bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variants of the CASP9 gene as candidate markers for primary response to anti-TNF therapy in Crohn's disease patients
Authors: Lykowska-Szuber Liliana , Walczak Michal , Stawczyk-Eder Kamila , Krela-Kazmierczak Iwona , Eder Piotr , Zakerska-Banaszak Oliwia , Dobrowolska Agnieszka , Skrzypczak-Zielinska Marzena 
Published: August 2023

Abstract
Anti-tumor necrosis factor (TNF) therapy is used to induce and maintain remission in Crohn’s disease (CD) patients. However, primary non-responders to initial treatment constitute 20–40% of cases. The causes of this phenomenon are still unknown. We aim to investigate the impact of the caspase 9 (CASP9) gene variants on the variable reactions of CD patients to anti-TNF therapy. The study group included 196 diagnosed and clinically characterized CD Polish patients following anti-TNF therapy. The sequence of the CASP9 gene was analyzed using next-generation and Sanger sequencing and was analyzed with the response to biological treatment. Using the RT-qPCR analysis, we estimated the CASP9 gene mRNA level in colon biopsies material from inflamed and non-inflamed tissue (21 CD patients: 14 responders and seven non-responders to anti-TNF therapy and six controls), as well as in vitro in a peripheral blood mononuclear cells (PBMCs) from CD patients (seven responders and seven non-responders to anti-TNF therapy) and eight controls. Our findings indicated association of variants rs1052571 and rs4645978 with response to anti-TNF monoclonal antibodies (mAbs). Moreover, we observed tendency for reduced expression after incubation with anti-TNF in the group of CD patients, in contrast to the control group. Our results suggest that response to anti-TNF therapy in CD patients may be an effect of variants of the CASP9 gene as a key effector of the internal pathway of apoptosis, however, further population and functional research are necessary.
Simplicial techniques for operator solutions of linear constraint systems
Authors: Chung Ho Yiu , Okay Cihan , Sikora Igor 
Published: August 2023

Abstract
A linear constraint system is specified by linear equations over the group Zd of integers modulo d. Their operator solutions play an important role in the study of quantum contextuality and non-local games. In this paper, we use the theory of simplicial sets to develop a framework for studying operator solutions of linear systems. Our approach refines the well-known group-theoretical approach based on solution groups by identifying these groups as algebraic invariants closely related to the fundamental group of a space. In this respect, our approach also makes a connection to the earlier homotopical approach based on cell complexes. Within our framework, we introduce a new class of linear systems that come from simplicial sets and show that any linear system can be reduced to one of that form. Then we specialize in linear systems that are associated with groups. We provide significant evidence for a conjecture stating that for odd d every linear system admitting a solution in a group admits a solution in Zd.
Mitochondrial Genome Amplification of Avian Haemosporidian Parasites from Single-Infected Wildlife Samples Using an Innovative Nested PCR Approach
Authors: Musa Sandrine 
Published: August 2023

Abstract
Haemosporidian parasites that infect birds (Apicomplexa: Haemosporida) are blood parasites that require multiple hosts for their lifecycle and cause malaria-like diseases. This group of parasites has provided valuable insights into host specificity, virulence, and parasite dispersal. Additionally, they have played a significant role in reshaping our understanding of the evolutionary history of apicomplexans. In order to accurately identify species and to address phylogenetic questions such as the timing of the haemosporidian radiation, the use of a sufficiently large genetic data set is crucial. However, acquiring this genetic data poses significant challenges. In this research, a sensitive nested PCR assay was developed. This assay allows for the easy amplification of complete mitochondrial genomes of haemosporidian parasites in birds, even during the chronic stage of infection. The effectiveness of this new nested PCR assay was evaluated using blood and tissue samples of single infected bird from previous studies. The approach involves amplifying four overlapping fragments of the mitochondrial genome and requires DNA extracts from single infected samples. This method successfully amplified the complete mitochondrial genomes of 24 distinct haemosporidian lineages found in various bird species. This data is invaluable for conducting phylogenetic analyses and accurately defining species. Furthermore, this study proposes the existence of at least 15 new species based on the genetic information obtained. Data regarding pGRW04, previously categorized as Plasmodium relictum like pSGS1 and pGRW11, indicates that the pGRW04 lineage is actually a separate, hidden species.
An Oscillating Reaction Network With an ExactClosed Form Solution in the Time Domain
Authors: Hellerstein Joseph 
Published: August 2023

Abstract
Background: Oscillatory behavior is critical to many life sustaining processes such as cell cycles, circadian rhythms, and notch signaling. Important biological functions depend on the characteristics of these oscillations (hereafter, oscillation characteristics or OCs): frequency (e.g., event timings), amplitude (e.g., signal strength), and phase (e.g., event sequencing).
Results: We develop and conduct a theoretical study of an oscillating reaction network to quantify the relationships between OCs and the structure and parameters of the reaction network. We consider a reaction network with two species that have dynamics that can be described by a system of linear differential equations. This makes it possible to construct a two species harmonic oscillator (2SHO). We obtain exact, closed-form formulas for the OCs of the 2SHO. These formulas are used to develop the parameterizeOscillator algorithm that parameterizes the 2SHO to achieve desired oscillation characteristics.
Conclusions: The OC formulas are employed to analyze the roles of the reactions in the network, and to comment on other studies of oscillatory reaction networks. For example, others have stated that nonlinear dynamics are required to create oscillations in reaction networks. Our 2SHO is a counter example to this claim in that 2SHO is an oscillating reaction network whose dynamics are described by a system of linear differential equations. A further insight of potential interest is that our formulas show that in order to obtain oscillations in the 2SHO, the rate of the reaction that causes negative feedback must exceed the rate of the reaction that causes positive feedback.
Disulfidptosis-related prognostic model based on multiomics and the significance of IL1B in ovarian cancer
Authors: Wang Kunyu , Li Bin 
Published: August 2023

Abstract
Background
Ovarian cancer (OC) is a significant health concern for women due to high mortality rates. Disulfidptosis is a newly discovered mechanism of caspase-driven programmed cell death that may be significant for cancer treatment.
Methods
The bulk RNA-seq data of 378 OC patients in TCGA-OV cohort and 174 patients in GSE53963 dataset, and the single-cell RNA-seq data of 4 high-grade SOC patients in GSE154600 were retrieved. The disulfidptosis score was calculated by gene set enrichment analysis (GSEA) based on the disulfidptosis pathway using the AddModuleScore function of the Seurat package. The patients were divided into the two groups based on the risk score, which were then compared using consensus clustering, WCGNA and functional enrichment analysis. LASSO regression and cox regression were performed to construct a risk score model. Immune cell infiltration was analyzed by xcell and ssGSEA. IL1B was knocked down in OC cell lines, and routine in vitro and in vivo functional assays were performed.
Results
We identified 6 cell clusters in OC and divided them on the basis of the disulfidptosis score. The two groups showed distinct functional difference. Likewise, OC patients divided into disulfidptosis score-related groups showed significant difference in survival status, along with enrichment of immune response-related pathways. Seven prognostic genes related to disulfidptosis were screened by Cox regression and LASSO regression analyses, and the risk score was calculated. The high-risk score was associated with significantly worse survival in the validation cohort. In addition, the abundance of activated T cells was higher, and that of Tregs and MDSCs were lower in the low-risk group compared to the high-risk group. Finally, IL1B silencing inhibited the proliferation, migration, and invasion of OC cells in vitro and in vivo.
Conclusion
The disulfidptosis-based risk model can accurately predict the prognosis and immune characteristics of OC patients. IL1B functions as an oncogene in OC, and is a promising therapeutic target.
Aspirin Responsiveness in a Cohort of Paediatric Patients With Bovine Jugular Venous Valves and Right Ventricle to Pulmonary Artery Conduits
Authors: Kelleher Sean T. , Regan Irene E. , Cox Dermot , Shaw Kathryn , Kenny Damien P. , Walsh Kevin P. , Franklin Orla , McMahon Colin J. 
Published: August 2023

Abstract
Objective: The aim of this study was to determine the rate of aspirin responsiveness in a cohort of paediatric patients with in-situ xenograft valved right ventricle to pulmonary artery (RV-PA) conduits and/or bovine jugular venous valves (BJV). Aspirin is routinely prescribed to these patients. Optimising anti-platelet therapy could promote valve longevity and reduce the risk of infective endocarditis in this at-risk group.
Materials and Methods: This was a prospective, observational study. Patients were recruited from both ward and outpatient settings. Patients were eligible if under 18 years and taking aspirin. Non-response to aspirin was defined as >20% platelet aggregation using light-transmission platelet aggregometry (LTA) and <50% platelet inhibition by thromboelastography with platelet mapping (TEGPM). Participants were invited to provide a confirmatory sample in cases of aspirin resistance and dose adjustments were made.
Results: Thirty patients participated. Median age was 9 years (2 months – 18 years). The majority (93%) had complex right ventricular outflow tract pathology. 13 (43%) had an RV-PA conduit, 24 (80%) had a BJV, with valve situated in conduit in 7 (23%) cases. Rate of aspirin non-response on initial testing was 23% (n=7/30) with median LTA 25.45% (24.9-40%) and TEG 13.25% (0-44%) in non-responders. Non-responders were more likely to be under 1 year. Two patients required dose increases and one patient non-adherence to dose was identified. In 4 patients repeat testing revealed normal results.
Conclusions The rate of aspirin non-response on laboratory testing in this cohort of patients was 23% and resulted in therapeutic intervention in 10%.
Association between blood lipid levels and risk of liver cancer: a systematic review and meta-analysis
Authors: Zhang Zhihui , Xu Shicong , Song Meixuan , Huang Weirong , Yan Manlin , Li Xianrong 
Published: August 2023

Abstract
Purpose: The association between blood lipid levels and the risk of developing liver cancer remains a subject of ongoing debate. In order to elucidate this association, we conducted a meta-analysis by systematically incorporating data from all relevant prospective cohort studies.
Method: We conducted a systematic search in PubMed, Embase, Web of Science, and The Cochrane Library, covering data from the inception of these databases up to July, 2023. This study included prospective cohort studies related to lipid profiles (e.g., total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein) that reported hazard ratios (HRs) or relative risks (RRs) with their corresponding 95% confidence intervals (95%CIs) to investigate their association with the risk of liver cancer. During the analysis process, we used fixed-effect or random-effects models based on the level of heterogeneity among the studies and obtained pooled risk ratios using these models. To ensure the robustness and reliability of the study findings, we also conducted sensitivity analyses and publication bias analyses.
Results: After conducting a systematic search, we identified 12 studies from a total of 11,904 articles, which were included in the meta-analysis. These studies encompassed a combined population of 10,765,221 participants, including 31,055 cases of liver cancer events. The analysis results revealed that the highest versus lowest pooled risk ratio for serum total cholesterol (TC) concentration was 0.45 (95% CI = 0.35-0.58, I2 = 78%). For triglycerides (TGs), the risk ratio was 0.67 (95% CI = 0.46-0.96, I2 = 86%), while for high-density lipoprotein (HDL-C), the risk ratio was 0.72 (95% CI = 0.58-0.90, I2 = 65%). Regarding low-density lipoprotein (LDL-C), the risk ratio was 0.51 (95% CI = 0.23-1.13, I2 = 93%).
Conclusion: The findings of this study indicate a negative association between serum levels of total cholesterol, triglycerides, and high-density lipoprotein with liver cancer, suggesting that higher concentrations of these lipids are associated with a reduced risk of liver cancer. However, no significant association has been found between low-density lipoprotein and liver cancer at present.
Tonic action of endothelin type B and dopamine D3 receptors in SHR and DOCA hypertensive rats: effects of intrarenally applied selective antagonists
Authors: Bądzyńska Bożena , Baranowska Iwona , Sadowski Janusz 
Published: August 2023

Abstract
Endothelins and renal dopamine contribute to control of renal function and arterial pressure in health and various forms of experimental hypertension, the action is mediated by tonic activity of specific receptors. We determined the action mediated by endothelin type B and dopamine D3 receptors (ETB-R, D3-R) in anesthetized spontaneously hypertensive (SHR) and in DOCA-salt hypertensive rats. In rats of both hypertension models infused during 60 min into the interstitium of in situ kidney were either ETB-R antagonist, BQ788 (0.67 mg kg-1 h-1) or D3-R antagonist, GR169031 (0.2 mg kg-1 h-1). Arterial pressure (MAP), renal artery blood flow (RBF, Transonic probe) and renal medullary blood flow (MBF, laser-Doppler) were measured along with sodium, water and total solute excretion (UNaV, V, UosmV). Experiments with ETB-R blockade confirmed their tonic vasodilator action in the whole kidney (RBF) and medulla (MBF) in both hypertension models. In SHR only, the first evidence was provided that ETB-R specifically increases transtubular backflux of non-electrolyte solutes, such as urea. In DOCA-salt rats ETB-R blockade caused an early decrease in water and salt transport whereas an increase was often reported from many previous studies. The most striking effect of D3-R blockade in SHR was a selective increase in MBF, which strongly suggested tonic vasoconstrictor action of these receptors in the renal medulla; this speaks against prevailing opinion that D3 receptors are virtually inactive in SHR. In our model variant of DOCA-salt rats D3-R blockade clearly caused a rapid major increase in MAP in parallel with depression of renal haemodynamics
Real-time cross-step detection using center-of-pressure based algorithm
Authors: Zadravec Matjaž , Matjačić Zlatko 
Published: August 2023

Abstract

Background
Gait event detection is crucial for assessment, evaluation and provision of biofeedback of during rehabilitation of walking. Existing online gait event detection algorithms mostly rely on add-on sensors, limiting their practicality. Instrumented treadmills offer a promising alternative by utilizing the Center of Pressure (CoP) signal for real-time gait event detection. However, current methods have limitations, particularly in detecting cross-step events during perturbed walking conditions.
Methods
We present and validate a real-time CoP-based algorithm to detect gait events and cross-steps, which combines thresholding and logic techniques. The algorithm was evaluated on CoP datasets from healthy participants, stroke survivors, and unilateral amputees that underwent perturbation-based balance assessments, encompassing different walking speeds. Real-time detected gait events were compared to offline identified counterparts in order to present related temporal delays and success rate.
Results
The proposed algorithm demonstrated high accuracy in detecting gait events during native gait, as well as cross-step events during perturbed walking conditions. It successfully recognized the majority of cross-steps, with a detection success rate of 94%. However, some misclassifications or missed events occurred, mainly due to the complexity of cross-step events. Temporal delays for heel-strikes during native gait and cross-step events averaged at 78 ms and 64 ms respectively, while toe-off delays were 126 ms and 111 ms respectively.
Conclusion
The proposed algorithm represents an advancement in gait event detection on instrumented treadmills. By leveraging the CoP signal, it successfully identifies gait events and cross-steps in real-time, providing valuable insights into human locomotion. The algorithm's ability to accommodate diverse CoP patterns enhance its applicability to a wide range of individuals and gait characteristics. The algorithm's performance was consistent across different populations, suggesting its potential for diverse clinical and research settings, particularly in the domains of gait analysis and rehabilitation practices.
Breast cancer diagnosed after age 70 years in Israeli BRCA1/BRCA2 pathogenic sequence variant carriers- A single institution experience
Authors: Bufman Hila , Faermann Renata , Halshtok-Neiman Osnat , Shalmon Anat , Gotlieb Michael , Samoocha David , Yagil Yael , Feldman Dana Madorsky , Friedman Eitan , Sklair-Levy Miri 
Published: August 2023

Abstract

Purpose
A semi-annual surveillance scheme from age 25–30 years is offered to BRCA1/BRCA2 pathogenic sequence variants (PSVs) carriers for early detection of breast cancer (BC). There is a paucity of data on the yield of adhering to this scheme beyond 70 years of age.
Methods
Female BRCA1/BRCA2 PSV carriers followed at the Meirav high-risk clinic, Sheba Medical center, Israel were eligible. Type and frequencies if use of Imaging modalities, breast biopsies and histological outcomes for participants after age 70 years were retrieved and analyzed.
Results
Overall, the study encompassed 88 consenting participants (46 BRCA1 carriers) mean age ± SD 73.7 ± 3.3 years (range 70–90 years), followed for an average of 3.8 years (range 1–11 years). Ten carriers (11.3%) were diagnosed with BC after age 70 years (mean age at diagnosis 72 ± 2 years) and an additional case was diagnosed with breast lymphoma. The imaging modality that has led to most diagnoses was MRI (8/11 cases). Eight of these 10 cases were previously diagnosed with BC prior to age 70 and in six, BC past 70 years was in the contralateral breast. The lesions size averaged 1.29 ± 0.75 cm, with IDC and DCIS diagnosed in 5 cases each, and none had lymph node involvement.
Conclusions
In ~ 10% of BRCA1/BRCA2 PSV carriers BC is diagnosed by breast imaging after age 70 years. If these results are validated in a larger study, the guidelines for the maximum age for BC surveillance in high risk women should be revisited.
Systemic Pan-Caner Analysis Identifies CACYBP as a Novel Biomarker for Cancer Prognosis and Immunity
Authors: Liang He-jun , Lin Lan-hui , Li Zhi-yu , Zhu Jing-yi , Gu Feng , Ma Lei , He Bo-yuan , Zhang Xiao-yan , Yuan Duo , Ge Yi , Chen Zhuo , Zhai Hui-Hong 
Published: August 2023

Abstract
Calcyclin-binding protein or siah-1-interacting protein (CACYBP/SIP), a target protein of calcyclin S100A6 and an essential component of E3 ubiquitin ligase, had been proven to play significant roles in some cancers, but its pan-cancer function remains unknown. In the present study, we used a series of databases, including TCGA, GTEx, CPTAC, HPA, cBioPortal, UCLCAN, UCSC, CancerSCEM, CancerSEA, CancerSEA, GEPIA2 and STRING to explore the potential roles of CACYBP in pan-cancer. We systematically revealed the expression patterns of CACYBP, and the potential associations between CACYB expression and genetic alternation, prognosis, DNA methylation, RNA modification, immune reactivity, tumor stemness and enrichment pathways in pan-cancer. The results showed that CACYBP was significantly increased in various cancers compared to corresponding normal tissues. CACYBP mutation was frequently presented in various cancers. In addition, CACYBP expression was significantly correlated with prognosis, DNA methylation, RNA methylation, immune cells infiltration, immune checkpoint genes (ICGs), immune scores, tumor mutational burden (TMB), microsatellite instability (MSI) and tumor stemness in various cancers. We also discovered that CACYBP was abundantly highly expressed in the majority of cancers at a single-cell level and was significantly positively correlated to the single-cell functions of certain tumors, such as the cell cycle, DNA damage and DNA repair. Furthermore, CACYBP-related genes were mainly enriched in signaling pathways correlated with the tumor microenvironment (TME) and cancer development. Taken together, CACYBP plays an essential role in oncogenesis, and might serve as a promising prognostic biomarker and immunotherapeutic target in human cancers.
Developing Formulation-based Standards for Installation and Operation of Exclusive Bus Lanes on Expressways using real-world data and simulation
Authors: Park Seongmin , Park Juneyoung , Yoon Youngkwon 
Published: August 2023

Abstract
Korea operates exclusive bus lanes (XBLs) on many of its expressways. As XBLs convert one lane of regular use traffic into bus-only traffic, they have a large impact on traffic flow, so careful judgment is required to determine if the operation is effective. However, XBLs have been installed based on only political judgment. Therefore, we sought to establish standards for the operation of expressway XBLs using the micro-traffic simulation and the multi-criteria value function methodology. Various scenarios were established based on traffic volume. Through an expert survey, the average speed and speed deviation values were determined. Also, value points were converted using average speed and speed deviation extracted from the simulation. In addition, quantitative operation standards were established using the converted value scores. Using the results of this study, we establish standards for the operation XBLs. Citing the results of this study, the new guidelines were implemented in February 2021, and sections of some XBLs have been abolished. Through this study, quantitative standards for the operation of XBLs, one of the management lane techniques necessary for sustainable highway operation, were prepared and applied to actual expressways. It is also expected to have a positive effect on safety, efficiency and environment.
WITHDRAWN: On New Congruences and Density Results for(k, 𝓁)-regular Bipartitions Modulo m
Authors: VIDYA K. N. 
Published: August 2023

Abstract
Let Bk,𝓁(n) denote the number of (k, 𝓁)-regular bipartitions. Recently, Dou discovered an infinite family of congruences modulo 11 for B3,11(n). She also presented several conjectures on Bk,𝓁(n). In this article, we establish infinite families of congruences for Bk,𝓁(n) modulo certain positive integers, for specific values of k, 𝓁. We next study the distribution of Bk,𝓁(n) for (k, 𝓁) ∈ {(3, 5),(2, 6),(2, 4),(4, 6)}. Moreover, we prove several infinite families of congruences modulo 2 and 3 for Bk,𝓁(n). We use arithmetic properties of modular forms and Hecke eigenforms to prove our results.