bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment persistence and colectomy-free outcomes in patients with ulcerative colitis receiving golimumab or adalimumab: a UK experience
Authors: Hoque Sami , Puenpatom Amy , Boccaletti Simona , Green Chloe , Black Christopher M , Roberts Jenna , Rajkovic Ivana , Milligan Gary 
Published: November 2020

ObjectiveTo examine real-world treatment persistence, colectomy-free survival and treatment switching patterns in UK patients with ulcerative colitis (UC) prescribed golimumab or adalimumab.DesignThis was a retrospective chart review study in adult patients diagnosed with UC using data from 16 National Health Service sites in the UK. Patient records were included in the study if they had initiated first or second-line adalimumab or golimumab between 1 March 2016 and 30 September 2017 (index date). Subjects were required for ≥6 months post treatment initiation. Demographics, clinical characteristics, treatment-related data and colectomy data were extracted over a follow-up period of 6–12 months. Treatment persistence rate was the primary outcome. Colectomy-free survival and treatment switching were secondary outcomes. Outcomes were compared between treatments using χ2tests and Fisher’s exact test for categorical variables. The t-tests were used for continuous variables. Time-to-event variables were evaluated using Kaplan-Meier curves and log-rank tests.ResultsThe study included a total of 183 patients (96 (52.5%) prescribed adalimumab; 87 (47.5%) golimumab), and patients were mostly first line (79.8%). Demographic and clinical characteristics were generally similar between treatment groups. Persistence rates within 12 months were 64.6% for adalimumab and 64.4% for golimumab (p=0.681). Overall, 20.2% switched to other therapy within 1 year, with 8.2% golimumab and 12.0% adalimumab switching to another biologic. Of patients prescribed adalimumab, 14.6% had ≥1 dose change, mainly dose escalations. In the 12 months post treatment initiation, 8.2% of patients underwent colectomy, with no significant difference in colectomy-free survival by treatment, p=0.73.ConclusionThis study provides evidence of clinical outcomes and real-world persistence for adalimumab and golimumab in UC. The persistence rates of both therapies were above 64.0% at 12 months following treatment initiation. In addition, the 1-year colectomy-free survival was relatively similar between the two treatments.
Managing outbreaks of highly contagious diseases in prisons: a systematic review
Authors: Beaudry Gabrielle , Zhong Shaoling , Whiting Daniel , Javid Babak , Frater John , Fazel Seena 
Published: November 2020

BackgroundThere are reports of outbreaks of COVID-19 in prisons in many countries. Responses to date have been highly variable and it is not clear whether public health guidance has been informed by the best available evidence. We conducted a systematic review to synthesise the evidence on outbreaks of highly contagious diseases in prison.MethodsWe searched seven electronic databases for peer-reviewed articles and official reports published between 1 January 2000 and 28 July 2020. We included quantitative primary research that reported an outbreak of a given contagious disease in a correctional facility and examined the effects of interventions. We excluded studies that did not provide detail on interventions. We synthesised common themes using the Synthesis Without Meta-analysis (SWiM) guideline, identified gaps in the literature and critically appraised the effectiveness of various containment approaches.ResultsWe identified 28 relevant studies. Investigations were all based in high-income countries and documented outbreaks of tuberculosis, influenza (types A and B), varicella, measles, mumps, adenovirus and COVID-19. Several themes were common to these reports, including the public health implications of infectious disease outbreaks in prison, and the role of interagency collaboration, health communication, screening for contagious diseases, restriction, isolation and quarantine, contact tracing, immunisation programmes, epidemiological surveillance and prison-specific guidelines in addressing any outbreaks.DiscussionPrisons are high-risk settings for the transmission of contagious diseases and there are considerable challenges in managing outbreaks in them. A public health approach to managing COVID-19 in prisons is required.PROSPERO registration numberCRD42020178827
Differential effect on different immune subsets of neoadjuvant chemotherapy in patients with TNBC
Authors: Massa Chiara , Karn Thomas , Denkert Carsten , Schneeweiss Andreas , Hanusch Claus , Blohmer Jens-Uwe , Zahm Dirk-Michael , Jackisch Christian , van Mackelenbergh Marion , Thomalla Jörg , Marme Frederik , Huober Jens , Müller Volkmar , Schem Christian , Mueller Anja , Stickeler Elmar , Biehl Katharina , Fasching Peter A , Untch Michael , Loibl Sibylle , Weber Karsten , Seliger Barbara 
Published: November 2020

BackgroundTriple-negative breast cancer (TNBC) is the most aggressive form of breast cancer (BC). Due to the absence of targets such as HER2 or hormone receptors, early TNBC is treated with surgery and chemotherapy. Since TNBC is also considered the most immunogenic type of BC with tumor infiltrating lymphocytes that are predictive for chemotherapy response and prognostic for patients′ survival, many different immunotherapeutic strategies are currently explored in clinical trials for the treatment of this disease. In order to efficiently combine chemotherapy with immunotherapy, it is important to evaluate the effect of chemotherapy on immune cells in vivo.MethodsPeripheral blood was taken from 56 patients with TNBC undergoing neoadjuvant chemotherapy with nanoparticle albumin-bound paclitaxel (Nab-Pac) followed by epirubicin and cyclophosphamide (EC) at three different time points. Multicolor flow cytometry was used to characterize the immune cell composition and functional properties along neoadjuvant chemotherapy.ResultsWhereas the first phase of the neoadjuvant chemotherapy did not significantly alter the patients′ immune cell composition, after the second phase of chemotherapeutic administration most B cells (>90%) were lost and the frequency of natural killer (NK) cells and CD4+ T lymphocytes decreased approximately to 50%. In contrast, the frequency of CD8+ T cells were less affected.ConclusionsDespite late consequences of Nab-Pac cannot be ruled out, these data suggest that different chemotherapeutics might have distinct effects on the immune cell repertoire and that different immune cell populations exhibit a specific susceptibility to these chemotherapies with B and NK cells being more affected than T cells. This might also have an impact on the combination of chemotherapies with immunotherapies.Trial registration numberNCT02685059.
Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?
Authors: Pennisi Alessandra , Rötig Agnès , Roux Charles-Joris , Lévy Raphaël , Henneke Marco , Gärtner Jutta , Teke Kisa Pelin , Sarioglu Fatma Ceren , Yiş Uluç , Konczal Laura L , Burkardt Deepika D , Wu Sulin , Gaignard Pauline , Besmond Claude , Hubert Laurence , Rio Marlène , Barcia Giulia , Munnich Arnold , Boddaert Nathalie , Schiff Manuel 
Published: November 2020

BackgroundBiallelic variants in PNPT1 cause a mitochondrial disease of variable severity. PNPT1 (polynucleotide phosphorylase) is a mitochondrial protein involved in RNA processing where it has a dual role in the import of small RNAs into mitochondria and in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This, in turn, prevents the activation of type I interferon response. Detailed neuroimaging findings in PNPT1-related disease are lacking with only a few patients reported with basal ganglia lesions (Leigh syndrome) or non-specific signs.Objective and methodsTo document neuroimaging data in six patients with PNPT1 highlighting novel findings.ResultsTwo patients exhibited striatal lesions compatible with Leigh syndrome; one patient exhibited leukoencephalopathy and one patient had a normal brain MRI. Interestingly, two unrelated patients exhibited cystic leukoencephalopathy resembling RNASET2-deficient patients, patients with Aicardi-Goutières syndrome (AGS) or congenital CMV infection.ConclusionWe suggest that similar to RNASET2, PNPT1 be searched for in the setting of cystic leukoencephalopathy. These findings are in line with activation of type I interferon response observed in AGS, PNPT1 and RNASET2 deficiencies, suggesting a common pathophysiological pathway and linking mitochondrial diseases, interferonopathies and immune dysregulations.
Endovascular management of torcular dural sinus malformations in children: the role of straight sinus occlusion
Authors: Smajda Stanislas , Söderman Michael , Dorfmüller Georg , Dorison Nathalie , Nghe Marie-Claire , Rodesch Georges 
Published: November 2020

BackgroundTorcular dural sinus malformations (tDSMs) with arteriovenous shunts are rare congenital intracranial vascular malformations that carry a high rate of neurologic impairment and death in the neonatal, infant and young pediatric population. Their impact on brain venous drainage, especially the deep venous system, is one of the key factors in the clinical prognosis and natural history of the disease. We describe our therapeutic strategy for tDSMs, disconnecting the reflux into the deep venous system by performing an endovascular straight sinus occlusion.MethodsAmong all children with dural sinus malformations seen between 2002 and 2020, we retrospectively reviewed those with tDSM in whom straight sinus occlusion had been performed.ResultsOur databank included nine patients with tDSM that were embolized. Mean age at the clinical onset was 8.9±9.6 months (min–max=0–31). Five patients presented a significant reflux in the straight sinus on digital subtraction angiography. Those patients were initially clinically worse (mean modified Rankin Scale (mRS) 3.8) than those who did not present with reflux (mean mRS 2.25), this reflux being responsible for intraventricular hemorrhage in three patients. The reflux was suppressed by transarterial embolization in one patient and by transvenous straight sinus occlusion in four patients. Staged endovascular treatment resulted in a complete cure in six patients without complications, and clinical improvement in all patients.ConclusionStraight sinus occlusion is a feasible technique that needs to be considered in the treatment strategy for tDSM with deep venous reflux in order to avoid or minimize brain damage.
Transradial versus transfemoral access for anterior circulation mechanical thrombectomy: analysis of 375 consecutive cases
Authors: Phillips Timothy John , Crockett Matthew Thomas , Selkirk Gregory D , Kabra Ruchi , Chiu Albert Ho Yuen , Singh Tejinder , Phatouros Constantine , McAuliffe William 
Published: November 2020

ObjectiveTo compare transradial artery access (TRA) to the gold standard of transfemoral artery access (TFA) in mechanical thrombectomy (MT) for stroke caused by anterior circulation large vessel occlusion.MethodsThe clinical outcomes, procedural speed, angiographic efficacy and safety of both techniques were analysed in 375 consecutive cases over an 18-month period in a high volume statewide neurointerventional service.ResultsThere was no significant difference in patient characteristics, stroke parameters, imaging techniques or intracranial techniques. The median time elapsed between CT scanning and reperfusion was 96.5 min (IQR 68–123) in the TFA group and 95 min (IQR 68–123) in the TRA group (p=0.456). Of 336 patients who were independent at presentation 58% (124/214) of the TFA group and 67% (82/122) of the TRA group had a modified Rankin score of 0–2 at 90-day follow-up (p=0.093). Cross-over from radial to femoral was 4.6% (4/130) compared with 1.6% cross-over from femoral to radial (4/245), but did not meet the predetermined level of statistical significance (OR 2.92, 95% CI 0.81 to 10.52), p=0.088) and did not impact median procedural speed. Adequate angiographic reperfusion, first pass reperfusion, embolisation to new territory and symptomatic intracranial haemorrhage were similar in both groups. There was a significant difference in major access site complications requiring an additional procedure. None of the TRA cases had a major access site complication but 6.5% (16/245) of the TFA cases did (p=0.003).ConclusionThis study suggests that using TRA for anterior circulation MT is fast, efficacious, safe and not inferior to the gold standard of TFA.
Transitions between cigarette, ENDS and dual use in adults in the PATH study (waves 1–4): multistate transition modelling accounting for complex survey design
Authors: Brouwer Andrew F , Jeon Jihyoun , Hirschtick Jana L , Jimenez-Mendoza Evelyn , Mistry Ritesh , Bondarenko Irina V , Land Stephanie R , Holford Theodore R , Levy David T , Taylor Jeremy M G , Fleischer Nancy L , Meza Rafael 
Published: November 2020

IntroductionEven prior to 2018, electronic nicotine delivery systems (ENDS) began to dramatically change the landscape of tobacco products and product use patterns in the USA.MethodsUsing a Markov multistate transition model accounting for complex survey design, transition rates between never, non-current, cigarette, ENDS and dual use states were estimated for 23 253 adult participants in waves 1–4 (approximately 2013–2017) of the Population Assessment of Tobacco and Health study. We made short-term transition projections and estimated HRs for age, sex, race/ethnicity, education and income.ResultsCigarette use was persistent among adults, with 89.7% (95% CI 89.1% to 90.3%) of exclusive cigarette users and 86.1% (95% CI 84.4% to 87.9%) of dual users remaining cigarette users (either exclusive or dual) after one wave. In contrast, ENDS use was less persistent, with 72.1% (95% CI 69.6% to 74.6%) of exclusive ENDS users and 50.5% (95% CI 47.8% to 53.3%) of dual users remaining ENDS users (with or without cigarettes) after one wave. Exclusive ENDS users were more likely to start cigarette use after one wave than either never users (HR 25.2; 95% CI 20.9 to 30.5) or non-current users (HR 5.0; 95% CI 4.3 to 5.8). Dual users of ENDS and cigarettes were more likely to stop using cigarettes than exclusive cigarette users (HR 1.9; 95% CI 1.6 to 2.3). Transition rates varied among sociodemographic groups.ConclusionsMultistate transition models are an effective tool for uncovering and characterising longitudinal patterns and determinants of tobacco use from complex survey data. ENDS use among US adults was less persistent than cigarette use prior to 2018.
Revisiting the restricted movement paradigm: the dispersal of Atlantic salmon fry from artificial redds
Authors: Eisenhauer Zachary J. , Christman Paul M. , Matte Jean-Michel , Ardren William R. , Fraser Dylan J. , Grant James W.A. 
Published: November 2020

The restricted movement paradigm (RMP) asserts that stream fishes are sedentary, living much of their lives within a single reach. To test the RMP, we implanted eyed Atlantic salmon eggs (Salmo salar) into a total of 19 artificial redds, in seven salmon-free streams, in 6 years, and estimated summer fry dispersal through electrofishing surveys. As expected, most fry dispersed downstream, but an average of 35% moved upstream. Surprisingly, fry moved just as far upstream as downstream (medians = 403 and 404 m, respectively). Fry were larger at lower densities and farther from redd sites, consistent with density-dependent growth, and larger upstream than downstream, possibly indicating that larger fry were better able to move upstream against the current. Dispersal distances were normally distributed around all but two of 19 redds, and half of the downstream dispersal curves were best described by unimodal distributions, consistent with a homogeneous movement strategy. Our data suggest that salmon fry were more mobile and move upstream more than previously thought, which should facilitate their stocking or reintroduction to new habitats.
Deciphering the mechanism of near-threshold $$J/\psi $$ photoproduction
Authors: Du Meng-Lin , Baru Vadim , Guo Feng-Kun , Hanhart Christoph , Meißner Ulf-G. , Nefediev Alexey , Strakovsky Igor 
Published: November 2020

AbstractThe photoproduction of the $$J/\psi $$

J
/
ψ

off the proton is believed to deepen our understanding of various physics issues. On the one hand, it is proposed to provide access to the origin of the proton mass, based on the QCD multipole expansion. On the other hand, it can be employed in a study of pentaquark states. The process is usually assumed to proceed through vector-meson dominance, that is the photon couples to a $$J/\psi $$

J
/
ψ

which rescatters with the proton to give the $$J/\psi p$$

J
/
ψ
p

final state. In this paper, we provide a compelling hint for and propose measurements necessary to confirm a novel production mechanism via the $$\varLambda _c \bar{D}^{(*)}$$

Λ
c

D

¯

(

∗
)

intermediate states. In particular, there must be cusp structures at the $$\varLambda _c \bar{D}^{(*)}$$

Λ
c

D

¯

(

∗
)

thresholds in the energy dependence of the $$J/\psi $$

J
/
ψ

photoproduction cross section. The same mechanism also implies the $$J/\psi $$

J
/
ψ

-nucleon scattering lengths of order 1 mfm. Given this, one expects only a minor contribution of charm quarks to the nucleon mass.
Bouncing solutions in f(T) gravity
Authors: Skugoreva Maria A. , Toporensky Alexey V. 
Published: November 2020

AbstractWe consider certain aspects of cosmological dynamics of a spatially curved Universe in f(T) gravity. Local analysis allows us to find conditions for bounces and for static solutions; these conditions appear to be in general less restrictive than in general relativity. We also provide a global analysis of the corresponding cosmological dynamics in the cases when bounces and static configurations exist, by constructing phase diagrams. These diagrams indicate that the fate of a big contracting Universe is not altered significantly when bounces become possible, since they appear to be inaccessible by a sufficiently big Universe.
The Impact of Liver Transplantation on Hepatocellular Carcinoma Mortality in the United States
Authors: Mahale Parag , Shiels Meredith S. , Lynch Charles F. , Chinnakotla Srinath , Wong Linda L. , Hernandez Brenda Y. , Pawlish Karen S. , Li Jie , Alverson Georgetta , Schymura Maria J. , Engels Eric A. 
Published: November 2020

AbstractBackground:Hepatocellular carcinoma (HCC) carries a poor prognosis. Liver transplantation (LT) is potentially curative for localized HCC. We evaluated the impact of LT on U.S. general population HCC-specific mortality rates.Methods:The Transplant Cancer Match Study links the U.S. transplant registry with 17 cancer registries. We calculated age-standardized incidence (1987–2017) and incidence-based mortality (IBM) rates (1991–2017) for adult HCCs. We partitioned population-level IBM rates by cancer stage and calculated counterfactual IBM rates assuming transplanted cases had not received a transplant.Results:Among 129,487 HCC cases, 45.9% had localized cancer. HCC incidence increased on average 4.0% annually [95% confidence interval (CI) = 3.6–4.5]. IBM also increased for HCC overall (2.9% annually; 95% CI = 1.7–4.2) and specifically for localized stage HCC (4.8% annually; 95% CI = 4.0–5.5). The proportion of HCC-related transplants jumped sharply from 6.7% (2001) to 18.0% (2002), and further increased to 40.0% (2017). HCC-specific mortality declined among both nontransplanted and transplanted cases over time. In the absence of transplants, IBM for localized HCC would have increased at 5.3% instead of 4.8% annually.Conclusions:LT has provided survival benefit to patients with localized HCC. However, diagnosis of many cases at advanced stages, limited availability of donor livers, and improved mortality for patients without transplants have limited the impact of transplantation on general population HCC-specific mortality rates.Impact:Although LT rates continue to rise, better screening and treatment modalities are needed to halt the rising HCC mortality rates in the United States.See related commentary by Zhang and Thrift, p. 435
Targeting Germline- and Tumor-Associated Nucleotide Excision Repair Defects in Cancer
Authors: Topka Sabine , Steinsnyder Zoe , Ravichandran Vignesh , Tkachuk Kaitlyn , Kemel Yelena , Bandlamudi Chaitanya , Winkel Madsen Mogens , Furberg Helena , Ouerfelli Ouathek , Rudin Charles M. , Iyer Gopa , Lipkin Steven M. , Mukherjee Semanti , Solit David B. , Berger Michael F. , Bajorin Dean F. , Rosenberg Jonathan E. , Taylor Barry S. , de Stanchina Elisa , Vijai Joseph , Offit Kenneth 
Published: November 2020

Abstract

Purpose:
Nucleotide excision repair (NER) gene alterations constitute potential cancer therapeutic targets. We explored the prevalence of NER gene alterations across cancers and putative therapeutic strategies targeting these vulnerabilities.

Experimental Design:
We interrogated our institutional dataset with mutational data from more than 40,000 patients with cancer to assess the frequency of putative deleterious alterations in four key NER genes. Gene-edited isogenic pairs of wild-type and mutant ERCC2 or ERCC3 cell lines were created and used to assess response to several candidate drugs.

Results:
We found that putative damaging germline and somatic alterations in NER genes were present with frequencies up to 10% across multiple cancer types. Both in vitro and in vivo studies showed significantly enhanced sensitivity to the sesquiterpene irofulven in cells harboring specific clinically observed heterozygous mutations in ERCC2 or ERCC3. Sensitivity of NER mutants to irofulven was greater than to a current standard-of-care agent, cisplatin. Hypomorphic ERCC2/3-mutant cells had impaired ability to repair irofulven-induced DNA damage. Transcriptomic profiling of tumor tissues suggested codependencies between DNA repair pathways, indicating a potential benefit of combination therapies, which were confirmed by in vitro studies.

Conclusions:
These findings provide novel insights into a synthetic lethal relationship between clinically observed NER gene deficiencies and sensitivity to irofulven and its potential synergistic combination with other drugs.
See related commentary by Jiang and Greenberg, p. 1833
The Diagnostic Value of Cardiac Deceleration Capacity in Vasovagal Syncope
Authors: Zheng Lihui , Sun Wei , Liu Shangyu , Liang Erpeng , Du Zhongpeng , Guo Jingrui , Wu Lingmin , Asirvatham Samuel J. , Yao Yan 
Published: November 2020

Background:
Increased parasympathetic activity is thought to play important roles in syncope events of patients with vasovagal syncope (VVS). However, direct measurements of the vagal control are difficult. The novel deceleration capacity (DC) of heart rate measure has been used to characterize the vagal modulation. This study aimed to assess vagal control in patients with VVS and evaluate the diagnostic value of the DC in VVS.

Methods:
Altogether, 161 consecutive patients with VVS (43±15 years; 62 males) were enrolled. Tilt table test was positive in 101 and negative in 60 patients. Sixty-five healthy subjects were enrolled as controls. DC and heart rate variability in 24-hour ECG, echocardiogram, and biochemical examinations were compared between the syncope and control groups.

Results:

DC was significantly higher in the syncope group than in the control group (9.6±3.3 versus 6.5±2.0 ms,
P
<0.001). DC was similarly increased in patients with VVS with a positive and negative tilt table test (9.7±3.5 and 9.4±2.9 ms,
P
=0.614). In multivariable logistic regression analyses, DC was independently associated with syncope (odds ratio=1.518 [95% CI, 1.301–1.770];
P
=0.0001). For the prediction of syncope, the area under curve analysis showed similar values when comparing single DC and combined DC with other risk factors (
P
=0.1147). From the receiver operator characteristic curves for syncope discrimination, the optimal cutoff value for the DC was 7.12 ms.

Conclusions:
DC>7.5 ms may serve as a good tool to monitor cardiac vagal activity and discriminate VVS, particularly in those with negative tilt table test.