee Proteeti , Collyar Deborah , Davies Helen , Futreal Andrew , Hwang E. Shelley , Jonkers Jos , Lips Esther H. , Navin Nicholas , Nik-Zainal Serena , Pinto Donna , Rea Daniel , Sawyer Elinor J. , Schmidt Marjanka , Stobart Hilary , Thompson Alastair , van Oirsouw Marja , van Rheenen Jacco , Verschuur Ellen , Wesseling Jelle , Wessels Lodewyk F.A. 
Published: January 2025

Summary:
As we cannot reliably distinguish indolent, low-risk ductal carcinoma in situ (DCIS) from potentially progressive, high-risk DCIS, all women with DCIS diagnosis undergo intensive treatment without any benefit. The PREvent ductal Carcinoma In Situ Invasive Overtreatment Now team was established to unravel DCIS biology and develop new multidisciplinary approaches for accurate risk stratification to tackle the global problem of DCIS overdiagnosis and overtreatment.
See related article by Bressan et al., p. 16
See related article by Stratton et al., p. 22
See related article by Goodwin et al., p. 34
Atypical Small Cell Lung Cancer: A New Malignancy Characterized by Chromothripsis, Carcinoid Tumors, and Wild-type RB1 and TP53
Authors: Nadeem Urooba , Drapkin Benjamin J. 
Published: January 2025

Summary:
Small cell lung cancer (SCLC) and pulmonary carcinoid tumors are traditionally seen as unrelated, with SCLC linked to smoking and characterized by biallelic loss of RB1 and TP53 and rapid progression. Rekhtman and colleagues upend these assumptions by discovering an “atypical” SCLC that arises in nonsmokers with intact RB1 and TP53 loci, chromothripsis-induced oncogene amplifications on extrachromosomal DNA, and frequent synchronous carcinoid tumors.
See related article by Rekhtman et al., p. 83
Peto’s Paradox Is Dead. Long Live Peto’s Paradox
Authors: Metzger Michael J. 
Published: January 2025

Summary:
In this issue, Compton and colleagues report the prevalence of neoplasia and malignant cancer in 292 species, based on 16,049 necropsy records, shedding light on susceptibility to cancer and the evolution of mechanisms that protect against cancer across a broad array of vertebrates.
See related article by Compton et al., p. 227
Increased Clonal Hematopoiesis in Long-term Survivors of Pediatric Hematopoietic Cell Transplantation
Authors: Müskens Konradin F. , Wieringa Nienke , van Bergen Maaike G.J.M. , Bense Joëll E. , te Pas Brigit M. , de Pagter Anne P.J. , Lankester Arjan C. , Bierings Marc B. , Neuberg Donna S. , Haitjema Saskia , Kremer Leontien C.M. , Huls Gerwin A. , Nierkens Stefan , Jansen Joop H. , Lindemans Caroline A. , de Graaf Aniek O. , Belderbos Mirjam E. 
Published: January 2025

Abstract
In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. In this study, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 nontransplanted controls. CH was detected in 16% of HCT recipients and 8% of controls at variant allele frequencies of 0.01 to 0.31. Mutations were predominantly in DNMT3A (80%) and TET2 (20%). Older hematopoietic age (OR: 1.07; P &lt; 0.001) and the HCT procedure (OR: 2.53; P = 0.02) independently increased the risk of CH, indicating both aging- and transplantation-induced effects. Large clones (variant allele frequency &gt;0.10) were found exclusively in HCT recipients. Notably, CH was also detected within 15 years after a cord blood HCT. Inflammatory processes around graft infusion were associated with CH presence. Future studies are required to track the evolution of posttransplant CH and its impact on future cardiovascular diseases, second malignancies, and overall survival.

Significance:
As survival of HCT recipients continues to improve, late treatment effects gain importance. We demonstrate that pediatric HCT recipients show increased risk of CH compared with age-matched controls. Prospective studies are crucial to understand the clinical implications of posttransplant CH in this young population.
Loss of NF1 Accelerates Uveal and Intradermal Melanoma Tumorigenesis, and Oncogenic GNAQ Transforms Schwann Cells
Authors: Longakit Anne Nathalie , Urtatiz Oscar , Luty Amy , Zhang Christina , Hess Chloe , Yoo Alyssa , Bourget Hannah , Van Raamsdonk Catherine D. 
Published: January 2025

Abstract
NF1 encodes the multifunctional tumor suppressor protein, neurofibromin, which is best known for its causative role in neurofibromatosis type 1 and in regulating MAPK signaling. Neurofibromin, in a context-specific manner, is involved in various tumorigenic processes, including those in melanocytes. This study investigated whether NF1 loss can collaborate with oncogenic GNAQ to promote melanoma in the dermis or eyes, in which the Gαq pathway is almost always activated. We found that heterozygous 17q11.2 loss that includes the NF1 locus is a recurrent phenomenon in human intradermal and uveal melanomas described in the literature. We studied the effects of Nf1 haploinsufficiency in mice expressing oncogenic GNAQQ209L in melanocytes and Schwann cells of peripheral nerves using the Plp1-creERT transgene with tamoxifen at 5 weeks of age. Nf1 haploinsufficiency accelerated melanoma formation and/or growth. RNA sequencing analysis found significant pathways related to cAMP signaling and myogenesis. In addition, 20% of the differentially expressed genes were homologous to genes for which expression correlates with prognosis in human uveal melanoma. Unexpectedly, we found that GNAQQ209L alone was sufficient to drive cutaneous nerve sheath tumors, with one GNAQQ209L-expressing Nf1 haploinsufficient mouse also developing a plexiform variant. These tumors strongly resembled neurofibromas. We searched the cBioPortal for Cancer Genomics database and found plexiform neurofibromas with the GNAQT96S hotspot mutation. The Plp1-creERT; GNAQQ209L model with tamoxifen at 5 weeks may be useful as a preclinical model for neurofibroma. Our studies emphasize the importance of GNAQ and NF1 in regulating neural crest–derived cells existing in a dermal-like environment.

Significance:
These results indicate that NF1 loss in intradermal and uveal melanomas is a potentially significant finding. They emphasize the importance of neurofibromin in cAMP signaling. They show for the first time that oncogenic GNAQ can transform Schwann cells in mice. The Plp1-creERT transgene with tamoxifen given at 5 weeks may be a particularly good strategy for modeling cutaneous neurofibroma and plexiform neurofibroma.