bluuebunny/crossref_metadata_2025_split huggingface dataset:
Counting Homomorphic Cycles in Degenerate Graphs
Authors: Gishboliner Lior , Levanzov Yevgeny , Shapira Asaf , Yuster Raphael 
Published: September 2022

Since counting subgraphs in general graphs is, by and large, a computationally demanding problem, it is natural to try and design fast algorithms for restricted families of graphs. One such family that has been extensively studied is that of graphs of bounded degeneracy (e.g., planar graphs). This line of work, which started in the early 80’s, culminated in a recent work of Gishboliner et al., which highlighted the importance of the task of counting homomorphic copies of cycles (i.e., cyclic walks) in graphs of bounded degeneracy.

Our main result in this paper is a surprisingly tight relation between the above task and the well-studied problem of
detecting (standard) copies
of directed cycles in
general directed
graphs. More precisely, we prove the following:

One can compute the number of homomorphic copies of

C
2k

and

C
2k+1

in
n
-vertex graphs of bounded degeneracy in time Õ(

n

d
k

), where the fastest
known
algorithm for detecting directed copies of

C
k

in general
m
-edge digraphs runs in time Õ(

m

d
k

).

Conversely, one can transform any

O(n

b
k

)

algorithm for computing the number of homomorphic copies of

C
2k

or of

C
2k+1

in
n
-vertex graphs of bounded degeneracy, into an Õ(

m

b
k

) time algorithm for detecting directed copies of

C
k

in general
m
-edge digraphs.

We emphasize that our first result does not use a black-box reduction (as opposed to the second result which does). Instead, we design an algorithm for computing the number of

C
k

-homomorphisms in degenerate graphs and show that one part of its
analysis
can be reduced to the analysis of the fastest known algorithm for detecting directed cycles in general digraphs, which was carried out in a recent breakthrough of Dalirrooyfard, Vuong and Vassilevska Williams. As a by-product of our algorithm, we obtain a new algorithm for detecting
k
-cycles in directed and undirected graphs of bounded degeneracy that is faster than all previously known algorithms for 7 ≤
k
≤ 11, and faster for all
k
≥ 7 if the matrix multiplication exponent is 2.
The multiple roles that IPv6 addresses can play in today's internet
Authors: Piraux Maxime , Barbette Tom , Rybowski Nicolas , Navarre Louis , Alfroy Thomas , Pelsser Cristel , Michel François , Bonaventure Olivier 
Published: September 2022

The Internet use IP addresses to identify and locate network interfaces of connected devices. IPv4 was introduced more than 40 years ago and specifies 32-bit addresses. As the Internet grew, available IPv4 addresses eventually became exhausted more than ten years ago. The IETF designed IPv6 with a much larger addressing space consisting of 128-bit addresses, pushing back the exhaustion problem much further in the future.
In this paper, we argue that this large addressing space allows reconsidering how IP addresses are used and enables improving, simplifying and scaling the Internet. By revisiting the IPv6 addressing paradigm, we demonstrate that it opens up several research opportunities that can be investigated today. Hosts can benefit from several IPv6 addresses to improve their privacy, defeat network scanning, improve the use of several mobile access network and their mobility as well as to increase the performance of multicore servers. Network operators can solve the multihoming problem more efficiently and without putting a burden on the BGP RIB, implement Function Chaining with Segment Routing, differentiate routing inside and outside a domain given particular network metrics and offer more fine-grained multicast services.
Expression and the Prognostic Value of Biglycan in Gastric Cancer
Authors: Hu Sizhe , Li Peipei , Wang Chenying , Liu Xiyong 
Published: September 2022

Background. Biglycan (BGN) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer. Material and Methods. Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets (

n
=
64

and

n
=
432

) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. Protein-protein interaction (PPI) analysis was performed on gastric cancer-related genes and BGN targets, and those interactions with

confidence

interval

CI

≥
0.7

were chosen to construct a PPI network. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Gene Transcription Regulation Database (GTRD) and ALGGEN-PROMO predicted the transcription factor binding sites (TFBSs) of the BGN promoter. BGN protein level in gastric cancer tissue was determined by immunohistochemistry (IHC). Bioinformatic analysis predicted the putative TFs of BGN. Results. For gastric cancer, the mRNA expression level of BGN in tumor tissue was significantly higher than that in normal tissue. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN was significantly enriched in gene signatures related to metastasis and poor prognosis, revealing that BGN might be associated with cell proliferation, poor differentiation, and high invasiveness of gastric cancer. Meanwhile, the putative TFs, including AR, E2F1, and TCF4, were predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion. High expression of BGN mRNA was significantly related to poor prognosis, which suggested that BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.
The cAMP/PKA/CREB and TGFβ/SMAD4 Pathways Regulate Stemness and Metastatic Potential in Colorectal Cancer Cells
Authors: Fujishita Teruaki , Kojima Yasushi , Kajino-Sakamoto Rie , Mishiro-Sato Emi , Shimizu Yasuhiro , Hosoda Waki , Yamaguchi Rui , Taketo Makoto Mark , Aoki Masahiro 
Published: September 2022

Abstract
Metastasis is responsible for the majority of deaths of patients with cancer. However, mechanisms governing metastasis in colorectal cancer remain largely unknown. Here we investigated how colorectal cancer cells acquire metastatic potential using a novel mouse model of colorectal cancer that spontaneously develops liver metastasis, generated by introducing sporadic mutations of Ctnnb1, Kras, Trp53, and Smad4 (CKPS) genes. Proteomic analyses revealed elevated expression of colorectal cancer stem cell markers ALCAM (CD166) and PROM1 (CD133) in colorectal cancer cells from the metastatic model compared with those from a nonmetastatic model. Spleen-to-liver metastasis assays using colorectal cancer cells derived from the CKPS model (CKPS cells) demonstrated the functional importance of ALCAM and PROM1 in initiating metastasis. Genetic and pharmacologic analyses using CKPS cells in 2D and spheroid culture revealed that expression of ALCAM and PROM1 is regulated positively and negatively by the cAMP/PKA/CREB and TGFβ/SMAD4 pathways, respectively. Consistently, phospho-CREB was expressed in both primary and metastatic lesions of CKPS mice and patients with colorectal cancer, and knockout of CREB in CKPS cells reduced their spheroid-forming and metastasis-initiating abilities. Treatment with a CREB inhibitor potentiated the effect of irinotecan in suppressing liver metastasis by CKPS cells. These results reveal the essential roles of ALCAM and PROM1, as well as their upstream regulators, the cAMP/PKA/CREB and TGFβ/SMAD4 pathways, in maintaining the stemness and metastatic potential of colorectal cancer cells and indicate that CREB inhibition may be a potential therapeutic strategy against metastatic colorectal cancer.

Significance:
This study identifies signaling pathways essential for maintaining the stemness and metastatic potential of colorectal cancer cells and proposes CREB as a therapeutic target in metastatic colorectal cancer.
Association Between Alcohol Consumption and Risk of Pancreatic Cancer: The Japan Public Health Center-Based Prospective Study
Authors: Okita Yuki , Sobue Tomotaka , Zha Ling , Kitamura Tetsuhisa , Iwasaki Motoki , Inoue Manami , Yamaji Taiki , Tsugane Shoichiro , Sawada Norie 
Published: September 2022

Abstract

Background:
Several studies have investigated the association between alcohol consumption and pancreatic cancer risk. However, these studies reported inconsistent results.

Methods:
This study included 95,812 participants from the Japan Public Health Center-Based Prospective Study, whose alcohol drinking habit was collected through the questionnaire of the baseline survey in 1990 to 1994 for Cohort I and in 1993 to 1995 for Cohort II, and followed-up until December 2013. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted Cox proportional hazard regression models.

Results:
During 1,969,101 person-years of follow-up, 598 patients (315 men and 283 women) were newly diagnosed with pancreatic cancer. No association was observed between alcohol consumption at baseline and pancreatic cancer risk in either men or women, even in the analyses conducted among men stratified by facial flushing responses or smoking status. When the population was limited to men whose alcohol drinking habit remained unchanged from the baseline survey to the 5-year follow-up survey, a significant association was observed in drinkers with alcohol consumption of 1 to 299 g/week compared with non/occasional drinkers (multivariable-adjusted HR, 1.73; 95% CI, 1.15–2.60).

Conclusions:
A significant association between alcohol consumption and pancreatic cancer risk was observed when the population was limited to men with a 5-year unchanged alcohol drinking habit and was particularly strong in never smokers.

Impact:
This study suggested an association between continuous alcohol consumption and pancreatic cancer risk in the Japanese population. However, further investigations using other cohort studies are required.
Comparative Microbiomics Analysis of Antimicrobial Antibody Response between Patients with Lung Cancer and Control Subjects with Benign Pulmonary Nodules
Authors: Shome Mahasish , Gao Weimin , Engelbrektson Anna , Song Lusheng , Williams Stacy , Murugan Vel , Park Jin G. , Chung Yunro , LaBaer Joshua , Qiu Ji 
Published: September 2022

AbstractBackground:CT screening can detect lung cancer early but suffers a high false-positive rate. There is a need for molecular biomarkers that can distinguish malignant and benign indeterminate pulmonary nodules (IPN) detected by CT scan.Methods:We profiled antibodies against 901 individual microbial antigens from 27 bacteria and 29 viruses in sera from 127 lung adenocarcinoma (ADC), 123 smoker controls (SMC), 170 benign nodule controls (BNC) individuals using protein microarrays to identify ADC and BNC specific antimicrobial antibodies.Results:Analyzing fourth quartile ORs, we found more antibodies with higher prevalence in the three BNC subgroups than in ADC or SMC. We demonstrated that significantly more anti-Helicobacter pylori antibodies showed higher prevalence in ADC relative to SMC. We performed subgroup analysis and found that more antibodies with higher prevalence in light smokers (≤20 pack-years) compared with heavy smokers (&gt;20 pack-years), in BNC with nodule size &gt;1 cm than in those with ≤1 cm nodules, and in stage I ADC than in stage II and III ADC. We performed multivariate analysis and constructed antibody panels that can distinguish ADC versus SMC and ADC versus BNC with area under the ROC curve (AUC) of 0.88 and 0.80, respectively.Conclusions:Antimicrobial antibodies have the potential to reduce the false positive rate of CT screening and provide interesting insight in lung cancer development.Impact:Microbial infection plays an important role in lung cancer development and the formation of benign pulmonary nodules.
PH-Binding Motif in PAR4 Oncogene: From Molecular Mechanism to Drug Design
Authors: Nag Jeetendra Kumar , Malka Hodaya , Sedley Shoshana , Appasamy Priyanga , Rudina Tatyana , Levi Tgst , Hoffman Amnon , Gilon Chaim , Uziely Beatrice , Bar-Shavit Rachel 
Published: September 2022

AbstractWhile the role of G-protein–coupled receptors (GPCR) in cancer is acknowledged, their underlying signaling pathways are understudied. Protease-activated receptors (PAR), a subgroup of GPCRs, form a family of four members (PAR1–4) centrally involved in epithelial malignancies. PAR4 emerges as a potent oncogene, capable of inducing tumor generation. Here, we demonstrate identification of a pleckstrin-homology (PH)-binding motif within PAR4, critical for colon cancer growth. In addition to PH–Akt/PKB association, other PH-containing signal proteins such as Gab1 and Sos1 also associate with PAR4. Point mutations are in the C-tail of PAR4 PH-binding domain; F347 L and D349A, but not E346A, abrogate these associations. Pc(4–4), a lead backbone cyclic peptide, was selected out of a mini-library, directed toward PAR2&4 PH-binding motifs. It effectively attenuates PAR2&4–Akt/PKB associations; PAR4 instigated Matrigel invasion and migration in vitro and tumor development in vivo. EGFR/erbB is among the most prominent cancer targets. AYPGKF peptide ligand activation of PAR4 induces EGF receptor (EGFR) Tyr-phosphorylation, effectively inhibited by Pc(4–4). The presence of PAR2 and PAR4 in biopsies of aggressive breast and colon cancer tissue specimens is demonstrated. We propose that Pc(4–4) may serve as a powerful drug not only toward PAR-expressing tumors but also for treating EGFR/erbB-expressing tumors in cases of resistance to traditional therapies. Overall, our studies are expected to allocate new targets for cancer therapy. Pc(4–4) may become a promising candidate for future therapeutic cancer treatment.
Examining the Linear Association Between Blood Pressure Levels and Cardiovascular Diseases in the Absence of Major Risk Factors in China
Authors: Zheng Ruizhi , Xu Yu , Li Mian , Lu Jieli , Wu Shujing , Niu Jingya , Zhao Zhiyun , Chen Li , Huo Yanan , Xu Min , Wang Tiange , Wang Shuangyuan , Lin Hong , Qin Guijun , Yan Li , Wan Qin , Chen Lulu , Shi Lixin , Hu Ruying , Tang Xulei , Su Qing , Yu Xuefeng , Qin Yingfen , Chen Gang , Gao Zhengnan , Wang Guixia , Shen Feixia , Luo Zuojie , Chen Yuhong , Zhang Yinfei , Liu Chao , Wang Youmin , Wu Shengli , Yang Tao , Li Qiang , Mu Yiming , Zhao Jiajun , Wang Weiqing , Ning Guang , Bi Yufang ,   for the 4C Study Group†
Published: September 2022

Background:
Many studies demonstrate a J-shaped association between blood pressure and cardiovascular diseases (CVDs), but the findings are plagued by confounding from other traditional cardiovascular risk factors (CVRFs). Our aims were to examine the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels with CVD in individuals without major CVRFs and whether there were thresholds for the association.

Methods:
In the 4C study (China Cardiometabolic Disease and Cancer Cohort), 36 042 CVRF-free participants without CVD, diabetes, dyslipidemia, hypertension, or smoking were identified during 2011 to 2012. Among CVRF-free participants, 17 476 CVRF-preferable individuals with better glycemic (fasting glucose, <110 mg/dL; 2-hour post-load glucose, <140 mg/dL) and lipid profile (total cholesterol, <200 mg/dL; LDL [low-density lipoprotein] cholesterol, <130 mg/dL) were selected. The total person-years of follow-up for CVRF-free subjects and CVRF-preferable subjects were 130 147 and 63 573 person-years, respectively. Information on the development of major CVDs was collected during 2014 to 2016. Cox proportional hazard models were performed to estimate the risks for incident CVD by SBP and DBP groups, respectively.

Results:
We found that both baseline SBP and DBP presented significantly linear associations with CVD risks in CVRF-free and CVRF-preferable participants. There is significant increase in the CVD risk among CVRF-free participants with baseline SBP level of 110 to 119 mm Hg (hazard ratio, 1.79 [95% CI, 1.19–2.71]), 120 to 129 mm Hg (hazard ratio, 2.03 [95% CI, 1.36–3.03]), and 130 to 139 mm Hg (hazard ratio, 2.15 [95% CI, 1.40–3.28]) compared with SBP <110 mm Hg. Significant increases were also observed for DBP level of 80 to 89 mm Hg (hazard ratio, 1.43 [95% CI, 1.03–1.97]) compared with DBP <70 mm Hg. Similar results were observed in CVRF-preferable participants.

Conclusions:
SBP and DBP with levels currently considered normal were significantly and linearly associated with incident CVD without thresholds above 110/70 mm Hg among Chinese adults without major CVRFs.
Determinants of Renewable Electricity Generation in Africa
Authors: Rashed Ahmed , Yong Chen-Chen , Soon Siew-Voon 
Published: September 2022

Abstract
Africa’s electricity insecurity issues are getting worse. However, there has been significant foreign direct investment (FDI) absorbed by the renewable electricity generation (REG) industry in the last twenty years. To date, the impact of FDI on REG in Africa has yet to be investigated. This study thus empirically examines REG determinants with a special focus on FDI in forty African countries between 2000 and 2019. By using the Prais-Winsten panel corrected standard errors model, a range of promising results are revealed. Importantly, we find compelling evidence that FDI inflows directly and indirectly limit, or even impede, REG development. What’s more, Africa’s population growth undermines REG. However, the encouraging result is that raising awareness in Africa of renewable energy boosts REG. We conclude that there is a necessity for the gradual reform of lax environmental laws and renewable energy education plans in Africa.
Into the Wild: Biological Timing in Natural Environments
Authors: Agostino Patricia V. , Golombek Diego A. 
Published: September 2022

Abstract
Biological timing (including circadian and interval timing) has mainly focused on rigorously controlled laboratory experiments. There are relatively few studies looking into interval timing behaviors in the wild, which could be understandable due to the complexity of the experimental design but are definitely needed in order to comprehend the adaptive value of such behavior. In this opinion paper we review some of the literature regarding timing observations under field conditions, including reports from birds and mammals, and propose a call-to-action to think about the need of a more naturalistic interpretation of time production and perception, as well as the advantage of designing more ‘natural’ settings in the laboratory.
Christianity seen by Muslims and Islam seen by Christians in the Period of Early Islamic Rule in the Middle East
Authors: Beaumont Mark 
Published: September 2022

Abstract
This paper highlights a context where Christians lived under Muslim rule. Muslim critique of Christianity was widespread, and Christians had to react to Muslim dominance by finding ways of responding to criticisms without incurring punishment for rebellious attitudes to their rulers. In the first two centuries after the Arab conquest of the largely Christian Middle East, Muslims viewed Christians as needing correction for their mistaken beliefs about the oneness of God in their deviant Trinity, about the humanity of Jesus in their insistence on his divine status, about the death of Jesus by crucifixion when this had not happened, and for their failure to recognise the finality of the Prophet Muḥammad in their suppression of testimony to his coming in the Bible. Christians viewed Muslims as heretics who had diverted from the true Christian faith in the Trinity and the divinity and crucifixion of Jesus and who looked for prophecies of Muḥammad in the Bible that did not exist. Muslims and Christians searched each other’s scriptures to persuade the other that their interpretations might need correcting. As the centuries passed in the Middle East, Christians steadily embraced Islam. By the time of the Mongol invasion in the thirteenth century, the vast majority of the population were Muslims.
Indonesia’s Hospitable Democracy
Authors: Wisdom Kyle 
Published: September 2022

Abstract
Although much scholarly work has been done to present the depth and diversity of Islam around the world, positive encounters between Islam and Christianity in modern democracies continue to merit exploration. Indonesia, the world’s largest Muslim majority nation, includes organizations and thinkers at the forefront of re-examining assumptions of Islamic orthodoxy. This article will present the current activities of Humanitarian Islam and its partnership with Christian organizations to build peace and shared civilizational values. Unique partnerships like this are possible through Muslim reform efforts, which have been underrepresented. These significant efforts are partly conceivable due to two Indonesian thought leaders, Nurcholish Madjid and Abdurrahman Wahid, who made significant contributions to Indonesian expressions of Islam. Two recent events in Indonesia show the progress and challenge for Christian minorities in Muslim majority contexts. While tension remains, Muslim reform efforts in Indonesia suggest possibilities for Islam’s peaceful integration with modern democracy and establishing conditions where Christian minority communities can thrive.
Serum Anion Gap Level Predicts All-Cause Mortality in Septic Patients: A Retrospective Study Based on the MIMIC III Database
Authors: Zhu Yao , He Zonglin , Jin Ya , Zhu Sui , Xu Weipeng , Li Bingxiao , Nie Chuan , Liu Guosheng , Lyu Jun , Han Shasha 
Published: September 2022

Purpose Sepsis is a significant threat in the intensive care unit (ICU) worldwide because it has high morbidity and mortality rates. Early recognition and diagnosis of sepsis are essential for the prevention of adverse outcomes. The present study aimed to quantitatively assess the association between serum anion gap (AG) levels and 30- and 90-day all-cause mortality among sepsis patients. Methods Clinical data of patients diagnosed with sepsis were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. Kaplan–Meier curves and Cox proportional hazards models were used to evaluate the association between serum AG levels and all-cause mortality. A receiver operating characteristic (ROC) curve was drawn to quantify the efficacy of using the serum AG level to predict all-cause mortality. Results A total of 3811 patients were included in the study. The Kaplan–Meier curves showed that patients with higher serum AG levels had a shorter survival time than those with lower levels. Serum AG levels were found to be highly effective in predicting all-cause mortality secondary to sepsis (30-day: AUROC = 0.703; 90-day: AUROC = 0.696). The Cox regression model further indicated that the serum AG level was an independent risk factor for 30- and 90-day mortality in sepsis (HR 3.44, 95% CI 2.97-3.99 for 30-day; HR 3.17, 95% CI 2.76-3.65 for 90-day, P < 0.001 for both). Conclusions High serum AG may be considered as an alternative parameter for predicting the death risk in sepsis when other variables are not immediately available. Prospective large-scale studies are needed to support its predictive value in the clinic.