bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robotic-assisted surgery and kinematic alignment in total knee arthroplasty (RASKAL study): a protocol of a national registry-nested, multicentre, 2×2 factorial randomised trial assessing clinical, intraoperative, functional, radiographic and survivorship outcomes
Authors: MacDessi Samuel J , Wernecke Gregory C , Bastiras Durga , Hooper Tamara , Heath Emma , Lorimer Michelle , Harris Ian 
Published: June 2022

IntroductionRobot-assisted surgery (RAS) and kinematic alignment (KA) are being increasingly adopted to improve patient outcomes in total knee arthroplasty (TKA). There is uncertainty around the individual or combined effect of these concepts compared with computer-assisted surgery (CAS) and mechanical alignment (MA), respectively. This study aims to assess the effectiveness of RAS, KA or both to improve clinical outcomes, functional measures, radiographic precision and prosthetic survivorship when compared with current gold standards of surgical care.Methods and analysisA national registry-nested, multicentre, double-blinded, 2×2 factorial, randomised trial will be undertaken with 300 patients undergoing primary unilateral TKA performed by 15 surgeons. The primary outcome will be the between-group differences in postoperative change over 2 years in the mean Knee injury and Osteoarthritis Outcome Score (KOOS-12), comparing first, RAS to CAS as its control, and second, KA to MA as its control. Secondary outcomes will include other knee-specific and general health patient-reported outcome measures (PROMs), intraoperative pressure loads as a measure of soft tissue balance, 6-month postoperative functional outcomes, radiological precision using CT imaging, complications and long-term prosthetic survivorship. The contribution of each patient’s unique coronal plane alignment of the knee phenotype to primary and secondary PROMs will be investigated. OMERACT-OARSI criteria and Patient Acceptable Symptom State outcome score thresholds for the KOOS-12 and Oxford Knee Score will be used in secondary analyses. Primary intention-to-treat and secondary per-protocol analyses will be performed. Statistical analysis will include a generalised linear mixed model for repeated measures for continuous KOOS-12 scores. Kaplan-Meier estimates with adjusted HRs of implant survivorship will be calculated.Ethics and disseminationEthics approval was obtained from Sydney Local Health District-Royal Prince Alfred Hospital (Approval X20-0494 and 2020/ETH02896 10.24/DEC20). Results will be submitted for publication in a peer-reviewed journal and presented in national, state and international meetings.Trial registration numberACTRN12621000205831.
Examining the intersection of child protection and public housing: development, health and justice outcomes using linked administrative data
Authors: Malvaso Catia , Montgomerie Alicia , Pilkington Rhiannon Megan , Baker Emma , Lynch John W 
Published: June 2022

ObjectiveWe described development, health and justice system outcomes for children in contact with child protection and public housing.DesignDescriptive analysis of outcomes for children known to child protection who also had contact with public housing drawn from the South Australian (SA) Better Evidence Better Outcomes Linked Data (BEBOLD) platform.SettingThe BEBOLD platform holds linked administrative records collected by government agencies for whole-population successive birth cohorts in SA beginning in 1999.ParticipantsThis study included data from birth registrations, perinatal, child protection, public housing, hospital, emergency department, early education and youth justice for all SA children born 1999–2013 and followed until 2016. The base population notified at least once to child protection was n=67 454.Primary outcome measureContact with the public housing system.Secondary outcome measuresHospitalisations and emergency department presentations before age 5, and early education at age 5, and youth justice contact before age 17.ResultsMore than 60% of children with at least one notification to child protection had contact with public housing, and 60.2% of those known to both systems were known to housing first. Children known to both systems experienced more emergency department and hospitalisation contacts, greater developmental vulnerability and were about six times more likely to have youth justice system contact.ConclusionsThere is substantial overlap between involvement with child protection and public housing in SA. Those children are more likely to face a life trajectory characterised by greater contact with the health system, greater early life developmental vulnerability and greater contact with the criminal justice system. Ensuring the highest quality of supportive early life infrastructure for families in public housing may contribute to prevention of contact with child protection and better life trajectories for children.
Presence of SARS-CoV-2 RNA in human corneal tissues donated in Italy during the COVID-19 pandemic
Authors: Ferrari Stefano , Franco Elena , Del Vecchio Claudia , Zorzi Ilaria , Fasolo Elisa , Crisanti Andrea , Ponzin Diego 
Published: June 2022

ObjectiveTo analyse corneal tissues from asymptomatic donors with a postmortem nasopharyngeal swab tested positive for the presence of SARS-CoV-2 RNA, and therefore, understand the role that corneal transplantation may have in viral transmission.Methods and analysisBetween March 2020 and October 2021, 101 corneas (out of 8154 collected in Italy) from 51 donors (out of a total of 4155 Italian donors) positive for SARS-CoV-2 after postmortem nasopharyngeal swab tests were analysed for the presence of SARS-CoV-2 RNA through real-time RT-PCR. When available, the corneal tissue storage media were also assessed. Corneas and/or storage media with confirmed presence of SARS-CoV-2 RNA were further investigated by isolating SARS-CoV-2 virions, which were used to infect VeroE6 target cells.ResultsOnly N=4 corneas and/or storage media out of 101 showed presence of SARS-CoV-2 RNA. No VeroE6 cell infection was detected with viral isolates, thus suggesting no presence of SARS-CoV-2 virions in corneal specimens and storage media.ConclusionsThe presence of SARS-CoV-2 in cornea specimens would seem to be more likely due to prolonged detection of RNA rather than to active viral replication, with very low risk of infectivity and transmission through keratoplasty.
Targeting of GSDMD sensitizes HCC to anti-PD-1 by activating cGAS pathway and downregulating PD-L1 expression
Authors: Lv Tingting , Xiong Xiaofeng , Yan Wei , Liu Mei , Xu Hongwei , He Qin 
Published: June 2022

BackgroundGasdermin D (GSDMD) is well known as a downstream of inflammasomes. However, the roles of GSDMD itself in hepatocellular carcinoma (HCC) remain unclear.MethodsTwo independent cohorts of patients with HCC were analyzed to evaluate the pathological relevance of GSDMD/pTBK1/PD-L1. GSDMD knockout (GSDMD-/-) mice, Alb-Cre mice administered with an adeno-associated virus (AAV) vector that expressed the gasdermin-N domain (AAV9-FLEX-GSDMD-N) and their wild-type littermates were used to induce hepatocarcinogenesis or metastatic HCC. Combination of anti-programmed cell death protein-1 (PD-1) and GSDMD inhibitor dimethyl fumarate (DMF) was used to test for improved therapeutic efficacy. RNA sequencing was used to explore the mechanisms how GSDMD promoted HCC progression.ResultsThe expression of GSDMD and GSDMD-N was upregulated in HCC tissues or metastatic HCC tissues and positive GSDMD expression indicated grim prognosis. Diethylnitrosamine/carbon tetrachloride or thioacetamide-treated GSDMD-/- mice exhibited decreased liver tumors. In contrast, AAV9-FLEX-GSDMD-N promoted hepatocarcinogenesis. RNA sequencing manifested that knockout of GSDMD impacted the cyclic GMP-AMP synthase (cGAS) pathway and immune-associated pathway. GSDMD damped cGAS activation by promoting autophagy via outputting potassium (K+) and promoted programmed death ligand-1 (PD-L1) expression by histone deacetylases/signal transducer and activator of transcription 1 (STAT1)-induced transactivation of PD-L1 via importing calcium (Ca2+). High Mobility Group Box 1/toll-like receptor 4 (TLR4)/caspase-1 pathway contributed to the overexpression and cleavage of GSDMD. Anti-PD-1 combining with DMF largely impaired HCC progression and metastasis.ConclusionsTargeting GSDMD could promote expression of interferons through inactivation of cGAS pathway and downregulated the PD-L1 expression. Therefore, combined anti-PD-1 and GSDMD inhibitor might serve as an effective treatment option for patients with HCC with GSDMD upregulation.
Evaluation of aneurysm rupture risk based upon flowrate-independent hemodynamic parameters: a multi-center pilot study
Authors: Zhang Mingzi , Hou Xiaoxi , Qian Yi , Chong Winston , Zhang Xin , Duan Chuan-Zhi , Ou Chubin 
Published: June 2022

BackgroundSpecifying generic flow boundary conditions in aneurysm hemodynamic simulations yields a great degree of uncertainty for the evaluation of aneurysm rupture risk. Herein, we proposed the use of flowrate-independent parameters in discriminating unstable aneurysms and compared their prognostic performance against that of conventional absolute parameters.MethodsThis retrospective study included 186 aneurysms collected from three international centers, with the stable aneurysms having a minimum follow-up period of 24 months. The flowrate-independent aneurysmal wall shear stress (WSS) and energy loss (EL) were defined as the coefficients of the second-order polynomials characterizing the relationships between the respective parameters and the parent-artery flows. Performance of the flowrate-independent parameters in discriminating unstable aneurysms with the logistic regression, Adaboost, and support-vector machine (SVM) methods was quantified and compared against that of the conventional parameters, in terms of sensitivity, specificity, and area under the curve (AUC).ResultsIn discriminating unstable aneurysms, the proposed flowrate-independent EL achieved the highest sensitivity (0.833, 95% CI 0.586 to 0.964) and specificity (0.833, 95% CI 0.672 to 0.936) on the SVM, with the AUC outperforming the conventional EL by 0.133 (95% CI 0.039 to 0.226, p=0.006). Likewise, the flowrate-independent WSS outperformed the conventional WSS in terms of the AUC (difference: 0.137, 95% CI 0.033 to 0.241, p=0.010).ConclusionThe flowrate-independent hemodynamic parameters surpassed their conventional counterparts in predicting the stability of aneurysms, which may serve as a promising set of hemodynamic metrics to be used for the prediction of aneurysm rupture risk when physiologically real vascular boundary conditions are unavailable.
Impact of PD1 and PDL1 immunotherapy on non-small cell lung cancer outcomes: a systematic review
Authors: Kanabar Shivani Setur , Tiwari Abhinav , Soran Vina , Balendran Prashanthan , Price Malcolm , Turner Alice Margaret 
Published: June 2022

IntroductionDespite comprising many cancer diagnoses, few treatments are suitable for patients with advanced non-small cell lung cancer (aNSCLC). Trials suggest blockade of programmed death 1 (PD1) or its ligand (PDL1) may be effective for these patients. However, this therapy’s impact on outcomes other than survival, and outcomes of patients not in trials, remains largely unknown. Therefore, we compared the effectiveness of PD1 and PDL1 immunotherapy to chemotherapy and placebo across multiple clinical outcomes.MethodsSix databases were searched on 12–13 October 2019 for randomised controlled trials (RCTs) and observational studies investigating nivolumab, pembrolizumab, atezolizumab or durvalumab. Study selection was performed independently by two reviewers. Data for overall survival, progression-free survival, adverse effects (AEs) and quality of life (QoL) were descriptively and meta-analysed. Factors impacting treatment outcomes, including PDL1 expression, were explored. The similarity between RCT and observational data was assessed.ResultsFrom 5423 search results, 139 full texts and abstracts were included. Immunotherapy was associated with a lower risk of death than both comparators. In RCTs, the incidence of treatment-related AEs was approximately 20% lower among patients using immunotherapy compared with chemotherapy. However, no other consistent benefits were observed. Progression-free survival results were inconsistent. Improvements to QoL varied according to the instrument used; however, QoL was not recorded widely. Survival results were similar between study designs; however, AEs incidence was lower in observational studies.DiscussionAmong patients with aNSCLC, immunotherapy improved overall survival and incidence of treatment-related AEs compared with chemotherapy. Benefits to progression-free survival and QoL were less consistent.PROSPERO registration numberCRD42019153345.
Relationship between Content and Activity of Cytochrome P450 and Induction of Heterocyclic Amine DNA Adducts in Human Liver Samples In vivo and In vitro
Authors: Baranczewski Pawel , Möller Lennart 
Published: June 2022

Abstract
This study was designed to estimate a correlation between metabolic activation phenotypes and formation of DNA adducts by heterocyclic amines (HCA) in 15 liver samples from healthy donors. The correlation between the amount of endogenous DNA adducts and the content of cytochrome P450 in human liver samples in vivo was statistically significant at r2 = 0.71 and P &lt; 0.005. Furthermore, the isolated human liver microsomes were treated in vitro with two HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-9H-pyrido[2,3-b]indole (AαC), which have been recognized to induce two DNA adducts: 3′,5′-diphosphate-N-(2′-deoxyguanosin-8-yl)-PhIP (3′,5′-pdGp-C8-PhIP) and 3′,5′-diphosphate-N-(2′-deoxyguanosin-8-yl)-AαC (3′,5′-pdGp-C8-AαC). The correlations between the amount of DNA adducts induced by both compounds in vitro and the content of cytochrome P450 in human microsomes are statistically significant at r2 = 0.69 and r2 = 0.62 (P &lt; 0.001), respectively. Furthermore, the level of DNA adducts after treatment with PhIP and AαC correlated with the activities of three isozymes of cytochrome P450: CYP1A1, CYP1A2, and CYP3A4. Therefore, three chemical inhibitors were used in the experiments: ellipticine against CYP1A1, furafylline against CYP1A2, and troleandomycin against CYP3A4. The highest inhibition levels in the formation of 3′,5′-pdGp-C8-PhIP and 3′,5′-pdGp-C8-AαC adducts were estimated to occur in the presence of furafylline at 56% and 69%, respectively. Ellipticine was involved in the inhibition of 40% of 3′,5′-pdG-C8-PhIP adducts and in only 18% of the inhibition of 3′,5′-pdGp-C8-AαC adducts. Troleandomycin did not significantly inhibit the formation of 3′,5′-pdGp-C8-PhIP adducts under these conditions, but it inhibited the formation of 31% of the 3′,5′-pdGpC8-AαC adducts. We conclude that the formation of DNA adducts can be used as a relevant marker of interindividual variability in the metabolic activation of HCAs in humans.
Associations among IRS1, IRS2, IGF1, and IGFBP3 Genetic Polymorphisms and Colorectal Cancer
Authors: Slattery Martha L. , Samowitz Wade , Curtin Karen , Ma Khe Ni , Hoffman Michael , Caan Bette , Neuhausen Susan 
Published: June 2022

Abstract
Introduction: Insulin, insulin-like growth factor (IGF), and IGF binding protein (IGFBP) are involved in cell growth and proliferation and are thought to be important in the etiology of colorectal cancer. We hypothesize that genetic polymorphisms of insulin receptor substrates (IRS-1 and IRS-2), IGF-I, and IGFBP-3 alter colorectal cancer risk because of their roles in the insulin-related signaling pathway. Methods: Data from a population-based incident case-control study of 1,346 colon cancer cases and 1,544 population-based controls and 952 rectal cancer cases and 1,205 controls were used to evaluate associations. Genetic polymorphisms of four genes were investigated: an IGF1 CA repeat, the IGFBP3 −202 A &gt; C, the IRS1 G972R, and the IRS2 G1057D. Results: Having at least one R allele (GR or RR) for IRS1 G972R was associated with an increased risk of colon cancer [odds ratio 1.4, 95% confidence interval (95% CI) 1.1-1.9]. The IRS2 G972R heterozygote GD genotype significantly reduced risk of colon cancer (odds ratio 0.8, 95% CI 0.6-0.9). Neither the IGF1 nor the IGFBP3 variants was associated independently with colon cancer, but there was an association when examined with IRS1. Individuals with an IRS1 R allele and IGF1 non-192 allele were at a 2-fold increased risk of colon cancer (95% CI 1.2-4.4). There was a 70% (95% CI 1.02-2.8) increased risk of colon cancer with an IRS1 R allele and the IGFBP3 AC or CC genotype. The IRS2 GD genotype reduced risk of colon cancer, except among those with an IRS1 R allele. No significant associations were seen in analyses of main effects or interactions of these variants and rectal cancer risk. Conclusions: Both IRS1 and IRS2 variants were associated with colon cancer risk independently. Associations were slightly stronger when polymorphisms in multiple genes were evaluated in conjunction with other genes rather than individually. These data suggest that the insulin-related pathway may be important in the etiology of colon cancer but not rectal cancer.
Subsite-Specific Colorectal Cancer Incidence Rates and Stage Distributions among Asians and Pacific Islanders in the United States, 1995 to 1999
Authors: Wu Xiaocheng , Chen Vivien W. , Martin Jim , Roffers Steven , Groves Frank D. , Correa Catherine N. , Hamilton-Byrd Elizabeth , Jemal Ahmedin 
Published: June 2022

Abstract
Objective: This study examined subsite-specific colorectal cancer incidence rates and stage distributions for Asians and Pacific Islanders (API) and compared the API data with data for Whites and African Americans. Methods: Data included 336,798 invasive colorectal cancer incident cases for 1995 to 1999 from 23 population-based central cancer registries, representing about two thirds of API population in the United States. Age-adjusted rates, using the 2000 U.S. standard population, and age-specific rates and stage distributions were computed by anatomic subsite, race, and gender. All rates were expressed per 100,000. SEs and rate ratios were calculated for rate comparison. A significance level of 0.05 was used for all analyses. Results: Overall, age-adjusted colorectal cancer incidence rates were significantly lower in API than in Whites and African Americans across anatomic subsites, particularly for proximal colon cancer in which rates were 40% to 50% lower in API males and females. Exception to this pattern was the significantly (10%) higher rectal cancer incidence rate in API males than in African American males. The incidence patterns by anatomic subsite within API differed from those of Whites and African Americans. Among API, the rate of rectal cancer (19.2 per 100,000) was significantly higher than the rates of proximal (15.2 per 100,000) and distal (17.7 per 100,000) colon cancers in males, with little variations in rates across anatomic subsites in females. In contrast, among White and African American males and females, proximal colon cancer rates were over 25% higher than the rates of distal colon and rectal cancers. Increases in age-specific rates with advancing age were more striking for proximal colon cancer than for distal colon and rectal cancers in Whites and African Americans, while age-specific rates were very similar for different subsites in API with parallel increases with advancing age, especially in API males. Similar to Whites and African Americans, in API, proximal colon cancers (32% to 35%) were also less likely to be diagnosed with localized stage compared with distal colon (38% to 42%) and rectal (44% to 52%) cancers. Conclusion: The patterns of subsite-specific colorectal cancer incidence in API, especially API males, differ from those of Whites and African Americans. Similar to Whites and African Americans, lower percentage of localized disease in API for proximal colon cancer than for distal colon and rectal cancers was also observed.
Number of Siblings and Risk of Hodgkin's Lymphoma
Authors: Chang Ellen T. , Montgomery Scott M. , Richiardi Lorenzo , Ehlin Anna , Ekbom Anders , Lambe Mats 
Published: June 2022

AbstractBackground: Epidemiologic evidence indicates that risk of Hodgkin's lymphoma (HL) in young adults is associated with correlates of delayed exposure to infection during childhood. In contrast, HL among children and older adults may be associated with earlier childhood infection. This study examines the associations of HL risk with having older or younger siblings. Methods: We conducted a case-control study in Sweden comparing 2,140 HL patients identified from the Swedish Cancer Register with 10,024 controls identified from national population registers. The Swedish Multi-Generation Register was used to link individuals to their parents and siblings. Results: Among young adults ages 15 to 39 years, the odds ratios (OR) associated with having one, two, and three or more older siblings, compared with none, were 0.96 [95% confidence interval (CI), 0.82-1.13], 0.88 (95% CI, 0.72-1.09), and 0.72 (95% CI, 0.55-0.93), respectively (P value for trend = 0.01). In contrast, number of older siblings was not associated with HL risk among children or older adults. Number of younger or total siblings, mother's age at birth, and father's occupation were not associated with HL at any age. The decreased risk of young-adult HL did not vary appreciably by age difference or sex of older siblings. Conclusions: Risk of HL was lower among young adults with multiple older but not younger siblings. Having older siblings is associated with earlier exposure to common childhood pathogens. Pediatric and older-adult HL were not associated with number of siblings, suggesting a different pathogenesis of disease in these age groups.
A Population-Based Case-Control Study of the XRCC1 Arg399Gln Polymorphism and Susceptibility to Bladder Cancer
Authors: Kelsey Karl T. , Park Sunyeong , Nelson Heather H. , Karagas Margaret R. 
Published: June 2022

Abstract
Cigarette smoking is the major cause of bladder cancer. Constituents in tobacco smoke can induce oxidative DNA damage requiring base excision repair. The Arg399Gln polymorphism in the DNA base excision repair gene XRCC1 is associated with several phenotypic markers of reduced DNA repair capacity. Results from several epidemiologic studies suggest that the Arg399Gln polymorphism may influence susceptibility to several cancers including bladder cancer; however, data from large population-based studies are lacking. In a population-based case-control study from New Hampshire, we observed a reduced risk among those homozygous for the Arg399Gln XRCC1 variant polymorphism compared with those with one or two wild-type alleles (odds ratio 0.6, 95% confidence interval 0.4-1.0). There was no indication of a gene-environment interaction between cigarette smoking and the variant genotype. Our data are consistent with a potential role of the XRCC1 Arg399Gln polymorphism in bladder cancer susceptibility and further suggest that there may be DNA lesions important in bladder carcinogenesis, repaired by the base excision repair mechanism, that are not directly associated with tobacco smoking.