bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of occlusion length in recanalized chronic total occlusion lesion: a retrospective cohort study with 5-year follow-up
Authors: Tian Tao , Guan Changdong , Gao Lijian , Song Lei , Yuan Jiansong , Hu Fenghuan , Dou Kefei , Tang Yida , Wu Yongjian , Yang Yuejin , Bai Yinxiao , Cui Jingang , Xu Bo , Qiao Shubin , Yang Weixian 
Published: July 2020

ObjectivesThis study sought to investigate the relationship between occlusion length and long-term outcomes of patients with recanalised chronic total occlusion (CTO) lesion.DesignA retrospective cohort study.SettingFuwai Hospital, National Center for Cardiovascular Disease, Beijing, ChinaParticipantsConsecutive patients with successfully recanalised CTO were included from January 2010 to December 2013.Primary and secondary outcome measuresThe primary endpoint of the present study was a composite event of all-cause death and myocardial infarction (MI). The secondary endpoints included target lesion revascularisation (TLR) and target vessel revascularisation (TVR).ResultsA total of 1987 patients were included and 1801 (90.6%) subjects completed 5-year follow-up in this study. Based on occlusion length, the patients were divided equally into two groups: short (length <15 mm, n=957) and long (length ≥15 mm, n=1030) CTO group. Kaplan-Meier survival curve showed no significant difference in the risk of the composite primary endpoint between short and long CTO groups (p=0.242). Receiver operating characteristic curve analysis also established occlusion length ≥15 mm as a cut-off value for predicting TLR and TVR, with an area under the curve of 0.604 (95% CI: 0.569 to 0.638, p<0.001) and 0.605 (95% CI: 0.572 to 0.638; p<0.001). Kaplan-Meier analysis revealed that the risks for TLR (p=0.002) and TVR (p=0.002) were higher in a patient with long CTO lesion. Multivariate Cox analysis also identified long CTO lesion as an independent predictor of TLR (HR: 1.539, 95% CI: 1.033 to 2.293; p=0.034) and TVR (HR: 1.476, 95% CI: 1.012 to 2.151; p=0.043).ConclusionPatients with long CTO lesion did not show a higher risk of death and MI after recanalisation, but had higher risks of TLR and TVR. Lesion with occlusion length ≥15 mm should be under close surveillance for restenosis after recanalisation.
Impact of the Norwegian National Patient Safety Program on implementation of the WHO Surgical Safety Checklist and on perioperative safety culture
Authors: Haugen Arvid Steinar , Søfteland Eirik , Sevdalis Nick , Eide Geir Egil , Nortvedt Monica Wammen , Vincent Charles , Harthug Stig 
Published: July 2020

ObjectivesOur primary objective was to study the impact of the Norwegian National Patient Safety Campaign and Program on Surgical Safety Checklist (SSC) implementation and on safety culture. Secondary objective was associations between SSC fidelity and safety culture. We hypothesised that the programme influenced on SSC use and operating theatre personnel’s safety culture perceptions.SettingA longitudinal cross-sectional study was conducted in a large Norwegian tertiary teaching hospital.ParticipantsWe invited 1754 operating theatre personnel to participate in the study, of which 920 responded to the surveys at three time points in 2009, 2010 and 2017.Primary and secondary outcome measuresPrimary outcome was the results of the patient safety culture measured by the culturally adapted Norwegian version of the Hospital Survey on Patient Safety Culture. Our previously published results from 2009/2010 were compared with new data collected in 2017. Secondary outcome was correlation between SSC fidelity and safety culture. Fidelity was electronically recorded.ResultsSurvey response rates were 61% (349/575), 51% (292/569) and 46% (279/610) in 2009, 2010 and 2017, respectively. Eight of the 12 safety culture dimensions significantly improved over time with the largest increase being ‘Hospital managers’ support to patient safety’ from a mean score of 2.82 at baseline in 2009 to 3.15 in 2017 (mean change: 0.33, 95% CI 0.21 to 0.44). Fidelity in use of the SSC averaged 88% (26 741/30 426) in 2017. Perceptions of safety culture dimensions in 2009 and in 2017 correlated significantly though weakly with fidelity (r=0.07–0.21).ConclusionThe National Patient Safety Program, fostering engagement from trust boards, hospital managers and frontline operating theatre personnel enabled effective implementation of the SSC. As part of a wider strategic safety initiative, implementation of SSC coincided with an improved safety culture.
Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma
Authors: Bedrose Sara , Miller Kevin Charles , Altameemi Lina , Ali Mohamed S , Nassar Sameh , Garg Naveen , Daher Marilyne , Eaton Keith D , Yorio Jeffrey Thomas , Daniel Davey B , Campbell Matthew , Bible Keith C , Ryder Mabel , Chintakuntlawar Ashish V , Habra Mouhammed Amir 
Published: July 2020

BackgroundThere is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.MethodsA retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC.ResultsEight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21–49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2–9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8–not reached) and median duration of therapy was 8.5 months (range 2–22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events.ConclusionsIn our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.
Biallelic loss-of-functionZFYVE19mutations are associated with congenital hepatic fibrosis, sclerosing cholangiopathy and high-GGT cholestasis
Authors: Luan Weisha , Hao Chen-Zhi , Li Jia-Qi , Wei Qing , Gong Jing-Yu , Qiu Yi-Ling , Lu Yi , Shen Cong-Huan , Xia Qiang , Xie Xin-Bao , Zhang Mei-Hong , Abuduxikuer Kuerbanjiang , Li Zhong-Die , Wang Li , Xing Qing-He , Knisely A S , Wang Jian-She 
Published: July 2020

BackgroundFor many children with intrahepatic cholestasis and high-serum gamma-glutamyl transferase (GGT) activity, a genetic aetiology of hepatobiliary disease remains undefined. We sought to identify novel genes mutated in children with idiopathic high-GGT intrahepatic cholestasis, with clinical, histopathological and functional correlations.MethodsWe assembled a cohort of 25 children with undiagnosed high-GGT cholestasis and without clinical features of biliary-tract infection or radiological features of choledochal malformation, sclerosing cholangitis or cholelithiasis. Mutations were identified through whole-exome sequencing and targeted Sanger sequencing. We reviewed histopathological findings and assessed phenotypical effects of ZFYVE19 deficiency in cultured cells by immunofluorescence microscopy.ResultsNine Han Chinese children harboured biallelic, predictedly complete loss-of-function pathogenic mutations inZFYVE19(c.314C>G, p.S105X; c.379C>T, p.Q127X; c.514C>T, p.R172X; c.547C>T, p.R183X; c.226A>G, p.M76V). All had portal hypertension and, at liver biopsy, histopathological features of the ductal plate malformation (DPM)/congenital hepatic fibrosis (CHF). Four children required liver transplantation for recurrent gastrointestinal haemorrhage. DPM/CHF was confirmed at hepatectomy, with sclerosing small-duct cholangitis. Immunostaining for two primary-cilium axonemal proteins found expression that was deficient intraluminally and ectopic within cholangiocyte cytoplasm. ZFYVE19 depletion in cultured cells yielded abnormalities of centriole and axoneme.ConclusionBiallelicZFYVE19mutations can lead to high-GGT cholestasis and DPM/CHF in vivo. In vitro, they can lead to centriolar and axonemal abnormalities. These observations indicate that mutation inZFYVE19results, through as yet undefined mechanisms, in a ciliopathy.
Congenital sensorineural hearing loss as the initial presentation ofPTPN11-associated Noonan syndrome with multiple lentigines or Noonan syndrome: clinical features and underlying mechanisms
Authors: Gao Xue , Huang Sha-Sha , Qiu Shi-Wei , Su Yu , Wang Wei-Qian , Xu Hui-Yan , Xu Jin-Cao , Kang Dong-Yang , Dai Pu , Yuan Yong-Yi 
Published: July 2020

BackgroundGermline variants inPTPN11are the primary cause of Noonan syndrome with multiple lentigines (NSML) and Noonan syndrome (NS), which share common skin and facial symptoms, cardiac anomalies and retardation of growth. Hearing loss is considered an infrequent feature in patients with NSML/NS. However, in our cohort, we identified a group of patients withPTPN11pathogenic variants that were primarily manifested in congenital sensorineural hearing loss (SNHL). This study evaluated the incidence ofPTPN11-related NSML or NS in patients with congenital SNHL and explored the expression ofPTPN11and the underlying mechanisms in the auditory system.MethodsA total of 1502 patients with congenital SNHL were enrolled. Detailed phenotype-genotype correlations were analysed in patients withPTPN11variants. Immunolabelling of Ptpn11 was performed in P35 mice. Zebrafish withPtpn11knockdown/mutant overexpression were constructed to further explore mechanism underlying the phenotypes.ResultsTen NSML/NS probands were diagnosed via the identification of pathogenic variants ofPTPN11, which accounted for ~0.67% of the congenital SNHL cases. In mice cochlea, Shp2, which is encoded byPtpn11, is distributed in the spiral ganglion neurons, hair cells and supporting cells of the inner ear. In zebrafish, knockdown ofptpn11aand overexpression of mutantPTPN11were associated with a significant decrease in hair cells and supporting cells. We concluded that congenital SNHL could be a major symptom inPTPN11-associated NSML or NS. Other features may be mild, especially in children.ConclusionScreening forPTPN11in patients with congenital hearing loss and variant-based diagnoses are recommended.
Lung cancer mortality in the French cohort of titanium dioxide workers: some aetiological insights
Authors: Guseva Canu Irina , Gaillen-Guedy Alan , Wild Pascal , Straif Kurt , Luce Danièle 
Published: July 2020

ObjectivesTitanium dioxide (TiO2) is widely used in construction, food, cosmetic and medical industry. The current evidence on TiO2carcinogenicity in humans is considered inadequate. As French participants of the European cohort of TiO2workers exhibited an increase in mortality from lung cancer, we aimed at investigating whether TiO2exposure, co-exposures or smoking can explain this increase.MethodsWe reanalysed the data of 833 French male workers (follow-up period 1968–1997) and used multiple imputation to complete their smoking status. We considered respirable TiO2dust as primary exposure of interest, estimated as continuous cumulative (mg/m3-year) and annual average (mg/m3) concentrations and binary and 4-class categorical variables, with cut-off values of 0.3 and 2.4 mg/m3(the German and American occupational exposure limits, respectively). For each exposure metric, we estimated HRs and associated 95% CIs, using Cox regression models adjusted for calendar period, exposure duration and smoking.ResultsThe fully adjusted model yielded a HR=3.7 (95% CI=0.79 to 17.95) for TiO2-exposed workers vs unexposed and a HR=27.33 (95% CI=4.35 to 171.84) for those exposed to >2.4 mg/m3as annual average concentration. Employment duration was negatively related with lung cancer mortality, therefore cumulative exposure had a small effect on mortality (HR=1.03 (95% CI=0.99 to 1.08) per mg/m3-year).ConclusionThis study suggests a positive relationship between TiO2exposure and lung cancer mortality in TiO2workers, whatever the exposure variable used, despite a limited statistical power in some models. The results question the current evidence on TiO2carcinogenicity in humans but need to be confirmed in other cohorts, using different statistical approaches.
Enhancing help-seeking behaviour among men who have sex with men at risk for sexually transmitted infections: the syn.bas.in randomised controlled trial
Authors: Achterbergh Roeland Christiaan Alfons , van Rooijen Martijn S , van den Brink Wim , Boyd Anders , de Vries Henry John Christiaan 
Published: July 2020

ObjectivesMen who have sex with men (MSM) are at increased risk for STIs and mental disorders. Syndemic theory holds that psychosocial issues co-occur and interact, and thus increase sexual risk behaviour. Psychosocial issue identification, referral and management might reduce risk behaviour.MethodsIn the syndemic-based intervention study, an open-label randomised controlled trial, MSM were enrolled at the STI outpatient clinic of the Public Health Service of Amsterdam. We screened participants using validated questionnaires on the following problem domains: alcohol and substance use, sexual compulsivity, anxiety, depression, attention deficit hyperactivity disorder, alexithymia, intimate partner violence and childhood sexual abuse. Individuals were randomly assigned (1:1) to receive either tailored, face-to-face feedback and help-seeking advice on mental health screening, or no feedback and no help-seeking advice. Participants were followed trimonthly for a year. The primary outcomes were self-reported and confirmed help-seeking behaviour.ResultsWe included 155 MSM: 76 in the intervention group and 79 in the control group. At inclusion, 128 participants (83.1%) scored positive in at least one problem domain. We found no significant differences in self-reported or confirmed help-seeking behaviour between the intervention and the control group: 41% vs 29% (p=0.14) and 28% vs 22% (p=0.44), respectively. There were also no differences in STI incidence and condomless anal sex acts between the two groups.ConclusionScreening showed high prevalence of problems related to mental health and substance use, while tailored feedback, advice and referral did not significantly increase help-seeking behaviour. Other interventions are needed to tackle the high burden of mental disorders among MSM.Trial registration numberNCT02859935.
Dragging of inertial frames in the composed black-hole-particle system and the weak cosmic censorship conjecture
Authors: Hod Shahar 
Published: July 2020

AbstractWe analyze a gedanken experiment in which a spinning particle that also possesses an extrinsic orbital angular momentum is captured by a spinning Kerr black hole. The gravitational spin-orbit interaction decreases the energy of the particle, thus allowing one to test the validity of the Penrose weak cosmic censorship conjecture in extreme situations that have not been analyzed thus far. It is explicitly shown that, to leading order in the black-hole-particle interactions, the linearized test particle can over-spin the black hole, thus exposing its inner spacetime singularity to external observers. However, we prove that the general relativistic effect of dragging of inertial frames by the orbiting particle contributes to the energy budget of the system a non-linear black-hole-particle interaction term that ultimately ensures the validity of the Penrose cosmic censorship conjecture in this type of gedanken experiments.
Endometrial Cancer Molecular Risk Stratification is Equally Prognostic for Endometrioid Ovarian Carcinoma
Authors: Krämer Pauline , Talhouk Aline , Brett Mary Anne , Chiu Derek S. , Cairns Evan S. , Scheunhage Daniëlla A. , Hammond Rory F.L. , Farnell David , Nazeran Tayyebeh M. , Grube Marcel , Xia Zhouchunyang , Senz Janine , Leung Samuel , Feil Lukas , Pasternak Jana , Dixon Katherine , Hartkopf Andreas , Krämer Bernhard , Brucker Sara , Heitz Florian , du Bois Andreas , Harter Philipp , Kommoss Felix K.F. , Sinn Hans-Peter , Heublein Sabine , Kommoss Friedrich , Vollert Hans-Walter , Manchanda Ranjit , de Kroon Cornelis D. , Nijman Hans W. , de Bruyn Marco , Thompson Emily F. , Bashashati Ali , McAlpine Jessica N. , Singh Naveena , Tinker Anna V. , Staebler Annette , Bosse Tjalling , Kommoss Stefan , Köbel Martin , Anglesio Michael S. 
Published: July 2020

Abstract

Purpose:
Endometrioid ovarian carcinoma (ENOC) is generally associated with a more favorable prognosis compared with other ovarian carcinomas. Nonetheless, current patient treatment continues to follow a “one-size-fits-all” approach. Even though tumor staging offers stratification, personalized treatments remain elusive. As ENOC shares many clinical and molecular features with its endometrial counterpart, we sought to investigate The Cancer Genome Atlas–inspired endometrial carcinoma (EC) molecular subtyping in a cohort of ENOC.

Experimental Design:
IHC and mutation biomarkers were used to segregate 511 ENOC tumors into four EC-inspired molecular subtypes: low-risk POLE mutant (POLEmut), moderate-risk mismatch repair deficient (MMRd), high-risk p53 abnormal (p53abn), and moderate-risk with no specific molecular profile (NSMP). Survival analysis with established clinicopathologic and subtype-specific features was performed.

Results:
A total of 3.5% of cases were POLEmut, 13.7% MMRd, 9.6% p53abn, and 73.2% NSMP, each showing distinct outcomes (P &lt; 0.001) and survival similar to observations in EC. Median OS was 18.1 years in NSMP, 12.3 years in MMRd, 4.7 years in p53abn, and not reached for POLEmut cases. Subtypes were independent of stage, grade, and residual disease in multivariate analysis.

Conclusions:
EC-inspired molecular classification provides independent prognostic information in ENOC. Our findings support investigating molecular subtype–specific management recommendations for patients with ENOC; for example, subtypes may provide guidance when fertility-sparing treatment is desired. Similarities between ENOC and EC suggest that patients with ENOC may benefit from management strategies applied to EC and the opportunity to study those in umbrella trials.
Vital Roles of Gremlin‐1 in Pulmonary Arterial Hypertension Induced by Systemic‐to‐Pulmonary Shunts
Authors: Meng Liukun , Teng Xiao , Liu Yao , Yang Chao , Wang Shengwei , Yuan Wen , Meng Jian , Chi Hongjie , Duan Lihua , Liu Xiaoyan 
Published: July 2020

Background
Heterozygous mutation in BMP (bone morphogenetic protein) receptor 2 is rare, but BMP cascade suppression is common in congenital heart disease–associated pulmonary arterial hypertension (CHD‐PAH); however, the underling mechanism of BMP cascade suppression independent of BMP receptor 2 mutation is unknown.

Methods and Results
Pulmonary hypertensive status observed in CHD‐PAH was surgically reproduced in rats. Gremlin‐1 expression was increased, but BMP cascade was suppressed, in lungs from CHD‐PAH patients and shunted rats, whereas shunt correction retarded these trends in rats. Immunostaining demonstrated increased gremlin‐1 was mainly in the endothelium and media of remodeled pulmonary arteries. However, mechanical stretch time‐ and amplitude‐dependently stimulated gremlin‐1 secretion and suppressed BMP cascade in distal pulmonary arterial smooth muscle cells from healthy rats. Under static condition, gremlin‐1 significantly promoted the proliferation and inhibited the apoptosis of distal pulmonary arterial smooth muscle cells from healthy rats via BMP cascade. Furthermore, plasma gremlin‐1 closely correlated with hemodynamic parameters in CHD‐PAH patients and shunted rats.

Conclusions
Serving as an endogenous antagonist of BMP cascade, the increase of gremlin‐1 in CHD‐PAH may present a reasonable mechanism explanation for BMP cascade suppression independent of BMP receptor 2 mutation.
Emergent Large Vessel Occlusion Stroke During New York City’s COVID-19 Outbreak
Authors: Majidi Shahram , Fifi Johanna T. , Ladner Travis R. , Lara-Reyna Jacques , Yaeger Kurt A. , Yim Benjamin , Dangayach Neha , Oxley Thomas J. , Shigematsu Tomoyoshi , Kummer Benjamin R. , Stein Laura K. , Weinberger Jesse , Fara Michael G. , De Leacy Reade , Dhamoon Mandip S. , Tuhrim Stanley , Mocco J 
Published: July 2020

Background and Purpose:
The 2019 novel coronavirus outbreak and its associated disease (coronavirus disease 2019 [COVID-19]) have created a worldwide pandemic. Early data suggest higher rate of ischemic stroke in severe COVID-19 infection. We evaluated whether a relationship exists between emergent large vessel occlusion (ELVO) and the ongoing COVID-19 outbreak.

Methods:
This is a retrospective, observational case series. Data were collected from all patients who presented with ELVO to the Mount Sinai Health System Hospitals across New York City during the peak 3 weeks of hospitalization and death from COVID-19. Patients’ demographic, comorbid conditions, cardiovascular risk factors, COVID-19 disease status, and clinical presentation were extracted from the electronic medical record. Comparison was made between COVID-19 positive and negative cohorts. The incidence of ELVO stroke was compared with the pre-COVID period.

Results:

Forty-five consecutive ELVO patients presented during the observation period. Fifty-three percent of patients tested positive for COVID-19. Total patients’ mean (±SD) age was 66 (±17). Patients with COVID-19 were significantly younger than patients without COVID-19, 59±13 versus 74±17 (odds ratio [95% CI], 0.94 [0.81–0.98];
P
=0.004). Seventy-five percent of patients with COVID-19 were male compared with 43% of patients without COVID-19 (odds ratio [95% CI], 3.99 [1.12–14.17];
P
=0.032). Patients with COVID-19 were less likely to be White (8% versus 38% [odds ratio (95% CI), 0.15 (0.04–0.81);
P
=0.027]). In comparison to a similar time duration before the COVID-19 outbreak, a 2-fold increase in the total number of ELVO was observed (estimate: 0.78 [95% CI, 0.47–1.08],
P
≤0.0001).

Conclusions:
More than half of the ELVO stroke patients during the peak time of the New York City’s COVID-19 outbreak were COVID-19 positive, and those patients with COVID-19 were younger, more likely to be male, and less likely to be White. Our findings also suggest an increase in the incidence of ELVO stroke during the peak of the COVID-19 outbreak.
Continuing or Settled? Prosecution of Israeli Settlements under Article 8(2)(b)(viii) of the Rome Statute
Authors: Yasar Aysev Uzay 
Published: July 2020

Abstract
This article provides a definitional framework for the concepts of instantaneous, continuous and continuing crimes, drawing from domestic and international legal authorities and applying these definitions to article 8(2)(b)(viii) of the Rome Statute of the International Criminal Court, which criminalizes transfer of population by the Occupying Power into an occupied territory. The article focuses on the interpretation of article 8(2)(b)(viii) as an instantaneous, continuous or continuing crime with reference to the Israeli settlement activities in the West Bank in order to assess whether the transfer of settlers into the West Bank prior to June 2014 – i.e. the date that the temporal jurisdiction of the ICC starts in the territory of the State of Palestine, can be investigated and prosecuted.