bluuebunny/crossref_metadata_2025_split huggingface dataset:
A c.544_618del75bp mutation in the splicing factor gene PRPF31 is involved in non‐syndromic retinitis pigmentosa by reducing the level of mRNA expression
Authors: Yang Dongzhi , Yao Qihui , Li Ya , Xu Yan , Wang Jun , Zhao Huiling , Liu Fuyong , Zhang Zhaojing , Liu Yang , Bie Xiaoshuai , Wang Yuanli , Xu Liyan , Luan Yingying , Yang Shangdong , Yang Ge , He Ying 
Published: February 2020

AbstractPurposeA previous study reported a novel c.544_618del75bp mutation in exon 7 of the PRPF31 gene in a Chinese family with autosomal dominant retinal pigmentosa (ADRP). However, the selected pedigree was a small part of the whole family and the function of the c.544_618del75bp mutation was not explored deeply. The aim of the present study was to validate the previous results and explore the functional significance of the c.544_618del75bp mutation.MethodsWe extended the size of the ADRP pedigree and sequenced DNA and cDNA of the PRPF31 gene for all members of the family and 100 healthy controls. Real‐time quantitative polymerase chain reaction (PCR) analysis was performed on the cDNA of patients in the family and cell culture, plasmids transfection and western blot analysis were done to evaluate the functional effect of the mutation in vitro.ResultsSanger sequencing showed that the mutation was present in all patients and absent in all normal individuals, except for participant III‐9. Bioinformatics analysis revealed that the c.544_618del75bp mutation caused a 25 amino acid deletion in the PRPF31 protein. In addition, the mRNA expression assay revealed that the mRNA expression level of the PRPF31 and RP9 genes were significantly lower in RP patients than controls (p < 0.05). Finally, the in vitro transfection assay demonstrated that the mRNA expression level of the mutant transfection group was significantly lower than the wild‐type transfection group (p < 0.05).ConclusionsOur study suggested that the c.544_618del75bp mutation in the PRPF31 gene was a causative mutation in this ADRP family and affected the expression of RP9 gene by influencing the formation of U4/U6‐U5 tri‐snRNP, eventually leading to the occurrence of RP.
Retention of Molten Corium in Calandria Vessel of PHWR With Moderator Drain Pipe
Authors: Pandey Pradeep , Kulkarni Parimal P. , Nayak Arun , Prasad Sumit V. 
Published: February 2020

Abstract
Retention of molten corium inside calandria vessel is crucial for arresting accident progression in pressurized heavy water reactors (PHWRs) during severe accidents. Our earlier tests have demonstrated corium retention and its cooling inside the calandria vessel of PHWRs through external cooling by vault water. However, the presence of nozzles and moderator drain pipe at the bottom of calandria vessel has not been considered in these studies. These nozzles and drain pipes used for moderator circulation can make the viability of corium retention even more challenging. Once the moderator has evaporated, debris reheating, compacting, and finally melting can cause the release of molten corium into the moderator recirculation system. This can lead to the relocation of corium beyond calandria vessel. The corium might reach the pump room or calandria vault after the failure of moderator drain pipe and/or moderator pump seals. This has severe consequences on containment integrity due to molten corium concrete interaction (MCCI). The risks posed by MCCI can be avoided if corium can be contained inside calandria vessel even with the presence of nozzles (at the bottom of the vessel) or if at all it enters into the drain line, does not cause its failure. Thus, it becomes crucial to evaluate the challenges faced by “in-vessel retention” (IVR) as a severe accident management strategy due to the presence of openings in the calandria vessel. Relatively colder debris present near the bottom of calandria vessel might help in obstructing the nozzles of the moderator drain line and can prevent the entry of hot molten corium into the moderator cooling line. The role of debris, therefore, becomes important under such scenarios for not just insulation of calandria vessel from hot corium but also for retention of corium within the vessel. In this article, these issues are addressed by conducting two sets of experiments for assessment of retention capability (IVR) of calandria vessel: (i) with the presence of debris and (ii) without debris at the bottom of calandria vessel. The moderator recirculation line was scaled to simulate the heat transfer from corium to vault water and solidification of corium simulant while flowing through the moderator drain pipe. It was observed that debris bed present at the bottom of the vessel helps in arresting the molten corium front and thus prevents corium from entering into moderator drain pipe. When experiments were conducted without debris, molten corium was found to be relocating in the moderator drain pipe. The drain pipe, however, did not fail under the thermal load.
Effect of Pulsation and Acceleration of Liquid Metal Turbulent Flow Through a Horizontal Channel by Large Eddy Simulation
Authors: Satish N. , Venkatasubbaiah K. 
Published: February 2020

Abstract
Pulsation and acceleration of liquid metal turbulent flow through a horizontal channel has been numerically studied using a large eddy simulation (LES) technique. The effect of inlet pulsation and acceleration on flow and heat transfer characteristics of low Prandtl number liquid metal flow have been investigated and reported here. Results have been presented for different Reynolds numbers, different amplitudes, and frequency with constant bottom wall thickness. The flow field is modeled as unsteady-state two-dimensional incompressible turbulent-forced convection flow. Turbulence is modeled using a LES technique. Two-dimensional unsteady-state heat conduction equation is solved to know the temperature distribution in the solid region. Finite difference method solver is developed for solving the governing equations using sixth-order accuracy of compact schemes. The average Nusselt number shows cyclic variation with respect to time in pulsation flows. The enhancement of heat transfer with pulsation at amplitude 0.4 and frequency 100 Hz is 6.51%. The rate of heat transfer increases in pulsation flow compared to quasi-steady flow. The inlet acceleration shows a significant effect on flow characteristics. The present results are compared with direct numerical simulation (DNS) results available in the literature and matching well with DNS data.
A Study of Temperature Distribution and Thermal Stresses in a Hot Rock Due to Rapid Cooling
Authors: Phuoc Tran X. , Massoudi Mehrdad , Wang Ping , McKoy Mark L. 
Published: February 2020

Abstract
Thermal stresses may be induced in a hot dry rock when a cold fluid is injected in the well. To study this problem, we look at the thermoelastic response of a hot rock that is suddenly cooled. The cooling is assumed to be either at a constant temperature or at a constant heat flux per unit depth. Our approach is to nondimensionalize the equations and perform a parametric study and look at the temperature distribution and the induced-thermal stresses. The results indicate that depending on the extent of cooling and the cooling time, thermal stresses can be induced. Numerical simulations on sandstone, with an initial uniform temperature of 473 K, are also carried out. The results show that if the cooling is due to the surface temperature maintained at 463 K (10 °C lower than the initial temperature of the hot rock), thermal stresses that are larger than the rock tensile strength could be induced. When the cooling is due to a constant surface heat flux, this temperature can be reached after about 777 days of cooling with a minimum value of a heat flux of −20 W/m.
The biology
,
function
,
and biomedical applications of exosomes
Authors: Kalluri Raghu , LeBleu Valerie S. 
Published: February 2020

Clinical uses of cellular communication
Exosomes are a type of extracellular vesicle that contain constituents (protein, DNA, and RNA) of the cells that secrete them. They are taken up by distant cells, where they can affect cell function and behavior. Intercellular communication through exosomes seems to be involved in the pathogenesis of various disorders, including cancer, neurodegeneration, and inflammatory diseases. In a Review, Kalluri and LeBleu discuss the biogenesis and function of exosomes in disease, highlighting areas where more research is needed. They also discuss the potential clinical applications of exosome profiling for diagnostics and exosome-mediated delivery of therapeutics to target disease cells.

Science
, this issue p.
eaau6977
Effects of participating in community assets on quality of life and costs of care: longitudinal cohort study of older people in England
Authors: Munford Luke Aaron , Wilding Anna , Bower Peter , Sutton Matt 
Published: February 2020

ObjectivesImproving outcomes for older people with long-term conditions and multimorbidity is a priority. Current policy commits to substantial expansion of social prescribing to community assets, such as charity, voluntary or community groups. We use longitudinal data to add to the limited evidence on whether this is associated with better quality of life or lower costs of care.DesignProspective 18-month cohort survey of self-reported participation in community assets and quality of life linked to administrative care records. Effects of starting and stopping participation estimated using double-robust estimation.SettingParticipation in community asset facilities. Costs of primary and secondary care.Participants4377 older people with long-term conditions.InterventionParticipation in community assets.Primary and secondary outcome measuresQuality-adjusted life years (QALYs), healthcare costs and social value estimated using net benefits.ResultsStarting to participate in community assets was associated with a 0.017 (95% CI 0.002 to 0.032) gain in QALYs after 6 months, 0.030 (95% CI 0.005 to 0.054) after 12 months and 0.056 (95% CI 0.017 to 0.094) after 18 months. Cumulative effects on care costs were negative in each time period: £−96 (95% CI £−512 to £321) at 6 months; £−283 (95% CI £−926 to £359) at 12 months; and £−453 (95% CI £−1366 to £461) at 18 months. The net benefit of starting to participate was £1956 (95% CI £209 to £3703) per participant at 18 months. Stopping participation was associated with larger negative impacts of −0.102 (95% CI −0.173 to −0.031) QALYs and £1335.33 (95% CI £112.85 to £2557.81) higher costs after 18 months.ConclusionsParticipation in community assets by older people with long-term conditions is associated with improved quality of life and reduced costs of care. Sustaining that participation is important because there are considerable health changes associated with stopping. The results support the inclusion of community assets as part of an integrated care model for older patients.
Randomised feasibility trial of the helping families programme-modified: an intensive parenting intervention for parents affected by severe personality difficulties
Authors: Day Crispin , Briskman Jackie , Crawford Mike J , Foote Lisa , Harris Lucy , Boadu Janet , McCrone Paul , McMurran Mary , Michelson Daniel , Moran Paul , Mosse Liberty , Scott Stephen , Stahl Daniel , Ramchandani Paul , Weaver Tim 
Published: February 2020

BackgroundSpecialist parenting intervention could improve coexistent parenting and child mental health difficulties of parents affected by severe personality difficulties.ObjectiveConduct a feasibility trial of Helping Families Programme-Modified (HFP-M), a specialist parenting intervention.DesignPragmatic, mixed-methods trial, 1:1 random allocation, assessing feasibility, intervention acceptability and outcome estimates.SettingsTwo National Health Service health trusts and local authority children’s social care.ParticipantsParents: (i) primary caregiver, (ii) 18 to 65 years, (iii) severe personality difficulties, (iv) proficient English and (v) capacity for consent. Child: (i) 3 to 11 years, (ii) living with index parent and (iii) significant emotional/behavioural difficulties.InterventionHFP-M: 16-session home-based intervention using parenting and therapeutic engagement strategies. Usual care: standard care augmented by single psychoeducational parenting session.OutcomesPrimary feasibility outcome: participant retention rate. Secondary outcomes: (i) rates of recruitment, eligibility and data completion, and (ii) rates of intervention acceptance, completion and alliance (Working Alliance Inventory-Short Revised). Primary clinical outcome: child behaviour (Eyberg Child Behaviour Inventory). Secondary outcomes: child mental health (Concerns About My Child, Child Behaviour Checklist-Internalising Scale), parenting (Arnold-O’Leary Parenting Scale, Kansas Parental Satisfaction Scale) and parent mental health (Symptom-Checklist-27). Quantitative data were collected blind to allocation.ResultsFindings broadly supported non-diagnostic selection criterion. Of 48 participants recruited, 32 completed post-intervention measures at mean 42 weeks later. Participant retention exceeded a priori rate (HFP-M=18; Usual care=14; 66.7%, 95% CI 51.6% to 79.6%). HFP-M was acceptable, with delivery longer than planned. Usual care had lower alliance rating. Child and parenting outcome effects detected across trial arms with potential HFP-M advantage (effect size range: 0.0 to 1.3).ConclusionHFP-M is an acceptable and potentially effective specialist parenting intervention. A definitive trial is feasible, subject to consideration of recruitment and retention methods, intervention efficiency and comparator condition. Caution is required in interpretation of results due to reduced sample size. No serious adverse events reported.Trial registration numberISRCTN14573230
Non-invasive techniques for stimulating urine production in non-toilet trained children: a systematic review
Authors: Chandy Mathew , Dewey Ann , Fogg Carole , Pilkington Karen 
Published: February 2020

BackgroundUrinary tract infection requires collection of a sterile urine specimen for diagnosis, which is difficult and time consuming in pre-continent children. This systematic review summarises evidence of the effectiveness of bladder stimulation techniques on urine collection in pre-continent children, compared with standard techniques.MethodsMEDLINE, PubMed, EMBASE and CINAHL were searched to May 2019. Selection, data extraction, risk of bias and quality assessment were undertaken by two independent reviewers. Inclusion: (1) all study designs; (2) pre-continent, age <3 years receiving bladder stimulation techniques; (3) outcomes including time to urine collection or contamination rates; (4) English-language articles. Exclusion: coexisting neurological disorders.ResultsThree randomised controlled trials (RCTs) were identified using three techniques in 568 participants aged 1 day to 35 months. Two RCTs demonstrated an increased success in voiding within 5 min, one using a finger tapping and lumbar paravertebral massage technique and the other cold saline-soaked gauze rubbed over the suprapubic region, compared with no active intervention. A third RCT using a mechanical vibration device demonstrated no difference in time to voiding from advice alone. Non-randomised studies compared different temperatures for the gauze intervention and tapping alone versus urine bags. Six uncontrolled studies tested the finger tapping and massage technique. Risk of bias was low for one RCT and unclear for two RCTs with the other studies rated poor to fair quality. Overall, the evidence on success rates was graded low for tapping plus massage and moderate for the gauze rubbing intervention. Adverse effects included crying and mild distress.DiscussionThe results suggest a positive effect of stimulation techniquesbut lack of replication in rigorous RCTs and heterogeneity of techniques and outcomes assessed prevent conclusive recommendations being made. Further RCTs are required comparing non-invasive stimulation methods and assessing time to successful collection, contamination rates, adverse effects, caregiver and clinical staff acceptability.
Prognostic value of perineural invasion in prostate needle biopsies: a population-based study of patients treated by radical prostatectomy
Authors: Ström Peter , Nordström Tobias , Delahunt Brett , Samaratunga Hema , Grönberg Henrik , Egevad Lars , Eklund Martin 
Published: February 2020

AimsDespite being one of the major pathways for the spread of malignant tumours, perineural invasion (PNI) has not conclusively been shown to have an independent prognostic value for prostate cancer. Prostatic biopsy constitutes the major pathology workload in prostate cancer and is the foundation for primary treatment decisions and for this reason we aimed to estimate the prognostic value of PNI in biopsies.MethodsWe followed 918 men who underwent radical prostatectomy (RP) from the prospective and population based STHLM3 study until biochemical recurrence with a median follow-up of 4.1 years. To strengthen the evidence, we combined the estimates from the largest studies targeting the prognostic value of PNI in the biopsy. We also estimated the OR of advanced stage as radical prostatectomy for PNI positive and negative men.ResultsThe estimated prognostic value based on our data suggested an approximately 50% increased risk of biochemical recurrence if PNI was present in the biopsy (p=0.06). Even though not statistically significant on the 5% level, this estimate is consistent with similar studies, and by combining the estimates there is in fact strong evidence in support of an independent prognostic value of PNI in the biopsy (p<0.0001). There was also an independent increased risk of advanced stage at RP for positive men (OR 1.85, p=0.005).ConclusionsThe evidence supporting a clinically relevant and independent prognostic value of PNI is strong enough to be considered for pathology reporting guidelines.
Survival after traumatic brain injury improves with deployment of neurosurgeons: a comparison of US and UK military treatment facilities during the Iraq and Afghanistan conflicts
Authors: Breeze John , Bowley Douglas M , Harrisson Stuart E , Dye Justin , Neal Christopher , Bell Randy S , Armonda Rocco A , Beggs Andrew D , DuBose Jospeh , Rickard Rory F , Powers David Bryan 
Published: February 2020

IntroductionTraumatic brain injury (TBI) is the most common cause of death on the modern battlefield. In recent conflicts in Iraq and Afghanistan, the US typically deployed neurosurgeons to medical treatment facilities (MTFs), while the UK did not. Our aim was to compare the incidence, TBI and treatment in US and UK-led military MTF to ascertain if differences in deployed trauma systems affected outcomes.MethodsThe US and UK Combat Trauma Registries were scrutinised for patients with HI at deployed MTFs between March 2003 and October 2011. Registry datasets were adapted to stratify TBI using the Mayo Classification System for Traumatic Brain Injury Severity. An adjusted multiple logistic regression model was performed using fatality as the binomial dependent variable and treatment in a US-MTF or UK-MTF, surgical decompression, US military casualty and surgery performed by a neurosurgeon as independent variables.Results15 031 patients arrived alive at military MTF after TBI. Presence of a neurosurgeon was associated with increased odds of survival in casualties with moderate or severe TBI (p<0.0001, OR 2.71, 95% CI 2.34 to 4.73). High injury severity (Injury Severity Scores 25–75) was significantly associated with a lower survival (OR 4×104, 95% CI 1.61×104 to 110.6×104, p<0.001); however, having a neurosurgeon present still remained significantly positively associated with survival (OR 3.25, 95% CI 2.71 to 3.91, p<0.001).ConclusionsPresence of neurosurgeons increased the likelihood of survival after TBI. We therefore recommend that the UK should deploy neurosurgeons to forward military MTF whenever possible in line with their US counterparts.
The fission experimental programme at the CERN n_TOF facility: status and perspectives
Authors:   the n_TOF  Collaboration, Colonna N. , Tsinganis A. , Vlastou R. , Patronis N. , Diakaki M. , Amaducci S. , Barbagallo M. , Bennett S. , Berthoumieux E. , Bacak M. , Cosentino G. , Cristallo S. , Finocchiaro P. , Heyse J. , Lewis D. , Manna A. , Massimi C. , Mendoza E. , Mirea M. , Moens A. , Nolte R. , Pirovano E. , Sabaté-Gilarte M. , Sibbens G. , Smith A. G. , Sosnin N. , Stamatopoulos A. , Tarrío D. , Tassan-Got L. , Vanleeuw D. , Ventura A. , Vescovi D. , Wright T. , Žugec P. 
Published: February 2020

AbstractNeutron-induced fission reactions play a crucial role in a variety of fields of fundamental and applied nuclear science. In basic nuclear physics they provide important information on properties of nuclear matter, while in nuclear technology they are at the basis of present and future reactor designs. Finally, there is a renewed interest in fission reactions in nuclear astrophysics due to the multi-messenger observation of neutron star mergers and the important role played by fission recycling in r-process nucleosynthesis. Although studied for several decades, many fundamental questions still remain on fission reactions, while modern applications and the development of more reliable nuclear models require high-accuracy and consistent experimental data on fission cross sections and other fission observables. To address these needs, an extensive fission research programme has been carried out at the n_TOF neutron time-of-flight facility at CERN during the last 18 years, taking advantage of the high energy resolution, high luminosity and wide energy range of the neutron beam, as well as of the detection and data acquisition systems designed for this purpose. While long-lived isotopes are studied on the 185 m long flight-path, the recent construction of a second experimental area at a distance of about 19 m has opened the way to challenging measurements of short-lived actinides. This article provides an overview of the n_TOF experimental programme on neutron-induced fission reactions along with the main characteristics of the facility, the various detection systems and data analysis techniques used. The most important results on several major and minor actinides obtained so far and the future perspectives of fission measurements at n_TOF are presented and discussed.
Phase diagrams of the disordered Bose-Hubbard model with cavity-mediated long-range and nearest-neighbor interactions
Authors: Zhang Chao , Rieger Heiko 
Published: February 2020

Abstract
Recent experiments with ultracold atoms in an optical lattice have realized cavity-mediated long-range interaction and observed the emergence of a supersolid phase and a density wave phase in addition to Mott insulator and superfluid phases. Here we consider theoretically the effect of uncorrelated disorder on the phase diagram of this system and study the two-dimensional Bose-Hubbard model with cavity-mediated long-range interactions and uncorrelated diagonal disorder. We also study the phase diagram of the extended Bose-Hubbard model with nearest-neighbor interactions in the presence of uncorrelated diagonal disorder. The extended Bose-Hubbard model with nearest-neighbor interactions has been realized in the experiment using dipolar interaction recently. With the help of quantum Monte Carlo simulations using the worm algorithm, we determine the phase diagram of those two models. We compare the phase diagrams of cavity-mediated long-range interactions with nearest-neighbor interactions. We show that two kinds of Bose glass phases exist: one with and one without density wave order. We also find that weak disorder enhances the supersolid phase.

Graphical abstract