bluuebunny/crossref_metadata_2025_split huggingface dataset:
Permutations and the divisor graph of [1,n]
Authors: McNew Nathan 
Published: December 2022

AbstractLet denote the set of permutations π ofnsuch that for each either or . These permutations can also be viewed as vertex‐disjoint directed cycle covers of the divisor graph on vertices with an edge between and if or . We improve on recent results of Pomerance by showing exists and that . We also obtain similar results for the set of permutations where for allj. The results rely on a graph theoretic result bounding the number of vertex‐disjoint directed cycle covers, which may be of independent interest.
Improving Simulation to Hardware Correlation of Autonomous Vehicles Operating on Low Friction Surfaces
Authors: Spike Nathan , Kurup Akhil , Chopp Derek , Bos Jeremy , Robinette Darrell 
Published: December 2022

Abstract
Simulation is a critical step in the development of autonomous driving technologies, allowing engineers to test control algorithms, path planners, and other dynamic vehicle behaviors in a risk-free, low-cost environment. Under normal driving conditions representative of paved, most vehicle models are suitable for accurate prediction of vehicle motion. On low friction surfaces, basic vehicle models do not display the variability in vehicle response to steering input that is observed on real-world low friction surfaces such as clear ice. This work presents distribution parameters for a stochastic friction grid map for use in simulating vehicle behavior on icy surfaces. Simulation data from rapid double lane changes are compared with vehicle response to the same paths on an ice rink test course. Strong correlation between the simulation and test vehicle is achieved with validation performed using previously developed control and path planning methods.
Atangana–Baleanu Semilinear Fractional Differential Inclusions With Infinite Delay: Existence and Approximate Controllability
Authors: Williams W. Kavitha , Vijayakumar V. , Nisar Kottakkaran Sooppy , Shukla Anurag 
Published: December 2022

Abstract
The main focus of this paper is centered around approximate controllability results of Atangana–Baleanu fractional differential systems with infinite delay. Using principles and ideas from the theory of multivalued maps, fractional calculus, and Bohnenblust–Karlin fixed point techniques, the key findings are established. We begin by emphasizing the existence of mild solutions, and then demonstrate the approximate controllability of the Atangana–Baleanu fractional control system. We then apply our findings to the theory of the neutral system.
Frequency-Energy Analysis of Coupled Linear Oscillator With Unsymmetrical Nonlinear Energy Sink
Authors: Al-Shudeifat Mohammad A. 
Published: December 2022

Abstract
The underlying nonlinear dynamical behavior of a linear oscillator (LO) attached with nonlinear energy sink (NES) is usually revealed by studying the LO-NES system on the frequency-energy plot (FEP). Accordingly, different kinds of periodic motions on the backbone curves of the nonlinear normal modes (NNMs) and their associated subharmonic branches are analyzed. Here, the considered unsymmetrical nonlinear energy sink (UNES) incorporates a cubic stiffness element in one direction of the motion and a weak linear restoring coupling stiffness in both directions of the motion. This UNES is attached with the LO in the LO-UNES system which is studied here on the FEP. Therefore, the obtained FEP of the LO-UNES system is generated and analyzed. Accordingly, several unsymmetrical backbone curves of periodic oscillations between the UNES mass and the LO mass at 1:1 resonance have been obtained for broad range of nonlinear frequency levels.
Detrital glass in a Bering Sea sediment core yields a ca. 160 ka Marine Isotope Stage 6 age for Old Crow tephra
Authors: Reyes Alberto V. , Jensen Britta J.L. , Woudstra Shaun H. , Bolton Matthew S.M. , Buryak Serhiy D. , Cook Mea S. , Harvey Jordan , Westgate John A. 
Published: December 2022

Abstract
For decades, the Old Crow tephra has been a prominent stratigraphic marker for the onset of Marine Isotope Stage (MIS) 5e, the last interglaciation, in subarctic northwest North America. However, new zircon U-Pb dates for the tephra suggest that the tephra was deposited ca. 207 ka during MIS 7, with wide-ranging implications for chronologies of glaciation, paleoclimate, relict permafrost, and phylogeography. We analyzed ~1900 detrital glass shards from 28 samples collected at Integrated Ocean Drilling Program Site U1345 in the Bering Sea, which has a well-constrained age model from benthic foraminiferal δ18O. Except for one possibly contaminant shard dated at 165 ka, Old Crow tephra was absent from all samples spanning 220–160 ka. Old Crow tephra appeared abruptly at 157 ka, comprising &gt;40% of detrital shards between 157 and 142 ka. This abrupt increase in the concentration of detrital Old Crow tephra, its absence in earlier intervals, and its presence at low concentrations in all samples between 134 and 15 ka collectively indicate that the tephra was deposited during the middle of MIS 6 with a likely age of 159 ± 8 ka. As a result, the late Quaternary chronostratigraphic framework for unglaciated northwest North America remains intact, and the timing of key events in the region (e.g., bison entry into North America; interglacial paleoclimate; permafrost history; the penultimate glaciation) does not require wholesale revision.
Metformin in pregnancy and risk of abnormal growth outcomes at birth: a register-based cohort study
Authors: Brand Kerstin MG , Thoren Robyn , Sõnajalg Jaak , Boutmy Emmanuelle , Foch Caroline , Schlachter Judith , Hakkarainen Katja M , Saarelainen Laura 
Published: December 2022

IntroductionWe previously reported an increased risk of being small for gestational age (SGA) and a decreased risk of being large for gestational age (LGA) after in utero exposure to metformin compared with insulin exposure. This follow-up study investigated if these observations remain when metformin exposure (henceforth, metformin cohort) is compared with non-pharmacological antidiabetic treatment of gestational diabetes mellitus (GDM; naïve cohort), instead of insulin.Research design and methods This was a Finnish population register-based cohort study from singleton children born during 2004–2016. Birth outcomes from metformin cohort (n=3964) and the naïve cohort (n=82 675) were used in the main analyses. Additional analyses were conducted in a subcohort, restricting the metformin cohort to children of mothers with GDM only (n=2361). Results were reported as inverse probability of treatment weighted OR (wOR), with the naïve cohort as reference.Results  No difference was found for the outcome of SGA between the cohorts in the main analyses (wOR 0.97, 95% CI 0.73 to 1.27) or in the additional analyses (wOR 1.01, 95% CI 0.75 to 1.37). No difference between the cohorts was found for the risk of LGA (wOR 0.91, 95% CI 0.75 to 1.11) in the main analyses but a decreased risk was observed in the additional analyses (wOR 0.72, 95% CI 0.56 to 0.92).Conclusions This follow-up study found no increase in the risk of SGA or LGA after in utero exposure to metformin, compared with drug-naïve GDM. The decreased risk of LGA in mothers with GDM may suggest residual confounding. The lack of increased SGA risk aligns with findings from studies using metformin in non-diabetic pregnancies. In contrast, lower birth weight and increased SGA birth risk were observed in GDM pregnancies for metformin versus insulin. Metformin should be avoided with emerging growth restriction in utero. The interplay of intrauterine hyperglycemia and pharmacological treatments needs further assessment.
Effects of prevention programmes on injury risk in military personnel: a
systematic review with meta-analysis
Authors: Bunn Priscila Dos Santos , Sodré R d S , Matos M I , Saliba G F , Silva G d P , Caldas R , Esteves J d S , Silva E B 
Published: December 2022

Introduction
Exercise programmes have been used to prevent injuries in military
personnel, as they can reduce modifiable risk factors for injuries. Our
aim was to review the literature to evaluate the effects of different
exercise protocols on the prevention of injuries in military
personnel.

Methods
A systematic literature review examined the effects of different
exercise protocols on the prevention of musculoskeletal injuries in the
military. Several databases were explored to find experimental studies
that investigated the effects of prevention programmes on the risk of
injury. We have extracted from the studies: profile of participants,
sample size, study design and characteristics of the control group (CG),
the type of intervention and the relative risk (RR) in the experimental
group and CG, with their significance levels. For data analysis, we used
the RevMan V.5.3 software. The measure of RR was investigated. The risk
of publication bias was analysed with Begg’s test.

Results
A total of 13 694 titles and studies were recovered from the
databases and by manual search. After the removal of duplicate titles
and studies that did not meet the eligibility criteria, 17 studies were
selected. The protocols were composed of neuromuscular training,
stretching, agility training or combined exercises. The meta-analysis
showed that injury prevention exercise programmes reduced the risk of
musculoskeletal injuries in military personnel by 14% (RR=0.86; 95%
CI=0.76 to 0.98).

Conclusion
Injury prevention exercise programmes promoted a slight reduction in
the risk of musculoskeletal injuries in military personnel.

Level of evidence
Very low.

Trial registration number
CRD 42017077946.
GPC2 antibody–drug conjugate reprograms the neuroblastoma immune milieu to enhance macrophage-driven therapies
Authors: Pascual-Pasto Guillem , McIntyre Brendan , Shraim Rawan , Buongervino Samantha N , Erbe Amy K , Zhelev Doncho V , Sadirova Shakhnozakhon , Giudice Anna M , Martinez Daniel , Garcia-Gerique Laura , Dimitrov Dimiter S , Sondel Paul M , Bosse Kristopher R 
Published: December 2022

BackgroundAntibody–drug conjugates (ADCs) that deliver cytotoxic drugs to tumor cells have emerged as an effective and safe anticancer therapy. ADCs may induce immunogenic cell death (ICD) to promote additional endogenous antitumor immune responses. Here, we characterized the immunomodulatory properties of D3-GPC2-PBD, a pyrrolobenzodiazepine (PBD) dimer-bearing ADC that targets glypican 2 (GPC2), a cell surface oncoprotein highly differentially expressed in neuroblastoma.MethodsADC-mediated induction of ICD was studied in GPC2-expressing murine neuroblastomas in vitro and in vivo. ADC reprogramming of the neuroblastoma tumor microenvironment was profiled by RNA sequencing, cytokine arrays, cytometry by time of flight and flow cytometry. ADC efficacy was tested in combination with macrophage-driven immunoregulators in neuroblastoma syngeneic allografts and human patient-derived xenografts.ResultsThe D3-GPC2-PBD ADC induced biomarkers of ICD, including neuroblastoma cell membrane translocation of calreticulin and heat shock proteins (HSP70/90) and release of high-mobility group box 1 and ATP. Vaccination of immunocompetent mice with ADC-treated murine neuroblastoma cells promoted T cell-mediated immune responses that protected animals against tumor rechallenge. ADC treatment also reprogrammed the tumor immune microenvironment to a proinflammatory state in these syngeneic neuroblastoma models, with increased tumor trafficking of activated macrophages and T cells. In turn, macrophage or T-cell inhibition impaired ADC efficacy in vivo, which was alternatively enhanced by both CD40 agonist and CD47 antagonist antibodies. In human neuroblastomas, the D3-GPC2-PBD ADC also induced ICD and promoted tumor phagocytosis by macrophages, which was further enhanced when blocking CD47 signaling in vitro and in vivo.ConclusionsWe elucidated the immunoregulatory properties of a GPC2-targeted ADC and showed robust efficacy of combination immunotherapies in diverse neuroblastoma preclinical models.
Anti-TGF-β/PD-L1 bispecific antibody promotes T cell infiltration and exhibits enhanced antitumor activity in triple-negative breast cancer
Authors: Yi Ming , Wu Yuze , Niu Mengke , Zhu Shuangli , Zhang Jing , Yan Yongxiang , Zhou Pengfei , Dai Zhijun , Wu Kongming 
Published: December 2022

BackgroundAgents blocking programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have been approved for triple-negative breast cancer (TNBC). However, the response rate of anti-PD-1/PD-L1 is still unsatisfactory, partly due to immunosuppressive factors such as transforming growth factor-beta (TGF-β). In our previous pilot study, the bispecific antibody targeting TGF-β and murine PD-L1 (termed YM101) showed potent antitumor effect. In this work, we constructed a bispecific antibody targeting TGF-β and human PD-L1 (termed BiTP) and explored the antitumor effect of BiTP in TNBC.MethodsBiTP was developed using Check-BODYTMbispecific platform. The binding affinity of BiTP was measured by surface plasmon resonance, ELISA, and flow cytometry. The bioactivity was assessed by Smad and NFAT luciferase reporter assays, immunofluorescence, western blotting, and superantigen stimulation assays. The antitumor activity of BiTP was explored in humanized epithelial-mesenchymal transition-6-hPDL1 and 4T1-hPDL1 murine TNBC models. Immunohistochemical staining, flow cytometry, and bulk RNA-seq were used to investigate the effect of BiTP on immune cell infiltration.ResultsBiTP exhibited high binding affinity to dual targets. In vitro experiments verified that BiTP effectively counteracted TGF-β-Smad and PD-L1-PD-1-NFAT signaling. In vivo animal experiments demonstrated that BiTP had superior antitumor activity relative to anti-PD-L1 and anti-TGF-β monotherapy. Mechanistically, BiTP decreased collagen deposition, enhanced CD8+T cell penetration, and increased tumor-infiltrating lymphocytes. This improved tumor microenvironment contributed to the potent antitumor activity of BiTP.ConclusionBiTP retains parent antibodies’ binding affinity and bioactivity, with superior antitumor activity to parent antibodies in TNBC. Our data suggest that BiTP might be a promising agent for TNBC treatment.
Double and multiple bangs at tau neutrino telescopes
Authors: Huang Guo-yuan 
Published: December 2022

AbstractIn light of the exciting campaign of cosmogenic neutrino detection, we investigate the double and multiple tau bangs detectable at future tau neutrino telescopes. Such events are expected from the Standard Model (SM) higher-order processes, which can be easily identified with broad techniques anticipated at future tau neutrino telescopes. We find that SM perturbative processes can already contribute observable double-bang events to telescopes with a sensitivity of collecting$${\mathcal {O}}(100)$$O(100)cosmogenic neutrino events. The detectable but suppressed rate in fact makes the double and multiple bangs an excellent probe of SM unknowns and possible new physics beyond. As a case study, the nonperturbative sphaleron process, which can copiously produce multiple tau bangs, is explored.
On the analogy between stochastic electrodynamics and nonrelativistic quantum electrodynamics
Authors: Santos Emilio 
Published: December 2022

AbstractI expose nonrelativistic quantum electrodynamics in the Weyl–Wigner representation. Hence, I prove that an approximation to first order in Planck constant has a formal analogy with stochastic electrodynamics (SED), that is classical electrodynamics of charged particles immersed in a random radiation filling space. The analogy elucidates why SED agrees with quantum theory for particle Hamiltonians quadratic in coordinates and momenta, but fails otherwise.
Remembering Oleksandr Mykolayovych Sharkovsky
Authors: Chua Leon O. , Chen Guanrong 
Published: December 2022

Professor Oleksandr M. Sharkovsky (December 7, 1936–November 21, 2022) was an honorary editorial board member of the International Journal of Bifurcation and Chaos. He left to the scientific world a famous Sharkovsky theorem established in his 1964 paper "Coexistence of Cycles of a Continuous Map of the Line into Itself," which laid the foundation of a new branch in the theory of dynamical systems — combinatorial dynamics. His contributions also include the Sharkovsky ordering, Sharkovsky space, Sharkovsky set, Sharkovsky stratification, and maximum period in the sense of Sharkovsky, among others. Professor Sharkovsky will be remembered forever.
Abstract A030: Deciphering the micro-RNA landscape of AKT isoforms and its clinical impact in patients with lung adenocarcinoma
Authors: Laliotis George , Lin Pauline 
Published: December 2022

Abstract
Over the last 25 years, AKT kinase has been thoroughly investigated and characterized as a crucial regulator of cellular homeostasis, affecting a plethora of essential molecular functions. The three identified isoforms of this kinase, namely AKT1, AKT2 and AKT3, often display opposing and antagonizing cellular functions. One of these important cellular functions is the expression and activation of micro-RNAs (miRNAs), an important RNA process that epigenetically regulates the human transcriptome. In the context of human cancer and based on several reports, AKT kinase has been associated with aberrant expression of oncogenic miRNAs, that in turn hijack oncogenic pathways, leading to tumor progression, metastasis and resistance to therapy, especially in lung adenocarcinoma (LUAD). Nevertheless, a comprehensive analysis of the impact of each AKT isoform on the regulation and enrichment of a specific miRNA signature in lung adenocarcinoma has yet to be performed. Here, we were willing to elucidate the miRNA epigenetic landscape and downstream targets, driven by each AKT isoform, and its clinical importance in patients with lung adenocarcinoma. To this extent, we utilized RNA-Seq and Small RNA-Seq data from The Cancer Genome Atlas (TCGA-LUAD) to identify the miRNA signatures related with the expression of each AKT isoform in LUAD. Gene Set Enrichment Analysis from RNA-Seq and miRNA levels analysis from Small RNA-Seq, identified a unique miRNA signature for each AKT isoform, demonstrating their largely opposing effect in miRNA profiling. In parallel analysis, in silico target analysis of the top 50 regulated miRNAs, demonstrated another set of unique targets for each isoform-dependent miRNA signature, which is involved in metabolism, DNA damage, RNA processing, cell survival, immune response and metastasis. More importantly, clinical and survival analysis revealed that the top 50 Differentially regulated miRNAs, ranked by q-value, for each isoform correlated with poor progression free survival in patients with LUAD. Collectively, our atlas of AKT isoform-driven miRNA landscapes implicates AKT as a global effector of miRNA landscape in lung adenocarcinoma. Due to the lack of reliable isoform-specific AKT inhibitors, the identification of the oncogenic miRNA networks regulated by each isoform, acts as an important transnational resource for the design and testing of inhibitors that bypass AKT inhibition toxicity, sparing its impactful physiological functions.
Citation Format: George Laliotis, Pauline Lin. Deciphering the micro-RNA landscape of AKT isoforms and its clinical impact in patients with lung adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr A030.
Abstract B003: Inactivation mutations of Kmt2c/d license a molecular “field effect” and prime the urothelium for tumorigenesis
Authors: Wang Naitao , Pachai Mohini R. , Li Dan , Lee Cindy , Warda Sarah , Xie Guojia , Qian Cheng , Wong Wai Pung E. , Yan Juan , Hu Wenhuo , Smith Alison , Ge Kai , Chandarlapaty Sarat , Iyer Gopakumar V. , Rosenberg Jonathan E. , Solit David B. , AI-Ahmadie Hikmat A. , Chi Ping , Chen Yu 
Published: December 2022

Abstract
Urothelial carcinoma (UC) is widely recognized to arise from a “field” of precancerous but histologically normal urothelium (HNU). The molecular mechanism that licenses the “field effect” remains elusive. Recent studies revealed prevalent KMT2C and KMT2D loss-of-function (LOF) mutations in HNU and cancer adjacent urothelium, suggesting their potential involvement in UC initiation. Here, we demonstrated that knockout (KO) of Kmt2c and/or Kmt2d in murine urothelial cells induced drastic alterations of cellular states by single cell RNA analysis, but was insufficient to induce robust histological changes. Kmt2c/d loss enhanced organoid formation efficiency, induced epithelial-mesenchymal transition (EMT), and impaired urothelial differentiation, indicating the augmented lineage plasticity after Kmt2c/d KO. Additionally, we identified that Kmt2c/d KO induced a pre-tumorigenic transcriptome with increased enrichments of gene sets associated with inflammation and decreased enrichments of gene sets associated with differentiation. Consequently, loss of Kmt2c/d sensitized urothelial cells to common oncogenic mutations to initiate UC in mouse models. We further observed that KO of Kmt2c/d increased tumorigenic susceptibility in carcinogen-induced UC model. Mechanistically, we observed decreased H3K4me1, H3K27Ac histone marks and decreased enhancer RNA production at the majority of enhancers that correlate with downregulation of urothelial specific lineage gene expression after Kmt2c/d KO. Furthermore, we observed increased Menin deposition on promoters of up-regulated genes. Blockade of Menin-KMT2A complex by small molecule inhibitor partially rescued the EMT and basal differentiation induced by Kmt2c/d KO. Together, our data posit that Kmt2c/d represents a key molecular determinant and their functional loss licenses a molecular “field effect” which primes the urothelium for oncogenic transformation.
Citation Format: Naitao Wang, Mohini R. Pachai, Dan Li, Cindy Lee, Sarah Warda, Guojia Xie, Cheng Qian, Wai Pung E. Wong, Juan Yan, Wenhuo Hu, Alison Smith, Kai Ge, Sarat Chandarlapaty, Gopakumar V. Iyer, Jonathan E. Rosenberg, David B. Solit, Hikmat A. AI-Ahmadie, Ping Chi, Yu Chen. Inactivation mutations of Kmt2c/d license a molecular “field effect” and prime the urothelium for tumorigenesis. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr B003.