bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial
Authors: Palma David A. , Olson Robert , Harrow Stephen , Gaede Stewart , Louie Alexander V. , Haasbeek Cornelis , Mulroy Liam , Lock Michael , Rodrigues George B. , Yaremko Brian P. , Schellenberg Devin , Ahmad Belal , Senthi Sashendra , Swaminath Anand , Kopek Neil , Liu Mitchell , Moore Karen , Currie Suzanne , Schlijper Roel , Bauman Glenn S. , Laba Joanna , Qu X. Melody , Warner Andrew , Senan Suresh 
Published: March 2020

AbstractPurposeThe oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long-term disease control, or even cure, if all sites of disease can be ablated. However, long-term randomized data testing this paradigm are lacking.MethodsWe enrolled patients with a controlled primary malignancy and 1-5 metastatic lesions, with all metastases amenable to stereotactic ablative radiotherapy (SABR). We stratified by the number of metastases (1-3 vs. 4-5) and randomized in a 1:2 ratio between palliative standard of care (SOC) treatments (Arm 1) vs. SOC plus SABR (Arm 2). We employed a randomized phase II screening design with a primary endpoint of overall survival (OS), using an alpha of 0.20 (wherein a p-value <0.20 indicates a positive trial). Secondary endpoints included progression-free survival (PFS), toxicity, and quality of life (QOL). Herein we present long-term outcomes from the trial.ResultsBetween 2012 and 2016, 99 patients were randomized (33 in Arm 1, 66 in Arm 2) at 10 centres internationally. Median age was 68 (range 43-89) and the majority (n=59; 60%) were male. The most common primary tumor types were breast (n=18), lung (n=18), colorectal (n=18), and prostate (n=16). Median follow-up was 51 months. Five-year OS was 17.7% in Arm 1 (95% confidence interval [CI]: 6-34%) vs. 42.3% in Arm 2 (95% CI: 28-56%; stratified log-rank p=0.006). Five-year PFS was ‘not reached’ in Arm 1 (3.2% [95% CI: 0-14%] at 4-years with last patient censored) and was 17.3% (95% CI: 8-30%) in Arm 2 (p=0.001). There were no new grade 2-5 adverse events and no differences in QOL between arms.ConclusionsWith extended follow-up, the impact of SABR on OS was larger in magnitude than in the initial analysis, and durable over time. There were no new safety signals, and SABR had no detrimental impact on QOL. (NCT01446744)FundingOntario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant
A single holiday was the turning point of the COVID-19 policy of Israel
Authors: Klausner Ziv , Fattal Eyal , Hirsch Eitan , Shapira Shmuel C. 
Published: March 2020

AbstractBackgroundThe impact of COVID-19 has been profound, and the public health challenge seem to be the most serious regarding respiratory viruses since the 1918 H1N1 influenza pandemic. In the absence of effective vaccine or biomedical treatment, the basic rules of public health measures have not changed, namely public distancing.MethodsWe analyzed epidemiological investigation reports during the first month of the outbreak in Israel. In addition, we present a deterministic compartment model and simulations of several scenarios emphasizing quarantine and isolation policies given their efficiency.ResultsWe identify an abrupt change from controlled epidemic regime to an exponential growth (R0 = 2.19) in light of the actual policy-makers decisions and public behavior in Israel. Our analysis show that before the abrupt change, the new cases trend was due to returning citizens infected abroad. The abrupt change followed a holiday in which social distancing was clearly inefficient and many public gatherings were held. We further discuss three different modeled scenarios of quarantine efficiency: high-, medium-, and low-efficiency.ConclusionsIsrael early lessons show that there is no allowance to compromise with the directive of social distancing. Even before the onset of the pandemic in Israel, fine-tuned but determined early decisions were taken by policy makers to monitor flight arrivals from Covid-19 affected regions and to limit public gatherings. Our analysis show that one particular holiday has shifted the occurrence curve from controlled regime to exponential growth. Therefore, even a short lapse in public responsiveness can have a dramatic effect.
Early Spread of SARS-Cov-2 in the Icelandic Population
Authors: Gudbjartsson Daniel F , Helgason Agnar , Jonsson Hakon , Magnusson Olafur T , Melsted Pall , Norddahl Gudmundur L , Saemundsdottir Jona , Sigurdsson Asgeir , Sulem Patrick , Agustsdottir Arna B , Eiriksdottir Berglind , Fridriksdottir Run , Gardarsdottir Elisabet E , Georgsson Gudmundur , Gretarsdottir Olafia S , Gudmundsson Kjartan R , Gunnarsdottir Thora R , Gylfason Arnaldur , Holm Hilma , Jensson Brynjar O , Jonasdottir Aslaug , Jonsson Frosti , Josefsdottir Kamilla S , Kristjansson Thordur , Magnusdottir Droplaug N , Roux Louise le , Sigmundsdottir Gudrun , Sveinbjornsson Gardar , Sveinsdottir Kristin E , Sveinsdottir Maney , Thorarensen Emil A , Thorbjornsson Bjarni , Löve Arthur , Masson Gisli , Jonsdottir Ingileif , Moller Alma , Gudnason Thorolfur , Kristinsson Karl G , Thorsteinsdottir Unnur , Stefansson Kari 
Published: March 2020

AbstractBACKGROUNDLimited data exist on how SARS-CoV-2 enters and spreads in the general population.METHODSWe used two strategies for SARS-CoV-2 testing: targeted testing of high-risk individuals (n=4,551) and a population screening (n=5,502). We sequenced SARS-CoV-2 from 340 individuals.RESULTSOn March 22 2020, 528 had tested positive for SARS-CoV-2 in the targeted testing (11.6%) and 50 in the population screening (0.9%); approximately 0.2% of the Icelandic population. Large fractions of positives had travelled outside Iceland (38.4% and 34.0%). Fewer under 10 years old were positive than those older: 2.8% vs. 12.3% for targeted testing (P=1.6e-9) and 0.0% vs. 1.0% for population screening (P=0.031). Fewer females were positive in the targeted testing than males (9.5% vs. 14.6%, P=6.8e-9). SARS-CoV-2 came from eight clades, seven A clades and one B clade. The clade composition differed between the testing groups and changed with time. In the early targeted testing, 65.0% of clades were A2a1 and A2a2 derived from Italian and Austrian skiing areas, but in the later targeted testing went down to 30.6% and were overtaken by A1a and A2a, the most common clades in the population screening.CONCLUSIONSARS-CoV-2 has spread widely in Iceland outside of the high-risk groups. Several strains cause these infections and their relative contribution changed rapidly. Children and females are less vulnerable than adults and males. To contain the pandemic we must increase the scope of the testing.
Suppression and Mitigation Strategies for Control of COVID-19 in New Zealand
Authors: James Alex , Hendy Shaun C. , Plank Michael J. , Steyn Nicholas 
Published: March 2020

AbstractA standard SEIR-type compartment model, parameterised for New Zealand, was used to simulate the spread of Covid19 in New Zealand and to test the effectiveness of various control strategies. Control aims can be broadly categorised as either suppression or mitigation. Suppression aims to keep cases to an absolute minimum for as long as possible. Mitigation aims to allow a controlled outbreak to occur, with the aim of preventing significant overloads on healthcare systems and gradually allowing the population to develop herd immunity.Both types of strategy are fraught with uncertainty. Suppression strategies can succeed in delaying an outbreak, but only for as long as such control measures can be sustained. Once controls are eased or restricted, an epidemic is likely to follow as no herd immunity has been acquired. The success or failure of mitigation strategies can depend sensitively on the timing and efficacy of control measures, and require the ability to bring rapidly growing outbreaks under immediate control when needed. This is as yet untested even for a combination of national interventions including case isolation, household quarantine, population-wide social distancing and closure of schools and universities.Although there are disadvantages to both types of approach, suppression has the advantage of buying time until a vaccine and/or treatment become available and allowing NZ to learn from rapidly unfolding events in other countries. A combination of successful suppression, strong border measures, and widespread contact tracing and testing resulting in containment could allow periods when control measures can be relaxed, but only if cases are reduced to a handful.Executive SummarySuppression strategies aim to keep the number of cases to an absolute minimum for as long as possible. This requires early and effective control interventions.Suppression can only delay an epidemic, not prevent it, but may buy enough time for a vaccine or treatment to become available.Mitigation strategies aim to control an epidemic so that herd immunity is acquired by the population without overwhelming healthcare systems.Mitigation strategies are likely to be very high risk: they are unproven internationally, potentially sensitive to uncertainty, and it may take years for herd immunity to be acquired.Strategy can be switched from suppression to mitigation. For example, once successful mitigation strategies have been tested in other countries. It is likely to be difficult or impossible to switch from a mitigation to a suppression strategy.A combination of successful suppression, strong border measures, and widespread contact tracing and testing resulting in containment could allow periods when control measures can be relaxed, but only if we can reduce cases to a handful.
Effectiveness of Isolation Policies in Schools: Evidence from a Mathematical Model of Influenza and COVID-19
Authors: Burns Adam A. C. , Gutfraind Alexander 
Published: March 2020

AbstractBackgroundNon-pharmaceutical interventions such as social distancing, school closures and travel restrictions are often implemented to control outbreaks of infectious diseases. For influenza in schools, the Center of Disease Control (CDC) recommends that febrile students remain isolated at home until they have been fever-free for at least one day and a related policy is recommended for SARS-CoV2 (COVID-19). Other authors proposed using a school week of four or fewer days of in-person instruction for all students to reduce transmission. However, there is limited evidence supporting the effectiveness of these interventions.MethodsWe introduced a mathematical model of school outbreaks that considers both intervention methods. Our model accounts for the school structure and schedule, as well as the time-progression of fever symptoms and viral shedding. The model was validated on outbreaks of seasonal and pandemic influenza and COVID-19 in schools. It was then used to estimate the outbreak curves and the proportion of the population infected (attack rate) under the proposed interventions.ResultsFor influenza, the CDC-recommended one day of post-fever isolation can reduce the attack rate by a median (interquartile range) of 29 (13 - 59)%. With two days of post-fever isolation the attack rate could be reduced by 70 (55 - 85)%. Alternatively, shortening the school week to four and three days reduces the attack rate by 73 (64 - 88)% and 93 (91 - 97)%, respectively. For COVID-19, application of post-fever isolation policy was found to be less effective and reduced the attack rate by 10 (5 - 17)% for a two-day isolation policy and by 14 (5 - 26)% for 14 days. A four-day school week would reduce the median attack rate in a COVID-19 outbreak by 57 (52 - 64)%, while a three-day school week would reduce it by 81 (79 - 83)%. In both infections, shortening the school week significantly reduced the duration of outbreaks.ConclusionsShortening the school week could be an important tool for controlling influenza and COVID-19 in schools and similar settings. Additionally, the CDC-recommended post-fever isolation policy for influenza could be enhanced by requiring two days of isolation instead of one.
A meta-analysis on the role of children in SARS-CoV-2 in household transmission clusters
Authors: Zhu Yanshan , Bloxham Conor J. , Hulme Katina D. , Sinclair Jane E. , Marcus Tong Zhen Wei , Steele Lauren E. , Noye Ellesandra C. , Lu Jiahai , Xia Yao , Chew Keng Yih , Pickering Janessa , Gilks Charles , Bowen Asha C. , Short Kirsty R 
Published: March 2020

ABSTRACTThe role of children in the spread of SARS-CoV-2 remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n=213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a paediatric index case. Asymptomatic index cases were associated with a lower secondary attack in contacts than symptomatic index cases (estimate risk ratio [RR], 0.17; 95% confidence interval [CI], 0.09-0.29). To determine the susceptibility of children to household infections the secondary attack rate (SAR) in paediatric household contacts was assessed. The secondary attack rate in paediatric household contacts was lower than in adult household contacts (RR, 0.62; 95% CI, 0.42-0.91). These data have important implications for the ongoing management of the COVID-19 pandemic, including potential vaccine prioritization strategies.40-word summaryIn household transmission clusters of SARS-CoV-2 children are unlikely to be the index case. Children are also less likely than adults to be infected with SARS-CoV-2 from a family member.
Diagnostic Indexes of a Rapid IgG/IgM Combined Antibody Test for SARS-CoV-2
Authors: Ying Liu , Yue-ping Liu , Bo Diao , Feifei Ren , Yue Wang , Jinya Ding , Qianchuan Huang 
Published: March 2020

[Abstract]ObjectiveCoronavirus disease 2019 (COVID-19) has become pandemic in the world. The need for IgG-IgM combined antibody test is booming, but data on diagnostic indexes evaluation was inadequate. The aim of this study was to evaluate diagnostic indexes of a rapid IgG-IgM combined antibody test for SARS-CoV-2.MethodsA total of 179 patients were enrolled. Serum were collected for IgG-IgM combined antibody test and corresponding nasal and pharyngeal swab specimens were collected for SARS-CoV-2 RT-PCR. According to SARS-CoV-2 RT-PCR results, patients under study were categorized as PCR positive group in 90 patients and PCR negative group in 89 patients.Results1. Of the 90 PCR positive samples, 77 were tested positive by SARS-CoV-2 IgG-IgM test kit, yielding a sensitivity of 85.6%. Meanwhile, of the 89 PCR negative sample, 8 samples were detected positive, resulting in a specificity of 91%. Positive predictive value, negative predictive value and accuracy of this test kit was 95.1%, 82.7%, and 88.3%, respectively. Kappa efficiency between IgG/IgM test kit and RT-PCR were 0.75. 2. Accuracy in mild/common and severe/critical subgroup were 73.9% and 97.7%, respectively. Accuracy in clinical confirmed, suspected cases and other disease subgroups were 70%, 60%, and 100%, respectively. 3. Patients were further divided into ‘0 - 7’, ‘8 - 15’ and ‘>= 16’ groups according to the time from illness onset to sample collection. Sensitivity, specificity and accuracy in these three groups were 18.8%, 77.8% and 40%; 100%, 50% and 87.5%; 100%, 64.3%, and 93.9, respectively.ConclusionThe sensitivity and specificity of this ease-of-use IgG/IgM combined test kit were adequate, plus short turnaround time, no specific requirements for additional equipment or skilled technicians, all of these collectively contributed to its competence for mass testing. At the current stage, it cannot take the place of SARA-CoV-2 nucleic acid RT-PCR, but can be served as a complementary option for RT-PCR. The combination of RT-PCR and IgG-IgM combined test kit could provide further insight into SARS-CoV-2 infection diagnosis.
Visual featural topography in the human ventral visual pathway
Authors: Fan Shijia , Wang Xiaosha , Wang Xiaoying , Wei Tao , Bi Yanchao 
Published: March 2020

AbstractVisual object recognition in humans and nonhuman primates is achieved by the ventral visual pathway (ventral occipital-temporal cortex, VOTC), which shows a well-documented object domain structure. An on-going question has been what type of information is processed in higher-order VOTC that underlies such observations, with recent evidence suggesting effects of certain visual features. Combining computational vision models, fMRI experiment using a parametric-modulation approach, and natural image statistics of common objects, we depicted the neural distribution of a comprehensive set of visual features in VOTC, identifying voxel sensitivities to specific feature sets across geometry/shape, Fourier power, and color. The visual feature combination pattern in VOTC is significantly explained by their relationships to different types of response-action computation (Fight-or-Flight, Navigation, and Manipulation), as derived from behavioral ratings and natural image statistics. These results offer the first comprehensive visual featural map in VOTC and a plausible theoretical explanation as a mapping onto different types of downstream response-action systems.
Efficient detection of pre-proinsulin by double antibody sandwich ELISA
Authors: Zhu Zhu , Ma Guoliang , Wang Li , Wang Han , Tang Hengfang , Wei Zhou , Wang Peng 
Published: March 2020

Abstract ObjectiveTo generate monoclonal antibodies against pre-proinsulin (PPI), and establish sandwich ELISA method to provide a basis for PPI detection in recombinant human insulin production.MethodsThe Balb /c mice were immunized with PPI, and the hybridomas secreting anti-PPI monoclonal antibodies were obtained by conventional cell fusion technique and ELISA screening.The antibody was purified using a Protein G gel column and identified for purity by SDS-PAGE. Pairing effect was found by the sandwich ELISA, and the specificity of the paired antibody was determined. A paired antibody with better specificity was selected to establish sandwich ELISA, and construct a quantitative curve, the accuracy and sensitivity of the method were evaluated.ResultsSix anti-PPI monoclonal antibodies were obtained, named P1, P2, P3, P4, P5 and P6, of which P5 had the highest titer. The sandwich ELISA method was established with P5 for plating and P2 for detection antibodie. The linear range of the quantitative curve of PPI by sandwich ELISA was 0. 645-82.5 pg/mL, the recovery was 89%–95%, and the limit of detection was 3.06 pg/mL.ConclusionSix monoclonal antibodies against PPI were generated and the sandwich ELISA method was established to detect PPI in process control and product release control for recombinant human insulin production.
Dynamic arm movements attenuate perceptual distortion of visual vertical induced during prolonged whole-body tilt
Authors: Tani Keisuke , Yamamoto Shinji , Kodaka Yasushi , Kushiro Keisuke 
Published: March 2020

AbstractAdditional gravitational cues generated by active body movements may play a role in the perception of gravitational space, but no experimental evidence has been shown on this. To investigate this possibility, we evaluated how arm movements made against gravity influenced the perceptual distortion of visual and postural vertical induced by prolonged whole-body tilt. In Experiment 1, participants were asked to perform static or dynamic arm movements during prolonged whole-body tilt and we assessed their effects on subjective visual vertical (SVV) at the tilt position (during-tiltsession) and after tilting back to the upright position (post-tiltsession). In Experiment 2, we evaluated how static or dynamic arm movements during prolonged tilt subsequently affected the subjective postural vertical (SPV). In Experiment 1, we observed that prolonged tilt induced the SVV shifts toward the side of body tilts in both sessions. The prolonged tilt-induced SVV shifts effectively decreased when performing dynamic arm movements in theduring-tiltsession, but not in thepost-tiltsession. In Experiment 2, the SPV shifted toward the side of prolonged body tilt, which was not significantly influenced by the performance of static or dynamic arm movements. Results of theduring-tiltsession suggest that the central nervous system utilizes additional cues generated by dynamic body movements for the perception of the visual vertical.
Effect of dioxins in milk on 3D-cultured primary buffalo granulosa cells, a pilot study for a prospective RT-LAMP colour reaction for dioxin toxicity
Authors: Singh Chhama , Pandey Mamta , Goud Emmagouni Sharath Kumar , Veerappa Vedamurthy G. , Singh Dheer , Onteru Suneel Kumar 
Published: March 2020

ABSTRACTDioxins are highly toxic environmental persistent organic pollutants. In several countries, their presence was also reported in cow and human milk samples in the range of 0.023-26.46 and 0.88-19.0 pg/gm of fat, respectively. The detection of dioxns in food samples has been relied on several expensive technologies, which do not represent their toxic effects on consumers. However, mammalian cell based bioassays have such potential to detect the toxins, while representing their toxic effects. Therefore, we tried a three-dimensionally (3D) cultured buffalo granulosa cell based RT-LAMP colour reaction for detecting the presence of added model dioxin, 2,3,7,8-tetrachlorodibenzodioxin (TCDD), in commercial milk. The 3D spheroids on the fifth day of culture were treated with different concentrations of TCDD (i.e. 0.02– 20 pg/ml) directly as well as indirectly through milk fat. After 24hrs of treatment, gene expression studies were performed on certain granulosa cell-specific (CYP19A1, ER-beta, FSHRandLHR) and selective TCDD-responsive (CYP1A1, CYP1B1andAHR) genes to identify the potential dioxin responsive gene for further RT-LAMP reaction. As theAHRexpression in 3D cultured buffalo granulosa cells appears to be a potential gene marker for sensing the added TCDD in the milk, a colour based RT-LAMP reaction was successfully attempted for its expression. However, future studies are needed to develop a dose-responsive colour reaction by considering the treatment time less than 24 hrs.
Prion protein lowering is a disease-modifying therapy across prion disease stages, strains, and endpoints
Authors: Minikel Eric Vallabh , Zhao Hien T , Le Jason , O’Moore Jill , Pitstick Rose , Graffam Samantha , Carlson George A , Kavanaugh Michael P , Kriz Jasna , Kim Jae Beom , Ma Jiyan , Wille Holger , Aiken Judd , McKenzie Deborah , Doh-ura Katsumi , Beck Matthew , O’Keefe Rhonda , Stathopoulos Jacquelyn , Caron Tyler , Schreiber Stuart L , Carroll Jeffrey B , Kordasiewicz Holly B , Cabin Deborah E , Vallabh Sonia M 
Published: March 2020

AbstractLowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delays disease onset in intracerebrally prion-infected mice in both prophylactic and delayed dosing paradigms. Here, we examine the efficacy of this therapeutic approach across diverse paradigms, varying the dose and dosing regimen, prion strain, treatment timepoint, and examining symptomatic, survival, and biomarker readouts. We recapitulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four additional prion strains. We demonstrate that less than 25% PrP suppression is sufficient to extend survival and delay symptoms in a prophylactic paradigm. Rise in both neuroinflammation and neuronal injury markers can be reversed by a single dose of PrP-lowering ASO administered after the detection of pathological change. Chronic ASO-mediated suppression of PrP beginning at any time up to early signs of neuropathology confers benefit similar to constitutive heterozygous PrP knockout. Remarkably, even after emergence of frank symptoms including weight loss, a single treatment prolongs survival by months in a subset of animals. These results support ASO-mediated PrP lowering, and PrP-lowering therapeutics in general, as a promising path forward against prion disease.