bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of cabazitaxel and the influence of clinical factors on the overall survival of patients with castration‐resistant prostate cancer: A local experience of a multicenter retrospective study
Authors: Takai Manabu , Kato Seiichi , Nakano Masahiro , Fujimoto Shota , Iinuma Koji , Ishida Takashi , Taniguchi Mitsuhiro , Tamaki Masayoshi , Uno Masahiro , Takahashi Yoshito , Komeda Hisao , Koie Takuya 
Published: September 2020

AbstractAimTo date, the optimal sequencing of life‐prolonging therapies for patients with metastatic castration‐resistant prostate cancer (mCRPC) remains unclear owing to a lack of prospective trials. This study aimed to evaluate the efficacy and safety of cabazitaxel (CBZ) treatment and examine the prognostic factors for oncological outcomes in patients with mCRPC who received CBZ after docetaxel (DOC).MethodsThis multi‐institutional retrospective study included 44 patients with mCRPC who received CBZ. All enrolled patients had histologically confirmed prostate cancer (PCa) with distant metastases and had received DOC before CBZ administration. The primary endpoint was the oncological outcomes, including the overall (OS) and progression‐free survival (PFS). The secondary endpoints were adverse events due to CBZ and rates of ≥30% reduction in prostate‐specific antigen (PSA) levels.ResultsThe median follow‐up period was 9.2 months (range, 0.2–34 months). During this time, 34 patients (77%) died of PCa. The median OS and PFS were 12.2 (range, 0.2–34 months) and 1.4 months (range, 0.4–17 months), respectively. According to the PSA decline rate, patients who achieved a ≥30% reduction in PSA levels had significantly longer OS than those who showed a <30% reduction in PSA levels (P = 0.002). Regarding the number of cycles of CBZ, patients who received ≥4 cycles of CBZ showed significantly longer OS than those who received <4 cycles of CBZ (P < 0.001). Patients who had visceral metastasis showed significantly shorter OS than those without visceral metastasis (P = 0.012).ConclusionThis study demonstrated that CBZ was effective and safe in Japanese local patients in a real‐world setting. Patients with mCRPC who received ≥4 cycles of CBZ showed a ≥30% reduction in the serum PSA levels, and did not have visceral metastasis might achieve longer OS.
Increased rates of cetuximab reactions in tick prevalent regions and a proposed protocol for risk mitigation
Authors: Yuile Alexander , Fanuli Claudia , van Nunen Sheryl , Diakos Connie , Clarke Stephen , Steiner Christian , MacMillan Robyn , Oatley Meredith , Pavlakis Nick 
Published: September 2020

AbstractBackgroundCetuximab is an anti‐epidermal growth factor receptor mouse‐human chimeric monoclonal antibody used to treat advanced colorectal cancers. Initial data suggest that severe infusion reactions occurred in 4.5%, many on first exposure. The majority of those with anaphylactic reactions possess predeveloped IgE antibodies to galactose‐alpha‐1,3‐galactose. It is thought that the vector for preexposure to alpha‐gal is antigen inoculation via tick bites. This retrospective study reviews the experience of two community cancer centers in high tick exposure areas in Sydney with cetuximab anaphylaxis and proposes a protocol to avoid this.MethodSevere cetuximab infusion reactions occurring in the Northern Cancer Institute Frenchs Forest and St Leonards clinics, Sydney, from May 2014 to February 2019 were recorded. Area of residence was then compared to areas of known high tick prevalence.ResultsA total of 87 patients received cetuximab in this period. Six patients (6.9%) experienced at least a grade 3 reaction, three females, age range 41–72 years (median 57.5 years). All were receiving cetuximab for metastatic colorectal cancer and their anaphylaxis occurred with the first infusion in all cases.ConclusionThese cases support the existing theory of increased rates of cetuximab anaphylaxis in areas of high tick prevalence. Given this, we recommend the following protocol for patients being considered for cetuximab therapy: known mammalian meat allergy as an absolute contraindication; all patients receiving cetuximab should have RAST (ImmunoCAP®) testing for alpha‐gal specific‐IgE‐specific antibodies before first infusion and those who test positive to be considered alternate therapy.
Cytotrophoblasts suppress macrophage‐mediated inflammation through a contact‐dependent mechanism
Authors: Eastman Alison J. , Vrana Erin N. , Grimaldo Maria T. , Jones Amanda D. , Rogers Lisa M. , Alcendor Donald J. , Aronoff David M. 
Published: September 2020

AbstractProblemGestational membrane (GM) infection provokes inflammation and can result in preterm prelabor rupture of membranes (PPROM). The choriodecidual layer of the GM includes decidual stromal cells (DSC), cytotrophoblasts (CTB), and macrophages (Mφ). Our laboratory has previously shown that DSCs suppress Mφ TNF‐α production through secreted prostaglandin E2. We hypothesized that CTBs would also inhibit Mφ cytokine expression through secreted mediators.Method of StudyTHP.1 Mφ‐like cells with an NF‐κB reporter construct or human blood monocyte‐derived Mφ were co‐cultured with the Jeg3 CTB cell line or primary human CTBs and challenged with group B streptococcus (GBS) or Toll‐like receptor (TLR) agonists. Conditioned medium generated from CTB cultures was applied to Mφ cultures before infection or treatment. Alternatively, CTBs were co‐incubated with, but physically separated from, Mφ and GBS or TLR‐stimulated. NF‐κB was assessed via alkaline phosphatase assay, and proinflammatory mediators were assessed by qRT‐PCR and ELISA.ResultsCTBs suppressed GBS‐ or TLR‐stimulated Mφ NF‐κB activity, and TNF‐α and MMP9 production. Direct physical contact between CTBs and Mφ was required for full immunosuppression. Immunosuppression could be overcome by increasing the ratio of Mφ to CTB.ConclusionsCTBs limit Mφ NF‐κB activation and production of TNF‐α and MMP9 through an as‐yet unknown, cell‐to‐cell contact‐mediated mechanism. This suppression is distinct from the PGE2‐mediated Mφ TNF‐α suppression by DSC, suggesting that DSCs and CTBs regulate Mφ inflammation through distinct mechanisms. How Mφ integrates these signals in an intact GM will be paramount to determining causes and prevention of PPROM.
The association between congenital heart disease and small for gestational age with regard to the prevalence and outcomes
Authors: Ishikawa Takamichi , Uchiyama Hiroki , Baba Toru , Ohishi Akira , Iijima Shigeo , Iwashima Satoru 
Published: September 2020

AbstractAimTo evaluate the association between small for gestational age (SGA) and the prevalence of congenital heart disease (CHD) and the association of the SGA status with the outcomes among infants with CHD.MethodsEchocardiography was performed within the first 5 days of life in 5664 consecutive infants. Infants were classified into four groups according to the presence or absence of SGA and CHD. All CHD infants were followed up until either spontaneous resolution of all cardiac lesions, invasive intervention or death. All newborns without CHD were followed for mortality until the final follow‐up date.ResultsA total of 303 infants were diagnosed with CHD, while 610 were diagnosed with SGA. Among the CHD infants, 56 were SGA, and 247 were not. A multivariable logistic regression analysis showed that the adjusted odds ratio of SGA (9.71, P < .001) was significantly higher than that of other parameters concerning predictors of invasive intervention or death. The mortality rate in the presence of both SGA and CHD (hazard ratio: 33.6, P < .001) was markedly higher than in the absence of both.ConclusionSGA was a significant predictor of invasive intervention for CHD. The combination of CHD and SGA carried a high risk of death beyond that of either alone.
Is the Death Penalty Debate Really Dead? Contrasting Capital Punishment Support in Canada and the United States
Authors: Rancourt Marc‐Antoine , Ouellet Catherine , Dufresne Yannick 
Published: September 2020

AbstractFor decades, capital punishment has been a highly divisive topic. Today, most democratic governments have done away with capital punishment, with few exceptions which include the United States. Drawing from the Canadian Election Study (2015) and the American National Election Study (2016), this article explores the underlying value systems that shape contemporary pro‐death penalty opinions in Canada and in the United States. Findings suggest that, in both countries, pro‐death penalty attitudes should be better understood as part of a “law and order syndrome.” In the United States, the distribution of attitudes toward death penalty is also the reflection of a partisan divide. Our results also support the hypothesis that government distrust increases death penalty support in Canada.
Apical pelvic organ prolapse repair via vaginal‐assisted natural orifice transluminal endoscopic surgery: Initial experience from a tertiary care hospital
Authors: Alay Ismail , Kaya Cihan , Cengiz Huseyin , Yildiz Sukru , Aslan Ozgur , Yasar Levent , Ekin Murat 
Published: September 2020

AbstractIntroductionNatural orifice transluminal endoscopic surgery has been used for gynecologic operations in recent years. The aim of the study is to describe our initial experience using vaginal‐assisted natural orifice transluminal endoscopic surgery (vNOTES) for apical pelvic organ prolapse repair.MethodsAfter patients underwent vaginal hysterectomy, vNOTES sacrocolpopexy (n = 4) or vNOTES high uterosacral ligament suspension (n = 7) were performed to treat symptomatic apical pelvic organ prolapse. Sociodemographic and clinical characteristics, Pelvic Organ Prolapse Quantification results, and recorded surgical data (eg, duration of surgery, intraoperative complications, additional prolapse and incontinence surgeries) were obtained from patient files and the hospital's database. Information from postoperative follow‐up visits, including complications and anatomical results, were also recorded.ResultsThe mean age of the patients was 60.7 ± 9.1 years. The mean total operative time was 121.3 ± 22.7 minutes. The mean operative time for vaginal hysterectomy, vNOTES sacrocolpopexy, and vNOTES uterosacral ligament suspension was 46 ± 11.9, 65 ± 38, 25 ± 8.2 minutes, respectively. There were no intraoperative and postoperative complications observed. The mean postoperative 24‐hour visual analog scale score was 3.5 ± 1.9 for vNOTES sacrocolpopexy patients and 3.2 ± 0.9 for vNOTES uterosacral ligament suspension patients. Only one patient in the vNOTES sacrocolpopexy group had a recurrence; she experienced stage 2 anterior compartment prolapse 8 months after surgery.ConclusionAs a treatment for apical pelvic organ prolapse, vNOTES is a feasible approach in both sacrocolpopexy and uterosacral ligament suspension.
Net benefit index: Assessing the influence of a biomarker for individualized treatment rules
Authors: Zhou Yiwang , Song Peter X.K. , Fu Haoda 
Published: September 2020

AbstractOne central task in precision medicine is to establish individualized treatment rules (ITRs) for patients with heterogeneous responses to different therapies. Motivated from a randomized clinical trial for Type 2 diabetic patients on a comparison of two drugs, that is, pioglitazone and gliclazide, we consider a problem: utilizing promising candidate biomarkers to improve an existing ITR. This calls for a biomarker evaluation procedure that enables to gauge added values of individual biomarkers. We propose an assessment analytic, termed as net benefit index (NBI), that quantifies a contrast between the resulting gain and loss of treatment benefits when a biomarker enters ITR to reallocate patients in treatments. We optimize reallocation schemes via outcome weighted learning (OWL), from which the optimal treatment group labels are generated by weighted support vector machine (SVM). To account for sampling uncertainty in assessing a biomarker, we propose an NBI‐based test for a significant improvement over the existing ITR, where the empirical null distribution is constructed via the method of stratified permutation by treatment arms. Applying NBI to the motivating diabetes trial, we found that baseline fasting insulin is an important biomarker that leads to an improvement over an existing ITR based only on patient's baseline fasting plasma glucose (FPG), age, and body mass index (BMI) to reduce FPG over a period of 52 weeks.
Child mortality estimation incorporating summary birth history data
Authors: Wilson Katie , Wakefield Jon 
Published: September 2020

AbstractThe United Nations' Sustainable Development Goal 3.2 aims to reduce under‐five child mortality to 25 deaths per 1000 live births by 2030. Child mortality tends to be concentrated in developing regions where information needed to assess achievement of this goal often comes from surveys and censuses. In both, women are asked about their birth histories, but with varying degrees of detail. Full birth history (FBH) data contain the reported dates of births and deaths of every surveyed mother's children. In contrast, summary birth history (SBH) data contain only the total number of children born and total number of children who died for each mother. Specialized methods are needed to accommodate this type of data into analyses of child mortality trends. We develop a data augmentation scheme within a Bayesian framework where for SBH data, birth and death dates are introduced as auxiliary variables. Since we specify a full probability model for the data, many of the well‐known biases that exist in this data can be accommodated, along with space‐time smoothing on the underlying mortality rates. We illustrate our approach in a simulation, showing robustness to model misspecification and that uncertainty is reduced when incorporating SBH data over simply analyzing all available FBH data. We also apply our approach to data from the Central region of Malawi and compare with the well‐known Brass method.
The Early Ontogeny of Reason Giving
Authors: Köymen Bahar , Tomasello Michael 
Published: September 2020

AbstractThe key context within which preschool children learn to justify beliefs with reasons is collaborative problem‐solving and decision‐making with peers, including in the moral domain, in which they engage with another coequal mind in a cooperative spirit. Evidence for this proposal comes from recent studies in which children demonstrated sensitivity to the common ground assumptions they shared with their peer partners in decision‐making, as well as an ability to provide reasons relevant to their shared understanding. Training studies suggest that discourse with others about reasons for beliefs provides children with the appropriate learning experiences. Internalizing this communicative process may be crucial for individual deliberative reasoning.
Global protected‐area coverage and human pressure on tidal flats
Authors: Hill Narelle K. , Woodworth Bradley K. , Phinn Stuart R. , Murray Nicholas J. , Fuller Richard A. 
Published: September 2020

AbstractTidal flats are a globally distributed coastal ecosystem important for supporting biodiversity and ecosystem services. Local to continental‐scale studies have documented rapid loss of tidal habitat driven by human impacts, but assessments of progress in their conservation are lacking. With an internally consistent estimate of distribution and change, based on Landsat satellite imagery, now available for the world's tidal flats, we examined tidal flat representation in protected areas (PAs) and human pressure on tidal flats. We determined tidal flat representation and its net change in PAs by spatially overlaying tidal flat maps with the World Database of Protected Areas. Similarly, we overlaid the most recent distribution map of tidal flats (2014–2016) with the human modification map (HMc) (range from 0, no human pressure, to 1, very high human pressure) to estimate the human pressure exerted on this ecosystem. Sixty‐eight percent of the current extent of tidal flats is subject to moderate to very high human pressure (HMc > 0.1), but 31% of tidal flat extent occurred in PAs, far exceeding PA coverage of the marine (6%) and terrestrial (13%) realms. Net change of tidal flat extent inside PAs was similar to tidal flat net change outside PAs from 1999 to 2016. Substantial shortfalls in protection of tidal flats occurred across Asia, where large intertidal extents coincided with high to very high human pressure (HMc > 0.4–1.0) and net tidal flat losses up to 86.4 km² (95% CI 83.9–89.0) occurred inside individual PAs in the study period. Taken together, our results show substantial progress in PA designation for tidal flats globally, but that PA status alone does not prevent all habitat loss. Safeguarding the world's tidal flats will thus require deeper understanding of the factors that govern their dynamics and effective policy that promotes holistic coastal and catchment management strategies.
Liver transplantation for combined hepatocellular‐cholangiocarcinoma: Outcomes and prognostic factors for mortality. A multicenter analysis
Authors: Jaradat Derar , Bagias Georgios , Lorf Thomas , Tokat Yaman , Obed Aiman , Oezcelik Arzu 
Published: September 2020

AbstractIntroductionCombined hepatocellular‐cholangiocarcinoma is rare and comprises features of hepatocellular carcinoma and cholangiocarcinoma. The treatment of choice has not yet been defined. The aim of the study was to analyze outcomes of patients with combined hepatocellular‐cholangiocarcinoma, who underwent liver transplantation.Material and MethodsAll patients with combined hepatocellular‐cholangiocarcinoma, who underwent liver transplantation, from January 2001 to August 2018 were identified. Pre‐, intra‐ and postoperative data were retrospectively assessed. A univariate analysis was performed to identify prognostic factors.ResultsA total number of 19 patients were included to this study. Perioperative death was seen in two patients (10.5%). Recurrent disease was reported in 11 patients (64.7%) within the median time of 4 months. One and three years survival rates were 57.1% (CI 0.301–1) and 38.1% (CI 0.137–1). Factors associated mortality were tumor size >3 cm, presence of lymphatic invasion, and prolonged ICU stay. Patients with mixed HCC‐CC lesions have significantly better survival compared to patients with separate lesions of HCC and CCC in one liver (p = .025).ConclusionAlthough overall survival rates are clearly decreased compared to HCC patients, liver transplantation should be taken under consideration for selected patients with early stage and real mixed HCC‐CC, who are likely to benefit from liver transplantation.
Risk factors for early development of cardiac allograft vasculopathy by intravascular ultrasound
Authors: Moayedi Yasbanoo , Fan Chun Po S. , Tremblay-Gravel Maxime , Miller Robert J. H. , Kawana Matsaka , Henricksen Erik , Parizo Justin , Wainwright Rebecca , Fearon William F. , Ross Heather J. , Khush Kiran K. , Teuteberg Jeffrey J. 
Published: September 2020

AbstractBackgroundCardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post‐transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor‐derived atherosclerosis (DA), early discontinuation of prednisone, and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS).MethodsRetrospective single‐center study of all adult transplant patients (2008‐2017) with serial IVUS at baseline and annually for 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥0.5 mm, and CAV development was defined as MIT ≥1 mm or an increase in MIT ≥0.5 mm at year 1 compared with baseline or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV.ResultsOf 282 patients screened, 186 patients had a 1‐year angiogram. The mean age of those included in the cohort was 51 ± 11 years, 70% were male, 58% were Caucasian, and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5 years is 41% in DA‐ vs. 59% in DA + (p = .012). Donor age was a strong predictor of DA (p = .016). Significant risk factors for CAV included male sex (HR = 4.141, p = .001), non‐Caucasian race (HR = 1.98, p = .011), BMI < 18 kg/m2 (HR = 4.596, p = .042), longer ischemic time (HR = 1.374, p = .028), older donor age (HR = 1.158, p = .009), and rejection with hemodynamic compromise within the first year (HR = 2.858, p = .043). Prednisone discontinuation within 1 year was associated with a lower risk of CAV (HR 0.58 p = .047). Initiation of proliferation signal inhibitors (PSI) within 2 years resulted in fewer cases of CAV (HR 0.397 p < .001).ConclusionIn patients with an angiogram at 1 year, those with DA were significantly more likely to develop CAV. Lower incidence of CAV by IVUS was seen in patients who discontinued prednisone in the first year or had initiation of a PSI within two years of transplantation. Knowledge of early IVUS may allow a more tailored approach to patient management.
What is Thy3a? A study of 336 Thy3a (AUS/FLUS) thyroid FNAs with histology compares UK RCPath with other reporting systems and shows how Thy3a subclassification can improve risk stratification and help address overuse of this category
Authors: van der Horst Cynthia , Wright Sylvia , Young David , Tailor Hitesh , Clark Louise 
Published: September 2020

AbstractIntroductionThy3a (AUS/FLUS) is an indeterminate and heterogeneous category in thyroid cytology. Thy3a reporting rates vary widely, with many laboratories documenting overuse. Subclassification of Thy3a helps with risk stratification. We aimed to investigate whether subclassification can also help address Thy3a overuse. We compare the UK reporting system with other terminologies.MethodsAn audit of thyroid fine needle aspirations (FNAs) reported at our institution between 2012 and 2017 was performed. Thy3a FNAs followed by histology were reviewed and subcategorised into four subgroups: Scanty Atypia (SA), Scanty Microfollicular (SMF), Favour Benign (FB) and Thyroiditis versus Neoplasm (TVN). Review and subclassification were blinded to histology outcomes. FNAs were correlated with histology and statistical analysis was performed.ResultsOur Thy3a rate was high (24% of all thyroid FNAs). For 336 Thy3a FNAs with histology, the malignancy rates of the four subgroups were: SA 68%, SMF 20%, FB 4%, TVN 31%. There were significant associations between subgroup and malignancy risk, and between subgroup and tumour risk. On histology, SA had more malignancies than expected and FB had fewer. SA and SMF had more tumours than expected and FB had fewer. SMF and Thy3f FNAs were similar in terms of tumour and malignancy outcomes.ConclusionsSubclassification of Thy3a FNAs into these four subgroups is recommended. This can improve risk stratification and help address overuse of Thy3a. We propose that some FB and SMF cases could be safely diverted to Thy2 and Thy3f respectively. We compare various reporting terminologies and question how indeterminate FNAs should be classified.