bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of anorectal cancer in patients with Crohn's disease and perianal fistula: a nationwide Danish cohort study
Authors: El‐Hussuna Alaa , Lemser Camilla Engel , Iversen Aske Thorn , Allin Kristine Højgaard , Jess Tine 
Published: April 2023

AbstractAimPatients with Crohn's disease (CD) often suffer from perianal fistulizing disease. Their risk of anorectal cancer remains uncertain. We aimed to examine the long‐term risk of anorectal cancer in a population‐based cohort of CD patients with anorectal fistula.MethodOur study population covered all individuals (n = 7 987 520) aged 15+ years living in Denmark from 1978 to 2018. We identified all patients with CD and anorectal fistula in the Danish National Patient Register (NPR) and 50 matched noninflammatory bowel disease (IBD) individuals from the general population. Using Cox regression analyses, we examined the risk of anorectal cancer in CD fistula patients versus non‐IBD individuals. All patients with CD were identified using codes from the International Classification of Diseases and their data extracted from the NPR. The main outcome measure was cases of anorectal cancer.ResultsA total of 2786 CD patients with anorectal fistula and 139 300 non‐IBD individuals were followed for 1 553 917 person‐years. During follow‐up, anorectal cancer was observed in 19 CD patients (0.68%) and 340 non‐IBD individuals (0.24%), corresponding to a 2.9‐fold increased hazard ratio (HR) of anorectal cancer in CD fistula patients (95% CI 1.80–4.53), with a particularly high risk of anal cancer (HR 15.13, 95% CI 6.88–33.31) and a mean time from CD fistula diagnosis to anorectal cancer of 6.7 (SD 6.5) years. The risk was slightly higher in women than men and had no apparent relation to treatment with tumour necrosis factor‐α inhibitors. Sensitivity analyses using CD nonfistula patients for comparison revealed similar results. Individual data on smoking and infection with human papilloma virus were not available.ConclusionPatients with CD and anorectal fistula have a three‐fold increased risk of anorectal cancer compared with the general population. The number needed to surveil to detect one case of anorectal cancer in this patient population was 2160 patients per year in patients with long‐standing fistula (>6 years).
Distributed system anomaly detection using deep learning‐based log analysis
Authors: Han Pengfei , Li Huakang , Xue Gang , Zhang Chao 
Published: April 2023

AbstractAnomaly detection is a key step in ensuring the security and reliability of large‐scale distributed systems. Analyzing system logs through artificial intelligence methods can quickly detect anomalies and thus help maintenance personnel to maintain system security. Most of the current works only focus on the temporal or spatial features of distributed system logs, and they cannot sufficiently extract the global features of distributed system logs to achieve a good correct rate of anomaly detection. To further address the shortcomings of existing methods, this paper proposes a deep learning model with global spatiotemporal features to detect the presence of anomalies in distributed system logs. First, we extract semi‐structured log events from log templates and model them as natural language. In addition, we focus on the temporal characteristics of logs using the bidirectional long short‐term memory network and the spatial invocation characteristics of logs using the Transformer. Extensive experimental evaluations show the advantages of our proposed model for distributed system log anomaly detection tasks. The optimal F1‐Score on three open‐source datasets and our own collected distributed system datasets reach 98.04%, 94.34%, 88.16%, and 97.40%, respectively.
Genome‐wide screen for anticancer drug resistance in haploid human embryonic stem cells
Authors: Segal Emanuel , Nissenbaum Jonathan , Peretz Mordecai , Golan‐Lev Tamar , Cashman Rivki , Philip Hagit , Reubinoff Benjamin E. , Kopper Oded , Benvenisty Nissim 
Published: April 2023

AbstractAnticancer drugs are at the frontline of cancer therapy. However, innate resistance to these drugs occurs in one‐third to one‐half of patients, exposing them to the side effects of these drugs with no meaningful benefit. To identify the genes and pathways that confer resistance to such therapies, we performed a genome‐wide screen in haploid human embryonic stem cells (hESCs). These cells possess the advantage of having only one copy of each gene, harbour a normal karyotype, and lack any underlying point mutations. We initially show a close correlation between the potency of anticancer drugs in cancer cell lines to those in hESCs. We then exposed a genome‐wide loss‐of‐function library of mutations in all protein‐coding genes to 10 selected anticancer drugs, which represent five different mechanisms of drug therapies. The genetic screening enabled us to identify genes and pathways which can confer resistance to these drugs, demonstrating several common pathways. We validated a few of the resistance‐conferring genes, demonstrating a significant shift in the effective drug concentrations to indicate a drug‐specific effect to these genes. Strikingly, the p53 signalling pathway seems to induce resistance to a large array of anticancer drugs. The data shows dramatic effects of loss of p53 on resistance to many but not all drugs, calling for clinical evaluation of mutations in this gene prior to anticancer therapy.
Assessing prioritization measures for a private land conservation program in the U.S. Prairie Pothole Region
Authors: Kemink Kaylan M. , Pressey Robert. L. , Adams Vanessa M. , Nolte Christoph , Olimb Sarah K. , Healey Aidan M. , Liu Boyan , Frerichs Todd , Renner Randy 
Published: April 2023

AbstractPrivate land conservation has become an important tool for protecting biodiversity and habitat, but methods for prioritizing and scheduling conservation on private land are still being developed. While return on investment methods have been suggested as a potential path forward, the different processes linking private landscapes to the socioeconomic systems in which they are embedded create unique challenges for scheduling conservation with this approach. We investigated a range of scheduling approaches within a return on investment framework for breeding waterfowl and broods in the Prairie Pothole Region of North Dakota, South Dakota, and Montana. Current conservation targeting for waterfowl in the region focuses mostly on the distribution and abundance of breeding waterfowl. We tested whether MaxGain approaches for waterfowl conservation differed from MinLoss approaches in terms of return on investment and which approach performed best in avoiding loss of waterfowl and broods separately. We also examined variation in results based upon the temporal scale of the abundance layers used for input and compared the region's current scheduling approach with results from our simulations. Our results suggested that MinLoss was the most efficient scheduling approach for both breeding waterfowl and broods and that using just breeding waterfowl to target areas for conservation programs might cause organizations to overlook important areas for broods, particularly over shorter timespans. The higher efficiency of MinLoss approaches in our simulations also indicated that incorporating probability of wetland drainage into decision‐making improved the overall return on investment. We recommend that future conservation scheduling for easements in the region and for private land conservation in general include some form of return on investment or cost‐effective analysis to make conservation more transparent.
Protect large trees for climate mitigation, biodiversity, and forest resilience
Authors: Mildrexler David J. , Berner Logan T. , Law Beverly E. , Birdsey Richard A. , Moomaw William R. 
Published: April 2023

AbstractProtecting the climate system requires urgently reducing carbon emissions to the atmosphere and increasing cumulative carbon stocks in natural systems. Recent studies confirm that large trees accumulate and store a disproportionate share of aboveground forest carbon. In the temperate forests of the western United States, a century of intensive logging drastically reduced large‐trees and older forest, but some large trees remain. However, recent changes to large tree management policy on National Forest lands east of the Cascade Mountains crest in Oregon and southeastern Washington allows increased harvesting of large‐diameter trees (≥53 cm or 21 inches) that account for just 3% of all stems, but hold 42% of total aboveground carbon. In this article, we describe synergies with protecting large trees for climate mitigation, biodiversity, and forest resilience goals to shift species composition, reduce fuel loads and stem density, and adapt to climatically driven increases in fire activity in eastern Oregon.
Children's social care and early intervention policy: Evidence from sure start
Authors: Anderberg Dan , Olympiou Christina 
Published: April 2023

AbstractWe study the effect of a key early intervention policy, designed to support families with children up to age 4, on the rate at which children up to age 9 are taken into social care. The gradual build‐up of over 3600 Sure Start Children's Centres (SSCCs), operated by Local Authorities (LAs) across England, created large spatial and cohort variation in the provision of a service that included health and parenting support, early learning and some childcare. LAs are also responsible for the safeguarding of children, and about 25 children per 10,000 are taken into care annually, in the majority of cases to protect them from abuse and neglect. SSCC provision may help to identify children at risk from maltreatment while also improving longer‐term outcomes. We therefore estimate the causal effect of SSCC provision on care entry rates, allowing separate effects for children within versus beyond the policy target age. Consistent with the hypothesized effects, our findings indicate that SSCC provision raised the care entry rate among children aged 0–4 (within target age), but reduced it for children aged 5–9 (beyond target age). We also provide corroborating evidence using data on Child Protection Plans and Serious Case Reviews.
Prenatal two‐and three‐dimensional echocardiographic diagnosis of ductal anomalous origin of the left pulmonary artery: Case report and literature review
Authors: Yang Xiang , Hou Qingsha , Li Xiuling , Yu Zeran , Dong Xudong , Yan Fang 
Published: April 2023

AbstractAlthough the ductal anomalous origin of the pulmonary artery (DOPA) constitutes a rare heart anomaly, this malformation has a high mortality rate due to the rapid development of pulmonary hypertension(PTH) and right heart failure. Case Presentation: We report a case of DOPA, in which ductus arteriosus originated from the left pulmonary artery. This article summarizes the embryogenesis, clinical manifestations, complications and prognosis, diagnosis and experience, and treatment strategies of DOPA. The most fundamental sonographic finding was the lack of confluence at the bifurcation of the main pulmonary artery. Scanning upper mediastinum views is essential for the diagnosis. In addition, three‐dimensional echocardiography with high‐definition flow imaging and spatio‐temporal image correlation technique facilitates the identification of the anomalous origin of the pulmonary artery. It should be considered a complementary modality in fetal cardiac examinations. Although rare, DOPA can be diagnosed prenatally, usually at the three‐vessel view (3VV). The early diagnosis of DOPA thus can prevent the potentially devastating effects of PHT and right heart failure.
Intracerebroventricular administration for delivery of antiseizure therapeutics: Challenges and opportunities
Authors: Fahoum Firas , Eyal Sara 
Published: April 2023

AbstractIntracerebroventricular (ICV) administration is increasingly being explored as a means for delivering antiseizure and antiepileptic therapies to epileptic brain tissue. This route bypasses the blood–brain barrier, thus enabling the delivery of therapeutics that are restricted from the brain, while reducing the risk of systemic adverse reactions. Nevertheless, projections from studies in patients with other diseases suggest that efficacy of some ICV‐delivered therapeutics may be limited when the epileptogenic tissue or network circuits are localized more than a few millimeters away from the ventricles. In this article, we present the characteristics of the cerebrospinal fluid as a drug administration site, the brain barriers, and their relevance to treating focal and generalized epilepsies. We refer to ICV delivery of advanced therapies for treating neurodevelopmental disorders with epilepsy. We describe properties of therapeutic compounds, from small molecules to RNA‐based therapeutics, proteins, and viral vectors, which can make them either fitting or poor candidates for ICV administration in epilepsy. We additionally provide an overview of preclinical studies and clinical trials involving the ICV route of delivery. Finally, we compare ICV delivery with other routes of administration that bypass the cerebral circulation. This review aims to provide information that will hopefully help investigators select candidate patients and therapeutics for ICV therapies, and to highlight advantages and challenges inherent to this approach.
Pyroptosis‐related gene signature elicits immune response in rosacea
Authors: Hu Xi‐min , Zheng Sheng‐yuan , Mao Rui , Zhang Qi , Wan Xin‐xing , Zhang Yi‐ya , Li Ji , Yang Rong‐hua , Xiong Kun 
Published: April 2023

AbstractRosacea is a complex chronic inflammatory skin disorder with high morbidity. Pyroptosis is known as a regulated inflammatory cell death. While its association with immune response to various inflammatory disorders is well established, little is known about its functional relevance of rosacea. So, we aimed to explore and enrich the pathogenesis involved in pyroptosis‐related rosacea aggravations. In this study, we evaluated the pyroptosis‐related patterns of rosacea by consensus clustering analysis of 45 ferroptosis‐related genes (FRGs), with multiple immune cell infiltration analysis to identify the pyroptosis‐mediated immune response in rosacea using GSE65914 dataset. The co–co‐work between PRGs and WGCNA‐revealed hub genes has established using PPI network. FRG signature was highlighted in rosacea using multi‐transcriptomic and experiment analysis. Based on this, three distinct pyroptosis‐related rosacea patterns (non/moderate/high) were identified, and the notably enriched pathways have revealed through GO, KEGG and GSEA analysis, especially immune‐related pathways. Also, the XCell/MCPcount/ssGSEA/Cibersort underlined the immune‐related signalling (NK cells, Monocyte, Neutrophil, Th2 cells, Macrophage), whose hub genes were identified through WGCNA (NOD2, MYD88, STAT1, HSPA4, CXCL8). Finally, we established a pyroptosis‐immune co‐work during the rosacea aggravations. FRGs may affect the progression of rosacea by regulating the immune cell infiltrations. In all, pyroptosis with its mediated immune cell infiltration is a critical factor during the development of rosacea.
Recruitment strategies in couple intervention studies: A systematic review of recruitment methods and sample characteristics in the United States from 2015 to 2020
Authors: Tseng Chi‐Fang , Miller Debra L. , Huerta Patricia , PettyJohn Morgan E. , Yzaguirre Melissa M. , Agundez J. C. , Wittenborn Andrea K. 
Published: April 2023

AbstractIncluding diverse participants in couple intervention studies is critical for developing an evidence base that informs best practices for all potential clients. Research has shown that subgroups of clients respond differently to different interventions and that interventions that have been adapted to fit the needs of a given population are more effective than non‐adapted interventions. Unfortunately, couple intervention samples often exclude participants with marginalized identities and culturally adapted couple intervention research is limited. The lack of information about best practices for diverse client subgroups perpetuates mental and relational health disparities. We conducted a systematic review to examine recruitment strategies and sampling characteristics of diverse races/ethnicities, incomes, ages, and sexual identities. We reviewed articles published between January 2015 and December 2020. Articles were eligible for inclusion in our review if they implemented an intervention with couples in the United States. Of 4054 articles identified, 54 articles were eligible for our review. Findings suggest that couple intervention studies lack diversity across multiple identity domains (i.e., races/ethnicities, incomes, ages, and sexual identities). Further, descriptions of recruitment strategies are often vague, limiting opportunities to better understand methods used to recruit diverse samples.
Sevoflurane and isoflurane anesthesia induce redox imbalance, but only sevoflurane impairs vascular contraction
Authors: Rocha Thalita L. A. , Borges Teubislete F. , Rodrigues Serginara D. , Martins Laisla Z. , da Silva Maria L. S. , Bonacio Gisele F. , Rizzi Elen , Dias‐Junior Carlos A. 
Published: April 2023

AbstractVolatile anesthetics may cause vascular dysfunction; however, underlying effects are unclear. The aim of the present study was to investigate whether sevoflurane and isoflurane affect vascular function, nitric oxide (NO) bioavailability, and biomarkers of oxidative stress and inflammation. Wistar rats were divided into three experimental groups: Not anesthetized (control group) or submitted to anesthesia with isoflurane (Iso group) or sevoflurane (Sevo group). Hemodynamic parameters were monitored during anesthesia, and blood gas values and biochemical determinants were analyzed. Isometric contractions were recorded in aortic rings. Vasoconstriction induced by potassium chloride (KCl) and phenylephrine (Phe) were measured. No differences in hemodynamic parameters and blood gasses variables were observed. Impaired KCl and Phe‐induced contractions were observed in endothelium‐intact aorta of Sevo compared to Iso and Control groups. Redox imbalance was found in Sevo and Iso groups. Reduced NO bioavailability and increased activity of matrix metalloproteinase 2 (MMP‐2) were observed in Sevo, but not in the Iso group. While reduced IL‐10 and IL‐1β were observed in Sevo, increases in IL‐1β in the Iso group were found. Sevoflurane, but not isoflurane, anesthesia impairs vasocontraction, and reduced NO and cytokines and increased MMP‐2 activity may be involved in vascular dysfunction after sevoflurane anesthesia.
Evaluation of therapeutic potential of ivermectin against complete Freund's adjuvant‐induced arthritis in rats: Involvement of inflammatory mediators
Authors: Khan Muhammad Usman Ali , Akhtar Tasleem , Naseem Nadia , Aftab Usman , Hussain Safdar , Shahzad Muhammad 
Published: April 2023

AbstractRheumatoid arthritis is a chronic systemic inflammatory disease with genetic manifestations. According to recently published case reports, patients taking corticosteroid medication for the management of rheumatoid arthritis develop strongloidiasis and are at high risk of developing associated infections. This study explored the antiarthritic role of ivermectin, a drug used in the treatment of strongyloides and to compare its results with dexamethasone. Thirty‐two male Wistar rats were randomly divided into four groups: control, diseased, dexamethasone, and ivermectin groups. Rheumatoid arthritis in all rats except the control group was induced by using complete Freund's adjuvant. After 7 days of rheumatoid arthritis induction, animals were treated with dexamethasone 5 mg/kg and ivermectin 6 mg/kg. Body weight, visual arthritic score, total leukocyte count, differential leukocyte count, proinflammatory genes, and histopathological findings were used to assess the effects of ivermectin on rheumatoid arthritis. Treatment with ivermectin showed a significant reduction in inflammatory cells levels, body weight, and visual arthritic score, indicating an improvement in the degree of inflammation as compared with the diseased group. Treatment with ivermectin and dexamethasone significantly reduced the augmentation in the mRNA expression levels of IL‐17, TLR‐2, TNF, and NF‐κB as a result of arthritic development. Ivermectin treatment also showed a significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to dexamethasone, a corticosteroid used for the treatment of rheumatoid arthritis. Ivermectin has significant antiarthritic properties and can be a novel treatment agent for the management of rheumatoid arthritis patients suffering from strongyloidiasis.
Influence of El Niño‐Southern Oscillation on bigeye and yellowfin tuna longline catch per unit effort in the equatorial Pacific
Authors: Domokos Réka 
Published: April 2023

AbstractBigeye tuna (BET) and yellowfin tuna (YFT) are economically important target species of pelagic fisheries worldwide, especially for tropical Pacific nations whose economies and food sources are heavily affected by commercial and sustenance tuna fishing. The El Niño‐Southern Oscillation (ENSO) has a strong effect on the oceanographic conditions in the equatorial Pacific, including BET and YFT equatorial habitat and fishing grounds. For optimal fisheries management, the effects of environmental variability such as ENSO on the stocks and on the performance of fisheries must be known and predictable. However, besides some model predictions, the effects of ENSO on these two tuna species are not well understood. In this study, I investigate the statistical relationships between past ENSO conditions and equatorial fisheries using the Multivariate ENSO Index, sea surface temperature (SST), and catch and effort records from the longline fisheries in the region. Results of this study indicate that El Niño events have both delayed and concurrent positive effects on BET and YFT catch per unit effort (CPUE). The delayed positive ENSO effect on CPUE is hypothesized to be the result of enhanced recruitment acting via different mechanisms in the west than in the east. The concurrent positive effects on CPUE could be due to catchability, abundance, and/or vertical distribution of BET and YFT relative to fishing gear and require further investigation. Further exploration of the mechanisms that may underlie the results presented here could lead to predictability of CPUE of these two tuna species.